Unveiling unconventional CH4-Xe compounds and their thermodynamic properties at extreme conditions.

Inert gases (e.g., He and Xe) can exhibit chemical activity at high pressure, reacting with other substances to form compounds of unexpected chemical stoichiometry. This work combines first-principles calculations and crystal structure predictions to propose four unexpected stable compounds of CH4Xe3, (CH4)2Xe, (CH4)3Xe, and (CH4)3Xe2 at pressure ranges from 2 to 100 GPa. All structures are composed of isolated Xe atoms and CH4 molecules except for (CH4)3Xe2, which comprises a polymerization product, C3H8, and hydrogen molecules. Ab initio molecular dynamics simulations indicate that pressure plays a very important role in the different temperature driving state transitions of CH4-Xe compounds. At lower pressures, the compounds follow the state transition of solid-plastic-fluid phases with increasing temperature, while at higher pressures, the stronger Xe-C interaction induces the emergence of a superionic state for CH4Xe3 and (CH4)3Xe2 as temperature increases. These results not only expand the family of CH4-Xe compounds, they also contribute to models of the structures and evolution of planetary interiors.

Cofitness network connectivity determines a fuzzy essential zone in open bacterial pangenome.

Most in silico evolutionary studies commonly assumed that core genes are essential for cellular function, while accessory genes are dispensable, particularly in nutrient-rich environments. However, this assumption is seldom tested genetically within the pangenome context. In this study, we conducted a robust pangenomic Tn-seq analysis of fitness genes in a nutrient-rich medium for Sinorhizobium strains with a canonical open pangenome. To evaluate the robustness of fitness category assignment, Tn-seq data for three independent mutant libraries per strain were analyzed by three methods, which indicates that the Hidden Markov Model (HMM)-based method is most robust to variations between mutant libraries and not sensitive to data size, outperforming the Bayesian and Monte Carlo simulation-based methods. Consequently, the HMM method was used to classify the fitness category. Fitness genes, categorized as essential (ES), advantage (GA), and disadvantage (GD) genes for growth, are enriched in core genes, while nonessential genes (NE) are over-represented in accessory genes. Accessory ES/GA genes showed a lower fitness effect than core ES/GA genes. Connectivity degrees in the cofitness network decrease in the order of ES, GD, and GA/NE. In addition to accessory genes, 1599 out of 3284 core genes display differential essentiality across test strains. Within the pangenome core, both shared quasi-essential (ES and GA) and strain-dependent fitness genes are enriched in similar functional categories. Our analysis demonstrates a considerable fuzzy essential zone determined by cofitness connectivity degrees in Sinorhizobium pangenome and highlights the power of the cofitness network in understanding the genetic basis of ever-increasing prokaryotic pangenome data.

Heterogeneous stiffness of the bone marrow microenvironment regulates the fate decision of haematopoietic stem and progenitor cells.

The bone marrow (BM) niches are the complex microenvironments that surround cells, providing various external stimuli to regulate a range of haematopoietic stem cell (HSC) behaviours. Recently, it has been proposed that the fate decision of HSCs is often correlated with significantly altered biophysical signals of BM niches. To thoroughly elucidate the effect of mechanical microenvironments on cell fates, we constructed 2D and 3D cell culture hydrogels using polyacrylamide to replicate the mechanical properties of heterogeneous sub-niches, including the inherent rigidity of marrow adipose tissue (2 kPa), perivascular tissue (8 kPa) and endosteum region (35 kPa) in BM. Our observations suggest that HSCs can respond to the mechanical heterogeneity of the BM microenvironment, exhibiting diversity in cell mechanics, haematopoietic pool maintenance and differentiated lineages. Hydrogels with higher stiffness promote the preservation of long-term repopulating HSCs (LT-HSCs), while those with lower stiffness support multi-potent progenitors (MPPs) viability in vitro. Furthermore, we established a comprehensive transcriptional profile of haematopoietic subpopulations to reflect the multipotency of haematopoietic stem and progenitor cells (HSPCs) that are modulated by niche-like stiffness. Our findings demonstrate that HSPCs exhibit completely distinct downstream differentiated preferences within hydrogel systems of varying stiffness. This highlights the crucial role of tissue-specific mechanical properties in HSC lineage decisions, which may provide innovative solutions to clinical challenges.

Genetically Enabling Phosphorus Fluoride Exchange Click Chemistry in Proteins.

Phosphorus Fluoride Exchange (PFEx), recently debuted in small molecules, represents the forefront of click chemistry. To explore PFEx's potential in biological settings, we developed amino acids PFY and PFK featuring phosphoramidofluoridates and incorporated them into proteins through genetic code expansion. PFY/PFK selectively reacted with nearby His, Tyr, Lys, or Cys in proteins, both in vitro and in living cells, demonstrating that proximity enabled PFEx reactivity without external reagents. The reaction with His showed unique pH-dependent properties and created thermally sensitive linkages. Additionally, Na2SiO3 enhanced PFEx reactions with Tyr and Cys. PFEx, by generating defined covalent P-N/O linkages, extends the utility of phosphorus linkages in proteins, aligning with nature's use of phosphate connectors in other biomolecules. More versatile and durable than SuFEx, PFEx in proteins expands the latent bioreactive arsenal for covalent protein engineering and will facilitate the broad application of this potent click chemistry in biological and biomedical fields.

Computational modeling of the rectangular non-aligned multi-injector for efficient fuel mixing in a supersonic combustion chamber.

The present investigation examines the usage of rectangular multi-injectors for fuel injection in a supersonic combustion chamber. To evaluate the fuel jet penetration and distribution, a computational method is applied to model the supersonic compressible flow with cross multi-fuel jets released from annular rectangular nozzles with different nozzle configurations. The main effort of this work is to evaluate the jet interactions in the existence of cross-supersonic flow. Fuel jet penetration and distribution are evaluated for three proposed injector arrangements to attain the more efficient option for better fuel mixing. Our results show that reducing injector space improves fuel mixing inside the combustor via creation of strong vortices. Beside, injection of air from internal nozzle increase fuel interactions and fuel mixing inside combustion chamber.

Transcranial direct current stimulation of the prefrontal and visual cortices diversely affects early and late perceptual learning.

BACKGROUND: Research has shown that visual perceptual learning (VPL) is related to modifying neural activity in higher level decision-making regions. However, the causal roles of the prefrontal and visual cortexes in VPL are still unclear. Here, we investigated how anodal transcranial direct current stimulation (tDCS) of the prefrontal and visual cortices modulates VPL in the early and later phases and the role of multiple brain regions. METHODS: Perceptual learning on the coherent motion direction identification task included early and later stages. After early training, participants needed to continuously train to reach a plateau; once the plateau was reached, participants entered a later stage. Sixty participants were randomly divided into five groups. Regardless of the training at the early and later stages, four groups received multitarget tDCS over the right dorsolateral prefrontal cortex (rDLPFC) and right middle temporal area (rMT), single-target tDCS over the rDLPFC, and single-target tDCS over the rMT or sham stimulation, and one group was stimulated at the ipsilateral brain region (i.e., left MT). RESULTS: Compared with sham stimulation, multitarget and two single-target tDCS over the rDLPFC or rMT improved posttest performance and accelerated learning during the early period. However, multitarget tDCS and two single-target tDCS led to equivalent benefits for VPL. Additionally, these beneficial effects were absent when anodal tDCS was applied to the ipsilateral brain region. For the later period, the above facilitating effects on VPL induced by multitarget or single-target tDCS disappeared. CONCLUSIONS: This study suggested the causal role of the prefrontal and visual cortices in visual motion perceptual learning by anodal tDCS but failed to find greater beneficial effects by simultaneously stimulating the prefrontal and visual cortices. Future research should investigate the functional associations between multiple brain regions to further promote VPL.

Global prevalence of norovirus gastroenteritis after emergence of the GII.4 Sydney 2012 variant: a systematic review and meta-analysis.

Introduction: Norovirus is widely recognized as a leading cause of both sporadic cases and outbreaks of acute gastroenteritis (AGE) across all age groups. The GII.4 Sydney 2012 variant has consistently prevailed since 2012, distinguishing itself from other variants that typically circulate for a period of 2-4 years. Objective: This review aims to systematically summarize the prevalence of norovirus gastroenteritis following emergence of the GII.4 Sydney 2012 variant. Methods: Data were collected from PubMed, Embase, Web of Science, and Cochrane databases spanning the period between January 2012 and August 2022. A meta-analysis was conducted to investigate the global prevalence and distribution patterns of norovirus gastroenteritis from 2012 to 2022. Results: The global pooled prevalence of norovirus gastroenteritis was determined to be 19.04% (16.66-21.42%) based on a comprehensive analysis of 70 studies, which included a total of 85,798 sporadic cases with acute gastroenteritis and identified 15,089 positive cases for norovirus. The prevalence rate is higher in winter than other seasons, and there are great differences among countries and age groups. The pooled attack rate of norovirus infection is estimated to be 36.89% (95% CI, 36.24-37.55%), based on a sample of 6,992 individuals who tested positive for norovirus out of a total population of 17,958 individuals exposed during outbreak events. Conclusion: The global prevalence of norovirus gastroenteritis is always high, necessitating an increased emphasis on prevention and control strategies with vaccine development for this infectious disease, particularly among the children under 5 years old and the geriatric population (individuals over 60 years old).

UiO-66/PIM-1 Mixed-Matrix Membrane for Hexane Isomer Separation.

The separation of high-octane dibranched alkanes from naphtha is critical in the refining of gasoline. To date, research on the membrane-based separation of alkane isomers has been limited, with a particular paucity of investigations into mixed-matrix membranes. Herein, the continuous and dense UiO-66/PIM-1 mixed-matrix membrane, which was prepared through precise control of the interfacial structure, was first applied to the differentiation of C6 alkane isomers. Due to the synergistic combination of UiO-66 with differential adsorption capabilities for alkanes and PIM-1 that possesses a cross-linkable structure, the resulting UiO-66/PIM-1-(20) membrane demonstrated remarkable separation performance and high stability. Pervaporation measurements showed that the mass fraction of 2,2-dimethylbutane in the feed side was increased from 50.0 to 75.8 wt % while an excellent flux of 1700 g m-2 h-1 was maintained over a continuous 40 h period. The UiO-66/PIM-1-(20) membrane, characterized by its facile replication and processing, shows potential for large-scale fabrication. This study offers a new approach to the membrane separation of alkane isomers.

High-Performance Monovalent Selective Cation Exchange Membranes with Ionically Cross-Linkable Side Chains: Effect of the Acidic Groups.

Inspired by the charge-governed protein channels located in the cell membrane, a series of polyether ether ketone-based polymers with side chains containing ionically cross-linkable quaternary ammonium groups and acidic groups have been designed and synthesized to prepare monovalent cation-selective membranes (MCEMs). Three acidic groups (sulfonic acid, carboxylic acid, and phenolic hydroxyl) with different acid dissociation constant (pKa) were selected to form the ionic cross-linking structure with quaternary ammonium groups in the membranes. The ionic cross-linking induced the nanophase separation and constructed ionic channels, which resulted in excellent mechanical performance and high cation fluxes. Interesting, the cation flux of membranes increased as the ionization of acidic groups increase, but the selectivity of MCEMs did not follow the same trend, which was mainly dependent on the affinity between the functional groups and the cations. Carboxyl group-containing MCEMs exhibited the best selectivity (9.01 for Li+/Mg2+), which was higher than that of the commercial monovalent cation-selective CIMS membrane. Therefore, it is possible to prepare stable MCEMs through a simple process using ionically cross-linkable polymers, and tuning acidic groups in the membranes provided an attractive approach to improving the cation flux and selectivity of MCEMs.

Enriching Nano-Heterointerfaces in Proton Conducting TiO2-SrTiO3@TiO2 Yolk-Shell Electrolyte for Low-Temperature Solid Oxide Fuel Cells.

A challenging task in solid oxide fuel cells (SOFCs) is seeking for an alternative electrolyte, enabling high ionic conduction at relatively low operating temperatures, i.e., 300-600 °C. Proton-conducting candidates, in particular, hold a significant promise due to their low transport activation energy to deliver protons. Here, a unique hierarchical TiO2-SrTiO3@TiO2 structure is developed inside an intercalated TiO2-SrTiO3 core as "yolk" decorating densely packed flake TiO2 as shell, creating plentiful nano-heterointerfaces with a continuous TiO2 and SrTiO3 "in-house" interfaces, as well the interfaces between TiO2-SrTiO3 yolk and TiO2 shell. It exhibits a reduced activation energy, down to 0.225 eV, and an unexpectedly high proton conductivity at low temperature, e.g., 0.084 S cm-1 at 550 °C, confirmed by experimentally H/D isotope method and proton-filtrating membrane measurement. Raman mapping technique identifies the presence of hydrogenated HO─Sr bonds, providing further evidence for proton conduction. And its interfacial conduction is comparatively analyzed with a directly-mixing TiO2-SrTiO3 composite electrolyte. Consequently, a single fuel cell based on the TiO2-SrTiO3@TiO2 heterogeneous electrolyte delivers a good peak power density of 799.7 mW cm-2 at 550 °C. These findings highlight a dexterous nano-heterointerface design strategy of highly proton-conductive electrolytes at reduced operating temperatures for SOFC technology.

Application of the Modified Grunow-Finke Risk Assessment Tool to the Sverdlovsk Anthrax Outbreak of 1979.

INTRODUCTION: The modified Grunow-Finke tool (mGFT) is an improved scoring system for distinguishing unnatural outbreaks from natural ones. The 1979 Sverdlovsk anthrax outbreak was due to the inhalation of anthrax spores from a military laboratory, confirmed by Russian President Boris Yeltsin in 1992. At the time the Soviet Union insisted that the outbreak was caused by meat contaminated by diseased animals. At the time there was no available risk assessment tool capable of thoroughly examine the origin of the outbreak. METHODS: This study aimed to retrospectively apply the mGFT to test its ability to correctly identify the origin of the Sverdlovsk anthrax outbreak of 1979 as unnatural, using data available up to 1992, before the disclosure of a laboratory leak. Data spanning from 1979 to 1992 were collected through literature reviews. Evidence related to each mGFT criterion was scored on a scale of 0 to 3 and independently reviewed by 3 assessors. These scores were then multiplied with a weighting factor and summed to obtain a maximum score. A final score exceeding 30 was indicative of an unnatural origin. RESULTS: The mGFT results assigned a total of 47 points to the Sverdlovsk anthrax outbreak, suggesting an unnatural origin with a 78% likelihood. CONCLUSIONS: These findings align with the confirmed unnatural origin of the outbreak, highlighting the value of tools such as the mGFT in identifying unnatural outbreaks. Such tools integrate both intelligence evidence and biological evidence in the identification of unnatural outbreaks. The use of such tools for identifying unnatural outbreaks is limited. Outbreak investigation can be improved if risk assessment tools become integral to routine public health practice and outbreak investigations.

DeepFusionCDR: Employing Multi-Omics Integration and Molecule-Specific Transformers for Enhanced Prediction of Cancer Drug Responses.

Deep learning approaches have demonstrated remarkable potential in predicting cancer drug responses (CDRs), using cell line and drug features. However, existing methods predominantly rely on single-omics data of cell lines, potentially overlooking the complex biological mechanisms governing cell line responses. This paper introduces DeepFusionCDR, a novel approach employing unsupervised contrastive learning to amalgamate multi-omics features, including mutation, transcriptome, methylome, and copy number variation data, from cell lines. Furthermore, we incorporate molecular SMILES-specific transformers to derive drug features from their chemical structures. The unified multi-omics and drug signatures are combined, and a multi-layer perceptron (MLP) is applied to predict IC50 values for cell line-drug pairs. Moreover, this MLP can discern whether a cell line is resistant or sensitive to a particular drug. We assessed DeepFusionCDR's performance on the GDSC dataset and juxtaposed it against cutting-edge methods, demonstrating its superior performance in regression and classification tasks. We also conducted ablation studies and case analyses to exhibit the effectiveness and versatility of our proposed approach. Our results underscore the potential of DeepFusionCDR to enhance CDR predictions by harnessing the power of multi-omics fusion and molecular-specific transformers. The prediction of DeepFusionCDR on TCGA patient data and case study highlight the practical application scenarios of DeepFusionCDR in real-world environments. Source code and datasets can be available on https://github.com/altriavin/DeepFusionCDR.

The association between dynamic changes in vitamin D and frailty alterations: A prospective analysis of UK Biobank participants.

BACKGROUND: Frailty is a common geriatric syndrome associated with reduced reserves and increased vulnerability to stressors among older adults. Vitamin D deficiency has been implicated in frailty, as it is essential for maintaining musculoskeletal functions. The relationship between dynamic changes in vitamin D levels and frailty over time has not been extensively studied. METHODS: This study utilized data from the UK Biobank. Baseline and longitudinal changes in vitamin D levels were measured. Frailty status was assessed using both the frailty phenotype and frailty index approaches and classified as robust, pre-frail, or frail. Changes in frailty status were assessed by frailty phenotype at baseline (2006-2010) and the follow-up (2012-2013). Mixed effect model was performed to examine the association between vitamin D levels and frailty status. Using multistate transition models, we assessed the impact of increasing vitamin D levels on the probabilities of transitioning between robust, pre-frail, and frail states. RESULTS: Based on the frailty phenotype, 287 926 individuals (64.8%) were identified as having various degrees of frailty (median age 58.00 [51.00, 64.00] years, 55.9% females). Using the frailty index approach, 250 566 individuals (56%) were found to have different levels of frailty (median age 59.00 [51.00, 64.00] years, 55.3% females). Baseline vitamin D levels were found to be significantly associated with frailty status (frailty phenotype: ORfrail 0.78, 95% CI [0.76, 0.79], P < 0.001; frailty index: ORfrail 0.80, 95% CI [0.78, 0.81], P < 0.001). Dynamic changes in vitamin D levels were also found to be associated with changes in frailty over time. Furthermore, increasing vitamin D levels were associated with a transition from frailty to a healthier status. A higher degree of vitamin D (estimated at 1 nmol/L) was associated with a lower risk of transitioning from robust to prefrail (HR 0.997, 95% CI [0.995, 0.999]) and from prefrail to frail (HR 0.992, 95% CI [0.988, 0.995]). CONCLUSIONS: This study highlights the importance of vitamin D in the context of frailty. Low vitamin D levels are associated with increased frailty risk, while increasing vitamin D levels may contribute to improving frailty status. Recognizing the relationship between vitamin D levels and frailty can inform personalized management and early interventions for frail individuals. Further research is needed to explore the potential effects of vitamin D interventions on frailty and deepen our understanding of the biological connections between vitamin D and frailty.

High sensitivity of dissolved organic carbon transport during hydrological events in a small subtropical karst catchment.

Dissolved organic carbon (DOC) and discharge are often tightly coupled, though these relationships in karst environments remain poorly constrained. In this study, DOC dynamics over 13 hydrological events, alongside monthly monitoring over an entire hydrological year were monitored in a small karst catchment, SW China. The concurrent analyses of power-law model and hysteresis patterns reveal that DOC behavior is generally transport-limited due to flushing effects of increased discharge but highly variable at both intra- and inter-event scales. The initial discharge at event onset and discharge-weighted mean concentration of DOC ([DOC]DW) of individual events can explain 37.7 % and 19.9 % of the variance of DOC behavior among events, respectively. The sustained dry-cold antecedent conditions make DOC hysteresis behavior during the earliest event complex and different from subsequent events. At event scale, the variability in DOC export is primarily controlled by [DOC]DW (explaining 64.3 %) and the yield of total dissolved solutes (YTDS, explaining 30.4 %), reflecting the impacts of variable hydrological connectivity and intense soil-water-rock interactions in this karst catchment. On an annual scale, DOC yield (YDOC, 222.86 kg C km-2) was mostly derived during the wet season (98.19 %) under the hydrological driving force. The difference in annual YDOC between this karst catchment and other regions can be well explained by annual water yield (Ywater, explaining 24.2 %) and [DOC] (explaining 35.4 %), whereas the variance in DOC export efficiency among catchments is almost exclusively controlled by [DOC] alone, independent of drainage area and annual Ywater. This study highlights the necessity of high-frequency sampling for modeling carbon biogeochemical processes and the particularity of the earliest hydrological events occurred after a long cold-dry period in karst catchments. Under the changing climate, whether DOC dynamics in karst catchments will present source-limited patterns during more extreme hydrological events merits further study.

Local adaptation of trophic strategy determined the tolerance of coral Galaxea fascicularis to environmental fluctuations.

The escalation of global change has resulted in heightened frequencies and intensities of environmental fluctuations within coral reef ecosystems. Corals originating from marginal reefs have potentially enhanced their adaptive capabilities in response to these environmental variations through processes of local adaptation. However, the intricate mechanisms driving this phenomenon remain a subject of limited investigation. This study aimed to investigate how corals in Luhuitou reef, a representative relatively high-latitude reef in China, adapt to seasonal fluctuations in seawater temperature and light availability. We conducted a 190-day plantation experiment with the widespread species, Galaxea fascicularis, in Luhuitou local, and from Meiji reef, a typical offshore tropical reef, to Luhuitou as comparison. Drawing upon insights from physiological adaptations, we focused on fatty acid (FA) profiles to unravel the trophic strategies of G. fascicularis to cope with environmental fluctuations from two origins. Our main findings are threefold: 1) Native corals exhibited a stronger physiological resilience compared to those transplanted from Meiji. 2) Corals from both origins consumed large quantities of energy reserves in winter, during which FA profiles of local corals altered, while the change of FA profiles of corals from Meiji was probably due to the excessive consumption of saturated fatty acid (SFA). 3) The better resilience of native corals is related to high levels of functional polyunsaturated fatty acid (PUFA), while insufficient nutrient reserves, possibly due to weak heterotrophic ability, result in the obstruction of the synthesis pathway of PUFA for corals from Meiji, leading to their intolerance to environmental changes. Consequently, we suggest that the tolerance of G. fascicularis to environmental fluctuations is determined by their local adapted trophic strategies. Furthermore, our findings underscore the notion that the rapid adaptation of relatively high-latitude corals to seasonal environmental fluctuations might not be readily attainable for their tropical counterparts within a brief timeframe.

The Mediating Effect of Coping Style in the Relationship Between Sleep Quality and Perceived Cognitive Impairment Among Breast Cancer Patients: A Cross-sectional Study.

BACKGROUND: Perceived cognitive impairment is a significant symptom experienced by breast cancer patients and may be affected by sleep quality. Coping styles have potential relevancies with both sleep quality and perceived cognitive impairment. However, the empirical evidence supporting their association among breast cancer patients is limited. OBJECTIVE: This study explored the associations between sleep quality, coping styles, and perceived cognitive impairment and tested the mediating role of coping styles in breast cancer patients. METHODS: A total of 294 breast cancer patients were included in this cross-sectional study. Patients were assessed using the Pittsburgh Sleep Index Scale, the Simplified Coping Styles Questionnaire, and the Functional Assessment of Cancer Therapy-Cognitive Functioning (Version 3) Scale. The data were analyzed using SPSS and Process macros. RESULTS: The direct effect of sleep quality on reported cognitive impairment was significant (ß = -0.245, P < .001). Furthermore, sleep quality was found to have a significant indirect effect on perceived cognitive impairment through positive coping style (ß = -0.026, P < .05) and negative coping style (ß = -0.131, P < .05). CONCLUSIONS: Our research suggests that sleep quality has both a direct effect on perceived cognitive impairment and an indirect effect through positive and negative coping styles in breast cancer patients. Moreover, negative coping style had a more pronounced mediating effect than positive coping style. IMPLICATIONS FOR PRACTICE: Clinical medical staff could reduce the perceived cognitive impairment of breast cancer patients by improving their sleep quality and encouraging them to adopt a more positive coping style.

Hypoxia-inducible factor prolyl hydroxylase inhibitor alleviates heatstroke-induced acute kidney injury by activating BNIP3-mediated mitophagy.

Hypoxia-induced inflammation and apoptosis are important pathophysiological features of heat stroke-induced acute kidney injury (HS-AKI). Hypoxia-inducible factor (HIF) is a key protein that regulates cell adaptation to hypoxia. HIF-prolyl hydroxylase inhibitor (HIF-PHI) stabilizes HIF to increase cell adaptation to hypoxia. Herein, we reported that HIF-PHI pretreatment significantly improved renal function, enhanced thermotolerance, and increased the survival rate of mice in the context of HS. Moreover, HIF-PHI could alleviate HS-induced mitochondrial damage, inflammation, and apoptosis in renal tubular epithelial cells (RTECs) by enhancing mitophagy in vitro and in vivo. By contrast, mitophagy inhibitors Mdivi-1, 3-MA, and Baf-A1 reversed the renoprotective effects of HIF-PHI. Mechanistically, HIF-PHI protects RTECs from inflammation and apoptosis by enhancing Bcl-2 adenovirus E18 19-kDa-interacting protein 3 (BNIP3)-mediated mitophagy, while genetic ablation of BNIP3 attenuated HIF-PHI-induced mitophagy and abolished HIF-PHI-mediated renal protection. Thus, our results indicated that HIF-PHI protects renal function by upregulating BNIP3-mediated mitophagy to improve HS-induced inflammation and apoptosis of RTECs, suggesting HIF-PHI as a promising therapeutic agent to treat HS-AKI.

Psychological impacts of lobectomy and total thyroidectomy in PTC measuring 1 to 4 cm with low to intermediate risk of recurrence.

PURPOSE: To investigate the implications of Lobectomy (LT) or total thyroidectomy (TT) on psychological distress and sleep quality in PTC patients with a low to intermediate risk of recurrence and tumors measuring 1 to 4 cm. METHODS: Patients who were admitted to our hospital between July 2021 and July 2022 were prospectively enrolled in this survey. Psychological distress and sleep quality were assessed at hospitalization, discharge, and 1, 3, and 6 months post-treatment using validated scales. Participants were divided into LT and TT groups, with propensity score matching (PSM) applied for analyses. RESULTS: Among 525 eligible PTC patients, 440 patients completed all the questionnaires throughout the follow-up. After PSM, 166 patients underwent LT, and 166 patients underwent TT were enrolled. The psychological distress and sleep quality of patients in the LT group remained relatively stable during the 6-month follow-up, but patients in the TT group may have faced greater sleep quality concerns in the longitudinal assessment. Additionally, the sleep quality of the TT group was also worse than that of the LT group postoperatively. CONCLUSIONS: The sleep quality rather than other psychological distress of patients with PTC with a low to intermediate risk of recurrence is associated with the extent of surgery.

Synergistic action and mechanism of scoparone, a key bioactive component of Artemisia capillaris, and spirodiclofen against spider mites.

BACKGROUND: Plants have numerous defensive secondary metabolites to withstand insect attacks. Scoparone, which is extracted from the medicinal plant Artemisia capillaris, has potent acaricidal effects on Tetranychus cinnabarinus. Spirodiclofen, derived from a tetronic acid derivative, is a potent commercial acaricide that is extensively used globally. However, whether scoparone has synergistic effects when used in conjunction with spirodiclofen and the underlying synergistic mechanism remains unclear. RESULTS: Scoparone exhibited a potent synergistic effect when it was combined with spirodiclofen at a 1:9 ratio. Subsequently, cytochrome P450 monooxygenase (P450) activity, RNA-Seq and qPCR assays indicated that the enzyme activity of P450 and the expression of one P450 gene from T. cinnabarinus, TcCYP388A1, were significantly inhibited by scoparone and spirodiclofen + scoparone; conversely, P450 was activated in spirodiclofen-exposed mites. Importantly, RNAi-mediated silencing of the TcCYP388A1 gene markedly increased the susceptibility of spider mites to spirodiclofen, scoparone and spirodiclofen + scoparone, and in vitro, the recombinant TcCYP388A1 protein could metabolize spirodiclofen. Molecular docking and functional analyses further indicated that R117, which is highly conserved in Arachnoidea species, may be a vital specific binding site for scoparone in the mite TcCYP388A1 protein. This binding site was subsequently confirmed using mutagenesis data, which revealed that this binding site was the sole site selected by scoparone in spider mites over mammalian or fly CYP388A1. CONCLUSIONS: These results indicate that the synergistic effects of scoparone and spirodiclofen on mites occurs through the inhibition of P450 activity, thus reducing spirodiclofen metabolism. The synergistic effect of this potent natural product on the detoxification enzyme-targeted activity of commercial acaricides may offer a sustainable strategy for pest mite resistance management. © 2024 Society of Chemical Industry.

Developmental isoform diversity in the human neocortex informs neuropsychiatric risk mechanisms.

RNA splicing is highly prevalent in the brain and has strong links to neuropsychiatric disorders; yet, the role of cell type-specific splicing and transcript-isoform diversity during human brain development has not been systematically investigated. In this work, we leveraged single-molecule long-read sequencing to deeply profile the full-length transcriptome of the germinal zone and cortical plate regions of the developing human neocortex at tissue and single-cell resolution. We identified 214,516 distinct isoforms, of which 72.6% were novel (not previously annotated in Gencode version 33), and uncovered a substantial contribution of transcript-isoform diversity-regulated by RNA binding proteins-in defining cellular identity in the developing neocortex. We leveraged this comprehensive isoform-centric gene annotation to reprioritize thousands of rare de novo risk variants and elucidate genetic risk mechanisms for neuropsychiatric disorders.