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The ion optical system is an important component of electron impact (EI) ion source, which uses electrostatic lens to extract ions in the ion chamber, further focus, accelerate and shape, and regulate the speed and energy of the ion beam. The performance of the ion optical system will directly affect the sensitivity and stability of the mass spectrometer. Based on the digital simulation, the ion optical system of EI source can be used to track the movement trajectory of ions from generation to the moment before entering the mass analyzer, which is helpful to deeply understand and recognize the dynamic behavior of ions in the system, and study the key influencing factors of ion movement. In this paper, the ion optical digital simulation system of EI source named Sim-EI-Lens-COM-V1.0 was developed. The geometric structure of each component in the simulation system can be uniformly configured and modified, which is suitable for the simulation of different types of ion optical systems. Based on the developed simulation system, two kinds of typical ion optics with cylindrical and sheet lenses were constructed. The key factors affecting the ion transport efficiency, such as geometric size and voltage parameter of each component in the simulation system, the species and total number of ions produced, and the time of the ion to pass through the system, were studied. Firstly, the influences of the electrostatic lens thickness on the ion dynamic behavior and transport efficiency were investigated. Then appropriate number and initial distribution of ions were selected, and the parametric scanning calculations of the voltage parameters were carried out. Through coarse, fine and precise adjustment of different voltage step values, the optimal voltage combinations of two typical ion optics systems were achieved. The performances of the two ion optical systems were compared under the optimal voltage combination. The result showed that the ion transmission in cylindrical lens ion optical system can reach to 97%, and it can reach more than 99% in sheet lens. The time for ions to pass through the system increases with the increasing of ion mass-charge ratio. The time to pass through the cylindrical lens is shorter than that of the sheet lens under the same ion mass-charge ratio. The radial energy distributions of ions at the outlet of the two ions optical systems are similar, and the axial energy distribution at the outlet of the sheet lens is more concentrated with higher consistency.

Abstract Background Thyroid nodules are common, and fine needle aspiration biopsy (FNAB) is essential for diagnosis and treatment. Patients’ service needs are rarely addressed and discussed. This study was to analyze the nursing service needs of patients undergoing outpatient thyroid FNAB. Methods Using the Delphi method, indicators of nursing service needs were established. A survey based on the Kano model was conducted from February to May 2024 to analyze service needs among patients undergoing thyroid FNAB. A quadrant analysis chart was used to visualize the impact of service characteristics on patient satisfaction. Results Among the 32 service needs, 12 items were in the improved category, 10 items were in the advantage category, 9 items were in the reserved category, and 1 item was in the observation category. Conclusions The Kano model effectively categorizes the service needs of outpatients undergoing thyroid FNAB, guiding healthcare providers to enhance patient satisfaction through optimized services. Trial registration The registration number is ChiCTR2400080522, and the registration date is January 30, 2024.

Metabolic engineering-driven microbial cell factories have made great progress in the efficient bioproduction of biochemical and recombinant proteins. However, the low efficiency and robustness of microbial cell factories limit their industrial applications. Harnessing microbial heterogeneity contributes to solving this. In this review, the origins of microbial heterogeneity and its effects on biosynthesis are first summarized. Synthetic biology-driven tools and strategies that can be used to improve biosynthesis by increasing and reducing microbial heterogeneity are then systematically summarized. Next, novel single-cell technologies available for unraveling microbial heterogeneity and facilitating heterogeneity regulation are discussed. Furthermore, a combined workflow of increasing genetic heterogeneity in the strain-building step to help in screening highly productive strains - reducing heterogeneity in the production process to obtain highly robust strains (IHP-RHR) facilitated by single-cell technologies was proposed to obtain highly productive and robust strains by harnessing microbial heterogeneity. Finally, the prospects and future challenges are discussed.

Silicone rubber composites with anti-ablation and thermal insulation properties were prepared with hot vulcanized silicone rubber as matrix, and polyarylacetylene, short carbon fiber, zirconia and carbon fiber cloth as anti-ablation fillers, and the effect of anti-ablation fillers on linear ablation rate and substrate temperature of the composites was investigated. The results showed that the linear ablation rate and substrate temperature of the composites were decreased with the sequential addition of the anti-ablation fillers. When the addition amount of polyarylacetylene, short carbon fiber, zirconia, and carbon fiber cloth were all 10 phr (mass), the resul-ting composite had the best anti-ablation and thermal insulation properties with a linear ablation rate of 0.043 mm/s and a substrate temperature of 70 ℃. This was mainly attributed to the ceramization-carbonization coupling reaction between the anti-ablation fillers and silicone rubber matrix, which led to the formation of a dense ablation layer that covered the surface of carbon fiber cloth.

Abstract Cancer-associated fibroblasts (CAFs) exert multiple tumor-promoting functions and are key contributors to drug resistance. The mechanisms by which specific subsets of CAFs facilitate oxaliplatin resistance in colorectal cancer (CRC) have not been fully explored. This study found that THBS2 is positively associated with CAF activation, epithelial-mesenchymal transition (EMT), and chemoresistance at the pan-cancer level. Together with single-cell RNA sequencing and spatial transcriptomics analyses, we identified THBS2 specifically derived from subsets of CAFs, termed THBS2 + CAFs, which could promote oxaliplatin resistance by interacting with malignant cells via the collagen pathway in CRC. Mechanistically, COL8A1 specifically secreted from THBS2 + CAFs directly interacts with the ITGB1 receptor on resistant malignant cells, activating the PI3K-AKT signaling pathway and promoting EMT, ultimately leading to oxaliplatin resistance in CRC. Moreover, elevated COL8A1 promotes EMT and contributes to CRC oxaliplatin resistance, which can be mitigated by ITGB1 knockdown or AKT inhibitor. Collectively, these results highlight the crucial role of THBS2 + CAFs in promoting oxaliplatin resistance of CRC by activating EMT and provide a rationale for a novel strategy to overcome oxaliplatin resistance in CRC.

Highlights Hierarchical melamine foam (MF)/polypyrrole (PPy) nanowire arrays (MF@PPy) were fabricated by electrochemical polymerization. The 3D porous PPy micro-skeleton and the 1D PPy nanowire arrays imparted the MF@PPy foams with high electromagnetic interference shielding performance of 19,928.57 dB cm2 g−1 via multiple attenuations. The PPy nanowire arrays achieved multifunctional integration including hydrophobicity, thermal insulation, and dynamic infrared thermal camouflage properties.

Abstract Lycopene is a high‐value‐added tetraterpenoid, which is widely used in cosmetics, medicine, food, and dietary supplements. The intracellular mevalonate pathway of Saccharomyces cerevisiae provides natural precursors for terpenoid product synthesis, so it is an excellent host for the heterologous production of lycopene. In this study, a recombinant strain named L10 with efficient lycopene production capability was constructed through multiple strategies, such as regulating the gene copy number of key enzymes, increasing nicotinamide adenine dinucleotide phosphate supply, and reducing squalene accumulation. Then, considering that intracellular lycopene accumulation can cause cytotoxicity to S. cerevisiae, we attempted to identify a transporter that can efficiently transport lycopene from intracellular to extracellular space. Molecular docking simulations predicted that the ATP‐binding cassette transporter Snq2p may be a potential transporter of lycopene, and its function in promoting lycopene secretion was further determined by overexpression verification. The lycopene secretion titer of the strain L10Z2 overexpressing Snq2p increased to 16.5 times that of the control at the shake‐flask level. After optimizing the galactose regulation system, the intracellular and secreted lycopene production of L11Z2 reached 2113.78 and 26.28 mg/L, respectively, after 150 h fed‐batch culture in a 3‐L bioreactor. This work provides a new research direction for efficient lycopene synthesis in S. cerevisiae cell factory.

Thinning silviculture is a forestry measure that can improve forest ecosystems and stand structure. Thinning can impact the properties and quality of poplar wood. This study investigated the effects of three different thinning intensities on the fiber morphology and crystallinity of poplar wood, providing a theoretical basis for the cultivation and rational processing of poplar plantations. The results indicated significant differences in the proportion of wet heartwood area among different thinning intensities. With increased thinning intensity, the wet heartwood area proportion rose, while it decreased with wood height under the same thinning intensity. Fiber length increased with thinning intensity, reaching a 16% increase at 50% thinning, as well as with sampling height. Fiber width grew with thinning intensity, initially widening, and then narrowing with height. Cell wall thickness first increased and then decreased with thinning intensity, peaking at 50% thinning. The fiber length-width ratio increased with thinning intensity and initially increased then decreased with height. The fiber-diameter-cavity ratio also increased with thinning intensity and height. Crystallinity showed a trend of first increasing and then decreasing with tree height, peaking at breast height, and it was higher in normal wood than in wet heartwood under the same thinning intensity.

Abstract Background Immune checkpoint inhibitors (ICIs) have greatly improved cancer treatment, but the role of genes related to T cell-mediated tumor killing (TTK) sensitivity in ovarian cancer (OV) is unclear. Methods This study analyzed 1367 OV patients and 11 independent cohorts. The unsupervised clustering was conducted to identify three tumor subtypes based on genes that regulate tumor cell sensitivity to TTK (GSTTKs). The biological characteristics, genetic variations, immunological landscape, and therapeutic evaluation for each subtype were further explored. Results Patients were divided into three reproducible subtypes based on 61 GSTKKs associated with prognosis. C1 was likely to be an invasive subtype with the worst prognosis and highly unstable genome. C2 might be an immune-active subtype with the best prognosis, high immune infiltration and preferable response to immunotherapy. C3 might be a metabolic subtype, resistant to immunotherapy, but sensitive to drug therapy. Following an extensive exploration into a variety of distinct molecular features between the three subtypes, the results suggested that C2 patients were considered to derive significant efficacy from immunotherapy. For C1 and C3 patients, chemotherapy might be an ideal treatment strategy. Conclusions In this study, three GSTKKs-based subtypes were identified by assessing TTK patterns in OV. These new insights further improved our understanding of GSTTKs and might refine clinical treatment strategies for OV patients.

Abstract To investigate the value and sensitivity of contrast-enhanced ultrasonography (CEUS) combined with fine-needle aspiration biopsy (FNAB) in the diagnosis of thyroid nodules. This study enrolled 120 patients with thyroid nodules who visited our hospital between July 2018 and January 2021. All patients underwent CEU and CEUS-guided FNAB. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of CEUS-guided FNAB for the qualitative diagnosis of thyroid nodules were significantly higher compared with CEUS only (P

Abstract Follicular lymphoma (FL) is an immune-responsive tumor with spontaneous remission. T cells play a pivotal role in the anti-lymphoma immune response. However, the dynamics of T cells during treatment, their impact on FL clinical outcomes, and the risk factors contributing to T-cell cytopenia remain largely unexplored. T-cell and their subsets in the peripheral blood of FL patients at diagnosis, during 2–4 cycles and after 6 cycles of treatment, as well as healthy individuals were detected by flow-cytometry. The predictive effects of T cells for early progression and risks for T-cell cytopenia were analyzed. FL patients exhibited a significant decrease in CD3+, CD4+, and CD8 + T cells compared to healthy individuals, with aging intensifying the decline of CD3+, and CD4 + T cells. Notably, a reduction in CD4 + T cells, predominantly contributing to treatment-related T-cell reduction, was only observed in patients undergoing Bendamustine-based regimens. Moreover, a significantly decreased CD4 + and CD8 + T-cell at diagnosis rather than after induction therapy was observed in patients with treatment failure. Furthermore, lower CD4 + T-cell (

Abstract Parkinsonian tremor (PT) and Essential tremor (ET) exist as upper limb tremors in clinical practice. Notably, their types of trembling share similar presentations and overlapping frequencies. To enhance objectivity and efficiency in the diagnosis of these two diseases, there is a pressing need for more objective tremor classification procedures. This study proposes a novel multimodal fusion network based on a cross-attention mechanism (MFCA-Net) to automate the classification of upper limb tremors between PTs and ETs. To this end, 140 patients with PTs and ETs were recruited, and acceleration and surface electromyography (sEMG) signals were collected from the forearm during tremor episodes. To comprehensively capture the global and local features of input signals, a multiscale convolution in MFCA-Net was designed. Furthermore, the cross-attention mechanism was applied to fuse the features of the two input signals. The results demonstrate that the final classification accuracy exceeded 97.18% when MFCA-Net was used. Compared with the single acceleration signal and single sEMG signal inputs, the recognition accuracies increased by 18.91% and 10.04%, respectively. Therefore, the proposed MFCA-Net in this study serves as an objective and potential tool for assisting clinicians in the diagnosis of PT and ET patients.

The die-casting process of ADC12 aluminum alloy right crankcase cover was simulated based on AnyCasting software, and the influence of pouring temperature, initial mold temperature and injection speed on the filling and solidification process of ADC12 right crankcase cover casting was explored by orthogonal experiment method. The optimal process parameters were obtained through optimization, and the die-casting mold was designed. The program was verified in production. The results show that the porosity and shrinkage of the right crankcase cover are mainly concentrated in the thick wall part. The sequence of process parameters that affect the residual melt modulus is pouring temperature, initial mold temperature, and injection speed; The best combination of process parameters: pouring temperature is ∼680 °C, initial mold temperature is ∼200 °C, injection speed is ∼5 m/s. By analyzing the filling process and temperature field simulation results, the casting structure, mold structure and cooling system were optimized, and the process plan was improved. The production verification was carried out according to the optimized process plan. The casting quality is good and has no obvious defects, which meets the actual production needs.

With the rise of healthy lifestyles, sports arenas have become important exercise venues for people. However, indoor air quality issues are becoming increasingly prominent, posing a potential threat to the health of athletes. Traditional indoor air quality monitoring systems often suffer from problems such as unreasonable layout of monitoring points and inaccurate data processing, making it difficult to effectively cope with complex indoor environments. This article proposes an intelligent monitoring system for indoor air quality in sports venues based on an improved cohesive hierarchical clustering algorithm to address these issues. The system optimizes the layout of monitoring points, combines real-time data collection on the Android platform, and accurately processes non smooth data using an improved cohesive hierarchical clustering algorithm based on BiLSTM. The experimental results show that the algorithm not only improves the accuracy of monitoring point selection, but also optimizes the number of monitoring points and effectively supplements missing data. In addition, the algorithm significantly reduces computational complexity and improves computational efficiency while ensuring clustering quality. Application testing shows that the indoor air environment monitoring system constructed in this article can obtain and analyze data in real time, effectively control the concentration of key pollutants such as PM2.5 and carbon dioxide, and create a healthier sports environment for sports venues. This study provides new ideas and methods for indoor air quality monitoring, which has important practical application value.

Abstract Background Castanopsis carlesii is a dominant tree species in subtropical evergreen broad-leaved forests and holds significant ecological value. It serves as an excellent timber tree species and raw material for cultivating edible fungi. Henry Chinquapin (Castanea henryi) wood is known for its hardness and resistance to water and moisture, making it an exceptional timber species. Additionally, its fruit has a sweet and fruity taste, making it a valuable food source. However, the mitogenomes of these species have not been previously reported. To gain a better understanding of them, this study successfully assembled high-quality mitogenomes of C. carlesii and Ca. henryi for the first time. Results Our research reveals that the mitochondrial DNA (mtDNA) of C. carlesii exhibits a unique multi-branched conformation, while Ca. henryi primarily exists in the form of two independent molecules that can be further divided into three independent molecules through one pair of long repetitive sequences. The size of the mitogenomes of C. carlesii and Ca. henryi are 592,702 bp and 379,929 bp respectively, which are currently the largest and smallest Fagaceae mitogenomes recorded thus far. The primary factor influencing mitogenome size is dispersed repeats. Comparison with published mitogenomes from closely related species highlights differences in size, gene loss patterns, codon usage preferences, repetitive sequences, as well as mitochondrial plastid DNA segments (MTPTs). Conclusions Our study enhances the understanding of mitogenome structure and evolution in Fagaceae, laying a crucial foundation for future research on cell respiration, disease resistance, and other traits in this family.

Abstract The aim of this study is to perform proteomic and metabolomic analyses in bilateral renal pelvis urine of patients with unilateral uric acid kidney stones to identify the specific urinary environment associated with uric acid stone formation. Using cystoscopy-guided insertion of ureteral catheters, bilateral renal pelvis urine samples are collected. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is employed to identify differentially expressed proteins and metabolites in the urine environment. Differentially expressed proteins and metabolites are further analyzed for their biological functions and potential metabolic pathways through Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. In the urine from the stone-affected side, eight differential proteins were significantly upregulated, and six metabolites were dysregulated. The uric acid stone urinary environment showed an excess of α-ketoisovaleric acid and 3-methyl-2-oxovaleric acid, which may contribute to the acidification of the urine. Functional and pathway analyses indicate that the dysregulated metabolites are mainly associated with insulin resistance and branched chain amino acid metabolism.

Abstract Hydrogen-bonded assembly of multiple components into well-defined icosahedral capsules akin to virus capsids has been elusive. In parallel, constructing robust zeolitic-like cluster-based supramolecular frameworks (CSFs) without any coordination covalent bonding linkages remains challenging. Herein, we report a cluster-based pseudoicosahedral H-bonded capsule Cu60, which is buckled by the self-organization of judiciously designed constituent copper clusters and anions. The spontaneous formation of the icosahedron in the solid state takes advantage of 48 charge-assisted CH···F hydrogen bonds between cationic clusters and anions (PF6 -), and is highly sensitive to the surface protective ligands on the clusters with minor structural modification inhibiting its formation. Most excitingly, an extended three-periodic robust zeolitic-like CSF, is constructed by edge-sharing the resultant icosahedrons. The perpendicular channels of the CSF feature unusual 3D orthogonal double-helical patterns. The CSF material not only keeps its single-crystal character in the desolvated phase, but also exhibits excellent chemical and thermal stabilities as well as long-lived phosphorescence emission.

Strengthening the expression level of integrated genes on the genome is crucial for consistently expressing key enzymes in microbial cell factories for efficient bioproduction in synthetic biology. In comparison to plasmid-based multi-copy expression, the utilization of chromosomal multi-copy genes offers increased stability of expression level, diminishes the metabolic burden on host cells, and enhances overall genetic stability. In this study, we developed the “BacAmp”, a stabilized gene integration expression and copy number amplification system for high-level expression in Bacillus subtilis, which was achieved by employing a combination of repressor and non-natural amino acids (ncAA)-dependent expression system to create a reversible switch to control the key gene recA for homologous recombination. When the reversible switch is turned on, genome editing and gene amplification can be achieved. Subsequently, the reversible switch was turned off therefore stabilizing the gene copy number. The stabilized gene amplification system marked by green fluorescent protein, achieved a 3-fold increase in gene expression by gene amplification and maintained the average gene copy number at 10 after 110 generations. When we implemented the gene amplification system for the regulation of N-acetylneuraminic acid (NeuAc) synthesis, the copy number of the critical gene increased to an average of 7.7, which yielded a 1.3-fold NeuAc titer. Our research provides a new avenue for gene expression in synthetic biology and can be applied in metabolic engineering in B. subtilis.

Abstract Background Tumor-infiltrating lymphocytes (TILs) are significantly implicated in regulating the tumor immune microenvironment (TIME) and immunotherapeutic response. However, little is known about the impact of the resident and exhausted status of TILs in hepatocellular carcinoma (HCC). Methods Single-cell RNA sequencing data was applied to discover resident and exhausted signatures of TILs. Survival outcomes, biological function, immune infiltration, genomic variation, immunotherapeutic efficacy, and sorafenib response were further explored the clinical significance and molecular association of TILs in HCC. Moreover, a candidate gene with predictive capability for the dismal subtype was identified through univariate Cox regression analysis, survival analysis, and the BEST website. Results Single-cell analysis revealed that CD8 + T, CD4 + T, and NK cells were strongly associated with resident and exhausted patterns. Specific resident and exhausted signatures for each subpopulation were extracted in HCC. Further multivariate Cox analysis revealed that the ratio of resident to exhausted CD4 + T cells in TIME was an independent prognostic factor. After incorporating tumor purity with the ratio of resident to exhausted CD4 + T cells, we stratified HCC patients into three subtypes and found that (i) CD4 residencyhighexhaustionlow subtype was endowed with favorable prognosis, immune activation, and sensitivity to immunotherapy; (ii) CD4 exhaustionhighresidencylow subtype was characterized by genome instability and sensitivity to sorafenib; (iii) Immune-desert subtype was associated with malignant-related pathways and poor prognosis. Furthermore, spindle assembly abnormal protein 6 homolog (SASS6) was identified as a key gene, which accurately predicted the immune-desert subtype. Prognostic analysis as well as in vitro and in vivo experiments further demonstrated that SASS6 was closely associated with tumor prognosis, proliferation, and migration. Conclusions The ratio of resident to exhausted CD4 + T cells shows promise as a potential biomarker for HCC prognosis and immunotherapy response and SASS6 may serve as a biomarker and therapeutic target for prognostic assessment of HCC.

Abstract There is a growing interest in the creation of engineered condensates formed via liquid–liquid phase separation (LLPS) to exert precise cellular control in prokaryotes. However, de novo design of cellular condensates to control metabolic flux or protein translation remains a challenge. Here, we present a synthetic condensate platform, generated through the incorporation of artificial, disordered proteins to realize specific functions in Bacillus subtilis. To achieve this, the “stacking blocks” strategy is developed to rationally design a series of LLPS-promoting proteins for programming condensates. Through the targeted recruitment of biomolecules, our investigation demonstrates that cellular condensates effectively sequester biosynthetic pathways. We successfully harness this capability to enhance the biosynthesis of 2’-fucosyllactose by 123.3%. Furthermore, we find that condensates can enhance the translation specificity of tailored enzyme fourfold, and can increase N-acetylmannosamine titer by 75.0%. Collectively, these results lay the foundation for the design of engineered condensates endowed with multifunctional capacities.

Abstract This research aimed to systematically uncover the metastatic characteristics and survival rates of lung cancer subtypes and to evaluate the impact of surgery at the primary tumor site on cancer-specific survival in DM lung cancer. We used the Surveillance, Epidemiology, and End Results (SEER) database (2010–2019) to identify primary lung cancers with DM at presentation (M1). Kaplan–Meier (KM) survival curves were generated and compared utilizing log-rank tests. Cox regression methods were employed to determine hazard ratios (HR) and 95% confidence intervals related to CSS factors. Inverse probability of treatment weighting (IPTW) was applied to reduce bias. We analyzed 77,827 M1 lung cancer cases, with 41.22% having DM at presentation. Bone metastasis was most common in ADC, ASC, SCC, LCC; brain in LCNEC; liver in SCLC. Lung was common in TC + AC and SCC. Long-term survival was best in TC + AC and worst in SCLC (p

Abstract Aims In an era of evolving diagnostic possibilities, existing diagnostic systems are not fully sufficient to promptly recognize patients with early‐stage hypertrophic cardiomyopathy (HCM) without symptomatic and instrumental features. Considering the sudden death of HCM, developing a novel diagnostic model to clarify the patients with early‐stage HCM and the immunological characteristics can avoid misdiagnosis and attenuate disease progression. Methods and results Three hundred eighty‐five samples from four independent cohorts were systematically retrieved. The weighted gene co‐expression network analysis, differential expression analysis (|log2(foldchange)| > 0.5 and adjusted P

ABSTRACT: Goose fatty liver (or foie gras) does not develop inflammation even in severe steatosis, which is different from human nonalcoholic fatty liver disease (NAFLD), and it is considered as a unique model for NAFLD study. The deubiquitinating enzyme, Ovarian Tumor (OTU)-Deubiquitinase 1 (OTUD1), is involved in various cell biological processes by regulating the expression of cytokines. Its role and mechanism in the formation of goose fatty liver however are not clear yet. This study determined the expression of OTUD1 in goose fatty liver versus normal liver and OTUD1 expression in goose primary liver treated with glucose, fatty acids and insulin using qPCR and immunoblotting assays. OTUD1 gene overexpression and subsequent transcriptome sequencing analysis were performed to identify the differentially expressed genes (DEG) and the pathways where the DEGs are enriched. Immunoprecipitation and protein mass spectrometry were employed to screen the interacting proteins of OTUD1. The results showed that both the mRNA and protein abundances of OTUD1 in goose fatty liver were higher than those of normal liver. In goose primary hepatocytes, palmitic acid and oleic acid both increased the protein levels of OTUD1, while glucose and insulin inhibited the expression of the protein. Overexpression of OTUD1 significantly affected the expression of genes and pathways related to inflammatory/immune responses and cell growth/death. The interacting proteins of OTUD1 are mainly related to membrane transport, immune/inflammatory response, ubiquitination and signaling pathways. The interaction between OTUD1 and AP1G1 was validated by co-immunoprecipitation and immunoblotting assays. Consistently, the relative ubiquitination level of AP1G1 in goose fatty liver was lower than that of normal liver, which is correlated with increased protein abundance of AP1G1 and OTUD1 in goose fatty liver. In conclusion, the increased protein abundance of OTUD1 in goose fatty liver can regulate the expression of cytokines and related pathways during the formation of goose fatty liver by promoting the deubiquitination of the interacting proteins of OTUD1, including AP1G1.

Vibration caused by shield tunneling construction have adverse impacts on surrounding environment. To ascertain the influence of shield tunneling construction on ambient vibration, based on the shield tunnel project of Zhijiang Road in Hangzhou, the on-site vibration tests were carried out on the deep soil and surface during the excavation, and the vibration characteristics and vibration attenuation law during shield construction were investigated. The results show that the main frequency of vibration near the vibration source is wide, and the response components can be observed at 0–100 Hz. Under the filtering effect of the surface-covering soil layer, the high-frequency components of the vibration response are significantly attenuated, and the surface vibration is mainly distributed within 40 Hz. In the shield crossing, the deep measurement point is 5 dB higher than the vibration level of the same position on the surface. After the shield is pushed forward 20 m, the average attenuation of the surface vibration response is 10 dB, and the average attenuation of the deep vibration response is 12 dB.

Osteopontin (OPN), a bioactive milk protein in breast milk, has diverse applications in food and medicine. OPN is predominantly extracted from fresh bovine milk; however, the concentration of OPN in bovine milk is exceedingly low. To address these issues, in the present study, we used Komagataella phaffii for the recombinant expression of human OPN (hOPN). The results of host cell screening revealed that X33 cells were more suitable than other K. phaffii hosts for hOPN expression, yielding a titer of 340.5 μg/L. Subsequently, it was observed that the extracellular production of hOPN significantly increased to 8.02 mg/L from strain XPSA01 using the PAOX1 promoter and the hybrid signal peptide PROSCW10-α. Meanwhile, the co-expression of transcription factors, translation factors, and molecular chaperones resulted in a 2.94-fold enhancement in extracellular hOPN production compared with that in XPSA01, resulting in a titer of 23.6 mg/L. Finally, the above strategies were combined to obtain the recombinant strain XPSA01-CP, which achieved titers of 35.6 and 128.5 mg/L hOPN in shake-flask fermentation and 3-L bioreactor, respectively. To the best of our knowledge, this is the highest extracellular yield of hOPN ever reported.

Background Cushing’s syndrome (CS) is associated with increased risk for heart failure, which often initially manifests as left ventricular diastolic dysfunction (LVDD). In this study, we aimed to explore the potential risk factors of LVDD in CS by incorporating body composition parameters.Methods A retrospective study was conducted on patients diagnosed with endogenous CS no less than 18 years old. The control group consisted of healthy individuals who were matched to CS patients in terms of gender, age, and BMI. LIFEx software (version 7.3) was applied to measure epicardial adipose tissue volume (EATV) on non-contrast chest CT, as well as abdominal adipose tissue and skeletal muscle mass at the first lumbar vertebral level. Echocardiography was used to evaluate left ventricular (LV) diastolic function. Body compositions and clinical data were examined in relation to early LVDD.Results A total of 86 CS patients and 86 healthy controls were enrolled. EATV was significantly higher in CS patients compared to control subjects (150.33 cm3 [125.67, 189.41] vs 90.55 cm3 [66.80, 119.84], p

Malaria remains a major public health concern. The rapid spread of resistance to antimalarial drugs is a major challenge for malaria eradication. Timely and accurate molecular monitoring based on practical detection methods is a critical step toward malaria control and elimination. In this study, two rapid detection techniques, allele-specific PCR (AS‒PCR) and recombinase-aided amplification (RAA) combined with CRISPR/Cas12a, were established, optimized and assessed to detect single nucleotide polymorphisms in the Plasmodium falciparum exonuclease (Pfexo) gene related to suspected piperaquine resistance. Moreover, phosphorothioate and artificial mismatches were introduced into the allele-specific primers for AS‒PCR, and crRNA-mismatched bases were introduced into the RAA‒CRISPR/Cas12a assay because crRNAs designed according to conventional rules fail to discriminate genotypes. As a result, the detection limits of the AS‒PCR and RAA‒CRISPR/Cas12a assays were 104 copies/μL and 103 copies/μL, respectively. The detection threshold for dried blood spots was 100‒150 parasites/μL, with no cross-reactivity against other genotypes. The average cost of AS‒PCR is approximately $1 per test and takes 2–3 h, whereas that of the RAA‒CRISPR/Cas12a system is approximately $7 per test and takes 1 h or less. Therefore, we provide more options for testing single nucleotide polymorphisms in the Pfexo gene, considering economic conditions and the availability of instruments, equipment, and reagents, which can contribute to the molecular monitoring of antimalarial resistance.

This paper proposes a design method for a wind tunnel balance that can compensate for inertial interference, aiming to address the issue of short effective time in pulse wind tunnels. This method also tackles the problem of the force measuring system’s inability to dampen quickly and the coupling of inertia vibration signals with the output signal of the balance, which affects aerodynamic measurement accuracy. The method calculates vibration displacement at specific positions of the balance structure using its acceleration, constructs compensation signals based on the relationship between these displacements and balance outputs, and then superimposes them onto the balance signal for compensation. The effectiveness of this compensation method is evaluated through finite element simulations and wind tunnel tests. The results demonstrate that by compensating for the balance signal, there is a significant reduction in the amplitude of the inertia vibration signal, leading to an enhancement in the repeatability accuracy of the measurement. This compensation method effectively solves under-compensation or over-compensation issues when accelerometers are placed on complex models with various modes, where obtaining accurate compensation signals becomes challenging. It provides a new technical approach to improve aerodynamic measurement accuracy by mitigating inertial interference during pulse wind tunnel testing.

Understanding environmental patterns of species diversity is essential for nature reserve planning and biodiversity conservation. In this study, we explored the birds’ alpha and beta diversity along the elevational gradients in Haba Snow Mountain Nature Reserve (hereafter, HBSM), a global biodiversity hotspot, and studied which environmental factor is the main driver in explaining alpha and beta diversity patterns. Our results indicated that taxonomic, functional, and phylogenetic alpha diversity consistently exhibited hump-shaped patterns with similar peaks. After controlling for species richness, both functional and phylogenetic alpha diversity increased with elevation, and the peaks at 3400–3700 m. Mean pairwise functional distance remained nearly constant along the elevation band, whereas mean pairwise phylogenetic distance shown hump-shaped pattern, and the predicted MPD peaked at the fifth band (3100–3400 m a.s.l). The functional and phylogenetic structure of bird communities in HBSM were more clustered along the elevation gradients, suggesting environmental filtering likely drove the assembly processes. Additionally, primary productivity (NDVI and/or habitat heterogeneity) and/or precipitation were robust predictors of variation in most diversity metrics. For multiple-site beta diversity, we observed that high turnover component in taxonomic, functional, and phylogenetic dimensions, indicating distinct bird assemblages across various elevational bands. In pairwise beta diversity, the spatial turnover of taxonomic and phylogenetic aspects was higher than nestedness, revealing species replacement occurs relatively frequently between evolutionarily related species with similar niche and functional traits. Overall, our findings highlight the importance of considering both different dimensions and multifaceted diversity when assessing elevational patterns of bird diversity. This study also provides valuable insights into the structuring mechanisms of bird communities and informs conservation planning along elevational gradients in HBSM, and offers a comprehensive case on species richness along elevational gradients.

Abstract Given the extensive heterogeneity and variability, understanding cellular functions and regulatory mechanisms through the analysis of multi‐omics datasets becomes extremely challenging. Here, a comprehensive modeling framework of multi‐omics machine learning and metabolic network models are proposed that covers various cellular biological processes across multiple scales. This model on an extensive normalized compendium of Bacillus subtilis is validated, which encompasses gene expression data from environmental perturbations, transcriptional regulation, signal transduction, protein translation, and growth measurements. Comparison with high‐throughput experimental data shows that EM_iBsu1209‐ME, constructed on this basis, can accurately predict the expression of 605 genes and the synthesis of 23 metabolites under different conditions. This study paves the way for the construction of comprehensive biological databases and high‐performance multi‐omics metabolic models to achieve accurate predictive analysis in exploring complex mechanisms of cell genotypes and phenotypes.

IntroductionThe oxygen reduction reaction (ORR) is a crucial determinant of the energy transformation capacity of fuel cells. This study investigates the performance of N and B dual-doped carbon in ORR.MethodsSix models using density functional theory (DFT) are developed to compare the performance of different doping strategies. A highly efficient dual-doped carbon ORR catalyst (S-850-1) is synthesized from Saccharina japonica, containing 4.54 at% N and 1.05 at% B atom.ResultsElectrochemical analysis reveals that S-850-1 significantly outperforms the nitrogen mono-doped carbon S-850, exhibiting a higher half-wave potential of 0.861 V and a greater limited current density of −5.60 mA cm⁻2, compared to S-850’s 0.838 V and −5.24 mA cm⁻2. Furthermore, S-850-1 surpasses the performance of 20% Pt/C, demonstrating enhanced durability and exceptional resistance to CO and methanol. The 1.40 V open circuit voltage produced by S-850-1 when integrated into a Zn-air battery can power an LED light.DiscussionBoth theoretical and practical evaluations validate the excellent ORR performance of nitrogen and boron dual-doped carbon, as evidenced by the agreement between the electrochemical results and DFT calculations. This work not only extends the range of ORR catalysts derived from biomass but also provides guidance on creating and producing affordable, effective catalysts that utilize natural resources.

Abstract The mechanism by which aging induces aortic aneurysm and dissection (AAD) remains unclear. A total of 430 participants were recruited for the screening of differentially expressed plasma microRNAs (miRNAs). We found that miR-1204 is significantly increased in both the plasma and aorta of elder patients with AAD and is positively correlated with age. Cell senescence induces the expression of miR-1204 through p53 interaction with plasmacytoma variant translocation 1, and miR-1204 induces vascular smooth muscle cell (VSMC) senescence to form a positive feedback loop. Furthermore, miR-1204 aggravates angiotensin II-induced AAD formation, and inhibition of miR-1204 attenuates β-aminopropionitrile monofumarate-induced AAD development in mice. Mechanistically, miR-1204 directly targets myosin light chain kinase (MYLK), leading to the acquisition of a senescence-associated secretory phenotype (SASP) by VSMCs and loss of their contractile phenotype. MYLK overexpression reverses miR-1204-induced VSMC senescence, SASP and contractile phenotypic changes, and the decrease of transforming growth factor-β signaling pathway. Our findings suggest that aging aggravates AAD via the miR-1204-MYLK signaling axis.

Abstract Background Logsplitter Injury is a type of high-energy ankle fracture dislocation. The mechanism of injury has not been described in detail. A detailed understanding of the radiological features and pathological changes can further guide treatment. Methods Between April 2009 and December 2018, a retrospective analysis was conducted on 62 patients with Logsplitter injury. The study analysed the characteristics of fibular injury, tibial injury, syndesmosis injury, medial injury and lateral ligament injury on preoperative X-ray and CT scans. The incidence of the different injury types was summarised. The correlation between Logsplitter injuries and the mechanisms causing them were analysed using the Lauge-Hansen classification of ankle fractures. Results The study provides data on the types of fractures observed. Of the total fractures, 98.4% were open fractures. The fibula injuries were classified as no fracture (1.6%), transverse or short oblique fractures (61.3%), butterfly fragments (25.8%), and comminuted fractures (11.3%). The tibial injuries included compression of lateral articular surfaces (38.7%) and posterior compressions (6.5%). Medial injuries, including medial malleolar fractures, accounted for 87.1%, and deltoid ligament rupture accounted for 12.9%. The study found that injuries to the syndesmosis consisted of simple ligament ruptures (11.3%), Tillaux fractures (8.1%), Volkmann fractures (43.5%), and Tillaux and Volkmann fractures (37.1%). In 12.9% of cases, there was a complete rupture of the lateral collateral ligament. Based on the Lauge-Hansen classification, 87.1% of injuries were pronation-abduction injuries, while 8.1% were pronation and external rotation injuries, and 1.6% were supination external rotation injuries. Furthermore, 3.2% of cases could not be classified. Conclusion The pathoanatomic characteristics of Logsplitter injury are diverse, with some cases accompanied by collateral ligament injury. It is important to note that these evaluations are objective and based on current results. The most common injury mechanism is vertical violence combined with abduction, although in some cases, it may be a vertical combined external-rotation injury. Level of evidence (4) case series. Trial registration This study has been approved by the ethical research committee of the Honghui Hospital of Xi’an Jiaotong University, under the code: 202,003,002.

Abstract Recently, the offline‐trained Siamese pipeline has drawn wide attention due to its outstanding tracking performance. However, the existing Siamese trackers utilise offline training to extract ‘universal’ features, which is insufficient to effectively distinguish between the target and fluctuating interference in embedding the information of the two branches, leading to inaccurate classification and localisation. In addition, the Siamese trackers employ a pre‐defined scale for cropping the search candidate region based on the previous frame's result, which might easily introduce redundant background noise (clutter, similar objects etc.), affecting the tracker's robustness. To solve these problems, the authors propose two novel sub‐network spatial employed to spatial feature embedding for robust object tracking. Specifically, the proposed spatial remapping (SRM) network enhances the feature discrepancy between target and distractor categories by online remapping, and improves the discriminant ability of the tracker on the embedding space. The MAML is used to optimise the SRM network to ensure its adaptability to complex tracking scenarios. Moreover, a temporal information proposal‐guided (TPG) network that utilises a GRU model to dynamically predict the search scale based on temporal motion states to reduce potential background interference is introduced. The proposed two network is integrated into two popular trackers, namely SiamFC++ and TransT, which achieve superior performance on six challenging benchmarks, including OTB100, VOT2019, UAV123, GOT10K, TrackingNet and LaSOT, TrackingNet and LaSOT denoting them as SiamSRMC and SiamSRMT, respectively. Moreover, the proposed trackers obtain competitive tracking performance compared with the state‐of‐the‐art trackers in the attribute of background clutter and similar object, validating the effectiveness of our method.

The Gaoligong Mountains are characterized by large variations in elevation and topography, which support high levels of biodiversity and endemism that remain largely understudied. Herein, based on the integration of morphological comparisons and phylogenetic reconstruction, we describe a new species of Rhacophorus from the northern Gaoligong Mountains, Yunnan Province, China. The new species, Rhacophorus dulongensis sp. nov., is morphologically distinguishable from its congeners based on the differences in body size, head length, tibia length, snout and tongue shape, toe webbing formula and coloration, ventral skin texture and coloration, dorsal pattern and coloration, body macroglands, iris coloration, and pattern of markings on flanks. Phylogenetically, it differs from its congeners by uncorrected p-distances of >4.8% for the 16S rRNA gene fragment. Rhacophorus dulongensis sp. nov. is likely to be found in Myanmar, considering its type locality lies close to the China-Myanmar border. The phylogenetic analysis revealed that the “widespread” species, R. rhodopus, is a species complex and a composite of five distinct lineages. The results revealed that R. napoensis is also found in Vietnam, making it a new country record for Vietnam. Interestingly, R. dulongensis sp. nov. likely breeds in bamboo, a hidden behavioral characteristic that makes them easy to overlook. Given the ongoing habitat loss and degradation in the region, further biological exploration is urgently needed in the Gaoligong Mountains as a biodiversity reservoir.

Abstract Cytidine triphosphate synthase (CTPS) plays a pivotal role in the de novo synthesis of cytidine triphosphate (CTP), a fundamental building block for RNA and DNA that is essential for life. CTPS is capable of directly binding to all four nucleotide triphosphates: adenine triphosphate, uridine triphosphate, CTP, and guanidine triphosphate. Furthermore, CTPS can form cytoophidia in vivo and metabolic filaments in vitro, undergoing regulation at multiple levels. CTPS is considered a potential therapeutic target for combating invasions or infections by viral or prokaryotic pathogens. Utilizing cryo‐electron microscopy, we determined the structure of Escherichia coli CTPS (ecCTPS) filament in complex with CTP, nicotinamide adenine dinucleotide (NADH), and the covalent inhibitor 6‐diazo‐5‐oxo‐ l‐norleucine (DON), achieving a resolution of 2.9 Å. We constructed a phylogenetic tree based on differences in filament‐forming interfaces and designed a variant to validate our hypothesis, providing an evolutionary perspective on CTPS filament formation. Our computational analysis revealed a solvent‐accessible ammonia tunnel upon DON binding. Through comparative structural analysis, we discern a distinct mode of CTP binding of ecCTPS that differs from eukaryotic counterparts. Combining biochemical assays and structural analysis, we determined and validated the synergistic inhibitory effects of CTP with NADH or adenine on CTPS. Our results expand our comprehension of the diverse regulatory aspects of CTPS and lay a foundation for the design of specific inhibitors targeting prokaryotic CTPS.

Spinal cord injury (SCI) is a devastating traumatic disease seriously impairing the quality of life in patients. Expectations to allow the hopeless central nervous system to repair itself after injury are unfeasible. Developing new approaches to regenerate the central nervous system is still the priority. Exosomes derived from mesenchymal stem cells (MSC-Exo) have been proven to robustly quench the inflammatory response or oxidative stress and curb neuronal apoptosis and autophagy following SCI, which are the key processes to rescue damaged spinal cord neurons and restore their functions. Nonetheless, MSC-Exo in SCI received scant attention. In this review, we reviewed our previous work and other studies to summarize the roles of MSC-Exo in SCI and its underlying mechanisms. Furthermore, we also focus on the application of exosomes as drug carrier in SCI. In particular, it combs the advantages of exosomes as a drug carrier for SCI, imaging advantages, drug types, loading methods, etc., which provides the latest progress for exosomes in the treatment of SCI, especially drug carrier.

Abstract Neurologic Rosai–Dorfman disease (RDD) is a rare type of non-Langerhans cell histiocytosis that affects the central nervous system. Most neurologic RDDs grow like meningiomas, have clear boundaries, and can be completely resected. However, a few RDDs are invasive and aggressive, and no effective treatment options are available because the molecular mechanisms involved remain unknown. Here, we report a case of deadly and glucocorticoid-resistant neurologic RDD and explore its possible pathogenic mechanisms via single-cell RNA sequencing. First, we identified two distinct but evolutionarily related histiocyte subpopulations (the C1Q+ and SPP1+ histiocytes) that accumulated in the biopsy sample. The expression of genes in the KRAS signaling pathway was upregulated, indicating gain-of-function of KRAS mutations. The C1Q+ and SPP1+ histiocytes were highly differentiated and arrested in the G1 phase, excluding the idea that RDD is a lympho-histio-proliferative disorder. Second, although C1Q+ histiocytes were the primary RDD cell type, SPP1+ histiocytes highly expressed several severe inflammation-related and invasive factors, such as WNT5A, IL-6, and MMP12, suggesting that SPP1+ histiocytes plays a central role in driving the progression of this disease. Third, oligodendrocytes were found to be the prominent cell type that initiates RDD via MIF and may resist glucocorticoid treatment via the MDK and PTN signaling pathways. In summary, in this case, we report a rare presentation of neurologic RDD and provided new insight into the pathogenic mechanisms of progressive neurologic RDD. This study will also offer evidence for developing precision therapies targeting this complex disease.

Abstract Cerebrospinal fluid tumor-derived DNA (CSF-tDNA) analysis is a promising approach for monitoring the neoplastic processes of the central nervous system. We applied a lung cancer-specific sequencing panel (CAPP-Seq) to 81 CSF, blood, and tissue samples from 24 lung cancer patients who underwent lumbar puncture (LP) for suspected leptomeningeal disease (LMD). A subset of the cohort (N = 12) participated in a prospective trial of osimertinib for refractory LMD in which serial LPs were performed before and during treatment. CSF-tDNA variant allele fractions (VAFs) were significantly higher than plasma circulating tumor DNA (ctDNA) VAFs (median CSF-tDNA, 32.7%; median plasma ctDNA, 1.8%; P

Abstract We report a breakthrough in the hardware implementation of energy-efficient all-spin synapse and neuron devices for highly scalable integrated neuromorphic circuits. Our work demonstrates the successful execution of all-spin synapse and activation function generator using domain wall-magnetic tunnel junctions. By harnessing the synergistic effects of spin-orbit torque and interfacial Dzyaloshinskii-Moriya interaction in selectively etched spin-orbit coupling layers, we achieve a programmable multi-state synaptic device with high reliability. Our first-principles calculations confirm that the reduced atomic distance between 5d and 3d atoms enhances Dzyaloshinskii-Moriya interaction, leading to stable domain wall pinning. Our experimental results, supported by visualizing energy landscapes and theoretical simulations, validate the proposed mechanism. Furthermore, we demonstrate a spin-neuron with a sigmoidal activation function, enabling high operation frequency up to 20 MHz and low energy consumption of 508 fJ/operation. A neuron circuit design with a compact sigmoidal cell area and low power consumption is also presented, along with corroborated experimental implementation. Our findings highlight the great potential of domain wall-magnetic tunnel junctions in the development of all-spin neuromorphic computing hardware, offering exciting possibilities for energy-efficient and scalable neural network architectures.

This paper reviews and summarizes recent progress in blue energy harvesting based on a triboelectric nanogenerator (TENG). This review covers TENG-based blue energy harvesters (BEHs) with different inertial units in spherical structures, derivative spherical structures, buoy structures, and liquid–solid contact structures. These research works have paved the way for TENG-based BEHs working under low-frequency waves and harvesting wave energy efficiently. The TENG-based BEH unit design and networking strategy are also discussed, along with highlighted research works. The advantages and disadvantages of different TENG structures with other inertial units are explored and discussed. Meanwhile, power management strategies are also mentioned in this paper. Thus, as a promising blue energy harvesting technology, the TENG is expected to significantly contribute to developing low-cost, lightweight, and high-performance BEHs supporting more frequent marine activities.

The interactions between corn amylose (CA) and Moringa oleifera seed salt-soluble protein (MOSP) were explored to improve the gel properties of MOSP. With increasing CA content, the MOSP-CA gel network structure was improved but the size of the gel porosity decreased firstly and then increased; the water holding retention (WHR) of MOSP-CA was decreased from approximately 94 % to 85.43 ± 2.54 %. The MOSP-CA-2.5 gel exhibited the best water holding stability (WHS), with a value of 37.1 ± 0.33 %. The MOSP-CA gel hardness increased with CA concentration, and MOSP-CA-2.5 showed relatively optimal cohesiveness, elasticity, adhesiveness, and chewiness. Meanwhile, MOSP-CA-2.5 exhibited gel strength. Incorporation of CA significantly increased the exposure of hydrophobic residues and the concentration-dependent increase in disulfide bonds in MOSP-CA gel. Thus, hydrophobic interactions, hydrogen bonds, and disulfide bonds collectively stabilized the structure of MOSP-CA gel. The findings would broaden the application of MOSP and improve the utilization value of MOSP in various industries.

ABSTRACT Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination is crucial for protecting vulnerable individuals, yet individuals with type 2 diabetes mellitus (T2DM) often exhibit impaired vaccine responses. Emerging evidence suggests that the composition of the host microbiota, crucial in immune regulation and development, influences vaccine efficacy. This study aimed to characterize the relationships between the SARS-CoV-2 inactivated vaccine and the host microbiota (specifically, gut and lung microbiota) of C57BL/6 mice with T2DM. Employing 16S rRNA metagenomic sequencing and ultra-high-performance liquid chromatography-mass spectrometry, we observed lower alpha diversity and distinct beta diversity in fecal microbiota before vaccination and in gut microbiota 28 days post-vaccination between T2DM mice and healthy mice. Compared with healthy mice, T2DM mice showed a higher Firmicutes/Bacteroidetes ratio 28 days post-vaccination. Significant alterations in gut microbiota composition were detected following vaccination, while lung microbiota remained unchanged. T2DM was associated with a diminished initial IgG antibody response against the spike protein, which subsequently normalized after 28 days. Notably, the initial IgG response positively correlated with fecal microbiota alpha diversity pre-vaccination. Furthermore, after 28 days, increased relative abundance of gut probiotics (Bifidobacterium and Lactobacillus) and higher levels of the gut bacterial tryptophan metabolite, indole acrylic acid, were positively associated with IgG levels. These findings suggest a potential link between vaccine efficacy and gut microbiota composition. Nonetheless, further research is warranted to elucidate the precise mechanisms underlying the impact of the gut microbiome on vaccine response. Overall, this study enhances our understanding of the intricate relationships among host microbiota, SARS-CoV-2 vaccination, and T2DM, with potential implications for improving vaccine efficacy.IMPORTANCEOver 7 million deaths attributed to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by 6 May 2024 underscore the urgent need for effective vaccination strategies. However, individuals with type 2 diabetes mellitus (T2DM) have been identified as particularly vulnerable and display compromised immune responses to vaccines. Concurrently, increasing evidence suggests that the composition and diversity of gut microbiota, crucial regulators of immune function, may influence the efficacy of vaccines. Against this backdrop, our study explores the complex interplay among SARS-CoV-2 inactivated vaccination, T2DM, and host microbiota. We discover that T2DM compromises the initial immune response to the SARS-CoV-2 inactivated vaccine, and this response is positively correlated with specific features of the gut microbiota, such as alpha diversity. We also demonstrate that the vaccination itself induces alterations in the composition and structure of the gut microbiota. These findings illuminate potential links between the gut microbiota and vaccine efficacy in individuals with T2DM, offering valuable insights that could enhance vaccine responses in this high-risk population.

AIM: To explore whether CD3ε is involved in the adaptive immunity of Aspergillus fumigatus (A. fumigatus) keratitis in mice and the role of innate and adaptive immunity in it. METHODS: Mice models of A. fumigatus keratitis were established by intra-stromal injection and corneal epithelial scratching. Subconjunctival injections of natamycin, wedelolactone, LOX-1 inhibitor (poly I) or Dectin-1 inhibitor (laminarin) were used to treat mice with A. fumigatus keratitis. Mice were pretreated by intraperitoneal injection of anti-mouse CD3ε. We observed the corneal infection of mice under the slit lamp microscope and made a clinical score. The protein expression of CD3ε and interleukin-10 (IL-10) was determined by Western blotting. RESULTS: With the disease progresses, the degree of corneal opacity and edema augmented. In the intra-stromal injection models, CD3ε protein expression began to increase significantly on the 2nd day. However, in the scraping epithelial method models, CD3ε only began to increase on the 3rd day. After natamycin treatment, the degree of corneal inflammation in mice was significantly attenuated on the 3rd day. After wedelolactone treatment, the severity of keratitis worsened. And the amount of CD3ε protein was also reduced, compared with the control group. By inhibiting LOX-1 and Dectin-1, there was no significant difference in CD3ε production compared with the control group. After inhibiting CD3ε, corneal ulcer area and clinical score increased, and IL-10 expression was downregulated. CONCLUSION: As a pan T cell marker, CD3ε participate in the adaptive immunity of A. fumigatus keratitis in mice. In our mice models, the corneas will enter the adaptive immune stage faster. By regulating IL-10, CD3ε exerts anti-inflammatory and repairs effects in the adaptive immune stage.

Abstract The torrent frogs of the genus Amolops represent a great anuran diversification in southern China and Southeast Asia. Previous studies have shown that, the diversity of this genus still remains underestimated. During herpetological surveys from 2021 to 2022, several Amolops specimens were collected from the international border regions of southwestern Yunnan Province, China. Herein, we utilized molecular phylogenetic and morphological data to identify these specimens. Our findings indicate the presence of a separate and previously unknown lineage in the A. viridimaculatus group, which we formally describe as a new species. Furthermore, the specimen from Xishuangbanna National Nature Reserve clustered with A. vitreus from the paratype, supporting the morphological diagnosis. Therefore, we describe a new species and a new species record for China. Our study contributes to the species richness of the genus Amolops as well as the diversity of amphibians in China. Notably, our discovery brings the total number of Amolops species to 85 and the total number of torrent frog species known to occur in China to 53. In addition, our study further confirmed that Yunnan and Indochina Peninsula have similar faunal composition, implying that more studies are needed to achieve a complete understanding of the species diversity and distribution pattern.