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Abstract Background Pangolin is one of the most endangered mammals with many peculiar characteristics, yet the understanding of its sensory systems is still superficial. Studying the genomic basis of adaptation and evolution of pangolin’s sensory system is expected to provide further potential assistance for their conservation in the future. Results In this study, we performed a comprehensive comparative genomic analysis to explore the signature of sensory adaptation and evolution in pangolins. By comparing with the aardvark, Cape golden mole, and short-beaked echidna, 124 and 152 expanded gene families were detected in the genome of the Chinese and Malayan pangolins, respectively. The enrichment analyses showed olfactory-related genomic convergence among five concerned mammals. We found 769 and 733 intact OR genes, and 704 and 475 OR pseudogenes in the Chinese and Malayan pangolin species, respectively. Compared to other mammals, far more intact members of OR6 and OR14 were identified in pangolins, particularly for four genes with large copy numbers (OR6C2, OR14A2, OR14C36, and OR14L1). On the genome-wide scale, 1,523, 1,887, 1,110, and 2,732 genes were detected under positive selection (PSGs), intensified selection (ISGs), rapid evolution (REGs), and relaxed selection (RSGs) in pangolins. GO terms associated with visual perception were enriched in PSGs, ISGs, and REGs. Those related to rhythm and sound perception were enriched in both ISGs and REGs, ear development and morphogenesis were enriched in ISGs, and mechanical stimulus and temperature adaptation were enriched in RSGs. The convergence of two vision-related PSGs (OPN4 and ATXN7), with more than one parallel substituted site, was detected among five concerned mammals. Additionally, the absence of intact genes of PKD1L3, PKD2L1, and TAS1R2 and just six single-copy TAS2Rs (TAS2R1, TAS2R4, TAS2R7, TAS2R38, TAS2R40, and TAS2R46) were found in pangolins. Interestingly, we found two large insertions in TAS1R3, distributed in the N-terminal ectodomain, just in pangolins. Conclusions We found new features related to the adaptation and evolution of pangolin-specific sensory characteristics across the genome. These are expected to provide valuable and useful genome-wide genetic information for the future breeding and conservation of pangolins.

Aiming at the multi-granularity knowledge discovery of users in online community, a method of dynamic user interest portrait based on Three-way Fuzzy Concept Lattice (3WFCL) is proposed to reveal the relationship between long-term and short-term interest drift, which improves the accuracy of the user portrait from a fuzzy perspective. Firstly, the label topic matrix of community users is constructed based on the topic analysis and the dynamic interest modelling is realized. Secondly, the environment migration index is calculated by extracting the topic and sentiment characteristics of the user environment. Meanwhile, interest inheritance is introduced into the calculation of interest characteristics, and interest attenuation vector is established to perceive the short-term interest label set dynamically. Finally, the membership degree of the three-way fuzzy interests is put forward into the multi-feature concept modelling of the long-term and short-term interest labels. Afterwards, the multi-granularity fuzzy association rules are generated to complete the multi-granularity characterization of differentiated interests by constructing the three fuzzy formal contexts. The effectiveness of the proposed method is validated on real data sets. The results show that it is of great significance to utilize the three-way fuzzy concept analysis into user portrait modelling, which is helpful to mine semantic association information and improve the analysis ability of fine-grained interest hierarchy.

ABSTRACT: Malate, a precursor in the ruminal propionate production pathway, competes with methanogenesis for metabolic hydrogen, offering a way to reduce ruminal methane (CH4) production in ruminants. However, cost considerations hinder widespread use of malate in ruminant diets. An alternative approach involves use of transient malate levels generated during seed germination via the glyoxylate cycle. This study investigated the methane-mitigating potential of malate-containing hydroponic fodder. Fodder samples with peak malate concentrations from alfalfa, forage pea, Italian ryegrass, rye, soybean, triticale, and wheat during germination were subjected to in vitro rumen fermentation using the Hohenheim gas test. The basal diet of in vitro fermentation comprised 40% grass silage, 40% maize silage, 15% hay, and 5% concentrate on a DM basis, with nutritional characteristics including 42.1% NDF, 25.0% ADF, 14.0% starch, 12.7% CP, and 3.5% ether extract, on a DM basis. Experimental treatments were fodder inclusion involving replacing 20% of the basal diet (20R) and, additionally, 100% replacement of the silages with alfalfa d 10 and rye d 9 (SR), the 2 high-malate fodders. Reductions in CH4 production were observed with soybean (20R, 6.7% reduction), alfalfa (20R, 6.6% reduction), and increased with rye (20R, 6.3% increase). In the setup replacing silages with high-malate fodders (SR), alfalfa decreased CH4 production (17.7%) but increased ammonia (174%), whereas rye increased CH4 production (35.8%). Organic matter digestibility increased with SR rye (12.6%). Marginal effects of dietary variables were analyzed in a generalized additive model. A negative relationship between dietary malate content and CH4 production was observed, whereas dietary NDF and starch content were positively correlated with CH4 production. In conclusion, malate within the hydroponic fodder could potentially reduce CH4 emissions in ruminants. However, achieving sufficient efficacy requires high malate content. Additionally, use of hydroponic fodder may increase the risk of nitrogen emissions. Animal studies are required for further investigation.

Complete skeletal muscle regeneration after traumatic injuries remains a challenge due to impaired regenerative capability and dysregulated microenvironments. Autophagy plays a crucial role in the muscle regeneration process by regulating myogenic and non-myogenic cells. Herein, we report a bioactive MXene hydrogel (FPGM) capable of upregulating autophagy and increasing muscle innervation to restore skeletal muscle structure and function. FPGM possessed excellent electrical conductivity, tissue adhesive ability and antioxidation, which could eliminate excess reactive oxygen species to reduce oxidative stress and decrease the secretion of pro-inflammatory cytokine. FPGM upregulated the autophagy level of myoblasts and promoted the migration and tube formation of endothelial cells as well as myogenic differentiation with negligible toxicity. FPGM accelerated muscle fiber formation and skeletal muscle regeneration by improving autophagy, which could regulate microenvironment through raising M2 macrophages to alleviate excessive inflammation, facilitating angiogenesis and decreasing fibrous scar tissue formation in vivo. Importantly, FPGM could efficiently restore muscle function by improving muscle innervation, tibialis anterior compound muscle action potential amplitude and neuromuscular conduction. This work demonstrates that bioactive MXene hydrogel should be a promising candidate for complete skeletal muscle regeneration.

The fibroblast growth factor receptor (FGFR) is a crucial receptor tyrosine kinase involved in essential biological processes, including growth, development, and tissue repair. However, FGFR gene mutations, including amplification, fusion, and mutation, can disrupt epigenetics, transcriptional regulation, and tumor microenvironment interactions, leading to cancer development. Targeting these kinase mutations with small molecule drugs or antibodies has shown clinical benefits. For example, erdafitinib is approved for treating locally advanced or metastatic urothelial cancer patients with FGFR2/FGFR3 mutations, and pemigatinib is approved for treating cholangiocarcinoma with FGFR2 fusion/rearrangement. Effective screening of FGFR variant patients is crucial for the clinical application of FGFR inhibitors. Various detection methods, such as polymerase chain reaction, next-generation sequencing, fluorescence in situ hybridization, and immunohistochemistry, are available, and their selection should be based on diagnostic and treatment decision-making needs. Our developed expert consensus aims to standardize the diagnosis and treatment process for FGFR gene mutations and facilitate the practical application of FGFR inhibitors in clinical practice.

Next-generation genome sequencing has revolutionized genetic testing, identifying numerous rare disease-associated gene variants. However, to impute pathogenicity, computational approaches remain inadequate and functional testing of gene variant is required to provide the highest level of evidence. The emergence of AlphaFold2 has transformed the field of protein structure determination, and here we outline a strategy that leverages predicted protein structure to enhance genetic variant classification. We used the gene IRF6 as a case study due to its clinical relevance, its critical role in cleft lip/palate malformation, and the availability of experimental data on the pathogenicity of IRF6 gene variants through phenotype rescue experiments in irf6-/- zebrafish. We compared results from over 30 pathogenicity prediction tools on 37 IRF6 missense variants. IRF6 lacks an experimentally derived structure, so we used predicted structures to explore associations between mutational clustering and pathogenicity. We found that among these variants, 19 of 37 were unanimously predicted as deleterious by computational tools. Comparing in silico predictions with experimental findings, 12 variants predicted as pathogenic were experimentally determined as benign. Even with the recently published AlphaMissense model, 15/18 (83%) of the predicted pathogenic variants were experimentally determined as benign. In comparison, mapping variants to the protein revealed deleterious mutation clusters around the protein binding domain, whereas N-terminal variants tend to be benign, suggesting the importance of structural information in determining pathogenicity of mutations in this gene. In conclusion, incorporating gene-specific structural features of known pathogenic/benign mutations may provide meaningful insights into pathogenicity predictions in a gene-specific manner and facilitate the interpretation of variant pathogenicity.

Cardiopulmonary exercise testing (CPET) refers to a method of measuring various indicators of the human body under gradually increasing exercise loads to objectively evaluate cardiopulmonary reserve function and exercise endurance. Currently, CPET detection systems primarily measure subjects' ECG, respiratory flow, oxygen (O2), and carbon dioxide (CO2) parameters. This paper introduces a non-invasive multi-parameter exercise cardiopulmonary function evaluation system that incorporates impedance cardiography monitoring. The system integrates impedance cardiography monitoring with conventional CPET detection parameters and detects changes in the hemodynamic parameters of the body during exercise, aiding in the evaluation of exercise capacity. Additionally, the system features a portable design with Wi-Fi wireless transmission, which enhances its applicability.

Abstract Respiratory infections caused by coronaviruses have posed serious and unpredictably public health threats; reliable animal models continue to be essential for advancing our understanding of the virus’s transmission, pathophysiology, and immunological mechanisms. In response to the critical need for centralized resources in coronavirus research, the COVID-AMD database (Coronavirus Disease Animal Model Database, https://www.uc-med.net/CoV-AMD ) has been developed as an integrated platform. Data was gathered from public literature databases, refined and integrated using ETL (Extract, Transform, Load) methodology. After data conversion and cleaning, COVID-AMD was implemented using MySQL relational database with jQuery and JBoss. COVID-AMD database consolidates comprehensive data on animal models infected with various CoVs, including MERS-CoV, SARS-CoV, and SARS-CoV-2, featuring methodologies for establishing infection models, clinical features, and phenotypic data. It catalogs 869 animal models across 29 species and 312 virus strains, covering five diseases and ten infection routes. With global and advanced search capabilities, it facilitated data preprocessing, integration, analysis, and visualization, and provided tools for comparative analysis, model recommendation and omics analysis based on model and phenotype data. The open access to this rich repository aims to enable rapid identification of animal models for CoVs, thereby accelerating the development and clinical trial progression of prospective therapeutics and vaccines.

Abstract Studying the correlation between resilience and carbon emissions in resource-based cities (RBCs) holds considerable significance for advancing regional sustainable development. Herein, by taking 18 RBCs in southwestern China as the research object, a carbon emission impact index system and an urban resilience index system were constructed. The resilience was quantified from the three dimensions of “resources - ecology - society”, and divided into high, medium, and low categories. Besides, the LSTM model was utilized to simulate carbon peak scenarios in different types of cities and analyze the specific path to achieve low-carbon development. As indicated by the research results, between 2005 and 2020, the resilience and carbon emissions of Southwest China’s RBCs presented fluctuations and showed an upward trend. Scenario simulation suggested that highly resilient cities were poised for sustainable development and necessitated a coordinated government structure; moderately resilient cities should prioritize clean energy development; and cities with low resilience should pursue steady growth, market expansion, and enhanced communication. Overall, this study provides support for the low-carbon development of RBCs.

Abstract Background Extracranial carotid artery aneurysm (ECCA) is an infrequent disease with an incidence of less than 1%. However, our understanding is still incomplete, and the preferred method to treat ECAA remains unknown. Methods To share our initial experience with treatment options for large ECCAs. We have retrospectively included 15 patients who underwent treatment at our institution from 2015 to 2022. The treatment modality, patient demography, aneurysm morphology, and clinical and radiographic follow-data were collected and analyzed in all patients. Results During the study period, 15 patients (with 19 ECCAs) were diagnosed and treated, of whom 8 (53.3%) were male. The average age of the patients was 53.6 years. The primary presenting symptoms was pulsatile neck mass (10/15, 66.7%). The etiology of ECAAs included atherosclerotic (6/15, 40.0%), infectious (3/15, 20.0%), and dissecting (1/15, 6.7%), and iatrogenic due to acupuncture (1/15, 6.7%). The mean ± SD maximal diameter of the aneurysms was 23.8 ± 14.1 mm, with more than half of patients having aneurysms larger than 25 mm (52.6%). 79.0% aneurysm had intraluminal thrombus at admission. Six patients underwent successful neurosurgical resection for a total of seven ECCAs. Five patients received endovascular interventional treatment. The remaining four patients who presented with seven ECCAs were placed under observation. The mean follow-up period was 28.1 months. Out of the patients who received treatment, it was discovered that 10 of them had completely occluded at the latest imaging study. During the course of conservative observation, it was observed that in one patient, the aneurysm disappeared and the parent vessel became thinner following anti-infection treatment. Out of all the patients, only one who was treated with Willis stent experienced a large area of cerebral infarction after treatment, which ultimately resulted in their death. Conclusions ECCA is rare and mostly present with mass effect. Neurosurgical treatment was more frequently feasible in large ECCAs, and endovascular surgery was the first choice for pseudoaneurysms and dissecting aneurysms. Anti-inflammation treatment was available for some infectious cases.

Abstract Background and purpose Neurodevelopmental disorders (NDDs) are characterized by abnormalities in brain development and neurobehaviors, including autism. The maternal–fetal interface (MFI) is a highly specialized tissue through which maternal factors affect fetal brain development. However, limited research exists on restoring and maintaining MFI homeostasis and its potential impact on NDDs. This study explores the role of placental indoleamine 2,3-dioxygenase (IDO-1) in MFI homeostasis and fetal brain development. Experimental Approach The maternal-fetal barrier was disrupted by sodium valproate (VPA) in pregnant mice, whose offspring show typical autism-like behaviors. Ultrastructural analysis and flow cytometric analysis were conducted to observe the morphological and immune system changes. Behavioral tests and immunofluorescence staining was used to investigate the ability and mechanism of taprenepag to alleviate the abnormal behaviors of VPA-exposed offspring and normalize the development of serotonergic neurons. Key results In VPA-exposed pregnant mice, the downregulation of IDO-1 led to maternal immune overactivation and disruption of maternal-fetal barrier, resulting in excessive 5-HT synthesis in the placenta. This process disrupted the development of the serotonergic neuronal system in the offspring, resulting in impaired development of serotonergic neurons, thalamocortical axons, and NDDs in the progeny. However, a single injection of taprenepag at E13.5 ultimately upregulated placental IDO-1 through amplifying the positive feedback loop COX-2/PGE2/PTGER-2/IDO-1 and abolished these alterations. Conclusion Taprenepag improved autism-like behaviors in the offspring of VPA-exposed mice by addressing placental IDO-1 downregulation. This study highlights the potential of targeting IDO-1 to mitigate MFI disruption and NDD development.

Abstract Background Dietary cholesterol promotes metabolic dysfunction-associated steatohepatitis (MASH), with hepatic macrophages central to disease pathology. However, the mechanisms by which cholesterol-loaded macrophages influence MASH remain unclear. Methods In this study, mice were fed a cholesterol-rich choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD). Hepatic cholesterol levels, inflammatory markers, and pro-inflammatory macrophage polarization were assessed. In vitro studies examined the impact of cholesterol on macrophage polarization, identifying 7-dehydrocholesterol reductase (DHCR7) as a key cholesterol- and inflammation-responsive enzyme. DHCR7 expression in macrophages from MASH patients and model mice was evaluated. Functional studies involving in vitro knockdown and overexpression experiments, were complemented using myeloid-specific DHCR7 knockout mice. RNA sequencing was performed on liver tissues from wild-type and DHCR7 knockout mice to identify affected signaling pathways. Results CDAHFD-fed mice exhibited local cholesterol accumulation and a pro-inflammatory macrophage phenotype in the liver. Cholesterol overload in vitro promoted M1 polarization and liver inflammation, reversible by simvastatin. DHCR7 expression, responded to cholesterol and polarization state, was downregulated in M1-polarized and hepatic macrophages from MASH patients and mice. DHCR7 suppression promoted pro-inflammatory phenotype, while its overexpression showed anti-inflammatory effects. Myeloid-specific DHCR7 deficiency in CDAHFD-fed mice worsened liver inflammation and pro-inflammatory macrophage infiltration. RNA sequencing identified the phosphoinositide 3-kinase (PI3K) pathway in DHCR7-regulated effects, with DHCR7-PI3K axis activation mitigating cholesterol-driven inflammation. Conclusions These findings unveil novel mechanistic insights into MASH pathogenesis, suggesting targeting macrophage-specific DHCR7 activation may offer a promising therapeutic strategy for MASH.

Abstract Background Hepatic encephalopathy (HE) represents a critical complications of end-stage liver disease, serving as an independent predictor of mortality among patients with cirrhosis. Despite effective treatment with rifaximin, some patients with HE still progress to recurrent episodes, posing a significant therapeutic challenge. Recurrent HE is defined as experiencing two or more episodes within a 6-month period. Previous research has suggested that FMT may emerge as a promising treatment for recurrent HE. However, there remains a critical need to explore the optimal dosage. This trial aims to abscess the efficacy and safety of two FMT dosages: 800 ml or 400 ml total bacterial count, including mortality and quality of life. Methods This multicenter, prospective, randomized controlled trial will enroll 100 eligible patients from 31 hospitals in China. Participants will be randomly assigned in a 1:1 ratio to either the high-dose group (800 ml total bacterial count) or the low-dose group (400 ml total bacterial count). The primary objective is to assess the efficacy and safety of both dosages on outcomes at 24 and 48 weeks, including mortality and quality of life. Discussion If either or both dosages of FMT demonstrate safe and effective treatment of recurrent HE, leading to improve quality of life and survival at 24 and 48 weeks, this trial would address a significant gap in the management of recurrent HE, carrying innovative and clinically significant implications. Trial registration NCT05669651 on ClinicalTrials.gov. Registered on 29 December 2022. CHiCTR2200067135 on China Registered Clinical Trial Registration Center. Registered on 27 December 2022.

The geometry processing of a point cloud 2-manifold (or point cloud surface) heavily depends on the discretization of differential geometry properties such as Gaussian curvature, mean curvature, principal curvature, and principal directions. Most of the existing algorithms indirectly compute these differential geometry properties by seeking a local approximation surface or fitting point clouds with certain polynomial functions and then applying the curvature formulas in classical differential geometry. This paper initially proposed a new discretized Laplace-Beltrami operator by applying an inherent distance parameter, which acts as the foundation for precisely estimating the mean curvature. Subsequently, the estimated mean curvature was taken as a strong constraint condition for estimating the Gaussian curvatures, principal curvatures, and principal directions by determining an optimal ellipse. The proposed methods are mainly based on the heat kernel function and do not require local surface reconstruction, thus belonging to truly mesh-free methods. We demonstrated the correctness of the estimated curvatures in both analytic and non-analytic models. Various experiments indicated that the proposed methods have high accuracy. As an exemplary application, we utilized the mean curvature for detecting features of point clouds.

Abstract The precise mechanisms regulating inflammatory and prorepair macrophages have not been fully elucidated, despite the pivotal role played by innate immunity in wound healing. We first employed a denervation wound model to validate the crosstalk between neurons and macrophages. Compared to normal wound healing, the denervation wound healing process involved fewer macrophages, decreased angiogenesis, and delayed wound healing. Consistent with the results of the scRNA-seq libraries, the number of early-phase wound proinflammatory and late-phase wound prorepair macrophages were decreased during the denervation wound healing process. We profiled early-phase and late-phase skin wounds in mice at the transcriptional and functional levels and compared them to those of normal wounds. We revealed a neuroimmune regulatory pathway driven by peripheral nerve-derived CSF1 that induces BMP2 expression in prorepair macrophages and enhances nerve regeneration. Crosstalk between neurons and macrophages facilitates the healing process of wounds and provides a potential strategy for wound healing therapy.

Abstract Background Increasing evidence suggests a link between the enzyme cathepsin S (CTSS) and tumour development. However, the potential involvement and molecular functions of CTSS in clear cell renal cell carcinoma (ccRCC) remain unclear. Methods We downloaded original data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases and integrated them using R. Kaplan–Meier plots of integrated expression scores were used to analyse survival outcomes. Additionally, we investigated mRNA expression, clinicopathological features, immune infiltrates, and single-cell sequencing analysis of CTSS in ccRCC. In vitro experiments were conducted with qRT-PCR and IHC staining. Results CTSS transcriptomic and proteomic levels were higher in ccRCC than in para-cancerous tissues. Low CTSS expression was correlated with poor prognosis in patients with ccRCC. Our data demonstrated that the expression of CTSS was strongly correlated with immune cell infiltration levels and gene markers of immune cells, chemokines, and receptors. Single-cell sequencing analysis demonstrated that CTSS expression was detectable in monocytes/macrophages. Finally, certain chemicals were confirmed to affect CTSS expression. Conclusion Our findings indicate that CTSS offers promise as a prognostic biomarker and novel immune-related therapeutic target for ccRCC.

Abstract The high-voltage oxygen redox activity of Li-rich layered oxides enables additional capacity beyond conventional transition metal (TM) redox contributions and drives the development of positive electrode active materials in secondary Li-based batteries. However, Li-rich layered oxides often face voltage decay during battery operation. In particular, although Li-rich positive electrode active materials with a high nickel content demonstrate improved voltage stability, they suffer from poor discharge capacity. Here, via physicochemical and electrochemical measurements, we investigate the correlation between oxygen redox activity and superstructure units in Li-rich layered oxides, specifically the fractions of LiMn6 and Ni4+-stabilized LiNiMn5 within the TM layer. We prove that an excess of LiNiMn5 hinders the extraction/insertion of lithium ions during Li metal coin cell charging/discharging, resulting in incomplete oxygen redox activity at a cell potential of about 3.3 V. We also demonstrate that lithium content adjustment could be a beneficial approach to tailor the superstructure units. Indeed, we report an improved oxygen redox reversibility for an optimized Li-rich layered oxide with fewer LiNiMn5 units.

Abstract Patients with rare diseases often experience prolonged diagnostic delays. Ordering appropriate genetic tests is crucial yet challenging, especially for general pediatricians without genetic expertise. Recent American College of Medical Genetics (ACMG) guidelines embrace early use of exome sequencing (ES) or genome sequencing (GS) for conditions like congenital anomalies or developmental delays while still recommend gene panels for patients exhibiting strong manifestations of a specific disease. Recognizing the difficulty in navigating these options, we developed a machine learning model trained on 1005 patient records from Columbia University Irving Medical Center to recommend appropriate genetic tests based on the phenotype information. The model achieved a remarkable performance with an AUROC of 0.823 and AUPRC of 0.918, aligning closely with decisions made by genetic specialists, and demonstrated strong generalizability (AUROC:0.77, AUPRC: 0.816) in an external cohort, indicating its potential value for general pediatricians to expedite rare disease diagnosis by enhancing genetic test ordering.

Abstract Background Wood-feeding termites have been employed as sources of novel and highly efficient lignocellulolytic enzymes due to their ability to degrade lignocellulose efficiently. As a higher wood-feeding termite, Globitermes sulphureus (Blattaria: Termitidae) plays a crucial role as a decomposer in regions such as Vietnam, Singapore, Myanmar, and Yunnan, China. However, the diversity of its gut microbiome and carbohydrate-active enzymes (CAZymes) remains unexplored. Here, we analyzed the diversity of hindgut microbial communities and CAZymes in a higher wood-feeding termite, G. sulphureus, and a lower wood-feeding termite, Coptotermes formosanus (Blattaria: Rhinotermitidae). Results 16S rRNA sequencing revealed that Spirochaetota, Firmicutes, and Fibrobacterota were the dominant microbiota in the hindgut of the two termite species. At the phylum level, the relative abundances of Proteobacteria and Bacteroidota were significantly greater in the hindgut of C. formosanus than in G. sulphureus. At the genus level, the relative abundances of Candidatus_Azobacteroides and Escherichia-Shigella were significantly lower in the hindgut of G. sulphureus than in C. formosanus. Metagenomic analysis revealed that glycoside hydrolases (GHs) with cellulases and hemicellulases functions were not significantly different between G. sulphureus and C. formosanus. Interestingly, the cellulases in G. sulphureus were mainly GH5_2, GH5_4, GH6, GH9, and GH45, while the hemicellulases were mainly GH11, GH8, GH10, GH11, GH26, and GH53. In C. formosanus, the cellulases were mainly GH6 and GH9, and the hemicellulases were mainly GH5_7, GH5_21, GH10, GH12, and GH53. In addition, β-glucosidase, exo-β-1,4-glucanase, and endo-β-1,4-glucanase activities did not differ significantly between the two termite species, while xylanase activity was higher in G. sulphureus than in C. formosanus. The bacteria encoding GHs in G. sulphureus were mainly Firmicutes, Fibrobacterota, and Proteobacteria, whereas Bacteroidota and Spirochaetota were the main bacteria encoding GHs in C. formosanus. Conclusions Our findings characterized the microbial composition and differences in the hindgut microbiota of G. sulphureus and C. formosanus. Compared to C. formosanus, G. sulphureus is enriched in genes encoding for hemicellulase and debranching enzymes. It also highlights the rich diversity of GHs in the hindgut microbiota of G. sulphureus, including the GH5 subfamily, GH6, and GH48, with the GH6 and GH48 not previously reported in other higher termites. These results strengthen the understanding of the diversity of termite gut microbiota and CAZymes.

Abstract Ruthenium (Ru) is widely recognized as a low-cost alternative to iridium as anode electrocatalyst in proton-exchange membrane water electrolyzers (PEMWE). However, the reported Ru-based catalysts usually only operate within tens of hours in PEMWE because of their intrinsically high reactivity of lattice oxygen that leads to irrepressible Ru leaching and structural collapse. Herein, we report a design concept by employing large-sized and acid-resistant lattice lead (Pb) as a second element to induce a pinning effect for effectively narrowing the moving channels of oxygen atoms, thereby lowering the reactivity of lattice oxygen in Ru oxides. The Pb-RuO2 catalyst presents a low overpotential of 188 ± 2 mV at 10 mA cm−2 and can sustain for over 1100 h in an acid medium with a negligible degradation rate of 19 μV h−1. Particularly, the Pb-RuO2-based PEMWE can operate for more than 250 h at 500 mA cm−2 with a low degradation rate of only 17 μV h−1. Experimental and theoretical calculation results reveal that Ru-O covalency is reduced due to the unique 6s−2p−4d orbital hybridization, which increases the loss energy of lattice oxygen and suppresses the over-oxidation of Ru for improved long-term stability in PEMWE.

Abstract Background Elevated homocysteine (Hcy) levels have been linked to cardiovascular disease (CVD), but their association with cardiometabolic multimorbidity (CMM) remains uncertain. Methods Data from the baseline survey of the China Northwest Cohort-Ningxia Project (CNC-NX) were used to recruit 22,566 participants. Demographic characteristics, lifestyle factors, and laboratory exam results were collected. Logistic regression was used to evaluate the association between Hcy levels and CMM risk. Restricted cubic splines (RCS) explored potential non-linear relationships, and subgroup analyses assessed the consistency of the association across distinct groups. Sensitivity analysis accounted for cluster variability. Results The final analysis included 18,126 participants. Higher Hcy levels were significantly associated with an increased risk of CMM (adjusted OR = 1.005, P = 0.003), with a linear relationship confirmed by RCS analysis (P for non-linearity = 0.142). There was a stronger association between Hcy-CMM in high-risk people, including elderly, males, and those with high BMI (P

Abstract The study aimed to assess the impact of changes in blood pressure on cardiovascular events in the Chinese population. It enrolled 33 179 Chinese participants aged ≥35 years (57.1% women) without CVD at baseline. BP status was defined according to the 2017 ACC/AHA hypertension guidelines. The type of BP change was defined as change in BP status from baseline to the end of follow‐up, included stable BP

Abstract Background Centrosomal protein of 55 kDa (CEP55) overexpression has been linked to tumor stage, aggressiveness of the tumor, poor prognosis, and metastasis. This study aims to elucidate the action of CEP55 in ovarian cancer (OC) and the regulation by the alpha-ketoglutarate-dependent dioxygenase alkB homolog 5 (ALKBH5)/Forkhead box protein P2 (FOXP2) axis. Methods Differentially expressed genes in OC were identified using in silico identification, followed by prognostic value assessment. Lentiviral vectors were constructed to downregulate CEP55 in OC cells, and colony formation, EdU, TUNEL, flow cytometry, Transwell assays, and Phalloidin staining were conducted. Transcription factors regulating CEP55 were predicted and verified, and rescue experiments were performed. The effect of ALKBH5-mediated demethylation on FOXP2 mRNA stability and OC cell cycle and EMT were analyzed. Results High expression of CEP55 in OC was linked to unsatisfactory prognosis of patients. Knockdown of CEP55 repressed proliferation, invasiveness, and epithelial-mesenchymal transition (EMT) while inducing apoptosis and cell cycle arrest in OC cells. FOXP2 bound to the promoter of CEP55 to repress CEP55 transcription. FOXP2 regulated transcriptional repression of CEP55 to impede the malignant progression of OC and inhibit tumor metastasis. ALKBH5-mediated demethylation modification induced mRNA degradation of FOXP2. Knockdown of ALKBH5 induced cell cycle arrest and inhibited EMT in OC cells. Conclusions ALKBH5 hinders FOXP2-mediated transcriptional repression of CEP55 to promote the malignant progression of OC via cell cycle and EMT.

Abstract. Recent advancements in the field of medical artificial intelligence (AI) have led to the widespread adoption of foundational and large language models. This review paper explores their applications within medical AI, introducing a novel classification framework that categorizes them as disease-specific, general-domain, and multi-modal models. The paper also addresses key challenges such as data acquisition and augmentation, including issues related to data volume, annotation, multi-modal fusion, and privacy concerns. Additionally, it discusses the evaluation, validation, limitations, and regulation of medical AI models, emphasizing their transformative potential in healthcare. The importance of continuous improvement, data security, standardized evaluations, and collaborative approaches is highlighted to ensure the responsible and effective integration of AI into clinical applications.

To screen eminent litchi varieties suitable for the development of natural antioxidant products, the total phenol, total proanthocyanidin, total flavonoid contents and A-type oligomeric procyanidin fractions in the pericarps of seven diverse litchi cultivars were analyzed. The in vitro antioxidant activities including DPPH, ABTS+ free radical scavenging and FRAP were determined. The results demonstrated that the total phenols, total proanthocyanidins, total flavonoids as well as total A-type oligomeric procyanidins contained in the pericarp extract of 'Hemaoli' were the highest. In addition, the primary and secondary mass spectra of the contained substances were analyzed and identified by electrospray liquid-mass spectrometry with quadrupole time-of-flight mass spectrometry (HPLC-Q-TOF-MS/MS). The mass spectrometry results demonstrated that the oligomeric procyanidin fractions contained in litchi pericarps were mainly epicatechin, procyanidin A2, procyanidin A4, A-type trimer and tetramer. Moreover, the content of A-type oligomeric procyanidins in litchi pericarp varied significantly (P

For decades micoorganisms have been engineered for the utilization of lignocellulose-based second-generation (2G) feedstocks, but with the concerns of increased levels of atmospheric CO2 causing global warming there is an emergent need to transition from the utilization of 2G feedstocks to third-generation (3G) feedstocks such as CO2 and its derivatives. Here, we established a yeast platform that is capable of simultaneously converting 2G and 3G feedstocks into bulk and value-added chemicals. We demonstrated that by adopting 3G substrates such as CO2 and formate, the conversion of 2G feedstocks could be substantially improved. Specifically, formate could provide reducing power and energy for xylose conversion into valuable chemicals. Simultaneously, it can form a concentrated CO2 pool inside the cell, providing thermodynamically and kinetically favoured amounts of precursors for CO2 fixation pathways, e.g., the Calvin–Benson–Bassham (CBB) cycle. Furthermore, we demonstrated that formate could directly be utilized as a carbon source by yeast to synthesize endogenous amino acids. The engineered strain achieved a one-carbon (C1) assimilation efficiency of 9.2%, which was the highest efficiency observed in the co-utilization of 2G and 3G feedstocks. We applied this strategy for productions of both bulk and value-added chemicals, including ethanol, free fatty acids (FFAs), and longifolene, resulting in yield enhancements of 18.4%, 49.0%, and ∼100%, respectively. The strategy demonstrated here for co-utilization of 2G and 3G feedstocks sheds lights on both basic and applied research for the up-coming establishment of 3G biorefineries.

Abstract Glioma has a poor prognosis, which is attributable to its inherent characteristics and lack of specific treatments. Immunotherapy plays a pivotal role in the contemporary management of malignancies. Despite the initiation of numerous immunotherapy-based clinical trials, their effects on enhancing glioma prognosis remain limited, highlighting the need for innovative and effective therapeutic targets and strategies to address this challenge. Since the 1990s, there has been a growing interest in cancer-testis antigens (CTAs) present in normal mammalian testicular germ cells and placental trophoblast cells, which exhibit reactivated expression in various tumor types. Mechanisms such as DNA methylation, histone modification, transcriptional regulation, and alternative splicing influence the expression of CTAs in tumors. The distinct expression patterns and robust immunogenicity of CTAs are promising tumor biomarkers and optimal targets for immunotherapy. Previous reports have shown that multiple CTAs are present in gliomas and are closely related to prognosis. The expression of these antigens is also associated with the immune response in gliomas and the effectiveness of immunotherapy. Significantly, numerous clinical trials, with IL13RA2 as a representative CTA member, have assessed the immunotherapeutic potential of gliomas and have shown favorable clinical efficacy. This review provides a comprehensive overview of the regulation and function of CTAs, summarizes their expression and role in gliomas, emphasizes their importance as immunotherapy targets in gliomas, and discusses related challenges and future interventions.

Abstract We propose a data-driven strategy for parameter selection in phase field nucleation models using machine learning and apply it to oxide nucleation in Fe-Cr alloys. A grand potential-based phase field model, incorporating Langevin noise, is employed to simulate oxide nucleation and benchmarked against the Johnson-Mehl-Avrami-Kolmogorov model. Three independent parameters in the phase field simulations (Langevin noise strength, numerical grid discretization and critical nucleation radius) are identified as essential for accurately modeling the nucleation behavior. These parameters serve as input features for machine learning classification and regression models. The classification model categorizes nucleation behavior into three nucleation density regimes, preventing invalid nucleation attempts in simulations, while the regression model estimates the appropriate Langevin noise strength, significantly reducing the need for time-consuming trial-and-error simulations. This data-driven approach improves the efficiency of parameter selection in phase field models and provides a generalizable method for simulating nucleation-driven microstructural evolution processes in various materials.

Abstract A strong driving force for charge separation and transfer in semiconductors is essential for designing effective photoelectrodes for solar energy conversion. While defect engineering and polarization alignment can enhance this process, their potential interference within a photoelectrode remains unclear. Here we show that oxygen vacancies in bismuth vanadate (BiVO4) can create defect dipoles due to a disruption of symmetry. The modified photoelectrodes exhibit a strong correlation between charge separation and transfer capability and external electrical poling, which is not seen in unmodified samples. Applying poling at −150 Volt boosts charge separation and transfer efficiency to over 90%. A photocurrent density of 6.3 mA cm−2 is achieved on the photoelectrode after loading with a nickel-iron oxide-based cocatalyst. Furthermore, using generated holes for methane partial oxidation can produce methanol with a Faradaic efficiency of approximately 6%. These findings provide valuable insights into the photoelectrocatalytic conversion of greenhouse gases into valuable chemical products.

Abstract The therapeutic efficacy of lung adenocarcinoma (LUAD), the most prevalent histological subtype of primary lung cancer, remains inadequate, with accurate prognostic assessment posing significant challenges. This study sought to elucidate the prognostic significance of mitochondrial-related genes in LUAD through an integrative multi-omics approach, aimed at developing personalized therapeutic strategies. Utilizing transcriptomic and single-cell RNA sequencing (scRNA-seq) data, alongside clinical information from publicly available databases, we first applied dimensionality reduction and clustering techniques to the LUAD single-cell dataset, focusing on the subclassification of fibroblasts, epithelial cells, and T cells. Mitochondrial-related prognostic genes were subsequently identified using TCGA-LUAD data, and LUAD cases were stratified into distinct molecular subtypes through consensus clustering, allowing for the exploration of gene expression profiles and clinical feature distributions across subtypes. By leveraging an ensemble of machine learning algorithms, we developed an Artificial Intelligence-Derived Prognostic Signature (AIDPS) model based on mitochondrial-related genes and validated its prognostic accuracy across multiple independent datasets. The AIDPS model demonstrated robust predictive power for LUAD patient outcomes, revealing significant differences in responses to immunotherapy and chemotherapy, as well as survival outcomes between risk groups. Furthermore, we conducted comprehensive analyses of tumor mutation burden (TMB), immune microenvironment characteristics, and genome-wide association study (GWAS) data, providing additional insights into the mechanistic roles of mitochondrial-related genes in LUAD pathogenesis. This study not only offers a novel approach to improving prognostic assessments in LUAD but also establishes a strong foundation for the development of personalized therapeutic interventions.

Abstract Background The tertiary lymphoid structures (TLSs) have an immunomodulatory function and have a positive impact on the survival outcomes of patients with oral squamous cell carcinoma (OSCC). However, there is a lack of standard approaches for quantifying TLSs and prognostic models using TLS-related genes (TLSRGs). These limitations limit the widespread use of TLSs in clinical practice. Methods A convolutional neural network was used to automatically detect and quantify TLSs in HE-stained whole slide images. By employing bioinformatics and diverse statistical methods, this research created a prognostic model using TCGA cohorts and explored the connection between this model and immune infiltration. The expression levels of three TLSRGs in clinical specimens were detected by immunohistochemistry. To facilitate the assessment of individual prognostic outcomes, we further constructed a nomogram based on the risk score and other clinical factors. Results TLSs were found to be an independent predictor of both overall survival (OS) and disease-free survival in OSCC patients. A larger proportion of the TLS area represented a better prognosis. After analysis, we identified 69 differentially expressed TLSRGs and selected three pivotal TLSRGs to construct the risk score model. This model emerged as a standalone predictor for OS and exhibited close associations with CD4 + T cells, CD8 + T cells, and macrophages. Immunohistochemistry revealed high expression levels of CCR7 and CXCR5 in TLS + OSCC samples, while CD86 was highly expressed in TLS- OSCC samples. The nomogram demonstrates excellent predictive ability for overall survival in OSCC patients. Conclusions This is the first prognostic nomogram based on TLSRGs, that can effectively predict survival outcomes and contribute to individual treatment strategies for OSCC patients.

Abstract Background Polyploidisation often results in genome rearrangements that may involve changes in both the single-copy sequences and the repetitive genome fraction. In this study, we performed a comprehensive comparative analysis of repetitive DNA, with a particular focus on ribosomal DNA (rDNA), in Brachypodium hybridum (2n = 4x = 30, subgenome composition DDSS), an allotetraploid resulting from a natural cross between two diploid species that resemble the modern B. distachyon (2n = 10; DD) and B. stacei (2n = 20; SS). Taking advantage of the recurrent origin of B. hybridum, we investigated two genotypes, Bhyb26 and ABR113, differing markedly in their evolutionary age (1.4 and 0.14 Mya, respectively) and which resulted from opposite cross directions. To identify the origin of rDNA loci we employed cytogenetic and molecular methods (FISH, gCAPS and Southern hybridisation), phylogenetic and genomic approaches. Results Unlike the general maintenance of doubled gene dosage in B. hybridum, the rRNA genes showed a remarkable tendency towards diploidisation at both locus and unit levels. While the partial elimination of 35S rDNA units occurred in the younger ABR113 lineage, unidirectional elimination of the entire locus was observed in the older Bhyb26 lineage. Additionally, a novel 5S rDNA family was amplified in Bhyb26 replacing the parental units. The 35S and 5S rDNA units were preferentially eliminated from the S- and D-subgenome, respectively. Thus, in the more ancient B. hybridum lineage, Bhyb26, 5S and 35S rRNA genes are likely expressed from different subgenomes, highlighting the complexity of polyploid regulatory networks. Conclusion Comparative analyses between two B. hybridum lineages of distinct evolutionary ages revealed that although the recent lineage ABR113 exhibited an additive pattern of rDNA loci distribution, the ancient lineage Bhyb26 demonstrated a pronounced tendency toward diploidisation manifested by the reduction in the number of both 35S and 5S loci. In conclusion, the age of the allopolyploid appears to be a decisive factor in rDNA turnover in B. hybridum.

Abstract Background Recent studies have highlighted the role of miR-5195-3p in suppressing cell growth in various cancers. However, the specific functional impact of miR-5195-3p in colorectal cancer (CRC) remain to be fully clarified. The importance of miR-5195-3p in CRC was evaluated, aiming to uncover its underlying molecular mechanism and identify it as a potential therapeutic target for CRC. Results Our research has shown that miR-5195-3p is markedly under-expressed in CRC tissues and cell cultures, with its reduced presence associated with a higher TNM stage, lymphatic invasion, and unfavorable survival outcome. Ectopic miR-5195-3p expression curtailed proliferation, migration, and invasion of SW1116 and HT29 cells. Additionally, we discovered that miR-5195-3p directly targets and negatively influences Toll-like receptor 4 (TLR4) in CRC cells. Moreover, an inverse relationship was noted between miR-5195-3p and TLR4 expression in CRC tissue samples. Notably, restoring TLR4 expression counteracted miR-5195-3p’s suppressive impact on cell growth, motility, invasiveness, epithelial-mesenchymal transition (EMT), and the TLR4/MyD88 signaling pathway in SW1116 and HT29 cells. Conclusions MiR-5195-3p suppresses the CRC cellular functions through the downregulation of TLR4/MyD88 signaling, indicating that targeting miR-5195-3p might offer a viable therapeutic strategy for CRC.

Abstract Purpose This study aimed to compare the differences in postoperative complications and long-term bowel function outcomes between patients with rectosigmoid Hirschsprung disease (HD) who underwent transanal endorectal pull-through (TEPT) beyond infancy (age> 1 year of age) and those during infancy (≤ 1 year of age). Methods All patients with rectosigmoid HD at Beijing Children’s Hospital between January 2011 and December 2020 were analyzed retrospectively. They were divided into two groups based on age at TEPT: group A was defined as patients who performed TEPT beyond infancy (age>1 year of age), and group B as patients who performed TEPT during infancy (age ≤ 1 year of age). Clinical details were collected from medical records. Bowel function outcomes were assessed by the Rintala questionnaire (age ≥ 4 years). Results A total of 339 patients were included: 216 (63.7%) who operated with TEPT beyond infancy (group A) and 123 (36.3%) during infancy (group B). Regarding postoperative complications, all patients suffering anastomosis leakage following TEPT (7/216, 3.2%) occurred in group A, and the rate of anastomosis leakage in group A was significantly higher than in group B (3.2% vs. 0.0%, p = 0.044). 228 patients (228/327, 69.7%) completed the Rintala questionnaire. There was no significant difference in long-term bowel function outcomes between the two groups. Conclusion Compared with patients who performed TEPT during infancy, those beyond infancy are more likely to suffer anastomosis leakage. however, the long-term bowel function outcomes seem comparable. Type of Study A retrospective single-center study. Level of evidence III.

Abstract Background Bacteria, Archaea, and Microeukaryotes comprise taxonomic domains that interact in mediating biogeochemical cycles in coastal waters. Many studies have revealed contrasting biogeographic patterns of community structure and assembly mechanisms in microbial communities from different domains in coastal ecosystems; however, knowledge of specific biogeographic patterns on microbial co-occurrence relationships across complex coastal environmental gradients remains limited. Using a dense sampling scheme at the regional scale, SSU rRNA gene amplicon sequencing, and network analysis, we investigated intra- and inter-domain co-occurrence relationships and network topology-based biogeographic patterns from three microbial domains in coastal waters that show environmental gradients across the inshore-nearshore-offshore continuum in the East China Sea. Results Overall, we found the highest complexity and connectivity in the bacterial network, the highest modularity in the archaeal network, and the lowest complexity, connectivity, and modularity in the microeukaryotic network. Although microbial co-occurrence networks from the three domains showed distinct topological features, they exhibited a consistent biogeographic pattern across the inshore-nearshore-offshore continuum. Specifically, the nearshore zones with intermediate levels of terrestrial impacts reflected by multiple environmental factors (including water temperature, salinity, pH, dissolved oxygen, and nutrient-related parameters) had a higher intensity of microbial co-occurrence for all three domains. In contrast, the intensity of microbial co-occurrence was weaker in both the inshore and the offshore zones at the two ends of the environmental gradients. Archaea occupied a central position in the microbial inter-domain co-occurrence network. In particular, members of the Thaumarchaeota Marine Group I (MGI, now placed within the Family Nitrosopumilaceae of the Phylum Thermoproteota) appeared to be the hubs in the biogeographic shift between inter-domain network modules across environmental gradients. Conclusions Our work offers new insights into microbial biogeography by integrating network features into biogeographic patterns, towards a better understanding of the potential of microbial interactions in shaping biogeographic patterns of coastal marine microbiota.

Abstract Aims We aim to integrate the parameters of two‐dimensional (2D) echocardiography and identify the high‐risk population for all‐cause mortality in patients with acute ST‐segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI). Methods The study involved a retrospective cohort population with STEMI who were admitted to Yongchuan Hospital of Chongqing Medical University between January 2016 and January 2019. Baseline data were collected, including 2D echocardiography parameters and left ventricular ejection fraction (LVEF). The parameters of 2D echocardiography were subjected to cluster analysis. Logistic regression models were employed to assess univariate and multivariate adjusted odds ratios (ORs) of cluster information in relation to all‐cause mortality. Four logistic regression models were generated, utilizing cluster information, clinical variables, clinical variables in conjunction with LVEF, and clinical variables in conjunction with LVEF and cluster information as predictive variables, respectively. The area under the curve (AUC) were utilized to evaluate the incremental risk stratification value of cluster information. Results The study included 633 participants with 28.8% female, a mean age of 65.68 ± 11.98 years. Over the course of a 3‐year follow‐up period, 108 (17.1%) patients experienced all‐cause mortality. Utilizing cluster analysis of 2D echocardiography parameters, the patients were categorized into two distinct clusters, with statistically significant differences observed in most clinical variables, echocardiography, and survival outcomes between the clusters. Multivariate regression analysis revealed that cluster information was independently associated with the risk of all‐cause mortality with adjusted OR 7.33 (95% confidence interval [CI] 3.99–14.06, P

AIM: To describe the distribution of ocular biometrics and to evaluate its associations with refractive error and to assess the contribution from ocular parameters to refractive error among Chinese myopic children. METHODS: This cross-sectional study evaluated subjects aged 8-12y. Keratometry, ocular biometry, and cycloplegic autorefraction were performed on each subject. Spherical equivalent refraction (SER) and ocular biometrics were assessed as a function of age and gender. The Pearson correlation analysis between SER and ocular biometrics was carried out. Multiple linear regression was performed to analyze the association between SER and ocular parameters. RESULTS: A total of 689 out of 735 participants (321 boys, 48.1%) were analyzed, with a mean SER of -2.98±1.47 diopter (D). Axial length (AL), anterior chamber depth (ACD), corneal radius of curvature (CR), horizontal visible iris diameter (HVID), central corneal thickness (CCT) and lens power (LP) showed normal distribution. The AL, AL/CR ratio, ACD and CR increased from 8 to 12y of age, while SER and LP decreased, HVID and CCT remained stable. There was no difference in gender. SER decreased by 0.929 D for every 1 mm increase in AL and decreased by 1.144 D for every 0.1 increase in AL/CR ratio. The Pearson correlation coefficient between SER and AL was -0.538 (P

Spinal cord ischemia/reperfusion (IR) injury (SCII) can cause major autonomic, sensory, and motor damage and loss. The upregulation of Nrf2, a primary orchestrator of the oxidative stress response, has beneficial effects in SCII. Here, we aimed to uncover a SCII-related transcription factor that is able to elevate Nrf2 expression. Rat PC12 cells were subjected to treatment with oxygen-glucose deprivation/reoxygenation (OGD/R) to induce an in vitro neuronal IR injury model. A rat model of SCII was established by blocking the left common carotid artery and aortic arch in SD rats. Cell viability and apoptosis were assessed by the CCK-8 assay and flow cytometry, respectively. IL-1β and TNF-α levels were detected by ELISA. The oxidative stress was tested by assessing ROS and MDA contents and SOD and GSH-Px activity. The NFATC2/Nrf2 relationship was predicted by bioinformatic analysis and validated by ChIP and luciferase reporter assays. Nrf2 and NFATC2 levels were reduced in PC12 cells after OGD/R treatment. Nrf2 increase significantly attenuated OGD/R-triggered inflammation, apoptosis and oxidative stress in PC12 cells. Moreover, Nrf2 increase alleviated spinal cord pathological changes, inflammation, apoptosis and oxidative stress in rats after SCII. Mechanistically, NFATC2 could activate Nrf2 transcription and promote its expression. Nrf2 reduction exerted a counteracting impact on NFATC2's anti-inflammation, anti-apoptosis and anti-oxidative stress functions in PC12 cells under OGD/R conditions. Our study demonstrates that the NFATC2/Nrf2 cascade has a regulatory capacity in inflammation, apoptosis and oxidative stress after SCII.

How to achieve intelligent, safe and efficient mining of rockburst coal seams is a major engineering and technical challenge facing deep coal mining. The core connotation of this issue lies in the intelligent, unmanned, and inherently safe mining of coal seams with rockburst. Through accurate perception and intelligent early warning of coal and rock burst risks, as well as self-adaptation and self-optimization of mining engineering, intelligent anti-burst and mining control technologies are formed to achieve a fundamental shift from engineering-induced disasters to engineering-prevented and mitigated disasters. By implementing measures such as mining source design, roof area fracturing, localized targeted management, and strengthening roadway support, a low-stress environment and safe roadway space are created for the safe and efficient mining of coal seams with rock burst. On this basis, a big data analysis software platform that integrates static geological, dynamic monitoring, working conditions, personnel positioning, production organization, historical data and other information, as well as an intelligent mining control system that integrates impact pressure decision-making information, has been developed. The anti-impact information source has been transformed into an intelligent mining control source, forming a new flexible intelligent mining model of "low pressure fast pushing, medium pressure slow mining, and high pressure production stop". Field application shows that in the intelligent anti-impact and control mining area, the degree of mine pressure in working face and roadway is smaller,, and the energy release of coal and rock is more stable, which is conducive to the reasonable release of impact mine production capacity.

Abstract Femtosecond laser pulses enable the synthesis of light across the electromagnetic spectrum and provide access to ultrafast phenomena in physics, biology, and chemistry. Chip-integration of femtosecond technology could revolutionize applications such as point-of-care diagnostics, bio-medical imaging, portable chemical sensing, or autonomous navigation. However, current chip-integrated pulse sources lack the required peak power, and on-chip amplification of femtosecond pulses has been an unresolved challenge. Here, addressing this challenge, we report >50-fold amplification of 1 GHz-repetition-rate chirped femtosecond pulses in a CMOS-compatible photonic chip to 800 W peak power with 116 fs pulse duration. This power level is 2–3 orders of magnitude higher compared to those in previously demonstrated on-chip pulse sources and can provide the power needed to address key applications. To achieve this, detrimental nonlinear effects are mitigated through all-normal dispersion, large mode-area and rare-earth-doped gain waveguides. These results offer a pathway to chip-integrated femtosecond technology with peak power levels characteristic of table-top sources.

Abstract Mural cells are central to vascular integrity and function. In this study, we demonstrate the innovative use of the transcription factor NKX3.1 to guide the differentiation of human induced pluripotent stem cells into mural progenitor cells (iMPCs). By transiently activating NKX3.1 in mesodermal intermediates, we developed a method that diverges from traditional growth factor-based differentiation techniques. This approach efficiently generates a robust iMPC population capable of maturing into diverse functional mural cell subtypes, including smooth muscle cells and pericytes. These iMPCs exhibit key mural cell functionalities such as contractility, deposition of extracellular matrix, and the ability to support endothelial cell-mediated vascular network formation in vivo. Our study not only underscores the fate-determining significance of NKX3.1 in mural cell differentiation but also highlights the therapeutic potential of these iMPCs. We envision these insights could pave the way for a broader use of iMPCs in vascular biology and regenerative medicine.

Objective The anterior controllable antedisplacement and fusion (ACAF) technique is a new procedure for the treatment of cervical ossification of the posterior longitudinal ligament (OPLL) that requires management of the disc adjacent to the ossification. This study describes a novel technique to reduce the number of fixed segments, namely, the “Klotski technique.” The efficacy of ACAF using the Klotski technique was compared with that of anterior cervical corpectomy and fusion (ACCF) in the treatment of OPLL with en bloc type dural ossification (DO). Methods The clinical data of 25 patients with severe OPLL and en bloc type DO who were treated by the ACAF Klotski technique or ACCF at our hospital from January 2020 to January 2022 were retrospectively analyzed. In the Klotski technique, the number of segments fused within the OPLL is limited. The antedisplacement space was designed according to the shape of the vertebrae-OPLL-DO complex (VODC). Then, the entire VODC was antedisplaced as in Klotski. Neurological function and image examination were assessed preoperatively and postoperatively. Complications associated with surgery were recorded. Results Patients were followed up for 24–36 months. There were 11 patients who were treated with ACAF and 14 patients who were treated with ACCF. At 2 weeks after surgery, the incidence of neurological deterioration was 21.4% (3 of 14) in the ACCF group and 9.1% (1 of 11) in the ACAF group. The incidence of intraoperative cerebrospinal fluid leakage (CFL) was 35.7% (5 of 14) in the ACCF group and 9.1% (1 of 11) in the ACAF group. The postoperative follow-up JOA scores of the patients in both groups were significantly better than their preoperative JOA scores (p

Pneumonia caused by novel coronavirus is an acute respiratory infectious disease. Its rapid spread in a short period of time has brought great challenges for global public health. The use of deep learning and radiomics methods can effectively distinguish the subtypes of lung diseases, provide better clinical prognosis accuracy, and assist clinicians, enabling them to adjust the clinical management level in time. The main goal of this study is to verify the performance of deep learning and radiomics methods in the classification of COVID-19 lesions and reveal the image characteristics of COVID-19 lung disease. An MFPN neural network model was proposed to extract the depth features of lesions, and six machine-learning methods were used to compare the classification performance of deep features, key radiomics features and combined features for COVID-19 lung lesions. The results show that in the COVID-19 image classification task, the classification method combining radiomics and deep features can achieve good classification results and has certain clinical application value.

Abstract The prevalence of autism spectrum disorders (ASDs) differs substantially between males and females, suggesting that sex-related neurodevelopmental factors are central to ASD pathogenesis. Numerous studies have suggested that abnormal brain specialization patterns and poor regional cooperation contribute to ASD pathogenesis, but relatively little is known about the related sex differences. Therefore, this study examined sex differences in brain functional specialization and cooperation among children with ASD. The autonomy index (AI) and connectivity between functionally homotopic voxels (CFH) derived from resting-state functional magnetic resonance imaging (rs-fMRI) were compared between 58 male and 13 female children with ASD. In addition, correlations were examined between regional CFH values showing significant sex differences and symptom scores on the autism behavior checklist (ABC) and childhood autism rating scale (CARS). Male children with ASD demonstrated significantly greater CFH in the left fusiform gyrus (FG) and right opercular part of the inferior frontal gyrus (IFGoperc) than female children with ASD. In addition, the CFH value of the left FG in male children with ASD was negatively correlated with total ABC score and subscale scores for sensory and social abilities. In contrast, no sex differences were detected in brain specialization. These regional abnormalities in interhemispheric cooperation among male children with ASD may provide clues to the neural mechanisms underlying sex differences in ASD symptomatology and prevalence. Autism spectrum disorders, sex, resting-state functional magnetic resonance imaging, cerebral specialization, interhemispheric cooperation.

Abstract Background Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne infection with a high case fatality rate. Significant gaps remain in studies analyzing the clinical characteristics of fatal cases. Methods From January 2017 to June 2023, 427 SFTS cases were included in this study. A total of 67 variables about their demographic, clinical, and laboratory data were collected. Univariate logistic regression and the least absolute shrinkage and selection operator (LASSO) method was used to screen predictors from the cohort. Multivariate logistic regression was used to identify independent predictors and nomograms were developed. Calibration, decision curves and area under the curve (AUC) were used to assess model performance. Results The multivariate logistic regression analysis screened out the four most significant factors, including age > 70 years (p = 0.001, OR = 2.516, 95% CI 1.452–4.360), elevated serum PT (p 8.0 μmol/L) (p

Abstract Computer haptics (CH) is about integration of tactile sensation and rendering in Metaverse. However, unlike computer vision (CV) where both hardware infrastructure and software programs are well developed, a generic tactile data capturing device that serves the same role as what a camera does for CV, is missing. Bioinspired by electrophysiological processes in human tactile somatosensory nervous system, here we propose a tactile scanner along with a neuromorphically-engineered system, in which a closed-loop tactile acquisition and rendering (re-creation) are preliminarily achieved. Based on the architecture of afferent nerves and intelligent functions of mechano-gating and leaky integrate-and-fire models, such a tactile scanner is designed and developed by using piezoelectric transducers as axon neurons and thin film transistor (TFT)-based neuromorphic circuits to mimic synaptic behaviours and neural functions. As an example, the neuron-like tactile information of surface textures is captured and further used to render the texture friction of a virtual surface for “recreating” a “true” feeling of touch.

Four new species of Yunguirius B. Li, Zhao & S.Q. Li, 2023 are described from China, namely: Yunguirius parvus Wei & Liu, sp. nov. (♀), Yunguirius trigonus Wei & Liu, sp. nov. (♀), Yunguirius wangqiqiae Wei & Liu, sp. nov. (♀), and Yunguirius xiannushanensis Wei & Liu, sp. nov. (♀).

Background: In the recent decade, there has been substantial progress in the technologies and philosophies associated with diagnosing and treating anterior cruciate ligament (ACL) injuries in China. The therapeutic efficacy of ACL reconstruction in re-establishing the stability of the knee joint has garnered widespread acknowledgment. However, the path toward standardizing diagnostic and treatment protocols remains to be further developed and refined. Objective: In this context, the Chinese Association of Orthopaedic Surgeons (CAOS) and the Chinese Society of Sports Medicine (CSSM) collaboratively developed an expert consensus on diagnosing and treating ACL injury, aiming to enhance medical quality through refining professional standards. Methods: The consensus drafting team invited experts across the Greater China region, including the mainland, Hong Kong, Macau, and Taiwan, to formulate and review the consensus using a modified Delphi method as a standardization approach. As members of the CSSM Lower Limb Study Group and the CAOS Arthroscopy and Sports Medicine Study Group, invited experts concentrated on two pivotal issues: “Graft Selection” and “Clinical Outcome Evaluation” during the second part of the consensus development. Results: This focused discussion ultimately led to a strong consensus on nine specific consensus terms. Conclusion: The consensus clearly states that ACL reconstruction has no definitive “gold standard” graft choice. Autografts have advantages in healing capability but are limited in availability and have potential donor site morbidities; allografts reduce surgical trauma but incur additional costs, and there are concerns about slow healing, quality control issues, and a higher failure rate in young athletes; synthetic ligaments allow for early rehabilitation and fast return to sport, but the surgery is technically demanding and incurs additional costs. When choosing a graft, one should comprehensively consider the graft's characteristics, the doctor's technical ability, and the patient's needs. When evaluating clinical outcomes, it is essential to ensure an adequate sample size and follow-up rate, and the research should include patient subjective scoring, joint function and stability, complications, surgical failure, and the return to sport results. Medium and long-term follow-ups should not overlook the assessment of knee osteoarthritis.

Grain boundary (GB) strengthening of metallic materials faces limitations as grain sizes are reduced to the nanoscale, primarily due to the transition from the strengthening to the softening effects. Understanding the intrinsic mechanisms behind such pronounced transitions is essential for optimizing the mechanical properties of nanocrystalline (NC) alloys. In this work, the critical grain size responsible for this transition is determined for NC CoCrNi medium-entropy alloys using molecular dynamics simulation, and the underlying mechanisms concerning varying temperatures and strain rates are systematically investigated for the samples with the critical grain size. The transition from Hall-Petch (HP) strengthening to Inverse Hall-Petch (IHP) softening is established by decreasing the average grain sizes from 21 nm to 3 nm. The critical grain size for the current alloys is estimated to be 12 nm, and the underlying deformation mechanisms are illustrated as follows: In the IHP regime, GB-mediated deformation becomes dominant, leading to softening. Conversely, in the HP regime, dislocation slip dominates the deformation mode, contributing to strengthening. It is found that an increase in temperature from 77 K to 1100 K leads to a decrease in the average flow stress and Young's modulus. Meanwhile, the deformation mechanisms change from dislocation slip (77K–700K) to GB-mediated deformation (700 K–1100 K). Furthermore, the underlying mechanisms correlating to the critical strain rate are uncovered. It can be attributed to the shift in deformation mechanisms from dislocation slip at relatively low strain rate regimes (5 × 107 s−1-2 × 109 s−1) to dislocation drag at relatively high strain rate regimes (2 × 109 s−1-5 × 109 s−1). Our atomistic insights into the tensile response of NC CoCrNi may provide a crucial basis for designing superior properties to meet the growing demands of advanced engineering fields.