Search

Abstract Background The aim of this retrospective cohort study was to assess the impact of day 3(D3) embryo cell number on the clinical pregnancy and neonatal outcomes of day 4(D4) single embryo transfer in fresh cycles. Methods The study included 431 day 4 single embryo transfer in fresh cycles conducted between December 2018 and June 2023. These cycles were divided into three groups according to the day 3 embryo cell number: 248 cycles in the 7 ~ 9-cell group, 149 cycles in the 10 ~ 13-cell group and 34 cycles in the >13-cell group, and clinical pregnancy outcomes and neonatal outcomes were compared among the three groups. Results The clinical outcomes with 10 ~ 13-cell were significantly higher than those of the 7 ~ 9-cell group, regardless of whether the female age was

Abstract Simplified rapid hydration has been proven to be non-inferior to standard hydration in preventing contrast-associated acute kidney injury among chronic kidney disease patients undergoing coronary angiography. The current investigation aimed to further confirm the feasibility and safety of the newly proposed hydration method-simplified rapid hydration (SH) in each risk stratification by Mehran risk score (MRS). Eligible patients (n = 954) randomized to the SH group and standard hydration group were allocated into 2 groups based on MRS: low to moderate-risk and high to very high-risk groups. Primary endpoints were the incidence of contrast-associated acute kidney injury (CA-AKI) and acute heart failure (AHF) (SH vs standard hydration). Secondary endpoints included serum creatinine (Scr), blood urea nitrogen (BUN), cystatin-C (Cys-C), and C-reactive protein (CRP) at 24 h, 48 h, and 72 h after PCI procedure, and the incidence of major adverse cardiac events (MACE). MRS was associated with a higher incidence of CA-AKI (OR = 1.101, 95%CI 1.049–1.156, P

Abstract Background Individuals who have experienced severe traumatic events are estimated to have a post-traumatic stress disorder (PTSD) prevalence rate ranging from 10 to 50%, while those not affected by trauma exposure are often considered to possess psychological resilience. However, the neural mechanisms underlying the development of PTSD, especially resilience after trauma, remain unclear. This study aims to investigate changes of cortical morphometric similarity network (MSN) in PTSD and trauma-exposed healthy individuals (TEHI), as well as the associated molecular alterations in gene expression, providing potential targets for the prevention and intervention of PTSD. Methods We recruited PTSD patients and TEHI who had experienced severe earthquakes, and healthy controls who had not experienced earthquakes. We identified alterations in the whole-brain MSN changes in PTSD and TEHI, and established associations between these changes and brain-wide gene expression patterns from the Allen Human Brain Atlas microarray dataset using partial least squares regression. Results At the neuroimaging level, we found not only trauma-susceptible changes in TEHI same as those in PTSD, but also unique neurobiological alterations to counteract the deleterious impact of severe trauma. We identified 1444 and 2214 genes transcriptionally related to MSN changes in PTSD and TEHI, respectively. Functional enrichment analysis of weighted gene expression for PTSD and TEHI revealed distinct enrichments in Gene Ontology biological processes and Kyoto Encyclopedia of Genes and Genomes pathways. Furthermore, gene expression profiles of astrocytes, excitatory neurons, and microglial cells are highly related to MSN abnormalities in PTSD. Conclusions The formation of resilience may be by an active compensatory process of the brain. The combination of macroscopic neuroimaging changes and microscopic human brain transcriptomics could offer a more direct and in-depth understanding of the pathogenesis of PTSD and psychological resilience, shedding light on new targets for the prevention and treatment of PTSD.

Abstract The occurrence of multiple primary lung cancer (MPLC) has witnessed a significant surge in recent years within the Chinese population. MPLC is distinguished by its potential genetic susceptibility and notable genetic heterogeneity. Investigating the etiology of MPLC holds substantial clinical importance.The whole genome sequencing (WGS) and genome-wide linkage analysis were performed in a family affected by a dominant form of lung abnormalities. Specifically, five family members were diagnosed with MPLC, while nine members had pulmonary nodules and one normal member. To confirm the potential pathogenic germline mutations sites, Sanger sequencing was performed in an additional 162 MPLC family patients. Furthermore, molecular biology experiments were conducted to investigate the function and the mechanism of the identified pathogenic mutation site in lung cancer A549 and H322, both in vitro and in vivo. Linkage analysis revealed the presence of shared genomic regions among affected family members. Subsequent exome sequencing identified a deleterious variant within these linkage intervals, specifically a heterozygous mutation in ETS-oncogene transcription factors 4 (ETV4). This particular variant was found in affected family members at a rate of 13 out of 15 individuals. Furthermore, ETV4 P433L mutation could be detected in an additional MPLC family patients and mutation frequency was 3.7% (6 out of 162). The ETV4 P433L mutations site was introduced into lung cancer cell lines, resulting in altered migration and stem-like properties of the cancer cells. Further investigation revealed that the activation of the Wnt/β-catenin signaling pathway, which is associated with stemness, could be attributed to the presence of the ETV4 P433L mutation, suggesting its involvement in tumor promotion. A novel pathogenic germline mutation, ETV4 P433L, was identified in a dominant MPLC family, with a mutation rate of 3.7% among MPLC family patients. The ETV4 P433L mutation was found to impact the stem-like properties and migration of tumors through Wnt/β-catenin signaling pathway.

After landing in the Utopia Planitia, Tianwen-1 formed the deepest landing crater on Mars, approximately 40 cm deep, exposing precious information about the mechanical properties of Martian soil. We established numerical models for the plume-surface interaction (PSI) and the crater formation based on Computational Fluid Dynamics (CFD) methods and the erosion model modified from Roberts’ Theory. Comparative studies of cases were conducted with different nozzle heights and soil mechanical properties. The increase in cohesion and internal friction angle leads to a decrease in erosion rate and maximum crater depth, with the cohesion having a greater impact. The influence of the nozzle height is not clear, as it interacts with the position of the Shock Diamond to jointly control the erosion process. Furthermore, we categorized the evolution of landing craters into the dispersive and the concentrated erosion modes based on the morphological characteristics. Finally, we estimated the upper limits of the Martian soil’s mechanical properties near Tianwen-1 landing site, with the cohesion ranging from 2612 to 2042 Pa and internal friction angle from 25° to 41°.

Measuring pore-water pressure (PWP) in frozen soils poses significant challenges in geotechnical testing experiments, and understanding PWP is crucial for unraveling the mechanism of frost heave generation in cold regions. This paper aims to clarify the development pattern of PWP in frozen soil through laboratory tests, specifically focusing on excess PWP generated under dynamic loading. Seven sets of triaxial tests were conducted to investigate the variations in excess PWP and deformation influenced by temperature, dynamic stress amplitude, and dry density. The results reveal that excess PWP in warm saturated frozen soil undergoes two stages: pore pressure increase and dissipation. The change of external factors mainly affects the peak value of excess PWP and the change rate of excess PWP. Unlike unfrozen soil, excess PWP has a small dissipation rate after the peak and may remain dynamically stable in the later stage of loading. In addition, two empirical models of excess PWP applicable to saturated frozen soils were proposed based on the developmental patterns of excess PWP in frozen soils, and the feasibility was validated using the results obtained from laboratory tests. The model is of great significance for predicting the development of excess PWP in frozen soil under dynamic load.

Abstract Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a rare autosomal dominant syndrome caused by a germline mutation in the fumarate hydratase (FH) gene that manifests with cutaneous leiomyomas, uterine fibroids, and renal cell cancer (RCC). Patients with HLRCC-associated RCC (HLRCC-RCC) have aggressive clinical courses, but there is no standardized therapy for advanced HLRCC-RCC. In this study, we described a case of aggressive HLRCC in a 33-year-old female who exhibited a novel heterozygous germline insertion mutation in exon 8 of the FH gene (c.1126 C > T; p.Q376*). The patient underwent laparoscopic resection of the right kidney, but metastases appeared within 3 months after surgery. Histological staining of the resected tumor revealed high expression levels of programmed cell death-ligand 1 (PD-L1). Therefore, the patient was treated with immunotherapy. The patient achieved a partial response to immunotherapy, and the treatment of metastatic lesions has continued to improve. A thorough literature review pinpointed 76 historical cases of HLRCC-RCC that had undergone immunotherapy. From this pool, 46 patients were selected for this study to scrutinize the association between mutations in the FH gene and the effectiveness of immunotherapy. Our results indicate that immunotherapy could significantly improve the overall survival (OS) of patients with HLRCC-RCC. However, no influence of different mutations in the FH germline gene on the therapeutic efficacy of immunotherapy was observed. Therefore, our study suggested that immunotherapy was an effective therapeutic option for patients with HLRCC regardless of the type of FH germline mutation.

Abstract Molybdenum (Mo) is an essential micronutrient required for plant growth but is prone to leaching from neutral and alkaline soils. The use of slow-release Mo sources could potentially reduce leaching losses from soils and increase crop yields. In this study, we assessed mechanochemistry as a green method to produce slow-release Mo sources. Molybdenum compounds (MoO3 or (NH4)6Mo7O24·4H2O) were mechanochemically (MC) treated with ZnO to synthesize compounds with a Mo content of 1–36%. Reduced Mo solubility after MC treatment, compared to the initial Mo source, was obtained with the MoO3 source and these composites were used for co-compaction with macronutrient fertilizers. Macronutrient pellets with 0.2% Mo were compacted using the 4% Mo and 36% Mo (characterized as ZnMoO4) compounds. A column dissolution test showed that the 4% Mo compound in a macronutrient carrier (DAP and MAP) only released around 40% of the total Mo compared to 80% for a non-MC treated control over 72 h. Column leaching using two soils revealed that the release behavior of Mo was strongly related to the pH of the leachate, which was affected by both the soil pH and the macronutrient carrier. More Mo was released when the MC-treated compound was co-compacted with diammonium phosphate (DAP) compared to monoammonium phosphate (MAP). The MC-treated compound with 4% Mo showed significantly less leaching than the control without ball milling when co-compacted with both MAP and DAP. In a pot trial with simulated leaching, the uptake of Mo was greater for the MC-treated 4% Mo compound co-compacted into DAP than for the other Mo sources. Overall, our results indicate that MC-treated MoO3–ZnO could be used as a slow-release Mo source in high-rainfall areas. Graphical Abstract

AIM: To evaluate the application of an intelligent diagnostic model for pterygium. METHODS: For intelligent diagnosis of pterygium, the attention mechanisms—SENet, ECANet, CBAM, and Self-Attention—were fused with the lightweight MobileNetV2 model structure to construct a tri-classification model. The study used 1220 images of three types of anterior ocular segments of the pterygium provided by the Eye Hospital of Nanjing Medical University. Conventional classification models—VGG16, ResNet50, MobileNetV2, and EfficientNetB7—were trained on the same dataset for comparison. To evaluate model performance in terms of accuracy, Kappa value, test time, sensitivity, specificity, the area under curve (AUC), and visual heat map, 470 test images of the anterior segment of the pterygium were used. RESULTS: The accuracy of the MobileNetV2+Self-Attention model with 281 MB in model size was 92.77%, and the Kappa value of the model was 88.92%. The testing time using the model was 9ms/image in the server and 138ms/image in the local computer. The sensitivity, specificity, and AUC for the diagnosis of pterygium using normal anterior segment images were 99.47%, 100%, and 100%, respectively; using anterior segment images in the observation period were 88.30%, 95.32%, and 96.70%, respectively; and using the anterior segment images in the surgery period were 88.18%, 94.44%, and 97.30%, respectively. CONCLUSION: The developed model is lightweight and can be used not only for detection but also for assessing the severity of pterygium.

BackgroundDermatomyositis (DM) is an autoimmune disease that primarily affects the skin and muscles. It can lead to increased mortality, particularly when patients develop associated malignancies or experience fatal complications such as pulmonary fibrosis. Identifying reliable biomarkers is essential for the early diagnosis and treatment of DM. This study aims to identify and validate pivotal diagnostic biomarker for DM through integrated bioinformatics analysis and clinical sample validation.MethodsGene expression datasets GSE46239 and GSE142807 from the Gene Expression Omnibus (GEO) database were merged for analysis. Differentially expressed genes (DEGs) were identified and subjected to enrichment analysis. Advanced machine learning methods were utilized to further pinpoint hub genes. Weighted gene co‐expression network analysis (WGCNA) was also conducted to discover key gene modules. Subsequently, we derived intersection gene from these methods. The diagnostic performance of the candidate biomarker was evaluated using analysis with dataset GSE128314 and confirmed by immunohistochemistry (IHC) in skin lesion biopsy specimens. The CIBERSORT algorithm was used to analyze immune cell infiltration patterns in DM, then the association between the hub gene and immune cells was investigated. Gene set enrichment analysis (GSEA) was performed to understand the biomarker’s biological functions. Finally, the drug-gene interactions were predicted using the DrugRep server.ResultsInterferon-stimulated gene 15 (ISG15) was identified by intersecting DEGs, advanced machine learning-selected genes and key module genes from WGCNA. ROC analysis showed ISG15 had a high Area under the curve (AUC) of 0.950. IHC findings confirmed uniformly positive expression of ISG15, particularly in perivascular regions and lymphocytes, contrasting with universally negative expression in controls. Further analysis revealed that ISG15 is involved in abnormalities in various immune cells and inflammation-related pathways. We also predicted three drugs targeting ISG15, supported by molecular docking studies.ConclusionOur study identifies ISG15 as a highly specific diagnostic biomarker for DM, ISG15 may be closely related to the pathogenesis of DM, demonstrating promising potential for clinical application.

Testicular aging manifests as impaired spermatogenesis and morphological alterations in Drosophila. Nonetheless, the comprehensive molecular regulatory framework remains largely undisclosed. This investigation illustrates the impact of copper overload on testicular aging and underscores the interplay between copper overload and lncRNA. Copper overload triggers Cuproptosis through the mitochondrial TCA cycle, facilitating intracellular interactions with Ferroptosis, thereby governing testicular aging. Dysfunction of lncRNA:CR43306 also contributes to testicular aging in Drosophila, emphasizing the significance of lncRNA:CR43306 as a novel aging-associated lncRNA. Moreover, copper overload exacerbates spermatid differentiation defects mediated by lncRNA:CR43306 deficiency through oxidative stress, copper, and iron transport. Therapeutically, Ferrostatin-1 and Resveratrol emerge as potential remedies for addressing testicular aging. This study offers perspectives on the regulatory mechanisms involving copper overload and lncRNA:CR43306 deficiency in the context of testicular aging.

Metagenomic shotgun sequencing data can identify microbes and their proportions. But metagenomic shotgun data profiling results obtained from multiple projects using different reference databases are difficult to compare and apply meta-analysis. Our work aims to create a novel collection of human gut prokaryotic genomes, named Microbiome Collection Navigator (MBCN). 2379 human gut metagenomic samples are screened, and 16,785 metagenome-assembled genomes (MAGs) are assembled using a standardized pipeline. In addition, MAGs are combined with the representative genomes from public prokaryotic genomes collections to cluster, and pan-genomes for each cluster's genomes are constructed to build Kraken2 and Bracken databases. The databases built by MBCN are more comprehensive and accurate for profiling metagenomic reads comparing with other collections on simulated reads and virtual bio-projects. We profile 1082 human gut metagenomic samples with MBCN database and organize profiles and metadata on the web program. Meanwhile, using MBCN as a reference database, we also develop a unified, standardized, and systematic metagenomic analysis pipeline and platform, named MicrobiotaCN (http://www.microbiota.cn) and common statistical and visualization tools for microbiome research are integrated into the web program. Taken together, MBCN and MicrobiotaCN can be a valuable resource and a powerful tool that allows researchers to perform metagenomic analysis by a unified pipeline efficiently.

Tripartite motif-containing protein 59 (TRIM59) is a biomarker for multiple tumors with crucial roles. However, the specific role of TRIM59 in germ cells remains largely unknown. Here, we investigated the effects and underlying regulatory mechanisms of TRIM59 on germ cells using the mouse spermatogonial cell line GC-1. Our results demonstrated that TRIM59 promoted proliferation and inhibited apoptosis of GC-1 cells. Mechanistically, TRIM59 maintained GC-1 cell behaviors through ubiquitination of AXIN1 to activate β-catenin signaling. Furthermore, activation of β-catenin signaling reversed the effects mediated by Trim59 knockdown in GC-1 cells. Collectively, our study revealed a major role and regulatory mechanism of TRIM59 in GC-1 cells, which sheds new light on the molecular pathogenesis of defects in spermatogenesis and may provide therapeutic targets for treatment of male infertility.

Randomized clinical trials (RCTs) of PCSK9 monoclonal antibody(mAb) specifically for Chinese patients have been limited. This multi-center RCT is to clarify the efficacy and safety of a novel mAb, Ebronucimab, in Chinese patients. Patients diagnosed with primary hypercholesterolemia, including Heterozygous Familial Hypercholesterolemia, or mixed dyslipidemia, were categorized by ASCVD risk and randomly assigned at a ratio of 2:1:2:1 to receive Ebronucimab 450 mg or matching placebo every 4 weeks (Q4W), or Ebronucimab 150 mg or matching placebo every 2 weeks (Q2W). The primary outcome was the percentage change of LDL-C from baseline to week 12 for all groups. The least squares mean reduction difference (95 %CI) in LDL-C from baseline to week 12 of Ebronucimab 450 mg Q4W and Ebronucimab 150 mg Q2W groups versus the placebo group was −59.13 (-64.103, −54.153) (Adjusted p

Nitrogen oxides (NOx), significant contributors to air pollution and climate change, form aerosols and ozone in the atmosphere. Accurate, timely, and transparent information on NOx emissions is essential for decision-making to mitigate both haze and ozone pollution. However, a comprehensive understanding of the trends and drivers behind anthropogenic NOx emissions from China—the world's largest emitter—has been lacking since 2020 due to delays in emissions reporting. Here we show a consistent decline in China's NOx emissions from 2020 to 2022, despite increased fossil fuel consumption, utilizing satellite observations as constraints for NOx emission estimates through atmospheric inversion. This reduction is corroborated by data from two independent spaceborne instruments: the TROPOspheric Monitoring Instrument (TROPOMI) and the Ozone Monitoring Instrument (OMI). Notably, a reduction in transport emissions, largely due to the COVID-19 lockdowns, slightly decreased China's NOx emissions in 2020. In subsequent years, 2021 and 2022, reductions in NOx emissions were driven by the industry and transport sectors, influenced by stringent air pollution controls. The satellite-based inversion system developed in this study represents a significant advancement in the real-time monitoring of regional air pollution emissions from space.

RING finger 187 (RNF187), a ubiquitin-ligating (E3) enzyme, plays a crucial role in the proliferation of cancer cells. However, it remains unclear whether RNF187 exhibits comparable functionality in the development of germline cells. To investigate the potential involvement of RNF187 in germ cell development, we conducted interference and overexpression assays using GC-2 cells, a mouse spermatocyte-derived cell line. Our findings reveal that the interaction between RNF187 and histone H3 increases the viability, proliferation, and migratory capacity of GC-2 cells. Moreover, we provide evidence demonstrating that RNF187 interacts with H3 and mediates the ubiquitination of H3 at lysine 57 (K57) or lysine 80 (K80), directly or indirectly resulting in increased cellular transcription. This is a study to report the role of RNF187 in maintaining the development of GC-2 cells by mediating histone H3 ubiquitination, thus highlighting the involvement of the K57 and K80 residues of H3 in the epistatic regulation of gene transcription. These discoveries provide a new theoretical foundation for further comprehensive investigations into the function of RNF187 in the reproductive system.

Freeze-thaw cycles (FTC) cause significant changes in the physical and mechanical properties of soil, leading to structural alterations that can seriously threaten the safety and longevity of engineering structures. To investigate the consolidation characteristics of soils subjected to FTC, 18 sets of consolidation compression tests were carried out with saturated clay. Using a modified consolidation apparatus, the changes in pore-water pressure (PWP) and strain during consolidation were measured, with a focus on the effects of dry density and the number of FTC. The results show that although the overall patterns of PWP and strain during consolidation are similar before and after FTC, variations in dry density and the number of FTC lead to significant differences in the measured values. Specifically, PWP decreases while soil deformation increases with an increasing number of FTC cycles, even across different dry density conditions. The most pronounced changes in PWP and strain occur during the first 1–3 FTC cycles, with some samples showing continued significant changes up to 3–5 cycles. However, beyond five FTC, the increments in PWP and strain become considerably smaller. Meanwhile, an approximate linear relationship was observed between the peak PWP and steady-state strain values during graded loading, with this linearity decreasing as dry density increases. In addition, the Burgers model was modified based on the measured dissipation pattern of PWP to overcome the shortcomings of the traditional Burgers model. The modified Burgers model provides a more accurate representation of the soil's deformation process following FTC compared to the traditional model. This study can provide theoretical guidance for predicting the deformation of soils after freeze-thaw cycles.

Seasonal influenza remains a significant public health concern globally, with annual vaccinations as the most effectively preventive measure. This study examines influenza vaccination coverage rates across different age groups in Pudong New Area, Shanghai, China, from 2013 to 2023. This study extracted influenza vaccination data from the Shanghai Immunization Planning Information System (SIPIS) of the Center for Disease Control and Prevention Shanghai’s Pudong New Area from 2013 to 2023. The analysis utilized weighted linear regression to compare vaccination rates over the study period. From 2013 to 2023, a cumulative total of 1,421,295 influenza vaccinations were administered in Pudong New Area, with the quadrivalent inactivated influenza vaccines (IIV4) and trivalent inactivated influenza vaccines (IIV3) comprising 56.8% and 42.9%, respectively. The overall average influenza vaccine coverage rate was 2.27% (95% CI: 2.26, 2.28). The 0–4 years group exhibited the highest average annual coverage rate of 22.52% (95% CI: 22.47, 22.57) among different age groups, in stark contrast to that of the 20–24 years age group, which had the lowest at 0.32% (95% CI: 0.31, 0.33). In terms of repeat vaccinations, a significant majority (86.87%) of recipients received only 1–2 doses, while just 13.13% received 3 or more doses. Although influenza vaccination coverage among preschool children in Pudong New Area is relatively high, it falls significantly short of WHO recommendations. Enhance the level of awareness of influenza vaccine among adults and provide a free influenza vaccination strategy for specific groups such as doctors, which is helpful to increase influenza vaccination rates among populations.

Abstract With the increasing incidence of kidney diseases, there is an urgent need to develop therapeutic strategies to combat post‐injury fibrosis. Immune cells, including platelets, play a pivotal role in this repair process, primarily through their released cytokines. However, the specific role of platelets in kidney injury and subsequent repair remains underexplored. Here, the detrimental role of platelets in renal recovery following ischemia/reperfusion injury and its contribution to acute kidney injury to chronic kidney disease transition is aimed to investigated. In this study, it is shown that depleting platelets accelerates injury resolution and significantly reduces fibrosis. Employing advanced single‐cell and spatial transcriptomic techniques, macrophages as the primary mediators modulated by platelet signals is identified. A novel subset of macrophages, termed “cycling M2”, which exhibit an M2 phenotype combined with enhanced proliferative activity is uncovered. This subset emerges in the injured kidney during the resolution phase and is modulated by platelet‐derived thrombospondin 1 (THBS1) signaling, acquiring profibrotic characteristics. Conversely, targeted inhibition of THBS1 markedly downregulates the cycling M2 macrophage, thereby mitigating fibrotic progression. Overall, this findings highlight the adverse role of platelet THBS1‐boosted cycling M2 macrophages in renal injury repair and suggest platelet THBS1 as a promising therapeutic target for alleviating inflammation and kidney fibrosis.

University students predominantly spend their time indoors, where prolonged exposure raises the risk of contact with microorganisms of concern. However, our knowledge about the microbial community characteristics on university campus and their underpinnings is limited. To address it, we characterized bacterial communities from the surfaces of various built environments typical of a university campus, including cafeterias, classrooms, dormitories, offices, meeting rooms, and restrooms, in addition to human skin. The classrooms harbored the highest α-diversity, while the cafeterias had the lowest α-diversity. The bacterial community composition varied significantly across different building types. Proteobacteria, Actinobacteria, Firmicutes, Bacteroidetes, and Cyanobacteria were common phyla in university buildings, accounting for more than 90 % of total abundance. Staphylococcus aureus was the most abundant potential pathogen in classrooms, dormitories, offices, restrooms, and on human skin, indicating a potential risk for skin disease infections in these buildings. We further developed a new quantitative pathogenic risk assessment method according to the threat of pathogens to humans and found that classrooms exhibited the highest potential risk. The fast expectation-maximization algorithm identified 59 %-86 % of bacterial sources in buildings, with the human skin as the largest bacterial source for most buildings. As the sources of bacteria were highly traceable, we showed that homogeneous selection, dispersal limitation, and ecological drift were major ecological forces that drove community assembly. Our findings have important implications for predicting the distribution and sources of indoor dust bacterial communities on university campus.

Background: Despite the known reproductive toxicity induced by triptolide (TP) exposure, the regulatory mechanism underlying testicular vacuolization injury caused by TP remains largely obscure. Methods: Male mice were subjected to TP at doses of 15, 30, and 60 μg/kg for 35 consecutive days. Primary Sertoli cells were isolated from 20-day-old rat testes and exposed to TP at concentrations of 0, 40, 80, 160, 320, and 640 nM. A Biotin tracer assay was conducted to assess the integrity of the blood–testis barrier (BTB). Transepithelial electrical resistance (TER) assays were employed to investigate BTB function in primary Sertoli cells. Histological structures of the testes and epididymides were stained with hematoxylin and eosin (H&E). The expression and localization of relevant proteins or pathways were assessed through Western blotting or immunofluorescence staining. Results: TP exposure led to dose-dependent testicular injuries, characterized by a decreased organ coefficient, reduced sperm concentration, and the formation of vacuolization damage. Furthermore, TP exposure disrupted BTB integrity by reducing the expression levels of tight junction (TJ) proteins in the testes without affecting basal ectoplasmic specialization (basal ES) proteins. Through the TER assay, we identified that a TP concentration of 160 nM was optimal for elucidating BTB function in primary Sertoli cells, correlating with reductions in TJ protein expression. Moreover, TP exposure induced changes in the distribution of the BTB and cytoskeleton-associated proteins in primary Sertoli cells. By activating the AKT/mTOR signaling pathway, TP exposure disturbed the balance between mTORC1 and mTORC2, ultimately compromising BTB integrity in Sertoli cells. Conclusion: This investigation sheds light on the impacts of TP exposure on testes, elucidating the mechanism by which TP exposure leads to testicular vacuolization injury and offering valuable insights into comprehending the toxic effects of TP exposure on testes.

Wastewater treatment is an important source of greenhouse gases (GHGs). Yet large uncertainties remain in the quantification of GHG emissions from municipal wastewater treatment plants (MWWTPs) in China. A high-resolution and technology-specific emission inventory is still lacking to support mitigation strategies of MWWTPs. Here we develop a plant-level and technology-based MWWTP emission inventory for China covering 8703 plants and 19 treatment technology categories by compiling and harmonizing the most up-to-date facility-level databases. China's methane (CH4) and nitrous oxide (N2O) emissions from MWWTPs in 2020 are estimated to be 150.6 Gg and 22.0 Gg, respectively, with the uncertainty range of −30% to 37% and −30% to 26% at 95% confidence interval. We find an emission inequality across cities, with the richest cities emitting two times more CH4 and N2O per capita from municipal wastewater treatment than the poorest cities. The emitted CH4 and N2O are dominated by Anaerobic/Anoxic/Oxic-, Sequencing Batch Reactor-, Oxidation Ditch-, and Anoxic/Oxic-based MWWTPs of less than 20 years old. Considering the relatively young age structure of China's MWWTPs, the committed emissions highlight the importance of reducing on-site GHG emissions by optimization of operating conditions and innovation management. The emission differences among our estimates, previous studies, and the Intergovernmental Panel on Climate Change guidelines are largely attributed to the uncertainties in emission factors, implying the urgent need for more plant-integrated measurements to improve the accuracy of emission accounting.

Granuloma formation is generally correlated with infection. Pulmonary granulomas caused by foreign bodies aspiration are uncommon. The clinical and radiologic features of such cases often lack specificity, which makes it difficult to distinguish from malignancy. Aspiration is usually not considered in the differential diagnosis of patients presenting with mass-like abnormalities on chest imaging. Occult aspiration history, diverse clinical manifestations, atypical imaging findings, and limited availability of pathogen detection techniques make the precise diagnosis a substantial challenge. Herein, we describe an older patient presenting with chest pain and worrisome lung masses/nodules that proved to be pulmonary granulomas caused by foreign matters aspiration. In addition, the patient developed Mendelson syndrome due to acute macroaspiration. Lung tissue metagenomics next-generation sequencing (mNGS) revealed Streptococcus intermedius, a normal flora of the oropharynx. The aim of this case was to underscore the importance of considering aspiration as a potential differential diagnosis of patients presenting with pulmonary granulomas, especially in patients with recurrent pneumonia or predisposing factors. In addition, mNGS act as a potential, rapid, and effective technique for diagnosing aspiration-related syndrome, showing satisfactory performance in identifying pathogens.

Real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) plays a crucial role in relative gene expression analysis, and accurate normalization relies on suitable reference genes (RGs). In this study, a pipeline for identifying candidate RGs from publicly available stem-related RNA-Seq data of different Populus species under various developmental and abiotic stress conditions is presented. DESeq2's median of ratios yielded the smallest coefficient of variance (CV) values in a total of 292 RNA-Seq samples and was therefore chosen as the method for sample normalization. A total of 541 stably expressed genes were retrieved based on the CV values with a cutoff of 0.3. Universal gene-specific primer pairs were designed based on the consensus sequences of the orthologous genes of each Populus RG candidate. The expression levels of 12 candidate RGs and six reported RGs in stems under different abiotic stress conditions or in different Populus species were assessed by RT-qPCR. The expression stability of selected genes was further evaluated using ΔCt, geNorm, NormFinder, and BestKeeper. All candidate RGs were stably expressed in different experiments and conditions in Populus. A test dataset containing 117 RNA-Seq samples was then used to confirm the expression stability, six candidate RGs and three reported RGs met the requirement of CV ≤ 0.3. In summary, this study was to propose a systematic and optimized protocol for the identification of constitutively and stably expressed genes based on RNA-Seq data, and Potri.001G349400 (CNOT2) was identified as the best candidate RG suitable for gene expression studies in poplar stems.

Purpose: We aimed to develop an artificial intelligence-based myopic maculopathy grading method using EfficientNet to overcome the delayed grading and diagnosis of different myopic maculopathy degrees. Methods: The cooperative hospital provided 4642 healthy and myopic maculopathy color fundus photographs, comprising the four degrees of myopic maculopathy and healthy fundi. The myopic maculopathy grading models were trained using EfficientNet-B0 to EfficientNet-B7 models. The diagnostic results were compared with those of the VGG16 and ResNet50 classification models. The leading evaluation indicators were sensitivity, specificity, F1 score, area under the receiver operating characteristic (ROC) curve area under curve (AUC), 95% confidence interval, kappa value, and accuracy. The ROC curves of the ten grading models were also compared. Results: We used 1199 color fundus photographs to evaluate the myopic maculopathy grading models. The size of the EfficientNet-B0 myopic maculopathy grading model was 15.6 MB, and it had the highest kappa value (88.32%) and accuracy (83.58%). The model's sensitivities to diagnose tessellated fundus (TF), diffuse chorioretinal atrophy (DCA), patchy chorioretinal atrophy (PCA), and macular atrophy (MA) were 96.86%, 75.98%, 64.67%, and 88.75%, respectively. The specificity was above 93%, and the AUCs were 0.992, 0.960, 0.964, and 0.989, respectively. Conclusion: The EfficientNet models were used to design grading diagnostic models for myopic maculopathy. Based on the collected fundus images, the models could diagnose a healthy fundus and four types of myopic maculopathy. The models might help ophthalmologists to make preliminary diagnoses of different degrees of myopic maculopathy.

Abstract Introduction Invasive Escherichia coli disease (IED) can lead to sepsis and death and is associated with a substantial burden. Yet, there is scarce information on the burden of IED in Asian patients. Methods This retrospective study used US hospital data from the PINC AI™ Healthcare database (October 2015–March 2020) to identify IED cases among patients aged ≥ 60 years. IED was defined as a positive E. coli culture in blood or other normally sterile body site (group 1 IED) or positive culture of E. coli in urine with signs of sepsis (group 2 IED). Eligible patients with IED were classified into Asian and non-Asian cohorts based on their reported race. Entropy balancing was used to create cohorts with similar characteristics. Outcomes following IED were descriptively reported in the balanced cohorts. Results A total of 646 Asian and 19,127 non-Asian patients with IED were included (median age 79 years; 68% female after balancing). For both cohorts, most IED encounters had community-onset (> 95%) and required hospitalization (Asian 96%, mean duration 6.9 days; non-Asian 95%, mean duration 6.8 days), with frequent admission to intensive care (Asian 35%, mean duration 3.3 days; non-Asian 34%, mean duration 3.5 days), all standardized differences [SD]

Abstract Lung squamous cell carcinoma (LUSC) is the second most common lung cancer worldwide, leading to millions of deaths annually. Although immunotherapy has expanded the therapeutic choices for LUSC and achieved considerable efficacy in a subset of patients, many patients could not benefit, and resistance was pervasive. Therefore, it is significant to investigate the mechanisms leading to patients’ poor response to immunotherapies and explore novel therapeutic targets. Using multiple public LUSC datasets, we found that Kallikrein-8 (KLK8) expression was higher in tumor samples and was correlated with inferior survival. Using a LUSC cohort (n = 190) from our center, we validated the bioinformatic findings about KLK8 and identified high KLK8 expression as an independent risk factor for LUSC. Function enrichment showed that several immune signaling pathways were upregulated in the KLK8 low-expression group and downregulated in the KLK8 high-expression group. For patients with low KLK8 expression, they were with a more active TME, which was both observed in the TCGA database and immune marker immunohistochemistry, and they had extensive positive relations with immune cells with tumor-eliminating functions. This study identified KLK8 as a risk factor in LUSC and illustrated the associations between KLK8 and cancer immunity, suggesting the potentiality of KLK8 as a novel immune target in LUSC.

Abstract Background Delamanid and bedaquiline are two of the most recently developed antituberculosis (TB) drugs that have been extensively studied in patients with multidrug-resistant TB. There is currently a need for more potent, less-toxic drugs with novel mechanisms of action that can be used in combination with these newer agents to shorten the duration of treatment as well as prevent the development of drug resistance. Quabodepistat (QBS) is a newly discovered inhibitor of decaprenylphosphoryl-β-D-ribose-2′-oxidase, an essential enzyme for Mycobacterium tuberculosis to synthesize key components of its cell wall. The objective of this study is to evaluate the safety, efficacy, and appropriate dosing of a 4-month regimen of QBS in combination with delamanid and bedaquiline in participants with drug-susceptible pulmonary TB in comparison with the 6-month standard treatment (i.e., rifampicin, isoniazid, ethambutol, and pyrazinamide). Methods This phase 2b/c, open-label, randomized, parallel group, dose-finding trial will enroll approximately 120 participants (including no more than 15% with human immunodeficiency virus [HIV] coinfection) aged ≥ 18 to ≤ 65 years at screening with newly diagnosed pulmonary drug-sensitive TB from ~8 sites in South Africa. Following a screening period of up to 14 days, eligible participants will be randomized in a ratio of 1:2:2:1 to one of four arms. Randomization will be stratified by HIV status and the presence of bilateral cavitation on a screening chest x-ray. After the end of the treatment period, participants will be followed until 12 months post randomization. The primary efficacy endpoint is the proportion of participants achieving sputum culture conversion in Mycobacteria Growth Indicator Tube by the end of the treatment period. The safety endpoints consist of adverse events, clinical laboratory tests, vital signs, physical examination findings, and electrocardiographic changes. Discussion QBS’s potent bactericidal activity and distinct mechanism of action (compared with other TB drugs currently available for human use) may make it an ideal candidate for inclusion in a novel treatment regimen to improve efficacy and potentially prevent resistance to concomitant TB drugs. This trial will assess the effectiveness, safety, and dosing of a new, shorter, QBS-based, combination anti-TB treatment regimen. Trial status ClinicalTrials.gov NCT05221502. Registered on February 3, 2022

Abstract Emissions from fossil fuel exploitation are a leading contributor to global anthropogenic methane emissions, but are highly uncertain. The lack of reliable estimates hinders monitoring of the progress on pledges towards methane reductions. Here we analyze methane emissions from exploitation of coal, oil and gas for major producing nations across a suite of bottom-up inventories and global inversions. Larger disagreement in emissions exists for the oil/gas sector across the inventories compared to coal, arising mostly from disparate data sources for emission factors. Moreover, emissions reported to the United Nations Framework Convention on Climate Change are lower than other bottom-up and inversion estimates, with many countries lacking reporting in the past decades. Finally, comparison with previous global inversions, revealed a strong influence of the prior inventory on the inferred sub-sectoral emissions magnitude. This study highlights the need to improve consensus on the methodological inputs among the bottom-up inventories in order to obtain more consistent inverse modelling results at the sub-sectoral level.

Abstract Background Polycystic ovary syndrome (PCOS) has unusual levels of hormones. The hormone receptors in the endometrium have a hostile effect and make the microenvironment unfavorable for embryo implantation. The use of gonadotropin stimulation during in vitro fertilization (IVF) may have an impact on embryo implantation and live birth rate. According to recent data, the clinical results of day 4 embryo transfer (D4 transfer) were on par with those of day 5 embryo transfer (D5 transfer) in IVF-ET. There are few studies comparing the outcomes of transplants with various etiologies and days. The purpose of this study was to determine which transfer day had the best result for PCOS patients undergoing IVF. Methods This retrospective cohort study was conducted in the Xingtai Infertility Specialist Hospital between January 2017 and November 2021. A total of 1,664 fresh ART cycles met inclusion criteria, including 242 PCOS transfers and 1422 tubal factor infertility transfers. Conclusions PCOS individuals had the highest live birth rate on D4 transferred. It was not need to culture embryos to blastocysts to optimize embryo transfer for PCOS women. This could be a novel approach to transplantation for PCOS.

The accurate identification of tomato maturity and picking positions is essential for efficient picking. Current deep-learning models face challenges such as large parameter sizes, single-task limitations, and insufficient precision. This study proposes MTS-YOLO, a lightweight and efficient model for detecting tomato fruit bunch maturity and stem picking positions. We reconstruct the YOLOv8 neck network and propose the high- and low-level interactive screening path aggregation network (HLIS-PAN), which achieves excellent multi-scale feature extraction through the alternating screening and fusion of high- and low-level information while reducing the number of parameters. Furthermore, We utilize DySample for efficient upsampling, bypassing complex kernel computations with point sampling. Moreover, context anchor attention (CAA) is introduced to enhance the model’s ability to recognize elongated targets such as tomato fruit bunches and stems. Experimental results indicate that MTS-YOLO achieves an F1-score of 88.7% and an mAP@0.5 of 92.0%. Compared to mainstream models, MTS-YOLO not only enhances accuracy but also optimizes the model size, effectively reducing computational costs and inference time. The model precisely identifies the foreground targets that need to be harvested while ignoring background objects, contributing to improved picking efficiency. This study provides a lightweight and efficient technical solution for intelligent agricultural picking.

AimConventional approaches to diagnosing common eye diseases using B-mode ultrasonography are labor-intensive and time-consuming, must requiring expert intervention for accuracy. This study aims to address these challenges by proposing an intelligence-assisted analysis five-classification model for diagnosing common eye diseases using B-mode ultrasound images.MethodsThis research utilizes 2064 B-mode ultrasound images of the eye to train a novel model integrating artificial intelligence technology.ResultsThe ConvNeXt-L model achieved outstanding performance with an accuracy rate of 84.3% and a Kappa value of 80.3%. Across five classifications (no obvious abnormality, vitreous opacity, posterior vitreous detachment, retinal detachment, and choroidal detachment), the model demonstrated sensitivity values of 93.2%, 67.6%, 86.1%, 89.4%, and 81.4%, respectively, and specificity values ranging from 94.6% to 98.1%. F1 scores ranged from 71% to 92%, while AUC values ranged from 89.7% to 97.8%.ConclusionAmong various models compared, the ConvNeXt-L model exhibited superior performance. It effectively categorizes and visualizes pathological changes, providing essential assisted information for ophthalmologists and enhancing diagnostic accuracy and efficiency.

China is now confronting the intertwined challenges of air pollution and climate change. Given the high synergies between air pollution abatement and climate change mitigation, the Chinese government is actively promoting synergetic control of these two issues. The Synergetic Roadmap project was launched in 2021 to track and analyze the progress of synergetic control in China by developing and monitoring key indicators. The Synergetic Roadmap 2022 report is the first annual update, featuring 20 indicators across five aspects: synergetic governance system and practices, progress in structural transition, air pollution and associated weather-climate interactions, sources, sinks, and mitigation pathway of atmospheric composition, and health impacts and benefits of coordinated control. Compared to the comprehensive review presented in the 2021 report, the Synergetic Roadmap 2022 report places particular emphasis on progress in 2021 with highlights on actions in key sectors and the relevant milestones. These milestones include the proportion of non-fossil power generation capacity surpassing coal-fired capacity for the first time, a decline in the production of crude steel and cement after years of growth, and the surging penetration of electric vehicles. Additionally, in 2022, China issued the first national policy that synergizes abatements of pollution and carbon emissions, marking a new era for China's pollution-carbon co-control. These changes highlight China's efforts to reshape its energy, economic, and transportation structures to meet the demand for synergetic control and sustainable development. Consequently, the country has witnessed a slowdown in carbon emission growth, improved air quality, and increased health benefits in recent years.

BackgroundThe coronary angiography-derived index of microvascular resistance (caIMR) correlates well with the index of microcirculatory resistance (IMR), which predicts microvascular obstruction (MVO). However, the relationship between caIMR and MVO remains unclear.AimTo evaluate the predictive ability of caIMR of MVO after ST-segment elevation myocardial infarction (STEMI).MethodsCaIMR was calculated using computational flow and pressure simulation in patients with STEMI in whom MVO status had been assessed by cardiac magnetic resonance (CMR) after successful primary percutaneous intervention at Peking University First Hospital between December 2016 and August 2019. The clinical, biochemical, echocardiographic, and CMR characteristics were assessed according to MVO status. The predictive value of the clinical parameters and caIMR was evaluated.ResultsFifty-three eligible patients were divided into an MVO group (n = 32) and a no-MVO group (n = 21). The caIMR tended to be higher in the MVO group (41.6 U vs. 30.1 U; p = 0.136). CaIMR and peak cardiac troponin-I (cTNI) were independent predictors of MVO (per 1-U increment in caIMR: odds ratio [OR] 1.044, 95% confidence interval [CI] 1.004–1.086, p = 0.030; per 1 ng/L increase in peak cTNI: OR 1.018, 95% CI 1.003–1.033, p = 0.022). In receiver-operating characteristic curve analysis, when a cut-off value of 45.17 U was used, caIMR had some ability to predict MVO (area under the curve 0.622, 95% CI 0.478–0.752, p = 0.127).ConclusionsCaIMR and peak cTNI were independent predictors of short-term MVO in patients with STEMI who had undergone successful primary percutaneous coronary intervention and may help to identify those at high risk of MVO.

Introduction To characterise age-mixing patterns among index cases and contacts of COVID-19, and explore when patients are most infectious during the disease process.Methods This study examined all initial 90 885 confirmed index cases in Shanghai and their 450 770 close contacts. A generalised additive mixed model was used to analyse the associations of the number of close contacts with different demographic and clinical characteristics. The effect of different exposure time windows on the infection of close contacts was evaluated using a modified mixed-effects Poisson regression.Results Analysis of contacts indicated that 82 467 (18.29%; 95% CI 18.17%, 18.42%) were second-generation cases. Our result indicated the q-index was 0.300 (95% CI 0.298, 0.302) for overall contact matrix, and that assortativity was greatest for students (q-index=0.377; 95% CI 0.357, 0.396) and weakest for people working age not in the labour force (q-index=0.246; 95% CI 0.240, 0.252). The number of contacts was 4.96 individuals per index case (95% CI 4.86, 5.06). Contacts had a higher risk if they were exposed from 1 day before to 3 days after the onset of symptoms in the index patient, with a maximum at day 0 (adjusted relative risk (aRR)=1.52; 95% CI 1.30, 1.76). Contacts exposed from 3 days before to 3 days after an asymptomatic index case had a positive reverse transcriptase-PCR (RT-PCR) result had a higher risk, with a maximum on day 0 (aRR=1.48; 95% CI 1.37, 1.59).Conclusions The greatest assortativity was for students and weakest for people working age not in the labour force. Contact in the household was a significant contributor to the infection of close contacts. Contact tracing should focus on individuals who had contact soon before or soon after the onset of symptoms (or positive RT-PCR test) in the index case.

In the history of country park studies, little attention has been given to evaluating the vitality of country parks, the comprehensive ecological, living and production benefits of country park construction, and the change in the carbon emission effect. The goal of this article will be to address these three issues. Based on multisource data, a country park vitality index system, regional comprehensive benefit evaluation index system and land use carbon emission estimation model were constructed to conduct quantitative estimation. The results showed that (1) the popularity index rather than the accessibility index was the key component of the vitality of country parks, followed by the connectivity index and the land use diversity index. (2) Ecological space and public open space in most of the whole land consolidation areas that centred on country park construction were significantly expanded, traffic accessibility and housing conditions were significantly improved, population agglomeration and landscape diversity index tended to increase, and the comprehensive goal of synergistic improvement in production, living and ecological benefits was achieved. (3) The whole land consolidation area dominated by country park construction had a better carbon emission reduction effect. Reducing inefficient construction land and increasing forestland are important measures to reduce carbon sources and increase carbon sinks. The results of this study have guiding value for the improvement of country park planning and construction and the optimization of the whole land consolidation area in Shanghai.

Abstract Background Numerous studies have demonstrated the potential of pirfenidone to enhance the prognosis of patients afflicted with idiopathic pulmonary fibrosis (IPF). Although N-acetylcysteine (NAC) is utilized as an antioxidant in IPF treatment, the combination of NAC and pirfenidone has produced inconsistent outcomes in certain studies. To assess the clinical effectiveness and safety of NAC plus pirfenidone (designated as the treatment group) versus pirfenidone monotherapy (designated as the control group), we conducted a systematic review and meta-analysis of randomized controlled trials (RCTs). Methods RCTs of NAC plus pirfenidone were reviewed searching from databases and networks of unpublished and published studies in any language. Using pair-wise meta-analysis, changes in pulmonary function test (PFT) parameters and safety were evaluated. Results Two independent reviewers selected and obtained data from 5 RCTs (n = 398), comprising 1 study from Japan, 1 from Europe, and 3 from China. NAS plus pirfenidone as compared to pirfenidone monotherapy for IPF may not reduce the incidence of skin effects(RR 1.26 [95%CI 0.64 to 2.45]) and mortality(RR 0.35 [95%CI 0.07 to 1.68])(both moderate certainty). NAS plus pirfenidone as compared to pirfenidone monotherapy for IPF may not reduce the incidence of at least one side effects(RR 1.00 [95%CI 0.84 to 1.19]; low certainty),severe side effects(RR 0.67 [95%CI 0.30 to 1.47]; low certainty) and gastrointestinal effects(RR 0.67 [95%CI 0.41 to 1.09]; low certainty) with possibly no effect in Δ%DLco(SMD -0.17 [95%CI -0.15 to 0.48]; low certainty). Meanwhile, the effect of NAS plus pirfenidone as compared to pirfenidone monotherapy on ΔFVC(SMD 0.18 [95%CI -0.68 to 1.05]), Δ%FVC(SMD -2.62 [95%CI -5.82 to 0.59]) and Δ6MWT(SMD -0.35 [95%CI -0.98 to 0.28]) is uncertain(extremely low certainty). Conclusion Moderate certainty evidence suggests that NAS plus pirfenidone, compared to pirfenidone monotherapy for IPF, does not reduce the incidence of skin effects and mortality.

Pterygium is a prevalent ocular disease that can cause discomfort and vision impairment. Early and accurate diagnosis is essential for effective management. Recently, artificial intelligence (AI) has shown promising potential in assisting clinicians with pterygium diagnosis. This paper provides an overview of AI-assisted pterygium diagnosis, including the AI techniques used such as machine learning, deep learning, and computer vision. Furthermore, recent studies that have evaluated the diagnostic performance of AI-based systems for pterygium detection, classification and segmentation were summarized. The advantages and limitations of AI-assisted pterygium diagnosis and discuss potential future developments in this field were also analyzed. The review aims to provide insights into the current state-of-the-art of AI and its potential applications in pterygium diagnosis, which may facilitate the development of more efficient and accurate diagnostic tools for this common ocular disease.

The freeze–thaw effect has a significant impact on the strength deterioration of tunnel-lining concrete in cold regions. Therefore, the strength deterioration characteristics of concrete in a tunnel were studied, and silicone coating materials were used to improve its frost resistance and durability under freeze–thaw cycles. Freeze–thaw cycle tests were conducted on concrete specimens with different coatings. The freeze–thaw damage phenomenon, dynamic elastic modulus, and mass loss of the specimens were used to evaluate the freeze–thaw durability of concrete strengthened with coatings. The results demonstrated that silicone coatings effectively prevented moisture and corrosive substances from infiltrating the concrete, thereby enhancing its durability; the silicone–polyether hybrid had the most significant frost resistance at 500 g/m2 and silane type III at 300 g/m2, with freezing resistance times of 175 and 300, respectively. During the freeze–thaw process, the strength reduction rate of specimens was much greater than the mass loss rate of concrete. Taking into account the water environment surrounding the lining concrete and the site temperature, an equivalent indoor freeze–thaw cycle conversion model was established. The results can provide an experimental basis for selecting better frost-resistant materials for tunnel concrete in cold regions.

Abstract. Background:. The HELIOS stent is a sirolimus-eluting stent with a biodegradable polymer and titanium oxide film as the tie-layer. The study aimed to evaluate the safety and efficacy of HELIOS stent in a real-world setting. Methods:. The HELIOS registry is a prospective, multicenter, cohort study conducted at 38 centers across China between November 2018 and December 2019. A total of 3060 consecutive patients were enrolled after application of minimal inclusion and exclusion criteria. The primary endpoint was target lesion failure (TLF), defined as a composite of cardiac death, non-fatal target vessel myocardial infarction (MI), and clinically indicated target lesion revascularization (TLR) at 1-year follow-up. Kaplan–Meier methods were used to estimate the cumulative incidence of clinical events and construct survival curves. Results:. A total of 2998 (98.0%) patients completed the 1-year follow-up. The 1-year incidence of TLF was 3.10% (94/2998, 95% closed interval: 2.54–3.78%). The rates of cardiac death, non-fatal target vessel MI and clinically indicated TLR were 2.33% (70/2998), 0.20% (6/2998), and 0.70% (21/2998), respectively. The rate of stent thrombosis was 0.33% (10/2998). Age ≥60 years, diabetes mellitus, family history of coronary artery disease, acute myocardial infarction at admission, and device success were independent predictors of TLF at 1 year. Conclusion:. The 1-year incidence rates of TLF and stent thrombosis were 3.10% and 0.33%, respectively, in patients treated with HELIOS stents. Our results provide clinical evidence for interventional cardiologists and policymakers to evaluate HELIOS stent. Clinical trial registration:. ClinicalTrials.gov, NCT03916432

AIM: To conduct a classification study of high myopic maculopathy (HMM) using limited datasets, including tessellated fundus, diffuse chorioretinal atrophy, patchy chorioretinal atrophy, and macular atrophy, and minimize annotation costs, and to optimize the ALFA-Mix active learning algorithm and apply it to HMM classification. METHODS: The optimized ALFA-Mix algorithm (ALFA-Mix+) was compared with five algorithms, including ALFA-Mix. Four models, including ResNet18, were established. Each algorithm was combined with four models for experiments on the HMM dataset. Each experiment consisted of 20 active learning rounds, with 100 images selected per round. The algorithm was evaluated by comparing the number of rounds in which ALFA-Mix+ outperformed other algorithms. Finally, this study employed six models, including EfficientFormer, to classify HMM. The best-performing model among these models was selected as the baseline model and combined with the ALFA-Mix+ algorithm to achieve satisfactory classification results with a small dataset. RESULTS: ALFA-Mix+ outperforms other algorithms with an average superiority of 16.6, 14.75, 16.8, and 16.7 rounds in terms of accuracy, sensitivity, specificity, and Kappa value, respectively. This study conducted experiments on classifying HMM using several advanced deep learning models with a complete training set of 4252 images. The EfficientFormer achieved the best results with an accuracy, sensitivity, specificity, and Kappa value of 0.8821, 0.8334, 0.9693, and 0.8339, respectively. Therefore, by combining ALFA-Mix+ with EfficientFormer, this study achieved results with an accuracy, sensitivity, specificity, and Kappa value of 0.8964, 0.8643, 0.9721, and 0.8537, respectively. CONCLUSION: The ALFA-Mix+ algorithm reduces the required samples without compromising accuracy. Compared to other algorithms, ALFA-Mix+ outperforms in more rounds of experiments. It effectively selects valuable samples compared to other algorithms. In HMM classification, combining ALFA-Mix+ with EfficientFormer enhances model performance, further demonstrating the effectiveness of ALFA-Mix+.

Abstract With the urgent need to implement the EU countries pledges and to monitor the effectiveness of Green Deal plan, Monitoring Reporting and Verification tools are needed to track how emissions are changing for all the sectors. Current official inventories only provide annual estimates of national CO2 emissions with a lag of 1+ year which do not capture the variations of emissions due to recent shocks including COVID lockdowns and economic rebounds, war in Ukraine. Here we present a near-real-time country-level dataset of daily fossil fuel and cement emissions from January 2019 through December 2021 for 27 EU countries and UK, which called Carbon Monitor Europe. The data are calculated separately for six sectors: power, industry, ground transportation, domestic aviation, international aviation and residential. Daily CO2 emissions are estimated from a large set of activity data compiled from different sources. The goal of this dataset is to improve the timeliness and temporal resolution of emissions for European countries, to inform the public and decision makers about current emissions changes in Europe.

Summary: Background: Liver cirrhosis (LC) is the highest risk factor for hepatocellular carcinoma (HCC) development worldwide. The efficacy of the guideline-recommended surveillance methods for patients with LC remains unpromising. Methods: A total of 4367 LCs not previously known to have HCC and 510 HCCs from 16 hospitals across 11 provinces of China were recruited in this multi-center, large-scale, cross-sectional study. Participants were divided into Stage Ⅰ cohort (510 HCCs and 2074 LCs) and Stage Ⅱ cohort (2293 LCs) according to their enrollment time and underwent Tri-phasic CT/enhanced MRI, US, AFP, and cell-free DNA (cfDNA). A screening model called PreCar Score was established based on five features of cfDNA using Stage Ⅰ cohort. Surveillance performance of PreCar Score alone or in combination with US/AFP was evaluated in Stage Ⅱ cohort. Findings: PreCar Score showed a significantly higher sensitivity for the detection of early/very early HCC (Barcelona stage A/0) in contrast to US (sensitivity of 51.32% [95% CI: 39.66%–62.84%] at 95.53% [95% CI: 94.62%–96.38%] specificity for PreCar Score; sensitivity of 23.68% [95% CI: 14.99%–35.07%] at 99.37% [95% CI: 98.91%–99.64%] specificity for US) (P

Globally, the power sector must undergo a profound transition to achieve the decarbonization development targets. Various roadmaps are implemented, but only from a macro perspective, lacking the consideration of the electricity market rules. In this paper, we develop and present a market-driven generation and transmission expansion planning (MGTEP) model considering the effectiveness of the electricity market. Specifically, generation and transmission companies incorporate hourly market trading and annual capacity investment into strategic decisions to maximize their profits, with the supply function equilibrium model to analyze bidding behaviors. An equivalent quadratic programming formulation is deployed to solve the trilevel MGTEP model. Meanwhile, the MGTEP model is coupled with decarbonization policies to support the state and federal government in assessing energy transition strategies. We implement the MGTEP model with carbon emission allowance and carbon tax policies for the southern China electricity market to achieve carbon peaking by 2030. Carbon emission allowance adopts an intensity-based cap based on generation companies' historical output. The case study results show that 50 % carbon emission allowance or 400 CNY/t carbon tax is required but with several drawbacks, including unsatisfactory decarbonization effect, excessive economic sacrifice, etc. Finally, the case study is extended to dual-track policies with different combinations of policies. An optimal combination is 70 % carbon emission allowance and 160 CNY/t carbon tax. In this case, the power sector's carbon dioxide emissions and electricity prices in the southern China electricity market would increase to 554.6 Mt and 864.34 CNY/MWh in 2030, respectively, along with a carbon price of 850 CNY/t.

The complex financial networks, with their nonlinear nature, often exhibit considerable noises, inhibiting the analysis of the market dynamics and portfolio optimization. Existing studies mainly focus on the application of the global motion filtering on the linear matrix to reduce the noise interference. To minimize the noise in complex financial networks and enhance timing strategies, we introduce an advanced methodology employing global motion filtering on nonlinear dynamic networks derived from mutual information. Subsequently, we construct investment portfolios, focusing on peripheral stocks in both the Chinese and American markets. We utilize the growth and decline patterns of the eigenvalue associated with the global motion to identify trends in collective market movement, revealing the distinctive portfolio performance during periods of reinforced and weakened collective movements and further enhancing the strategy performance. Notably, this is the first instance of applying global motion filtering to mutual information networks to construct an investment portfolio focused on peripheral stocks. The comparative analysis demonstrates that portfolios comprising peripheral stocks within global-motion-filtered mutual information networks exhibit higher Sharpe and Sortino ratios compared to those derived from global-motion-filtered Pearson correlation networks, as well as from full mutual information and Pearson correlation matrices. Moreover, the performance of our strategies proves robust across bearish markets, bullish markets, and turbulent market conditions. Beyond enhancing the portfolio optimization, our results provide significant potential implications for diverse research fields such as biological, atmospheric, and neural sciences.

The rock characteristic and size–frequency distribution (SFD) on Mars are important for understanding the geologic and geomorphic history of the surface, for evaluating the trafficability of roving, and for planning the potential infrastructure construction. Tianwen-1, China’s first autonomous Mars exploration mission, formed an excavated depression during touchdown, which has been the deepest depression on the Martian surface so far compared with others. According to the images captured using the Navigation and Terrain Cameras (NaTeCams) onboard the rover, Zhurong, the SFD of rocks is calculated and compared inside the excavated depression, within and out of the blast zone. For the first time, the rock size distribution inside the excavated depression is obtained, exposing the geological features of the shallow subsurface on Mars at a depth of tens of centimeters, which will surely be important for future drilling missions. It is found that the rock abundance in the depression is smaller than the original abundance on the surface, and the distribution of rocks in the blast zone on the surface is greatly influenced by the touchdown. In addition, based on the fractal dimension of rock sizes, the rocks (>10 mm) at the shallow subsurface of the Zhurong landing site may experience two different geological processes.

Temporary plugging and diversion fracturing technology play a vital role in boosting the production of tight reservoirs. The increase of net pressure in fractures is the core of temporary plugging diversion fracturing, which is closely related to the permeability of temporary plugging aggregates. However, the evolution of the permeability of temporary plugging bodies has received limited research attention. In this paper, a novel experimental system for evaluating the permeability capacity of temporary plugging agents is firstly established. This device allows us to measure critical parameters such as injection pressure, length and permeability of the temporary plugging body during the experimentation. Additionally, we assess the pressure-bearing capacity of the temporary plugging agent using a specialized experimental setup for temporarily plugging fractures. Throughout the experiment, we collect data on time consumption at different pressure levels and the volume of injected liquid. Furthermore, we conduct a comparative analysis of the pressure-bearing effects of five types of temporary plugging materials. Our experimental results reveal some interesting findings. Pure granular CDD-1 does not effectively form a substantial length, and we observe no significant relationship between the length and permeability of the temporary plugging body. In contrast, temporary plugging materials mainly composed of powder exhibit a uniform permeability of the temporary plugging body, blending both powder and particles. Moreover, temporary plugging bodies primarily formed by powder, uniform mixtures of powder and particles, and predominantly particle-based plugging bodies (with consideration of powder) demonstrate lower permeability, rendering them more favorable for temporary plugging purposes. This study sheds light on the permeability characteristics of different temporary plugging materials, contributing to a better understanding of their efficacy in temporary plugging and diversion fracturing applications. The findings could inform the selection and optimization of temporary plugging agents, ultimately enhancing the efficiency and success of tight reservoir production.

ABSTRACTA safe and effective vaccine is urgently needed to combat the global threat of multidrug-resistant (MDR) Neisseria gonorrhoeae. We screened 26 gonococcal proteins discovered by an artificial intelligence-driven platform called Efficacy Discriminative Educated Network (EDEN) trained to identify novel, protective vaccine antigens against pathogenic bacteria for efficacy in the mouse vaginal colonization model of gonorrhea. Combinations of two to three antigens adjuvanted with GLA-SE (induces TH1 responses) yielded 11 groups that were used to vaccinate mice. An inverse correlation was noted between the complement-dependent bactericidal activity of antisera from each of the 11 groups and the burden of gonococcal colonization. The combination of NGO1549 (FtsN; cell divisome protein) and NGO0265 (predicted cell division protein) most substantially reduced the burden of colonization by MDR strain WHO X. The EDEN prediction score for each group of antigens correlated positively with reductions in overall bacterial burden, providing evidence for its predictive potential. FtsN and NGO0265 administered either individually, in combination, or as a chimeric protein significantly attenuated gonococcal vaginal colonization by all three test strains. IgG in antisera from mice immunized with the chimeric NGO0265-FtsN protein supported the complement-dependent killing of all 50 (100%) gonococcal isolates tested. The efficacy of the chimeric NGO0265-FtsN vaccine required the membrane attack complex (C5b-9) of complement, evidenced by loss of efficacy in complement C9−/− mice. In conclusion, a chimeric molecule comprising NGO0265 and FtsN adjuvanted with GLA-SE elicits IgG with broad anti-gonococcal bactericidal activity, attenuates gonococcal colonization in a complement-dependent manner, and represents a promising gonococcal vaccine candidate.IMPORTANCEVaccines to curb the global spread of multidrug-resistant gonorrhea are urgently needed. Here, 26 vaccine candidates identified by an artificial intelligence-driven platform (Efficacy Discriminative Educated Network[EDEN]) were screened for efficacy in the mouse vaginal colonization model. Complement-dependent bactericidal activity of antisera and the EDEN protective scores both correlated positively with the reduction in overall bacterial colonization burden. NGO1549 (FtsN) and NGO0265, both involved in cell division, displayed the best activity and were selected for further development. Both antigens, when fused to create a chimeric protein, elicited bactericidal antibodies against a wide array of gonococcal isolates and significantly attenuated the duration and burden of gonococcal colonization of mouse vaginas. Protection was abrogated in mice that lacked complement C9, the last step in the formation of the membrane attack complex pore, suggesting complement-dependent bactericidal activity as a mechanistic correlate of protection of the vaccine. FtsN and NGO0265 represent promising vaccine candidates against gonorrhea.