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Abstract Leeches are famous for their high medical value and wide environmental adaptability. Among them, cave leeches are a very fascinating and rare group, which is an important component in the study of adaptive evolution of leeches. However, no study has yet reported a reference genome for this group. In this study, we assembled a high-quality chromosome-level genome of the cave terrestrial leech Sinospelaeobdella cavatuses, through Illumina and PacBio sequencing, alongside chromosome conformation capture techniques. The resulting genome spans 153.67 Mb across 9 pseudochromosomes(range: 11.33 to 23.53 Mb), with a mounting rate of up to 95.37% and features an N50 length of 17.15 Mb. This genome is composed of 35.16% repetitive elements and contains 21180 predicted protein-coding genes. Decoding the S. cavatuses genome not only promotes future studies on study of its phylogeny, evolution, and behavior, but also provides valuable resources for in-depth investigation on adaptive evolution of leech.

Abstract Urbanization and industrialization generate vast amounts of solid waste, posing significant threats to the biotic and abiotic components of the environment. Solid wastes-derived carbonaceous catalysts (SW-CCs) represent an effective strategy for resource utilization, and SW-CCs are gradually applied in environmental remediation and energy fields. However, the effects of the properties of SW-CCs on their catalytic activity remain inadequately understood. A comprehensive review of the applications of SW-CCs in environmental remediation and energy fields is yet to be achieved. It is necessary to systematically review the latest research progress of SW-CCs in environmental remediation and energy fields. First of all, this review summarizes the influences of various factors on the properties of SW-CCs and how these properties affect the catalytic activity. Subsequently, it explores the recent research progress and existing issues in the applications of SW-CCs in environmental remediation (persulfate activation, photocatalysis, and Fenton-like oxidation) and the energy sector (H2 production, biodiesel production, and CO2 conversion). Finally, future research prospects and recommendations are provided to facilitate further development and application of SW-CCs. This review offers new insights into the resource utilization of solid waste and the development of efficient and practical carbonaceous catalysts. Graphical Abstract

This study analyzes the production process of traditional Chinese velvet flowers and their cultural inheritance and innovative applications. Through literature review, case studies, and field research, it explores the historical evolution of velvet flower craftsmanship, its technical characteristics, and its application in modern design. The research shows that velvet flower craftsmanship has been revitalized with the help of intangible cultural heritage protection and modern design, demonstrating new vitality in the fashion and home decor fields. This paper proposes strategies for promoting the global dissemination and sustainable development of velvet flower craftsmanship, guiding the modernization of traditional handicrafts.

Abstract Background The effectiveness of adipose-derived stem cells (ADSCs) in therapy diminishes with age. It has been reported that transcription factors (TFs) play a crucial role in the aging and functionality of stem cells. Nevertheless, there is limited understanding regarding the involvement of TFs in the aging mechanism of ADSCs. Methods RNA sequencing (RNA-seq) was utilized to discern the differentially expressed genes in ADSCs obtained from donors of varying ages. TFs exhibiting significant variations across age groups were identified and subsequently validated. ADSCs were manipulated to exhibit either enhanced expression or reduced levels of HES1 and STAT1 via lentivirus transfection and small interfering RNA (siRNA) techniques. The impact of these genetic alterations on ADSCs’ proliferation, migration, and cellular senescence was assessed using EdU, transwell, and senescence-activated β-galactosidase (SA-β-gal) staining assays. The DNA sequences bound by HES1 were investigated through the CUT & Tag assay. Lastly, the therapeutic efficacy of aged ADSCs with HES1 overexpression was evaluated in skin injury model of male Sprague-Dawley rats. Results 678 genes showed differential expression between ADSCs obtained from young and old donors (Y-ADSCs and O-ADSCs), with 47 of these genes being TFs. Notably, the expression of the TF hairy and enhancer of split 1 (HES1) was notably reduced in ADSCs from old donors. Introducing HES1 overexpression in aged ADSCs resulted in improved cellular function and the suppression of cellular senescence, while reducing HES1 levels in young ADSCs had the opposite effect. Mechanistically, HES1 was found to interact with the promoter region of another TF, signal transducer and activator of transcription 1 (STAT1), to inhibit its transcription. Knocking down STAT1 could fully reverse the negative effects caused by decreased HES1 in ADSCs, leading to a reduction in the secretion of pro-inflammatory cytokines such as TNF-α, IL-6, and IL-8. Ultimately, restoring HES1 expression in aged ADSCs demonstrated enhanced therapeutic potential in promoting skin wound healing. Conclusion HES1 acts as an inhibitor of cellular senescence in the aging progression of ADSCs through the modulation of STAT1 expression, suggesting a promising avenue for rejuvenating senescent ADSCs and improving wound healing.

Abstract This study aimed to observe the characteristics of foot posture asymmetry and abnormal gait in patients with unilateral and bilateral knee osteoarthritis (KOA) and to explore the association between foot posture asymmetry, abnormal gait and the clinical symptoms and severity of KOA. Sixty patients with KOA were allocated as follows: unilateral group (UG; n = 30) and bilateral group (BG; n = 30). We accessed foot posture, foot posture asymmetry, gait and plantar pressure parameters and symmetry index, clinical symptom-related scores and disease severity, and investigated the relationship between these variables. The results showed that the overall percentage of asymmetry and severe asymmetry in foot posture were lower in BG than in UG. There was substantial asymmetry in many gait indicators within the two groups, but no significant differences were observed between the two groups. Moreover, foot posture asymmetry, multiple gait and plantar pressure parameters and symmetry indices were closely related to clinical symptoms and disease severity. In conclusion, both unilateral and bilateral KOA patients have foot posture asymmetry and gait asymmetry, but the foot posture asymmetry of the former is more severe than that of the latter. Intervention for this population should treat simultaneously both knee joints. The evaluation and monitoring of foot posture asymmetry, gait and plantar pressure parameters and symmetry indices can provide a more comprehensive and scientific basis for the prevention and treatment of KOA.

In this paper, Index Modulation (IM) aided Generalized Space-Time Block Coding (GSTBC) is proposed, which intrinsically exploits the benefits of IM concept, diversity gain and spatial multiplexing gain. Specifically, the information bits are partitioned into U groups, with each being modulated by IM symbols (i.e. Spatial Modulation (SM), Quadrature SM (QSM),etc). Next, the structure of GSTBC is invoked for each K IM symbol, and a total of μ ​= ​U/K GSTBC codes are transmitted via T time slots. A Block Expectation Propagation (B-EP) detector is designed for the proposed IM-GSTBC structure. Moreover, the theoretical Average Bit Error Probability (ABEP) is derived for our IM-GSTBC system, which is confirmed by the simulation results and helpful for performance evaluation. Simulation results show that our proposed IM-GSTBC system is capable of striking an efficient trade-off between spatial multiplexing gain, spatial diversity gain as well as implementation cost imposed for both small-scale and large-scale MIMO antenna configurations.

Abstract The NLRP3 inflammasome plays a crucial role in inflammatory responses, particularly in alcohol-related liver disease (ALD). Given that NLRP3 has emerged as a potential therapeutic target for ALD, the development of effective inhibitors is of great importance. In this study, we trained 11 regression models, and the results showed that LightGBM, Random Forest, and XGBoost performed the best, achieving R² values of 0.774, 0.755, and 0.719, respectively. Using machine learning models and physical methods, we screened more than 11.5 million compounds from Asinex, Princeton, UkrOrgSynthesis, Chemdiv, Chembridge, Alinda, Enamine, and Lifechemicals, which led to the identification of 26 potential NLRP3 inhibitors. Furthermore, molecular dynamics simulations and MMGBSA binding energy calculations confirmed the stability of the interactions between NLRP3 and three key molecules: 19,655,631 (source Chembridge), 38,214,692 (source Chembridge), and Z1180203703 (source Enamine). Additionally, ADMET analysis revealed their favorable pharmacokinetic properties. This study provides insights and candidate molecules for discovering NLRP3 inhibitors, potentially applicable in treating related diseases.

Abstract This open-label, single-arm, phase 2 trial evaluated the efficacy and safety of neoadjuvant sintilimab combined with anlotinib and chemotherapy, followed by adjuvant sintilimab, for resectable NSCLC. Forty-five patients received anlotinib (10 mg, QD, PO, days 1–14), sintilimab (200 mg, day 1), and platinum-based chemotherapy of each three-week cycle for 3 cycles, followed by surgery within 4–6 weeks. Adjuvant sintilimab (200 mg) was administered every 3 weeks. The primary endpoint was achieving a pathological complete response (pCR). From June 10, 2021 through October 10, 2023, 45 patients were enrolled and composed the intention-to-treat population. Twenty-six patients (57.8%) achieved pCR, and 30 (66.7%) achieved major pathological response (MPR). Forty-one patients underwent surgery. In the per-protocol set (PP set), 63.4% (26/41) achieved pCR, and 73.2% achieved MPR. The median event-free survival was not attained (95% CI, 25.1-NE). During the neoadjuvant treatment phase, grade 3 or 4 treatment-related adverse events were observed in 25 patients (55.6%), while immune-related adverse events were reported in 7 patients (15.6%). We assessed vascular normalization and infiltration of immune-related cells by detecting the expression of relevant cell markers in NSCLC tissues with mIHC. Significant tumor microenvironment changes were observed in pCR patients, including reduced VEGF+ cells and CD4+Foxp3+ Treg cells, and increased perivascular CD4+ T cells, CD39+CD8+ T cells, and M1 macrophages. In conclusion, perioperative sintilimab and neoadjuvant anlotinib plus chemotherapy achieved pCR in a notable proportion of patients with resectable NSCLC and were associated with profound changes in the tumour microenvironment (ClinicalTrials.gov NCT05400070).

ObjectiveTo explore the impact of sex on the efficacy of first-line programmed death-1 (PD-1) blockade plus chemotherapy in patients with advanced lung adenocarcinoma and its potential biological mechanisms. MethodsThe clinical and pathological characteristics and follow-up data of 163 patients with advanced lung adenocarcinoma without driver gene alterations at Shanghai Pulmonary Hospital affiliated to Tongji University from October 2018 to October 2023 were retrospectively collected. Among them, 103 patients received first-line PD-1 blockade plus chemotherapy (51 males and 52 females) and 60 patients received first-line standard platinum-based doublet chemotherapy (39 males and 21 females). Patients were divided into male group and female group. Clinical characteristics, efficacy, progression-free survival (PFS), and overall survival (OS) were compared between the two groups. Kaplan-Meier method was used to plot the survival curves of male and female patients, and log-rank test was used for significance evaluation. Cox proportional hazards model was used to analyze the factors influencing PFS and OS. Multiplex immunofluorescence (mIF) assays were used to analyze the differences of protein expression levels of programmed death-ligand 1 (PD-L1), CD8, CD68, CD4, and FOXP3 between male and female groups in baseline tumor sample. ResultsIn patients receiving first-line PD-1 blockade plus chemotherapy, the median PFS in female group and male group was 13.0 months and 6.8 months, respectively (HR＝0.39, 95%CI 0.25-0.62; P＜0.01). The median OS in female group and male group was 46.2 months and 17.3 months, respectively (HR＝0.30, 95%CI 0.18-0.50; P＜0.01). In patients receiving first-line chemotherapy, the median PFS in female group and male group was 5.7 months and 5.5 months, respectively (P＞0.05); the median OS in female group and male group was 21.7 months and 17.7 months, respectively (P＞0.05). The results of the Cox proportional hazards model showed that sex was an independent factor influencing PFS and OS in patients receiving first-line PD-1 blockade plus chemotherapy (P＜0.05). The results of mIF showed that pretreatment tumor samples of female patients had a significantly higher expression level of CD8 than male patients (P＜0.05), while the expression level of PD-L1, CD68, CD4 and FOXP3 was similar between female and male groups. ConclusionsCompared to male patients, female patients with advanced lung adenocarcinoma benefit more from the first-line PD-1 blockade plus chemotherapy. The increased expression level of CD8 in pretreatment tumor samples of female patients would be the potential mechanism.

Abstract Background Adjacent segment disease (ASD) is a common and serious complication that can develop in the mid- to long-term after lumbar fusion surgery. However, the underlying mechanisms of ASD are not yet fully understood. This study aimed to develop and validate a risk prediction model for ASD in patients who underwent transforaminal lumbar interbody fusion (TLIF) for lumbar degenerative diseases. Methods Patients with lumbar degenerative disease who underwent TLIF between January 2015 and December 2016 were included in the retrospective study. The participants were divided into two groups: ASD and non-ASD. Univariate and multivariate logistic regression analyses were performed to identify factors influencing ASD after TLIF surgery. The receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA) were used to evaluate the model’s discrimination, calibration and clinical value, respectively. Results A total of 11.5% (59/513) of patients developed ASD. Higher BMI, lower BMD, higher disc grade, and reduced disc height were identified as independent risk factors for ASD after TLIF. The model demonstrated good discrimination in both the training and validation sets, with calibration and Hosmer-Lemeshow tests confirming accuracy, and DCA demonstrating clinical applicability. Conclusions The nomogram model demonstrated promise in predicting ASD in patients who underwent TLIF, aiding clinicians in selecting the most suitable surgical approach and optimizing surgical decisions.

The steel industry is considered an important basic sector of the national economy, and its high energy consumption and carbon emissions make it a major contributor to climate change, especially in China. The majority of crude steel in China is produced via the energy- and carbon-intensive blast furnace–basic oxygen furnace (BF–BOF) route, which greatly relies on coking coal. In recent years, China’s steel sector has made significant progress in energy conservation and emission reduction, driven by decarbonization policies and regulations. However, due to the huge output of crude steel, the steel sector still produces 15% of the total national CO2 emissions. The direct reduced iron (DRI) plus scrap–electric arc furnace (EAF) process is currently considered a good alternative to the conventional route as a means of reducing CO2 emissions and the steel industry’s reliance on iron ore and coking coal, since the gas-based DRI plus scrap–EAF route is expected to be more promising than the coal-based one. Unfortunately, almost no DRI is produced in China, seriously restricting the development of the EAF route. Here, we highlight the challenges and pathways of the future development of DRI, with a focus on China. In the short term, replacing natural gas with coke oven gas (COG) and byproduct gas from the integrated refining and chemical sector is a more economically feasible and cleaner way to develop a gas-based route in China. As the energy revolution proceeds, using fossil fuels in combination with carbon capture, utilization, and storage (CCUS) and hydrogen will be a good alternative due to the relatively low cost. In the long term, DRI is expected to be produced using 100% hydrogen from renewable energy. Both the development of deep processing technologies and the invention of a novel binder are required to prepare high-quality pellets for direct reduction (DR), and further research on the one-step gas-based process is necessary.

Abstract Objective This meta-analysis aims to compare the clinical efficacy of mesh non-fixation and fixation in laparoscopic transabdominal preperitoneal (TAPP) inguinal hernia repair, systematically evaluating the application value of the mesh non-fixation technique in clinical settings. Methods A computerized search of PubMed, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov databases was conducted to identify randomized controlled trials (RCTs) comparing mesh non-fixation and fixation in TAPP inguinal hernia repair. Meta-analysis was performed using RevMan 5.3 software, and the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) evidence grading system was employed for outcome quality assessment. Publication bias analysis was performed using Begg’s test. A trial sequential analysis (TSA) was performed using TSA 0.9.5.10 Beta software. Results A total of nine RCTs involving 1,879 inguinal hernia patients were included. Meta-analysis results demonstrated that, compared to the fixation group, the non-fixation group exhibited significantly lower seroma occurrence rate [RR = 0.43, 95% CI (0.20, 0.89), P = 0.02, heterogeneity P = 0.28, I²=22%], Visual Analog Scale (VAS) pain score at 6 months postoperatively [MD=-0.21, 95% CI (-0.29, -0.12), P

Abstract Globally, CRC ranks as a principal cause of mortality, with projections indicating a substantial rise in both incidence and mortality by the year 2040. The immunological responses to cancer heavily rely on the function of CD4Tconv. Despite this critical role, prognostic studies on CRC-related CD4Tconv remain insufficient. In this investigation, transcriptomic and clinical data were sourced from TCGA and GEO. Initially, we pinpointed CD4TGs using single-cell datasets. Prognostic genes were then isolated through univariate Cox regression analysis. Building upon this, 101 machine learning algorithms were employed to devise a novel risk assessment framework, which underwent rigorous validation using Kaplan-Meier survival analysis, univariate and multivariate Cox regression, time-dependent ROC curves, nomograms, and calibration plots. Furthermore, GSEA facilitated the examination of these genes’ potential roles. The RS derived from this model was also analyzed for its implications in the TME, and its potential utility in immunotherapy and chemotherapy contexts. A novel prognostic model was developed, utilizing eight CD4TGs that are significantly linked to the outcomes of patients with CRC. This model’s RS showcased remarkable predictive reliability for the overall survival rates of CRC patients and strongly correlated with malignancy levels. RS serves as an autonomous prognostic indicator, capable of accurately forecasting patient prognoses. Based on the median value of RS, patients were categorized into subgroups of high and low risk. The subgroup with higher risk demonstrated increased immune infiltration and heightened activity of genes associated with immunity. This investigation’s establishment of a CD4TGs risk model introduces novel biomarkers for the clinical evaluation of CRC risks. These biomarkers may enhance therapeutic approaches and, in turn, elevate the clinical outcomes for patients with CRC by facilitating an integrated treatment strategy.

Abstract Background The aim of this study was to explore the relationships between teaching competence, career development, industrial orientation, and specialty construction in the case of intelligent medicine specialties in universities of traditional Chinese medicine, as well as the influencing factors of specialty construction. Methods Two-stage sampling with unequal probability was conducted to distribute self-administered questionnaires in the fieldwork. A structural equation model was built to investigate the influencing factors of specialty construction. Forty-two teachers were recruited and completed the questionnaire. Results The study found that teaching competence, career development, and industrial orientation positively affect specialty construction at a significant level. Career development and industrial orientation play chain mediating roles in the effect of teaching competence on specialty construction. Conclusions In the construction of intelligent medicine specialties, a professional curriculum system should be built that caters to industrial demand and is combined with industrial development, the traditional mode of teaching should be transformed, and the transformation of theoretical knowledge into practical ability should be promoted. Innovations in teaching modes should be achieved by introducing information technology, and the teacher evaluation system should be optimized.

Abstract Extensive studies indicate that mitochondria dysfunction is pivotal for Alzheimer’s disease (AD) pathogenesis; while cumulative evidence suggests that increased mitochondrial stress response (MSR) may mitigate neurodegeneration in AD, explorations to develop a MSR-targeted therapeutic strategy against AD are scarce. We combined cell biology, molecular biology, and pharmacological approaches to unravel a novel molecular pathway by which NAD+-boosting agent nicotinamide mononucleotide (NMN) regulates MSR in AD models. Here, we report dyshomeostasis plasma UPRmt-mitophagy-mediated MSR profiles in AD patient samples. NMN restores NAD+ metabolic profiles and improves MSR through the ATF4-dependent UPRmt pathway in AD-related cross-species models. At the organismal level, NAD+ repletion with NMN supplementation ameliorates mitochondrial proteotoxicity, decreases hippocampal synaptic disruption, decreases neuronal loss, and brain atrophy in mice model of AD. Remarkably, omics features of the hippocampus with NMN show that NMN leads to transcriptional changes of genes and proteins involved in MSR characteristics, principally within the astrocyte unit rather than microglia and oligodendrocytes. In brief, our work provides evidence that MSR has an active role in the pathogenesis of AD, as reducing mitochondrial homeostasis via atf4 depletion in AD mice aggravates the hallmarks of the disease; conversely, bolstering mitochondrial proteostasis by NMN decreases protein aggregation, restores memory performance, and delays disease progression, ultimately translating to increased healthspan.

To examine the effects and mechanisms of Camellia petelotii Chi extract on the rat model of non-alcoholic fatty liver disease (NAFLD), a set of ten SD rats was randomly chosen as the blank group, while the remaining 50 rats were given a high-sugar, high-fat emulsion to develop the model of non-alcoholic fatty liver disease. After 14 days, the rats were separated into different groups based on their serum total cholesterol (TC) levels. These groups included the model group, the simvastatin group (8 mg/kg), and the Camellia petelotii Chi high, medium, and low dose groups (260, 130, 65 mg/kg). The medication was administered continuously for 6 weeks. Before the last administration, an oral glucose tolerance test (OGTT) was performed, and the area under the blood glucose curve (AUC) was calculated. Both serum and liver tissues were collected to examine the concentrations of total cholesterol (TC), triacylglycerol (TG), high-density lipoprotein (HDL-C), low-density lipoprotein (LDL-C), and free fatty acid (FFA). In addition, TC and TG were measured to evaluate the amount of lipids in the liver, while glutamic-pyruvic transaminase (ALT) and glutamic oxaloacetic transaminase (AST) were examined to assess liver function. The levels of malondialdehyde (MDA) was measured to evaluate the extent of lipid peroxidation in the liver, while the activity of superoxide dismutase (SOD) was also evaluated. Serum inflammatory factors interleukin 6 (IL-6), interleukin 8 (IL-8), and tumor necrosis factor (TNF-α) were determined in rats. Serum insulin (FINS) was measured and the insulin resistance index (HOMA-IR) was calculated. The HE staining technique was employed to examine the pathomorphological alterations in the liver and determine the non-alcoholic fatty liver disease activity score (NAS). The gene and protein expression of Toll-like receptor 4 (TLR-4) and nuclear factor κB (NF-κB) were determined in liver tissue. The results showed that compared with the model group, AUC, HOMA-IR and serum levels of FINS, TG, TC, LDL-C, FFA, ALT, AST, IL-6, IL-8, TNF were significantly lower (P

Abstract Background The recent Maternal Immune Activation (MIA) theory suggests maternal systemic inflammation may serve as a mediator in associations between prenatal maternal adversities and neurodevelopmental diseases in offspring. Given the co-exposure to multiple adversities may be experienced by pregnant person, it is unclear whether a quantitative index can be developed to characterize the inflammation related exposure level, and whether this index is associated with neurodevelopmental delays in offspring. Methods Based on Jiangsu Birth Cohort (JBC), a total of 3051 infants were included in the analysis. Inflammation related Prenatal Adversity Index (IPAI) was constructed using maternal data. Neurodevelopmental outcomes were assessed using the Bayley Scales of Infant and Toddler Development, third edition, screening test in one year. Multivariate linear regression and Poisson regression model were performed to analyze the associations between IPAI and neurodevelopment in offspring. Results Compared with “low IPAI” group, offspring with “high IPAI” have lower scores of cognition, receptive communication, expressive communication, and fine motor. The adjusted β were − 0.23 (95%CI: -0.42, -0.04), -0.47 (95%CI: -0.66, -0.28), -0.30 (95%CI: -0.49, -0.11), and − 0.20 (95%CI: -0.33, -0.06). Additionally, the elevated risk for noncompetent development of cognition and receptive communication among “high IPAI” group was observed. The relative risk [RR] and 95% confidence interval [CI] were 1.35 (1.01, 1.69) and 1.37 (1.09, 1.72). Conclusions Our results revealed a significant association between higher IPAI and lower scores across cognition, receptive communication, expressive communication, and fine motor domains, and an increased risk of noncompetent development in the cognition and receptive communication domains.

Abstract The traditional control method of doubly fed induction generators (DFIGs) has poor robustness due to the excessive use of machine parameters, and does not fully consider the control conditions of nonideal power grids, resulting in serious fluctuations in current and power under grid disturbances. To solve these problems, model‐free predictive rotor current control (MFPRCC) based on an ultra‐local model is proposed in this article. The ultra‐local model is adaptive because it can accurately emulate the overall structure of the system and estimate the total disturbance of the system in real time. Under a nonideal grid, the cascaded delayed signal cancellation (CDSC) modules are connected in series behind the outer power loop to extract the fundamental component of the rotor current reference. The proposed method is compared with the traditional model predictive rotor current control (MPRCC) method, and the effectiveness of the proposed method is verified on a 1.5 kW DFIG experimental platform.

Abstract. Background:. Programmed death 1 (PD-1) blockade plus chemotherapy has become the new first-line standard of care for patients with advanced non-small-cell lung cancer (NSCLC). Yet not all NSCLC patients benefit from this regimen. This study aimed to investigate the predictors of PD-1 blockade plus chemotherapy in untreated advanced NSCLC. Methods:. We integrated clinical, genomic, and survival data from 287 patients with untreated advanced NSCLC who were enrolled in one of five registered phase 3 trials and received PD-1 blockade plus chemotherapy or chemotherapy alone. We randomly assigned these patients into a discovery cohort (n = 125), a validation cohort (n = 82), and a control cohort (n = 80). The candidate genes that could predict the response to PD-1 blockade plus chemotherapy were identified using data from the discovery cohort and their predictive values were then evaluated in the three cohorts. Immune deconvolution was conducted using transcriptome data of 1014 NSCLC patients from The Cancer Genome Atlas dataset. Results:. A genomic variation signature, in which one or more of the 15 candidate genes were altered, was correlated with significantly inferior response rates and survival outcomes in patients treated with first-line PD-1 blockade plus chemotherapy in both discovery and validation cohorts. Its predictive value held in multivariate analyses when adjusted for baseline parameters, programmed cell death ligand 1 (PD-L1) expression level, and tumor mutation burden. Moreover, applying both the 15-gene panel and PD-L1 expression level produced better performance than either alone in predicting benefit from this treatment combination. Immune landscape analyses revealed that tumors with one or more variation in the 15-gene panel were associated with few immune infiltrates, indicating an immune-desert tumor microenvironment. Conclusion:. These findings indicate that a 15-gene panel can serve as a negative prediction biomarker for first-line PD-1 blockade plus chemotherapy in patients with advanced NSCLC.

Accurate estimation of natural gas consumption plays a crucial role in energy planning, economic stability, environmental protection, and investment decisions. Despite numerous predictive studies related to natural gas consumption, most of these studies focus on univariate prediction tasks, lacking a reasonable and efficient multivariate prediction approach. To obtain precise forecasting results, this paper constructs a new adaptive grey multivariate prediction model called AGMPM(r,N) based on the fractional-order accumulation operation and grey system theory. It is found that AGMPM(r,N) can degenerate into some grey multivariable prediction models by replacing its own hyperparameters, which reflects its uniformity. In addition, the new model is unbiased for some special time series. In particular, the grey wolf optimizer is used to facilitate the model solution process. To validate the effectiveness of AGMPM(r,N), AGMPM(r,N) and 27 competing algorithms (9 natural gas consumption prediction methods, 10 multivariate prediction models, 7 machine learning algorithms and a statistical predictive model) are used to study the natural gas consumption in China. In addition, ablation experiments are executed. The results of experimental analysis show that the MAPE and MAE of AGMPM(r,N) are 2.795% and 89.880, respectively, which are superior to all competing methods and ablation models.

Due to the lack of design guidance for high-performance Cr–V steel, it is challenging to identify the target steel within a vast design space. In this paper, a design loop combining property-oriented design criteria and machine learning prediction model is proposed. Based on the design criteria, the alloying values of the initial sample and the allowable variation range are given to narrow the search space. Then, the machine learning model is employed to predict properties across all design nodes within the design space. The results suggest that the samples within the design space, meeting the proposed design criteria, demonstrate higher hardness. However, wear resistance decreases rapidly as Cr increases and V/Cr decreases. The predicted optimal sample C2.1V3Cr4Mo2.5 is prepared and its properties are measured, showing that the absolute errors between the measured and predicted values are less than 5%. In addition, C2.1V3Cr4Mo2.5 is more cost-effective than Cr26 and V10. This design loop facilitates the rapid selection of the most promising steel for experimentation and provides a new avenue for the development of wear-resistant alloy steels.

Background: Histopathology diagnosis is often regarded as the final diagnostic method for malignant tumors; however, it has some drawbacks. This study explored a computer-aided diagnostic method that can be used to identify benign and malignant gastric cancer using histopathological images. Methods: The most suitable process was selected through multiple experiments by comparing multiple methods and features for classification. First, the U-net was applied to segment the image. Next, the nucleus was extracted from the segmented image, and the minimum spanning tree (MST) diagram structure that can capture the topological information was drawn. The third step was to extract the graph-curvature features of the histopathological image according to the MST image. Finally, by inputting the graph-curvature features into the classifier, the recognition results for benign or malignant cancer can be obtained. Results: During the experiment, we used various methods for comparison. In the image segmentation stage, U-net, watershed algorithm, and Otsu threshold segmentation methods were used. We found that the U-net method, combined with multiple indicators, was the most suitable for segmentation of histopathological images. In the feature extraction stage, in addition to extracting graph-edge and graph-curvature features, several basic image features were extracted, including the red, green and blue feature, gray-level co-occurrence matrix feature, histogram of oriented gradient feature, and local binary pattern feature. In the classifier design stage, we experimented with various methods, such as support vector machine (SVM), random forest, artificial neural network, K nearest neighbors, VGG-16, and inception-V3. Through comparison and analysis, it was found that classification results with an accuracy of 98.57% can be obtained by inputting the graph-curvature feature into the SVM classifier. Conclusion: This study created a unique feature, the graph-curvature feature, based on the MST to represent and analyze histopathological images. This graph-based feature could be used to identify benign and malignant cells in histopathological images and assist pathologists in diagnosis.

The discrete element method (DEM) has been extensively utilized to investigate the mechanical properties of granules, particularly their microscopic behavior, overcoming limitations in field tests such as cost, time consumption, and soil condition restrictions. To ensure the development of reliable DEM simulations, proper contact model selection and parameter calibration are essential. In this research, a DEM parameter calibration method that could represent the nonlinear relationship between clayey soil pressure and sinkage at different moisture contents was proposed. Firstly, the sinking modulus K and the soil deformation exponent n were identified to reflect the nonlinear pressure–sinkage relationship. Then, sensitive DEM parameters on the soli pressure–sinkage relationship were investigated and calibrated, and the effect of moisture content on them was explored. Finally, the transfer of soil internal stress during subsidence was analyzed using the constructed discrete element model. The average error of the sinking modulus K and the soil deformation exponent n between the DEM and the experimental result at four moisture contents were 4.7% and 4.9%, respectively. The relative error of soil internal stress between simulation and experiment was 6.7%, 4.4%, and 9.7% at depths of 50 mm, 100 mm, and 150 mm, respectively. The soil particle trajectory, soil internal stress distribution, and variations during plate pressure–sinkage progress were analyzed by the constructed DEM model. The results demonstrated good agreement with theoretical models and experimental findings. The proposed clayey soil DEM modeling process that considers the pressure–sinkage nonlinear relationship at different moisture contents can be applied in machine-soil research.

In this paper, efficient signal detectors are designed for Orthogonal Time Frequency Space (OTFS) modulation with Index Modulation (IM) systems. Firstly, the Minimum Mean Squared Error (MMSE) based linear equalizer and its corresponding soft-aided decision are studied for OTFS-IM. To further improve the performance, a Vector-by-Vector-aided Message Passing (VV-MP) detector and its associated soft-decision are proposed, where each IM symbol is considered an entire vector utilized for message calculation and passing. Simulation results are shown that the OTFS-IM system relying on the proposed detectors is capable of providing considerable Bit Error Rate (BER) performance gains over the OTFS and Orthogonal Frequency Division Multiplex (OFDM) with IM systems.

Orbital Angular Momentum (OAM) waves are characterized by helical wave fronts and orthogonality between different modes. Therefore, OAM waves have huge potential in improving wireless communications' channel capacity and radar imaging's resolution. Consequently, the generation and application of OAM waves have attracted a lot of attention. And many methods are proposed to generate OAM waves. Although antenna array is the most popular method of generating OAM waves, OAM waves generated by antenna array have redundant modes. However, all advantages of OAM waves are closely related to infinite OAM modes. Thus, to better apply OAM waves to wireless communications and radar, it is very important to reduce unnecessary OAM modes and improve the OAM mode purity. In order to improve the OAM mode purity, two combined antenna arrays composed of X direction antenna and Y direction antenna array are proposed in this paper. The X direction antenna array and the Y direction antenna array are supplied by the excitations with the same amplitude and fixed phase shift. The overall phase shift of the X direction antenna array is π/2 more or less than that of the Y direction antenna array. The results of formulas and antenna models in CST show that the combined antenna arrays can generate OAM waves with less redundant modes in x component, y component and z component. Besides, the z component carries pure OAM modes.

Abstract Peritoneal recurrence (PR) in gastric cancer after curative resection has poor prognosis. Therefore, we aimed to construct a nomogram to predict PR, and establish PR score for risk stratification to guide adjuvant chemotherapy. A total of 315 patients with gastric cancer after radical surgery were included, and randomly stratified into training group (n = 221) and validation group (n = 94). Univariate and multivariate analyses were used to determine predictive factors of PR. The nomogram was constructed to predict the risk of PR. We utilized the time-dependent area under the receiver operating characteristic (ROC) curves (AUCs), calibration curves, and decision curve analysis (DCA) to evaluate the performance of the nomogram. Multivariate analysis showed that tumor site, N stage, preoperative CEA, and postoperative CA199 were independent predictors of PR. A nomogram was constructed to predict PR based on these factors. The AUC value was 0.755 in the training group and 0.715 in the validation group. The calibration curves showed good agreement between prediction and observation in the training and validation groups. The decision curve analysis displayed a good net benefit of the nomogram. The novel PR score was developed and patients were stratified into the low-, medium-, and high -risk groups. For the high-risk group, postoperative adjuvant chemotherapy significantly improved patients' overall survival (OS) and disease-free survival (DFS). The establishment of nomogram facilitates the prediction of PR after radical gastrectomy, and a novel PR score may help guide adjuvant chemotherapy for gastric cancer.

The Anqing section of the Yangtze (Changjiang) River in Anhui Province, China, is one of the most important migratory routes and distribution of the highly valued diadromous estuarine tapertail anchovy Coilia nasus. In the past, this section has suffered a severe loss of C. nasus resources caused by human activities, especially overfishing and water pollution. Since 2019, a fishing ban policy for the species in the Yangtze River has been introduced in China for resource restoration. Otoliths are calcium carbonate structures, and otolith microchemistry can provide detailed life history information that can be used to compare habitat use between different saline water bodies. To study the habitat history of C. nasus in the Anqing section of the Yangtze River after the implementation of the fishing ban, we examined the microchemical characteristics (Sr and Ca) of otoliths from the long (previously named C. ectenes) and short maxillary (previously named C. brachygnathus) types of anchovy using electron probe X-ray microanalysis (EPMA). Line-transect analysis of Sr/Ca ratios suggested that the short maxillary type of C. nasus could be divided into two groups. The otolith Sr/Ca ratios (calculated and expressed as Sr/Ca ×1, 000) of one group were always < 3.0, indicating their freshwater residency. Those of the other group had phases of low (< 3.0, believed to be indicative of a freshwater habitat) and high values (> 3.0, believed to be indicative of a brackish or seawater habitat), indicating that anchovies not only have a freshwater habitat history with low salinity but also a brackish habitat history with high salinity. The latter group of anchovies were typically anadromous C. nasus, as the Sr/Ca ratio of the otoliths of C. nasus fluctuated significantly and coincided with variations between freshwater and estuarine brackish or seawater (i.e., anchovies experienced not only freshwater habitats but also brackish water habitats at different stages of their life history). The Sr content mapping of EPMA with different color patterns for freshwater (blue), brackish water (green-yellow) and seawater (red) habitats also confirmed the results obtained from the line-transect analysis. Our results demonstrated that the population composition of C. nasus in the Anqing section of the Yangtze river became complex, and there was coexistence of freshwater resident and anadromous C. nasus in the Anqing section of the Yangtze River in Anhui Province, China (i.e., freshwater resident and anadromous short maxillary and anadromous long maxillary type C. nasus). This phenomenon may suggest a restoration of C. nasus resource diversity after the implementation of the fishing ban in the Anqing section of the Yangtze River.

An innovative technology for the direct reduction of copper slag was studied while smelting Cu-Fe alloy by carbon to recover the main valuable elements from the copper smelting slag. The melting temperature of samples first decreased, followed by an increase in Fe3O4 content in slag. The melting temperature reached the minimum temperature of 1157 °C once the Fe3O4 content was about 8 wt%. The recovery rate of copper and iron first increased gradually, followed by a rapid increase in the modifier (CaO). Subsequently, the rise in the recovery rate slowed down. The reduction rate of copper and iron only increased by 1.61% and 1.05% from 5 wt% CaO to 10 wt% CaO, but significantly increased by 8.89% and 14.21% from 10 wt% CaO to 25 wt% CaO, and remained almost unchanged beyond 25 wt% CaO. This could be attributed to the reaction between modifier (CaO) and silicate in acidic copper slag to generate low melting point composite oxide while replacing free iron oxides, improving the melting properties and reduction reaction. Meanwhile, the recovery rates of copper and iron increased with the increase of reaction time, reaction temperature, and reduction agent in a certain range. To obtain good element yield, the optimum conditions for reducing copper and iron from the molten copper slag were determined to be 1500 °C, 14 wt% C, 20–25 wt% CaO, and 60–80 min. The recovery rates of iron and copper reached about 90% and 85%, and the contents of iron and copper in alloy reached about 91–93 wt% and 5–7 wt%, respectively. The tailing was mainly composed of Ca3Si3O9, Ca(Mg,Al)(Si,Al)2O6, and SiO2, which could be used as a raw material for cement and pelletizing.

Abstract In this paper, we present a new type of isolator based on one-way surface magnetoplasmons (SMPs) at microwave frequencies, and it is the first time that an experimental prototype of isolator with wideband and ultra-high isolation is realized using SMP waveguide. The proposed model with gyromagnetic and dielectric layers is systematically analyzed to obtain the dispersion properties of all the possible modes, and a one-way SMP mode is found to have the unidirectional transmission property. In simulation and experiment with metallic waveguide loaded with yttrium–iron–garnet (YIG) ferrite, the scattering parameters and the field distributions agree well with the analysis and verify the one-way transmission property. The isolation is found to be as high as 80 dB and the typical value of insertion loss is 1 dB. Besides, the one-way transmission band can be controlled by changing the magnetic bias. From theoretical analysis and simulation, it is found that with a tiny value of 10 Oe of the magnetic bias, the relative bandwidth can be tuned to be greater than 50%. Compared with conventional isolators, this one-way SMP isolator has the advantages of ultra-high isolation, wide relative frequency band, and requires much smaller bias field, which has promising potential in non-reciprocal applications.

Abstract Objective This study aimed to compare the impact of case-based learning (CBL) versus lecture-based learning (LBL) on dental students' clinical decision-making regarding DF severity using Visual Analog Scale (VAS) scoring. Methods Eighty first-year graduate dental students were randomly assigned to either the CBL (n = 38) or LBL (n = 42) groups. Both groups received instruction on DF diagnosis, with CBL involving small group sessions analyzing real cases and LBL involving traditional lectures. Effectiveness was assessed by presenting 32 dental fluorosis cases with Thylstrup-Fejerskov Index (TSIF) scores ranging from 0 to 7 through slide presentations to both groups for VAS assessment. Five evaluators of each group randomly selected were asked to repeat the rating 2 weeks later. Statistical analysis included two-way ANOVA for group and gender differences, intra-class correlation coefficient (ICC) for reliability, and Spearman correlation coefficients for validity. Results Variations in VAS scores were observed between CBL and LBL groups, with no significant gender impact. Excellent inter- and intra-evaluator agreement was found for VAS scoring in both groups, indicating its reliability. Validation against established indices (such as DI and TSIF) demonstrated strong correlations, with CBL students exhibiting higher correlations. Conclusions CBL enhances students' clinical decision-making and proficiency in DF diagnosis, as evidenced by more consistent and accurate VAS scoring compared to LBL. These findings highlight the importance of innovative educational strategies in dental curricula, with implications for improving training quality and clinical outcomes. Trial registration: The study was registered at the Clinical Research Center, Hospital of Stomatology, Wuhan University (Registration code: HGGC-036).

Abstract Metasurfaces are capable of fully reshaping the wavefronts of incident beams in desired manners. However, the requirement for external light excitation and the resonant nature of their meta-atoms, make challenging their on-chip integration. Here, we introduce the concept and design of a fresh class of metasurfaces, driven by unidirectional guided waves, capable of arbitrary wavefront control based on the unique dispersion properties of unidirectional guided waves rather than resonant meta-atoms. Upon experimentally demonstrating the feasibility of our designs in the microwave regime, we numerically validate the introduced principle through the design of several microwave meta-devices using metal-air-gyromagnetic unidirectional surface magneto-plasmons, agilely converting unidirectional guided modes into the wavefronts of 3D Bessel beams, focused waves, and controllable vortex beams. We, further, numerically demonstrate sub-diffraction focusing, which is beyond the capability of conventional metasurfaces. Our unfamiliar yet practical designs may enable full, broadband manipulation of electromagnetic waves on deep subwavelength scales.

Abstract Environmental and physiological situations can challenge the balance between protein synthesis and folding capacity of the endoplasmic reticulum (ER) and cause ER stress, a potentially lethal condition. The unfolded protein response (UPR) restores ER homeostasis or actuates programmed cell death (PCD) when ER stress is unresolved. The cell fate determination mechanisms of the UPR are not well understood, especially in plants. Here, we integrate genetics and ER stress profiling with natural variation and quantitative trait locus analysis of 350 natural accessions of the model species Arabidopsis thaliana. Our analyses implicate a single nucleotide polymorphism to the loss of function of the general PCD regulator BON-ASSOCIATED PROTEIN2 (BAP2) in UPR outcomes. We establish that ER stress-induced BAP2 expression is antagonistically regulated by the UPR master regulator, inositol-requiring enzyme 1 (IRE1), and that BAP2 controls adaptive UPR amplitude in ER stress and ignites pro-death mechanisms in conditions of UPR insufficiency.

This study employed optical microscopy (OM), scanning electron microscopy (SEM), and energy-dispersive X-ray spectroscopy (EDS) to investigate the impact of vanadium (V) on the microstructure and mechanical properties of gray cast iron (GCI) HT250. Additionally, Thermo-Calc software was employed to explore the influence of V on the solidification process. The results indicate that adding trace amounts of V in GCI forms a face-centered cubic VC phase, with the precipitation temperature of the VC phase gradually increasing. When the V content reaches 0.28 wt%, the VC phase begins to precipitate during the eutectic reaction. The incorporation of V consumes carbon, reducing the graphite content and promoting the formation of type D graphite. As the V content increases, there is an enlargement in the pearlite area ratio, a decrease in the pearlite layer spacing, and a reduction in the size of eutectic cells. These microstructural alterations lead to enhanced mechanical properties. The tensile strength peaks at 336 MPa with a V content of 0.77 wt%, representing a 29% increase compared to samples without added V. Similarly, the Vickers hardness increases with increasing V content, reaching a peak of 373 HV at 0.92 wt% V, a 27% increase compared to samples without V addition. However, at this point, the tensile strength decreases to 322 MPa.

To achieve the goal that China and Nepal jointly announce the new height of Mount Qomolangma (MQ), the campaign of Qomolangma Height Survey (QHS) was carried out from 2019 to 2020. A high precision geoid model realizing the common height datum for both sides is necessary for determining the unique height of MQ. However, high altitude and rugged topography make it extremely difficult to conduct terrestrial gravity measurements in this region, the accuracy of geoid model is restricted by terrestrial gravity data gaps. In the campaign of 2020 QHS, the airborne gravity survey was carried out over MQ and its surrounding areas, the airborne gravity data covering an area of 12,700 km2 were successfully collected. For the first time, the high precision observations of terrestrial gravity and BeiDou Navigation Satellite System (BDS) at the peak of MQ were collected. These datasets pave the way for the precise determination of the orthometric height of MQ. According to the definition of the International Height Reference System (IHRS), we developed the IHRS-based gravimetric quasigeoid model by combining the airborne and terrestrial gravity data. Validations against highly accurate GNSS leveling data at 61 benchmarks demonstrate that the accuracy of the quasigeoid model is 3.8 cm, and the addition of airborne gravity data improves the accuracy by 51.3%. Based on the IHRS, the final orthometric height of the snow surface of the peak of MQ is determined to be 8848.86 m.

Abstract Background Tuberculosis (TB) remains a global public health event of great concern, however epidemic data on TB covering entire areas during the special period of the COVID-19 epidemic have rarely been reported. We compared the dissemination and multidrug-resistance patterns of Mycobacterium tuberculosis complex (MTBC) in the main urban area of Luoyang City, China (including six municipal jurisdictions) and nine county and township areas under its jurisdiction, aimed to establish the epidemiology of TB in this region and to provide reference for precision anti-TB in places with similar settings. Methods From 2020 to 2022, sputum samples were collected from 18,504 patients with confirmed, suspected and unexcluded TB in 10 designated TB medical institutions. Insertion sequence 6110 was amplified by PCR (rpoB gene detection if necessary) to confirm the presence of MTBC. PCR-positive specimens were analyzed by multicolor melting curve analysis to detect multidrug resistance. Results Among the 18,504 specimens, 2675 (14.5%) were MTBC positive. The positive rate was higher in the main urban area than in the county and township areas (29.8% vs. 10.9%, p 60 years were the largest group infected with MTBC in the main urban area, compared with individuals aged

To investigate the effects of different extraction processes on the physicochemical properties and volatile flavor compounds of chicken oil. This study used three different extraction processes, namely dry, wet and microwave to extract chicken oil. The physicochemical properties of chicken oil extracted by different processes were comprehensively compared. At the same time, the volatile substance composition was determined by headspace gas chromatography-mass spectrometry, and the key volatile flavor component composition differences in chicken oil extracted by different processes were established by combining relative odor activity values, principal component analysis, and cluster analysis. The results showed that the chicken oil cooked by dry method had the lowest brightness, a redder and yellower color, and a lower content of malondialdehyde. Wet cooking chicken oil had the highest brightness, a greenish or yellowish color, and a lower acid value. The chicken oil cooked by microwave had a slightly darker brightness, lighter yellow and red, higher extraction rate, better oxidation stability, and shorter cooking time. A total of 49 volatile flavor compounds were identified in chicken oil samples extracted using different extraction methods. Among them, 39, 41, and 44 volatile flavor compounds were extracted from chicken oil using dry, wet, and microwave methods, respectively, with a total of 30 volatile flavor compounds. By combining ROAV and PCA, (E,E)-2,4-heptadienal, 1-octen-3-ol, hexanal, (E)-2-deceenal, 1-pentanol, octanal, (E,E)-2,4-decadienal, and 3-methylbutanal were identified as the main characteristic flavor compounds of chicken oil. The characteristic flavor substances extracted from chicken oil by microwave method had a high content and a variety of types. This study indicated that microwave technology had the advantages of relatively short time consumption, high yield, good oxidation stability and high content with variety of characteristic flavor substances in chicken oil, making it a worthwhile approach for further research and exploration of chicken oil extraction.

IntroductionGynophore-pod strength is one of important mechanical properties that affect mechanized harvesting quality in peanut. Yet its molecular regulation remains elusive.MethodsWe measured gynophore-pod strength across three environments using a recombinant inbred line (RIL) population derived from a cross between Yuanza9102 and Xuzhou68-4, followed by QTL mapping. Lines with extreme gynophore-pod strength from the RILs were selected to perform anatomical analysis and transcriptome analysis to elucidate the underlying molecular mechanisms governing gynophore-pod strength.Results and discussionBoth genotypic factor and environments affected gynophore-pod strength significantly, and its broad sense heritability (h2) was estimated as 0.77. Two QTLs that were stable in at least two environments were detected. qGPS.A05-1 was mapped 4cM (about 1.09Mb) on chromosome A05, and qGPS.B02-1 was mapped 3cM (about 1.71Mb) on chromosome B02. Anatomical analysis showed higher lignin content in lines with extreme high gynophore-pod strength compared to those with extreme low gynophore-pod strength. Additionally, comparative transcriptome analysis unveiled that phenylpropanoid biosynthesis was the main pathway associated with high gynophore-pod strength. Further, we predicted VJ8B3Q and H82QG0 as the candidate genes for qGPS.A05-1 and qGPS.B02-1, respectively. The two stable QTLs and their associated markers could help modify gynophore-pod strength. Our findings may offer genetic resources for the molecular-assisted breeding of new peanut varieties with improved mechanized harvesting quality.

Pulmonary alveolar proteinosis (PAP) is characterized by the accumulation of surfactant material in alveoli. Few aPAP cases with a history of dust inhalation show both paves stone-like changes and micronodules in the chest CT scan. We present a 52-year-old male patient withsilicosis complicated with aPAP due to long-term dust inhalation during the construction of bridge piers columns. In this case report, chest CT of the patient displayed nonuniform ground-glass and patchy shadows in both lungs, paving stone-like changes, as well as diffuse distribution of high-density small nodular shadows, and the nodules tended to confluence.

Linezolid-resistant enterococci have increased in recent years due to the worldwide spread of acquired resistance genes (cfr, optrA, and poxtA) in clinical, animal, and environmental settings. This study investigated the carriage of optrA-positive enterococci among patients in the anorectal surgery ward in Hangzhou, China, and characterized the genetic context of optrA. A total of 173 wound secretion samples were obtained to screen optrA-positive enterococci. Of the 173 samples, 15 (8.67%) were positive for optrA, including 12 Enterococcus faecalis, two E. faecium, and one E. hirae. Multilocus sequence type analysis revealed that 12 optrA-positive E. faecalis isolates belonged to eight different sequence types (STs), of which ST16 was the main type. Eight optrA variants were identified, whose optrA flanking regions with a fexA gene downstream were bounded by different mobile genetic elements. Furthermore, the optrA gene in 8 out of 15 optrA-positive enterococci could be successfully transferred through conjugation. The findings revealed a high carriage rate of optrA in enterococci from one anorectal surgery ward in China. The dissemination of optrA-positive enterococci isolates in clinical settings should be continually monitored.

Objective This study aims to explore the optimal predictors of HBV-associated HCC using Lasso, and establish a prediction model. Methods A retrospective analysis was conducted on patients who underwent CBC and CRP testing between January 2016 and March 2024. The study population comprised 5441 cases divided into three cohorts: non-HBV-infected (1333 cases), HBV-infected (1023 cases), and HBV-associated HCC (3085 cases). A value of CRP

BackgroundThis study aimed to characterize the oral and gut microbiota in prediabetes mellitus (Pre-DM) and type 2 diabetes mellitus (T2DM) patients while exploring the association between tongue manifestations and the oral-gut microbiota axis in diabetes progression.MethodsParticipants included 30 Pre-DM patients, 37 individuals with T2DM, and 28 healthy controls. Tongue images and oral/fecal samples were analyzed using image processing and 16S rRNA sequencing. Machine learning techniques, including support vector machine (SVM), random forest, gradient boosting, adaptive boosting, and K-nearest neighbors, were applied to integrate tongue image data with microbiota profiles to construct predictive models for Pre-DM and T2DM classification.ResultsSignificant shifts in tongue characteristics were identified during the progression from Pre-DM to T2DM. Elevated Firmicutes levels along the oral-gut axis were associated with white greasy fur, indicative of underlying metabolic changes. An SVM-based predictive model demonstrated an accuracy of 78.9%, with an AUC of 86.9%. Notably, tongue image parameters (TB-a, perALL) and specific microbiota (Escherichia, Porphyromonas-A) emerged as prominent diagnostic markers for Pre-DM and T2DM.ConclusionThe integration of tongue diagnosis with microbiome analysis reveals distinct tongue features and microbial markers. This approach significantly improves the diagnostic capability for Pre-DM and T2DM.

Objectives: The epidemical and clinical features of distinct hantavirus infections exhibit heterogeneity. However, the evolving epidemics and distinct determines of the two hantavirus infections remain uncertain. Methods: Data on hemorrhagic fever with renal syndrome (HFRS) cases and genotyping were collected from multiple sources to explore the distribution dynamics of different endemic categories. Four modelling algorithms were used to examine the relationship between infected hantavirus genotypes in HFRS patients, as well as assess the impacts of urbanization-related factors on HFRS incidence. Results: The number of cities dominated by Hantaan (HTNV) and Seoul (SEOV) viruses was projected to decrease between two phases, while the mixed endemic cities increased. Patients with SEOV infection predominantly presented gastrointestinal symptoms. The modeling analysis revealed that built-up land and real GDP demonstrated the highest contribution to HTNV and SEOV infections, respectively. The impact of nightlight index and park green land was more pronounced in HTNV-dominant cities, while cropland, impervious surface, and floor space of commercialized buildings sold contributed more to HFRS incidence in SEOV-dominant cities. Conclusions: Our findings fill a gap for the three endemic categories of HFRS, which may guide the development of targeted prevention and control measures under the conditions of urbanization development.

Myocardial ischemia causes extensive damage, further exacerbated by reperfusion, a phenomenon called myocardial ischemia/reperfusion injury (MIRI). Nowadays, the pathological mechanisms of MIRI have received extensive attention. Oxidative stress, multiple programmed cell deaths, inflammation and others are all essential pathological mechanisms contributing to MIRI. Mitochondria are the energy supply centers of cells. Numerous studies have found that abnormal mitochondrial function is an essential ''culprit'' of MIRI, and mitophagy mediated by the phosphatase and tensin homolog (PTEN)-induced kinase 1 (PINK1)/Parkin signaling pathway is an integral part of maintaining mitochondrial function. Therefore, exploring the association between the PINK1/Parkin signaling pathway-mediated mitophagy and MIRI is crucial. This review will mainly summarize the crucial role of the PINK1/Parkin signaling pathway-mediated mitophagy in MIR-induced several pathological mechanisms and various potential interventions that affect the PINK1/Parkin signaling pathway-mediated mitophagy, thus ameliorating MIRI.

ABSTRACT Harmful algal blooms (HABs) often occur in estuaries due to their unique environmental heterogeneity, posing significant environmental and human health risks. However, there is limited understanding of the community composition and community‐level change points (thresholds) of harmful microalgae in subtropical estuaries. This study explored harmful microalgae community structure and thresholds in the Dafengjiang River estuary using a metabarcoding approach. The results revealed 63 harmful microalgae species, and major species included Guinardia flaccida, Prorocentrum cordatum, Thalassiosira punctigera, Pseudo‐nitzschia galaxiae and T. gravida. Nonparametric change‐point analysis and threshold indicator taxa analysis (TITAN) showed threshold responses of harmful microalgae community structure to ammonium (57.5–60 μg·L−1), total phosphorus (27.8–28.5 μg·L−1) and dissolved inorganic phosphorus (14.5–28 μg·L−1) along the salinity gradient. Wider environmental thresholds were also found in hypersaline areas. Additionally, Pyrodinium bahamense, Pfiesteria piscicida, Skeletonema tropicum and T. punctigera were sensitive to environmental changes and thus could be used as bioindicators. Overall, our study unveiled diverse abrupt transitions of harmful microalgal communities, providing a risk assessment for human health and ecological safety in subtropical estuary ecosystems.

As a high heat flux linear plasma device designed for studying divertor materials in future fusion reactors, HIT-PSI(Plasma Surface Interaction device at Harbin Institute of Technology) has been successfully constructed and has maintained stable operation since its completion. The characteristics of He plasma beams in HIT-PSI are investigated by emission spectroscopy and an infrared camera, with preliminary irradiation experiments conducted by bombarding tungsten with the beam. For relatively conservative discharge parameters, HIT-PSI achieved a steady-state heat flux capacity of ∼40 MW/m2 using infrared measurements, with the full width at half maximum (FWHM) of the heat flux beam reaching 4 mm. These characteristics make HIT-PSI an advanced platform for testing divertor materials and plasma-facing components, providing essential experimental supports for research and development of high-performance divertor materials.

Abstract Arboviruses, transmitted by medical arthropods, pose a serious health threat worldwide. During viral infection, Post Translational Modifications (PTMs) are present on both host and viral proteins, regulating multiple processes of the viral lifecycle. In this study, a mammalian E3 ubiquitin ligase WWP2 (WW domain containing E3 ubiquitin ligase 2) is identified, which interacts with the NS1 protein of Zika virus (ZIKV) and mediates K63 and K48 ubiquitination of Lys 265 and Lys 284, respectively. WWP2‐mediated NS1 ubiquitination leads to NS1 degradation via the ubiquitin‐proteasome pathway, thereby inhibiting ZIKV infection in mammalian hosts. Simultaneously, it is found Su(dx), a protein highly homologous to host WWP2 in mosquitoes, is capable of ubiquitinating NS1 in mosquito cells. Unexpectedly, ubiquitination of NS1 in mosquitoes does not lead to NS1 degradation; instead, it promotes viral infection in mosquitoes. Correspondingly, the NS1 K265R mutant virus is less infectious to mosquitoes than the wild‐type (WT) virus. The above results suggest that the ubiquitination of the NS1 protein confers different adaptations of ZIKV to hosts and vectors, and more importantly, this explains why NS1 K265‐type strains have become predominantly endemic in nature. This study highlights the potential application in antiviral drug and vaccine development by targeting viral proteins' PTMs.

BackgroundThe pancreas plays an important role in the nutrition and metabolism of the whole body. Many disease processes including obesity, diabetes mellitus (DM), acute or chronic pancreatitis, and pancreatic carcinoma result in abnormality of pancreas morphology and function. Magnetic resonance imaging (MRI) provides quantitative parameters including T1, T2, and apparent diffusion coefficient (ADC) values for evaluating normal and abnormal pancreas. Based on the normal range of these quantitative parameters, pancreatic abnormality could be detected early. However, the range and the relationship of T1, T2, and ADC values with gender and age groups using the same dataset have not been explored.PurposeTo establish the ranges of MRI tissue and functional parameters, including T1, T2, and ADC values, in healthy adult pancreas and their correlations with gender, subregion, and age.Materials and methodsThe T1, T2, and ADC values of healthy pancreas in 86 adults were measured using a 3.0-T MRI scanner. The average T1, T2, and ADC values were obtained in the whole pancreas and subregions (head, neck, body, and tail). Their correlations with gender and age were investigated.ResultsThe T1, T2, and ADC values of the whole pancreas from all subjects were 870.07 ± 61.86 ms, 44.07 ± 6.14 ms, and 1.072 ± 0.212 × 10−3 mm2/s, respectively. T2 values were significantly different between genders (P < 0.05). No significant differences were found between subregions. The T1, T2, and ADC values differed significantly among the age groups (P < 0.05). The T1 value revealed a moderately positive correlation, while the T2 and ADC values displayed negative correlations with age (r = 0.31, −0.45, and −0.39, respectively). The combination of T1, T2, and ADC values achieved the highest AUC value and showed a significant difference compared to T1, T2, and ADC values alone in predicting age older than 45 years.ConclusionThis study established the normal ranges of T1, T2, and ADC. We found that T2 is different between men and women, and T1, T2, and ADC are age-dependent. These results could be useful for quantitative MRI of pancreatic disease.