Search

Abstract As a medium to understand the nature of glass transition, ultrastable glasses have garnered increasing attention for their significance in fundamental science and technological applications. Most studies have produced ultrastable glasses through a surface-controlled process using physical vapor deposition. Here, we demonstrate an approach to accessing ultrastable glasses via the glass-to-glass transition, a bulk transformation that is inherently free from size constraints and anisotropy. The resulting ultrastable glass exhibits a significantly enhanced density (improved by 2.3%), along with high thermodynamic, kinetic, and mechanical stability. Furthermore, we propose that this method of accessing ultrastable glasses is general for metallic glasses, based on the examination of the competitive relationship between the glass-to-glass transition and crystallization. This strategy is expected to facilitate the proliferation of the ultrastable glass family, helping to resolve the instability issues of glass materials and devices and deepen our understanding of glasses and the glass transition.

Abstract Background Alternative splicing (AS) is a process that facilitates the differential inclusion of exonic sequences from precursor messenger RNAs, significantly enhancing the diversity of the transcriptome and proteome. In cancer, pathogenic AS events are closely related to cancer progression. This study aims to investigate the role and regulatory mechanisms of AS in gastric cancer (GC). Methods We analyzed AS events in various tumor samples and identified hnRNPU as a key splicing factor in GC. The effects of hnRNPU on cancer progression were assessed through in vitro and in vivo experiments. Gene knockout models and the FTO inhibitor (meclofenamic acid) were used to validate the interaction between hnRNPU and FTO and their impact on AS. Results We found that hnRNPU serves as a key splicing factor in GC, and its high expression is associated with poor clinical prognosis. Genetic depletion of hnRNPU significantly reduced GC progression. Mechanistically, the m6A demethylase FTO interacts with hnRNPU transcripts, decreasing the m6A modification levels of hnRNPU, which leads to exon 14 skipping of the MET gene, thereby promoting GC progression. The FTO inhibitor meclofenamic acid effectively inhibited GC cell growth both in vitro and in vivo. Conclusion The FTO/hnRNPU axis induces aberrant exon skipping of MET, thereby promoting GC cell growth. Targeting the FTO/hnRNPU axis may interfere with abnormal AS events and provide a potential diagnostic and therapeutic strategy for GC. Graphical Abstract Schematic model for the findings of this work: Aberrant hnRNPU in GC binds FTO. The m6A-modified hnRNPU transcripts are recognized by m6A reader YTHDF3 and subsequently demethylated by FTO. This demethylation enhances the stability of hnRNPU mRNA, consequently promoting alternative splicing of MET. The altered splicing pattern ultimately contributes to the proliferation of GC cells.

Abstract Background The emergence of Multidrug-Resistant Tuberculosis (MDR-TB) poses a significant threat to global tuberculosis control efforts. This study aimed to examine the influence of mutations in Toxin-Antitoxin system genes on the global transmission of MDR-TB caused by Mycobacterium tuberculosis (M. tuberculosis). Methods Whole-genome sequencing was conducted on 13,518 M. tuberculosis isolates. Genes of the Toxin-Antitoxin system were obtained from the National Center for Biotechnology Information (NCBI) Gene database. Techniques such as Random Forest, Gradient Boosting Decision Tree, and Generalized Linear Mixed Models were employed to identify mutation sites in Toxin-Antitoxin system-related genes that facilitated the transmission of MDR-TB. Results 4,066 (30.08%) were identified as MDR-TB strains of all analyzed isolates. We found significant associations between specific gene mutations and MDR-TB transmission clusters including mutations in Rv0298 (G213A), Rv1959c (parE1, C88T), Rv1960c (parD1, C134T), Rv1991A (maze, G156A), Rv2547 (vapB, C54G), Rv2862A (vapB23, T2C), and Rv3385c (vapB46, G70A). Additionally, several gene mutations associated with MDR-TB transmission clades such as Rv1956 (higA, G445T), Rv1960c (parD1, C134T), and Rv1962A (vapB35, G99A) were noted. Certain gene mutations including vapB35 (G99A), higA (G445T), and parD1 (C134T) correlated with cross-regional transmission clades. Conclusion This study highlights the significant association between specific gene mutations in the Toxin-Antitoxin system and the global transmission of MDR-TB, providing valuable insights for developing targeted interventions to control MDR-TB.

Abstract Background Endometrial cancer (EC) presents significant clinical challenges due to its heterogeneity and complex pathophysiology. SAMHD1, known for its role as a deoxynucleotide triphosphate triphosphohydrolase, has been implicated in the progression of various cancers, including EC. This study focuses on elucidating the role of SAMHD1 in EC through its impact on TRIM27-mediated PTEN ubiquitination. Results Utilizing a combination of bioinformatics and cellular biology techniques, we investigated the interactions among SAMHD1, TRIM27, and PTEN. Our findings reveal that SAMHD1 modulates PTEN ubiquitination via TRIM27, impacting key pathways involved in EC pathogenesis. These interactions suggest a critical mechanism by which SAMHD1 could influence tumor behavior and progression in EC. Conclusions The results from this study underscore the potential of targeting the SAMHD1-TRIM27-PTEN axis as a therapeutic strategy in EC. By providing new insights into the molecular mechanisms underlying EC progression, our research supports the development of novel therapeutic approaches that could contribute to improve treatment strategies for patients with EC.

Abstract Water structures at electrolyte/electrode interfaces play a crucial role in determining the selectivity and kinetics of electrochemical reactions. Despite extensive experimental and theoretical efforts, atomic-level details of ion-specific water structures on metal surfaces remain unclear. Here we show, using scanning tunneling microscopy and noncontact atomic force microscopy, that we can visualize water layers containing alkali metal cations on a charged Au(111) surface with atomic resolution. Our results reveal that Li+ cations are elevated from the surface, facilitating the formation of an ice-like water layer between the Li+ cations and the surface. In contrast, K+ and Cs+ cations are in direct contact with the surface. We observe that the water network structure transitions from a hexagonal arrangement with Li+ to a distorted hydrogen-bonding configuration with Cs+. These observations are consistent with surface-enhanced infrared absorption spectroscopy data and suggest that alkali metal cations significantly impact hydrogen evolution reaction kinetics and efficiency. Our findings provide insights into ion-specific water structures on metal surfaces and underscore the critical role of spectator ions in electrochemical processes.

Abstract Some patients with polycystic ovarian syndrome (PCOS) suffered from metabolic syndrome (MetS) including dyslipidemia, hyperinsulinism, but the underlying mechanism is unclear. Although C-terminal Binding Protein 1 (CTBP1) is a transcriptional co-repressor frequently involved in hormone secretion disorders and MetS-associated diseases, the role of CTBP1 in PCOS is rarely reported. In the present study, we found that CTBP1 expression was significantly elevated in primary granulosa cells (pGCs) derived from the PCOS with MetS patients and was positively associated with serum triglyceride, but negatively correlated with serum estradiol (E2) or high-density lipoprotein. Mechanistic study suggested that CTBP1 physically bound to the promoter II of cytochrome P450 family 19 subfamily A member 1 (CYP19A1) to inhibit the aromatase gene transcription and expression, resulting in the reduced E2 synthesis. Moreover, CTBP1 interacted with the phosphorylated SREBP1a at S396 in nuclei, leading to the FBXW7-dependent protein degradation, resulting in the reduced lipid droplets formation in pGCs. Therefore, we conclude that CTBP1 in GCs dysregulates the synthesis of steroid hormones and lipids through suppression of aromatase expression and promotion of SREBP1a protein degradation in PCOS patients, which may offer some fresh insights into the potential pathological mechanism for this tough disease.

Abstract We aimed to explore the mineralization characteristics of soil organic carbon(SOC) under different plant species in semi-arid grassland and provide basic soil carbon cycling data. Leymus chinensis, Stipa krylovii Roshev, Artemisia frigida, and Agrophorn cristam (L.) Gaertn were selected as the plant species. Incubation experiment were conducted on SOC mineralization in soil aggregates with particle sizes of > 2, 1–2, 0.25–1, and 2 mm was the highest, exceeding that of A. cristam (L.) Gaertn by approximately 136.14%. S. krylovii Roshev (70.73%), L. chinensis (58.05%), and A. frigida (33.73%) exhibited pronounced promotion effects on mineralization. The potential SOC mineralization of S. krylovii Roshev was the greatest among all species at the same soil particle size. The potential SOC mineralization was highest at a particle size of > 2 mm for all plant types. All plant types increased the SOC mineralization rate and cumulative mineralization in soils with large particle sizes, the mineralization reaction occurred more strongly. Organic carbon cumulative SOC mineralization rapidly increased in all tests during the first 20 days and gradually slowed thereafter.

Tumor mutation burden (TMB), defined as the number of somatic mutations of tumor DNA, is a well-recognized immunotherapy biomarker endorsed by regulatory agencies and pivotal in stratifying patients for clinical decision-making. However, measurement errors can compromise the accuracy of TMB assessments and the reliability of clinical outcomes, introducing bias into statistical inferences and adversely affecting TMB thresholds through cumulative and magnified effects. Given the unavoidable errors with current technologies, it is essential to adopt modeling methods to determine the optimal TMB-positive threshold. Therefore, we proposed a universal framework, TMBocelot, which accounts for pairwise measurement errors in clinical data to stabilize the determination of hierarchical thresholds. TMBocelot utilizes a Bayesian approach based on the stationarity principle of Markov chains to implement an enhanced error control mechanism, utilizing moderately informative priors. Simulations and retrospective data from 438 patients reveal that TMBocelot outperforms conventional methods in terms of accuracy, consistency of parameter estimations, and threshold determination. TMBocelot enables precise and reliable delineation of TMB-positive thresholds, facilitating the implementation of immunotherapy. The source code for TMBocelot is publicly available at https://github.com/YixuanWang1120/TMBocelot.

Abstract TP53 mutation (TP53-mut) correlates with inferior survival in many cancers, whereas its prognostic role in diffuse large B-cell lymphoma (DLBCL) is still in controversy. Therefore, more precise risk stratification needs to be further explored for TP53-mut DLBCL patients. A set of 2637 DLBCL cases from multiple cohorts, was enrolled in our analysis. Among the 2637 DLBCL patients, 14.0% patients (370/2637) had TP53-mut. Since missense mutations account for the vast majority of TP53-mut DLBCL patients, and most non-missense mutations affect the function of the P53 protein, leading to worse survival rates, we distinguished patients with missense mutations. A TP53 missense mutation risk model was constructed based on a 150-combination machine learning computational framework, demonstrating excellent performance in predicting prognosis. Further analysis revealed that patients with high-risk missense mutations are significantly associated with early progression and exhibit dysregulation of multiple immune and metabolic pathways at the transcriptional level. Additionally, the high-risk group showed an absolutely suppressed immune microenvironment. To stratify the entire cohort of TP53-mut DLBCL, we combined clinical characteristics and ultimately constructed the TP53 Prognostic Index (TP53PI) model. In summary, we identified the truly high-risk TP53-mut DLBCL patients and explained this difference at the mutation and transcriptional levels.

Abstract Fetal adenocarcinoma of the lung (FLAC) is a rare form of lung adenocarcinoma and was divided into high-grade (H-FLAC) and low-grade (L-FLAC) subtypes. Despite the existence of some small case series studies, a comprehensive multi-omics study of FLAC has yet to be undertaken. In this study, we depicted the multi-omics landscapes of this rare lung cancer type by performing multi-regional sampling on 20 FLAC cases. A comparison of multi-omics profiles revealed significant differences between H-FLAC and L-FLAC in a multi-omic landscape. Two subtypes also showed distinct relationships between multi-layer intratumor heterogeneity (ITH). We discovered that a lower genetic ITH was significantly associated with worse recurrence-free survival and overall survival in FLAC patients, whereas higher methylation ITH in H-FLAC patients suggested a short survival. Our findings highlight the complex interplay between genetic and transcriptional heterogeneity in FLAC and suggest that different types of ITH may have distinct implications for patient prognosis.

Abstract Background Gastric cancer is the fifth most common cancer type. Most patients are diagnosed at advanced stages with poor prognosis. A non-invasive assay for the detection of early-stage gastric cancer is highly desirable for reducing associated mortality. Methods We collected a prospective study cohort of 110 stage I–II gastric cancer patients and 139 non-cancer individuals. We performed whole-genome sequencing with plasma samples and profiled four types of cell-free DNA (cfDNA) characteristics, fragment size pattern, copy number variation, nucleosome coverage pattern, and single nucleotide substitution. With these differential profiles, we developed an ensemble model to detect gastric cancer signals. Further, we validated the assay in an in-house first validation cohort of 73 gastric cancer patients and 94 non-cancer individuals and an independent second validation cohort of 47 gastric cancer patients and 49 non-cancer individuals. Additionally, we evaluated the assay in a hypothetical 100,000 screening population by Monte Carlo simulation. Results Our cfDNA-based assay could distinguish early-stage gastric cancer from non-cancer at an AUROC of 0.962 (95% CI: 0.942–0.982) in the study cohort, 0.972 (95% CI: 0.953–0.992) in the first validation cohort and 0.937 (95% CI: 0.890–0.983) in the second validation cohort. The model reached a specificity of 92.1% (128/139) and a sensitivity of 88.2% (97/110) in the study cohort. In the first validation cohort, 91.5% (86/94) of non-cancer individuals and 91.8% (67/73) of gastric cancer patients were correctly identified. In the second validation cohort, 89.8% (44/49) of non-cancer individuals and 87.2% (41/47) of gastric cancer patients were accurately classified. Conclusions We introduced a liquid biopsy assay using multiple dimensions of cfDNA characteristics that could accurately identify early-stage gastric cancer from non-cancerous conditions. As a cost-effective non-invasive approach, it may provide population-wide benefits for the early detection of gastric cancer. Trial registration This study was registered on ClinicalTrials.gov under the identifier NCT05269056 on March 7, 2022.

Background: Spinal cord injury (SCI) is a devastating neurological disease in which astrocytes play a central role. Understanding the relationship between different subtypes of astrocytes and neuron subtypes during the progression of SCI is critical to understanding the disease. Methods and results: In this study, single-cell RNA sequencing (scRNA-seq) was used to analyze the transcriptome data of acute, subacute and intermediate stages of SCI in mice as well as normal tissues. Different subtypes of astrocytes and neuronal cells were identified and their dynamic changes and functionalities during the development of SCI. An intriguing discovery was the identification of a specific subtype of astrocytes characterized by unique expression of Gap43, Vim, Aldoc, and Mt1. This subtype of cells shows similarities in gene expression with neurons and potentially transitioned into neurons during the course of SCI. Furthermore, we have uncovered the important role of the glycolytic pathway in this cellular transformation process. Furthermore, through cellular interaction analysis, we validated pathways (mdk-ptprz1,ptn-ptprz1,ptn-sdc3) associated with the potential conversion of these specific cell subsets into neurons. Finally, these cells were observed by fluorescence microscopy and critical gene expressions were validated by Western blot. Conclusions: The results of this study not only deepen our understanding of the mechanisms underlying SCI, but also provide new insights and opportunities for the development of novel therapeutic strategies and interventions.

BackgroundPatient-targeted Googling (PTG) is an unavoidable aspect of the internet era, offering both opportunities and risks. However, no PTG studies have been conducted in Asian contexts to date. Additionally, existing research has provided limited exploration of factors influencing PTG practices, particularly regarding the professional differences between psychiatrists and psychologists. This study seeks to address these research gaps.MethodA total of 943 licensed psychiatrists and psychologists working in China completed an online survey. The survey included their attitudes towards PTG (including general attitude, application situations, reasons for/against PTG) and their actual practice of PTG.Results250(26.5%) respondents reported using PTG. Among them, 151(60.4%) respondents sought consent from clients before use, and 142(56.8%) respondents discussed search results with clients after use. Chinese psychiatrists and psychologists have contradictory attitudes, with concerns but also recognition of its possible positive effects, and expressing a need for more guidance. Compared to psychiatrists or those working in public institutions, psychologists and those working in private institutions report greater concerns about PTG but engage in it more frequently.ConclusionsAlthough the sample is limited, the study reveals notable differences in attitudes and practice of PTG among Chinese psychiatrists and psychologists, which may be related to their distinct professional roles and workplace environments. These findings suggest the need for further research to better understand the underlying factors contributing to these differences. Moreover, the results highlight the importance of developing tailored ethical guidelines and targeted training programs to address PTG practices for psychiatrists and psychologists in China.

Genetic factors play significant roles in the tumorigenicity of lung cancer; however, there is lack of systematic and large‐scale characterization of pathogenic germline variants for lung cancer. In this study, germline variants in 146 preselected cancer‐susceptibility genes were detected in 17 904 Chinese lung cancer patients by clinical next‐generation sequencing. Among 17 904 patients, 1738 patients (9.7%) carried 1840 pathogenic/likely pathogenic (P/LP) variants from 87 cancer‐susceptibility genes. SBDS (SBDS ribosome maturation factor) (1.37%), TSHR (thyroid stimulating hormone receptor) (1.20%), BLM (BLM RecQ like helicase) (0.62%), BRCA2 (BRCA2 DNA repair associated) (0.62%), and ATM (ATM serine/threonine kinase) (0.45%) were the top five genes with the highest overall prevalence. The top mutated pathways were all involved in DNA damage repair (DDR). Case–control analysis showed SBDS c.184A>T(p.K62*), TSHR c.1574T>C(p.F525S), BRIP1 (BRCA1 interacting helicase 1) c.1018C>T(p.L340F), and MUTYH (mutY DNA glycosylase) c.55C>T(p.R19*) were significantly associated with increased lung cancer risk (q value

Abstract Background Lipids found in plant seeds are essential for controlling seed dormancy, dispersal, and defenses against biotic and abiotic stress. Additionally, these lipids provide nutrition and energy and are therefore important to the human diet as edible oils. Acer truncatum, which belongs to the Aceaceae family, is widely cultivated around the world for its ornamental value. Further because its seed oil is rich in unsaturated fatty acids (UFAs)- i.e. α-linolenic acid (ALA) and nervonic acid (NA)- and because it has been validated as a new food resource in China, the importance of A. truncatum has greatly risen. However, it remains unknown how UFAs are biosynthesized during the growth season, to what extent environmental factors impact their content, and what areas are potentially optimal for their production. Results In this study, transcriptome and metabolome of A. truncatum seeds at three representative developmental stages was used to find the accumulation patterns of all major FAs. Cumulatively, 966 metabolites and 87,343 unigenes were detected; the differential expressed unigenes and metabolites were compared between stages as follows: stage 1 vs. 2, stage 1 vs. 3, and stage 2 vs. 3 seeds, respectively. Moreover, 13 fatty acid desaturases (FADs) and 20 β-ketoacyl-CoA synthases (KCSs) were identified, among which the expression level of FAD3 (Cluster-7222.41455) and KCS20 (Cluster-7222.40643) were consistent with the metabolic results of ALA and NA, respectively. Upon analysis of the geographical origin-affected diversity from 17 various locations, we found significant variation in phenotypes and UFA content. Notably, in this study we found that 7 bioclimatic variables showed considerable influence on FAs contents in A. truncatum seeds oil, suggesting their significance as critical environmental parameters. Ultimately, we developed a model for potentially ecological suitable regions in China. Conclusion This study provides a comprehensive understanding of the relationship between metabolome and transcriptome in A. truncatum at various developmental stages of seeds and a new strategy to enhance seed FA content, especially ALA and NA. This is particularly significant in meeting the increasing demands for high-quality edible oil for human consumption. The study offers a scientific basis for A. truncatum’s novel utilization as a woody vegetable oil rather than an ornamental plant, potentially expanding its cultivation worldwide.

Abstract Green hydrogen production is crucial for a sustainable future, but current catalysts for the oxygen evolution reaction (OER) suffer from slow kinetics, despite many efforts to produce optimal designs, particularly through the calculation of descriptors for activity. In this study, we develop a dataset of density functional theory calculations of bulk and surface perovskite oxides, and adsorption energies of OER intermediates, which includes compositions up to quaternary and facets up to (555). We demonstrate that per-site properties of perovskite oxides such as Bader charge or band center can be tuned through element substitution and faceting, and develop a machine learning model that accurately predicts these properties directly from the local chemical environment. We leverage these per-site properties to identify promising perovskites with high theoretical OER activity. The identified design principles and promising materials provide a roadmap for closing the gap between current artificial catalysts and biological enzymes such as photosystem II.

Abstract Treatment of bone defects remains crucial challenge for successful bone healing, which arouses great interests in designing and fabricating ideal biomaterials. In this regard, the present study focuses on developing a novel fluffy scaffold of poly Lactide-co-glycolide (PLGA) composites with hydroxyapatite (HA) scaffold used in bone defect repair in rabbits. This fluffy PLGA/HA composite scaffold was fabricated by using multi-electro-spinning combined with biomineralization technology. In vitro analysis of human bone marrow mesenchymal stem cells (BMSCs) seeded onto fluffy PLGA/HA composite scaffold showed their ability to adhere, proliferate and cell viability. Transplant of fluffy PLGA/HA composite scaffold in a rabbit model showed a significant increase in mineralized tissue production compared to conventional and fluffy PLGA/HA composite scaffold. These findings are promising for fluffy PLGA/HA composite scaffolds used in bone defects. Graphical Abstract

Spatial and temporal information about cropping patterns of single and multiple crops is important for monitoring crop production and land-use intensity. We used time-series MODIS NDVI 8-day composite data to develop annual cropping pattern products at a 250 m spatial resolution for China, covering the period from 2001 to 2023. To address the potential impacts of varying parameters in both data pre-processing and the peak detection algorithm on the accuracy of cropping pattern mapping, we employed a grid-search method to fine-tune these parameters. This process focused on optimizing the Savitzky–Golay smoothing window size and the peak width parameters using a calibration dataset. The results highlighted that an optimal combination of a five to seven MODIS composite window size in Savitzky–Golay smoothing and a peak width of four MODIS composites achieved good overall mapping accuracy. Pixel-wise accuracy assessments were conducted for the selected mapping years of 2001, 2011, and 2021. Overall accuracies were between 89.7% and 92.0%, with F1 scores ranging from 0.921 to 0.943. Nationally, this study observed a fluctuating trend in multiple cropping percentages, with a notable increase after 2013, suggesting shifts toward more intensive agricultural practices in recent years. At a finer spatial scale, the combination of Mann–Kendall and Sen’s slope analyses revealed that approximately 12.9% of 3 km analytical windows exhibited significant changes in cropping intensity. We observed spatial clusters of increasing and decreasing crop intensity trends across provinces such as Hebei, Shandong, Shaanxi, and Gansu. This study underscores the importance of data smoothing and peak detection methods in analyzing high temporal resolution remote sensing data. The generation of annual single/multiple cropping pattern maps at a 250 m spatial resolution enhances our comprehension of agricultural dynamics through time and across different regions.

Donkeys are particularly at risk of hyperlipemia. Hyperlipemia is a metabolic disease caused by the mobilization of fatty acids from adipose tissue, which often impacts pregnant and lactating jennies (female donkeys) during periods of negative energy balance. This study aimed to evaluate the levels of lipids, biochemical parameters, selected antioxidant elements and oxidative stress parameters in late pregnant jennies affected by hyperlipemia. Compared with the healthy jennies, the hyperlipemic animals exhibited significantly elevated levels of triglycerides (TGs), total cholesterol (T-CHO) and low-density lipoprotein cholesterol (p < 0.05), coupled with reduced levels of high-density lipoprotein cholesterol and albumin (ALB) (p < 0.05). The serum levels of biochemical parameters related to liver function, such as aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase (AKP) and cholinesterase (CHE), showed a significant increase in the hyperlipemia group compared to the healthy group (p < 0.05). The serum level of selenium was significantly lower (p < 0.05) and positively correlated with TGs (r = 0.85) and ALB (r = 0.73) in the hyperlipemia group. The hyperlipemic jennies showed diminished serum levels of antioxidant capacity and increased levels of malondialdehyde (MDA). The area under the curve values for T-CHO, ALB, AKP, CHE, total superoxide dismutase, glutathione and MDA were relatively high. Thus, our findings reflect metabolic disorders, liver dysfunction and oxidative stress in late pregnant hyperlipemic jennies, providing a basis for the improvement of clinical diagnostic methods and early prevention and control of hyperlipemia in jennies.

PurposeThis systematic review and meta-analysis aimed to evaluate the efficacy of repetitive transcranial magnetic stimulation (rTMS) in postherpetic neuralgia (PHN).MethodsThrough an extensive search in four databases until October 2023, we selected five randomized controlled trials adhering to our specific criteria, involving 257 patients in total. For continuous outcomes, the standardized mean difference (SMD) was calculated. Heterogeneity among the studies was assessed using Cochran’s I2 and Q statistics, adopting a random-effects model for I2 values over 50%. For assessing potential publication bias, we utilized both funnel plot and Egger’s test.ResultsOur analysis found that rTMS reduced the overall visual analogue scale (VAS) (SMD: −1.52, 95% CI: −2.81 to −0.23, p = 0.02), VAS at 1 month post-treatment (SMD: −2.21, 95% CI: −4.31 to −0.10, p = 0.04), VAS at 3 months post-treatment (SMD: −1.51, 95% CI: −2.81 to −0.22, p = 0.02), as well as patients’ global impression of change scale (PGIC) (SMD: −1.48, 95% CI: −2.87 to −0.09, p = 0.04) and short-form McGill pain questionnaire (SF-MPQ) (SMD: −1.25, 95% CI: −2.41 to −0.09, p = 0.03) compared to the sham-rTMS group.ConclusionOur study suggests that rTMS might have a potential alleviating effect on PHN symptoms. However, due to the limited number of studies and variations in rTMS parameters, larger sample studies involving more diverse populations, as well as further clarification of the most appropriate stimulation protocol, are still needed.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, Identifier ID: CRD42023488420.

The morphology of lettuce roots in hydroponics is affected by the flow environment of nutrient solutions. Regulating the flow rate therefore ensures quality and yield; however, the mechanisms underlying this impact have not been fully elucidated, and breakthroughs in regulatory methods are thus lacking. Herein, lettuce was grown in a hydroponic solution at three different flow rates, the root morphology indicators (such as root length and surface area) were evaluated, the hormone levels of roots grown under different flow conditions were measured, and the correlations between plant hormones and root morphology were analyzed. Transcriptomic analysis was conducted on roots at varying flow rates to investigate the differential expression of genes involved in the synthesis and signal transduction pathways of auxin, abscisic acid (ABA), ethylene, and jasmonic acid. Results showed that these plant hormones were closely related to root morphology. Compared to a non-flow environment, a flow environment promoted the synthesis of plant hormones in the roots and enhanced the signal transduction of certain hormones, such as auxin. However, it had a negative impact on the signal transduction of certain hormones, specifically ethylene. The flow of the nutrients regulated root morphogenesis by influencing the synthesis and transduction of plant hormones, which affected overall plant growth. During the same growth period, lettuce grown under suitable flow conditions had a higher fresh weight than lettuce grown under no-flow conditions. Although such flow would increase the electricity cost of operating water pumps, lettuce could be harvested in advance at appropriate flow rates, thereby reducing the energy consumed in plant factories through lighting and temperature regulation, which are the largest contributors to energy consumption. This study examined the impact of the nutrient solution flow environment as a positive stimulus for plant growth, and it provides a reference for strategically regulating the flow rate in plant factories to improve yield and save energy. Future research should explore the effects of other cultivation and flow methods on the growth of different plants and apply these findings to practical production.

Abstract Intraperitoneal dissemination is the main method of epithelial ovarian cancer (EOC) metastasis, which is related to poor prognosis and a high recurrence rate. Circular RNAs (circRNAs) are a novel class of endogenous RNAs with covalently closed loop structures that are implicated in the regulation of tumor development. In this study, hsa_circ_0001546 is downregulated in EOC primary and metastatic tissues vs. control tissues and this phenotype has a favorable effect on EOC OS and DFS. hsa_circ_0001546 can directly bind with 14‐3‐3 proteins to act as a chaperone molecule and has a limited positive effect on 14‐3‐3 protein stability. This complex recruits CAMK2D to induce the Ser324 phosphorylation of Tau proteins, changing the phosphorylation status of Tau bound to 14‐3‐3 and ultimately forming the hsa_circ_0001546/14‐3‐3/CAMK2D/Tau complex. The existence of this complex stimulates the production of Tau aggregation, which then induces the accumulation of lipid peroxides (LPOs) and causes LPO‐dependent ferroptosis. In vivo, treatment with ferrostatin‐1 and TRx0237 rescued the inhibitory effect of hsa_circ_0001546 on EOC cell spreading. Therefore, based on this results, ferroptosis caused by Tau aggregation occurs in EOC cells, which is not only in Alzheimer's disease‐ or Parkinson's disease‐related cells and this kind of ferroptosis driven by the hsa_circ_0001546/14‐3‐3/CAMK2D/Tau complex is LPO‐dependent rather than GPX4‐dependent is hypothesized.

Abstract Insights into changes in genome base composition underlying crop domestication can be gained by using comparative genomics. With this approach, previous studies have reported that crop genomes during domestication accumulate more nucleotides adenine (A) and thymine (T) (termed as [AT]‐increase) across polymorphic sites. However, the potential influence of the environment or its factors, for example, solar ultraviolet (UV) radiation and temperature, on the [AT]‐increase has not been well elucidated. Here, we investigated the [AT]‐increase in barley (Hordeum vulgare L.) and rice (Oryza sativa L.) and the association with natural environments, where accessions are distributed. With 12,798,376 and 2,861,535 single‐nucleotide polymorphisms from 368 barley and 1375 rice accessions, respectively, we discovered that [AT] increases from wild accessions to improved cultivars, and genomic regions with larger [AT]‐increase tend to have higher UV‐related motif frequencies, suggesting solar UV radiation as a potential factor in driving genome variation. To link [AT] change with the geographic distribution, we gathered georeferenced accessions and examined their local environments. Interestingly, negative correlations between [AT] and environmental factors were observed (r = −0.39 ∼ −0.75) and modern accessions with higher [AT] values, as compared with wild relatives, are from the environments with lower solar UV radiation or lower temperature. With [AT] and environmental factors as phenotypes, genome‐wide association mapping identified three candidate genes that have the potential to contribute to [AT] variation under the effect of environmental conditions. Our findings provide genomic and environmental insights into evolutionary pattern of DNA base composition and underlying mechanisms.

Abstract Flexibility has become increasingly important considering the intermittency of variable renewable energy in low-carbon energy systems. Electrified transportation exhibits great potential to provide flexibility. This article analyzed and compared the flexibility values of battery electric vehicles and fuel cell electric vehicles for planning and operating interdependent electricity and hydrogen supply chains while considering battery degradation costs. A cross-scale framework involving both macro-level and micro-level models was proposed to compute the profits of flexible EV refueling/charging with battery degradation considered. Here we show that the flexibility reduction after considering battery degradation is quantified by at least 4.7% of the minimum system cost and enlarged under fast charging and low-temperature scenarios. Our findings imply that energy policies and relevant management technologies are crucial to shaping the comparative flexibility advantage of the two transportation electrification pathways. The proposed cross-scale methodology has broad implications for the assessment of emerging energy technologies with complex dynamics.

Objective: To investigate the interrelationship between cardiovascular health awareness, risk perception, behavioural intention, and INTERHEART risk stratification in a middle-aged adult population in Malaysia. Methods: A cross-sectional survey with convenience sampling was conducted during November 2022 and January 2023. Participants completed validated questionnaires assessing cardiovascular health awareness, risk perception of cardiovascular diseases, behavioural intention towards adopting healthy habits, and INTERHEART risk stratification score (IHRS) based on established risk factors. A total of 602 respondents were included in the final analysis. Data were analysed with independent t-test/one-way ANOVA or Mann- Whitney/Kruskai-Wailis to test the differences, Pearson correlation or linear regression test to analyze the association of independent and dependent variables. Results: There was a significant positive correlation between medical knowledge related to cardiovascular disease (CVD) and knowledge related to CVD risk prevention, risk perception, behavioural intention and IHRS (P

Electroencephalogram (EEG) signals are widely utilized in the field of cognitive workload decoding (CWD). However, when the recognition scenario is shifted from subject-dependent to subject-independent or spans a long period, the accuracy of CWD deteriorates significantly. Current solutions are either dependent on extensive training datasets or fail to maintain clear distinctions between categories, additionally lacking a robust feature extraction mechanism. In this paper, we tackle these issues by proposing a Bi-Classifier Joint Domain Adaptation (BCJDA) model for EEG-based cross-time and cross-subject CWD. Specifically, the model consists of a feature extractor, a domain discriminator, and a Bi-Classifier, containing two sets of adversarial processes for domain-wise alignment and class-wise alignment. In the adversarial domain adaptation, the feature extractor is forced to learn the common domain features deliberately. The Bi-Classifier also fosters the feature extractor to retain the category discrepancies of the unlabeled domain, so that its classification boundary is consistent with the labeled domain. Furthermore, different adversarial distance functions of the Bi-Classifier are adopted and evaluated in this model. We conduct classification experiments on a publicly available BCI competition dataset for recognizing low, medium, and high cognitive workload levels. The experimental results demonstrate that our proposed BCJDA model based on cross-gradient difference maximization achieves the best performance.

Self-report measures (e.g., Likert scales) are widely used to evaluate subjective health perceptions. Recently, the visual analog scale (VAS), a slider-based scale, has become popular owing to its ability to precisely and easily assess how people feel. These data can be influenced by the response style (RS), a user-dependent systematic tendency that occurs regardless of questionnaire instructions. Despite its importance, especially in between-individual analysis, little attention has been paid to handling the RS in the VAS (denoted as response profile (RP)), as it is mainly used for within-individual monitoring and is less affected by RP. However, VAS measurements often require repeated self-reports of the same questionnaire items, making it difficult to apply conventional methods used for Likert scales. In this study, we developed a novel RP characterization method for various types of repeatedly measured VAS data. This approach involves modeling RP as distributional parameters $\boldsymbol {\theta } $ through a mixture of RS-like distributions, and addressing the issue of unbalanced data through bootstrap sampling for treating repeated measures. We assessed the effectiveness of the proposed method using simulated pseudo-data and an actual dataset from an empirical study. The assessment of parameter recovery showed that our method accurately estimated the RP parameter $\boldsymbol {\theta } $ , demonstrating its robustness. Moreover, applying our method to an actual VAS dataset revealed the presence of individual RP heterogeneity, even in repeated VAS measurements, similar to the findings for Likert scales. Our proposed method enables RP heterogeneity-aware VAS data analysis, similar to Likert-scale data analysis.

Reducing urban transportation carbon emissions is a fashionable task around the globe. Electric cars, fuel cell cars, hydrogen cars, restriction policies, etc. are all aimed at this goal. But they are all expensive to make them into reality. Transportation management can also provide some contribution to this, like optimizing operation rules such as Left-turn Waiting Area Twice Startup. From the stop line to the Left-turn Waiting Area (LWA), one vehicle will start twice with more emissions due to the engine’s inefficient operating range. We proposed an Accurate Left-turn One-time Startup Model (ALOSM) based on the LWA rule, which includes the intersection geometry parameters, traffic light timing schemes, vehicle start speeds, vehicle operation speeds, and fuel vehicle ratios. Make the Left-turn Vehicle (LV) waiting behind the stop line during the through vehicle light green. Calculate the left-turn green light adjustment duration and make the LV and the last through vehicle across at one moment. With real collected data in a symbolic intersection in Xi’an, China, the simulation result shows vehicle emission would be reduced by 13% and traffic efficiency would increase by 5% in this single intersection. The whole city of 5 million vehicles would reduce 2,087.88 kg CO emission in one day due to estimation.

The contamination of soil with the heavy metal cadmium (Cd) is increasingly prominent and severely threatens food security in China. Owing to its low cost, suitable efficacy, and ability to address the shortcomings of plant remediation by enhancing the ability of plants to take up Cd, plant–microbe combination remediation technology has become a research hotspot in heavy metal pollution remediation. A pot experiment was performed to examine the effects of inoculation with the plant-growth-promoting bacterium Brevibacillus sp. SR-9 on the biomass, Cd accumulation, and soil nutrients of hybrid Pennisetum. The purpose of this study was to determine how Brevibacillus sp. SR-9 alleviates stress caused by heavy metal contamination. High-throughput sequencing and metabolomics were used to determine the effects of inoculation on the soil bacterial community composition and microbial metabolic functions associated with hybrid Pennisetum. The results suggest that mutation of Brevibacillus sp. SR-9 effectively alleviates Cd pollution stress, leading to increased biomass and accumulation of Cd in hybrid Pennisetum. The aboveground biomass and the root weight increased by 12.08% and 27.03%, respectively. Additionally, the accumulation of Cd in the aboveground sections and roots increased by 21.16% and 15.50%, respectively. Measurements of the physicochemical properties of the soil revealed that the strain Brevibacillus sp. SR-9 slightly increased the levels of available phosphorus, total nitrogen, total phosphorus, and available potassium. High-throughput DNA sequencing revealed that Brevibacillus sp. SR-9 implantation modified the composition of the soil bacterial community by increasing the average number of Actinobacteria and Bacillus. The total nitrogen content of the soil was positively correlated with the Actinobacteria abundance, total phosphorus level, and available phosphorus level. Metabolomic analysis revealed that inoculation affected the abundance of soil metabolites, and 59 differentially abundant metabolites were identified (p < 0.05). Among these, 14 metabolites presented increased abundance, whereas 45 metabolites presented decreased abundance. Fourteen metabolic pathways were enriched in these metabolites: the folate resistance pathway, the ABC transporter pathway, D-glutamine and D-glutamic acid metabolism, purine metabolism, and pyrimidine metabolism. The abundance of the metabolites was positively correlated with the levels of available phosphorus, total potassium, total phosphorus, and total nitrogen. According to correlation analyses, the development of hybrid Pennisetum and the accumulation of Cd are strongly associated with differentially abundant metabolites, which also impact the abundance of certain bacterial populations. This work revealed that by altering the makeup of microbial communities and their metabolic processes, bacteria that promote plant development can mitigate the stress caused by Cd. These findings reveal the microbiological mechanisms through which these bacteria increase the ability of hybrid Pennisetum to take up the Cd present in contaminated soils.

This study was designed to develop a 30 m resolution land cover dataset to improve the performance of regional weather forecasting models in East China. A 10-class land cover mapping scheme was established, reflecting East China’s diverse landscape characteristics and incorporating a new category for plastic greenhouses. Plastic greenhouses are key to understanding surface heterogeneity in agricultural regions, as they can significantly impact local climate conditions, such as heat flux and evapotranspiration, yet they are often not represented in conventional land cover classifications. This is mainly due to the lack of high-resolution datasets capable of detecting these small yet impactful features. For the six-province study area, we selected and processed Landsat 8 imagery from 2015–2018, filtering for cloud cover. Complementary datasets, such as digital elevation models (DEM) and nighttime lighting data, were integrated to enrich the inputs for the Random Forest classification. A comprehensive training dataset was compiled to support Random Forest training and classification accuracy. We developed an automated workflow to manage the data processing, including satellite image selection, preprocessing, classification, and image mosaicking, thereby ensuring the system’s practicality and facilitating future updates. We included three Weather Research and Forecasting (WRF) model experiments in this study to highlight the impact of our land cover maps on daytime and nighttime temperature predictions. The resulting regional land cover dataset achieved an overall accuracy of 83.2% and a Kappa coefficient of 0.81. These accuracy statistics are higher than existing national and global datasets. The model results suggest that the newly developed land cover, combined with a mosaic option in the Unified Noah scheme in WRF, provided the best overall performance for both daytime and nighttime temperature predictions. In addition to supporting the WRF model, our land cover map products, with a planned 3–5-year update schedule, could serve as a valuable data source for ecological assessments in the East China region, informing environmental policy and promoting sustainability.

The Cu–15Ni–8Sn alloy ingot was prepared in the medium-frequency induction melting furnace. The hot extruded alloy was treated by solid solution at 840 °C for 60 min and aging at 400 °C for different times (0 miñ480 min). The effect of aging time on the evolution of the nanophase of Cu–15Ni–8Sn alloy and the strengthening-toughening mechanism were studied. The results show that at the beginning of aging, the alloy undergoes spinodal decomposition, the wavelength of the modulated structure is approximately 3∼7 nm, the ordered phase transformation of D022 and L12 occurs simultaneously, and the ordered phase size is approximately 5 nm. With the extension of aging time, the modulated structure became coarser, and the wavelength of the modulated structure increased to 5–9 nm. At the same time, the D022 ordered phase changed to the L12 ordered phase, and a continuous distribution of elliptical discontinuous precipitation appeared at the grain boundary. The ratio of the long and short axes of the discontinuous precipitation was approximately 4.7. In the late aging period, the D022 ordered phase was basically transformed into the L12 ordered phase, and discontinuous precipitation, which is incompatible with the matrix, extended into the crystal. After 120 min of aging at 400 °C, the hardness, strength, and elongation of the alloy are 105.4 HRB, 839.8 MPa and 9.6 %, respectively. The peak-aging states D022 and L12 coexist in an orderly phase at the nanoscale, and this nanoscale strengthening phase is completely integrated with the matrix, which improves the strength and toughness of the alloy. The research results can provide support for the development of high-performance copper alloys in the ocean.

The presence of large genomic rearrangements (LGRs) has been heavily investigated in breast and ovarian cancer. However, correlations between LGRs and cancer types beyond these two have not been extensively profiled, likely due to the highly inefficient methods of detecting these types of alterations. This study utilized next‐generation sequencing (NGS) to analyze and classify the germline LGR profile in 17 025 cancer patients across 22 cancer types. We characterized newly identified LGRs based on predicted pathogenicity and took a closer look at genes that acquire both germline and somatic mutations within our samples. The detection method for LGRs was validated using droplet digital polymerase chain reaction (ddPCR) assay of commonly investigated LGR genes. In total, 15 659 samples from across 22 cancer types were retained for analysis after filtering. We observed that, in our cohort, the cancer types with the highest proportion of germline LGRs were ovarian cancer (4.7%), renal cell carcinoma (2.5%), breast cancer (2%), glioma (1.8%) and thyroid carcinoma (1.8%). Annotation of detected germline variants revealed several genes—MSH2, FANCA and PMS2—that contain novel LGRs. We observed co‐occurrences between germline LGRs in MSH2 and somatic single nucleotide variants/insertion and deletions (SNVs/InDels) in BRCA2, KTM2B, KDM5A, CHD8, and HNF1A. Furthermore, our analysis showed that samples with pathogenic and likely pathogenic germline LGRs tended to also have higher mutational burden, chromosomal instability, and microsatellite instability ratio compared to samples with pathogenic germline SNVs/InDels. In this study, we demonstrated the prevalence of pathogenic germline LGRs beyond breast and ovarian cancer. The profiles of these pathogenic or likely pathogenic alterations will fuel further investigations and highlight new understanding of LGRs across multiple cancer types.

Purpose: This investigation was conceived to engineer and appraise a pioneering clinical nomogram, crafted to bridge the extant chasm in literature regarding the postoperative risk stratification for deep vein thrombosis (DVT) in the aftermath of lower extremity orthopedic procedures. This novel tool offers a sophisticated and discerning algorithm for risk prediction, heretofore unmet by existing methodologies. Methods: In this retrospective observational study, clinical records of hospitalized patients who underwent lower extremity orthopedic surgery were collected at the Wuxi TCM Hospital Affiliated to the Nanjing University of Chinese Medicine between Jan 2017 and Oct 2019. The univariate and multivariate analysis with the backward stepwise method was applied to select features for the predictive nomogram. The performance of the nomogram was evaluated with respect to its discriminant capability, calibration ability, and clinical utility. Result: A total of 5773 in-hospital patients were eligible for the study, with the incidence of deep vein thrombosis being approximately 1 % in this population. Among 31 variables included, 5 of them were identified to be the predictive features in the nomogram, including age, mean corpuscular hemoglobin concentration (MCHC), D-dimer, platelet distribution width (PDW), and thrombin time (TT). The area under the receiver operating characteristic (ROC) curve in the training and validation cohort was 85.9 % (95%CI: 79.96 %–90.04 %) and 85.7 % (95%CI: 78.96 %–90.69 %), respectively. Both the calibration curves and decision curve analysis demonstrated the overall satisfactory performance of the model. Conclusion: Our groundbreaking nomogram is distinguished by its unparalleled accuracy in discriminative and calibrating functions, complemented by its tangible clinical applicability. This innovative instrument is set to empower clinicians with a robust framework for the accurate forecasting of postoperative DVT, thus facilitating the crafting of bespoke and prompt therapeutic strategies, aligning with the rigorous standards upheld by the most esteemed biomedical journals.

Abstract The genomic origin and development of the biphasic lung adenosquamous carcinoma (ASC) remain inconclusive. Here, we derived potential evolutionary trajectory of ASC through whole-exome sequencing, Stereo-seq, and patient-derived xenografts. We showed that EGFR and MET activating mutations were the main drivers in ASCs. Phylogenetically, these drivers and passenger mutations found in both components were trunk clonal events, confirming monoclonal origination. Comparison of multiple lesions also revealed closer genomic distance between lymph node metastases and the ASC component with the same phenotype. However, as mutational signatures of EGFR-positive lung squamous carcinomas (LUSCs) were more comparable to EGFR-positive ASCs than to wild-type LUSCs, we postulated different origination of these LUSCs, with ASC being the potential intermediate state of driver-positive LUSCs. Spatial transcriptomic profiling inferred transformation from adenocarcinoma to squamous cell carcinoma, which was then histologically captured in vivo. Together, our results explained the development of ASC and provided insights into future clinical decisions.

Abstract Background Locoregional recurrence is of high risk and is associated with a poor prognosis in terms of OS for non‐small cell lung cancer (NSCLC). Local control is essential for radical cure of NSCLC. Previous studies have investigated the clinicopathological risk factors for locoregional recurrence, but the genomic biomarkers associated with locoregional recurrence have been inadequately studied. Methods A total of 118 patients who underwent tumor resection with mutation‐detected tumor specimens were included. Tumor samples at surgery and pretreatment/postoperative blood samples were collected for mutational profiling. Results Among 48 patients with disease recurrence, 46% developed locoregional recurrence (LR) and 75% developed distant metastasis (DM). The 3‐year actuarial risk of LR and DM was 25% and 43%, respectively. The first sites of failure were locoregional only (29%), locoregional and distant (10%), and distant only (61%). Patients with LR showed significantly higher ctDNA level than those with only DM at the time of initial recurrence. On multivariate analysis of baseline risk factors, the presence of allele frequency heterogeneity and baseline ctDNA shedding were found to be independently associated with a higher risk of LR. Patients with disruptive TP53 mutations had significantly lower LR‐free survival as compared to patients with wild‐type TP53 or nondisruptive mutations. EGFR mutations showed a favorable prognostic value for LR and is not induced by EGFR tyrosine kinase inhibitor therapy. Both disruptive TP53 mutation and EGFR mutation remained the significant prognostic factor after adjustment for histological type, pathologic nodal stage and adjuvant therapy. Conclusions Nearly half of disease recurrences after surgery for NSCC involved locoregional sites. We identified genomic biomarkers from baseline tumor and ctDNA samples which showed promising prognostic value for LR only. This can help identify patients who had a higher risk of locoregional recurrence regardless of the risk of distant metastasis.

Abstract Objectives Aberrantly expressed circular RNAs (circRNAs) have been detected in many types of tumors. Hence, they are currently investigated as candidate biomarkers for diagnostic and potential targets for therapy in cancers. The objective of this study was to assess the expression profile of circRNA in lung adenocarcinoma (LUAD). Methods This study included 14 pairs of postoperative lung adenocarcinoma specimens, including cancer tissues and matched adjacent tissues. Second‐generation sequencing was applied to the specimens to determine the circRNA expression in them among the 5242 distinct circRNAs detected. Results We identified a total of 18 significantly dysregulated circRNAs in the LUAD tissues: upregulation in four and downregulation in 14. ROC (The receiver operating characteristic curve) further suggested that hsa_circ_0120106, has_circ_0007342, has_circ_0005937, and circRNA_0000826 could potentially be used as biomarkers in the diagnosis of LUAD. Furthermore, study of the circRNA–microRNA (miRNA)–messenger RNA (mRNA) revealed interactions between the 18 dysregulated circRNA and several cancer‐related miRNAs. Finally, a further Kyoto Encyclopedia of Genes and Genomes analysis showed that the cell cycle phase transition, p53 signaling pathway, AMP‐activated protein kinase (AMPK) relative signaling pathway, and so on were key putative pathways in the process of LUAD. Conclusions These findings demonstrated the correlation between abnormality in circRNA expression and LUAD, which lays the foundation of making CircRNAs candidate biomarkers in the diagnosis of LUAD.

In satellite imagery, clouds obstruct the ground information, directly impacting various downstream applications. Thus, cloud annotation/cloud detection serves as the initial preprocessing step in remote sensing image analysis. Recently, deep learning methods have significantly improved in the field of cloud detection, but training these methods necessitates abundant annotated data, which requires experts with professional domain knowledge. Moreover, the influx of remote sensing data from new satellites has further led to an increase in the cost of cloud annotation. To address the dependence on labeled datasets and professional domain knowledge, this paper proposes an automatic cloud annotation method for satellite remote sensing images, CloudAUE. Unlike traditional approaches, CloudAUE does not rely on labeled training datasets and can be operated by users without domain expertise. To handle the irregular shapes of clouds, CloudAUE firstly employs a convex hull algorithm for selecting cloud and non-cloud regions by polygons. When selecting convex hulls, the cloud region is first selected, and points at the edges of the cloud region are sequentially selected as polygon vertices to form a polygon that includes the cloud region. Then, the same selection is performed on non-cloud regions. Subsequently, the fast KD-Tree algorithm is used for pixel classification. Finally, an uncertainty method is proposed to evaluate the quality of annotation. When the confidence value of the image exceeds a preset threshold, the annotation process terminates and achieves satisfactory results. When the value falls below the threshold, the image needs to undergo a subsequent round of annotation. Through experiments on two labeled datasets, HRC and Landsat 8, CloudAUE demonstrates comparable or superior accuracy to deep learning algorithms, and requires only one to two annotations to obtain ideal results. An unlabeled self-built Google Earth dataset is utilized to validate the effectiveness and generalizability of CloudAUE. To show the extension capabilities in various fields, CloudAUE also achieves desirable results on a forest fire dataset. Finally, some suggestions are provided to improve annotation performance and reduce the number of annotations.

ObjectiveDespite the clear association of TyG-BMI with prediabetes and the progression of diabetes, no study to date has examined the relationship between TyG-BMI and the reversal of prediabetes to normoglycemia.Methods25,279 participants with prediabetes who had physical examinations between 2010 and 2016 were enrolled in this retrospective cohort study. The relationship between baseline TyG-BMI and regression to normoglycemia from prediabetes was examined using the Cox proportional hazards regression model in this study. Additionally, the nonlinear association between TyG-BMI and the likelihood of regression to normoglycemia was investigated using the Cox proportional hazards regression with cubic spline function. Competing risk multivariate Cox regression analysis was conducted, with progression to diabetes as a competing risk for prediabetes reversal to normoglycemia. Furthermore, subgroup analyses and a series of sensitivity analyses were performed.ResultsAfter adjusting for covariates, the results showed that TyG-BMI was negatively associated with the probability of returning to normoglycemia (per 10 units, HR=0.970, 95% CI: 0.965, 0.976). They were also nonlinearly related, with an inflection point for TyG-BMI of 196.46. The effect size (HR) for TyG-BMI to the right of the inflection point (TyG-BMI ≥ 196.46) and the probability of return of normoglycemia was 0.962 (95% CI: 0.954, 0.970, per 10 units). In addition, the competing risks model found a negative correlation between TyG-BMI and return to normoglycemia (SHR=0.97, 95% CI: 0.96-0.98). Sensitivity analyses demonstrated the robustness of our results.ConclusionThis study demonstrated a negative and nonlinear relationship between TyG-BMI and return to normoglycemia in Chinese adults with prediabetes. Through active intervention, the combined reduction of BMI and TG levels to bring TyG-BMI down to 196.46 could significantly increase the probability of returning to normoglycemia.

The construction of cities and economic development lead to more and more serious environmental pollution, and the concept of green and low-carbon city has been proposed. Therefore, a series of requirements have been put forward for transportation. CO and other pollutants will be produced in the exhaust of conventional fuel vehicles, which will seriously affect the urban environment, especially at intersections with large passenger and vehicle flows. When multiple roads, especially more than 4 roads, intersect on urban roads, traffic organization can usually be achieved by using a roundabout. However, due to the limited capacity of the conventional roundabout, with the rapid increase of the traffic volume, and there are many vehicles in the circle lane change and interweaving behavior. This has caused serious congestion at the roundabout, the significantly increase in pollutants emissions and the decline in air quality. As an unconventional design, the turbo roundabouts use canalized traffic to allowed drivers to select the appropriate lanes in advance depending on their destinations so that different lanes within the circle do not interfere with one another, which improves the safety of the intersection while ensuring capacity. The main purpose of this paper is to analyze the traffic efficiency and safety of the conventional roundabout scheme and turbo roundabout scheme for five-way intersections. Using VISSIM to simulate different forms of roundabout and analyzing the six selected evaluation indicators. The number of vehicles in different entrance lanes and the diameter of the circle are selected as sensitivity factors for sensitivity analysis. Finally, the factor analysis method (FAM) is used to classify the six indicators into two categories: traffic efficiency and traffic safety, so as to comprehensively evaluate the different schemes. The results show that the difference in performance between the two schemes was not significant at low traffic volumes. At high traffic volumes, the turbo roundabout was better than the conventional roundabout in terms of emissions, safety and throughput efficiency. CO emissions from vehicles on conventional roundabout are generally higher than those on turbo roundabout, up to 53.62%. Therefore, the turbo roundabout is more appropriate for heavy traffic conditions.

Open material databases storing thousands of material structures and their properties have become the cornerstone of modern computational materials science. Yet, the raw simulation outputs are generally not shared due to their huge size. In this work, we describe a cloud-based platform to enable fast post-processing of the trajectories and to facilitate sharing of the raw data. As an initial demonstration, our database includes 6286 molecular dynamics trajectories for amorphous polymer electrolytes (5.7 terabytes of data). We create a public analysis library at https://github.com/TRI-AMDD/htp_md to extract ion transport properties from the raw data using expert-designed functions and machine learning models. The analysis is run automatically on the cloud, and the results are uploaded onto an open database. Our platform encourages users to contribute both new trajectory data and analysis functions via public interfaces. Finally, we create a front-end user interface at https://www.htpmd.matr.io/ for browsing and visualization of our data. We envision the platform to be a new way of sharing raw data and new insights for the materials science community.

The effect of cathodic polarization on stress corrosion cracking (SCC) of 35CrMo steel for high strength fasteners in seawater was investigated by electrochemical measurement, slow strain rate tensile tests and fracture analyses. The results demonstrated that the 35CrMo steel with a typical tempered martensite microstructure has some SCC susceptibility at the open circuit potential (OCP), and the susceptibility decreases as the potential is shifted negatively until −850 mV vs. SCE, at which the steel presents the lowest SCC susceptibility due to the inhibition of anodic dissolution (AD) and little hydrogen evolution. The SCC sensitivity increases significantly as the applied potential further shifts negatively because of intensive hydrogen evolution. The fractures are transgranular at all potentials. AD is considered to be the main cracking mechanism at OCP, while hydrogen embrittlement becomes dominant at the potential below −850 mV vs. SCE.

Abstract HER2-positive gastric cancer (GC) makes up 15–20% of all GC incidences, and targeted therapy with trastuzumab is the standard of treatment. However, the mechanisms of resistance to trastuzumab are still not fully understood and presents a significant challenge in clinical practice. In this study, whole exome sequencing (WES) was performed on paired tumor tissues before trastuzumab treatment (at baseline) and at progressive disease (PD) in 23 GC patients. Clinicopathological and molecular features that may be associated with primary and/or acquired resistance to trastuzumab were identified. Lauren classification of intestinal type was associated with a more prolonged progression-free survival (PFS) than diffuse type (HR = 0.29, P = 0.019). Patients with low tumor mutation burden (TMB) showed significantly worse PFS, while high chromosome instability (CIN) was correlated with prolonged OS (HR = 0.27; P = 0.044). Patients who responded to treatment had a higher CIN than nonresponders, and a positive trend towards increasing CIN was observed as response improved (P = 0.019). In our cohort, the most common genes to acquire mutations are AURKA, MYC, STK11, and LRP6 with four patients each. We also discovered an association between clonal branching pattern and survival, with an extensive clonal branching pattern being more closely related to a shorter PFS than other branching patterns (HR = 4.71; P = 0.008). We identified potential molecular and clinical factors that provide insight regarding potential association to trastuzumab resistance in advanced HER2-positive GC patients.

Abstract Background Kinase domain duplications (KDDs) have recently been recognized as oncogenic mutations and possible association with drug resistance in cancers. Method Here, targeted sequencing was performed with the tumor tissue and/or plasma from 65 cancer patients with KDDs. Result Intact KDDs were identified in approximately 0.1% of the total population across multiple cancer types. EGFR KDD was first identified in colorectal cancer and breast cancer, whereas FGFR2 KDD was first identified in gastric cancer. Tumors with EGFR KDD displayed lower concurrent TP53 gene alterations (p = 0.03) and slightly higher chromosome instability (p = 0.27) compared to tumors with non‐EGFR‐KDDs. Immune pathway analysis further revealed the enrichment of the cytokine receptors pathway (93%) in the KDD carriers. Hyperprogression‐related gene mutations were identified in four cases. Conclusion Collectively, our data revealed the genomic features of KDD alterations in a multi‐cancer cohort, providing more information for the potential treatment application in the KDD carriers.

Abstract Statins have been proven to be effective in minimizing the risk of cardiovascular adverse events, however, their effect on BP variability is debatable with respect to their significance and their use as a potential anti‐hypertensive. Using a meta‐analysis approach, the aim of this study was to explore whether certain statins have the potential to lower blood pressure (BP). For the period 2002–2022, Scopus, PubMed, Web of Science, and the Cochrane Central Register of Controlled Trials databases were searched for the studies that examined the effect of statins on blood pressure in normotensive or hypertensive individuals. Randomized controlled clinical trials that investigated this effect were included based on our inclusion criteria. Our primary outcomes were changes in systolic and diastolic blood pressure (DBP). The final analysis of the study included 49 RCTs involving 45 173 participants randomized to receive either statins or placebo. Among the two groups, the total weighted mean difference (WMD) for systolic blood pressure (ΔSBP) was –1.42 (95% CI: –2.38, –0.46; p = .004) and diastolic blood pressure (ΔDBP) was 0.82 (95% CI: –1.28, –0.36; p = .0005). Despite various studies suggesting the efficacy of statins in blood pressure lowering to be significant and non‐significant both, we observed a decrease in SBP and DBP both, although the change was not as large and could be considered significant. A large multicenter, multi‐ethnic, large sample pool size, and a long period follow‐up study is still required to assert these claims.

Abstract Stage III non‐small cell lung cancer (NSCLC) encompasses a group of diseases with high heterogeneity. Such patients should actively receive comprehensive treatments. It is imperative for all stage III NSCLC patients to receive consultation with a multiple disciplinary team, which allows the development of a proposal for clinical diagnosis and treatment. In this consensus, stage III NSCLC is divided into two types (operable and inoperable) according to different clinical conditions. Resectable NSCLC is further subdivided into two conditions (with or without driver genes). For each clinical scenario, this consensus emphasizes that the foundation of any medical decisions regarding the optimal diagnostic or therapy procedure is scientific evidence from clinical research. Finally, based on the level of evidence and strength of recommendations, this consensus provides recommendations for the management of stage III NSCLC from six perspectives. The objective of this consensus is to help clinicians choose the best treatment and promote the standardization of stage III NSCLC diagnosis and treatment in China.

Abstract Background Acral melanoma (AM) is the most common subtype in Chinese melanoma patients with a very poor prognosis. However, our understanding of the disease pathogenesis and molecular landscape is limited by the few studies that have been conducted. Here, we profiled the clinical characteristics, mutational landscapes and tumor immune microenvironment of AM patients to gain insights into disease characteristics and potential treatment strategies. Methods A total of 90 AM patients were enrolled and their tissue samples were subjected to next-generation sequencing and multiplexed immunohistochemistry tests. Kaplan–Meier curves and log-rank tests were used to analyze the prognostic potential of various genetic aberrations and immune cell compositions in AM. Results The median disease-free survival was 21.3 months and estimated median overall survival (OS) was 60 months. More advanced stages, older ages and thickness of greater than 4 mm were associated with worse prognosis in AM patients (HR = 2.57, 95% CI 1.25–5.29, p = 0.01; HR = 2.77, 95% CI 1.22–6.28, p = 0.02; HR = 3.43, 95% CI 1.51–7.82, p

The current use of elastography ultrasound faces challenges, including vulnerability to subjective manipulation, echo signal attenuation, unknown risks of elastic pressure and high imaging hardware cost. Here, the author shows a virtual elastography to empower low-end ultrasound devices with state-of-art elastography function.

Abstract Background Compound epidermal growth factor receptor (EGFR) mutations are less responsive to tyrosine kinase inhibitors (TKIs) than single EGFR mutations in non-small cell lung cancer (NSCLC). However, the detailed clinical characteristics and prognosis of various compound EGFR mutations remain to be elucidated. Methods We retrospectively studied the next-generation sequencing (NGS) data of treatment-naïve tumors from 1025 NSCLC patients with compound EGFR mutations, which were sub-categorized into different combinations of common mutations (19-Del and EGFR exon 21 p.L858R), rare mutations, and variants of uncertain significance (VUSs). Prognosis and drug resistance to first-line TKIs were analyzed in 174 and 95 patients, respectively. Results Compound EGFR mutations were enriched with EGFR exon 21 p.L858R and rare mutations, but not 19-Del (P