Notes

Changes in perioperative medicine.
Although IL-9 has potent anti-tumor activity in adoptive cell transfer therapy, some models suggest that it can promote tumor growth. Here, we show that IL-9 signaling is associated with poor outcomes in patients with various forms of lung cancer, and is required for lung tumor growth in multiple mouse models. CD4+ T cell-derived IL-9 promotes the expansion of both CD11c+ and CD11c- interstitial macrophage populations in lung tumor models. Mechanistically, the IL-9/macrophage axis requires arginase 1 (Arg1) to mediate tumor growth. Indeed, adoptive transfer of Arg1+ but not Arg1- lung macrophages to Il9r-/- mice promotes tumor growth. Moreover, targeting IL-9 signaling using macrophage-specific nanoparticles restricts lung tumor growth in mice. Lastly, elevated expression of IL-9R and Arg1 in tumor lesions is associated with poor prognosis in lung cancer patients. Thus, our study suggests the IL-9/macrophage/Arg1 axis is a potential therapeutic target for lung cancer therapy.Lipid metabolism plays an instructive role in regulating stem cell state and differentiation. However, the roles of lipid mobilization and utilization in stem cell-driven regeneration are unclear. Planarian flatworms readily restore missing tissue due to injury-induced activation of pluripotent somatic stem cells called neoblasts. Here, we identify two intestine-enriched orthologs of apolipoprotein b, apob-1 and apob-2, which mediate transport of neutral lipid stores from the intestine to target tissues including neoblasts, and are required for tissue homeostasis and regeneration. Inhibition of apob function by RNAi causes head regression and lysis in uninjured animals, and delays body axis re-establishment and regeneration of multiple organs in amputated fragments. Furthermore, apob RNAi causes expansion of the population of differentiating neoblast progeny and dysregulates expression of genes enriched in differentiating and mature cells in eight major cell type lineages. We conclude that intestine-derived lipids serve as a source of metabolites required for neoblast progeny differentiation.Despite aerobic activity requiring up to tenfold increases in air intake, human populations in high-altitude hypoxic environments can sustain high levels of endurance physical activity. While these populations generally have relatively larger chest and lung volumes, how thoracic motions actively increase ventilation is unknown. Here we show that rib movements, in conjunction with chest shape, contribute to ventilation by assessing how adulthood acclimatization, developmental adaptation, and population-level adaptation to high-altitude affect sustained aerobic activity. We measured tidal volume, heart rate, and rib-motion during walking and running in lowland individuals from Boston (~ 35 m) and in Quechua populations born and living at sea-level (~ 150 m) and at high altitude (> 4000 m) in Peru. We found that Quechua participants, regardless of birth or testing altitudes, increase thoracic volume 2.0-2.2 times more than lowland participants (p  less then  0.05). Further, Quechua individuals from hypoxic environments have deeper chests resulting in 1.3 times greater increases in thoracic ventilation compared to age-matched, sea-level Quechua (p  less then  0.05). Thus, increased thoracic ventilation derives from a combination of acclimatization, developmental adaptation, and population-level adaptation to aerobic demand in different oxygen environments, demonstrating that ventilatory demand due to environment and activity has helped shape the form and function of the human thorax.Developing highly active and durable electrocatalysts for acidic oxygen evolution reaction remains a great challenge due to the sluggish kinetics of the four-electron transfer reaction and severe catalyst dissolution. Here we report an electrochemical lithium intercalation method to improve both the activity and stability of RuO2 for acidic oxygen evolution reaction. The lithium intercalates into the lattice interstices of RuO2, donates electrons and distorts the local structure. Therefore, the Ru valence state is lowered with formation of stable Li-O-Ru local structure, and the Ru-O covalency is weakened, which suppresses the dissolution of Ru, resulting in greatly enhanced durability. Meanwhile, the inherent lattice strain results in the surface structural distortion of LixRuO2 and activates the dangling O atom near the Ru active site as a proton acceptor, which stabilizes the OOH* and dramatically enhances the activity. This work provides an effective strategy to develop highly efficient catalyst towards water splitting.The aim of this study was to determine the properties and quality characteristics of hair and cashmere fibres of three goat breeds raised in Southwest China, namely; Dazu black goat (DBG, n = 203; ♂99, ♀104), Inner Mongolia cashmere goat (IMCG, n = 65; 21♂, 44♀) and their first cross (F1, n = 79; 39♂, 40♀). Totals of 5219, 2130 and 2981 fibre samples, from the three breeds respectively, were taken prior to shearing at 32.5 ± 01.25 months of age from four body sites; shoulder, side-portion, abdomen and leg. Breed effect was significant (P  0.01) for IMCG. IMCG recorded the longest value for cashmere lengths followed by DBG, while F1 recorded the lowest (P = 0.001), whilst F1 recorded the biggest (P = 0.001) diameter whereas no differences existed between parents' breeds. The cortical cell lengths of IMCG and DBG were 94.57 and 86.85 μm without significant difference detected between breeds. Differences between hair length and diameter for body sites of the studied goat breeds were significant (P  less then  0.01) but between whiteness, cashmere diameter and diameter of cortical cells were not. Sex had no significant effect on all hair/cashmere properties. Quality characteristics of cashmere fibres from IMCG and F1 were better (P  less then  0.001) than from DBG. Leg hair diameter, curl recovery rate and cashmere diameter were superior in the crossbred F1 compared to pure breed parents, and DBG was superior to IMCG for fibre elasticity and intensity traits. FGF-5 gene was detected as a candidate gene for hair and cashmere traits in IMCG breed. Whilst, KIT gene was found to be associated with coat colour in the studied breeds. NSC 23766 Extra investigations to examine more cashmere goat breeds and crosses are needed to discover genetic variability in cashmere production locally and worldwide.The COVID-19 pandemic triggered the development of numerous diagnostic tools to monitor infection and to determine immune response. Although assays to measure binding antibodies against SARS-CoV-2 are widely available, more specific tests measuring neutralization activities of antibodies are immediately needed to quantify the extent and duration of protection that results from infection or vaccination. We previously developed a 'Serological Assay based on a Tri-part split-NanoLuc® (SATiN)' to detect antibodies that bind to the spike (S) protein of SARS-CoV-2. Here, we expand on our previous work and describe a reconfigured version of the SATiN assay, called Neutralization SATiN (Neu-SATiN), which measures neutralization activity of antibodies directly from convalescent or vaccinated sera. The results obtained with our assay and other neutralization assays are comparable but with significantly shorter preparation and run time for Neu-SATiN. As the assay is modular, we further demonstrate that Neu-SATiN enables rapid assessment of the effectiveness of vaccines and level of protection against existing SARS-CoV-2 variants of concern and can therefore be readily adapted for emerging variants.Phosphorus (P) is an essential element for all organisms. Because P fertilizers are a non-renewable resource and high fixation in soils, sustainable agriculture requires researchers to improve crop P acquisition efficiency. Here, we report a strong association signal at a locus of CPU1 (component of phosphorus uptake 1), from a genome-wide association study of P acquisition efficiency in a soybean core collection grown in the field. A SEC12-like gene, GmPHF1, is identified as the causal gene for CPU1. GmPHF1 facilitates the ER (endoplasmic reticulum) exit of the phosphate transporter, GmPT4, to the plasma membrane of root epidermal cells. A common SNP in an upstream open reading frame (uORF) of GmPHF1, which alters the abundance of GmPHF1 in a tissue-specific manner, contributes to P acquisition diversity in soybean. A natural genetic variation conditions diversity in soybean P acquisition, which can be used to develop P-efficient soybean genotypes.Folded proteins are assumed to be built upon fixed scaffolds of secondary structure, α-helices and β-sheets. Experimentally determined structures of >58,000 non-redundant proteins support this assumption, though it has recently been challenged by ~100 fold-switching proteins. Though ostensibly rare, these proteins raise the question of how many uncharacterized proteins have shapeshifting-rather than fixed-secondary structures. Here, we use a comparative sequence-based approach to predict fold switching in the universally conserved NusG transcription factor family, one member of which has a 50-residue regulatory subunit experimentally shown to switch between α-helical and β-sheet folds. Our approach predicts that 24% of sequences in this family undergo similar α-helix ⇌ β-sheet transitions. While these predictions cannot be reproduced by other state-of-the-art computational methods, they are confirmed by circular dichroism and nuclear magnetic resonance spectroscopy for 10 out of 10 sequence-diverse variants. This work suggests that fold switching may be a pervasive mechanism of transcriptional regulation in all kingdoms of life.The COVID-19 pandemic continues to impact daily life, including health system operations, despite the availability of vaccines that are effective in greatly reducing the risks of death and severe disease. Misperceptions of COVID-19 vaccine safety, efficacy, risks, and mistrust in institutions responsible for vaccination campaigns have been reported as factors contributing to vaccine hesitancy. This study investigated COVID-19 vaccine hesitancy globally in June 2021. Nationally representative samples of 1,000 individuals from 23 countries were surveyed. Data were analyzed descriptively, and weighted multivariable logistic regressions were used to explore associations with vaccine hesitancy. Here, we show that more than three-fourths (75.2%) of the 23,000 respondents report vaccine acceptance, up from 71.5% one year earlier. Across all countries, vaccine hesitancy is associated with a lack of trust in COVID-19 vaccine safety and science, and skepticism about its efficacy. Vaccine hesitant respondents are also highly resistant to required proof of vaccination; 31.7%, 20%, 15%, and 14.8% approve requiring it for access to international travel, indoor activities, employment, and public schools, respectively. For ongoing COVID-19 vaccination campaigns to succeed in improving coverage going forward, substantial challenges remain to be overcome. These include increasing vaccination among those reporting lower vaccine confidence in addition to expanding vaccine access in low- and middle-income countries.
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