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Abstract Background At present, embryologists are attempting to use conventional in vitro fertilization (cIVF) as an alternative to intracytoplasmic sperm injection (ICSI) for preimplantation genetic testing (PGT). However, the potential parental contamination origin of sperm cells and cumulus cells is considered the main limiting factor in the inability of cIVF embryos to undergo PGT. Methods In this study, we established an IVF-PGTA assay for parental contamination tests with a contamination prediction model based on allele frequencies and linkage disequilibrium (LD) to compute the log-likelihood ratio (LLR) under competing ploidy hypotheses, and then verified its sensitivity and accuracy. Finally, comparisons of the effectiveness of SNP-based analysis and LLR-based IVF-PGTA among 40 cIVF embryos was performed, based on both statistical analysis of the parental contamination rate and chromosomal ploidy concordance rate between TE biopsy and ICM isolations. Results With IVF-PGTA assay, biopsies with 10% maternal contamination could be detected accurately, and contamination caused by sperm cells could be eliminated completely. Utilizing LLR-based or single Nucleotide Polymorphism (SNP) -based analyses, our comprehensive examination of 40 clinically discarded fresh cIVF embryos revealed an absence of paternal contamination. Strikingly, the LLR-based analysis uniquely revealed a mere instance of 24% maternal contamination within the trophectoderm cell (TE) biopsy of 5* embryo. Furthermore, it was solely through this analysis that embryo (9-F) was identified as a triploid of paternal origin. Conclusions In this study, we developed a new bioinformatics analysis method for identifying parental contamination during IVF-PGT, especially for couples with nonmale factor infertility.

Although Li–S batteries have a high theoretical capacity, their application are significantly hindered by the complex shuttle effect of polysulfides. To address the issues, in this paper, Ni2V2O7 prepared by a simple method is proposed as an efficient catalyst for S cathodes. Ni2V2O7 composed of Ni–O octahedra and V–O tetrahedra has a specific electronic structure. The Ni and V atoms interacted, enabling a fast kinetics of polysulfide redox. Moreover, Ni2V2O7 contains metal sites (Ni and V) and oxygen vacancies, providing a high adsorption capacity and abundant active sites for polysulfide redox. Therefore, Li–S batteries consisting of Ni2V2O7-based cathodes exhibit an excellent cycling stability with a capacity of 1061 mAh g−1 and capacity retention of 87.6% after 150 cycles at 0.2 C. Moreover, at 1 C rate, the batteries exhibit a capacity of 706 mAh g−1 after 300 cycles with a minimal capacity decay of only 0.08% per cycle.

Abstract As an abundant agricultural and forestry biomass resource, hemicelluloses are hard to be effectively degraded and utilized by microorganisms due to the constraints of membrane and metabolic regulations. Herein, we report a synthetic extracellular metabolic pathway with hemicellulose-degrading-enzymes controllably displayed on Escherichia coli surface as engineered bacterial consortia members for efficient utilization of xylan, the most abundant component in hemicellulose. Further, we develop a hemicellulose/O2 microbial fuel cell (MFC) configuring of enzyme-engineered bacterial consortia based bioanode and bacterial-displayed laccase based biocathode. The optimized MFC exhibited an open-circuit voltage of 0.71 V and a maximum power density (P max) of 174.33 ± 4.56 µW cm−2. Meanwhile, 46.6% (w/w) α-ketoglutarate was produced in this hemicellulose fed-MFC. Besides, the MFC retained over 95% of the P max during 6 days’ operation. Therefore, this work establishes an effective and sustainable one-pot process for catalyzing renewable biomass into high-value products and electricity in an environmentally-friendly way.

Manual semen evaluation methods are subjective and time-consuming. In this study, a deep learning algorithmic framework was designed to enable non-invasive multidimensional morphological analysis of live sperm in motion, improve current clinical sperm morphology testing methods, and significantly contribute to the advancement of assisted reproductive technologies. We improved the FairMOT tracking algorithm by incorporating the distance and angle of the same sperm head movement in adjacent frames, as well as the head target detection frame IOU value, into the cost function of the Hungarian matching algorithm. For sperm morphology, we used the BlendMask segmentation method to segment individual sperm. SegNet was used to separate the head, midpiece, and principal piece comments from each sperm. Experienced in vivo sperm physicians confirmed a morphological accuracy percentage of 90.82%. A total of 1272 samples were collected from multiple tertiary hospitals for validation of the system, which were also evaluated by physicians. The results of our system were highly consistent with those of manual microscopy. This study realized the automated detection of progressive motility and morphology of sperm simultaneously, which is crucial for selection of morphologically normal and motile sperm for intracytoplasmic sperm injection.

The sublevel caving method has been widely used in the mines for mining medium-thick and steeply inclined orebodies, but the problem of ore loss and dilution still exists during the mining process and has yet to be fundamentally solved. In order to realize the green mining with the coordination of resources and environment, an insert drawing technology is proposed to address this issue with the medium-thick and steeply inclined orebody as the research object based on the structural principles of the insert within the silo. The influencing factors mainly considered in this paper are the orebody dip angle, thickness, and sublevel height. Eighteen experiments of the insert drawing with the conventional cut-off grade drawing with respect to these three factors were designed to investigated the impacts of these three factors on ore loss and dilution. The experimental results indicate that the ore recovery rate of the insert drawing technology is higher than that of the conventional cut-off grade drawing in mining ore bodies of different thicknesses and dip angles. In conditions of the same mixing rate of the waste rock, the ore recovery rate of the insert drawing technology is 69.09% to 82.9%, which is higher than that of the conventional cut-off grade drawing by 12.66% to 30.88%. Furthermore, the ore recovery ratio increases with the increasing the orebody dip angle when it is between 60° and 85°. On the other hand, the ore recovery rate of the insert drawing technology is higher than that of the conventional cut-off grade drawing in mining ore bodies when the orebody thickness ranges from 6 m to 10 m. Additionally, when it is between 10 m and 14 m, the ore recovery ratio increases with the increasing the sublevel height. Meanwhile, the mechanism of the insert drawing technology is studied. By setting up the insert structure and changing the opening and closing sequence of the clapboard in the quarry, the ore-rock flow path is changed, the ore flow range and flow rate is increased, and the ore-rock contact is controlled, thus ore loss and depletion is reduced. Research demonstrations that the insert drawing technology is superior to the conventional cut-off grade drawing, enrich and improve the issue of ore loss and dilution in an expict manner. This technology provides valuable technical support for mining medium-thick, steeply inclined orebodies.

Abstract With an increasing demand for environmentally friendly refrigeration, the solid‐state refrigeration based on the electrocaloric effect (ECE) has been drawn extensive attention. It is a challenge to maintain a large adiabatic temperature change (∆T) over a broad temperature span. Herein, the authors designed and synthesised (0.74‐x) Na0.5Bi0.5TiO3‐0.06BaTiO3‐0.2SrTiO3‐xBi(Mg0.5Zr0.5)O3 (abbreviated as NBT‐xBMZ) (x = 0, 0.02, 0.04, 0.06 and 0.08) lead‐free relaxor ferroelectrics. Their microstructures, dielectric properties, ferroelectric properties, ECEs and the structure‐property relationships were investigated. Via doping with BMZ, an enhanced relaxor feature and a wider temperature range where multi‐phases coexist were achieved. The relaxor ferroelectric characteristics were illustrated using the Vogel‐Fulcher relation. The indirectly calculated ECE results showed that the optimal ΔT of 1.11 K was obtained for the x = 0.02 sample at 90°C and 70 kV/cm over a wide Tspan of 120°C, providing a potential ECE material. The direct ECE results procured using thermocouple indicated that the maximal ∆T of 2.14 K and ∆T/∆E of 0.31 K m/MV were achieved in the same sample at 70°C and 7 MV/m and the variation trend of ECE results was consistent with the indirect results. Moreover, the multi‐phases coexistent strategy can be extended to other materials system to generate a large ΔT over a wide temperature range.

Abstract The latest discovery of high temperature superconductivity near 80 K in La3Ni2O7 under high pressure has attracted much attention. Many proposals are put forth to understand the origin of superconductivity. The determination of electronic structures is a prerequisite to establish theories to understand superconductivity in nickelates but is still lacking. Here we report our direct measurement of the electronic structures of La3Ni2O7 by high-resolution angle-resolved photoemission spectroscopy. The Fermi surface and band structures of La3Ni2O7 are observed and compared with the band structure calculations. Strong electron correlations are revealed which are orbital- and momentum-dependent. A flat band is formed from the Ni-3d $${}_{{z}^{2}}$$ z 2 orbitals around the zone corner which is ~ 50 meV below the Fermi level and exhibits the strongest electron correlation. In many theoretical proposals, this band is expected to play the dominant role in generating superconductivity in La3Ni2O7. Our observations provide key experimental information to understand the electronic structure and origin of high temperature superconductivity in La3Ni2O7.

Abstract Background 1,5-pentanediol (1,5-PDO) is a linear diol with an odd number of methylene groups, which is an important raw material for polyurethane production. In recent years, the chemical methods have been predominantly employed for synthesizing 1,5-PDO. However, with the increasing emphasis on environmentally friendly production, it has been a growing interest in the biosynthesis of 1,5-PDO. Due to the limited availability of only three reported feasible biosynthesis pathways, we developed a new biosynthetic pathway to form a cell factory in Escherichia coli to produce 1,5-PDO. Results In this study, we reported an artificial pathway for the synthesis of 1,5-PDO from lysine with an integrated cofactor and co-substrate recycling and also evaluated its feasibility in E.coli. To get through the pathway, we first screened aminotransferases originated from different organisms to identify the enzyme that could successfully transfer two amines from cadaverine, and thus GabT from E. coli was characterized. It was then cascaded with lysine decarboxylase and alcohol dehydrogenase from E. coli to achieve the whole-cell production of 1,5-PDO from lysine. To improve the whole-cell activity for 1,5-PDO production, we employed a protein scaffold of EutM for GabT assembly and glutamate dehydrogenase was also validated for the recycling of NADPH and α-ketoglutaric acid (α-KG). After optimizing the cultivation and bioconversion conditions, the titer of 1,5-PDO reached 4.03 mM. Conclusion We established a novel pathway for 1,5-PDO production through two consecutive transamination reaction from cadaverine, and also integrated cofactor and co-substrate recycling system, which provided an alternative option for the biosynthesis of 1,5-PDO.

BackgroundChronic kidney disease (CKD) is a prevalent chronic condition that poses a significant threat to human health. There is a close connection between the gut and kidneys, jointly influencing the onset and progression of CKD through the “gut-kidney axis.” Traditional Chinese medicine has shown potential in CKD treatment, but the specific mechanisms require further investigation.ObjectivesThis study aims to explore the protective effects of Mizhuo Enema (MZGCY) on kidney function in CKD rats by regulating the TLR4/MyD88/NF-κB signaling pathway.MethodsThe researcher employed a CKD rat model, which was divided into four groups: Control, Model, half-dose Mizhuo Guanchangye (1/2 MZGCY), and full-dose Mizhuo Guanchangye (MZGCY). Post enema administration, assessments were conducted on kidney function indicators, which included blood urea nitrogen (BUN), serum creatinine (SCR), and 24-h urinary protein. Additionally, measurements were taken for intestinal toxic substances such as indoxyl sulfate (IS) and lipopolysaccharide (LPS), as well as inflammatory factors interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α). Examinations of pathological changes in both the intestines and kidneys were also performed. During this process, immunofluorescence was utilized to detect the expression levels of proteins toll-like receptor 4 (TLR4), myeloid differentiation primary response 88 (MyD88), and nuclear factor kappa B (NF-κB) in the intestinal tissues.ResultsIt was found that after enema treatment, the BUN, SCR, and 24-h urinary protein levels in the MZGCY and 1/2 MZGCY groups significantly decreased, indicating notable improvement in kidney function. Compared to the model group, the IS, LPS, IL-6, and TNF-α levels in the MZGCY and 1/2 MZGCY groups were significantly reduced. Immunofluorescence showed a marked decrease in the expression of TLR4, MyD88, and NF-κB proteins in the intestines of the MZGCY group.ConclusionMZGCY significantly reduces the levels of intestinal toxins and inflammatory factors in the serum of CKD rats by interfering with the TLR4/MyD88/NF-κB signaling pathway, thereby improving intestinal and renal pathological changes and delaying CKD progression. This study demonstrates that MZGCY has significant renal protective effects, providing a new potential approach for CKD treatment.

IntroductionMale pattern baldness (MPB), also known as androgenetic alopecia, represents the most prevalent form of progressive hair loss in humans. It is characterized by a distinctive pattern of hair loss progression from the scalp; however, its underlying mechanism remains elusive and is influenced by hereditary, immune, and environmental factors. Genome-wide association studies (GWASs) have uncovered numerous risk genes/loci among European individuals with MPB. However, the validation of these susceptibility genes/loci within Han Chinese men remains largely unexplored. The aim of this study was to investigate whether the 71 susceptibility loci identified in a recent GWAS among European men also confer risk for MPB in Chinese men.MethodsForty-seven single nucleotide polymorphisms (SNPs) previously reported in GWASs of MPB were selected and genotyped in independent individuals comprising 499 Han Chinese cases and 1,489 controls using the Sequenom MassArray system. After stringent quality control measures, 25 SNPs were subjected to statistical analyses. Cochran–Armitage trend test was used to evaluate the association between SNPs and disease susceptibility. To address multiple tests, Bonferroni correction was conducted, setting the threshold for statistical significance at a p-value

BackgroundTemporal bone computed tomography (CT) helps diagnose chronic otitis media (COM). However, its interpretation requires training and expertise. Artificial intelligence (AI) can help clinicians evaluate COM through CT scans, but existing models lack transparency and may not fully leverage multidimensional diagnostic information. ObjectiveWe aimed to develop an explainable AI system based on 3D convolutional neural networks (CNNs) for automatic CT-based evaluation of COM. MethodsTemporal bone CT scans were retrospectively obtained from patients operated for COM between December 2015 and July 2021 at 2 independent institutes. A region of interest encompassing the middle ear was automatically segmented, and 3D CNNs were subsequently trained to identify pathological ears and cholesteatoma. An ablation study was performed to refine model architecture. Benchmark tests were conducted against a baseline 2D model and 7 clinical experts. Model performance was measured through cross-validation and external validation. Heat maps, generated using Gradient-Weighted Class Activation Mapping, were used to highlight critical decision-making regions. Finally, the AI system was assessed with a prospective cohort to aid clinicians in preoperative COM assessment. ResultsInternal and external data sets contained 1661 and 108 patients (3153 and 211 eligible ears), respectively. The 3D model exhibited decent performance with mean areas under the receiver operating characteristic curves of 0.96 (SD 0.01) and 0.93 (SD 0.01), and mean accuracies of 0.878 (SD 0.017) and 0.843 (SD 0.015), respectively, for detecting pathological ears on the 2 data sets. Similar outcomes were observed for cholesteatoma identification (mean area under the receiver operating characteristic curve 0.85, SD 0.03 and 0.83, SD 0.05; mean accuracies 0.783, SD 0.04 and 0.813, SD 0.033, respectively). The proposed 3D model achieved a commendable balance between performance and network size relative to alternative models. It significantly outperformed the 2D approach in detecting COM (P≤.05) and exhibited a substantial gain in identifying cholesteatoma (P

More and more attention has been focused on Li7La3Zr2O12 (LLZO) because of the high ionic conductivity and excellent chemical stability. It is great significance to find suitable dopants for locking cubic LLZO and improving the conductivity of Li+ ions. The uniform nano powder can be obtained by the sol gel synthetic method, which is conducive to maintaining high sintering activity. In this work, Ga and Nb dual doped LLZO solid electrolyte powders were synthesized via sol gel method, and Ga and Nb dual doped LLZO solid electrolyte ceramic were obtained via traditional solid state sintering method. The phase and microstructure of Ga and Nb co-doped LLZO solid electrolyte were analyzed by combine X-ray diffraction with scanning electron microscope. The impedance of Ga and Nb dual doped LLZO (Li6.8-3xGaxLa3Zr1.8Nb0.2O12 (0≤x≤0.3)) solid electrolyte was measured by the electrochemical workstation, and then the conductivity was calculated. The results show that when the doping amount of Ga is x=0.2, it is a pure cubic LLZO structure with the highest conductivity value of 3.7×10-4 S cm-1 (tested at room temperature) due to the sample has a high relative density and reaches the optimal Li+ vacancy concentration.

Ultra-high performance concrete (UHPC) is a cementitious composite characterized by its ultra-high durability attributes and mechanical properties. It is primarily used in large-span and ultra-high-rise structures for control of deflections. However, its mechanical properties decrease significantly after exposure to fire or high temperatures, limiting its applicability. In this paper, the exceptional characteristics of glazed hollow beads (GHBs), including their lightweight, high strength, and thermal insulating properties, were utilized to develop a novel fire-resistant UHPC. UHPC specimens with varying GHB content were prepared, and the corresponding mass loss, thermal performance degradation, and compressive strength after exposure to high temperatures were evaluated. The test results demonstrate that adding GHBs can improve the fire resistance of UHPC. With 40 % (by volume) GHB addition, the resulting UHPC could retain 47 % of its original compressive strength even after exposed to 800°C. The effects of temperature on the UHPC microstructure were analyzed using scanning electron microscopy and X-ray computed tomography. It was found that the combination of polypropylene fibers and GHBs created a release channel for vapor pressure within the concrete, thereby enhancing its high-temperature resistance. This study proposes a practical solution to enhance the high-temperature resistance of UHPC.

Background Complex interconnections are evident among gut microbiota, circulating metabolites, inflammatory cytokines, and the pathogenesis of abdominal aortic aneurysms (AAA), with the causal dynamics yet to be comprehensively elucidated. The primary objective of this study was to elucidate the potential causal relationships involving gut microbiota-mediated plasma metabolites, inflammatory cytokines, and AAA.Methods We utilized data from genome-wide association studies predominantly comprising individuals of European ancestry, encompassing four major gut microbiota signatures, 233 plasma metabolite signatures (N = 136,016), 91 inflammatory cytokine signatures (N = 14,824), and AAA signatures (N = 1,458,875). Mendelian randomization (MR), employed in a two-sample format, was utilized as a tool to investigate the potential causal pathways from gut microbiota to the development of AAA. Additionally, a two-step MR approach was employed to dissect the impact of plasma metabolites and inflammatory cytokines on the relationship between gut microbiota and AAA and to ascertain the mediated fractions.Results Our findings indicate that five phylum or family-identical bacteria, 175 plasma metabolites, and seven inflammatory factors are causally associated with AAA. Among them, five bacterial species from the same phylum or family, identified from different GWAS data, were strongly associated with AAA. Of these, two exhibited negative causality and three exhibited positive causality. We found that the phylum Firmicutes and the families Oscillospiraceae might reduce the risk of AAA, whereas the families Prevotellaceae, Sutterellaceae, and Aminobacteriaceae might increase the risk of AAA. Further screening indicated that phylum Firmicutes id.1672 (GCST90017114) may confer a protective effect against AAA by reducing triglyceride levels in medium/small high-density lipoprotein (HDL).Conclusion MR analysis has delineated a causal pathway from gut microbiota, through plasma circulating metabolites and inflammatory cytokines, to the pathogenesis of AAA. The role of intestinal flora and certain biomarkers may provide a reference for the diagnosis of AAA, and contribute to the prevention, diagnosis, and treatment of AAA disease.

Sapce-borne gravitational wave antennas, such as LISA and LISA-like mission (Taiji and Tianqin), will offer novel perspectives for exploring our Universe while introduce new challenges, especially in data analysis. Aside from the known challenges like high parameter space dimension, superposition of large number of signals etc., gravitational wave detections in space would be more seriously affected by anomalies or non-stationarities in the science measurements. Considering the three types of foreseeable non-stationarities including data gaps, transients (glitches), and time-varying noise auto-correlations, which may come from routine maintenance or unexpected disturbances during science operations, we developed a deep learning model for accurate signal extractions confronted with such anomalous scenarios. Our model exhibits the same performance as the current state-of-the-art models do for the ideal and anomaly free scenario, while shows remarkable adaptability in extractions of coalescing massive black hole binary signal against all three types of non-stationarities and even their mixtures. This also provide new explorations into the robustness studies of deep learning models for data processing in space-borne gravitational wave missions.

Glioblastomas are known for their poor clinical prognosis, with recurrent tumors often exhibiting greater invasiveness and faster growth rates compared to primary tumors. To understand the intratumoral changes driving this phenomenon, we employed single-cell sequencing to analyze the differences between two pairs of primary and recurrent glioblastomas. Our findings revealed an upregulation of ferroptosis in endothelial cells within recurrent tumors, identified by the significant overexpression of the NOX4 gene. Further analysis indicated that knocking down NOX4 in endothelial cells reduced the activity of the ferroptosis pathway. Utilizing conditioned media from endothelial cells with lower ferroptosis activity, we observed a decrease in the growth rate of glioblastoma cells. These results highlighted the complex role of ferroptosis within tumors and suggested that targeting ferroptosis in the treatment of glioblastomas requires careful consideration of its effects on endothelial cells, as it may otherwise produce counterproductive outcomes.

Periampullary carcinoma is a malignant gastrointestinal tumor originating from the head of the pancreas, distal bile duct, duodenum, or the ampulla of Vater. Currently, surgery remains the primary treatment option, yet the postoperative recurrence rate remains high. Chemotherapy is the main approach for controlling postoperative recurrence. Histologically, periampullary carcinoma is categorized into two types: intestinal (IN) and pancreaticobiliary (PB) subtype. Each subtype requires different therapeutic approaches, with the PB type primarily treated with gemcitabine and the IN type with 5-FU. Despite these options, patient outcomes are still unsatisfactory. In recent years, the feasibility of immunotherapy in tumor treatment has been increasingly evidenced, although research on its efficacy in periampullary carcinoma treatment is still limited. In this report, we present a case of a periampullary carcinoma patient who experienced recurrence and metastasis after undergoing radical pancreatoduodenectomy and receiving gemcitabine-based chemotherapy post-surgery. Through next-generation sequencing (NGS), we identified high expression levels of programmed cell death-ligand 1 (PD-L1) with a combined positive score (CPS) of 35, high tumor mutation burden (TMB-H), and high microsatellite instability (MSI-H) in this patient. Therefore, we implemented a combination therapy using Tislelizumab and chemotherapy. According to the latest follow-up, the tumors are effectively controlled. Our utilization of immunotherapy combined with chemotherapy holds significant implication for the treatment of periampullary carcinoma.

Trichloroethylene (TCE), a widely distributed environmental chemical contaminant, is extensively dispersed throughout the environment. Individuals who are exposed to TCE may manifest occupational medicamentose-like dermatitis due to trichloroethylene (OMDT). Renal impairment typically manifests in the initial phase of OMDT and is intricately linked to the disease progression and patient outcomes. Although recombinant human tumor necrosis factor-α receptor II fusion protein (rh TNFR:Fc) has been employed in the clinical management of OMDT, there was no substantial improvement in renal function observed in patients following one week of treatment. This study primarily examined the mechanism of TNFα- and IFNγ-induced endothelial cells (ECs) PANoptosis in TCE-induced kidney injury and hypothesized that the synergistic effect of TNFα and IFNγ could be the key factor affecting the efficacy of rh TNFR:Fc therapy in OMDT patients. A TCE-sensitized mouse model was utilized in this study to investigate the effects of TNFα and IFNγ neutralizing antibodies on renal vascular endothelial cell PANoptosis. The gene of interferon regulatory factor 1 (IRF1) in human umbilical vein endothelial cells (HUVEC) was silenced by using small interfering RNA (siRNA), and the cells were then treated with TNFα and IFNγ recombinant protein to investigate the mechanism of TNFα combined with IFNγ-induced PANoptosis in HUVEC. The findings indicated that mice sensitized to TCE exhibited increased levels of PANoptosis-related markers in renal endothelial cells, and treatment with TNFα and IFNγ neutralizing antibodies resulted in a significant reduction in PANoptosis and improvement in renal function. In vitro experiments demonstrated that silencing IRF1 could reverse TNFα and IFNγ-induced PANoptosis in endothelial cells. These results suggest that the efficacy of rh TNFR:Fc may be influenced by TNFα and IFNγ-mediated PANoptosis in kidney vascular endothelial cells. The joint application of TNFα and IFNγ neutralizing antibody represented a solid alternative to existing therapeutics.

In the railway system environment, the interconnection of a vast array of intelligent sensing devices has brought about revolutionary changes in the management and monitoring of railway transportation. However, this also poses challenges to the communication service quality within the railway Internet of Things (IoT). Through collective intelligence and collaboration, the nodes within the railway IoT can not only share data and information but also work synergistically to enhance the overall intelligence level and improve decision-making quality of the network. Therefore, this paper proposes a reconnection mechanism based on the computation of node game-theoretic benefits and optimizes this process with the concept of swarm intelligence collaboration. Initially, the game-theoretic benefit values of the nodes in the railway IoT network are calculated. Subsequently, based on the weight priority of the edges, the two edges with the larger weights are selected, and connections are established between nodes with similar game-theoretic benefit values to enhance the network’s robustness. This approach enables rapid networking and efficient communication transmission within the railway IoT, providing robust assurance for the safe and stable operation of the railway.

Entrepreneurial behavior has been substantially addressed in entrepreneurship literature, but the mechanisms by which social capital influences entrepreneurial behavior among college students remain unclear, especially the potential mediating and moderating interplay among them. Therefore, drawing on social capital theory and the Stimulus-Organism-Response (S-O-R) model, this study proposed a moderated mediation model of social capital on entrepreneurial behavior. Sample data were collected via questionnaires from entrepreneurial team members participating in the Innovation and Entrepreneurship Competition in Southwest China. Results showed that (1) social capital has a positive impact on entrepreneurial behavior; (2) entrepreneurial passion partially mediates the relationship between social capital and entrepreneurial behavior; and (3) entrepreneurial risk perception positively moderates the relationship between entrepreneurial passion and behavior and thus enhances the mediating effect of entrepreneurial passion. This study provides insights into the internal mechanism of social capital on entrepreneurial behavior and also offers practical guidance for individuals, universities, and governments.

Abstract Background Glycemic control for patients with diabetes in the surgical department is often unsatisfactory. Compounding this issue is the fact that conventional glucose management models are often inefficient and difficult to monitor over time. Objective To investigate the impact of inpatient glucose team-based management on glycemic control and hospital days in surgical patients with diabetes. Methods A retrospective analysis was conducted on 4156 patients with diabetes in the surgical department who received inpatient management of diabetes at a tertiary medical center from June 2020 to May 2022. Based on whether they received inpatient glucose team-based management, the surgical patients with diabetes were divided into two groups: the inpatient glucose team-based management (GM group, consisting of 1698 participants) and the conventional blood glucose management group (control group, consisting of 2458 participants). We compared the two groups in terms of glycemic control, hospital days, and health-care costs. Multiple logistic regression analysis was performed to build the hospital days prediction model and nomogram. Finally, the performance of the model was evaluated. Results The rate of glucose detection was higher in the GM group at 2 h postprandial (P

Abstract Objective Preimplantation genetic testing for monogenic disorders (PGT-M) has been used for over 20 years to detect many serious genetic conditions. However, there is still a lack of reference materials (RMs) to validate the test performance during the development and quality control of PGT-M. Method Sixteen thalassemia cell lines from four thalassemia families were selected to establish the RMs. Each family consisted of parents with heterozygous mutations for α- and/or β-thalassemia and two children, at least one of whom carried a homozygous thalassemia mutation (proband). The RM panel consisted of 12 DNA samples (parents and probands in 4 families) and 4 simulated embryos (cell lines constructed from blood samples from the four nonproband children). Four accredited genetics laboratories that offer verification of thalassemia samples were invited to evaluate the performance of the RM panel. Furthermore, the stability of the RMs was determined by testing after freeze‒thaw cycles and long-term storage. Results PGT-M reference materials containing 12 genome DNA (gDNA) reference materials and 4 simulated embryo reference materials for thalassemia testing were successfully established. Next-generation sequencing was performed on the samples. The genotypes and haplotypes of all 16 PGT-M reference materials were concordant across the four labs, which used various testing workflows. These well-characterized PGT-M reference materials retained their stability even after 3 years of storage. Conclusion The establishment of PGT-M reference materials for thalassemia will help with the standardization and accuracy of PGT-M in clinical use.

Abstract Background Immune checkpoint inhibitors (ICIs) have contributed to a significant advancement in the treatment of cancer, leading to improved clinical outcomes in many individuals with advanced disease. Both preclinical and clinical investigations have shown that ICIs are associated with atherosclerosis and other cardiovascular events; however, the exact mechanism underlying this relationship has not been clarified. Methods Patients diagnosed with stages III or IV non-small cell lung cancer (NSCLC) at the Wuhan Union Hospital from March 1, 2020, to April 30, 2022, were included in this retrospective study. Coronary artery calcium (CAC) volume and score were assessed in a subset of patients during non-ECG-gated chest CT scans at baseline and 3, 6, and 12 months after treatment. Propensity score matching (PSM) was performed in a 1:1 ratio to balance the baseline characteristics between the two groups. Results Overall, 1458 patients (487 with ICI therapy and 971 without ICI therapy) were enrolled in this cardiovascular cohort study. After PSM, 446 patients were included in each group. During the entire period of follow-up (median follow-up 23.1 months), 24 atherosclerotic cardiovascular disease (ASCVD) events (4.9%) occurred in the ICI group, and 14 ASCVD events (1.4%) in the non-ICI group, before PSM; 24 ASCVD events (5.4%) occurred in the ICI group and 5 ASCVD events (1.1%) in the non-ICI group after PSM. The CAC imaging study group comprised 113 patients with ICI therapy and 133 patients without ICI therapy. After PSM, each group consisted of 75 patients. In the ICI group, the CAC volume/score increased from 93.4 mm3/96.9 (baseline) to 125.1 mm3/132.8 (at 12 months). In the non-ICI group, the CAC volume/score was increased from 70.1 mm3/68.8 (baseline) to 84.4 mm3/87.9 (at 12 months). After PSM, the CAC volume/score was increased from 85.1 mm3/76.4 (baseline) to 111.8 mm3/121.1 (12 months) in the ICI group and was increased from 74.9 mm3/76.8 (baseline) to 109.3 mm3/98.7 (12 months) in the non-ICI group. Both cardiovascular events and CAC progression were increased after the initiation of ICIs. Conclusions Treatment with ICIs was associated with a higher rate of ASCVD events and a noticeable increase in CAC progression.

Abstract Gene delivery to, and expression in, the mouse brain is important for understanding gene functions in brain development and disease, or testing gene therapies. Here, we describe an approach to express a transgene in the mouse brain in a cell-type-specific manner. We use stereotaxic injection of a transgene-expressing adeno-associated virus into the mouse brain via the intracerebroventricular route. We demonstrate stable and sustained expression of the transgene in neurons of adult mouse brain, using a reporter gene driven by a neuron-specific promoter. This approach represents a rapid, simple, and cost-effective method for global gene expression in the mouse brain, in a cell-type-specific manner, without major surgical interventions. The described method represents a helpful resource for genetically engineering mice to express a therapeutic gene, for gene therapy studies, or to deliver genetic material for genome editing and developing knockout animal models.

With the rapid development of information technology, the problem of curve matching has appeared in many application domains, including sequence analysis, signals processing, speech recognition, etc. Many similarity measures have been studied for matching curves based on Euclidean distance, which shows fragility in portraying the morphological information of curve data. In this paper, we propose a novel weighted composite curve dissimilarity metric (WCDM). First, the WCDM measures the dissimilarity based on the higher-order semantic difference between curve shapes and location difference. These two differences are calculated using the curvature difference and Euclidean distance between the curves, respectively. Second, a new dynamic weighting function is defined by employing the relationship between the trends of the curves. This function aims at adjusting the contributions of the curvature difference and the Euclidean distance to compose the dissimilarity measure WCDM. Finally, to ascertain the rationality of the WCDM, its metric properties are studied and proved theoretically. Comparison experiments on clustering and classification tasks are carried out on curve sets transformed from UCR time series datasets, and an application analysis of the WCDM is conducted on spectral data. The experimental results indicate the effectiveness of the WCDM. Specifically, clustering and classification based on the WCDM are superior to those based on ED, DTW, Hausdorff, Fréchet, and LCSS on at least 8 out of 14 datasets across all evaluation indices. In particular, the Purity and ARI on the Beetlefly dataset are improved by more than 7.5%, while accuracy on the Beef, Chinatown, and OliveOil datasets increases by 13.32%, 10.08%, and 12.83%, respectively.

The magnetic separation and cleaning module, as a core component of the fully automated chemiluminescence immunoassay (CLIA) analyzer, encounters issues including high magnetic bead loss rate, long cleaning time, and poor cleaning effect. Based on a simulation analysis using COMSOL, we proposed a novel magnetic separation and cleaning module applied to a fully automated CLIA analyzer. The module adopted a method of arranging spliced rectangular magnets on opposite sides, where the same polarity faced each other, as well as a three-stage magnetic bead collection method. With the proposed method, the total cleaning process can be accomplished within 225 s; the total magnetic bead loss rate over three rounds of cleaning is 6.03%, whereas that of traditional instruments is 25.85%; the coefficient of variation (CV) of the magnetic bead loss rate is less than 0.5%; effective cleaning of free markers is achieved under various sample conditions. Compared with traditional CLIA instruments, this method comprehensively improves key performance indicators of the magnetic separation and cleaning module, providing a reference for similar modules in fully automated CLIA analyzers and positively impacting the accuracy of CLIA for the detection of disease biomarkers.

The negative high-pass filter feedback of the grid current (NFGCF) can offer active damping for the LCL-type grid-connected inverter. Due to the control delay in digital control systems, this damping can cause the system to exhibit non-minimum phase behavior within specific frequency ranges. This study proposes a joint active damping approach that combines grid current feedback and the point of common coupling (PCC) voltage unit feedforward. The proposed method introduces a dynamic damping region that varies with grid impedance. By developing suitable damping loop control parameters, this region can span the entire frequency range, even exceeding the Nyquist frequency fs/2. The research results demonstrate that the proposed approach enhances robustness against variations in grid impedance and eliminates non-minimum phase behavior. Simulation and experimental outcomes validate the effectiveness of this joint active damping method.

Efficiency has always been one of the most critical indicators for evaluating wireless power transfer (WPT) systems. To achieve fast maximum energy efficiency tracking (MEET), this paper provides an innovative control method utilizing the hill climbing-golden section search (HC-GSS) method of an LCC-S compensated WPT system. The receiver side includes a buck-boost converter that regulates the output current or voltage to meet output requirements. In the meantime, the buck-boost converter on the transmitter side is managed by the HC-GSS approach for MEET by minimizing the input power under the premise of output stability. Compared with the conventional P&O method, the HC-GSS method can eliminate the trade-off between the oscillation and convergence rate because it is designed for different system stages. In this WPT system, there is no need for direct communication between the transmitter and receiver. Therefore, the system is potentially cheaper to implement and does not suffer from annoying communication delays, which are prevalent in underwater environments for unmanned underwater vehicles’ (UUV) WPT systems. Both the simulation and experiment results show that this method can improve the efficiency of the WPT system without communication. The proposed method remains valid with coupler displacement as it does not include the mutual inductance of the system.

BackgroundImmune checkpoint inhibitors (ICIs) have left a deep impression in the treatment of non-small cell lung cancer (NSCLC), however, not all patients benefit from it. The purpose of this study was to investigate the prognostic value of baseline bone mineral density (BMD) derived from chest computed tomography (CT) scans in NSCLC patients treated with ICIs.MethodsThis study included patients with advanced NSCLC who underwent ICI treatment at the Wuhan Union Hospital from March 2020 to October 2022. Baseline BMD was evaluated at non-contrast chest CT at the level of first lumbar vertebra. Patients were divided into BMD-lower group and BMD-higher group according to the optimal cutoff value calculated by X-tile software. Baseline characteristics of the two groups were compared and variables between the two groups were balanced by propensity score matching (PSM) analysis. We calculated the objective response rate (ORR) and disease control rate (DCR) of the two groups and analyzed overall survival (OS) and progression-free survival (PFS) using BMD and other clinical indexes through Cox regression models and Kaplan-Meier survival curves.ResultsA total of 479 patients were included in this study, and all patients were divided into BMD-lower group (n=270) and BMD-higher group (n=209). After PSM analysis, each group consisted of 150 patients. ORR (43.3% vs. 43.5% before PSM, P = 0.964; 44.7% vs. 44.7% after PSM, P = 1.000) and DCR (91.1% vs. 94.3% before PSM, P = 0.195; 93.3% vs. 96.7% after PSM, P =0.190) were similar in two groups. There was no statistically significant relationship between BMD degree and PFS before (16.0 months vs. 18.0 months, P = 0.067) and after PSM analysis (17.0 months vs. 19.0 months, P = 0.095). However, lower BMD was associated with shorter OS both before (20.5 months vs. 23.0 months, P< 0.001) and after PSM analysis (20.0 months vs. 23.0 months, P = 0.008).ConclusionLower baseline BMD is associated with worse clinical outcomes in NSCLC patients treated with ICIs. As a reliable and easily obtained individual prognostic biomarker, BMD can become a routine detection indicator before immunotherapy.

Resumo Fundamento O infarto do miocárdio com elevação do segmento ST (IAMCSST) é uma das principais causas de doenças cardiovasculares fatais, que têm sido a principal causa de mortalidade em todo o mundo. O diagnóstico na fase inicial beneficiaria a intervenção clínica e o prognóstico, mas ainda falta a exploração dos biomarcadores do IAMCSST. Objetivos Neste estudo, conduzimos uma análise bioinformática para identificar potenciais biomarcadores cruciais no progresso do IAMCSST. Métodos Obtivemos GSE59867 para pacientes com IAMCSST e doença arterial coronariana estável (DACE). Genes diferencialmente expressos (GDEs) foram selecionados com o limiar de |log2fold change| > 0,5 e p < 0,05. Com base nesses genes, conduzimos análises de enriquecimento para explorar a relevância potencial entre genes e para rastrear genes centrais. Posteriormente, os genes centrais foram analisados para detectar miRNAs relacionados e DAVID para detectar fatores de transcrição para análise posterior. Finalmente, o GSE62646 foi utilizado para avaliar a especificidade dos GDEs, com genes demonstrando resultados de AUC superiores a 75%, indicando seu potencial como candidatos a biomarcadores. Posteriormente, os genes centrais foram analisados para detectar miRNAs relacionados e DAVID para detectar fatores de transcrição para análise posterior. Finalmente, o GSE62646 foi utilizado para avaliar a especificidade dos GDEs, com genes demonstrando resultados de AUC superiores a 75%, indicando seu potencial como candidatos a biomarcadores. Resultados 133 GDEs entre DACE e IAMCSST foram obtidos. Em seguida, a rede PPI de GDEs foi construída usando String e Cytoscape, e análises posteriores determinaram genes centrais e 6 complexos moleculares. A análise de enriquecimento funcional dos GDEs sugere que as vias relacionadas à inflamação, metabolismo e imunidade desempenham um papel fundamental na progressão de DACE para IAMCSST. Além disso, foram previstos miRNAs relacionados, has-miR-124, has-miR-130a/b e has-miR-301a/b regularam a expressão do maior número de genes. Enquanto isso, a análise dos fatores de transcrição indica que EVI1, AML1, GATA1 e PPARG são os genes mais enriquecidos. Finalmente, as curvas ROC demonstram que MS4A3, KLRC4, KLRD1, AQP9 e CD14 exibem alta sensibilidade e especificidade na previsão de IAMCSST. Conclusões Este estudo revelou que imunidade, metabolismo e inflamação estão envolvidos no desenvolvimento de IAMCSST derivado de DACE, e 6 genes, incluindo MS4A3, KLRC4, KLRD1, AQP9, CD14 e CCR1, poderiam ser empregados como candidatos a biomarcadores para IAMCSST.

Background: The association between bone morphogenetic protein 10 (BMP10) and atrial fibrillation (AF) has been widely investigated by observational studies, but their causal relationships remain inconclusive. Here, we aimed to evaluate the causal effect of BMP10 on the risk of AF through single-nucleotide polymorphisms. Methods: A Mendelian randomization (MR) analytic framework was applied to data from two BMP10-specific genome-wide association studies comprising a total of 11,036,163 single-nucleotide polymorphisms of European ancestry. Instrument genetic variants associated with BMP10 were selected. A total of 12 AF-specific genome-wide association studies comprising a total of 5,095,117 European participants were included. Summary statistic-based methods of inverse variance weighted, MR Egger, weighted median, simple mode, and weighted mode methods were used. Pleiotropy and sensitivity were assessed. Results: Specific to AF-specific genome-wide association studies, we found that BMP10 was not associated with AF among different methods (all P > 0.05). We further identified no significant horizontal pleiotropy (all P > 0.05) and no fundamental impact among various data. Conclusions: This large-scale population study upon data from BMP10- and AF-specific genome-wide association studies and a longitudinal biobank cohort indicates plausible non-causal associations between BMP10 and AF in the European populations. Further studies regarding ancestral diversity are warranted to validate such causal associations.

Abstract Background Congenital myasthenic syndrome is a heterogeneous group of inherited neuromuscular transmission disorders. Variants in RAPSN are a common cause of CMS, accounting for approximately 14%–27% of all CMS cases. Whether preimplantation genetic testing for monogenic disease (PGT‐M) could be used to prevent the potential birth of CMS‐affected children is unclear. Methods Application of WES (whole‐exome sequencing) for carrier testing and guidance for the PGT‐M in the absence of a genetically characterized index patient as well as assisted reproductive technology were employed to prevent the occurrence of birth defects in subsequent pregnancy. The clinical phenotypes of stillborn fetuses were also assessed. Results The family carried two likely pathogenic variants in RAPSN(NM_005055.5): c.133G>A (p.V45M) and c.280G>A (p.E94K). And the potential birth of CMS‐affected child was successfully prevented, allowing the family to have offspring devoid of disease‐associated variants and exhibiting a normal phenotype. Conclusion This report constitutes the first documented case of achieving a CMS‐free offspring through PGT‐M in a CMS‐affected family. By broadening the known variant spectrum of RAPSN in the Chinese population, our findings underscore the feasibility and effectiveness of PGT‐M for preventing CMS, offering valuable insights for similarly affected families.

Osteosarcoma is a malignant bone cancer that originates from the bone with the strongest invasiveness. Tumor formation strongly correlates with immune cell infiltration into the tumor immune microenvironment (TIME). Therefore, we aimed to identify TIME-related biomarkers as potential prognostic markers of osteosarcoma. The mRNA and long noncoding RNA (lncRNA) transcriptome data of 88 patients with osteosarcoma and the expression profile of GSE99671 were downloaded from The Cancer Genome Atlas and Gene Expression Omnibus, respectively. Immune infiltration scores and types were evaluated using ESTIMATE and CIBERSORT. A linear model was established to identify the differentially expressed genes (DEGs) and lncRNAs (DElncRNAs). Functional enrichment analysis of DEGs was conducted by Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, gene set enrichment analysis, and gene set variation analysis. DElncRNAs were analyzed using a weighted gene co-expression network. Least absolute shrinkage and selection operator regression was applied to screen for prognostic markers. Patient survival was predicted by the risk score and analyzed by receiver operating characteristic curve. Clinical features affecting patient survival were assessed. Immune infiltration positively correlated with osteosarcoma patient survival. Different immune cell infiltrates in patients with osteosarcma may serve as prognostic indicators and targets for immunotherapy. In total, 1125 DEGs, 80 DElncRNAs, and 11 pairs of co-expressed lncRNA-mRNAs were identified. DEGs in the three modules were associated with immune infiltration into the TIME. Four DElncRNAs, namely AC015819.1, AC015911.3, AL365361.1, and USP30-AS1, showed good prognostic ability for osteosarcoma and were positively correlated with the immune score. Tumor metastasis and risk scores alone were good prognostic indicators, and a combination of the two variables can better predict the prognosis of osteosarcoma. We identified four lncRNAs, AC015819.1, AC015911.3, AL365361.1, and USP30-AS1, as potential biomarkers for osteosarcoma prognosis.

Abstract Background Preimplantation genetic testing for aneuploidy (PGT-A) was demonstrated to be superior to conventional IVF in reducing the incidence of miscarriage and abnormal offspring after the first embryo transfer (ET). PGT-A requires several embryo trophectoderm cells, but its negative impacts on embryo development and long-term influence on the health conditions of conceived children have always been a concern. As an alternative, noninvasive PGT-A (niPGT-A) approaches using spent blastocyst culture medium (SBCM) achieved comparable accuracy with PGT-A in several pilot studies. The main objective of this study is to determine whether noninvasive embryo viability testing (niEVT) results in better clinical outcomes than conventional IVF after the first embryo transfer. Furthermore, we further investigated whether niEVT results in higher the live birth rate between women with advanced maternal age (AMA, > 35 years old) and young women or among patients for whom different fertilization protocols are adopted. Methods This study will be a double-blind, multicenter, randomized controlled trial (RCT) studying patients of different ages (20–43 years) undergoing different fertilization protocols (in vitro fertilization [IVF] or intracytoplasmic sperm injection [ICSI]). We will enroll 1140 patients at eight reproductive medical centers over 24 months. Eligible patients should have at least two good-quality blastocysts (better than grade 4 CB). The primary outcome will be the live birth rate of the first embryo transfer (ET). Secondary outcomes will include the clinical pregnancy rate, ongoing pregnancy rate, miscarriage rate, cumulative live birth rate, ectopic pregnancy rate, and time to pregnancy. Discussion In this study, patients who undergo noninvasive embryo viability testing (niEVT) will be compared to women treated by conventional IVF. We will determine the effects on the pregnancy rate, miscarriage rate, and live birth rate and adverse events. We will also investigate whether there is any difference in clinical outcomes among patients with different ages and fertilization protocols (IVF/ICSI). This trial will provide clinical evidence of the effect of noninvasive embryo viability testing on the clinical outcomes of the first embryo transfer. Trial registration Chinese Clinical Trial Registry (ChiCTR) Identifier: ChiCTR2100051408. 9 September 2021.

Abstract Background Sesquiterpenes are designated as a large class of plant-derived natural active compounds, which have wide applications in industries of energy, food, cosmetics, medicine and agriculture. Neither plant extraction nor chemical synthesis can meet the massive market demands and sustainable development goals. Biosynthesis in microbial cell factories represents an eco-friendly and high-efficient way. Among several microorganisms, Saccharomyces cerevisiae exhibited the potential as a chassis for bioproduction of various sesquiterpenes due to its native mevalonate pathway. However, its inefficient nature limits biosynthesis of diverse sesquiterpenes at industrial grade. Results Herein, we exploited an artificial synthetic malonic acid-acetoacetyl-CoA (MAAC) metabolic pathway to switch central carbon metabolic flux for stable and efficient biosynthesis of sesquiterpene-based high-density biofuel precursor in S. cerevisiae. Through investigations at transcription and metabolism levels, we revealed that strains with rewired central metabolism can devote more sugars to β-caryophyllene production. By optimizing the MVA pathway, the yield of β-caryophyllene from YQ-4 was 25.8 mg/L, which was 3 times higher than that of the initial strain YQ-1. Strain YQ-7 was obtained by introducing malonic acid metabolic pathway. Combing the optimized flask fermentation process, the target production boosted by about 13-fold, to 328 mg/L compared to that in the strain YQ-4 without malonic acid metabolic pathway. Conclusion This designed MAAC pathway for sesquiterpene-based high-density biofuel precursor synthesis can provide an impressive cornerstone for achieving a sustainable production of renewable fuels.

To provide a comprehensive analysis of how an intricate landscape environment comprising various landscape elements influences driving safety and comfort. Beginning with the individual design of the tunnel body section, which includes the roof, sidewalls, road surface, and sidewalk facade markings, this paper references the driver’s biomass index to identify design alterations that satisfy basic safety requirements through simulated driving experiments. Subsequently, employing orthogonal experimental design and semi-supervised clustering algorithms, we ascertain the optimal combination of the four main landscape elements of the tunnel body section that align with both safety and comfort objectives. The experimental findings demonstrate that a safe and comfortable landscape design for urban tunnel sections does not entail a single optimal design; rather, any landscape design conforming to the criterion of “patterned landscapes are set on the side walls and roofs of the tunnel instead of the surface of the road” is the optimal design.

Aiming at real-time detection of UAVs, small UAV targets are easily missed and difficult to detect in complex backgrounds. To maintain high detection performance while reducing memory and computational costs, this paper proposes the SEB-YOLOv8s detection method. Firstly, the YOLOv8 network structure is reconstructed using SPD-Conv to reduce the computational burden and accelerate the processing speed while retaining more shallow features of small targets. Secondly, we design the AttC2f module and replace the C2f module in the backbone of YOLOv8s with it, enhancing the model’s ability to obtain accurate information and enriching the extracted relevant information. Finally, Bi-Level Routing Attention is introduced to optimize the Neck part of the network, reducing the model’s attention to interfering information and filtering it out. The experimental results show that the mAP50 of the proposed method reaches 90.5% and the accuracy reaches 95.9%, which are improvements of 2.2% and 1.9%, respectively, compared with the original model. The mAP50-95 is improved by 2.7%, and the model’s occupied memory size only increases by 2.5 MB, effectively achieving high-accuracy real-time detection with low memory consumption.

Abstract Kagome lattices of various transition metals are versatile platforms for achieving anomalous Hall effects, unconventional charge-density wave orders and quantum spin liquid phenomena due to the strong correlations, spin-orbit coupling and/or magnetic interactions involved in such a lattice. Here, we use laser-based angle-resolved photoemission spectroscopy in combination with density functional theory calculations to investigate the electronic structure of the newly discovered kagome superconductor CsTi3Bi5, which is isostructural to the AV3Sb5 (A = K, Rb or Cs) kagome superconductor family and possesses a two-dimensional kagome network of titanium. We directly observe a striking flat band derived from the local destructive interference of Bloch wave functions within the kagome lattice. In agreement with calculations, we identify type-II and type-III Dirac nodal lines and their momentum distribution in CsTi3Bi5 from the measured electronic structures. In addition, around the Brillouin zone centre, $${{\mathbb{Z}}}_{2}$$ Z 2 nontrivial topological surface states are also observed due to band inversion mediated by strong spin-orbit coupling.

Abstract Background and objective The pathogenesis and pathophysiology of idiopathic normal pressure hydrocephalus (iNPH) remain unclear. Homocysteine may reduce the compliance of intracranial arteries and damage the endothelial function of the blood-brain barrier (BBB), which may be the underlying mechanism of iNPH. The overlap cases between deep perforating arteriopathy (DPA) and iNPH were not rare for the shared risk factors. We aimed to investigate the relationship between serum homocysteine and iNPH in DPA. Methods A total of 41 DPA patients with iNPH and 49 DPA patients without iNPH were included. Demographic characteristics, vascular risk factors, laboratory results, and neuroimaging data were collected. Multivariable logistic regression analysis was performed to investigate the relationship between serum homocysteine and iNPH in DPA patients. Results Patients with iNPH had significantly higher homocysteine levels than those without iNPH (median, 16.34 mmol/L versus 14.28 mmol/L; P = 0.002). There was no significant difference in CSVD burden scores between patients with iNPH and patients without iNPH. Univariate logistic regression analysis demonstrated that patients with homocysteine levels in the Tertile3 were more likely to have iNPH than those in the Tertile1 (OR, 4.929; 95% CI, 1.612–15.071; P = 0.005). The association remained significant after multivariable adjustment for potential confounders, including age, male, hypertension, diabetes mellitus, atherosclerotic cardiovascular disease (ASCVD) or hypercholesterolemia, and eGFR level. Conclusion Our study indicated that high serum homocysteine levels were independently associated with iNPH in DPA. However, further research is needed to determine the predictive value of homocysteine and to confirm the underlying mechanism between homocysteine and iNPH.

In recent years, some expressway tunnels have started broadcasting warning sounds, such as fire alarms, to improve driver attention and traffic safety. However, there is few research on it, and in contrast to previous studies, we have considered different evaluation indices and through field measurement to determine the effectiveness of this practice. The characteristics of three warning sound signals, i.e., fire alarm, dynamic music, and voice command, in a tunnel were analyzed usingMATLAB. Considering pupil diameter and blink duration as evaluation indexes, the change in the mental state of the driver after hearing a warning sound was analyzed. Based on Markov chain theory, the change in the gaze region and gaze shift of the driver under the condition of a warning sound was analyzed. Results shows fire alarms and voice commands can increase the mental load of drivers, but the degree of impact was not determined. Dynamic music does not affect the mental load of the driver. The fire alarm and dynamic music attracted the attention of the driver; conversely, as the voice command warns the driver to focus on safety, it did not impact the attention of the driver. The research results provide a scientific reference for the selection of warning sounds in expressway tunnels and new research ideas for the prevention of traffic injuries in expressway tunnels.

The microbial conversion of alkanes to methane in hydrocarbon-contaminated environments is an intrinsic bioremediation strategy under anoxic conditions. However, the mechanism of microbial methanogenic alkane degradation is currently unclear. Under ten years of continuous efforts, we obtained a methanogenic n-alkane-degrading (C15–C20) enrichment culture that exhibited sustained improvements in the kinetic properties of methane production. The integrated metagenomic and metatranscriptomic analyses revealed that n-alkanes were mainly attacked by members of Desulfosarcinaceae, Firmicutes, and Synergistetes using the fumarate addition strategy, and were then further degraded in a common effort by Tepidiphilus members. Meanwhile, the abundant members of Anaerolineaceae were mainly responsible for cell debris recycling. However, according to the metatranscriptomic analyses, methane was predicted to be produced mainly via H2-dependent methylotrophic methanogenesis, primarily from necromass-derived trimethylamine mediated by Methanomethyliaceae within the candidate phylum Verstraetearchaeota. These findings reveal that H2-dependent methylotrophic methanogens, as well as methylotrophic methanogens, may play important ecological roles in the carbon cycle of hydrocarbon enriched subsurface ecosystems.

Growing interface structure of pearlite in 100Mn13 high carbon high manganese steel was studied after 1323 K solution treatment and subsequently 823 K aging treatment by Scanning Electron Microscope (SEM) and Transmission Electron Microscope (TEM). The results show that longer pearlite lamellae consisting of ferrite lamella and cementite lamella are formed in initial growth stage of pearlite colony, in which there are protrusions and branches in M3C/γ interface. The cementite lamella is divided along (01¯0) M3C into two parts which differ in some respects, such as edge dislocations, (01¯0) M3C lattice arrangement. Besides, edge interface of ferrite lamella is wavy morphology including two peaks presenting small curvature radius, which accommodate more C atoms under the premise of meeting composition condition for transformation to accelerate the transformation. The growth physical model of cementite lamella with protrusions and branches, ferrite lamella with two peaks and three troughs are respectively proposed.

BackgroundWe explored the characteristics of single-cell differentiation data in glioblastoma and established prognostic markers based on CRYAB to predict the prognosis of glioblastoma patients. Aberrant expression of CRYAB is associated with invasive behavior in various tumors, including glioblastoma. However, the specific role and mechanisms of CRYAB in glioblastoma are still unclear.MethodsWe assessed RNA-seq and microarray data from TCGA and GEO databases, combined with scRNA-seq data on glioma patients from GEO. Utilizing the Seurat R package, we identified distinct survival-related gene clusters in the scRNA-seq data. Prognostic pivotal genes were discovered through single-factor Cox analysis, and a prognostic model was established using LASSO and stepwise regression algorithms. Moreover, we investigated the predictive potential of these genes in the immune microenvironment and their applicability in immunotherapy. Finally, in vitro experiments confirmed the functional significance of the high-risk gene CRYAB.ResultsBy analyzing the ScRNA-seq data, we identified 28 cell clusters representing seven cell types. After dimensionality reduction and clustering analysis, we obtained four subpopulations within the oligodendrocyte lineage based on their differentiation trajectory. Using CRYAB as a marker gene for the terminal-stage subpopulation, we found that its expression was associated with poor prognosis. In vitro experiments demonstrated that knocking out CRYAB in U87 and LN229 cells reduced cell viability, proliferation, and invasiveness.ConclusionThe risk model based on CRYAB holds promise in accurately predicting glioblastoma. A comprehensive study of the specific mechanisms of CRYAB in glioblastoma would contribute to understanding its response to immunotherapy. Targeting the CRYAB gene may be beneficial for glioblastoma patients.

BackgroundImmunotherapy, represented by immune checkpoint inhibitors (ICIs), is a major breakthrough in cancer treatment. Studies have reported that the use of ICIs is associated with an increase in the pulmonary artery to ascending aorta diameter (PAD/AoD) ratio. However, the impact of PAD/AoD ratio progression on the prognosis of patients is unclear.MethodsThis retrospective cohort study included patients with stage III or IV non-small cell lung cancer (NSCLC) treated with ICIs at the Wuhan Union Hospital between March 1, 2020, and September 1, 2022. The baseline and post-treatment PAD/AoD ratios of patients were evaluated through chest CT scans. The primary outcome of this study was overall survival (OS), while the secondary outcomes included progression-free survival (PFS), objective response rate (ORR) and disease control rate (DCR).ResultsThe PAD/AoD ratio increased after the initiation of ICIs (from 0.75 to 0.78; P < 0.001). A total of 441 patients were divided into severe group (n=221) and non-severe group (n=220) according to the median increase of PAD/AoD ratio (1.06). Compared with the non-severe group, the severe group had a lower DCR (87.8% vs. 96.0%, P = 0.005) and ORR (87.5% vs. 96.0%, P = 0.063). Over the entire duration of follow-up (median 22.0 months), 85 (38.5%) patients in the severe group and 30 (7.3%) patients in the non-severe group died. An increased PAD/AoD ratio was associated with shorter PFS (Hazard ratio (HR): 1.48 [95% CI, 1.14 to 1.93]; P = 0.003) and OS (HR: 3.50 [95% CI, 2.30 to 5.30]; P < 0.001). Similar results were obtained across subgroups.ConclusionsICI treatment exacerbates an increase in the PAD/AoD ratio in patients with cancer, and greater increase in the PAD/AoD ratio was associated with a worse prognosis. PAD/AoD ratio could be a biomarker to stratify prognosis of NSCLC patients treated with ICIs.

The nitrogen vacancy (NV) color centers are a solid-state quantum system with the ability to maintain long coherence times at room temperatures. NV centers have potential applications in quantum detection, which necessitates their positioning at minimal distances from surfaces. However, the existing methods for fabricating NV centers are cumbersome, expensive, and difficult to control. This study investigates the etching mechanism of transition metals on diamond under plasma conditions and develops a method for producing shallow NV centers on the surface of high pressure and high temperature diamond. Our proposed method enables the production of shallow NV centers below the surface in the longitudinal direction, while simultaneously allowing precise control over the lateral distribution. Moreover, the operating costs associated with our technique are significantly lower than those of ion implantation and electron irradiation. This research contributes to the advancement of iron-etching diamond processing technology, and the proposed method facilitates the more portable preparation of shallow color centers in specific regions, enabling the realization of locally controllable and scalable coupled quantum systems.

ABSTRACT: More and more studies have demonstrated that proteasomal degradation occurs in the development of various diseases, including ventricular remodeling, which is a cardiac pathological change and seriously makes patient outcomes worse. Our preliminary results showed that Guanxin V, an effective and safe complementary and alternative medicine for ventricular remodeling, reverses ventricular hypertrophy by transforming growth factor-beta 1 (TGF-β1), but the specific mechanism needs to be explored. The left anterior descending coronary artery was ligated to build a ventricular remodeling model. Cardiac function and histopathology were measured. Fibrosis-related indicators were detected. Moreover, cardiomyocytes were exposed to hydrogen peroxide to construct an in vitro model of ventricular remodeling. The stability of the Vimentin protein was assessed with cycloheximide and MG132. Endogenous and exogenous TGF-β1-Vimentin interactions were detected by co-immunoprecipitation. Guanxin V significantly eased heart function and improved fibrosis in ventricular remodeling. Mechanistically, Guanxin V promoted TGF-β1-mediated proteasomal degradation of Vimentin and reduced the TGF-β1-Vimentin interaction. Here, we reported a completely new mechanism, Guanxin V alleviates ventricular remodeling by promoting and targeting TGF-β1-mediated proteasomal degradation of Vimentin, which provides a new target for the management of ventricular remodeling and lays the foundation for the further clinical promotion of Guanxin V.

Abstract Human diseases, particularly infectious diseases and cancers, pose unprecedented challenges to public health security and the global economy. The development and distribution of novel prophylactic and therapeutic vaccines are the prioritized countermeasures of human disease. Among all vaccine platforms, viral vector vaccines offer distinguished advantages and represent prominent choices for pathogens that have hampered control efforts based on conventional vaccine approaches. Currently, viral vector vaccines remain one of the best strategies for induction of robust humoral and cellular immunity against human diseases. Numerous viruses of different families and origins, including vesicular stomatitis virus, rabies virus, parainfluenza virus, measles virus, Newcastle disease virus, influenza virus, adenovirus and poxvirus, are deemed to be prominent viral vectors that differ in structural characteristics, design strategy, antigen presentation capability, immunogenicity and protective efficacy. This review summarized the overall profile of the design strategies, progress in advance and steps taken to address barriers to the deployment of these viral vector vaccines, simultaneously highlighting their potential for mucosal delivery, therapeutic application in cancer as well as other key aspects concerning the rational application of these viral vector vaccines. Appropriate and accurate technological advances in viral vector vaccines would consolidate their position as a leading approach to accelerate breakthroughs in novel vaccines and facilitate a rapid response to public health emergencies.