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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Acupuncture for generalized anxiety disorder: a study protocol for a randomized controlled trial.

During the COVID-19 outbreak, there was a sharp increase in generalized anxiety disorder (GAD). Acupuncture therapy has the advantages of accurate clinical efficacy, safety and reliability, few adverse reactions, and no dependence, and is gradually becoming one of the emerging therapies for treating GAD. We present a study protocol for a randomized clinical trial with the aim of exploring the mechanism of brain plasticity in patients with GAD and evaluate the effectiveness and reliability of acupuncture treatment. Transcranial magnetic stimulation (TMS) will be used to assess cortical excitability in GAD patients and healthy people. Sixty-six GAD patients meeting the inclusion criteria will be randomly divided into two groups: TA group, (treatment with acupuncture and basic western medicine treatment) and SA group (sham acupuncture and basic western medicine treatment). Twenty healthy people will be recruited as the control group (HC). The parameters that will be evaluated are amplitude of motor evoked potentials (MEPs), cortical resting period (CSP), resting motor threshold (RMT), and Hamilton Anxiety Scale (HAMA) score. Secondary results will include blood analysis of γ-aminobutyric acid (GABA), glutamate (Glu), glutamine (Gln), serotonin (5-HT), and brain-derived nerve growth factor (BDNF). Outcomes will be assessed at baseline and after the intervention (week 8). This study protocol is the first clinical trial designed to detect differences in cerebral cortical excitability between healthy subjects and patients with GAD, and the comparison of clinical efficacy and reliability before and after acupuncture intervention is also one of the main contents of the protocol. We hope to find a suitable non-pharmacological alternative treatment for patients with GAD.

Efficient Catalytic Elimination of Toxic Volatile Organic Compounds via Advanced Oxidation Process Wet Scrubbing with Bifunctional Cobalt Sulfide/Activated Carbon Catalysts.

Advanced oxidation process (AOP) wet scrubber is a powerful and clean technology for organic pollutant treatment but still presents great challenges in removing the highly toxic and hydrophobic volatile organic compounds (VOCs). Herein, we elaborately designed a bifunctional cobalt sulfide (CoS2)/activated carbon (AC) catalyst to activate peroxymonosulfate (PMS) for efficient toxic VOC removal in an AOP wet scrubber. By combining the excellent VOC adsorption capacity of AC with the highly efficient PMS activation activity of CoS2, CoS2/AC can rapidly capture VOCs from the gas phase to proceed with the SO4•- and HO• radical-induced oxidation reaction. More than 90% of aromatic VOCs were removed over a wide pH range (3-11) with low Co ion leaching (0.19 mg/L). The electron-rich sulfur vacancies and low-valence Co species were the main active sites for PMS activation. SO4•- was mainly responsible for the initial oxidation of VOCs, while HO• and O2 acted in the subsequent ring-opening and mineralization processes of intermediates. No gaseous intermediates from VOC oxidation were detected, and the highly toxic liquid intermediates like benzene were also greatly decreased, thus effectively reducing the health toxicity associated with byproduct emissions. This work provided a comprehensive understanding of the deep oxidation of VOCs via AOP wet scrubber, significantly accelerating its application in environmental remediation.

Cross-ancestry atlas of gene, isoform, and splicing regulation in the developing human brain.

Neuropsychiatric genome-wide association studies (GWASs), including those for autism spectrum disorder and schizophrenia, show strong enrichment for regulatory elements in the developing brain. However, prioritizing risk genes and mechanisms is challenging without a unified regulatory atlas. Across 672 diverse developing human brains, we identified 15,752 genes harboring gene, isoform, and/or splicing quantitative trait loci, mapping 3739 to cellular contexts. Gene expression heritability drops during development, likely reflecting both increasing cellular heterogeneity and the intrinsic properties of neuronal maturation. Isoform-level regulation, particularly in the second trimester, mediated the largest proportion of GWAS heritability. Through colocalization, we prioritized mechanisms for about 60% of GWAS loci across five disorders, exceeding adult brain findings. Finally, we contextualized results within gene and isoform coexpression networks, revealing the comprehensive landscape of transcriptome regulation in development and disease.

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.

Role of MIC levels and 23S rRNA mutation sites to clarithromycin in 14-day clarithromycin bismuth quadruple therapy for Helicobacter pylori eradication: A prospective trial in Beijing.

Background: Rising clarithromycin resistance undermines Helicobacter pylori (H. pylori) treatment efficacy. We aimed to determine clarithromycin's minimum inhibitory concentration (MIC) levels and identify specific mutation sites in the 23S ribosomal subunit (23S rRNA) that predict treatment outcomes in a 14-day regimen of clarithromycin bismuth quadruple therapy (amoxicillin 1g, clarithromycin 500 mg, rabeprazole 10 mg, and colloidal bismuth pectin 200 mg). Materials and methods: We included adult H. pylori patients who hadn't previously undergone clarithromycin-based treatment, either as initial or rescue therapy. Exclusions were made for penicillin allergy, recent use of related medications, severe illnesses, or inability to cooperate. Patients underwent a 14-day clarithromycin bismuth quadruple therapy. Gastric mucosa specimens were obtained during endoscopy before eradication. MIC against amoxicillin and clarithromycin was determined using the E-test method. The receiver operating characteristic (ROC) curve helped to find the optimal clarithromycin resistance MIC breakpoint. Genetic sequences of H. pylori 23S rRNA were identified through Sanger Sequencing. (ChiCTR2200061476). Results: Out of 196 patients recruited, 92 met the inclusion criteria for the per-protocol (PP) population. The overall intention-to-treat (ITT) eradication rate was 80.00 % (84/105), while the modified intention-to-treat (MITT) and PP eradication rates were 90.32 % (84/93) and 91.30 % (84/92) respectively. No amoxicillin resistance was observed, but clarithromycin resistance rates were 36.19 % (38/105), 35.48 % (33/93), and 34.78 % (33/92) in the ITT, MITT, and PP populations respectively. Compared with the traditional clarithromycin resistance breakpoint of 0.25 µg/mL, a MIC threshold of 12 µg/mL predicted better eradication. Among 173 mutations on 152 sites in the 23S rRNA gene, only the 2143A > G mutation could predict eradication outcomes (p < 0.000). Conclusions: Interpretation of elevated MIC values is crucial in susceptibility testing, rather than a binary "susceptible" or "resistant" classification. The 2143A > G mutation has limited specificity in predicting eradication outcomes, necessitating further investigation into additional mutation sites associated with clarithromycin resistance.

Evolution Characterization and Pathogenicity of an NADC34-like PRRSV Isolated from Inner Mongolia, China.

Porcine reproductive and respiratory syndrome virus (PRRSV) is a pathogen that causes severe abortions in sows and high piglet mortality, resulting in huge economic losses to the pig industry worldwide. The emerging and novel PRRSV isolates are clinically and biologically important, as there are likely recombination and pathogenic differences among PRRSV genomes. Furthermore, the NADC34-like strain has become a major epidemic strain in some parts of China, but the characterization and pathogenicity of the latest strain in Inner Mongolia have not been reported in detail. In this study, an NADC34-like strain (CHNMGKL1-2304) from Tongliao City, Inner Mongolia was successfully isolated and characterized, and confirmed the pathogenicity in pigs. The phylogenetic tree showed that this strain belonged to sublineage 1.5 and had high homology with the strain JS2021NADC34. There is no recombination between CHNMGKL1-2304 and any other domestic strains. Animal experiments show that the CHNMGKL1-2304 strain is moderately virulent to piglets, which show persistent fever, weight loss and high morbidity but no mortality. The presence of PRRSV nucleic acids was detected in both blood, tissues, nasal and fecal swabs. In addition, obvious pathological changes and positive signals were observed in lung, lymph node, liver and spleen tissues when subjected to hematoxylin-eosin (HE) staining and immunohistochemistry (IHC). This report can provide a basis for epidemiological investigations and subsequent studies of PRRSV.