Notes

TGF-β hang-up could get over cancer primary resistance to PD-1 restriction: A mathematical model.
Comparing pre- and post-COVID-19 period, we observed a significant increase in the rate of DKA (37.5%-49.4%, p < .0001). The fraction of moderate (+5.4%) and severe (+3.4%) DKA cases increased significantly (p=.0089), and more episodes required assisted ventilation (+2.1%, p=.0337). Two episodes of DKA during 2020/2021 period were fatal. By region, change in DKA frequency correlated with initial COVID-19 death toll (March/April 2020) (R=.6, p=.0287) and change in T1D incidence (R=.7, p=.0080).

The clinical picture of new-onset children T1D in Poland deteriorated over a 2-year period. The observed increase in the frequency of DKA and its severity were significantly associated with the overlapping timing of the COVID-19 epidemic.
The clinical picture of new-onset children T1D in Poland deteriorated over a 2-year period. The observed increase in the frequency of DKA and its severity were significantly associated with the overlapping timing of the COVID-19 epidemic.Sensitivity and speed of detection are contradicting demands that profoundly impact the electrical sensing of molecular biomarkers. Although single-molecule sensitivity can now be achieved with single-nanotube field-effect transistors, these tiny sensors, with a diameter less than 1 nm, may take hours to days to capture the molecular target at trace concentrations. Here, we show that this sensitivity-speed challenge can be addressed using covalently functionalized double-wall CNTs that form many individualized, parallel pathways between two electrodes. Each carrier that travels across the electrodes is forced to take one of these pathways that are fully gated chemically by the target-probe binding events. This sensor design allows us to electrically detect Lyme disease oligonucleotide biomarkers directly at the physiological high-salt concentrations, simultaneously achieving both ultrahigh sensitivity (as low as 1 fM) and detection speed ( less then 15 s). This unexpectedly simple strategy may open opportunities for sensor designs to broadly achieve instant detection of trace biomarkers and real-time probing of biomolecular functions directly at their physiological states.Isomers with minimal structural dissimilarities are promising research objects to obtain a comprehensive understanding of structure-property relationships; however, comparability of isomeric structures is a prerequisite. Herein, two quasi-structurally isomeric 13-nuclei copper nanoclusters (Cu NCs) (Cu13a and Cu13b) containing highly similar Cu13 kernels and different arrangements of peripheral ligands were obtained using a solvent-induced strategy. The exotic chloride ion is shown to play a prominent role in inducing the selective formation of two quasi-isomers, where the comparative study to establish a structure-property relationship was realized. Due to the charge transition from chlorine to the copper core (X(Cl)M(Cu)CT), the molecular oxygen activation of Cu13a showed higher singlet oxygen (1O2) and lower superoxide radical (O2•-) yields compared to those of Cu13b, which gives it better catalytic selectivity for the 1O2 involved selective oxidation of sulfides. The present work not only offers a controllable strategy for the rational design and synthesis of quasi-structurally isomeric Cu NCs but also provides a pathway to boost catalytic selectivity by a halogen to metal core charge transition.Wild birds are known to harbor and discharge antibiotic-resistant bacteria (ARB) and their associated antibiotic resistance genes (ARGs). However, assessments of their contribution to the dissemination of antibiotic resistance in the environment are limited to culture-dependent bacterial snapshots. Here, we present a high-throughput sequencing study that corroborates extensive ARG exchange between wild bird feces and their habitats and implies the need to scrutinize high-mobility birds as potential vectors for global propagation of ARGs. We characterized the resistome (281 ARGs) and microbiome of seven wild bird species and their terrestrial and aquatic habitats. The resistomes of bird feces were influenced by the microbial community structure, mobile genetic elements (MGEs), and residual antibiotics. We designated 33 ARGs found in more than 90% of the bird fecal samples as core ARGs of wild bird feces, among which 16 ARGs were shared as core ARGs in both wild bird feces and their habitats; these genes represent a large proportion of both the bird feces (35.0 ± 15.9%) and the environmental resistome (29.9 ± 21.4%). One of the most detected β-lactam resistance genes (blaTEM, commonly harbored by multidrug resistant "superbugs") was used as molecular marker to demonstrate the high interconnectivity of ARGs between the microbiomes of wild birds and their habitats. Overall, this work provides a comprehensive analysis of the wild bird resistome and underscores the importance to consider genetic exchange between animals and the environment in the One Health approach.Robust capuchin monkeys (Sapajus spp.) are distributed widely in the Neotropics and may be able to survive in modified landscapes because of their omnivorous, opportunistic diet. The poorly known and endangered crested capuchin monkey (Sapajus robustus) is endemic to the Atlantic Forest in Bahia, Minas Gerais and Espírito Santo states, Brazil. We collected data on diet and home range for a crested capuchin group with access to forest and cultivated areas. We hypothesized that with access to cultivated exotic fruit, capuchins would use cultivated areas more for feeding during the season of fruit scarcity in the surrounding forest and have a small home range size because of higher fruit availability. Both the forest and the cultivated areas peaked in fruit availability in the wet season, with a low proportion of trees producing fruit in the dry season; cultivated areas had a higher proportion of trees in fruit compared to the forest throughout the study. While monkeys consumed exotic fruits like jackfruit and oil palm, we recorded more samples of them eating forest fruits than exotic fruits in all but 1 month, and they consumed a more diverse array of forest fruits (56 species) but only six exotic species. Home range size was relatively small compared with other studies 120.5 ha across the year (wet season 102 ha, dry season 111.5 ha). Natural and human-intensified fruit sources in a protected area without hunting may have allowed monkeys to maintain a smaller home range size. The group composition changed during the study; this also likely influenced home range use. Studies focused on robust capuchin groups that utilize agricultural or cultivated foods may underestimate home range needs for groups without access to human-intensified food sources. Studying crested capuchin ecology in additional locations will be important for establishing a sound species conservation program.NMR spectroscopy is a powerful tool to investigate molecular structure and dynamics. The poor sensitivity of this technique, however, limits its ability to tackle questions requiring dilute samples. Low-concentration photochemically induced dynamic nuclear polarization (LC-photo-CIDNP) is an optically enhanced NMR technology capable of addressing the above challenge by increasing the detection limit of aromatic amino acids in solution up to 1000-fold, either in isolation or within proteins. Here, we show that the absence of NMR-active nuclei close to a magnetically active site of interest (e.g., the structurally diagnostic 1Hα-13Cα pair of amino acids) is expected to significantly increase LC-photo-CIDNP hyperpolarization. Then, we exploit the spin-diluted tryptophan isotopolog Trp-α-13C-β,β,2,4,5,6,7-d7 and take advantage of the above prediction to experimentally achieve a ca 4-fold enhancement in NMR sensitivity over regular LC-photo-CIDNP. This advance enables the rapid (within seconds) detection of 20 nM concentrations or the molecule of interest, corresponding to a remarkable 3 ng detection limit. Finally, the above Trp isotopolog is amenable to incorporation within proteins and is readily detectable at a 1 μM concentration in complex cell-like media, including Escherichia coli cell-free extracts.Periodontal disease is a major threat to oral health and would further contribute to systemic diseases without timely control. We aimed to evaluate the relation between periodontal disease, periodontal treatment and carotid intima-media thickness (CIMT) based on available epidemiological and clinical evidence. PubMed and Scopus were searched for relevant studies through May 2021. Observational studies reporting risk estimates with 95% confidence intervals (95% CIs) for the association between periodontal disease (including periodontitis and gingivitis) and risk of increased CIMT (defined as CIMT value that exceeded the cut-off value of clinical and prognostic significance), as well as interventional studies providing mean values with standard deviations of CIMT before and after periodontal intervention, were included. Random-effect models for meta-analysis were used to calculate the summary effect estimates with 95% CIs. A total of 406 citations were retrieved from electronic databases and 45 full-text articles were screened, leaving 11 articles using ultrasound to measure CIMT with 8744 participants included. Pooled results of seven cross-sectional studies involving 8558 participants indicated that compared to those without periodontitis, patients with periodontitis and those with severe periodontitis had an odds ratio of 1.42 (95% CI 1.16, 1.75) and 1.70 (95% CI 1.24, 2.33) for increased CIMT, respectively. Although publication bias was detected in these results, odds ratios corrected by the trim-and-fill method were still statistically significant. Results of four non-randomized controlled trials with 186 patients suggested that periodontal intervention may help reduce CIMT in patients with periodontal disease in the short term. Periodontitis, especially severe periodontitis, was significantly associated with the risk of increased CIMT. Periodontal intervention might help slow the progression of carotid intima-media thickening in patients with periodontal disease in the short term.Constrained density functional theory (CDFT) is a powerful tool for the prediction of electron transfer parameters in condensed phase simulations at a reasonable computational cost. In this work we present an extension to CDFT in the popular mixed Gaussian/plane wave electronic structure package CP2K, implementing the additional force terms arising from a constraint based on Hirshfeld charge partitioning. This improves upon the existing Becke partitioning scheme, which is prone to give unphysical atomic charges. We verify this implementation for a variety of systems electron transfer in (H2O)2+ in a vacuum, electron tunnelling between oxygen vacancy centers in solid MgO, and electron self-exchange in aqueous Ru2+-Ru3+. We find good agreement with previous plane-wave CDFT results for the same systems, but at a significantly lower computational cost, and we discuss the general reliability of condensed phase CDFT calculations.We report a mechanistic investigation of calcium bistriflimide-mediated sulfur(VI)-fluoride exchange (SuFEx) between sulfonyl fluorides and amines. We determine the likely pre-activation resting state─a calcium bistriflimide complex with ligated amines─thus allowing for corroborated calculation of the SuFEx activation barrier at ∼21 kcal/mol, compared to 21.5 ± 0.14 kcal/mol derived via kinetics experiments. Transition state analysis revealed (1) a two-point calcium-substrate contact that activates the sulfur(VI) center and stabilizes the leaving fluoride and (2) a 1,4-diazabicyclo[2.2.2]octane additive that provides Brønsted-base activation of the nucleophilic amine. CX-5461 datasheet Stable Ca-F complexes upon sulfonamide formation are likely contributors to inhibited catalytic turnover, and a proof-of-principle redesign provided evidence that sulfonamide formation is feasible with 10 mol % calcium bistriflimide.
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