Notes

Calbindin adjusts Kv4.A single trafficking along with excitability in dentate granule tissue through CaMKII-dependent phosphorylation.
A Carefully Lowered Mathematical Style regarding Organoid Growth.
[Profiles of epidemiological-nutritional transition along with stress regarding morbimortality through COVID-19 in Argentina: the enviromentally friendly study].

Small bowel obstruction is potentially life-threatening; however, the incidence of surgery for small bowel obstruction is unknown, the patient characteristics are poorly described, and the triggers for giving antibiotics with possible influence on complications are unclear. The aims of this study were to fill these gaps to describe the incidence and the characteristics of patients undergoing surgery for small bowel obstruction and to identify triggers for giving antibiotics and the association with postoperative infections.

From July 1, 2014, to July 31, 2015, we included adult patients undergoing surgery for small bowel obstruction at 3 hospitals representing one Danish region. We collected information on patient characteristics, diagnosis, antibiotics, and infectious complications until postoperative day 90 and survival until 1 year.

The 3 hospitals serve a population of 656,353 adults, and treatment is free of charge. A total of 192 patients underwent emergency surgery for small bowel obstruction in % received prophylactic antibiotics triggered by elevated C-reactive protein or bowel resection. We found no association between antibiotic use and infectious complications.
Exposure to vitamin D in early life has been associated with improved bone mineralization, but no studies have investigated the combined effect of pregnancy supplementation and childhood 25(OH)D concentrations on bone health.

We analyzed the effect of serum 25(OH)D concentrations at age 6 months and 6 years and the combined effect with prenatal high-dose vitamin D (2800vs. 400 IU/day) on bone mineral density (BMD) and content (BMC) assessed by dual-energy X-ray absorptiometry (DXA) scans at age 3 and 6 years and longitudinal risk of fractures in a double-blinded, randomized clinical trial in the Copenhagen Prospective Studies on Asthma in Childhood 2010 (COPSAC
) mother-child cohort with enrollment from March 4, 2009, to November 17, 2010, and clinical follow-up until January 31, 2019 (NCT00856947). All participants randomized to intervention and with complete data were included in the analyses.

At age 6 months, serum 25(OH)D concentration was measured in 93% (
=541) of 584 children. Children with sufion with prenatal high-dose vitamin D supplementation reduced the risk of fractures.

The study was supported by The Lundbeck Foundation R16-A1694, The Danish Ministry of Health 903,516, The Danish Council for Strategic Research 0603-00280B and The European Research Council 946,228.
The study was supported by The Lundbeck Foundation R16-A1694, The Danish Ministry of Health 903,516, The Danish Council for Strategic Research 0603-00280B and The European Research Council 946,228.
Low back pain (LBP) is the most common diagnosis responsible for sick leave, long-term disability payments, and early retirements. Studies have suggested that the relatively small proportion of patients referred to a specialist for treatment, either conservative or surgical, accounts for most of the total costs of back pain. However, a complete and long-term picture of the socioeconomic burden associated with these two treatment regimens is lacking.

From a cohort encompassing the entire population in Denmark (5.8 million inhabitants), we identified patients with LBP referred to specialised treatment, either conservative or surgical, during 2007-2016. According to treatment modality, two different cohorts were constructed. Each patient was matched with ten background population controls based on age, sex, region of residency and time of treatment (month and year). Using extensive, nationwide register data, the healthcare costs and loss of productivity from two years before the first intervention until 2018ndicate that measures of successful treatment need to be more nuanced.
The results show that patients referred to specialised treatment of LBP display poor socioeconomic prognosis, regardless of conservative or surgical treatment modality. This development was reinforced in patients undergoing multiple surgeries and was also observed among spouses to the patients. Our findings of substantial loss of productivity across subgroups indicate that measures of successful treatment need to be more nuanced.
Diabetic kidney disease with nephrotic-range proteinuria (NRP) is commonly associated with rapid kidney function loss, increased cardiovascular risk, and premature mortality. We explored the effect of empagliflozin in patients with type 2 diabetes and cardiovascular disease, complicated by presence of this major risk factor for progressive kidney disease, in a
analysis of data from the EMPA-REG OUTCOME trial (NCT01131676).

Cox proportional hazards models were used to investigate the risk of cardiovascular and kidney outcomes in participants with and without NRP, defined by urine albumin-to-creatinine ratio (UACR) ≥2200mg/g at baseline. Annual loss of eGFR during chronic treatment (eGFR slopes) and hypothetical time to projected end-stage kidney disease (ESKD), conditioning upon linearity of eGFR change over time if a patient did not decease before projected ESKD, were calculated using a random-intercept random-coefficient model. Safety was described based on investigator-reported adverse events.

112 low kidney function loss and delay the estimated onset of projected ESKD in patients with type 2 diabetes and cardiovascular disease complicated by NRP.The nomenclatural type material of Rhizophagus intraradices (basionym Glomus intraradices) was originally described from a trap pot culture established with root fragments, subcultures of which later became registered in the INVAM culture collection as FL 208. Subcultures of FL 208 (designated as strain ATT 4) and a new strain, independently isolated from the type location (ATT 1102), were established as both pot cultures with soil-like substrate and in vitro root organ culture. Long-term sampling of these cultures shows spores of the species to have considerable morphological plasticity, not described in the original description. Size, shape and other features of the spores were much more variable than indicated in the protologue. Phylogenetic analyses confirmed earlier published evidence that sequences from all R. intraradices cultures formed a monophyletic clade, well separated from, and not representing a sister clade to, R. irregularis. Moreover, new phylogenetic analyses show that Rhizoglomus venetianum and R. irregularis are synonymous. The morphological characters used to separate these species exemplify the difficulties in species recognition due to the high phenotypic plasticity in the genus Rhizophagus. Rhizophagus intraradices is morphologically re-described, an epitype is designated from a single-spore isolate derived from ATT 4, and R. venetianum is synonymised with R. irregularis.We studied a number of sub-Saharan collections of corticioid Xylodon and Lyomyces species, including several types. Morphological descriptions and molecular analyses based on the ribosomal DNA loci nuc rDNA ITS1-5.8S-ITS2 and when possible nuc 28S rDNA, allow us to introduce four new species L. densiusculus, X. angustisporus, X. dissiliens, and X. laxiusculus. DNA barcodes for X. submucronatus and X. pruniaceus are published for the first time and X. pruniaceus is re-described.Ips subelongatus (Coleoptera, Scolytinae) is an important bark beetle species that infests Larix spp. in Asia. Individuals of this beetle are vectors of ophiostomatoid fungi, on their exoskeletons, that are transmitted to infested trees. In this study, the symbiotic assemblage of ophiostomatoid fungi associated with I. subelongatus in Northeast China was studied. Fungal isolates were identified based on their morphological characters and sequences of ITS, beta-tubulin, elongation factor 1-alpha and calmodulin gene regions. In total, 48 isolates were collected and identified, residing in six taxa. These included a novel species, described here as Ophiostoma gmelinii sp. nov.Polyozellus and Pseudotomentella are two genera of closely related, ectomycorrhizal fungi in the order Thelephorales; the former stipitate and the latter corticioid. Both are widespread in the Northern Hemisphere and many species from both genera seem to be restricted to old growth forest. This study aimed to a) identify genetic regions useful in inferring the phylogenetic relationship between Polyozellus and Pseudotomentella, b) infer this relationship with the regions identified and c) make any taxonomic changes warranted by the result. RPB2, mtSSU and nearly full-length portions of nrLSU and nrSSU were found to be comparatively easy to sequence and provide a strong phylogenetic signal. A STACEY species tree of these three regions revealed that Polyozellus makes Pseudotomentella paraphyletic. As a result, nearly all species currently placed in Pseudotomentella were recombined to Polyozellus. Pseudotomentella larsenii was found to be closer to Tomentellopsis than Polyozellus, but its placement needs further study and it was hence not recombined.Hymenobolus agaves has been reported only in Europe and Africa on the American plant Agave americana (Asparagaceae). This fungus has never been found in the native range of its host, in arid ecosystems of northern and central Mexico and Texas, USA. It has been suggested to be a pathogen that can kill its host. The fungus grows on succulent leaf bases of the plant. The morphology - black apothecia with a hymenium that disintegrates when asci mature and dark ornamented ascospores - make this species very distinctive, but it has been collected and reported only a few times since its first description. Its systematic position has been unclear, and it has been treated as incertae sedis, that is of uncertain placement, in Leotiomycetes. With recent collections and additional data on the ecology of H. agaves, we use integrative taxonomy (DNA sequences, morphology, ecology) to show its relationships is with Cenangiaceae.Soil fungi play a crucial role in soil quality and fertility in being able to break down organic matter but are frequently also observed to play a role as important plant pathogens. As part of a Citizen Science Project initiated by the Westerdijk Fungal Biodiversity Institute and the Utrecht University Museum, which aimed to describe novel fungal species from Dutch garden soil, the diversity of fusarioid fungi (Fusarium and other fusarioid genera), which are members of Nectriaceae (Hypocreales) was investigated. Preliminary analyses of ITS and LSU sequences from more than 4 750 isolates obtained indicated that 109 strains belong to this generic complex. Based on multi-locus phylogenies of combinations of cmdA, tef1, rpb1, rpb2 and tub2 alignments, and morphological characteristics, 25 species were identified, namely 22 in Fusarium and three in Neocosmospora. Furthermore, two species were described as new namely F. vanleeuwenii from the Fusarium oxysporum species complex (FOSC), and F. wereldwijsianum from the Fusarium incarnatum-equiseti species complex (FIESC). Other species encountered in this study include in the FOSC F. curvatum, F. nirenbergiae, F. oxysporum and three undescribed Fusarium spp.; in the FIESC F. clavus, F. croceum, F. equiseti, F. flagelliforme and F. toxicum; Fusarium tricinctum species complex F. flocciferum and F. torulosum; the Fusarium sambucinum species complex F. culmorum and F. graminearum; the Fusarium redolens species complex F. redolens; and the Fusarium fujikuroi species complex F. verticillioides. Three species of Neocosmospora were encountered, namely N. solani, N. stercicola and N. tonkinensis. Although soil fungal diversity has been well studied in the Netherlands, this study revealed two new species, and eight new records F. clavus, F. croceum, F. flagelliforme, F. odoratissimum, F. tardicrescens, F. toxicum, F. triseptatum and N. stercicola.We describe a novel sequestrate genus and species, Asperosporus subterraneus gen. DOTAP chloride clinical trial et sp. link2 nov., found associated with nursery production of ferns in south Florida. This truffle species has a unique combination of morphological characters among described Agaricaceae in that it lacks a stipe or columella, has large, ornamented spores, the fresh sporocarps rapidly stain pink-red when cut or bruised, and they have a rancid smell. Although this fungus does not appear to be a direct plant pathogen, the hyphae of A. subterraneus produce a thick hydrophobic mycelial mat that binds the organic matter and therefore prevents water and fertilizer from being absorbed by plants, consequently causing wilting and chlorosis. Using morphological characteristics and phylogenetic reconstruction based on the internal transcribed spacer (ITS), partial large subunit nuclear ribosomal DNA (LSU), second largest subunit of RNA polymerase II (rpb2) and translation elongation factor 1-alpha (tef1) regions, we describe this taxon as a new genus and species in Agaricaceae.A fungal survey of the Gcwihaba Cave from Botswana found Aspergillus to be one of the more common fungal genera isolated. The 81 Aspergillus strains were identified using CaM sequences and comparing these to a curated reference dataset. Nineteen species were identified representing eight sections (sections Candidi, Circumdati, Flavi, Flavipedes, Nidulantes, Nigri, Terrei and Usti). One strain could not be identified. Morphological characterisation and multigene phylogenetic analyses confirmed it as a new species in section Flavipedes and we introduce it below as A. okavangoensis. The new species is most similar to A. iizukae, both producing conidiophores with vesicles typically wider than 20 μm. The new species, however, does not produce Hülle cells and its colonies grow slower than those of A. iizukae on CYA at 37 °C (14-15 vs 18-21 mm) and CREA (15-16 vs 23-41mm).Hysterangiales (Phallomycetidae, Agaricomycetes, Basidiomycota) is a diverse, nearly cosmopolitan order of predominantly hypogeous, sequestrate, ectomycorrhizal fungi. Expanding on previously published phylogenies, we significantly increased sampling of Hysterangiales specimens, emphasizing representatives from Australia. Using protein-coding genes atp6 (adenosine triphosphate synthase subunit 6) and tef1 (translation elongation factor 1-á), we recovered 26 provisional novel genera, and corroborated existing genera and families. Further, two new suborders (Phallogastrineae subord. nov. link= DOTAP chloride clinical trial and Hysterangineae subord. nov.) and a new family (Phallogastraceae fam. link2 nov.) are described, and three new combinations made to Phallogaster. Aspects of classification and biogeography are presented.The Iodosphaeriaceae is represented by the single genus, Iodosphaeria, which is composed of nine species with superficial, black, globose ascomata covered with long, flexuous, brown hairs projecting from the ascomata in a stellate fashion, unitunicate asci with an amyloid apical ring or ring lacking and ellipsoidal, ellipsoidal-fusiform or allantoid, hyaline, aseptate ascospores. Members of Iodosphaeria are infrequently found worldwide as saprobes on various hosts and a wide range of substrates. Only three species have been sequenced and included in phylogenetic analyses, but the type species, I. phyllophila, lacks sequence data. In order to stabilize the placement of the genus and family, an epitype for the type species was designated after obtaining ITS sequence data and conducting maximum likelihood and Bayesian phylogenetic analyses. Iodosphaeria foliicola occurring on overwintered Alnus sp. leaves is described as new. Five species in the genus form a well-supported monophyletic group, sister to the Pseudosporidesmiaceae in the Xylariales. Selenosporella-like and/or ceratosporium-like synasexual morphs were experimentally verified or found associated with ascomata of seven of the nine accepted species in the genus. Taxa included and excluded from Iodosphaeria are discussed.A smut fungus that hinders wiregrass restoration efforts in longleaf pine-grassland ecosystems was collected from Aristida stricta and A. beyrichiana (Poaceae) in three states in the southeastern USA. Morphological and phylogenetic characteristics of this fungus were examined. These data show that the specimens from both plant species were infected by the same fungus and represent a new species of Langdonia. The new species differs morphologically from other species of Langdonia by teliospores being solitary and not compacted into spore balls. Spore wall ornamentation and teliospore size also differ from other Langdonia species. Phylogenetic analyses of DNA sequences of the ITS, LSU, and EF-1α supported separation of the species from A. stricta and A. beyrichiana from other Langdonia species. Based on these results, a new species, Langdonia walkerae, is proposed.Three new fungal species in the Clavicipitaceae (Hypocreales, Ascomycota) associated with plants were collected in Thailand. Morphological characterisation and phylogenetic analyses based on multi-locus sequences of LSU, RPB1 and TEF1 showed that two species belong to Aciculosporium and Shimizuomyces. Morakotia occupies a unique clade and is proposed as a novel genus in Clavicipitaceae. Shimizuomyces cinereus and Morakotia fusca share the morphological characteristic of having cylindrical to clavate stromata arising from seeds. Aciculosporium siamense produces perithecial plates and occurs on a leaf sheath of an unknown panicoid grass.Three Australian species with sequestrate basidiome forms are recorded for the first time in the genus Lactifluus based on nuclear ITS-LSU and morphological data. These species represent three rare independent evolutionary events resulting in sequestrate basidiomes arising from agaricoid species in three different sections in two subgenera. All three species have highly reduced basidiome forms, and no species with intermediate forms have been found. Lactifluus dendriticus is unique in the genus in having highly branched, dendritic terminal elements in the pileipellis. We provide full descriptions of two species Zelleromyces dendriticus (= Lactifluus dendriticus comb. nov.) in Lactifluus subg. Lactifluus sect. Gerardii, and Lactifluus geoprofluens sp. nov. in Lf. subg. Lactifluus sect. Lactifluus. A reduced description is provided for the third, Lactifluus sp. prov. KV181 in Lf. subg. Pseudogymnocarpi sect. Pseudogymnocarpi, as it is currently known from a single sequence.We describe the first species of Lentinula from Africa, Lentinula madagasikarensis sp. nov. The new taxon, which was collected from central Madagascar, is strikingly similar to L. edodes, the shiitake mushroom. A BLAST search using ITS sequences from L. madagasikarensis as the query retrieves a mix of Lentinula, Gymnopus, Marasmiellus, and other members of Omphalotaceae as the top hits. A 28S phylogeny of the Omphalotaceae confirms placement of L. madagasikarensis within Lentinula. An ITS phylogeny places L. madagasikarensis as the sister group of L. aciculospora, which is a neotropical species. Lentinula madagasikarensis is characterized by robust basidiomata with vinaceous pilei, prominent floccose scales near the pileus margin, florets of sphaeropedunculate cheilocystidia, and subcylindrical basidiospores. This report constitutes a 4 000-mile, trans-oceanic range extension for Lentinula.Deciphering the regulatory network for human naive and primed pluripotency is of fundamental theoretical and applicable significance. Here, by combining quantitative proteomics, phosphoproteomics, and acetylproteomics analyses, we revealed RNA processing and translation as the most differentially regulated processes between naive and primed human embryonic stem cells (hESCs). Although glycolytic primed hESCs rely predominantly on the eukaryotic initiation factor 4E (eIF4E)-mediated cap-dependent pathway for protein translation, naive hESCs with reduced mammalian target of rapamycin complex (mTORC1) activity are more tolerant to eIF4E inhibition, and their bivalent metabolism allows for translating selective mRNAs via both eIF4E-dependent and eIF4E-independent/eIF4A2-dependent pathways to form a more compact naive proteome. Globally up-regulated proteostasis and down-regulated post-translational modifications help to further refine the naive proteome that is compatible with the more rapid cycling of naive hESCs, where CDK1 plays an indispensable coordinative role. These findings may assist in better understanding the unrestricted lineage potential of naive hESCs and in further optimizing conditions for future clinical applications.Antibiotic-associated diarrhea (AAD) affects a significant proportion of patients receiving antibiotics. We sought to understand if differences in the gut microbiome would influence the development of AAD. We administered a 3-day course of amoxicillin-clavulanate to 30 healthy adult volunteers, and analyzed their stool microbiome, using 16S rRNA gene sequencing, at baseline and up to 4 weeks post antibiotic administration. Lower levels of gut Ruminococcaceae were significantly and consistently observed from baseline until day 7 in participants who developed AAD. Overall, participants who developed AAD experienced a greater decrease in microbial diversity. The probability of AAD could be predicted based on qPCR-derived levels of Faecalibacterium prausnitzii at baseline. Our findings suggest that a lack of gut Ruminococcaceae influences development of AAD. Quantification of F. prausnitzii in stool prior to antibiotic administration may help identify patients at risk of AAD, and aid clinicians in devising individualized treatment regimens to minimize such adverse effects.Microbiota-host interaction plays an important role in cancer predisposing, initiation, progression, and response to therapy. Here, we explored the composition of lung tissue microbiota in 143 Chinese patients through conducting 16S rRNA gene sequencing, while TP53 mutation in tumor cells was assessed simultaneously. We found PAH-degrading microbes were more abundant in lung tumor microbiota from smokers. Furthermore, TP53 mutation was more prevalent in smokers, and TP53-mutated tumor harbored more Massilia, as well as Acidovorax that was also capable of degrading PAH. Further analysis showed DNA recombination and repair pathway was enriched in microbiota of smokers, which was convergent to the alteration occurred in tumor cells. Meanwhile, the microbiota of TP53-mutated tumor also exhibited dysregulation of p53 signaling pathway. Our results provided insights into the association of lung commensal microbes with tobacco exposure and host gene mutation, suggesting microbiota and tumor cells might undergo convergent alteration and mutually benefit each other.Mitigating and adapting to climate change requires decarbonizing electricity while ensuring resilience of supply, since a warming planet will lead to greater extremes in weather and, plausibly, in power outages. Although it is well known that long-duration outages severely impact economies, such outages are usually not well characterized or modeled in grid infrastructure planning tools. DOTAP chloride clinical trial Here, we bring together data and modeling techniques and show how they can be used to characterize and model long-duration outages. We illustrate how to integrate outages in planning tools for one promising mode of resilient energy supply-microgrids. Failing to treat these extremes in models can lead to microgrid designs (1) that do not realize their full value of resilience, since models do not see the benefits of protecting against extremes, and (2) that appear reliable on paper yet do not actually protect against extremes. Although utilities record power interruptions, lack of access to that data is hindering research on resilience; making datasets available publicly would substantially aid efforts to improve grid planning tools.Electrocatalysis is an indispensable technique for small-molecule transformations, which are essential for the sustainability of society. Electrocatalysis utilizes electricity as an energy source for chemical reactions. Hydrogen is considered the "fuel for the future," and designing electrocatalysts for hydrogen production has thus become critical. Furthermore, fuel cells are promising energy solutions that require robust electrocatalysts for key fuel cell reactions such as the interconversion of oxygen to water. Concerns regarding the rising concentration of atmospheric carbon dioxide have prompted the search for CO2 conversion methods. One promising approach is the electrochemical conversion of CO2 into commodity chemicals and/or liquid fuels, but such chemistry is highly energy demanding because of the thermodynamic stability of CO2. All of the above-mentioned electrocatalytic processes rely on the selective input of multiple protons (H+) and electrons (e-) to yield the desired products. Biological enzymes evolved in nature to perform such redox catalysis and have inspired the design of catalysts at the molecular and atomic levels. While it is synthetically challenging to mimic the exact biological environment, incorporating functional outer coordination spheres into molecular catalysts has shown promise for advancing multi-H+ and multi-e- electrocatalysis. From this Perspective, herein, catalysts with outer coordination sphere(s) are selected as the inspiration for developing new catalysts, particularly for the reductive conversion of H+, O2, and CO2, which are highly relevant to sustainability. The recent progress in electrocatalysis and opportunities to explore beyond the second coordination sphere are also emphasized.Obesity is known to affect female reproduction, as evidenced by obese patients suffering from subfertility and abnormal oogenesis. However, the underlying mechanisms by which obesity impairs folliculogenesis are poorly documented. Here, we performed comprehensive single-cell transcriptome analysis in both regular diet (RD) and obese mouse models to systematically uncover how obesity affects ovarian follicle cells and their interactions. We found an increased proportion of Inhbb highly expressed granulosa cells (GCs) among all the GC subpopulations in obese mice. Under obese conditions, excessive androgen secreted from endocrine theca cells (ETCs) may contribute to the imbalanced change of GC subtypes through ETCs-GCs interactions. This is alleviated by enzalutamide, an androgen receptor antagonist. We also identified and confirmed typical GC markers, such as Marcks and Prkar2b, for sensitive evaluation of female fertility in obesity. These data represent a resource for studying transcriptional networks and cell-cell interactions during folliculogenesis under physiological and pathological conditions.Autoimmune thyroid disease (AITD) is caused by aberrant activation of the immune system allowing autoreactive B and T cells to target the thyroid gland leading to disease. Although AITD is more frequently diagnosed in adults, children are also affected but rarely studied. Here, we performed phenotypic and functional characterization of peripheral blood immune cells from pediatric and adult-onset AITD patients and age-matched controls using mass cytometry. Major findings indicate that unlike adult-onset AITD patients, pediatric AITD patients exhibit a decrease in anergic B cells (BND) and DN2 B cells and an increase in immature B cells compared to age-matched controls. These results indicate alterations in peripheral blood immune cells seen in pediatric-onset AITD could lead to rapid progression of disease. Hence, this study demonstrates diversity of AITD by showing differences in immune cell phenotypes and function based on age of onset, and may inform future therapies.The mammalian heart beats incessantly with rhythmic mechanical activities generating acids that need to be buffered to maintain a stable intracellular pH (pHi) for normal cardiac function. Even though spatial pHi non-uniformity in cardiomyocytes has been documented, it remains unknown how pHi is regulated to match the dynamic cardiac contractions. Here, we demonstrated beat-to-beat intracellular acidification, termed pHi transients, in synchrony with cardiomyocyte contractions. The pHi transients are regulated by pacing rate, Cl-/HCO3 - transporters, pHi buffering capacity, and β-adrenergic signaling. Mitochondrial electron-transport chain inhibition attenuates the pHi transients, implicating mitochondrial activity in sculpting the pHi regulation. The pHi transients provide dynamic alterations of H+ transport required for ATP synthesis, and a decrease in pHi may serve as a negative feedback to cardiac contractions. Current findings dovetail with the prevailing three known dynamic systems, namely electrical, Ca2+, and mechanical systems, and may reveal broader features of pHi handling in excitable cells.Two-dimensional (2D) van der Waals (vdW) ferromagnets have opened new avenues for manipulating spin at the limits of single or few atomic layers, and for creating unique magneto-exciton devices through the coupling of ferromagnetic (FM) orders and excitons. However, 2D vdW ferromagnets explored so far have rarely possessed exciton behaviors; to date, FM CrI3 have been revealed to show ligand-field photoluminescence correlated with FM ordering, but typically with a broad emission peak. Here, we report a straightforward approach to realize strong coupling of narrow helical emission and FM orders in CrI3 through microsphere cavity. The resonant whispering-gallery modes (WGM) of SiO2 microspheres cause strong oscillation helical emissions with a full width at half-maximum (FWHM) of ∼5 nm under continuous wave excitation. Reversible magnetic coding of helical luminescence is realized in the range of 950-1100 nm. This work enables numerous opportunities for creating magnetic encoding lasing for photonic integrated chips.Rho guanosine triphosphatase (GTPases), as molecular switches, have been identified to be dysregulated and involved in the pathogenesis of various rheumatic diseases, mainly including rheumatoid arthritis, osteoarthritis, systemic sclerosis, and systemic lupus erythematosus. Downstream pathways involving multiple types of cells, such as fibroblasts, chondrocytes, synoviocytes, and immunocytes are mediated by activated Rho GTPases to promote pathogenesis. Targeted therapy via inhibitors of Rho GTPases has been implicated in the treatment of rheumatic diseases, demonstrating promising effects. In this review, the effects of Rho GTPases in the pathogenesis of rheumatic diseases are summarized, and the Rho GTPase-mediated pathways are elucidated. Therapeutic strategies using Rho GTPase inhibitors in rheumatic diseases are also discussed to provide insights for further exploration of targeted therapy in preclinical studies and clinical practice. Future directions on studies of Rho GTPases in rheumatic diseases based on current understandings are provided.The neuropeptide F (NPF) and its short version (sNPF) mediate food- and stress-related responses in solitary insects. In the honeybee, a social insect where food collection and defensive responses are socially regulated, only sNPF has an identified receptor. Here we increased artificially sNPF levels in honeybee foragers and studied the consequences of this manipulation in various forms of appetitive and aversive responsiveness. Increasing sNPF in partially fed bees turned them into the equivalent of starved animals, enhancing both their food consumption and responsiveness to appetitive gustatory and olfactory stimuli. Neural activity in the olfactory circuits of fed animals was reduced and could be rescued by sNPF treatment to the level of starved bees. In contrast, sNPF had no effect on responsiveness to nociceptive stimuli. Our results thus identify sNPF as a key modulator of hunger and food-related responses in bees, which are at the core of their foraging activities.The most efficient light-harvesting antennae found in nature, chlorosomes, are molecular tubular aggregates (TMAs) assembled by pigments without protein scaffolds. Here, we discuss a classification of chlorosomes as a unique tubular plastic crystal and we attribute the robust energy transfer in chlorosomes to this unique nature. To systematically study the role of supramolecular tube chirality by molecular simulation, a role that has remained unresolved, we share a protocol for generating realistic tubes at atomic resolution. We find that both the optical and the mechanical behavior are strongly dependent on chirality. The optical-chirality relation enables a direct interpretation of experimental spectra in terms of overall tube chirality. The mechanical response shows that the overall chirality regulates the hardness of the tube and provides a new characteristic for relating chlorosomes to distinct chirality. Our protocol also applies to other TMA systems and will inspire other systematic studies beyond lattice models.The rapid development and spread of antibiotic resistance necessitate the development of novel strategies for antibiotic discovery. Symbah-1, a synthetic peptide antibiotic, was identified in a high-throughput antibacterial screen of random peptide sequences. Symbah-1 functions through membrane disruption and contains broad spectrum bactericidal activity against several drug-resistant pathogens. Circular dichroism and high-resolution mass spectrometry indicate symbah-1 has a β-hairpin structure induced by lipopolysaccharide and is cyclized via an intramolecular disulfide bond. Together these data classify symbah-1 as an uncommon synthetic member of the β-hairpin antimicrobial peptide class. Symbah-1 displays low hemolysis but loses activity in human serum. Characterization of a symbah-1 peptide library identified two variants with increased serum activity and protease resistance. The method of discovery and subsequent characterization of symbah-1 suggests large synthetic peptide libraries bias toward macrocyclic β-hairpin structure could be designed and screened to rapidly expand and better understand this rare peptide antibiotic class.Thousands of biomedical scientific articles, including those describing genes associated with human diseases, are published every week. Computational methods such as text mining and machine learning algorithms are now able to automatically detect these associations. In this study, we used a cognitive computing text-mining application to construct a knowledge network comprising 3,723 genes and 99 diseases. We then tracked the yearly changes on these networks to analyze how our knowledge has evolved in the past 30 years. Our systems approach helped to unravel the molecular bases of diseases and detect shared mechanisms between clinically distinct diseases. It also revealed that multi-purpose therapeutic drugs target genes that are commonly associated with several psychiatric, inflammatory, or infectious disorders. By navigating this knowledge tsunami, we were able to extract relevant biological information and insights about human diseases.Glucose-responsive ATP-sensitive potassium channels (KATP) are expressed in a variety of tissues including nervous systems. The depolarization of the membrane potential induced by glucose may lead to hyperexcitability of neurons and induce excitotoxicity. However, the roles of KATP in the peripheral nervous system (PNS) are poorly understood. Here, we determine the roles of KATP in the PNS using KATP-deficient (Kir6.2-deficient) mice. We demonstrate that neurite outgrowth of dorsal root ganglion (DRG) neurons was reduced by channel closers sulfonylureas. However, a channel opener diazoxide elongated the neurite. KATP subunits were expressed in mouse DRG, and expression of certain subunits including Kir6.2 was increased in diabetic mice. In Kir6.2-deficient mice, the current perception threshold, thermal perception threshold, and sensory nerve conduction velocity were impaired. Electron microscopy revealed a reduction of unmyelinated and small myelinated fibers in the sural nerves. In conclusion, KATP may contribute to the development of peripheral neuropathy.Natural control of HIV-1 is a characteristic of less then 1% of HIV-1-infected individuals, so called elite controllers (EC). In this study, we sought to identify signaling pathways associated with the EC phenotype using integrative proteo-transcriptomic analysis and immunophenotyping. We found HIF signaling and glycolysis as specific traits of the EC phenotype together with dysregulation of HIF target gene transcription. A higher proportion of HIF-1α and HIF-1β in the nuclei of CD4+ and CD8+ T cells in the male EC were observed, indicating a potential increased activation of the HIF signaling pathway. Furthermore, intracellular glucose levels were elevated in EC even as the surface expression of the metabolite transporters Glut1 and MCT-1 were decreased on lymphocytes indicative of unique metabolic uptake and flux profile. Combined, our data show that glycolytic modulation and altered HIF signaling is a unique feature of the male EC phenotype that may contribute to natural control of HIV-1.The RecQ family of helicases are important for maintenance of genomic integrity. Although functions of constructive subdomains of this family of helicases have been extensively studied, the helical hairpin (HH) in the RecQ-C-terminal domain (RQC) has been underappreciated and remains poorly understood. Here by using single-molecule fluorescence resonance energy transfer, we found that HH in the human BLM transiently intercepts different numbers of nucleotides when it is unwinding a double-stranded DNA. Single-site mutations in HH that disrupt hydrogen bonds and/or salt bridges between DNA and HH change the DNA binding conformations and the unwinding features significantly. Our results, together with recent clinical tests that correlate single-site mutations in HH of human BLM with the phenotype of cancer-predisposing syndrome or Bloom's syndrome, implicate pivotal roles of HH in BLM's DNA unwinding activity. Similar mechanisms might also apply to other RecQ family helicases, calling for more attention to the RQC helical hairpin.Interleukin-32 (IL-32) is a nonclassical cytokine expressed in cancers, inflammatory diseases, and infections. Its expression is regulated by two different oxygen sensing systems; HIF1α and cysteamine dioxygenase (ADO), indicating that IL-32 may be involved in the response to hypoxia. We here demonstrate that endogenously expressed, intracellular IL-32 interacts with components of the mitochondrial respiratory chain and promotes oxidative phosphorylation. Knocking out IL-32 in three myeloma cell lines reduced cell survival and proliferation in vitro and in vivo. High-throughput transcriptomic and MS-metabolomic profiling of IL-32 KO cells revealed that cells depleted of IL-32 had perturbations in metabolic pathways, with accumulation of lipids, pyruvate precursors, and citrate. IL-32 was expressed in a subgroup of myeloma patients with inferior survival, and primary myeloma cells expressing IL-32 had a gene signature associated with immaturity, proliferation, and oxidative phosphorylation. In conclusion, we demonstrate a previously unrecognized role of IL-32 in the regulation of plasma cell metabolism.Coordination between osteogenesis and angiogenesis is required for bone homeostasis. Here, we show that miR-29cb2 is a bone-specific miRNA and plays critical roles on angiogenesis-osteogenesis coupling during bone remodeling. Mice with deletion of miR-29cb2 exhibit osteopenic phenotypes and osteoblast impairment, accompanied by pronounced decreases in specific H vessels. The decrease in bone miR-29cb2 was associated with pathological ovariectomy stimuli. Mechanistically, hypoxia-inducible factor (HIF)-3α, as a target for miR-29cb2, inhibits HIF-1α activity by competitively bonding with HIF-1β. Notably, miR-29cb2 in peripheral blood (PB) nearly is undetectable in sham and significantly increases in ovariectomy mice. Further evaluation from osteoporosis patients demonstrates similar signatures. ROC analysis shows miR-29cb2 in PB has higher sensitivity and specificity for diagnosing osteoporosis when compared with four clinical biomarkers. Collectively, these findings reveal that miR-29cb2 is essential for bone remodeling by inhibiting HIF-3α and elevated bone-specific miR-29cb2 in PB, which may be a promising biomarker for bone loss.Isolation of long-term hematopoietic stem cell (HSC) is possible by utilizing flow cytometry with multiple cell surface markers. However, those cell surface phenotypes do not represent functional HSCs after in vitro culture. Here we show that cultured HSCs express mast cell-related genes including Cd244. After in vitro culture, phenotypic HSCs were divided into CD244- and CD244+ subpopulations, and only CD244- cells that have low mast cell gene expression and maintain HSC-related genes sustain reconstitution potential. The result was same when HSCs were cultured in an efficient expansion medium containing polyvinyl alcohol. Chemically induced endoplasmic reticulum (ER) stress signal increased the CD244+ subpopulation, whereas ER stress suppression using a molecular chaperone, TUDCA, decreased CD244+ population, which was correlated to improved reconstitution output. These data suggest CD244 is a potent marker to exclude non-functional HSCs after in vitro culture thereby useful to elucidate mechanism of functional decline of HSCs during ex vivo treatment.We introduce techniques for probing the dynamics of triplet states. We employ these tools, along with conventional techniques, to develop a detailed understanding of a complex chemical system a negative-tone, radical photoresist for multiphoton absorption polymerization in which isopropylthioxanthone (ITX) is the photoinitiator. This work reveals that the same color of light used for the 2-photon excitation of ITX, leading to population of the triplet manifold through intersystem crossing, also depletes this triplet population via linear absorption followed by reverse intersystem crossing (RISC). Using spectroscopic tools and kinetic modeling, we identify the reactive triplet state and a non-reactive reservoir triplet state. We present compelling evidence that the deactivation channel involves RISC from an excited triplet state to a highly vibrationally excited level of the electronic ground state. The work described here offers the enticing possibility of understanding, and ultimately controlling, the photochemistry and photophysics of a broad range of triplet processes.Hybrid lead halide ABX3 perovskite solar cells (PSCs) have emerged as a strong competitor to the traditional solar cells with a certified power conversion efficiency beyond 25% and other remarkable features such as light weight, solution processability, and low manufacturing cost. Further development on the efficiency and stability brings forth increasing attention in the component regulation, such as partial or entire substitution of A/B/X sites by alternative elements with similar size. However, the relationships between composition, property, and performance are poorly understood. Here, the instability of PSCs from the photon-, moisture-, thermal-, and mechanical-induced degradation was first summarized and discussed. In addition, the component regulation from the A/X sites is highlighted from the aspects of band level alignment, charge-carrier dynamics, ion migration, crystallization behavior, residual strain, stoichiometry, and dimensionality control. Finally, the perspectives and future outlooks are highlighted to guide the rational design and practical application of PSCs.Atomically thin two-dimensional (2D) metal oxides exhibit unique optical, electrical, magnetic, and chemical properties, rendering them a bright application prospect in high-performance smart devices. Given the large variety of both layered and non-layered 2D metal oxides, the controllable synthesis is the critical prerequisite for enabling the exploration of their great potentials. In this review, recent progress in the synthesis of 2D metal oxides is summarized and categorized. link3 Particularly, a brief overview of categories and crystal structures of 2D metal oxides is firstly introduced, followed by a critical discussion of various synthesis methods regarding the growth mechanisms, advantages, and limitations. Finally, the existing challenges are presented to provide possible future research directions regarding the synthesis of 2D metal oxides. This work can provide useful guidance on developing innovative approaches for producing both 2D layered and non-layered nanostructures and assist with the acceleration of the research of 2D metal oxides.Natural fiber reinforced composites (FRC) are of great interests, because of their biodegradability, recyclability, and environmental benefits over synthetic FRC. Natural jute FRC could provide an environmentally sustainable, light weight, and cost-effective alternative to synthetic FRC. However, the application of natural jute FRC is limited because of their poor mechanical and interfacial properties. Graphene and its derivatives could potentially be applied to modify jute fiber surface for manufacturing natural FRC with excellent mechanical properties, and lower environmental impacts. Here, we review the physical and chemical treatments, and graphene-based modifications of jute fibers, and their effect on mechanical properties of jute FRC. We introduce jute fiber structure, chemical compositions, and their potential applications first. We then provide an overview of various surface treatments used to improve mechanical properties of jute FRC. We discuss and compare various graphene derivative-based surface modifications of jute fibers, and their impact on the performance of FRC. Finally, we provide our future perspective on graphene-based jute fibers research to enable next generation strong and sustainable FRC for high performance engineering applications without conferring environmental problems.Recently, as an elementary material, tellurium (Te) has received widespread attention for its high carrier mobility, intriguing topological properties, and excellent environmental stability. However, it is difficult to obtain two-dimensional (2D) Te with high crystalline quality owing to its intrinsic helical chain structure. Herein, a facile strategy for controllable synthesis of high-quality 2D Te nanoflakes through chemical vapor transport in one step is reported. With carefully tuning the growth kinetics determined mainly by temperature, tellurium nanoflakes in lateral size of up to ∼40 μm with high crystallinity can be achieved. We also investigated the second harmonic generation of Te nanoflakes, which demonstrates that it can be used as frequency doubling crystals and has potential applications in nonlinear optical devices. In addition, field effect transistor devices based on the 2D Te nanoflakes were fabricated and exhibited excellent electrical properties with high mobility of 379 cm2 V-1 s-1.The HIV-1 capsid is the target for the antiviral drugs GS-CA1 and Lenacapavir (GS-6207). We investigated the mechanism by which GS-CA1 and GS-6207 inhibit HIV-1 infection. HIV-1 inhibition by GS-CA1 did not require CPSF6 in CD4+ T cells. Contrary to PF74 that accelerates uncoating of HIV-1, GS-CA1 and GS-6207 stabilized the core. GS-CA1, unlike PF74, allowed the core to enter the nucleus, which agrees with the fact that GS-CA1 inhibits infection after reverse transcription. Unlike PF74, GS-CA1 did not disaggregate preformed CPSF6 complexes in nuclear speckles, suggesting that PF74 and GS-CA1 have different mechanisms of action. GS-CA1 stabilized the HIV-1 core, possibly by inducing a conformational shift in the core; in agreement, HIV-1 cores bearing N74D regained their ability to bind CPSF6 in the presence of GS-CA1. We showed that GS-CA1 binds to the HIV-1 core, changes its conformation, stabilizes the core, and thereby prevents viral uncoating and infection.Chronic graft-versus-host disease (cGVHD) targets include the oral mucosa and salivary glands after allogeneic hematopoietic stem cell transplant (HSCT). Without incisional biopsy, no diagnostic test exists to confirm oral cGVHD. Consequently, therapy is often withheld until severe manifestations develop. This proteomic study examined saliva and human salivary gland for a biomarker profile at first onset of oral cGVHD prior to initiation of topical steroid therapy. Whole saliva collected at onset of biopsy-proven oral GVHD was assessed using liquid chromatography-coupled tandem mass spectrometry with identification of 569 proteins, of which 77 significantly changed in abundance. ZG16B, a secretory lectin protein, was reduced 2-fold in oral cGVHD saliva (p less then 0.05), and significantly decreased in salivary gland secretory cells affected by cGVHD. Single-cell RNA-seq analysis of healthy MSG localized ZG16B expression to two discrete acinar cell populations. Reduced ZG16B expression may indicate specific cGVHD activity and possibly general salivary gland dysfunction.Segmentation and tagmatization have contributed to the preeminent success of arthropods since their first appearance in the Cambrian. However, the exact mechanism of segmentogenesis is still insufficiently known in living and extinct groups. Here, we describe the postembryonic development of a Waptiid arthropod Chuandianella ovata from the early Cambrian Chengjiang biota, South China. The new data illuminate a complex dynamic pattern of anamorphosis and epimorphosis, and a three-step process of segmentogenesis, i.e., the elongation of the terminal segment, delineation of an incipient segment, and full separation of a new segment. Compensatory growth is accomplished by rapid growth of new segments and/or generation of additional segments, which results in the trimorphism of the posterior tagma. Such complex developmental dynamics has rarely been known in the arthropod fossil record and its presence in early history helps to understand the rapid diversification of arthropods in the early Cambrian.The 30+ unique ligands of the TGFβ family signal by forming complexes using different combinations of type I and type II receptors. Therapeutically, the extracellular domain of a single receptor fused to an Fc molecule can effectively neutralize subsets of ligands. Increased ligand specificity can be accomplished by using the extracellular domains of both the type I and type II receptor to mimic the naturally occurring signaling complex. Here, we report the structure of one "type II-type I-Fc" fusion, ActRIIB-Alk4-Fc, in complex with two TGFβ family ligands, ActA, and GDF11, providing a snapshot of this therapeutic platform. link3 The study reveals that extensive contacts are formed by both receptors, replicating the ternary signaling complex, despite the inherent low affinity of Alk4. Our study shows that low-affinity type I interactions support altered ligand specificity and can be visualized at the molecular level using this platform.HIV-specific T cells have diminished effector function and fail to control/eliminate the virus. IL-27, a member of the IL-6/IL-12 cytokine superfamily has been shown to inhibit HIV replication. However, whether or not IL-27 can enhance HIV-specific T cell function is largely unknown. In the present manuscript, we investigated the role of IL-27 signaling in human T cells by evaluating the global transcriptional changes related to the function of HIV-specific T cells. We found that T cells from people living with HIV (PLWH), expressed higher levels of STAT1 leading to enhanced STAT1 activation upon IL-27 stimulation. Observed IL-27 induced transcriptional changes were associated with IFN/STAT1-dependent pathways in CD4 and CD8 T cells. Importantly, IL-27 dependent modulation of T-bet expression promoted IFNγ secretion by TIGIT+HIVGag-specific T cells. This new immunomodulatory effect of IL-27 on HIV-specific T cell function suggests its potential therapeutic use in cure strategies.
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