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The intestinal mucus barrier is an important line of defense against gut pathogens. Damage to this barrier brings bacteria into close contact with the epithelium, leading to intestinal inflammation. Therefore, its restoration is a promising strategy for alleviating intestinal inflammation. This study showed that Abelmoschus manihot polysaccharide (AMP) fortifies the intestinal mucus barrier by increasing mucus production, which plays a crucial role in the AMP-mediated amelioration of colitis. IL-10-deficient mouse models demonstrated that the effect of AMP on mucus production is dependent on IL-10. Moreover, bacterial depletion and replenishment confirmed that the effects of AMP on IL-10 secretion and mucus production were mediated by Akkermansia muciniphila. These findings suggest that plant polysaccharides fortify the intestinal mucus barrier by maintaining homeostasis in the gut microbiota. This demonstrates that targeting mucus barrier is a promising strategy for treating intestinal inflammation.

Abstract Background Mechanical unloading-induced bone loss threatens prolonged spaceflight and human health. Recent studies have confirmed that osteoporosis is associated with a significant reduction in bone microvessels, but the relationship between them and the underlying mechanism under mechanical unloading are still unclear. Methods We established a 2D clinostat and hindlimb-unloaded (HLU) mouse model to simulate unloading in vitro and in vivo. Micro-CT scanning was performed to assess changes in the bone microstructure and mass of the tibia. The levels of CD31, Endomucin (EMCN) and histone deacetylase 6 (HDAC6) in tibial microvessels were detected by immunofluorescence (IF) staining. In addition, we established a coculture system of microvascular endothelial cells (MVECs) and osteoblasts, and qRT‒PCR or western blotting was used to detect RNA and protein expression; cell proliferation was detected by CCK‒8 and EdU assays. ChIP was used to detect whether HDAC6 binds to the miRNA promoter region. Results Bone mass and bone microvessels were simultaneously significantly reduced in HLU mice. Furthermore, MVECs effectively promoted the proliferation and differentiation of osteoblasts under coculture conditions in vitro. Mechanistically, we found that the HDAC6 content was significantly reduced in the bone microvessels of HLU mice and that HDAC6 inhibited the expression of miR-375-3p by reducing histone acetylation in the miR-375 promoter region in MVECs. miR-375-3p was upregulated under unloading and it could inhibit MVEC proliferation by directly targeting low-density lipoprotein-related receptor 5 (LRP5) expression. In addition, silencing HDAC6 promoted the miR-375-3p/LRP5 pathway to suppress MVEC proliferation under mechanical unloading, and regulation of HDAC6/miR-375-3p axis in MVECs could affect osteoblast proliferation under coculture conditions. Conclusion Our study revealed that disuse-induced bone loss may be closely related to a reduction in the number of bone microvessels and that the modulation of MVEC function could improve bone loss induced by unloading. Mechanistically, the HDAC6/miR-375-3p/LRP5 pathway in MVECs might be a promising strategy for the clinical treatment of unloading-induced bone loss.

Cooked rice and the vegetables like lettuce are common kitchen waste, which are carbonaceous materials and have the potential as feedstock for the production of activated carbon. Cooking is similar to hydrothermal treatment (HTC), which might impact the subsequent activation of kitchen waste. In this study, the HTC of lettuce, rice, or their mixture and the activation of the resulting hydrochars were conducted. The results indicated that cross-polymerization between the N-containing organics from lettuce and the sugar derivatives from rice took place in their co-HTC, which significantly increased the hydrochar yield. Activation of the hydrochar from the co-HTC generated the AC with a yield of 2 times that from direct activation of mixed lettuce/rice. However, the co-HTC facilitated aromatization, reducing reactivity with K2C2O4 in activation and producing the AC with main micropores and low specific surface area. Activation of the hydrochar from HTC of rice followed the above trend, while that from lettuce was the opposite. The organics in lettuce were thermally unstable and could not undergo sufficient aromatization. The activation of hydrochar from HTC of lettuce thus generated the AC with the lowest yield, but the highest specific surface area (1684.9 m2/g), abundant mesopores, and superior capability for adsorption of tetracycline. However, the environmental impacts and energy consumption for the production of AC from the hydrochar of lettuce were higher than that from hydrochar of co-HTC.

Singerocybe alboinfundibuliformis (Seok et al.) Yang, Qin & Takah 2014 is an edible mushroom distributed in several East or Southeast Asian countries. Herein, we report the mitochondrial genome of S. alboinfundibuliformis based on Illumina sequencing data. The overall length of the mitochondrial genome is 64,279 bp, with a GC content of 29.0%. It contains 14 typical protein-coding genes, 27 tRNA genes, two rRNA genes, and 13 intergenic ORFs. Most of these genes (39 out of 56) are transcribed at the forward strand, and few (17 out of 56) are transcribed at the reverse strand. Among these genes, only the rnl gene is invaded by an intron, and all other genes are intron-free. Phylogenetic analysis based on mitochondrial amino acid sequences supports the phylogenetic position of S. alboinfundibuliformis in Clitocybaceae, being close to Lepista sordida (Schumach.) Singer 1951. This study serves as a springboard for future investigation on fungal evolution in Clitocybaceae.

Bird’s nest fungi involve six different genera, but only one of these genera (i.e. Cyathus) have available mitochondrial genomes (mitogenomes) to date. In this study, we report the first mitogenome in the genus Nidula with Nidula shingbaensis K. Das & R.L. Zhao 2013 as a representative. The mitogenome is a circular molecule of 65,793 bp with a GC content of 26.2%. There are a total of 43 genes, including 14 typical protein-coding genes, 26 tRNA genes, two rRNA genes, and one free-standing intergenic open reading frame (ORF). Three introns (two in cox1 and one in cob) are present in the mitogenome, with each containing an ORF encoding for a LAGLIDADG endonuclease. Phylogenetic analysis based on mitochondrial amino acid sequences confirms the phylogenetic placement of N. shingbaensis in Nidulariaceae in Agaricales. This study serves as a springboard for future investigation on fungal evolution in Nidulariaceae.

Chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) is a novel MRI technology to image certain compounds at extremely low concentrations. Long acquisition time to measure signals at a set of offset frequencies of the Z-spectra and to repeat measurements to reduce noise pose significant challenges to its applications. This study explores correlations of CEST MR images along the spatial and Z-spectral dimensions to improve MR image quality and robustness of magnetization transfer ratio (MTR) asymmetry estimation via a joint k-ω reconstruction model. The model was formulated as an optimization problem with respect to MR images at all frequencies ω, while incorporating regularizations along the spatial and spectral dimensions. The solution was subject to a self-consistency condition that the Z-spectrum of each pixel follows a multi-peak data fitting model corresponding to different CEST pools. The optimization problem was solved using the alternating direction method of multipliers. The proposed joint reconstruction method was evaluated on a simulated CEST MRI phantom and semi-experimentally on choline and iopamidol phantoms with added Gaussian noise of various levels. Results demonstrated that the joint reconstruction method was more tolerable to noise and reduction in number of offset frequencies by improving signal-to-noise ratio (SNR) of the reconstructed images and reducing uncertainty in MTR asymmetry estimation. In the choline and iopamidol phantom cases with 10.5% noise in the measurement data, our method achieved an averaged SNR of 31.0 dB and 32.2 dB compared to the SNR of 24.7 dB and 24.4 dB in the conventional reconstruction approach. It reduced uncertainty of the MTR asymmetry estimation over all regions of interest by 54.4% and 43.7%, from 1.71 and 2.38 to 0.78 and 1.71, respectively.

Abstract Duchenne muscular dystrophy (DMD) affecting 1 in 3500–5000 live male newborns is the frequently fatal genetic disease resulted from various mutations in DMD gene encoding dystrophin protein. About 70% of DMD-causing mutations are exon deletion leading to frameshift of open reading frame and dystrophin deficiency. To facilitate translating human DMD-targeting CRISPR therapeutics into patients, we herein establish a genetically humanized mouse model of DMD by replacing exon 50 and 51 of mouse Dmd gene with human exon 50 sequence. This humanized mouse model recapitulats patient’s DMD phenotypes of dystrophin deficiency and muscle dysfunction. Furthermore, we target splicing sites in human exon 50 with adenine base editor to induce exon skipping and robustly restored dystrophin expression in heart, tibialis anterior and diaphragm muscles. Importantly, systemic delivery of base editor via adeno-associated virus in the humanized male mouse model improves the muscle function of DMD mice to the similar level of wildtype ones, indicating the therapeutic efficacy of base editing strategy in treating most of DMD types with exon deletion or point mutations via exon-skipping induction.

Abstract Background The advances in deep learning-based pathological image analysis have invoked tremendous insights into cancer prognostication. Still, lack of interpretability remains a significant barrier to clinical application. Methods We established an integrative prognostic neural network for intrahepatic cholangiocarcinoma (iCCA), towards a comprehensive evaluation of both architectural and fine-grained information from whole-slide images. Then, leveraging on multi-modal data, we conducted extensive interrogative approaches to the models, to extract and visualize the morphological features that most correlated with clinical outcome and underlying molecular alterations. Results The models were developed and optimized on 373 iCCA patients from our center and demonstrated consistent accuracy and robustness on both internal (n = 213) and external (n = 168) cohorts. The occlusion sensitivity map revealed that the distribution of tertiary lymphoid structures, the geometric traits of the invasive margin, the relative composition of tumor parenchyma and stroma, the extent of necrosis, the presence of the disseminated foci, and the tumor-adjacent micro-vessels were the determining architectural features that impacted on prognosis. Quantifiable morphological vector extracted by CellProfiler demonstrated that tumor nuclei from high-risk patients exhibited significant larger size, more distorted shape, with less prominent nuclear envelope and textural contrast. The multi-omics data (n = 187) further revealed key molecular alterations left morphological imprints that could be attended by the network, including glycolysis, hypoxia, apical junction, mTORC1 signaling, and immune infiltration. Conclusions We proposed an interpretable deep-learning framework to gain insights into the biological behavior of iCCA. Most of the significant morphological prognosticators perceived by the network are comprehensible to human minds. Graphical Abstract

Abstract Pleural empyema can lead to significant morbidity and mortality despite chest drainage and antibiotic treatment, necessitating novel and minimally invasive interventions. Fusobacterium nucleatum is an obligate anaerobe found in the human oral and gut microbiota. Advances in sequencing and puncture techniques have made it common to detect anaerobic bacteria in empyema cases. In this report, we describe the case of a 65-year-old man with hypertension who presented with a left-sided encapsulated pleural effusion. Initial fluid analysis using metagenomic next-generation sequencing (mNGS) revealed the presence of Fusobacterium nucleatum and Aspergillus chevalieri. Unfortunately, the patient experienced worsening pleural effusion despite drainage and antimicrobial therapy. Ultimately, successful treatment was achieved through intrapleural metronidazole therapy in conjunction with systemic antibiotics. The present case showed that intrapleural antibiotic therapy is a promising measure for pleural empyema.

Abstract The flashover in vacuum is a rapid interfacial discharge across the insulator surface when subjected to high applied voltage. Here a theoretical model covering above‐surface processes is introduced. The model calculates the flashover threshold in vacuum, with revised secondary electron emission avalanche theory and improved desorbed neutral transport model. The model serves as the first part of an integrated flashover model, aiming for consistent treatment of both above‐surface and subsurface processes during the entire flashover development. The flashover threshold is obtained by combining the desorbed neutral pressure at given applied voltage and the gas breakdown criterion dictated by the Paschen's law. An analytical formula for threshold estimation containing physical parameters, and a simplified formula consisting of empirical coefficients are introduced, catering for both conceptual understanding and practical application. The derived formulae are validated by experimental data for a variety of insulator materials. The theory generalisation for non‐uniform electric field distribution is further discussed.

Abstract Background The 2018/2023 ESC/ESH Guidelines underlined a gap how baseline cardiovascular disease (CVD) risk predicted blood pressure (BP) lowering benefits. Further, 2017 ACC/AHA Guideline and 2021 WHO Guideline recommended implementation studies about intensive BP control. Now, to bridge these guideline gaps, we conducted a post hoc analysis to validate whether the baseline CVD risk influences the effectiveness of the intensive BP control strategy, which was designed by China Rural Hypertension Control Project (CRHCP). Methods This is a post hoc analysis of CRHCP, among which participants were enrolled except those having CVD history, over 80 years old, or missing data. Subjects were stratified into quartiles by baseline estimated CVD risk and then grouped into intervention and usual care group according to original assignment in CRHCP. Participants in the intervention group received an integrated, multi-faceted treatment strategy, executed by trained non-physician community health-care providers, aiming to achieve a BP target of

Abstract Introduction Recent advancements in androgenetic alopecia (AGA) treatment have highlighted the efficacy of botulinum toxin (BoNT). However, inconsistencies in injection sites and depths warrant attention. It remains unclear which injection strategy is most beneficial for patients. Methods This split-scalp randomized controlled trial divided each enrolled participant’s scalp along the midline: one side was randomized to receive intramuscular BoNT injections in the surrounding muscles, while the other side received intradermal BoNT injections directly into the balding areas. This study evaluated the impact of treatment on hair density and diameter through trichoscopic examinations conducted at baseline and 12 weeks post treatment. Additionally, assessments of pain and overall safety were integrated into the study protocol. Results Twenty-nine patients completed the study, with significant improvements in hair density observed in the intramuscular injection group compared to the intradermal group (p

Abstract Background Underutilization of implantable cardioverter defibrillators (ICD) to prevent sudden cardiac death (SCD) in post-myocardial infarction (MI) patients remains an issue across several geographies. A better understanding of risk factors for SCD in post-MI patients from regions with low ICD adoption rates will help identify those who will benefit from an ICD. This analysis assessed risk factors for all-cause and cardiovascular-related mortality in post-MI patients from the Improve Sudden Cardiac Arrest (SCA) Bridge Trial. Results For the entire cohort, the overall 1-year mortality rate was 5.9% (88/1491) and 3.4% (51/1491) for all-cause and cardiovascular mortality, respectively, with 76.5% of all cardiac deaths being from SCD. A multivariate model determined increased age, reduced left ventricular ejection fraction (LVEF), increased time from myocardial infarction to hospital admission, being female, being from Southeast Asia (SEA), and having coronary artery disease to be significant risk factors for all-cause mortality. The risk factors for cardiovascular-related mortality revealed increased age, reduced LVEF, and being from SEA as significant risk factors. Conclusions We show several characteristics as being predictors of cardiovascular-related mortality in post-MI patients from the Improve SCA Bridge study. Patients who experience an MI and present with these characteristics would benefit from a referral to an electrophysiologist for further SCD risk stratification and management and possible subsequent ICD implantation to reduce unnecessary death.

Interactions of cellulose- and lignin-derived intermediates have been well documented during pyrolysis of lignocellulosic biomass. The reaction network for the interactions is rather complex, as cellulose-derived volatiles could interact/react with not only lignin-derived volatiles but also lignin-derived char and vice versa. To probe specifically the impacts of cellulose-derived volatiles on the lignin-derived char or the opposite, herein the sequential pyrolysis was performed by arranging cellulose in the upper bed with lignin in the lower bed or lignin above with cellulose below at 350 and 650 °C, respectively. The results indicated that the sequential pyrolysis of cellulose→lignin or lignin→cellulose at 350 °C induced increased char yield from formation of carbonaceous deposits via volatiles-char interactions. Compared with the lignin-derived volatiles, the cellulose-derived volatiles, especially aldehyde fractions, were more reactive towards the lignin-derived char at 350 °C, forming oxygen-rich lignin-derived char with a higher yield, an abundance of aliphatic structures and consequently lower thermal stability. In sequential pyrolysis of lignin→cellulose, more aromatics-rich species were deposited on cellulose-derived char, but the lignin-derived volatiles were less reactive for enhancing the char yield. At 650 °C, instead of polymerisation of the volatiles on the char, either the cellulose- or lignin-derived char catalyzed the cracking of the counterpart volatiles to remove the aliphatic functionalities, which made the char more aromatic and thermally more stable.

Abstract Pathologic α-synuclein (α-syn) spreads from cell-to-cell, in part, through binding to the lymphocyte-activation gene 3 (Lag3). Here we report that amyloid β precursor-like protein 1 (Aplp1) interacts with Lag3 that facilitates the binding, internalization, transmission, and toxicity of pathologic α-syn. Deletion of both Aplp1 and Lag3 eliminates the loss of dopaminergic neurons and the accompanying behavioral deficits induced by α-syn preformed fibrils (PFF). Anti-Lag3 prevents the internalization of α-syn PFF by disrupting the interaction of Aplp1 and Lag3, and blocks the neurodegeneration induced by α-syn PFF in vivo. The identification of Aplp1 and the interplay with Lag3 for α-syn PFF induced pathology deepens our insight about molecular mechanisms of cell-to-cell transmission of pathologic α-syn and provides additional targets for therapeutic strategies aimed at preventing neurodegeneration in Parkinson’s disease and related α-synucleinopathies.

Abstract Silk nanofibrils (SNFs), the fundamental building blocks of silk fibers, endow them with exceptional properties. However, the intricate mechanism governing SNF assembly, a process involving both protein conformational transitions and protein molecule conjunctions, remains elusive. This lack of understanding has hindered the development of artificial silk spinning techniques. In this study, we address this challenge by employing a graphene plasmonic infrared sensor in conjunction with multi-scale molecular dynamics (MD). This unique approach allows us to probe the secondary structure of nanoscale assembly intermediates (0.8–6.2 nm) and their morphological evolution. It also provides insights into the dynamics of silk fibroin (SF) over extended molecular timeframes. Our novel findings reveal that amorphous SFs undergo a conformational transition towards β-sheet-rich oligomers on graphene. These oligomers then connect to evolve into SNFs. These insights provide a comprehensive picture of SNF assembly, paving the way for advancements in biomimetic silk spinning.

Abstract Background Human endogenous retrovirus subfamily H long terminal repeat associating protein 2, (HHLA2), a member of B7 family, exhibits heightened expression in various malignant tumors. However, the exact functions of HHLA2 in pancreatic cancer (PC) remain incompletely elucidated. Methods We initially conducted an analysis of the B7 family members’ expression pattern in pancreatic tumor samples and adjacent normal tissues using The Cancer Genome Atlas (TCGA) database. Subsequently, immunohistochemistry, RT-qPCR and western blot methods were used to assess HHLA2 expression levels in PC tissues and cell lines. Furthermore, after silencing HHLA2 in PC cell lines, cell migration and proliferation of PC cells were detected by wound healing and CCK-8 assays, and cell invasion of PC cells was detected by transwell assays. We also investigated the regulation of epithelial-mesenchymal transition (EMT) markers and levels of EGFR, MEK, ERK1/2, mTOR and AKT via western blot analysis. Finally, the correlation between HHLA2 expression and immune infiltration was further explored. Results Silencing of HHLA2 resulted in the inhibition of PC cell proliferation, migration and invasion, potentially through the suppression of the EGFR/MAPK/ERK and mTOR/AKT signaling pathway. Additionally, silencing HHLA2 led to the inhibition of M2-type polarization of tumor associated macrophages (TAMs). Conclusion The knockdown of HHLA2 was observed to inhibit the migration and invasion of PC cells through the regulation of the EMT process and EGFR/MAPK/ERK and mTOR/AKT pathway. Furthermore, silencing HHLA2 was found to modulate M2 polarization of TAMs. These finding suggest that HHLA2 could be a promising therapeutic target for Pancreatic cancer.

A visual/smartphone colorimetric system was developed for the sensitive and selective detection of sulfide ion (S2−) using chemical vapor generation (CVG) as a gaseous sampling technique. S2− in samples were converted into H2S after the addition of H2SO4, which separated from the solution during CVG process, ensuring high efficiency of vapor generation (sensitivity) and eliminated interferences (selectivity). The H2S was subsequently reacted with Pb-BTC and PbS was thus formed, causing the test paper turned to black. It was utilized for the detection of S2− by visual/smartphone colorimetric system. Detectable limits of 0.05 μg/mL and 0.2 μg/mL were obtained under smartphone mode and visual mode, respectively. Furthermore, this colorimetric system was successfully used for the analysis of S2− in several beer samples and water samples, with recoveries ranging 97 %–111 %. This system represents a potential miniaturized, easy used and high-effective method for rapid and on-site detection of S2−.

A gas pressure meter-based portable/miniaturized analytical kit was established for rapid and on-site detection of oxalate. Potassium permanganate (KMnO4) and oxalate solution were mixed together in bottle-in-bottle reaction device, a simple oxidation reaction process occurred within 6 min and carbon dioxide (CO2) was generated, inducing the pressure of the sealed bottle changed, which was measured by a portable gas pressure meter. A detectable range of 0.1–6 μmol mL−1 and a detection limit of 0.064 μmol mL−1 were achieved. The proposed analytical method was further used for the analysis of several real samples (spinach, beverages and water samples), with the recoveries of 89–111%. Considering the interferences from the complicated matrix, calcium chloride (CaCl2) was served as a precipitant, oxalate (C2O42−) was precipitated with Ca2+ to form precipitation (CaC2O4), CaC2O4 was then separated from the matrix by centrifuge/filter, eliminating the interferences. It is a rapid, easy-used and interference-free analytical system/device for oxalate on-site and real time analysis.

Abstract Membranes with precise Li+/Na+ and Li+/K+ separations are imperative for lithium extraction from brine to address the lithium supply shortage. However, achieving this goal remains a daunting challenge due to the similar valence, chemical properties, and subtle atomic‐scale distinctions among these monovalent cations. Herein, inspired by the strict size‐sieving effect of biological ion channels, a membrane is presented based on nonporous crystalline materials featuring structurally rigid, dimensionally confined, and long‐range ordered ion channels that exclusively permeate naked Li+ but block Na+ and K+. This naked‐Li+‐sieving behavior not only enables unprecedented Li+/Na+ and Li+/K+ selectivities up to 2707.4 and 5109.8, respectively, even surpassing the state‐of‐the‐art membranes by at least two orders of magnitude, but also demonstrates impressive Li+/Mg2+ and Li+/Ca2+ separation capabilities. Moreover, this bioinspired membrane has to be utilized for creating a one‐step lithium extraction strategy from natural brines rich in Na+, K+, and Mg2+ without utilizing chemicals or creating solid waste, and it simultaneously produces hydrogen. This research has proposed a new type of ion‐sieving membrane and also provides an envisioning of the design paradigm and development of advanced membranes, ion separation, and lithium extraction.

Abstract Background Comprehensive data on patients at high risk of sudden cardiac death (SCD) in emerging countries are lacking. The aim was to deepen our understanding of the SCD phenotype and identify risk factors for death among patients at high risk of SCD in emerging countries. Methods Patients who met the class I indication for implantable cardioverter-defibrillator (ICD) implantation according to guideline recommendations in 17 countries and regions underrepresented in previous trials were enrolled. Countries were stratified by the WHO regional classification. Patients were or were not implanted with an ICD at their discretion. The outcomes were all-cause mortality and SCD. Results We enrolled 4222 patients, and 3889 patients were included in the analysis. The mean follow-up period was 21.6 ± 10.2 months. There were 433 (11.1%) instances of all-cause mortality and 117 (3.0%) cases of SCD. All-cause mortality was highest in primary prevention (PP) patients from Southeast Asia and secondary prevention (SP) patients from the Middle East and Africa. The SCD rates among PP and SP patients were both highest in South Asia. Multivariate Cox regression modelling demonstrated that in addition to the independent predictors identified in previous studies, both geographic region and ICD use were associated with all-cause mortality in patients with high SCD risk. Primary prophylactic ICD implantation was associated with a 36% (HR = 0.64, 95% CI 0.531–0.802, p

Abstract Background Nonalcoholic fatty liver disease (NAFLD) is a leading public health problem worldwide. Approximately one fourth of patients with nonalcoholic fatty liver (NAFL) progress to nonalcoholic steatohepatitis (NASH), an advanced stage of NAFLD. Hence, there is an urgent need to make a better understanding of NAFLD heterogeneity and facilitate personalized management of high-risk NAFLD patients who may benefit from more intensive surveillance and preventive intervene. Methods In this study, a series of bioinformatic methods were performed to identify NAFLD progression-specific pathways and genes, and three machine learning approaches were combined to construct a risk-stratification gene signature to quantify risk assessment. In addition, bulk RNA-seq, single-cell RNA-seq (scRNA-seq) transcriptome profiling data and whole-exome sequencing (WES) data were comprehensively analyzed to reveal the genomic alterations and altered pathways between distinct molecular subtypes. Results Two distinct subtypes of NAFL were identified with the NAFLD progression-specific genes, and one subtype has a high similarity of the inflammatory pattern and fibrotic potential with NASH. The established risk-stratification gene signature could discriminate advanced samples from overall NAFLD. COL1A2, one key gene closely related to NAFLD progression, is specifically expressed in fibroblasts involved in hepatocellular carcinoma (HCC), and significantly correlated with EMT and angiogenesis in pan-cancer. Moreover, the β-catenin/COL1A2 axis might play a critical role in fibrosis severity and inflammatory response during NAFLD-HCC progression. Conclusion In summary, our study provided evidence for the necessity of molecular classification and established a risk-stratification gene signature to quantify risk assessment of NAFLD, aiming to identify different risk subsets and to guide personalized treatment.

Abstract Background The association of dietary patterns and longitudinal changes in brain volume has rarely been investigated in Japanese individuals. We prospectively investigated this association in middle-aged and older Japanese community-dwelling adults. Methods Data with a 2-year follow-up from the sixth wave (July 2008 to July 2010; baseline) to the seventh (July 2010 to July 2012; follow-up) of the National Institute for Longevity Sciences-Longitudinal Study of Aging project were analyzed. Dietary intake was assessed using a 3-day dietary record, and longitudinal volume changes (%) in the total gray matter (TGM), total white matter, and frontal, parietal, occipital, temporal, and insular lobes were assessed using 3-dimensional T1 magnetic resonance imaging scans. Multiple factor analysis and hierarchical clustering revealed sex-specific dietary patterns. Associations between dietary patterns and annual brain-volume changes (%) were evaluated using general linear models adjusted for age, apoprotein E genotype, body mass index, medical history, lifestyle behaviors, socioeconomic factors, and energy intake. Results Among the 1636 participants (age: 40.3–89.2 years), three dietary patterns were determined for men (n = 815; Western; Vegetable-Fruit-Dairy; and Traditional Japanese diets) and women (n = 821; Western; Grain-Vegetable-Fruit; and Traditional Japanese diets). Compared to women following the Western diet, those on the Traditional Japanese diet had less TGM atrophy. Multivariable-adjusted β (95% confidence interval) of the annual change (%) of TGM was − 0.145 (-0.287 to -0.002; P = 0.047), which correlated with reduced parietal lobe atrophy. No association between dietary pattern and brain atrophy was observed in men. Conclusions Adherence to healthy dietary patterns, with higher consumption of whole grains, seafood, vegetables, fruits, mushrooms, soybean products, and green tea, potentially confers a protective effect against brain atrophy in middle-aged and older Japanese women but not in men. Further research to confirm these results and ascertain the underlying mechanisms is required. This study highlights the importance of sex-specific effects on the relationship between dietary patterns and brain health in diverse populations.

Abstract Background Fluvoxamine is one of the selective serotonin reuptake inhibitors (SSRIs) that are regarded as the first-line drugs to manage mental disorders. It has been also recognized with the potential to treat inflammatory diseases and viral infection. However, the effect of fluvoxamine on autoimmune diseases, particularly type 1 diabetes (T1D) and the related cellular and molecular mechanisms, are yet to be addressed. Method Herein in this report, we treated NOD mice with fluvoxamine for 2 weeks starting from 10-week of age to dissect the impact of fluvoxamine on the prevention of type 1 diabetes. We compared the differences of immune cells between 12-week-old control and fluvoxamine-treated mice by flow cytometry analysis. To study the mechanism involved, we extensively examined the characteristics of CD4+ T cells with fluvoxamine stimulation using RNA-seq analysis, real-time PCR, Western blot, and seahorse assay. Furthermore, we investigated the relevance of our data to human autoimmune diabetes. Result Fluvoxamine not only delayed T1D onset, but also decreased T1D incidence. Moreover, fluvoxamine-treated NOD mice showed significantly attenuated insulitis coupled with well-preserved β cell function, and decreased Th1 and Th17 cells in the peripheral blood, pancreatic lymph nodes (PLNs), and spleen. Mechanistic studies revealed that fluvoxamine downregulated glycolytic process by inhibiting phosphatidylinositol 3-kinase (PI3K)-AKT signaling, by which it restrained effector T (Teff) cell differentiation and production of proinflammatory cytokines. Conclusion Collectively, our study supports that fluvoxamine could be a viable therapeutic drug against autoimmunity in T1D setting.

Abstract Background Although body mass index (BMI) and grip strength (GS) are both predictors of disability, their joint effect on predicting incident disability remains uncertain. We examined whether the effect of BMI on incident disability can be modulated by GS in community‐dwelling older people in Japan. Methods A total of 1486 community‐dwellers in Japan (731 men and 755 women, aged 65–82 years) who participated in the 2nd to 7th waves of the National Institute for Longevity Sciences‐Longitudinal Study of Aging (NILS‐LSA) project, were followed up to 20 years. Twelve subgroups were created according to the intersections of GS (sex‐specific tertiles: low, intermediate, and high) and BMI (underweight 1,

Objectives: The development of effective treatments for non-small cell lung cancer (NSCLC), particularly targeting the KRASG12C mutation, remains a challenge. In this study, we investigated the therapeutic potential of VT204, a small molecule inhibitor of KRASG12C, in NSCLC. Methods: To achieve the objectives, we conducted a comprehensive set of experimental methods. In vitro experiments involved the investigation of VT204 on proliferation, apoptosis, cell cycle dynamics, migration, invasion, and on the RAF/MEK/ERK signaling pathway in NCI-H358 cells. In addition, in vivo experiments were performed to evaluate the influence of VT204 on tumor growth. Results: We demonstrated that VT204 effectively suppressed cell proliferation in NCI-H358 cells, with significant inhibition observed at a concentration of 8 μM. Colony formation assays further supported the inhibitory effect of VT204 on NCI-H358 cell growth. Moreover, VT204 exhibited notable effects on suppressing migration and invasion capacities of NCI-H358 cells, indicating its potential as a metastasis-inhibiting agent. Mechanistic investigations revealed that VT204 induced apoptosis and G2M-phase cell cycle arrest in NCI-H358 cells. Additionally, VT204 modulated the RAF/MEK/ERK signaling pathway, leading to reduced phosphorylation of ERK. In vivo studies using xenograft models confirmed the inhibitory effect of VT204 on NCI-H358 tumor growth. Conclusion: These findings highlight VT204 as a promising therapeutic candidate for NSCLC targeting the KRASG12C mutation.

Neovascular age-related macular degeneration (nARMD) is an important cause of visual impairment and blindness in the elderly, with choroidal neovascularization in the macula as the main pathological feature. The onset of nARMD is closely related to factors including age, oxidative stress, and lipid metabolism. Vascular endothelial growth factor (VEGF) is an important factor contributing to nARMD as well as choroidal neovascularization and retinal leakage formation. At present, anti-VEGF therapy is the only treatment that improves vision and halts disease progression in most patients, making anti-VEGF drugs a landmark development for nARMD treatment. Although intravitreal injection of anti-VEGF drugs has become the first-line treatment for nARMD, this treatment has many shortcomings including repeated injections, poor or no response in some patients, and complications such as retinal fibrosis. As a result, several new anti-VEGF drugs are being developed. This review provides a discussion of these new anti-VEGF drugs for the treatment of nARMD.

BackgroundNutritional profiling system (NPS) holds promise as a public health tool for companies to measure product healthiness and for individuals in making healthier food choices. The Meiji NPS for adults specifically targets lifestyle-related diseases prevalent among Japan’s adult population, including overweight/obesity, hypertension, diabetes, and dyslipidemia. This study examined the cross-sectional association between the Meiji NPS for adults Dietary Index (MNfA-DI) and indicators of lifestyle-related diseases in a population.MethodsThe study comprised 1,272 middle-aged individuals (40–64 years, 50.1% male) who participated in the seventh wave (2010–2012) of the National Institute for Longevity Sciences—Longitudinal Study of Aging project, with no missing data on three-day dietary records. The MNfA-DI was computed at the individual diet level (accounting for the whole diet) using arithmetic energy-weighted means. A higher MNfA-DI indicated a greater nutritional quality of an individual’s overall diet. Lifestyle-related disease indicators included body mass index (BMI, kg/m2), body fat (%), systolic and diastolic blood pressure (mmHg), fasting plasma glucose (mg/dL), HbA1c (%), triglyceride levels (mg/dL), LDL, and HDL cholesterol levels (mg/dL). A multiple regression model was used to assess the association between the MNfA-DI and lifestyle-related disease indicators, adjusting for demographics, socioeconomic status, lifestyle factors, disease history, and energy intake as covariates, depending on the outcome.ResultsThe median (interquartile range) age and MNfA-DI were 53.0 (46.0, 59.0) years and 10.1 (6.0, 14.0) points, respectively. MNfA-DI was negatively associated with body fat [partial regression coefficient (95% confidence interval) −0.04 (−0.07, −0.01)], diastolic blood pressure [−0.08 (−0.17, −0.002)], fasting plasma glucose [−0.18 (−0.33, −0.01)], and triglyceride [−1.36 (−2.16, −0.55)]. Additionally, MNfA-DI was also associated with almost indicators (except for LDL and HDL cholesterol) among participants with a BMI between 18.5 and 24.9 kg/m2.ConclusionThese findings suggest that the Meiji NPS for adults could be associated with a lower risk of lifestyle-related diseases. In addition, from a public health nutrition perspective, the Meiji NPS for adults may be useful to assess the food healthiness of the adult population.

Abstract Rechargeable magnesium batteries (RMBs) have garnered significant attention due to their potential to provide high energy density, utilize earth‐abundant raw materials, and employ metal anode safely. Currently, the lack of applicable cathode materials has become one of the bottleneck issues for fully exploiting the technological advantages of RMBs. Recent studies on Mg cathodes reveal divergent storage performance depending on the electrolyte formulation, posing interfacial issues as a previously overlooked challenge. This minireview begins with an introduction of representative cathode‐electrolyte interfacial phenomena in RMBs, elaborating on the unique solvation behavior of Mg2+, which lays the foundation for interfacial chemistries. It is followed by presenting recently developed strategies targeting the promotion of Mg2+ desolvation in the electrolyte and alternative cointercalation approaches to circumvent the desolvation step. In addition, efforts to enhance the cathode‐electrolyte compatibility via electrolyte development and interfacial engineering are highlighted. Based on the abovementioned discussions, this minireview finally puts forward perspectives and challenges on the establishment of a stable interface and fast interfacial chemistry for RMBs.

Pulmonary infections pose formidable challenges in clinical settings with high mortality rates across all age groups worldwide. Accurate diagnosis and early intervention are crucial to improve patient outcomes. Artificial intelligence (AI) has the capability to mine imaging features specific to different pathogens and fuse multimodal features to reach a synergistic diagnosis, enabling more precise investigation and individualized clinical management. In this study, we successfully developed a multimodal integration (MMI) pipeline to differentiate among bacterial, fungal, and viral pneumonia and pulmonary tuberculosis based on a real-world dataset of 24,107 patients. The area under the curve (AUC) of the MMI system comprising clinical text and computed tomography (CT) image scans yielded 0.910 (95% confidence interval [CI]: 0.904–0.916) and 0.887 (95% CI: 0.867–0.909) in the internal and external testing datasets respectively, which were comparable to those of experienced physicians. Furthermore, the MMI system was utilized to rapidly differentiate between viral subtypes with a mean AUC of 0.822 (95% CI: 0.805–0.837) and bacterial subtypes with a mean AUC of 0.803 (95% CI: 0.775–0.830). Here, the MMI system harbors the potential to guide tailored medication recommendations, thus mitigating the risk of antibiotic misuse. Additionally, the integration of multimodal factors in the AI-driven system also provided an evident advantage in predicting risks of developing critical illness, contributing to more informed clinical decision-making. To revolutionize medical care, embracing multimodal AI tools in pulmonary infections will pave the way to further facilitate early intervention and precise management in the foreseeable future.

Summary: High salt (HS) consumption is a risk factor for multiple autoimmune disorders via disturbing immune homeostasis. Nevertheless, the exact mechanisms by which HS exacerbates rheumatoid arthritis (RA) pathogenesis remain poorly defined. Herein, we found that heightened phosphorylation of PDPK1 and SGK1 upon HS exposure attenuated FoxO1 expression to enhance the glycolytic capacity of CD4 T cells, resulting in strengthened Th17 but compromised Treg program. GSK2334470 (GSK), a dual PDPK1/SGK1 inhibitor, effectively mitigated the HS-induced enhancement in glycolytic capacity and the overproduction of IL-17A. Therefore, administration of GSK markedly alleviated HS-exacerbated RA progression in collagen-induced arthritis (CIA) model. Collectively, our data indicate that HS consumption subverts Th17/Treg homeostasis through the PDPK1-SGK1-FoxO1 signaling, while GSK could be a viable drug against RA progression in clinical settings.

PurposeTo evaluate the utility of supine roll test (SRT) and alternative positional tests, such as head-shaking test (HST), seated supine positioning test (SSPT), bow and lean test (BLT), and rapid axial roll test (RART) in determining the affected semicircular canal of horizontal semicircular canal benign paroxysmal positional vertigo (HSC-BPPV).MethodsIn an observational cohort study, 553 patients diagnosed with HSC-BPPV were divided into five groups in terms of different positional tests received: SRT group (n = 110), HST+ SRT (n = 112), BLT + SRT (n = 114), SSPT+SRT (n = 108) and RART+SRT (n = 109). The same method was used for the last four groups: The patients were first subjected to different alternative positional tests and then to SRT, and the nystagmus was observed separately to determine the affected side. The primary outcomes compared included the accuracy and sensitivity of these tests in the determination of the affected semicircular canal in HSC-BPPV.ResultsPatients with nystagmus elicited by positional tests accounted for 84.99% (470/553). The elicitation rate of nystagmus of SRT was lowest, being 77.27% (85/110). The elicitation rate of nystagmus were higher in the test groups than in the control group, and RART+SRT group yielded the highest elicitation rate of nystagmus (95.41%, 104/109). Among the alternative positional tests, RART attained the highest elicitation rate of nystagmus (101/109, 92.66%). Comparison between alternative positional tests and SRT, RART and SRT showed obviously better agreement in determining the affected semicircular canal (85.45%, 96/109) and eliciting nystagmus (95.41%, Kappa = 0.642), but no difference was found in curative effect when the affected side was accurately determined (χ2 = 1.618, p = 0.655).ConclusionAll alternative positional tests are helpful for eliciting nystagmus in patients with HSC-BPPV, and the significant advantages of RART include high-sensitivity in eliciting nystagmus and high accuracy in determining the affected semicircular canal, which provided objective support for the correct diagnosis of HSC-BPPV and the successful reduction of otolith.

IntroductionMaize/soybean intercropping is a common cropping practice in Chinese agriculture, known to boost crop yield and enhance soil fertility. However, the role of below-ground interactions, particularly root exudates, in maintaining intercropping advantages in soybean/maize intercropping systems remains unclear.MethodsThis study aimed to investigate the differences in root exudates between intercropping and monocropping systems through two pot experiments using metabolomics methods. Multiple omics analyses were conducted to explore correlations between differential metabolites and the community of Arbuscular Mycorrhizal Fungi (AMF), shedding light on the mechanisms underlying the dominance of intercropping from the perspective of root exudates-soil microorganism interactions.Results and discussionThe study revealed that intercropping significantly increased the types and contents of root exudates, lowered soil pH, increased the availability of nutrients like available nitrogen (AN) and available phosphorus (AP), and enhanced AMF colonization, resulting in improving the community composition of AMF. Besides, root exudates in intercropping systems differed significantly from those in monocropping, with 41 and 39 differential metabolites identified in the root exudates of soybean/maize, predominantly amino acids and organic acids. The total amount of amino acids in the root exudates of soybean intercropping was 3.61 times higher than in monocropping. Additionally, the addition of root exudates significantly improved the growth of soybean/maize and AMF colonization, with the mycorrhizal colonization rate in intercropping increased by 105.99% and 111.18% compared to monocropping, respectively. The identified metabolic pathways associated with root exudates were closely linked to plant growth, soil fertility improvement, and the formation of AMF. Correlation analysis revealed a significant relationship (P < 0.05) between certain metabolites such as tartaric acid, oxalic acid, malic acid, aspartic acid, alanine, and the AMF community. Notably, the photosynthetic carbon fixation pathway involving aspartic acid showed a strong association with the function of Glomus_f_Glomerace, the dominant genus of AMF. A combined analysis of metabolomics and high throughput sequencing revealed that the root exudates of soybean/maize intercropping have direct or indirect connections with AMF and soil nutrients.ConclusionThis suggests that the increased root exudates of the soybean/maize intercropping system mediate an improvement in AMF community composition, thereby influencing soil fertility and maintaining the advantage of intercropping.

Abstract Objective To explore the efficacy of serplulimab plus chemotherapy in esophageal squamous cell carcinoma (ESCC) patients with liver metastases. Methods A post hoc exploratory analysis of ASTRUM‐007 study was performed, focusing on the association between the liver metastases status and the clinical outcomes. A systematic literature search of electronic databases was conducted to identify eligible randomized controlled trials for the meta‐analysis. Study‐level pooled analyses of hazard ratios (HRs) for PFS according to liver metastases were performed. Results The post hoc analysis of ASTRUM‐007 showed that although patients with liver metastases had a worse prognosis comparing with the non‐liver metastases patients in both treatment arms (serplulimab plus chemotherapy arm: median PFS, 5.7 vs. 6.6 months, HR 1.57 [95% CI, 1.15–2.13]; median OS, 13.7 vs. 15.3 months, HR 1.48 [95% CI, 1.09–1.98]; placebo plus chemotherapy arm: median PFS, 4.3 vs. 5.5 months, HR 1.58 [95% CI, 1.01–2.39]; median OS, 10.3 vs. 11.2 months, HR 1.32 [95% CI, 0.84–2.00]), OS and PFS benefits derived from serplulimab plus chemotherapy versus placebo plus chemotherapy in this study were observed in both patients with liver metastases (HR of PFS: 0.60; 95% CI, 0.37–0.97; HR of OS: 0.68; 95% CI, 0.43–1.11) and the non‐liver metastases patients (HR of PFS: 0.62; 95% CI, 0.49–0.80; HR of OS: 0.69; 95% CI, 0.55–0.87) with similar magnitude. Three randomized controlled trials were included in the meta‐analysis. Pooled HRs demonstrated that the addition of anti‐PD‐1 antibodies significantly improved PFS compared to chemotherapy alone regardless of liver metastases status. Conclusions This study reveals that the presence of liver metastases is a poor prognostic factor but does not affect the improvements in both PFS and OS brought by adding PD‐1 blockade to chemotherapy in ESCC patients. Predictive biomarkers for survival in these patients warrant further investigation.

Background Circular RNAs (circRNAs) are a large class of RNAs present in mammals. Among these, circCamsap1 is a well-acknowledged circRNA with significant implications, particularly in the development and progression of diverse tumors. However, the potential consequences of circCamsap1 depletion in vivo on male reproduction are yet to be thoroughly investigated. Methods The presence of circCamsap1 in the mouse testes was confirmed, and gene expression analysis was performed using reverse transcription quantitative polymerase chain reaction. CircCamsap1 knockout mice were generated utilizing the CRISPR/Cas9 system. Phenotypic analysis of both the testes and epididymis was conducted using histological and immunofluorescence staining. Additionally, fertility and sperm motility were assessed. Results Here, we successfully established a circCamsap1 knockout mouse model without affecting the expression of parental gene. Surprisingly, male mice lacking circCamsap1 (circCamsap1−/−) exhibited normal fertility, with no discernible differences in testicular and epididymal histology, spermatogenesis, sperm counts or sperm motility compared to circCamsap1+/+ mice. These findings suggest that circCamsap1 may not play an essential role in physiological spermatogenesis. Nonetheless, this result also underscores the complexity of circRNA function in male reproductive biology. Therefore, further research is necessary to elucidate the precise roles of other circRNAs in regulating male fertility.

BackgroundGliomas constitute a category of malignant tumors originating from brain tissue, representing the majority of intracranial malignancies. Previous research has demonstrated the pivotal role of CLEC7A in the progression of various cancers, yet its specific implications within gliomas remain elusive. The primary objective of this study was to investigate the prognostic significance and immune therapeutic potential of CLEC7A in gliomas through the integration of bioinformatics and clinical pathological analyses.MethodsThis investigation involved examining and validating the relationship between CLEC7A and glioma using samples from Hospital, along with data from TCGA, GEO, GTEx, and CGGA datasets. Subsequently, we explored its prognostic value, biological functions, expression location, and impact on immune cells within gliomas. Finally, we investigated its potential impact on the chemotaxis and polarization of macrophages.ResultsThe expression of CLEC7A is upregulated in gliomas, and its levels escalate with the malignancy of tumors, establishing it as an independent prognostic factor. Functional enrichment analysis revealed a significant correlation between CLEC7A and immune function. Subsequent examination of immune cell differential expression demonstrated a robust association between CLEC7A and M2 macrophages. This conclusion was further substantiated through single-cell analysis, immunofluorescence, and correlation studies. Finally, the knockout of CLEC7A in M2 macrophages resulted in a noteworthy reduction in macrophage chemotaxis and polarization factors.ConclusionCLEC7A expression is intricately linked to the pathology and molecular characteristics of gliomas, establishing its role as an independent prognostic factor for gliomas and influencing macrophage function. It could be a promising target for immunotherapy in gliomas.

Multipotent mesenchymal stem cells (MSCs) have high self-renewal and multi-lineage differentiation potentials and low immunogenicity, so they have attracted much attention in the field of regenerative medicine and have a promising clinical application. MSCs originate from the mesoderm and can differentiate not only into osteoblasts, cartilage, adipocytes, and muscle cells but also into ectodermal and endodermal cell lineages across embryonic layers. To design cell therapy for replacement of damaged tissues, it is essential to understand the signaling pathways, which have a major impact on MSC differentiation, as this will help to integrate the signaling inputs to initiate a specific lineage. Hedgehog (Hh) signaling plays a vital role in the development of various tissues and organs in the embryo. As a morphogen, Hh not only regulates the survival and proliferation of tissue progenitor and stem populations but also is a critical moderator of MSC differentiation, involving tri-lineage and across embryonic layer differentiation of MSCs. This review summarizes the role of Hh signaling pathway in the differentiation of MSCs to mesodermal, endodermal, and ectodermal cells.

Emerging evidence suggested that zinc finger protein 831 (ZNF831) was associated with immune activity and stem cell regulation in breast cancer. Whereas, the roles and molecular mechanisms of ZNF831 in oncogenesis remain unclear. ZNF831 expression was significantly diminished in breast cancer which was associated with promoter CpG methylation but not mutation. Ectopic over-expression of ZNF831 suppressed breast cancer cell proliferation and colony formation and promoted apoptosis in vitro, while knockdown of ZNF831 resulted in an opposite phenotype. Anti-proliferation effect of ZNF831 was verified in vivo. Bioinformatic analysis of public databases and transcriptome sequencing both showed that ZNF831 could enhance apoptosis through transcriptional regulation of the JAK/STAT pathway. ChIP and luciferase report assays demonstrated that ZNF831 could directly bind to one specific region of STAT3 promoter and induce the transcriptional inhibition of STAT3. As a result, the attenuation of STAT3 led to a restraint of the transcription of Bcl2 and thus accelerated the apoptotic progression. Augmentation of STAT3 diminished the apoptosis-promoting effect of ZNF831 in breast cancer cell lines. Furthermore, ZNF831 could ameliorate the anti-proliferation effect of capecitabine and gemcitabine in breast cancer cell lines. Our findings demonstrate for the first time that ZNF831 is a novel transcriptional suppressor through inhibiting the expression of STAT3/Bcl2 and promoting the apoptosis process in breast cancer, suggesting ZNF831 as a novel biomarker and potential therapeutic target for breast cancer patients.

The article examines the formation of the fiscal policy of the People's Republic of China and the fiscal policy of Ukraine. The theoretical aspects of the formation of fiscal policy are highlighted, the stages of the formation of the fiscal policy of China and Ukraine in historical retrospect are given. The description of reforming the fiscal and tax system of China is carried out with reference to the achieved successes in the socio-economic development of the country. An overview of the trade and economic relations between Ukraine and China is provided. Based on the current state of the socio-economic situation of both countries, the prospects for the development of Ukrainian-Chinese economic activity are described and the need to harmonize the fiscal policies of the countries is substantiated.

Abstract Invasive diseases caused by the globally distributed commensal yeast Candida tropicalis are associated with mortality rates of greater than 50%. Notable increases of azole resistance have been observed in this species, particularly within Asia-Pacific regions. Here, we carried out a genetic population study on 1571 global C. tropicalis isolates using multilocus sequence typing (MLST). In addition, whole-genome sequencing (WGS) analysis was conducted on 629 of these strains, comprising 448 clinical invasive strains obtained in this study and 181 genomes sourced from public databases. We found that MLST clade 4 is the predominant azole-resistant clone. WGS analyses demonstrated that dramatically increasing rates of azole resistance are associated with a rapid expansion of cluster AZR, a sublineage of clade 4. Cluster AZR isolates exhibited a distinct high-level azole resistance, which was induced by tandem duplications of the ERG11 A395T gene allele. Ty3/gypsy-like retrotransposons were found to be highly enriched in this population. The alarming expansion of C. tropicalis cluster AZR population underscores the urgent need for strategies against growing threats of antifungal resistance.

Abstract Background Hepatocellular carcinoma (HCC) is a primary liver malignancy that is now relatively common worldwide. TMEM79 has been reported to play diagnostic and prognostic markers in a variety of cancers and was found to be closely associated with immune infiltration. SMG5 is associated with immune cell infiltration in HCC. Multiple nonsense-mediated mRNA processes require the involvement of SMG5. TMEM79 and SMG5 complexes may be prognostic markers for prostate cancer. However, the relationship between TMEM79 expression in HCC and prognosis, its role and mechanism of action, and its relationship with SMG5 have not been studied. This article focuses on not only the prognostic role of TMEM79 and its biological significance, including immuno-infiltration, tumor mutations and drug sensitivity, but also the interaction with SMG5 in HCC. Methods Differential expression analysis and the multiCox proportional hazards regression analyses of TMEM79 and SMG5 were performed by multiple databases. Then, use IHC to verify our results. Subsequently, we used R software to analyze the clinical phenotype of both: analysis of clinicopathological features, enrichment analysis, analysis of immune infiltration, analysis of immune checkpoints, analysis of drug sensitivity, and immunotherapy. Results Both the database studies and the results of our research group showed that TMEM79 and SMG5 were differentially expressed in HCC and normal tissues. Validation of immunohistochemistry showed that differential expression of TMEM79 and SMG5, which influenced the prognosis of patients with HCC, could be an independent prognostic factor. Results of the TCGA database study showed that TMEM79 and SMG5 were correlated with immune infiltration, immune checkpoints, drug sensitivity, and immunotherapy. We typed TMEM79-related molecules in HCC according to R software. Two types of TMEM79 correlated with clinical features, survival of patients with HCC, and immune infiltration. Conclusion TMEM79 are highly expressed in HCC and play an important role in the prognosis of patients with HCC. TMEM79 and SMG5 are positively correlated and may both associated with immune infiltration, and closely linked to immune checkpoints, drug sensitivity, and immunotherapy in HCC.

Abstract Background Prior study reported that mushroom consumption was associated with a lower incidence of hyperuricemia, but there is limited evidence on this association. We conducted a collaborative study to investigate the association between mushroom intake and hyperuricemia in middle-aged and older populations. Methods We used data from the National Health and Nutrition Examination Survey (NHANES) in the U.S. (2007–2018) and the National Institute for Longevity Sciences-Longitudinal Study of Aging (NILS-LSA) in Japan (1997–2012). Consumption of mushroom (g/day) were measured by one- or two-day dietary recall in NHANES and by 3-day dietary records in the NILS-LSA. Hyperuricemia was defined using uric acid levels as > 420 μmol/L and > 350 μmol/L in NHANES for men and women, respectively; in the NILS-LSA, serum uric acid was repeatedly measured at baseline and follow-up surveys. Hyperuricemia was defined as uric acid levels > 416.4 μmol/L for men and ≥ 356.9 μmol/L for women. Logistic regression models in NHANES (cross-sectionally) and Generalized Estimation Equations in NILS-LSA (longitudinally) were performed. Results A total of 5,778 NHANES participants (mean (SD) age: 53.2 (9.6) years) and 1,738 NILS-LSA (mean (SD) age: 53.5 (11.2) years) were included. Mushrooms were consumed by 5.7% of participants in NHANES and 81.2% in NILS-LSA. We did not observe a significant association between mushroom intakes and hyperuricemia in the NHANES men and women. However, in the NILS-LSA, compared to non-consumers, a higher mushroom intake was associated with a lower risk of incident hyperuricemia in men under 65 years old. The adjusted odds ratio (95% CI) for non-consumers, participants with middle, and the highest consumption of mushrooms were 1.00 (Ref.), 0.77 (0.44, 1.36), and 0.55 (0.31, 0.99), respectively (P-trend = 0.036). No association was found in women in NILS-LSA. Conclusions Mushroom consumption was associated with a lower risk of incident hyperuricemia in Japanese men.

Abstract SUMOylation is an evolutionary conserved regulatory mechanism, in which Ubc9 is the only E2 conjugating enzyme. Previous studies demonstrated that SUMOylation is involved in multiple biological processes, but its role in dendritic cells (DCs) remains to be fully addressed. Herein in this report, we found that DCs deficient in Ubc9 protected mice from dextran sulfate sodium (DSS)-induced colitis, as evidenced by the ameliorated weight loss, colon length, and disrupted colon structure. Mechanistically, Ubc9 mediated SUMOylation of RBPJ, by which it stabilized RBPJ from ubiquitin-mediated degradation to enhance its transcriptional activity, while Ciita, a critical transcription factor, is a direct target downstream of RBPJ, which forms an enhanceosome complex to transcribe the expression of MHC II genes. Therefore, loss of Ubc9 abolished RBPJ SUMOylation, which was coupled with reduced Ciita transcription, thereby attenuating the expression of MHC class II genes. As a consequence of defective MHC II expression, Ubc9 -/- DCs were featured by the impaired capability to process antigen and to prime effector CD4+ T cells, thereby protecting mice from DSS-induced colitis. Together, our results shed novel insight into the understanding of SUMOylation in the regulation of DC functions in pathological conditions.

[Introduction] The proposal of the "dual carbon" strategy has given new requirements and connotations to the reduction of energy consumption intensity and the "dual control" of the total amount. On the premise of adhering to the priority of energy efficiency, we should fully consider the stage of regional development and reasonably ensure the "dual control" indicators are decomposed and implemented layer by layer. [Method] Taking the decomposition of the "dual control" indicators of energy consumption in the "14th Five-Year Plan" of a certain city as an example, this paper selected quantifications that could reflect the economic level, energy consumption volume, energy-saving potential and the completion of the energy-saving goals of the "13th Five-Year Plan" indicators of each district and county (city) and built a combined weighting assignment model based on the combination of hierarchical analysis and objective weighting to calculate the weight of each indicator, obtaining the "dual control" indicator distribution results, and then used clustering analysis to carry out the differentiation of the indicator system and cluster aggregation. [Result] By comparing the results of combination weighting and clustering analysis, the regional energy consumption intensity reduction target decomposition algorithm based on multi-indicator combination weighting and clustering analysis can obtain basically consistent results. [Conclusion] Based on the results of the above two methods, the actual economic development and government management needs, the energy consumption management targets of different levels are obtained, which takes into account regional development differences, conforms to the national "14th Five-Year Plan" energy consumption "dual control" system requirements and decomposition principle, and has the characteristics of replicability and promotion.

The interaction between the surrounding rock and the support structure in a circular water conveyance tunnel with lining comprises two main aspects: internal and external hydraulic pressures, and the contact load between the post-excavation lining and the surrounding rock. There is currently no reasonable calculation method to consider both factors simultaneously. Therefore, by utilizing the assumption of smooth contact between the surrounding rock and the lining, an analytical model for a circular water conveyance tunnel with lining is developed through the complex function method. Smooth contact indicates continuity of radial contact stress, coordination of radial displacement, and the absence of shear stress transmission. Considering the inner and outer boundary stress conditions of the lining, two sets of undetermined analytical functions are established, corresponding to internal and external water pressure, as well as the contact stress between the surrounding rock and the lining. Ultimately, the stress and displacement components at any point within the surrounding rock and lining can be derived under the conditions outlined in this study. The analytical model elucidates the mechanism of load transfer within the circular water conveyance tunnel with lining, considering the combined effects of internal and external water pressure and excavation loads. Of particular note, it quantifies the restrictive impact of external water pressure on lining hydrofracturing when subjected to high internal water pressure. Additionally, the model offers a theoretical foundation for designing and assessing support structures for use in long-distance water conveyance projects.

Oil serves as the essential fuel and economic foundation of contemporary industry. However, the use of traditional light crude oil has exceeded its supply, making it challenging to meet the energy needs of humanity. Consequently, the extraction of heavy oil has become crucial in addressing this demand. This research focuses on the synthesis of several water-soluble catalysts that can work along with reservoir minerals to catalyze the hydrothermal cracking process of heavy oil. The goal is to effectively reduce the viscosity of heavy oil and lower the cost of its extraction. Based on the experimental findings, it was observed that when oil sample 1 underwent hydrothermal cracking at a temperature of 180 °C for a duration of 4 h, the amount of water added and catalyst used were 30% and 0.2% of the oil sample dosage, respectively. It was further discovered that the synthesized Mn(II)C was able to reduce the viscosity of oil sample 1 by 50.38%. The investigation revealed that the combination of Mn(II)C + K exhibited a significant synergistic catalytic impact on reducing viscosity. Initially, the viscosity reduction rate was 50.38%, which climbed to 61.02%. Subsequently, when catalyzed by the hydrogen supply agent isopropanol, the rate of viscosity reduction rose further to 91.22%. Several methods, such as freezing point analysis, thermogravimetric analysis, DSC analysis, component analysis, gas chromatography, wax crystal morphology analysis, and GC-MS analysis, were conducted on aqueous organic matter derived from heavy oil after undergoing different reaction systems. These analyses confirmed that the viscosity of the heavy oil was decreased. By studying the reaction mechanism of the model compound and analyzing the aqueous phase, the reaction largely involves depolymerization between macromolecules, breakdown of heteroatom chains, hydrogenation, ring opening, and other related consequences. These actions diminish the strength of the van der Waals force and hydrogen bond in the recombinant interval, impede the creation of a grid-like structure in heavy oil, and efficiently decrease its viscosity.

Background: Although workplace violence is prevalent in the healthcare system, the relationship between workplace violence, job satisfaction, and burnout among healthcare workers (HCWs) in mobile cabin hospitals in China during the COVID-19 pandemic has not yet been investigated. This study analyzes the mediating effects of perceived stress and work environment in the relationship between workplace violence, job satisfaction, and burnout. Methods: A cross-sectional study was conducted in December 2022 on 1,199 frontline HCWs working in mobile cabin hospitals in Chongqing, China, during the COVID-19 pandemic. Multiple linear regression and mediation analysis were performed. Results: A positive correlation was observed between workplace violence and burnout (r = 0.420, P

Abstract Background For a long time, the prevailing viewpoint suggests that shorter telomere contribute to chromosomal instability, which is a shared characteristic of both aging and cancer. The newest research presented that T cell immune deficiency rather than chromosome instability predisposes patients with short telomere syndromes to some cancers. However, the relationship between genetically determined telomere length (TL) and immune cells remains unclear. Methods The two‐sample Mendelian randomization analysis was conducted to elucidate the potential causal relationship. The genetic data of TL and immune cells were obtained from the Genome‐Wide Association Study. The inverse variance weighted (IVW) method was used to estimate the effects primarily and another four methods were as a supplement. Sensitivity analysis was used to test the results. Results The IVW method showed a significant correlation between TL and the percentage of T cells in lymphocytes (odds ratio [OR]: 1.222, 95% confidence interval [CI]: 1.014–1.472, p = .035), indicating that shorter TL significantly increases the risk of low T cell percentage. Further analysis of T cell subsets indicated that shorter TL may primarily lead to a lower percentage of Natural Killer T cells (OR: 1.574, 95% CI: 1.281–1.935, p

Abstract The spread of prion‐like protein aggregates is a common driver of pathogenesis in various neurodegenerative diseases, including Alzheimer's disease (AD) and related Tauopathies. Tau pathologies exhibit a clear progressive spreading pattern that correlates with disease severity. Clinical observation combined with complementary experimental studies has shown that Tau preformed fibrils (PFF) are prion‐like seeds that propagate pathology by entering cells and templating misfolding and aggregation of endogenous Tau. While several cell surface receptors of Tau are known, they are not specific to the fibrillar form of Tau. Moreover, the underlying cellular mechanisms of Tau PFF spreading remain poorly understood. Here, it is shown that the lymphocyte‐activation gene 3 (Lag3) is a cell surface receptor that binds to PFF but not the monomer of Tau. Deletion of Lag3 or inhibition of Lag3 in primary cortical neurons significantly reduces the internalization of Tau PFF and subsequent Tau propagation and neuron‐to‐neuron transmission. Propagation of Tau pathology and behavioral deficits induced by injection of Tau PFF in the hippocampus and overlying cortex are attenuated in mice lacking Lag3 selectively in neurons. These results identify neuronal Lag3 as a receptor of pathologic Tau in the brain，and for AD and related Tauopathies, a therapeutic target.