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Flooding of paddy fields enhances methane (CH 4 ) emissions and arsenic (As) mobilisation, which are crucial issues for agricultural greenhouse gas emissions and food safety. Birnessite (δ-MnO 2 ) is a common natural oxidant and scavenger for heavy metals. In this study, birnessite was applied to As-contaminated paddy soil. The capacity for simultaneously alleviating CH 4 emissions and As mobility was explored. Soil microcosm incubation results indicated that birnessite addition simultaneously reduced CH 4 emissions by 47 %-54 % and As release by 38 %-85 %. The addition of birnessite decreased the dissolved organic carbon (DOC) contents and altered its chemical properties. Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS) results showed that birnessite reduced the labile fractions of proteins, carbohydrates, lignins, tannins, and unsaturated hydrocarbons, however, increased the abundance of condensed aromatic structures, suggesting the polymerisation of dissolved organic matter (DOM) by birnessite. The degradation of labile fractions and the polymerisation of DOM resulted in an inventory of recalcitrant DOM, which is difficult for microbes to metabolise, thus inhibiting methanogenesis. In contrast, birnessite addition increased CH 4 oxidation, as the particulate methane monooxygenase (pmoA) gene abundance increased by 30 %. The enhanced polymerisation of DOM by birnessite also increased As complexation with organics, leading to the transfer of As to the organic bound phase. In addition, the decrease in ferrous ion [Fe(II)] concentrations with birnessite indicated that the reductive dissolution of Fe oxides was suppressed, which limited the release of arsenite [As(III)] under reducing conditions. Furthermore, birnessite decreased As methylation and shaped the soil microbial community structure by enriching the metal-reducing bacterium Bacillus. Overall, our results provide a promising method to suppress greenhouse gas emissions and the risk of As contamination in paddy soils, although further studies are needed to verify its efficacy and effectiveness under field conditions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

The chemoresistance and systemic toxicity of cisplatin (CDDP) severely limit its application in the treatment of non-small cell lung cancer (NSCLC). Here, I-124 labeled cancer cell membrane biomimetic nanovesicles loading Polyphyllin VI (PPVI) and CDDP (termed 124 I-P/C@CMLvs) were constructed to enhance the sensitivity and efficacy of CDDP. The radiochemical purity (RCP) of 124 I-P/C@CMLvs reached more than 99% and maintained reliable stability in vitro. Micro-positron emission tomography (micro-PET) imaging of I-124 quantitatively revealed the distribution and specific homologous tumor targeting ability of 124 I-P/C@CMLvs in vivo with superior diagnosis performance, beneficial for dynamically monitoring the efficacy against NSCLC. Loaded PPVI significantly strengthened the sensitivity of NSCLC to CDDP therapy and exerted synergistic anti-tumor effect in vitro and in vivo, which was achieved by PPVI promoting p53 deubiquitination and stimulating reactive oxygen species (ROS) production to trigger the crosstalk between the amplification of GPX4 signaling-mediated ferroptosis and NLRP3/GSDMD/Caspase-1 axis-mediated pyroptosis. 124 I-P/C@CMLvs also significantly stimulated the infiltration of immune cells including dendritic cells, CD8 + T cells, and CD4 + T cells in tumor tissues ( P < 0.05). The combination of 124 I-P/C@CMLvs and anti-PD-L1 therapy further synergistically promoted NSCLC regression. Altogether, 124 I-P/C@CMLvs provide a transformational solution to the challenge of improving CDDP sensitivity and realizing the integration of diagnosis, treatment, and monitoring of NSCLC.

Our study aims to explore the effects of neoadjuvant chemotherapy (NACT) on tumour cells and immune cells in the immune microenvironment of patients with high-grade serous ovarian cancer (HGSOC). Single-cell RNA sequencing data of paired ovarian cancer tissues were analysed before and after NACT in 11 patients with HGSOC. The effect of NACT on two major cell components of the tumour microenvironment, epithelial cells and CD8+T cells, was investigated. The mechanisms of epithelial cell evasion by NACT and immune killing were explored from the perspectives of gene expression, functional characteristics, transcriptional regulation, and cell communication. Key targets for reversing NACT resistance were identified and possible therapeutic strategies proposed. While NACT improved the de novo differentiation of anti-tumour CD8+T cells, enhancing their anti-tumour function, it increased the proportion of cancer cells with high HSP90B1 expression. Thus, the potential reasons for NACT resistance were identified as: 1) high levels of endoplasmic reticulum stress (ERS) characteristics, 2) high expression of the MDK-NCL ligand-receptor pair between them and exhausted CD8+T cells before NACT, and 3) high expression of the NECTIN2-TIGIT immune ligand-receptor pair between them and exhausted CD8+T cells after NACT. Thus, our study reveals the mechanisms underlying NACT resistance in patients with HGSOC from the perspective of the independent and interactive roles of cancer cells and CD8+T cells. We propose therapeutic strategies targeting the ERS marker HSP90B1 and the immune escape marker MDK before or during NACT, while targeting NECTIN2 blockade after NACT. This approach may offer new insights into combination treatments for patients with HGSOC displaying NACT resistance., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

For the first time, polystyrene sulfonic acid solution (PSS) was observed to emit blue fluorescence. The photoluminescence (PL) behavior of PSS under different concentrations, pH values and magnetic field strengths was investigated, revealing the diversity and tunability of its PL properties. PSS possesses remarkable down-conversion properties and strong responsiveness to external magnetic fields.

Background: Autoimmune diseases are a group of disorders characterized by abnormal immune responses that mistakenly target and attack healthy cells, tissues, and organs, resulting in inflammation and tissue damage. Omega-3 fatty acids possess anti-inflammatory activities and may decrease abnormal immune activity. However, the role of omega-3 fatty acids in various autoimmune diseases is still unclear. This umbrella review and Mendelian randomization (MR) study aims to summarize the highest available evidence on omega-3 fatty acids and autoimmune disease., Methods: We conducted an umbrella review by searching electronic databases to identify systematic reviews and meta-analyses. The selection criteria included systematic reviews with or without meta-analysis, which evaluated omega-3 fatty acids as the exposure and autoimmune disease as the outcome variable. Two authors independently assessed the overlapping and quality of the reviews using the AMSTAR-2 tool. We also performed MR studies to investigate the potential causal effect of fatty acids on the risk of various autoimmune diseases, utilizing data from the meta-analysis of the UKB-TOPMed and FinnGen cohorts., Result: The umbrella review identified 21 studies (8 systematic reviews and 13 meta-analyses) on 9 autoimmune diseases and 30 diseases in the MR study. AMSTAR 2 categorized the quality of evidence in six studies as critically low, six studies as low, eight studies as moderate, and one as high-quality evidence. The consistent result between the review and the MR study demonstrated the benefit of omega-3 fatty acids on rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Additionally, in our summary review, omega-3 fatty acids can improve disease activity and inflammation biomarkers; however, MR studies provided no consistent evidence for the causal effects of omega-3 fatty acids on psoriasis, multiple sclerosis (MS), type 1 diabetes (T1D), IgA nephropathy (IgAN), juvenile idiopathic arthritis (JIA), Crohn's disease (CD), and ulcerative colitis (UC)., Conclusion: The current study presented solid evidence highlighting the advantageous impact of omega-3 fatty acids on SLE and RA. This was achieved through the reduction of disease risk, the decrease of disease activity, and the mitigation of inflammatory biomarkers. To stratify another autoimmune illness, it is necessary to carry out rigorous evaluations to surpass the existing findings and enhance understanding in this domain., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

To clarify the synergistic pathogenic mechanism of Nicotiana benthamiana double infection with alfalfa mosaic virus (AMV) and white clover mosaic virus (WCMV), AMV and WCMV co-inoculation of N. benthamiana as treatment and single inoculation of AMV or WCMV and phosphate buffer solution (pH 7.0, PBS) as control, respectively. The concentrations and the relative expression of AMV and WCMV coat proteins were determined by a double antibody sandwich enzyme-linked immune sorbent assay (DAS-ELISA) and real-time fluorescence quantitative PCR (RT-qPCR) in a double infection of N. benthamiana with AMV and WCMV. Meanwhile, virion morphology, ultrastructure morphology, and chlorophyll content were observed and determined by electron microscopy. The results showed that the diseased symptoms were more serious, and virus concentration and relative expression of AMV and WCMV coat proteins were also higher in N. benthamiana double infection with AMV and WCMV than in AMV or WCMV single infection. The main symptoms manifested as severe mottle mosaic, shrinkage, and chlorosis. The concentrations of AMV and WCMV were 182.23 pg/mL and 148.77 pg/mL of double infection with AMV and WCMV, which were 1.75-fold and 1.62-fold than AMV and WCMV single infection, respectively. The relative expression of AMV and WCMV coat proteins was 4.25-fold and 2.50-fold than the single virus infection, respectively. Electron microscopy also observed that chloroplast malformation, cell membrane deformation, contents dissolution, grana lamella disorder, fat granules increased and enlarged, starch granules enlarged, and mitochondria were seriously malformed in a double infection of N. benthamiana with AMV and WCMV. The chlorophyll content was significantly lower for double infection with AMV and WCMV than for AMV or WCMV single-infected and CK, reduced by 31.52 %, 22.83 %, and 76.09 %, respectively. This is the first report of a double infection of N. benthamiana with AMV and WCMV that increases both virus concentrations and synergistically changes both host organelle ultrastructure and chlorophyll content., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests. Liang qiaolan reports financial support was provided by National Natural Science Foundation of China. Liang qiaolan reports a relationship with National Natural Science Foundation of China that includes: consulting or advisory, funding grants, paid expert testimony, speaking and lecture fees, and travel reimbursement. Liang qiaolan, chen ying e has patent pending to liang qiaolan. The authors declare no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Argonaute (AGO), a component of RNA-induced silencing complexes (RISCs), is a representative RNA-binding protein (RBP) known to bind with mature microRNAs (miRNAs) and is directly involved in post-transcriptional gene silencing. However, despite the biological significance of miRNAs, the roles of other miRNA-binding proteins (miRBPs) remain unclear in the regulation of miRNA loading, dissociation from RISCs and extracellular release. In this study, we performed protein arrays to profile miRBPs and identify 118 RBPs that directly bind to miRNAs. Among those proteins, the RBP quaking (QKI) inhibits extracellular release of the mature microRNA let-7b by controlling the loading of let-7b into extracellular vesicles via additional miRBPs such as AUF1 (also known as hnRNPD) and hnRNPK. The enhanced extracellular release of let-7b after QKI depletion activates Toll-like receptor 7 (TLR7) and promotes the production of proinflammatory cytokines in recipient cells, leading to brain inflammation in the mouse cortex. Thus, this study reveals the contribution of QKI to the inhibition of brain inflammation via regulation of extracellular let-7b release., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2024. Published by The Company of Biologists Ltd.)

Objective: This study was performed to explore the clinical significance of the expression of human beta-defensin 2 (HBD-2) and chemokine ligand 1/2 (CXCL-1/2) in psoriasis vulgaris., Methods: This study retrospectively included the study group (n = 160) and control group (n = 100) for analysis. The levels of inflammatory indicators, blood biochemical indicators, and immune indicators using ELISA. The psoriasis area and severity index (PASI) was used to evaluate disease severity. Levels of HBD-2, CXCL-1, CXCL-2 and CCL20 were determined by RT-PCR. The correlations of HBD-2, CXCL-1 and CXCL-2 levels with CCL20 and PASI scores were analyzed. The diagnostic value of HBD-2, CXCL-1 and CXCL-2 in psoriasis vulgaris was analyzed by ROC curve., Results: HBD-2, CXCL-1 and CXCL-2 were highly expressed in the lesions of psoriasis vulgaris patients, and were positively correlated with CCL20 and PASI score. HBD-2, CXCL-1 and CXCL-2 alone or in combination had high diagnostic value for psoriasis vulgaris and severe psoriasis, and the combined diagnostic value of the three was higher than that of a single indicator., Conclusion: HBD-2, CXCL-1, and CXCL-2 levels are closely related to the severity of psoriasis vulgaris and can effectively diagnose the occurrence and progression of psoriasis vulgaris.

Genomic copy number changes are associated with antifungal drug resistance and virulence across diverse fungal pathogens, but the rate and dynamics of these genomic changes in the presence of antifungal drugs are unknown. Here we optimized a dual-fluorescent reporter system in the diploid pathogen Candida albicans to quantify haplotype-specific copy number variation (CNV) and loss of heterozygosity (LOH) at the single-cell level with flow cytometry. We followed the frequency and dynamics of CNV and LOH at two distinct genomic locations in the presence and absence of antifungal drugs in vitro and in a murine model of candidiasis. Copy number changes were rapid and dynamic during adaptation to fluconazole and frequently involved competing subpopulations with distinct genotypes. This study provides quantitative evidence for the rapid speed at which diverse genotypes arise and undergo dynamic population-level fluctuations during adaptation to antifungal drugs in vitro and in vivo., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Purpose: The aim of this study was to investigate the application of PSMA-RADS version 2.0 in assessment of pulmonary metastases in patients with prostate cancer and whether PSMA PET/CT parameters provide incremental value., Patients and Methods: From October 2016 to July 2023, PC patients with pulmonary opacities (including pulmonary metastases, lung cancer, and pulmonary benign opacities) who underwent Al 18 F-PSMA-BCH PET/CT scans were retrospectively analyzed. CT imaging characteristics, including the longest diameter, density, smoothness, lobulation, pleural retraction, and vacuole sign, as well as PET parameters including SUV max and tumor-to-background ratio, were measured and analyzed. Additionally, the pulmonary PSMA-RADS score for each patient was determined. Independent predictors of pulmonary metastases were identified through univariate analysis and multivariate logistic regression analysis, which were utilized to construct a parallel diagnostic test. The differential diagnostic performances were evaluated using receiver operating characteristic analysis., Results: A total of 148 pulmonary opacities from 96 patients were retrospectively included. The number of pulmonary benign opacities, lung cancer, and pulmonary metastases were 48 (32.4%), 20 (13.5%), and 80 (54.1%), respectively. The number of opacities across different PSMA-RADS scores from 2 to 5 was 8 (5.4%), 88 (59.5%), 7 (4.7%), and 45 (30.4%). SUV max and smooth edges were independent predictors of pulmonary metastases (both P < 0.05), and the AUC of the parallel test for these 2 parameters was 0.86 (95% confidence interval: 0.79, 0.94; P < 0.001). Furthermore, the diagnostic accuracy of the parallel test across PSMA-RADS score from 2 to 5 was 85.7%, 79.6%, 100%, and 92.9%, respectively., Conclusions: Al 18 F-PSMA-BCH PET/CT parameters were helpful in differentiating pulmonary metastases in PC patients and provided incremental value when integrated with PSMA-RADS version 2.0., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To comprehensively assess the impact of aging, cigarette smoking, and chronic obstructive pulmonary disease (COPD) on pulmonary physiology using 129 Xe MR., Methods: A total of 90 subjects were categorized into four groups, including healthy young (HY, n = 20), age-matched control (AMC, n = 20), asymptomatic smokers (AS, n = 28), and COPD patients (n = 22). 129 Xe MR was utilized to obtain pulmonary physiological parameters, including ventilation defect percent (VDP), alveolar sleeve depth (h), apparent diffusion coefficient (ADC), total septal wall thickness (d), and ratio of xenon signal from red blood cells and interstitial tissue/plasma (RBC/TP)., Results: Significant differences were found in the measured VDP (p = 0.035), h (p = 0.003), and RBC/TP (p = 0.003) between the HY and AMC groups. Compared with the AMC group, higher VDP (p = 0.020) and d (p = 0.048) were found in the AS group; higher VDP (p < 0.001), d (p < 0.001) and ADC (p < 0.001), and lower h (p < 0.001) and RBC/TP (p < 0.001) were found in the COPD group. Moreover, significant differences were also found in the measured VDP (p < 0.001), h (p < 0.001), ADC (p < 0.001), d (p = 0.008), and RBC/TP (p = 0.032) between the AS and COPD groups., Conclusion: Our findings indicate that pulmonary structure and functional changes caused by aging, cigarette smoking, and COPD are various, and show a progressive deterioration with the accumulation of these risk factors, including cigarette smoking and COPD., Clinical Relevance Statement: Pathophysiological changes can be difficult to comprehensively understand due to limitations in common techniques and multifactorial etiologies. 129 Xe MRI can demonstrate structural and functional changes caused by several common factors and can be used to better understand patients' underlying pathology., Key Points: Standard techniques for assessing pathophysiological lung function changes, spirometry, and chest CT come with limitations. 129 Xe MR demonstrated progressive deterioration with accumulation of the investigated risk factors, without these limitations. 129 Xe MR can assess lung changes related to these risk factors to stage and evaluate the etiology of the disease., (© 2024. The Author(s), under exclusive licence to European Society of Radiology.)

The pathophysiology of hypertrophic scar (HS) shares similarities with cancer. HOXC10, a gene significantly involved in cancer development, exhibits higher expression levels in HS than in normal skin (NS), suggesting its potential role in HS regulation. And the precise functions and mechanisms by which HOXC10 influences HS require further clarification. Gene and protein expressions were analyzed using raeal-time quantitative polymerase chain reaction (RT-qPCR) and western blot techniques. Cell proliferation and migration were evaluated using EdU proliferation assays, CCK-8 assays, scratch assays, and Transwell assays. Chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assays were conducted to investigate the interactions between HOXC10 and STMN2. HOXC10 and STMN2 expression levels were significantly higher in HS tissues compared with NS tissues. Silencing HOXC10 led to decreased activation, proliferation, migration, and fibrosis in hypertrophic scar fibroblasts (HSFs). Our findings also indicate that HOXC10 directly targets STMN2. The promotional effects of HOXC10 knockdown on HSF activation, proliferation, migration, and fibrosis were reversed by STMN2 overexpression. We further demonstrated that HOXC10 regulates HSF activity through the TGF-β/Smad signaling pathway. HOXC10 induces the activation and fibrosis of HSFs by promoting the transcriptional activation of STMN2 and engaging the TGF-β/Smad signaling pathway. This study suggests that HOXC10 could be a promising target for developing treatments for HS., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

This study explored the feasibility of employing hyperspectral imaging (HSI) technology to quantitatively assess the effect of silicon (Si) on lead (Pb) content in oilseed rape leaves. Aiming at the defects of hyperspectral data with high dimension and redundant information, this paper proposed two improved feature wavelength extraction algorithms, repetitive interval combination optimization (RICO) and interval combination optimization (ICO) combined with stepwise regression (ICO-SR). The entire oilseed rape leaves were taken as the region of interest (ROI) to extract the visible near-infrared hyperspectral data within the 400.89-1002.19 nm range. In data processing, Savitzky-Golay (SG) smoothing, detrending (DT), and multiple scatter correction (MSC) were utilized for spectral data preprocessing, while recursive feature elimination (RFE), iteratively variable subset optimization (IVSO), ICO, and the two enhanced algorithms were employed to identify characteristic wavelengths. Subsequently, based on the spectral data of preprocessing and feature extraction, partial least squares regression (PLSR) and support vector regression (SVR) methods were used to construct various Pb content prediction models in oilseed rape leaves, with a comparison and analysis of each model performance. The results indicated that the two improved algorithms were more efficient in extracting representative spectral information than conventional methods, and the performance of SVR models was better than PLSR models. Finally, to further improve the prediction accuracy and robustness of the SVR models, the whale optimization algorithm (WOA) was introduced to optimize their parameters. The findings demonstrated that the MSC-RICO-WOA-SVR model achieved the best comprehensive performance, with R p 2 of 0.9436, RMSEP of 0.0501 mg/kg, and RPD of 3.4651. The results further confirmed the great potential of HSI combined with feature extraction algorithms to evaluate the effectiveness of Si in alleviating Pb stress in oilseed rape and provided a theoretical basis for determining the appropriate amount of Si application to alleviate Pb pollution in oilseed rape., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objectives: Individuals with Down syndrome (DS) have a higher incidence of hearing loss (HL) compared with their peers without developmental disabilities. Little is known about the associations between HL and functional hearing for individuals with DS. This study investigated two aspects of auditory functions, "what" (understanding the content of sound) and "where" (localizing the source of sound), in young adults with DS. Speech reception thresholds in quiet and in the presence of interferers provided insight into speech recognition, that is, the "what" aspect of auditory maturation. Insights into "where" aspect of auditory maturation were gained from evaluating speech reception thresholds in colocated versus separated conditions (quantifying spatial release from masking) as well as right versus left discrimination and sound location identification. Auditory functions in the "where" domain develop during earlier stages of cognitive development in contrast with the later developing "what" functions. We hypothesized that young adults with DS would exhibit stronger "where" than "what" auditory functioning, albeit with the potential impact of HL. Considering the importance of auditory working memory and receptive vocabulary for speech recognition, we hypothesized that better speech recognition in young adults with DS, in quiet and with speech interferers, would be associated with better auditory working memory ability and receptive vocabulary., Design: Nineteen young adults with DS (aged 19 to 24 years) participated in the study and completed assessments on pure-tone audiometry, right versus left discrimination, sound location identification, and speech recognition in quiet and with speech interferers that were colocated or spatially separated. Results were compared with published data from children and adults without DS and HL, tested using similar protocols and stimuli. Digit Span tests assessed auditory working memory. Receptive vocabulary was examined using the Peabody Picture Vocabulary Test Fifth Edition., Results: Seven participants (37%) had HL in at least 1 ear; 4 individuals had mild HL, and 3 had moderate HL or worse. Participants with mild or no HL had ≥75% correct at 5° separation on the discrimination task and sound localization root mean square errors (mean ± SD: 8.73° ± 2.63°) within the range of adults in the comparison group. Speech reception thresholds in young adults with DS were higher than all comparison groups. However, spatial release from masking did not differ between young adults with DS and comparison groups. Better (lower) speech reception thresholds were associated with better hearing and better auditory working memory ability. Receptive vocabulary did not predict speech recognition., Conclusions: In the absence of HL, young adults with DS exhibited higher accuracy during spatial hearing tasks as compared with speech recognition tasks. Thus, auditory processes associated with the "where" pathways appear to be a relative strength than those associated with "what" pathways in young adults with DS. Further, both HL and auditory working memory impairments contributed to difficulties in speech recognition in the presence of speech interferers. Future larger-sized samples are needed to replicate and extend our findings., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: Substance use disorder has been associated with increased morbidity in COVID-19 infection. However, less is known about the impact of active substance use and medications for opioid use disorder (MOUD) on COVID-19 outcomes. We conducted a retrospective cohort study to evaluate the impact of substance use, namely, cannabis, cocaine, alcohol, sedative and opioid use; and buprenorphine or methadone on COVID-19 morbidity and mortality., Methods: Using electronic health record data at a large urban hospital system, patients who tested positive for COVID-19 between January 1, 2020, and December 31, 2021, were included. Substance use was identified from urine toxicology and MOUD prescriptions within 90 days prior to admission. COVID-19 outcomes included mortality, ICU admission, need for intubation, and number and duration of hospitalizations. Multivariable logistic regression was performed controlling for variables such as age, sex, medical comorbidity, tobacco use, and social disadvantage., Results: Among COVID-19-positive patients (n = 17,423), sedative, cannabis, cocaine, and opioid use was associated with statistically significant increases in need for ICU care, need for ventilatory support, number of hospitalizations, and duration of hospitalization. Substance use was not associated with an increase in all-cause mortality. There were no statistically significant differences between methadone, buprenorphine, and other opioids on COVID-19 outcomes., Conclusions: Active substance use was associated with increased morbidity in COVID-19 infection. MOUD was not associated with worse COVID-19 outcomes compared to other opioids. Future studies focused on MOUD treatments that reduce morbidity may help improve clinical outcomes in COVID-19., Competing Interests: The authors do not have any financial conflicts of interest. Nicholaus Christian's effort was sponsored by HSR&D postdoctoral fellowship through the VA Office of Academic Affairs. Rajiv Radhakrishnan's effort was supported by NIDA grant (R21DA057540). The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official view of NIH, VA or the funding agencies., (Copyright © 2024 American Society of Addiction Medicine.)

Background: FLNC gene variants have predominantly been reported in adult populations with cardiomyopathies, and early-onset cases are less common. The genotype-phenotype relationship indicates that dilated cardiomyopathy (DCM) is often associated with FLNC truncating variants., Methods: We conducted a comprehensive genetic analysis using next generation sequencing (NGS) to identify FLNC variants in patients with cardiovascular conditions. Detailed phenotypic and variant analyses were performed to characterize the clinical features and genetic alterations. Minigene assays and structural modeling were used to investigate the pathogenicity caused by the identified variants., Results: In a cohort of 58 patients, novel heterozygous FLNC variants, c.3962A > T (p.Glu1321Val) and c.7543C > T (p.Leu2515Phe), were identified in patients presenting with dilated and mixed restrictive/hypertrophic cardiomyopathies, respectively. The c.3962A > T variant disrupted normal splicing, as demonstrated through the splicing prediction tool and minigene studies, further emphasizing its pathogenic potential., Conclusion: For missense variants of FLNC in patients with DCM, the splicing effect of the variant should be carefully checked. Early detection and intervention are crucial given the high risk of sudden cardiac death and severe cardiac complications., (© 2024. The Author(s).)

2-Ethylhexyl diphenyl phosphate (EHDPP), ubiquitously monitored in environmental media, is highly bioaccumulative and may pose long-term risks, even after short-term exposure. In this investigation, larval zebrafish were exposed to 0.05, 0.5, and 5.0 μg/L EHDPP from 4 to 120 h postfertilization (hpf) to examine the long-term neurotoxicity effects of early exposure. Exposure to 5.0 μg/L EHDPP yielded hyperactive locomotor behavior, which was characterized by increased swimming speed, larger turning angles, and heightened sensitivity to light-dark stimulation. The predicted targets of EHDPP (top 100 potential macromolecules) were primarily associated with brain diseases like Alzheimer's disease (AD). Comparisons of differentially expressed genes (DEGs) from AD patients (GSE48350) and RNA-seq data from EHDPP-exposed zebrafish confirmed consistently abnormal regulatory pathways. EHDPP's interaction with M1 and M5 muscarinic acetylcholine receptors likely disrupted calcium homeostasis, leading to mitochondrial dysfunction and neurotransmitter imbalance as well as abnormal locomotor behavior. Especially, 5.0 μg/L EHDPP exposure during early development (4-120 hpf) triggered early- and midstage AD-like symptoms in adulthood (180 dpf), characterized by cognitive confusion, aggression, blood-brain barrier disruption, and mitochondrial damage in brains. These findings provide deep insights into the long-term neurotoxicity effects and Alzheimer's disease risks of early EHDPP exposure at extremely low dosages.

Purpose: To investigate whether a bounce in plasma Epstein-Barr virus (EBV) DNA during posttreatment surveillance of nasopharyngeal carcinoma (NPC) informs the risk of clinical recurrence and its implication for early therapeutic intervention., Methods: 950 non-disseminated NPC patients with completed remission in 3 months after treatment were retrospectively screened. Detectable EBV DNA with no evidence of clinical relapse during follow-up was deemed as DNA bounce. The diagnostic and prognostic performance of EBV DNA bounce was assessed for subsequent failures., Results: Tumor recurrence occurred in 6.6 %, 10.1 % and 65.8 % in the group with persistently negative EBV DNA, single positive test and ≥ 2 positive tests, respectively. EBV DNA bounce over twice was associated with worse disease-free survival (DFS), locoregional recurrence-free survival (LRRFS), and distant metastasis-free survival (DMFS) than the other two groups. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy for the prediction of recurrence were 0.56, 0.95, 0.66, 0.93 and 0.90 using two positive tests, which were hence deemed as biological relapse. Serial cutoffs (EBV DNA 1 ≥ 40 copies/ml or EBV DNA 2 ≥100 copies/ml) further defined a high-risk subgroup with an eventual recurrence rate of 77.9 % and 3-year DFS of merely 20.5 %. Prophylactic medical intervention with capecitabine or S1 significantly improved the 3-year DFS when compared to those with observation., Conclusions: The earliest two positive tests of EBV DNA represent a biomarker of biological relapse that allows early detection of clinical recurrence in EBV-related NPC. For high-risk biological relapse, preemptive intervention provides potential survival benefits., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Sandwich composites made of particle-filled hollow sphere structures (PHSS) and steel sheets offer excellent lightweight and damping properties, ideal for high-speed machine tool components under dynamic loads. Previous research has focused on single particle-filled hollow sphere (PHS) and small PHSS, leaving a gap understanding of PHSS/steel sandwich composites. In this study a test rig was developed, and Design of Experiments and Response Surface Analysis were used to investigate the effects of sheet and core thickness (design parameters), filling ratio, and particle size (particle parameters) on the damping performance of PHSS/steel sandwiches. The results indicate that the design parameters have a significant influence on damping performance. The interaction between design and particle parameters also substantially affects damping. Minimizing particle size, increasing filling ratio, thinning the face layer, and thickening the core layer significantly improve structural damping. To address manufacturing tolerances, a finite element (FE) model-based optimization was developed to accurately determine PHSS material parameters. These parameters were used in an FE model of the PHSS-steel composite, with identified contact parameters minimizing measurement and simulation differences. The homogenized material model and the linear model using global damping parameters accurately reproduce the dynamic properties of the PHSS-steel sandwich composite in low vibration modes., (© 2024. The Author(s).)

Background: Large soft tissue defects of the lower limb and foot are common occurrence in clinical practice and a considerable number of flaps have been used to treat them. However, there have been few reports using the superficial inferior epigastric artery (SIEA) flap. This review aims to present the experience of using the SIEA flaps for the repair of large soft tissue defects of the lower limb and foot., Methods: A retrospective review of data from 11 patients who underwent coverage of lower limb and foot defects exceeding 120 cm 2 (15 × 9 cm) using SIEA flaps from March 2018 to July 2022 were retrospectively reviewed. The average size of the defects was 18 × 11 cm 2 (range 15 × 9 cm 2 -32 × 16 cm 2 ). Flap survival rates, surgical complications and overall long-term outcomes were recorded., Results: All 11 flaps survived. One flap was partially necrotic at the edge and healed after several changes of dressing. Additionally, one flap presented with mild venous congestion. The mean follow-up period was 18 months (ranging from 12 to 30 months). The mean size of the flaps was 20 × 12 cm 2 (range 17 × 9 cm 2 -34 × 18 cm 2 ). The flaps were observed to be aesthetically pleasing and exhibited a well-defined texture. The donor wounds were successfully closed primarily, with only linear scarring remaining., Conclusions: The SIEA flap is characterised by concealed donor area, superficial vascular location, easy access and primary closure, which results in favourable aesthetic outcomes. It is an appropriate choice for the repair of large soft tissue defects of the lower limb and foot., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Liu, Xie, Chu, Zhou, Luo and Li.)

Nature often provides invaluable insights into technological innovation and the construction of nanomaterials. Inspired by the pitaya fruit's strategy of wrapping seeds within its pulp to enhance seed survival, a unique nanocomposite based on metal-organic framework (MOF)-encapsulated CuS nanoparticles (NPs) is developed. This design effectively addresses the challenge of short retention time afforded by CuS NPs for therapeutic and imaging purposes. The MOF acts as the "pitaya pulp" protecting the internal CuS NPs ("pitaya seeds"), thereby increasing their retention time in vivo. This system exhibits triple-enzyme-mimicking activities and is proposed for application in photoacoustic and magnetic resonance imaging-guided therapies, including chemodynamic therapy, photothermal therapy, and cuproptosis-related therapy. The exceptional enzyme-mimicking activities of superoxide dismutase, catalase, and peroxidase not only produce oxygen to alleviate hypoxia but also generate a reactive oxygen species (ROS) storm for effective tumor destruction. By combining these multienzymatic properties, superior photothermal performance, and Cu-induced cuproptosis, nanozyme-treated mice exhibited an 84% inhibition of tumor growth-approximately double the effect observed in mice treated with CuS NPs alone. This study presents a smart strategy for integrating imaging with therapeutic modalities, achieving exceptional outcomes for precise imaging-guided tumor therapy., (© 2024 Wiley‐VCH GmbH.)

Single-crystalline covalent organic frameworks (COFs) are highly desirable toward understanding their pore chemistry and functions. Herein, two 50-100 μm single-crystalline three-dimensional (3D) COFs, TAM-TFPB-COF and TAPB-TFS-COF, were prepared from the condensation of 4,4',4″,4‴-methanetetrayltetraaniline (TAM) with 3,3',5,5'-tetrakis(4-formylphenyl)bimesityl (TFPB) and 3,3',5,5'-tetrakis(4-aminophenyl)bimesityl (TAPB) with 4,4',4″,4‴-silanetetrayltetrabenzaldehyde (TFS), respectively, in 1,4-dioxane under the catalysis of acetic acid. Single-crystal 3D electron diffraction reveals the triply interpenetrated dia-b networks of TAM-TFPB-COF with atom resolution, while the isostructure of TAPB-TFS-COF was disclosed by synchrotron single-crystal X-ray diffraction and synchrotron powder X-ray diffraction with Le Bail refinements. The nitrogen sorption measurements at 77 K disclose the microporosity nature of both activated COFs with their exceptionally high Brunauer-Emmett-Teller surface areas of 3533 and 4107 m 2 g -1 , representing the thus far record high specific surface area among imine-bonded COFs. This enables the activated COFs to exhibit also the record high methane uptake capacities up to 28.9 wt % (570 cm 3 g -1 ) at 25 °C and 200 bar among all COFs reported thus far. This work not only presents the structures of two single-crystalline COFs with exceptional microporosity but also provides an example of atom engineering to adjust permanent microporous structures for methane storage.

Driving anger is a serious global issue that poses risks to road safety, thus necessitating the development of effective detection and intervention methods. This study investigated the feasibility of using smartphones to capture facial expressions to detect event-related driving anger. Sixty drivers completed the driving tasks in scenarios with and without multi-stage road events and were induced to angry and neutral states, respectively. Their physiological signals, facial expressions, and subjective data were collected. Four feature combinations and six machine learning algorithms were used to construct driving anger detection models. The model combining facial features and the XGBoost algorithm outperformed models using physiological features or other algorithms, achieving an accuracy of 87.04% and an F1-score of 85.06%. Eyes, mouth, and brows were identified as anger-sensitive facial areas. Additionally, incorporating individual characteristics into models further improved classification performance. This study provides a contactless and highly accessible approach for event-related driving anger detection. Practitioner Summary: This study proposed a cost-effective and contactless approach for event-related and real-time driving anger detection and could potentially provide insights into the design of emotional interactions in intelligent vehicles.

Reasonable construction of high activity and selectivity electrocatalysts is crucial to achieve efficient ethanol oxidation reaction (EOR). However, the oxidation of ethanol tends to produce CO species that poison the active centers of the EOR electrocatalysts. Herein, a unique amorphous CrO x -protected defect-rich ultrafine Pd nanowires (CrO x -Pd NWs) is developed. On the one hand, the CrO x layer can act as a protective layer to maintain the structure of the nanowire. On the other hand, it can play the role of OH regulator to optimize the adsorption energy barrier of intermediate species in Pd nanowire, thereby enhancing the ability of the catalyst to resist CO poisoning. The CrO x -Pd NWs exhibit excellent EOR performance with 3.64 times higher mass activity and 50 mV lower CO electro-oxidation potential than commercial Pd black. The results show that the CrO x layer promotes the dissociation of H 2 O into OH ads , while the CrO x transfers electrons to neighboring Pd atoms optimizing the electronic configuration of Pd, thus selectively oxidizing ethanol to acetate and preventing the formation of toxic * CO. This work provides an effective strategy for the synthesis of nanowire materials with oxide/metal interfaces and offers new ideas for the design of catalysts that can efficiently drive EOR., (© 2024 Wiley‐VCH GmbH.)

Background Context: Longer posterior lumbar interbody fusion (PLIF) surgeries for individuals with lumbar spinal stenosis are linked to more complications and negatively affect recovery after the operation. Therefore, there is a critical need for a method to accurately predict patients who are at risk for prolonged operation times., Purpose: This research aimed to develop a clinical model to predict prolonged operation time for patients undergoing PLIF procedures., Study Design/setting: This study employs a machine-learning approach to analyze data retrospectively collected., Patient Sample: 3233 patients diagnosed with lumbar spinal stenosis (LSS) had posterior lumbar interbody fusion (PLIF) at 22 hospitals in China from January 2015 to December 2022., Outcome Measures: The primary outcome was operation time. Prolonged operation time defined as exceeded 75% of the overall surgical duration, which mean exceeding 240 minutes., Methods: A total of 3233 patients who underwent PLIF surgery with lumbar spinal stenosis (LSS) were divided into one training group and four test groups based on different district areas. The training group included 1569 patients, while Test1 had 541, Test2 had 403, Test3 had 351, and Test4 had 369 patients. Variables consisted of demographics, perioperative details, preoperative laboratory examinations and other Additional factors. Six algorithms were employed for variable screening, and variables identified by more than two screening methods were incorporated into the final model. In the training cohort, a 10-fold cross-validation (CV) and Bayesian hyperparameter optimization techniques were utilized to construct a model using eleven machine learning algorithms. Following this, the model was evaluated using four separate external test sets, and the mean Area Under the Curve (AUC) was computed to determine the best-performing model. Further performance metrics of the best model were evaluated, and SHapley Additive exPlanations(SHAP) were used for interpretability analysis to enhance decision-making transparency. Ultimately, an online calculator was created., Results: Among the various machine learning models, the Random Forest achieved the highest performance in the validation set, with AUROC scores of 0.832 in Test1, 0.834 in Test2, 0.816 inTest3, 0.822 in Test4) compared with other machine learning models. The top contributing variables were number of levels fusion, pre-APTT, weight and age. The predictive model was further refined by developing a web-based calculator for clinical application. (https://wenle.shinyapps.io/PPOT&#95;LSS/) CONCLUSIONS: This predictive model can facilitate identification of risk for prolonged operation time following PLIF surgery. Predictive calculators are expected to improve preoperative planning, identify patients with high risk factors, and help clinicians facilitating the improvement of treatment plans and the implementation of clinical intervention., Competing Interests: Declaration of competing interests None., (Copyright © 2024. Published by Elsevier Inc.)

Chiral structures and functions are essential natural components in biominerals and biological crystals. Chiral molecules direct inorganics through chiral growth of facets or screw dislocation of crystal clusters. As chirality promoters, they initiate an asymmetric hierarchical self-assembly in a quasi-thermodynamic steady state. However, achieving chiral assembly requires a delicate balance between intricate interactions. This complexity causes the roles of achiral-chiral and inorganic components in crystallization to remain ambiguous. Here, we elucidate a definitive mechanism using an achiral-chiral ligand strategy to assemble inorganics into hierarchical, self-organized superstructures. Achiral ligands cluster inorganic building blocks, while chiral ligands impart chiral rotation. Achiral and chiral ligands can flexibly modulate the chirality of superstructures by fully using their competition in coordination chemistry. This dual-ligand strategy offers a versatile framework for engineering chiroptical nanomaterials tailored to optical devices and metamaterials with optical activities across a broad wavelength range, with applications in imaging, detection, catalysis, and sensing.

The brain is the central hub of the entire nervous system. Its development is a lifelong process guided by a genetic blueprint. Understanding how genes influence brain development is critical for deciphering the formation of human cognitive functions and the underlying mechanisms of neurological disorders. Recent advances in multi-omics techniques have now made it possible to explore these aspects comprehensively. However, integrating and analyzing extensive multi-omics data presents significant challenges. Here, we introduced MAPbrain (http://bigdata.ibp.ac.cn/mapBRAIN/), a multi-omics atlas of the primate brain. This repository integrates and normalizes both our own lab's published data and publicly available multi-omics data, encompassing 21 million brain cells from 38 key brain regions and 436 sub-regions across embryonic and adult stages, with 164 time points in humans and non-human primates. MAPbrain offers a unique, robust, and interactive platform that includes transcriptomics, epigenomics, and spatial transcriptomics data, facilitating a comprehensive exploration of brain development. The platform enables the exploration of cell type- and time point-specific markers, gene expression comparison between brain regions and species, joint analyses across transcriptome and epigenome, and navigation of cell types across species, brain regions, and development stages. Additionally, MAPbrain provides an online integration module for users to navigate and analyze their own data within the platform., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Introduction: Glucagon-like peptide-1 receptor agonists are novel medications with proven efficacy in treating type 2 diabetes mellitus, and are increasingly being used for weight loss. They may potentially have benefit in treating metabolic disorders; however, evidence is sparse with regards to treating high blood pressure (BP). We performed a systematic review, meta-analysis and meta-regression investigating the efficacy of GLP-1 RAs in lowering BP in obese or overweight patients., Methods: Three electronic databases (PubMed, EMBASE, and CENTRAL) were systematically searched for randomized controlled trials (RCTs) published from inception to 13 February 2024. Pair-wise meta-analysis and random effects meta-regression models were utilized. Fixed effects meta-regression was used to unify treatment effects across different GLP-1 RA doses., Results: We included a total of 30 RCTs with a combined population of 37 072 patients. GLP-1 RAs demonstrated a mean systolic BP (SBP) reduction of -3.37 mmHg [95% confidence interval (CI) -3.95 to -2.80] and a mean diastolic BP (DBP) reduction of -1.05 mmHg (95% CI -1.46 to -0.65) compared with placebo. This effect was consistent across subgroups for diabetic status, formulation of GLP-1 RA, follow-up duration and route of administration for both SBP and DBP, with the exception of subgroups investigating exenatide. Meta-regression suggested no significant correlation between BP reduction and baseline characteristics such as age, percentage of male patients, HbA1c, weight, BMI, and percentage of patients with hypertension., Conclusion: Our meta-analysis suggests significant BP reduction benefits from GLP-1 RA use in obese or overweight patients, consistent across diabetic status, duration of treatment, and across route of administration., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

The emulsion gel composed of proteins and polysaccharides exhibits significant potential as a targeted delivery system for bioactives in the gastrointestinal tract. In this study, a composite emulsion was prepared by using sodium caseinate (NaCas) and gellan gum (GG), which was subsequently crosslinked with transglutaminase (TG), glucono-δ-lactone (GDL), and calcium ions (Ca 2+ ) to form emulsion gels. The physicochemical properties of the NaCas/GG emulsion gels were characterized to verify the effects of zeaxanthin dipalmitate encapsulation and protection, and a possible mechanism was discussed. The appearance and microscopy analyses revealed that the Ca 2+ -induced NaCas/GG emulsion gel exhibited superior shape retention and a denser network structure compared to GDL or TG crosslinking methods. The rheological analysis demonstrated that the Ca 2+ -crosslinked emulsion gels had higher modulus and hardness than their TG- or GDL- crosslinked counterparts. Infrared spectroscopy, molecular docking, and gelling force analysis revealed that the gelation mechanism of these emulsion gels primarily involved carbonyl-amide group crosslinking reactions, hydrogen bonding, and hydrophobic interactions. Furthermore, the Ca 2+ -crosslinked emulsion gel encapsulating zeaxanthin dipalmitate exhibited excellent thermal stability, resistance to gastrointestinal conditions, and stability. Overall, the above findings highlight that using Ca 2+ crosslinking in NaCas/GG composite emulsion yields edible composite materials with enhanced functional performance, thereby expanding the possibilities for food gel design strategies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Esophageal stenosis is a troublesome complication after circumferential ESD. This study examined the efficacy of betulin gel in preventing esophageal stenosis after ESD in a porcine model., Methods: Twelve pigs were randomized to betulin group and control group evenly. At the distal esophagus, circumferential ESD was performed in all animals. In the betulin group, betulin gel was applied at days 1, 3, and 7. Endoscopy examination was performed at day 3, 1 week, 2 weeks, and 4 weeks post-ESD. Then pigs were killed for macroscopic and histologic esophageal evaluation., Results: The rate of esophageal stricture was lower in the betulin group (53.3 ± 12.5% vs 88.3% ± 2.9, p = 0.02). Betulin-treated pigs had lower dysphagia score (2.0 ± 0 vs 3.3 ± 0.5, p < 0.001), less weight loss (11.78% ± 2.16 vs 15.85% ± 3.63, p = 0.04), and better passability of the open and closed biopsies forceps (83.33% vs. 0%, p = 0.015, and 100% vs. 0%, p = 0.002) 4 weeks post-ESD. Histologically, better re-epithelization (63.2 ± 10.7 mm vs 22.8 ± 10.1 mm, p < 0.001), slighter submucosal fibrosis (0.95 ± 0.17 mm vs 2.32 ± 0.48 mm, p = 0.002), lower muscularis propria damage score (1 vs 3, p < 0.001), and less inflammatory cells (307 vs 675 per high-power field, p = 0.002) were noted in the betulin group. The expression levels of TGF-β1, collagen i, collagen III, and α-SMA were significantly lower in the betulin group compared to the control group (p < 0.05)., Conclusions: Betulin gel shows promise in reducing fibrosis, enhancing repair, and preventing esophageal stricture after ESD, suggesting a potential new strategy for prevention., (© 2024. The Author(s) under exclusive licence to The Japan Esophageal Society.)

1D flexible fibers assembled 3D porous networked ceramic fiber aerogels (CFAs) are developed to overcome the brittleness of traditional ceramic particle aerogels. However, existing CFAs with disordered and quasi-ordered structures fail to balance the relationship between flexibility, robustness, and thermal insulation. Creating novel architectural CFAs with an excellent combination of performances has proven extremely challenging. In this paper, a novel strategy is adopted to fabricate porous mullite fibrous aerogels (MFAs) with ordered structures by combining fiber sedimentation and electric field-induced fiber alignment techniques. For the first time, electric field-induced alignment of ceramic fibers is utilized to prepare bulk aerogels on a large scale. The resulting MFAs exhibit ultra-low high-temperature thermal conductivity of 0.0830 W m -1 K -1 at 1000 °C, anisotropic mechanical and sound absorption performances, and multifunctionality in terms of the combination of thermal insulation, sound absorption, and hydrophobicity. The successful synthesis of such fascinating materials may provide new insights into the design and development of multifunctional CFAs for various applications., (© 2024 Wiley‐VCH GmbH.)

The advancement of electronic devices necessitates the development of three-dimensional (3D) high-precision conductive microstructures, which have extensive applications in bio-electronic interfaces, soft robots, and electronic skins. Two-photon polymerization (TPP) based 3D printing is a critical technique that offers unparalleled fabrication resolution in 3D space for intricate conductive structures. While substantial progress has been made in this field, this review summarizes recent advances in the 3D printing of conductive microstructures via TPP, mainly focusing on the essential criteria of photoresist resins suitable for TPP. Further preparation strategies of these photoresists and methods for constructing 3D conductive microstructures via TPP are discussed. The application prospects of 3D conductive microstructures in various fields are discussed, highlighting the imperative to advance their additive manufacturing technology. Finally, strategic recommendations are offered to enhance the construction of 3D conductive microstructures using TPP, addressing prevailing challenges and fostering significant advancements in manufacturing technology., (© 2024 Wiley‐VCH GmbH.)

As a subset of mononuclear phagocytes in the central nervous system, microglia play a crucial role in immune defense and homeostasis maintenance. Microglia can regulate their states in response to specific signals of health and pathology. Microglia-mediated neuroinflammation is a pathological hallmark of neurodegenerative diseases, neurological damage and neurological tumors, underscoring its key immunoregulatory role in these conditions. Intriguingly, a substantial body of research has indicated that extracellular vesicles can mediate intercellular communication by transporting cargoes from parental cells, a property that is also reflected in microenvironmental signaling networks involving microglia. Based on the microglial characteristics, we briefly outline the biological features of extracellular vesicles and focus on summarizing the integrative role played by microglia in the maintenance of nervous system homeostasis and progression of different neurological diseases. Extracellular vesicles may engage in the homeostasis maintenance and pathological process as a medium of intercellular communication. Here, we aim to provide new insights for further exploration of neurological disease pathogenesis, which may provide theoretical foundations for cell-free therapies., Competing Interests: Declaration of competing interest The authors declare that they have no relevant financial or nonfinancial interests to disclose that are relevant to the content of this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Mitochondrial genes and nuclear genes cooperate closely to maintain the functions of mitochondria, especially in the oxidative phosphorylation (OXPHOS) pathway. However, mitochondrial genes among arthropod lineages have dramatic evolutionary rate differences. Haplodiploid arthropods often show fast-evolving mitochondrial genes. One hypothesis predicts that the small effective population size of haplodiploid species could enhance the effect of genetic drift leading to higher substitution rates in mitochondrial and nuclear genes. Alternatively, positive selection or compensatory changes in nuclear OXPHOS genes could lead to the fast-evolving mitochondrial genes. However, due to the limited number of arthropod genomes, the rates of evolution for nuclear genes in haplodiploid species, besides hymenopterans, are largely unknown. To test these hypotheses, we used data from 76 arthropod genomes, including 5 independently evolved haplodiploid lineages, to estimate the evolutionary rates and patterns of gene family turnover of mitochondrial and nuclear genes., Results: We show that five haplodiploid lineages tested here have fast-evolving mitochondrial genes and fast-evolving nuclear genes related to mitochondrial functions, while nuclear genes not related to mitochondrion showed no significant evolutionary rate differences. Among hymenopterans, bees and ants show faster rates of molecular evolution in mitochondrial genes and mitochondrion-related nuclear genes than sawflies and wasps. With genome data, we also find gene family expansions and contractions in mitochondrion-related genes of bees and ants., Conclusions: Our results reject the small population size hypothesis in haplodiploid species. A combination of positive selection and compensatory changes could lead to the observed patterns in haplodiploid species. The elevated evolutionary rates in OXPHOS complex 2 genes of bees and ants suggest a unique evolutionary history of social hymenopterans., (© 2024. The Author(s).)

To tackle the clinical challenge of noninvasively assessing immunotherapy efficacy in patients, here we used positron emission tomography (PET) with 68 Ga-grazytracer, which targets granzyme B, a crucial effector molecule secreted by activated CD8 + T cells. In this phase 1/2 clinical trial (NCT05000372) involving a diverse cohort of 24 patients with solid tumors and lymphomas who received immunotherapies, including immune checkpoint inhibitors (either alone or with chemotherapies) and chimeric antigen receptor-T cell therapy, we examined the in vivo behaviors of 68 Ga-grazytracer. Primary endpoints were safety, biodistribution, granzyme B specificity, and the predictive utility of 68 Ga-grazytracer, while secondary endpoint was the relationship between 68 Ga-grazytracer uptake and tumor immune phenotype. 68 Ga-grazytracer exhibited a safe profile and specifically targeted granzyme B in patients. 68 Ga-grazytracer PET showed superior predictive value for short-term prognosis and progression-free survival than those of conventional assessment criteria, including RECIST 1.1 and PERCIST. Moreover, the uptake of 68 Ga-grazytracer in tumors was significantly higher in those with a "non-desert" immune phenotype than those with an immune "desert" phenotype, thereby meeting the primary and secondary endpoints of this trial. Collectively, we successfully visualized CD8 + T cell effector function in humans using 68 Ga-grazytracer PET, offering insights for enhancing immunotherapy assessment, patient stratification and treatment planning., (© 2024. The Author(s).)

Background: Large Hemispheric Infarction (LHI) is a devastating disease with high mortality. This study aimed to use electroencephalography (EEG) to evaluate the death risk of LHI patients and identify suitable evaluation time., Methods: This study retrospectively collected clinical and EEG data from 73 LHI patients, dividing them into death and survival group at discharge. EEG data was classified as 1-5 days and 6-14 days after onset according to the time intervals of cerebral edema. Regression and receiver operator characteristic curve (ROC) analysis were applied to explore the impact of temporal changes in various EEG and clinical features on death., Results: The areas under ROC curve (AUC) of death prediction for non-α frequency on non-infarct side at 6-14 days after onset was significantly higher than that at 1-5 days (p = 0.004). And there was no significant difference between the AUC of seizure activity for death prediction at 1-5 days and 6-14 days (p = 0.418). Multivariate regression analysis revealed that non-α frequency on non-infarct side and seizure activity at 6-14 days after onset were the independent risk factors for the death of LHI patients. Additionally, above two EEG features significantly improved the death predictive efficacy of clinical features in LHI patients with the integrated discrimination improvement index (IDI) of 0.174 (p = 0.015) and the net reclassification improvement (NRI) of 1.314 (p<0.001)., Conclusions: Non-α frequency on non-infarct side and seizure activity were reliable indicators for death prediction. 6-14 days after onset was the better time window for death evaluation of LHI patients through EEG., (© 2024. Fondazione Società Italiana di Neurologia.)

Background: Ovarian cancer is the most mortality malignancy in gynecology. N7-methylguanosine (m7G) is one of the most prevalent RNA modifications in the development and progression of cancer. The aim of this study is to investigate the effect of m7G-related lncRNA on ovarian cancer in terms of instruction prognosis and immunotherapy., Methods: After integrating and processing the RNA expression profiles with the clinical sample information in the TCGA database, we initially screened to the m7G-related lncRNAs by Spearman correlation analysis, and subsequently obtained a prognostic model constructed by five m7G-related lncRNAs with Univariate Cox analysis, LASSO regression analysis, and Multivariate Cox regression analysis, after which we further evaluated and validated the prognostic value of the model using Kaplan-Meier survival analysis, Principal component analysis, Nomogram, and ROC curve. In addition, based on this risk model, we explored the differentially enriched pathways and functions of the high and low risk groups, and characterized the immune cells, immune functions, gene mutations, and drug sensitivity between the two groups., Results: After a series of rigorous filtering, we finally attained a prognostic risk model consisting of KRT7-AS, USP30-AS1, ZFHX4-AS1, ACAP2-IT1, and TWSG1-DT which is excellent in predicting the prognostic survival of ovarian cancer patients as well as existing as an independent prognostic factor. Moreover, the model has certain relevance in the immune cells and functions between high and low risk groups, and simultaneously, the signature has the role of guiding the option of immunotherapy and chemotherapeutic drugs., Conclusion: Altogether, our study established a tight connection between m7G-associated lncRNAs and ovarian cancer, with potential that the prognostic patterns contribute to steering the prognosis of ovarian cancer patients, measuring the efficacy of immunotherapeutic approaches, and detecting effective chemotherapeutic agents., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Li, Wang, Zhang, Quan and Zhou.)

Pueraria is a time-honored food and medicinal plant, which is widely used in China. Puerarin, the main component extracted from pueraria, has a variety of pharmacological characteristics. In recent years, puerarin has received increasing attention for its significant hepatoprotective effects, such as metabolic dysfunction-associated steatotic liver disease, alcohol-related liver disease, and hepatic carcinoma. This paper explores the pharmacological effects of puerarin on various liver diseases through multiple mechanisms, including inflammation factors, oxidative stress, lipid metabolism, apoptosis, and autophagy. Due to its restricted solubility, pharmacokinetic studies revealed that puerarin has a low bioavailability. However, combining puerarin with novel drug delivery systems can improve its bioavailability. Meanwhile, puerarin has very low toxicity and high safety, providing a solid foundation for its further. In addition, this paper discusses puerarin's clinical trials, highlighting its unique advantages. Given its excellent pharmacological effects, puerarin is expected to be a potential drug for the treatment of various liver diseases., (© 2024. The Author(s).)

Ethnopharmacological Relevance: Flos Trollii (FT) is the dried flower of Trollius Chinensis Bunge of Ranunculaceae with the pharmacological properties of anti-inflammatory, antibacterial, antiviral, anti-oxidative. The herb FT is not only a traditional Chinese medicine (TCM) but also an extensively utilized ethnic medicine, employed by diverse ethnic groups including Mongolian, Tibetan, and Kazakh., Aim of Study: FT was taken as an example to construct a strategy of quality markers (Q-markers) identification based on effect, property flavor material basis, and rapid quantitative evaluation using near-infrared (NIR) spectroscopy and chemometric methods of TCM., Materials and Methods: Initially, the anti-inflammatory efficacy of FT from three places of origin was evaluated using the RAW264.7-cell inflammatory model, and the bitter property flavor was characterized using an electronic tongue. The high-performance liquid chromatography(HPLC) fingerprint of FT was generated, and the quality of FT from different origins was evaluated employing chemometrics. Next, potential anti-inflammatory and bitter property flavor compounds were screened utilizing a fingerprinting-effect relationship and fingerprinting-property flavor relationship model using partial least squares regression (PLSR). The Q-markers of the FT were confirmed based on the testability principle. Then, a swift, uncomplicated, and precise Q-marker content of the FT prediction model was developed by adopting NIR., Results: The main common fingerprinting peaks affecting FT's efficacy and property flavor were screened. Five of these compounds, 2″-O-beta-L-galactopyranosylorientin, orientin, vitexin, veratric acid, and isoquercitrin, characterized using HPLC and ultra-high performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS), could be regarded as Q-markers of FT. Q-marker content of the FT prediction model developed adopting NIR spectroscopy was rapid and effective., Conclusion: According to the strategy proposed in this study, a quantitative NIR spectroscopic method to identify Q-markers could be a tool to improve the QC efficiency of TCM., Competing Interests: Declaration of competing interest The authors declared that they have no conflicts of interest to this work. We declare that we do not have any commercial or associative interest that represents a conflict of interest in connection with the work submitted., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Skeletal muscle adaptation to exercise involves various phenotypic changes that enhance the metabolic and contractile functions. One key regulator of these adaptive responses is the activation of AMPK, which is influenced by exercise intensity. However, the mechanistic understanding of AMPK activation during exercise remains incomplete. In this study, we utilized an in vitro model to investigate the effects of mechanical loading on AMPK activation and its interaction with the mTOR signaling pathway. Proteomic analysis of muscle cells subjected to static loading (SL) revealed distinct quantitative protein alterations associated with RNA metabolism, with 10% SL inducing the most pronounced response compared to lower intensities of 5% and 2% as well as the control. Additionally, 10% SL suppressed RNA and protein synthesis while activating AMPK and inhibiting the mTOR pathway. We also found that SRSF2, necessary for pre-mRNA splicing, is regulated by AMPK and mTOR signaling, which, in turn, is regulated in an intensity-dependent manner by SL with the highest expression in 2% SL. Further examination showed that the ADP/ATP ratio was increased after 10% SL compared to the control and that SL induced changes in mitochondrial biogenesis. Furthermore, Seahorse assay results indicate that 10% SL enhances mitochondrial respiration. These findings provide novel insights into the cellular responses to mechanical loading and shed light on the intricate AMPK-mTOR regulatory network in muscle cells.

Background: The urgent need for affordable and rapid detection methodologies for foodborne pathogens, particularly Escherichia coli (E. coli), highlights the importance of developing efficient and widely accessible diagnostic systems. Dark field microscopy, although effective, requires specific isolation of the target bacteria which can be hindered by the high cost of producing specialized antibodies. Alternatively, M13 bacteriophage, which naturally targets E. coli, offers a cost-efficient option with well-established techniques for its display and modification. Nevertheless, its filamentous structure with a large length-diameter ratio contributes to nonspecific binding and low separation efficiency, posing significant challenges. Consequently, refining M13 phage methodologies and their integration with advanced microscopy techniques stands as a critical pathway to improve detection specificity and efficiency in food safety diagnostics., Methods: We employed a dual-plasmid strategy to generate a truncated M13 phage (tM13). This engineered tM13 incorporates two key genetic modifications: a partial mutation at the N-terminus of pIII and biotinylation at the hydrophobic end of pVIII. These alterations enable efficient attachment of tM13 to diverse E. coli strains, facilitating rapid magnetic separation. For detection, we additionally implemented a convolutional neural network (CNN)-based algorithm for precise identification and quantification of bacterial cells using dark field microscopy., Results: The results obtained from spike-in and clinical sample analyses demonstrated the accuracy, high sensitivity (with a detection limit of 10 CFU/μL), and time-saving nature (30 min) of our tM13-based immunomagnetic enrichment approach combined with AI-enabled analytics, thereby supporting its potential to facilitate the identification of diverse E. coli strains in complex samples., Conclusion: The study established a rapid and accurate detection strategy for E. coli utilizing truncated M13 phages as capture probes, along with a dark field microscopy detection platform that integrates an image processing model and convolutional neural network., (© 2024. The Author(s).)

Acute lung injury (ALI) is a severe complication in clinical settings. Alert diagnosis and severity assessment of ALI is pivotal to ensure curative treatment and increase survival rates. However, the development of a precise ALI diagnostic strategy remains a pending task. Here, leveraging neutrophil's inflammation-homing and physiological barrier-navigating capability, a facile strategy is proposed for achieving targeted 19 F-MRI detection of ALI based on the nanoengineered neutrophil internalized with perfluorocarbon nanoemulsion (Neu@PFC). The remodeling process poses a negligible impact on the neutrophil's inherent activation and transmigration functions. The migratory behavior of Neu@PFC toward pneumonia is confirmed in vivo using an LPS-induced ALI murine model. Direct intratracheal (i.t.) administration contributes to a vast deposition of Neu@PFC within the lung, allowing for real-time 19 F-MRI visualization and the potential to predict progressive pneumonia. Furthermore, intravenous (i.v.) administration of Neu@PFC enables quantitative assessment of the extent of ALI due to the chemokine-guided neutrophil migration. This study not only provides a pathway to diagnose ALI, but also sheds light on the neutrophil recruitment and activation cues in different tissues and inflammatory conditions, which is a prerequisite for developing potential therapeutic approaches., (© 2024 Wiley‐VCH GmbH.)

The ProteinPaint Hi-C tool (ppHiC) facilitates web-based visualization and collaborative exploration of Hi-C data, a vital resource for understanding three-dimensional genomic structures. ppHiC allows researchers to easily analyze large Hi-C datasets on a web browser without requiring the computational expertise that has heretofore limited access to this complex genomic data. The platform is compatible with multiple Hi-C data versions and boasts a highly customizable interface, including a configuration panel for the precise adjustment of key visualization parameters. The tool's interactive features offer a broad range of views, from whole-genome landscapes to detailed interactions between pairs of loci, that are accessible within a single, integrated environment. Here, we demonstrate how using ppHiC to visualize an altered chromatin conformational landscape in neuroblastoma can inform understanding of the genomic rearrangements in this cancer., Competing Interests: Authors declare no competing interest., (© 2024 The Authors.)

In our ongoing research on bambusicolous Xylariomycetidae fungi, three new microfungi taxa were collected and identified as members of the genera Amphibambusa , Arecophila , and Nigropunctata . Amphibambusaaureae sp. nov. , Arecophilagaofengensis sp. nov. , and Nigropunctataxiaohensis sp. nov. are introduced based on morphological comparisons and phylogenetic analyses using combined ITS, LSU, tub2 , and tef 1α loci. Comprehensive morphological descriptions, illustrations, and a phylogenetic tree showcasing the placement of these new taxa are provided. Additionally, keys to Amphibambusa and Nigropunctata are provided., Competing Interests: The authors have declared that no competing interests exist., (Xin Zhou, Kamran Habib, Wenyu Zeng, Yulin Ren, Xiangchun Shen, Jichuan Kang, Qirui Li.)

Metal halide perovskite light-emitting diodes (PeLEDs) are ideal for high-resolution displays due to their tunable emission, narrow spectra, and low-cost processing. Colloidal FAPbBr 3 perovskite quantum dots (PeQDs) enhance radiative recombination, making them efficient for pure-green PeLEDs. However, their low stability and surface defects limit their practical application. Here, we address these challenges by proposing an in situ surface repair strategy using benzhydroxamic acid (BHA) as a modifier. We demonstrated that BHA can coordinate with Pb 2+ ions and form hydrogen bonds with FA + and halide ions, effectively reducing nonradiative recombination and maintaining the integrity of the PeQDs. High-quality FAPbBr 3 PeQDs with a photoluminescence quantum yield (PLQY) of up to 92.5% were achieved, leading to pure-green PeLEDs with an external quantum efficiency (EQE) of 24.8% and a maximum luminance of 40,231 cd m -2 , providing a feasible and promising perspective for advanced solid-state lighting and displays.