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Abstract Information technology has brought about significant changes in enterprises, and new work situations have led to new problems. Employee resistance to new technologies, their ability to learn, and their ability to utilize personal resources to improve work engagement in the face of technological pressure are important factors that companies need to consider when undergoing digital transformation. The influence mechanism of configuration effects on factors around employee work engagement has not been explored, and technostress creators have rarely been included in the configuration as influencing factors in previous studies. On the basis of the job demands-resources (JD-R) model and trait activation theory, this study explored the factors that affect employees’ work engagement at the level of job demands and personal resources. The fuzzy-set qualitative comparative analysis (fsQCA) method was used to investigate the influence of technical stressors, self-efficacy, and the Big Five personality traits on employees’ work engagement. Through a survey of 225 employees in the context of enterprise digital transformation, the results show three driving paths that promote employees’ work engagement: openness to experience conscientiousness, self-efficacy driven, and inhibition to technical stressors. The study also analyzed employees’ low work engagement state, which is driven by an inhibition of agreeableness and extraversion. This research enriches the study of factors influencing work engagement in the digital transformation of enterprises.

This study proposes a hybrid network model based on data enhancement to address the problem of low accuracy in photovoltaic (PV) power prediction that arises due to insufficient data samples for new PV plants. First, a time-series generative adversarial network (TimeGAN) is used to learn the distribution law of the original PV data samples and the temporal correlations between their features, and these are then used to generate new samples to enhance the training set. Subsequently, a hybrid network model that fuses bi-directional long-short term memory (BiLSTM) network with attention mechanism (AM) in the framework of deep & cross network (DCN) is constructed to effectively extract deep information from the original features while enhancing the impact of important information on the prediction results. Finally, the hyperparameters in the hybrid network model are optimized using the whale optimization algorithm (WOA), which prevents the network model from falling into a local optimum and gives the best prediction results. The simulation results show that after data enhancement by TimeGAN, the hybrid prediction model proposed in this paper can effectively improve the accuracy of short-term PV power prediction and has wide applicability.

The hot deformation behavior of modified N50 austenitic stainless steel in the temperature range 950∼1250 °C and strain rate range of 0.01–50/s was studied by uniaxial compression experiment. The processing map and the constitutive equation for the finite element simulation were established, and the recrystallization mechanism was discussed. The results indicated that the dominant deformation mode DDRX (discontinuous dynamic recrystallization) increased with the rise of deformation temperature while the CDRX (continuous dynamic recrystallization) was on the contrary. There is a decrease in global recrystallization with increasing strain rate, up to a threshold 1/s beyond which the global recrystallization began significantly promotion owing to not only the adiabatic heat and higher stored energy, but also quick Post-DRX mechanism induced by delay quenching. The reasonable hot working interval was determined by a hot working map, then the most suitable hot extrusion parameters (1180°C-100 mm/s) were further obtained with the help of finite element simulation, and ultimately, the industrial hot extrusion trials of N50 pipes with Post-DRX features were further completed. The tensile performance of final jacket pipes was far beyond the current mainstream low-temperature austenitic structural steel and met the requirements of the new generation of superconducting coil jacket materials.

Colorectal cancer (CRC) is a prevalent tumour with high morbidity rates worldwide, and its incidence among younger populations is rising. Early diagnosis of CRC can help control the associated mortality. Fungi are common microorganisms in nature. Recent studies have shown that fungi may have a similar association with tumours as bacteria do. As an increasing number of tumour-associated fungi are discovered, this provides new ideas for the diagnosis and prognosis of tumours. The relationship between fungi and colorectal tumours has also been recently identified by scientists. Therefore, this paper describes the limitations and prospects of the application of fungi in diagnosing CRC and predicting CRC prognosis.

Abstract Immune checkpoint inhibitors (PD‐1/PD‐L1 and CTLA‐4 blockade) have revolutionized the treatment landscape in non‐small cell lung cancer (NSCLC). Secondary resistance to immunotherapy (IO), which poses a substantial challenge in clinical settings, occurs in several initial responders. Currently, new treatment approaches have been extensively evaluated in investigational studies for these patients to tackle this difficult problem; however, the lack of consistency in clinical definition, uniform criteria for enrollment in clinical trials, and interpretation of results remain significant hurdles to progress. Thus, our expert panel comprehensively synthesized data from current studies to propose a practical clinical definition of secondary resistance to immunotherapy in NSCLC in metastatic and neoadjuvant settings. In addition to patients who received IO alone (including IO‐IO combinations), we also generated a definition for patients treated with chemotherapy plus IO. This consensus aimed to provide guidance for clinical trial design and facilitate future discussions with investigators. It should be noted that additional updates in this consensus are required when new data is available.

Abstract Background Several studies have explored which COS protocol yields a higher blastocyst euploidy rate, but findings have been inconsistent. The present study aimed to explore whether controlled ovarian stimulation (COS) protocols was associated with euploid blastocyst rate in pre-implantation genetic testing for aneuploidy (PGT-A) cycles. Methods The study was a retrospective study where data were obtained from three reproductive medicine centers. The study included PGT-A cycles with the GnRH-a, GnRH-ant, or PPOS protocols, and the data on patient demographics, protocols, and embryonic outcomes were collected for the PGT-A cycles performed between January 2019 and August 2022. Results This study included 457 PGT-A cycles from three reproductive medicine centers, with 152, 126, and 179 cycles performed using the PPOS, GnRH-a, and GnRH-ant protocols, respectively. The baseline characteristics of the three groups show no significant differences were observed in female BMI, infertility type, and infertility duration among the PPOS, GnRH-a, and GnRH-ant protocol groups. The study found no significant association between Gn dosage, Gn duration, and blastocyst euploidy. The mean number of euploidy blastocysts in PPOS protocol was significantly lower than that of GnRH-a protocol and GnRH-ant protocol (0.75 ± 0.92 vs. 1.79 ± 1.78 vs. 1.80 ± 1.67). The euploidy rate per biopsy blastocyst (48.4% vs. 49.1% vs. 33.1%), per oocyte retrieved (15.0% vs. 14.7% vs. 10.5%), and per MII oocyte (17.7% vs. 16.4% vs. 11.7%) were significantly higher in the cycles using the GnRH-ant and GnRH-a protocols than that of PPOS protocol group. Regression analyses indicated that, compared with the PPOS protocol, the GnRH-ant protocol was positively associated with the euploid blastocyst rate and the mean number of euploid blastocysts, whereas the GnRH-a protocol showed no such relationship. Limitations and reasons for caution The main limitation of this study was the retrospective design. Although this study also used other tests to account for confounding factors and reduce potential bias, multiple tests have its own weaknesses. Conclusions GnRH-ant protocol was the most effective for PGT-A cycles. The findings emphasize the need for personalized treatment strategies, considering patient demographics, and optimizing COS protocols to enhance the chances of successful outcomes in ART procedures.

AbstractContext Diabetic wounds (DW) are a complication of diabetes and slow wound healing is the main manifestation. Methylene blue (MB) has been shown to exhibit therapeutic effects on diabetes-related diseases.Objective To investigate the mechanisms of action of MB-nanoemulsion (NE) in the treatment of DW.Materials and methods The concentration of MB-NE used in the in vivo and in vitro experiments was 0.1 mg/mL. Streptozocin-induced diabetic mice were used as models. The mice were separated into nondiabetic, diabetic, MB-NE treated, and NE-treated groups. Intervention of high glucose-induced human umbilical vein endothelial cells using MB-NE. The mechanism by which MB-NE promotes DW healing is investigated by combining histological analysis, immunofluorescence analysis, TUNEL and ROS assays and western blotting.Results In diabetic mice, the MB-NE accelerated DW healing (p

The Hutubi gas field was put into production in 1998 and then converted into an underground gas storage (UGS) facility in 2013, and since then a cluster of earthquakes associated with seasonal injection and extraction activities have been recorded nearby. To evaluate the fault stability and seismic potential, we established a pseudo-3D geomechanical model to simulate the process of seasonal injection and extraction. Reservoir pore pressures from 1998 to 2019 were obtained through multiphase reservoir simulation and validated by history matching the field injection and production data. We then imported pore pressures into the geomechanical model to simulate the poroelastic perturbation on faults for over 20 years. The fidelity of this model was validated by comparing the simulated surface deformation with global positioning system (GPS) measured data. We used Coulomb failure stress (CFS) as the indicator for the likelihood of fault slippage. The simulation results show that the location of the induced earthquake cluster was within the positive Coulomb stress perturbation (ΔCFS) area, in which fault slippage was promoted. In addition, ΔCFS at the earthquake location kept increasing after the injection began. These findings could explain the induced earthquakes with the Coulomb failure stress theory. Furthermore, we conducted a parameter sensitivity study on the dominant factors such as the maximum operating pressure (MOP), frictional coefficient, and dip angle of the pre-existing fault. The results indicate that the magnitude of ΔCFS caused by seasonal injection and extraction decreases with distance; MOPs are constrained to 32.9, 36.2, and 39.5 MPa according to different ΔCFS thresholds; the critical dip angle ranges are 0–20° and 80°–100°; and strengthening the fault friction can either increase or decrease the seismic potential. This study can help determine the MOP for Hutubi underground gas storage (HTB UGS) and provide a framework for simulating the potential causes of induced seismicity for other sites.

The research on the thermal decomposition of propellant is critical to determining its safe storage life. The thermogravimetry (TG) testing of nitramine propellants plasticized by nitroglycerin (NG), glycidyl azide polymer (GAP), 2,2-dinitropropanol hexanoate (DNPH), and N-butyl-2-nitratoethylnitramine (BuNENA) was performed under non-isothermal circumstances. The thermal decomposition mechanism of propellant was then analyzed using the model-fitting method, and the storage life was predicted based on the mechanism. The results show that when heated to the same mass loss, the temperature of GAP-NC-RDX, BuNENA-NC-RDX, and DNPH-NC-RDX is higher than that of NG-NC-RDX. GAP-NC-RDX, BuNENA-NC-RDX, and DNPH-NC-RDX propellants have superior thermal stability to that of NG-NC-RDX. The kinetic mechanism functions and equations of the propellants were calculated, and multi-step reaction models of the thermal decomposition were built. The major thermal decomposition mechanism of nitramine propellants was discovered to be composite autocatalytic decomposition (Kamal-Sourour equation), which means that the reaction of reactants and the reaction catalyzed by products occur in tandem. The decomposition depth of propellants increases as the temperature rises during the same storage time. The storage lifetimes of GAP-NC-RDX, BuNENA-NC-RDX, DNPH-NC-RDX, and NG-NC-RDX propellants at 288 K are 28.71 years, 24.49 years, 18.34 years, and 16.33 years, respectively. The inclusion of GAP, DNPH, and BuNENA in the formulation improves the storage life of propellant more than NG. This study offers an attractive strategy for analyzing the decomposition mechanism of propellant with a multi-step decomposition reaction and forecasting its storage life.

Benign prostatic hyperplasia (BPH), characterized by the non-malignant enlargement of the prostate, exhibits a pronounced association with inflammation resulting from androgen receptor (AR) deficiency. Ferroptosis, a cell death mechanism triggered by iron-dependent lipid peroxidation and closely linked to inflammation, has yet to be fully understood in the context of BPH. Using RNA sequencing, we observed a significant elevation of taurine-upregulated gene 1 (TUG1) long noncoding RNA (lncRNA) in BPH tissues compared to normal prostate tissue. High levels of TUG1 exhibited a discernible correlation with both prostate volume and the extent of inflammatory infiltration in BPH patients. The suppression of TUG1 not only led to a reduction in prostate size but also ameliorated AR-deficiency-induced prostatic hyperplasia. Mechanistically, a decrease in AR in prostate luminal cells prompted macrophage aggregation and the release of IL-1β, subsequently fostering the transcription of TUG1 via MYC. Induced TUG1, through competitive binding with miR-188-3p, facilitated the expression of GPX4, thereby diminishing intracellular ROS levels and impeding ferroptosis in prostate luminal cells. Notably, the ferroptosis inducer JKE-1674 alleviated inflammation-induced prostatic hyperplasia in vivo. Together, these findings suggest that AR deficiency crucially inhibits ferroptosis, promoting BPH via the TUG1/miR-188-3p/GPX4 signaling axis, and making ferroptosis induction a promising therapeutic strategy for BPH patients with AR deficiency.

Batch scheduling is a crucial part of pipeline enterprise operation management, especially in the context of market-oriented operation. It involves 3 main tasks: quickly preparing batch plans, accurately tracking interface movement, and operation condition in real time. Normally, the completion of multi-product pipeline batch scheduling depends on simulation models or optimization models and corresponding conventional solving algorithm. However, this approach becomes inefficient when applied to large-scale systems. The rapid development of machine learning has brought new ideas to batch scheduling research. This paper first reviews the current state of batch scheduling technology, and suggests that applying machine learning to it is a promising development direction. Then, we summarize the progress of machine learning applications in batch planning, interface movement tracking, and operational condition monitoring, and point out their limitations. Finally, considering the separation of refined oil production, transportation, and sales processes, 5 recommendations are put forward: oil supply and demand prediction and pipeline capacity prediction, batch planning, batch interface movement tracking, mixed oil development monitoring, and pipeline operation condition identification.

Cucumber (Cucumis sativus L.) belongs to the cucumber genus of the Cucurbitaceae family, and the selection of cultivars with minimal or no lateral branches can enhance the cultivation management efficiency. The growth of lateral branches is inhibited by strigolactone. To investigate the regulatory mechanism of strigolactone on the lateral branch development in cucumber, the cultivar LZ1 exhibiting multiple lateral branches was selected as the experimental material. The axillae of the plants were infiltrated with 1, 5, and 10 μmol·L−1 germination releaser 24 (GR24) at the four- to five-leaf stage. It was identified that 1 μmol·L−1 GR24 exhibited the most potent inhibitory effect on cucumber lateral branches. Additionally, exogenous strigolactone decreased the auxin content in the apical bud and axillae and increased the auxin content in the stem. This inhibited polar auxin transport in the axillary bud and promoted polar auxin transport in the apical bud. The content of strigolactone in the axilla region of cucumbers was elevated, whereas the synthesis and expression of cytokinin in the same area were reduced. A low concentration of GR24 induced the expression of cucumber branched 1 (csbrc1), whereas a high concentration of GR24 downregulated the expression of cucumber lateral suppressor (cscls) and blind (csblind), which inhibited the growth of cucumber lateral branches.

Abstract The morphological variation in Schizothorax oconnori, Schizothorax waltoni, and their natural hybrids was examined using conventional and image‐based analysis approaches. In total, 38 specimens of S. oconnori, 35 of S. waltoni, and 37 natural hybrids were collected from the Shigatse to the Lhasa section of the Yarlung Zangbo River during June and July 2021. A total of 21 morphometric, 4 meristic, and 27 truss variables were employed for the classification of S. oconnori, S. waltoni, and natural hybrids. Principal component analysis (PCA) and factor analysis (FA), as well as discriminant function analysis (DFA) and cluster analysis (CA), were conducted to identify differences based on traditional and truss measurements. Four principal components explained 75.92% of the variation among the morphometric characters, while five principal components accounted for 79.69% of the variation among the truss distances. FA results showed that factor 1 was associated with head shape, and factor 2 was associated with fins based on morphometric characters. Among the truss characters, factor 1 was related to head shape, and factor 2 was related to chest shape. In DFA, morphometric measurements achieved higher accuracy (100%) compared to truss distances (94.55%). The head morphology of hybrids exhibited intermediate traits between S. oconnori and S. waltoni. Both morphometry‐based and truss‐based clustering indicated that the morphology of natural hybrids leaned toward S. oconnori. In conclusion, the combination of morphometric and truss analysis is beneficial for classifying S. oconnori, S. waltoni, and their natural hybrids. The presence of natural hybrids could be considered an evolutionary response to the differentiation of nutritional and spatial niches in the middle Yarlung Zangbo River.

Verticillium wilt, caused by Verticillium dahliae, is a soil-borne disease affecting eggplant. Wild eggplant, recognized as an excellent disease-resistant resource against verticillium wilt, plays a pivotal role in grafting and breeding for disease resistance. However, the underlying resistance mechanisms of wild eggplant remain poorly understood. This study compared two wild eggplant varieties, LC-2 (high resistance) and LC-7 (sensitive) at the phenotypic, transcriptomic, and metabolomic levels to determine the molecular basis of their resistance to verticillium wilt. These two varieties exhibit substantial phenotypic differences in petal color, leaf spines, and fruit traits. Following inoculation with V. dahliae, LC-2 demonstrated significantly higher activities of polyphenol oxidase, superoxide dismutase, peroxidase, phenylalanine ammonia lyase, β-1,3 glucanase, and chitinase than did LC-7. RNA sequencing revealed 4,017 differentially expressed genes (DEGs), with a significant portion implicated in processes associated with disease resistance and growth. These processes encompassed defense responses, cell wall biogenesis, developmental processes, and biosynthesis of spermidine, cinnamic acid, and cutin. A gene co-expression analysis identified 13 transcription factors as hub genes in modules related to plant defense response. Some genes exhibited distinct expression patterns between LC-2 and LC-7, suggesting their crucial roles in responding to infection. Further, metabolome analysis identified 549 differentially accumulated metabolites (DAMs) between LC-2 and LC-7, primarily consisting of compounds such as flavonoids, phenolic acids, lipids, and other metabolites. Integrated transcriptome and metabolome analyses revealed the association of 35 gene–metabolite pairs in modules related to the plant defense response, highlighting the interconnected processes underlying the plant defense response. These findings characterize the molecular basis of LC-2 resistance to verticillium wilt and thus have potential value for future breeding of wilt-resistant eggplant varieties.

Background: Esophageal cancer (EC) is a prevalent malignancy with heterogeneous outcomes. This study explores the significance of anoikis-related long non-coding RNAs (lncRNAs) in EC, aiming to unravel their molecular roles and clinical implications. Methods: Transcriptome and clinical data were obtained from TCGA database for EC samples. We identified anoikis-related genes and lncRNAs by Pearson correlation analysis. The risk score model hinged on prognostic lncRNAs filtered from multiple steps. Risk scores were calculated using the derived formula, and categorized patients into low- and high-risk groups. Model robustness was assessed through Kaplan-Meier (KM) survival analysis and Receiver Operating Characteristic (ROC) curve, with clinical utility achieved via a constructed nomogram. We also explored the interplay between the risk score and immune cell infiltration, and investigated drug sensitivity. Results: We identified 2365 anoikis-related lncRNAs through co-expression analysis, including 1415 significant lncRNAs differentially expressed between normal and tumor samples. A risk score model was constructed from ten prognostic lncRNAs. The risk score model effectively stratified patients based on the median score, and its predictive capacity was validated through KM survival, ROC curve analyses, and the external GSE53622 dataset. The nomogram provided a practical tool for individualized prognosis evaluation. We unveiled significant correlations between specific immune cell subsets and the risk score. Eosinophils and common lymphoid progenitors exhibited positive associations, while endothelial cells and myeloid dendritic cells showed negative correlations. Drug sensitivity analysis revealed potential sensitive drugs for EC treatment that aligned with the risk subgroups. Conclusion: This study established an anoikis-related lncRNAs risk score model that may predict the prognosis, immune infiltration, and drug sensitivity in EC, in hope of facilitating tailored patient management.

Soil microorganisms can be used as one of the important indicators of wetland ecosystem restoration. To study the effects of different restoration stages on soil microbial community composition and diversity in Naolihe Wetland, we employed a “time and space parallel” method. Four restoration stages, namely corn field (Corn), short-term restoration wetland (2 years, ST), long-term restoration wetland (8 years, LT) and natural wetland (>25 years, NW), were selected to represent the restoration time and geographical location in Naolihe Nature Wetland. We investigated the composition and diversity of soil microbial communities in different restoration wetland (from corn fields to natural wetlands) by using 16S rRNA and ITS rRNA gene sequencing. We also performed chemical experiments to measure soil enzyme activity and physicochemical properties at each sampling site. The results showed that soil physicochemical properties and enzyme activities significantly differed with the extension of wetland restoration years (p

Flower color is a classic example of an ecologically important trait under selection in plants. Understanding the genetic mechanisms underlying shifts in flower color can provide key insights into ecological speciation. In this study, we investigated the genetic basis of flower color divergence in Barthea barthei, a shrub tree species exhibiting natural variation in flower color. We assembled a high-quality genome assembly for B. barthei with a contig N50 of 2.39 Mb and a scaffold N50 of 16.21 Mb. The assembly was annotated with 46,430 protein-coding genes and 1,560 non-coding RNAs. Genome synteny analysis revealed two recent tetraploidization events in B. barthei, estimated to have occurred at approximately 17 and 63 million years ago. These tetraploidization events resulted in massive duplicated gene content, with over 70% of genes retained in collinear blocks. Gene family members of the core regulators of the MBW complex were significantly expanded in B. barthei compared to Arabidopsis, suggesting that these duplications may have provided raw genetic material for the evolution of novel regulatory interactions and the diversification of anthocyanin pigmentation. Transcriptome profiling of B. barthei flowers revealed differential expression of 9 transcription factors related to anthocyanin biosynthesis between the two ecotypes. Six of these differentially expressed transcription factors were identified as high-confidence candidates for adaptive evolution based on positive selection signals. This study provides insights into the genetic basis of flower color divergence and the evolutionary mechanisms underlying ecological adaptation in plants.

Hot-compression bonding (HCB) as an advanced technique for preparation of large-size homogenized components is widely applied. Despite the fact that interfacial healing mechanisms during HCB have been extensively investigated, the interfacial healing mechanisms in duplex superalloys still need to be clarified. This article investigates effect of deformation temperature on multiple interface (γ′-γ′, γ-γ, γ-γ′) healing mechanism of dual-phase superalloys. The healing mechanism of γ-γ interface at different temperatures involves a necklace-like distribution of discontinuous dynamic recrystallization (DDRX) grains occupying original interface. With increasing deformation temperature, the healing mechanism of γ′-γ′ interface transforms from DDRX to diffusion bonding due to weakening of strain concentration. Simultaneously, as deformation temperature increases, the deformation mechanism of primary γ′ phase transforms from shearing by stacking fault to dislocation pairs. At deformation temperature 1100 °C, the healing mechanism of γ′-γ interface is heterogeneous epitaxial recrystallization (HERX) induced by primary γ′ phase driven by diffusion of Cr element in dislocation pairs. However, as deformation temperature decreases, healing mechanism in γ′-γ interface transforms into DDRX. Although interfacial healing mechanism is transformed at different deformation temperatures, the synergistic action of different recrystallization mechanisms ensures that mechanical properties of joints reached the same level as those of base material.

The aim of this study was to investigate the effects and mechanisms of action of extract of Adventitious Root of Ginseng (GARE) on a mouse model of Type 1 diabetes mellitus (T1DM). Firstly, using network pharmacology methods to predict relevant targets. The main active components of GARE were analyzed using Liquid Chromatography-Tandem Mass Spectrometry (LC-MS). Mice were then divided into multiple experimental groups and a T1DM model was established. The results showed that GARE significantly reduced blood glucose levels in mice, while also decreasing the levels of total cholesterol (TC), triglycerides (TG), and glycosylated hemoglobin (GHb). GARE increased the activity of antioxidant enzymes and reduced the expression of inflammatory factors in the liver. Furthermore, GARE exerted its protective effects by inhibiting the PI3K/AKT/mTOR signaling pathway. These findings suggest that GARE may have potential therapeutic effects for T1DM and provide a theoretical basis for the development and utilization of adventitious root of ginseng (GAR) resources.

Background Immune-based therapies are commonly employed to combat hepatocellular carcinoma (HCC). However, the presence of immune-regulating elements, especially regulatory T cells (Tregs), can dramatically impact the treatment efficacy. A deeper examination of the immune-regulation mechanisms linked to these inhibitory factors and their impact on HCC patient outcomes is warranted. Methods We employed multicolor fluorescence immunohistochemistry (mIHC) to stain Foxp3, cytokeratin, and nuclei on an HCC tissue microarray (TMA). Leveraging liver cancer transcriptome data from TCGA, we built a prognostic model focused on Treg-associated gene sets and represented it with a nomogram. We then sourced liver cancer single-cell RNA sequencing data (GSE140228) from the GEO database, selectively focusing on Treg subsets, and conducted further analyses, including cell-to-cell communication and pseudo-time trajectory examination. Results Our mIHC results revealed a more substantial presence of Foxp3 + Tregs in HCC samples than in adjacent normal tissue samples ( P < .001). An increased presence of Foxp3 + Tregs in HCC samples correlated with unfavorable patient outcomes ( HR = 1.722, 95% CI :1.023-2.899, P = .041). The multi-factorial prognosis model we built from TCGA liver cancer data highlighted Tregs as a standalone risk determinant for predicting outcomes ( HR = 3.84, 95% CI: 2.52-5.83, P < .001). Re-analyzing the scRNA-seq dataset (GSE140228) showcased distinctive gene expression patterns in Tregs from varying tissues. Interactions between Tregs and other CD4 + T cell types were predominantly governed by the CXCL13/CXCR3 signaling pathway. Communication pathways between Tregs and macrophages primarily involved MIF-CD74/CXCR4, LGALS9/CD45, and PTPRC/MRC1. Additionally, macrophages could influence Tregs via HLA-class II and CD4 interactions. Conclusion An elevated presence of Tregs in HCC samples correlated with negative patient outcomes. Elucidating the interplay between Tregs and other immune cells in HCC could provide insights into the modulatory role of Tregs within HCC tissues.

In the post-genomic era, virus-induced gene silencing (VIGS) has played an important role in research on reverse genetics in plants. Commonly used Agrobacterium-mediated VIGS inoculation methods include stem scratching, leaf infiltration, use of agrodrench, and air-brush spraying. In this study, we developed a root wounding–immersion method in which 1/3 of the plant root (length) was cut and immersed in a tobacco rattle virus (TRV)1:TRV2 mixed solution for 30 min. We optimized the procedure in Nicotiana benthamiana and successfully silenced N. benthamiana, tomato (Solanum lycopersicum), pepper (Capsicum annuum L.), eggplant (Solanum melongena), and Arabidopsis thaliana phytoene desaturase (PDS), and we observed the movement of green fluorescent protein (GFP) from the roots to the stem and leaves. The silencing rate of PDS in N. benthamiana and tomato was 95–100%. In addition, we successfully silenced two disease-resistance genes, SITL5 and SITL6, to decrease disease resistance in tomatoes (CLN2037E). The root wounding–immersion method can be used to inoculate large batches of plants in a short time and with high efficiency, and fresh bacterial infusions can be reused several times. The most important aspect of the root wounding–immersion method is its application to plant species susceptible to root inoculation, as well as its ability to inoculate seedlings from early growth stages. This method offers a means to conduct large-scale functional genome screening in plants.

Abstract Temozolomide (TMZ) represents the cornerstone of therapy for glioblastoma (GBM). However, acquisition of resistance limits its therapeutic potential. The human kinome is an undisputable source of druggable targets, still, current knowledge remains confined to a limited fraction of it, with a multitude of under‐investigated proteins yet to be characterized. Here, following a kinome‐wide RNAi screen, pantothenate kinase 4 (PANK4) isuncovered as a modulator of TMZ resistance in GBM. Validation of PANK4 across various TMZ‐resistant GBM cell models, patient‐derived GBM cell lines, tissue samples, as well as in vivo studies, corroborates the potential translational significance of these findings. Moreover, PANK4 expression is induced during TMZ treatment, and its expression is associated with a worse clinical outcome. Furthermore, a Tandem Mass Tag (TMT)‐based quantitative proteomic approach, reveals that PANK4 abrogation leads to a significant downregulation of a host of proteins with central roles in cellular detoxification and cellular response to oxidative stress. More specifically, as cells undergo genotoxic stress during TMZ exposure, PANK4 depletion represents a crucial event that can lead to accumulation of intracellular reactive oxygen species (ROS) and subsequent cell death. Collectively, a previously unreported role for PANK4 in mediating therapeutic resistance to TMZ in GBM is unveiled.

The Hehuang Valley (HV) is a key development area in the Qinghai Province; understanding changes in the vegetation within this area is of great significance if we are to maintain the ecological quality of this regional environment. Based on the 30 m spatial resolution Normalized difference vegetation index (NDVI) time series dataset, this paper analyzes the spatial and temporal characteristics and evolutionary trends of NDVI in the HV from 2001 to 2020 under the influences of climate change and human activities, by applying Mann-Kendall trend analysis, the Hurst index, and residual analysis. Analysis showed that firstly, high NDVI values (>0.5) were distributed in the low elevation areas of the HV except for towns and cropland, while the low NDVI values (

IntroductionUltraviolet (UV) light is a known trigger of both cutaneous and systemic disease manifestations in lupus patients. Lupus skin has elevated expression of type I interferons (IFNs) that promote increased keratinocyte (KC) death after UV exposure. The mechanisms by which KC cell death is increased by type I IFNs are unknown.MethodsHere, we examine the specific cell death pathways that are activated in KCs by type I IFN priming and UVB exposure using a variety of pharmacological and genetic approaches. Mice that overexpress Ifnk in the epidermis were exposed to UVB light and cell death was measured. RNA-sequencing from IFN-treated KCs was analyzed to identify candidate genes for further analysis that could drive enhanced cell death responses after UVB exposure.ResultsWe identify enhanced activation of caspase-8 dependent apoptosis, but not other cell death pathways, in type I IFN and UVB-exposed KCs. In vivo, overexpression of epidermal Ifnk resulted in increased apoptosis in murine skin after UVB treatment. This increase in KC apoptosis was not dependent on known death ligands but rather dependent on type I IFN-upregulation of interferon regulatory factor 1 (IRF1).DiscussionThese data suggest that enhanced sensitivity to UV light exhibited by lupus patients results from type I IFN priming of KCs that drives IRF1 expression resulting in caspase-8 activation and increased apoptosis after minimal exposures to UVB.

Purpose: Leptin resistance represents a primary pathological manifestation in obesity. Investigating potential treatments and associated mechanisms to restore leptin sensitivity is crucial for effective obesity management. This study aimed to explore the therapeutic potential of acupoints catgut embedding (ACE) in addressing obesity and its associated leptin resistance. Methods: A simple obesity model was established by subjecting C57 male mice to a high-fat diet (HFD) for 12 weeks, followed by ACE treatment administered to half of the obese mice for a duration of 4 weeks. The levels of leptin and its receptor-lepRb, were assessed using enzyme-linked immunosorbent assay (ELISA) and Western blot analysis, respectively. Autophagy progression markers were evaluated through quantitative polymerase chain reaction (qPCR) and Western blot analysis. Also, the liver autophagosomes were photographed using electron microscopy. The role of autophagy in regulating leptin resistance was elucidated using an autophagy suppression model. Results: Comparative analyses demonstrated that ACE treatment resulted in a significant reduction in body weight and blood lipid levels compared to the HFD group. Furthermore, serum leptin levels decreased, while liver lepRb expression increased following ACE treatment. The mRNA and protein expression levels of autophagy in liver were adjusted by ACE treatment. Interestingly, the beneficial effects of ACE were attenuated upon the administration of an autophagy inhibitor. Additionally, ACE treatment led to the activation of the AMPK-mTOR signaling pathway, a crucial regulator of autophagy. Conclusion: These findings suggest that ACE therapy holds promise for recovering leptin resistance by enhancing autophagy progression, mediated via the AMPK-mTOR signaling pathway in liver.

Compound pollution with cadmium (Cd) and zinc (Zn) is common in nature. The effects of compounded Cd and Zn on the growth and development of Iris pseudacorus in the environment and the plant’s potential to remediate heavy metals in the environment remain unclear. In this study, the effects of single and combined Cd and Zn stress on I. pseudacorus growth and the enrichment of heavy metals in I. pseudacorus seedlings were investigated. The results showed that under Cd (160 μM) and Zn (800 μM) stress, plant growth was significantly inhibited and photosynthetic performance was affected. Cd+Zn200 (160 μM + 200 μM) reduced the levels of malondialdehyde, hydrogen peroxide, and non-protein thiols by 31.29%, 53.20%, and 13.29%, respectively, in the aboveground tissues compared with levels in the single Cd treatment. However, Cd+Zn800 (160 μM + 800 μM) had no effect. Cd and Zn800 inhibited the absorption of mineral elements, while Zn200 had little effect on plants. Compared with that for Cd treatment alone, Cd + Zn200 and Cd+Zn800 reduced the Cd content in aboveground tissues by 54.15% and 49.92%, respectively, but had no significant effect on Cd in the root system. Zn significantly reduced the Cd content in subcellular components and limited the content and proportion of Cd extracted using water and ethanol. These results suggest that a low supply of Zn reduces Cd accumulation in aboveground tissues by promoting antioxidant substances and heavy metal chelating agents, thus protecting the photosynthetic systems. The addition of Zn also reduced the mobility and bioavailability of Cd to alleviate its toxicity in I. pseudacorus.

Background: Dietary nutrient intake contributes to urination; however, the association between dietary nutrient intake, especially that of fat, and urinary incontinence (UI) is not well understood. The most common types of UI include stress UI (SUI) and urgency UI (UUI). Objective: To investigate the potential effect(s) of dietary fat intake on UI and explore its mechanism of action in relation to body mass index (BMI). Methods: A cross-sectional survey of data from 15,121 individuals (20–85 years of age) from the National Health and Nutrition Examination Survey (2001–2008), a random population-based sample, was performed. Data regarding dietary nutrient intake were collected through 24 h dietary recall interviews. UI and covariate data were collected through in-person interviews. UI was assessed according to the American Urological Association Symptom Index. The odds ratio (OR) for SUI and UUI were calculated using multivariate logistic regression analysis. The mediation effect was estimated using observational mediation analysis. Results: Higher total fat intake was positively associated with increased odds for developing UI (OR 1.44 [95% confidence interval (CI) 1.08–1.93]). Females who consumed more saturated fatty acids (SFA), monounsaturated fatty acids (MUFA), and polyunsaturated fatty acids (PUFA) were more likely to develop SUI. BMI partially explained the association between total fat, SFA, MUFA, and PUFA and SUI; the proportions of the mediation effect of BMI were 14.7%, 13.0%, 18.7%, and 16.3%, respectively. Conclusions: Results of this study emphasize the key role of dietary fat intake in the prevalence of UI. Higher fat intake was positively associated with UI and BMI partially mediated the effect of fat intake on SUI.

ABSTRACT: Fine particulate matter (PM2.5) has been widely regarded as an important environmental risk factor that has widely influenced health of both animals and humans. Lung injury is the main cause of PM2.5 affecting respiratory tract health. Gut microbiota participates in the development of lung injury in many pathological processes. However, there is still unknown the specific effects of PM2.5 on the gut-lung axis in broilers. Thus, we conducted a broiler model based on 3-wk-old male Arbor Acres broiler to explore the underlying mechanism. Our results showed that PM2.5 exposure triggered TLR4 signaling pathway and induced the increase of IL-6, IFN-γ, TNF-α expression as well as the decrease of IL-10 expression in the lung. Inhaled PM2.5 exposure significantly altered the gut microbiota diversity and community. Specifically, PM2.5 exposure decreased α diversity and altered β diversity of gut microbiota, and reduced the abundance of DTU089, Oscillospirales, Staphylococcus, and increased the Escherichia-Shigella abundance, leading to the increase of gut-derived lipopolysaccharides (LPS). Moreover, PM2.5 significantly disrupted the intestinal epithelial barrier by reducing the expression of muc2 and claudin-1 to increase intestinal permeability, which possibly facilitated the LPS translocation into the blood. Spearman analysis revealed that gut microbiota dysbiosis was positively related to TLR4, TNF-α, and IFN-γ expression in the lung. In summary, our results showed that PM2.5 exposure induced lung injury by causing inflammation and triggering TLR4 signaling pathway, and also induced gut microbiota dysbiosis resulting in the overproduction of gut-derived LPS. And gut microbiota dysbiosis may be associated with lung injury. The above results provide basis data to comprehend the potential role of gut microbiota dysbiosis in the lung injury as well as providing a new regulatory target for alleviating lung injury associated with environmental pollutants.

Colorectal cancer (CRC), one of the most common malignancies in the world, urgently requires more treatment strategies. Although there has been much research on probiotics, limited research has been done in treating cancer. The purpose of this study was to investigate the role of Bifidobacterium longum (B. longum) in the prevention and treatment of CRC. Through Cell Counting Kit-8 and Colony Formation Assays, 8 h and a B. longum count of 1 × 108 CFU/ml were chosen as the best cocultivation conditions with CRC cells. The role of B. longum in inhibiting the progression of CRC cells was verified by a series of functional and immunofluorescence assays. For instance, in vivo assays have verified that B. longum could alleviate CRC progression. In addition, according to the results of in vivo assays and clinical statistical analysis, B. longum could reduce diarrhea symptoms. Mechanistically, by 16S and RNA sequencing, it was found that B. longum could affect the development of CRC by regulating the composition of gut microbes and enhancing immune function. The B. longum might inhibit the occurrence and development of CRC and relieve diarrhea symptoms by regulating intestinal microbes and immune function.

China’s constantly rapid economic growth accompanying by a low overall inflation has long been mysterious in macroeconomics. The core purpose of this paper is to solve this puzzle. Therefore, we integrate overdetermined set of equations into a MUCSVO model to explore the volatility mechanism of the overall inflation from a sectoral perspective. Our key findings include: 1) the hedging effect of sectoral inflation fluctuations principally accounts for China’s long-run stable overall inflation; 2) the main contradiction of China’s inflation has been shifting from high price levels in the traditional food and residence categories to rising prices in the health care category; 3) as the proportions of inflation in the food and residence categories fall steadily, sectoral inflation weights become more evenly distributed. In conclusion, China’s overall inflation and deflation will be much less likely to occur, while inflation is still of sectoral imbalance. Unusual price fluctuations in the food and health care categories, which are highly relevant to basic living standards of the low-income group, deserve close attention in particular. Overall, besides solving the puzzle of China’s low inflation, our model is applicable to economies that do not publish inflation weights, which is a useful extension of core inflation measurement. First published online 15 March 2024

Exhausted CD8+T cells represent a distinct cellular lineage that emerges during both chronic infections and cancers. Recent studies have shown that persistent antigen exposure can drive the differentiation of precursor exhausted CD8+T cells, termed Tpex cells, which are characterized as TCF-1+PD-1+CD8+T cells. Elevated Tpex cell frequencies in the tumor microenvironment (TME) are associated with improved overall survival (OS) in cancer patients and heightened responsiveness to anti-PD-1 therapy. In our present study, we utilized multi-color immunohistochemistry (mIHC) to determine the localization and clinical implications of tumor-infiltrating Tpex cells within the TME of human colorectal cancer (CRC) tissues. We also conducted a multi-omics integrative analysis using single-cell RNA sequencing (scRNA-seq) data derived from both the murine MC38 tumor model and human CRC tissues. This analysis helped delineate the transcriptional and functional attributes of Tpex cells within the CRC TME. Furthermore, we employed spatial transcriptome sequencing data from CRC patients to investigate the interactions between Tpex cells and other immune cell subsets within the TME. In conclusion, our study not only established a method for Tpex cell detection using mIHC technology but also confirmed that assessing Tpex cells within the CRC TME could be indicative of patients’ survival. We further uncovered the transcriptional and functional characteristics of Tpex cells in the TME and ascertained their pivotal role in the efficacy of immunotherapy against CRC.

Energetic plasticizers are an essential component of propellants and have a significant impact on their performance, such as energy, combustion, and mechanics. Therefore, there is significant practical value in understanding how plasticizers affect the performance of propellants. In this work, the glass transition temperatures of several energetic plasticizers were compared. By adding energetic plasticizers with good compatibility with the propellant and a low glass transition temperature to the propellant, nitramine gun propellants containing different energetic plasticizers were prepared through a semi-solvent method. The compatibility, thermal behavior, phase structure, composition, mechanical properties, energy, and combustion performance of the nitramine gun propellants were characterized. The influence of plasticizers on the phase structure of the propellant and its mechanism on the combustion performance of the propellant were discussed. Energetic plasticizers GAPE, DNPH, and BuNENA have good compatibility and chemical stability with NC-RDX and display good plasticization. GAPE–NC–RDX, DNPH–NC–RDX, and BuNENA–NC–RDX propellants exhibit stable combustion performance at −40 °C, 20 °C, and 50 °C. Compared with the nitramine gun propellant plasticized with NG, the impact strength of the propellant plasticized with DNPH and BuNENA increased by 108.1 % and 17.2 % at −40 °C, respectively. This work offers a solution to improve the phase structure, mechanical properties, and combustion stability of heterogeneous gun propellants and provides a way to suppress the excessive burning rate and flame temperature of propellants.

Thermal barrier coating (TBC) materials can improve energy conversion efficiency and reduce fossil fuel use. Herein, novel rare earth tantalates RETaO4, as promising candidates for TBCs, were reassembled into multi-component solid solutions with a monoclinic structure to further depress thermal conductivity via an entropy strategy. The formation mechanisms of oxygen vacancy defects, dislocations, and ferroelastic domains associated with the thermal conductivity are demonstrated by aberration-corrected scanning transmission electron microscopy. Compared to single-RE RETaO4 and 8YSZ, the intrinsic thermal conductivity of (5RE1/5)TaO4 was decreased by 35%–47% and 57%–69% at 1200 ℃, respectively, which is likely attributed to multi-scale phonon scattering from Umklapp phonon–phonon, point defects, domain structures, and dislocations. r¯RE3+/rTa5+ and low-temperature thermal conductivity are negatively correlated, as are the ratio of elastic modulus to thermal conductivity (E/κ) and high-temperature thermal conductivity. Meanwhile, the high defects’ concentration and lattice distortion in high-entropy ceramics enhance the scattering of transverse-wave phonons and reduce the transverse-wave sound velocity, leading to a decrease in the thermal conductivity and Young’s modulus. In addition, 5HEC-1 has ultra-low thermal conductivity, moderate thermal expansion coefficients, and high hardness among three five-component high-entropy samples. Thus, 5HEC-1 with superior thermal barrier and mechanical properties can be used as promising thermal insulating materials.

Abstract Based on existing researches, field drillings and numerical simulations are carried out in this paper to analyze the problems of subsidence control in the goaf of multi-layer inclined coal seam. Midas/GTS NX is used to build a three-dimensional calculation model of the goaf. A new method of using borehole data to check simulation parameters is proposed. The whole process of goaf excavation, construction of roadbed (pile foundation) and grouting treatment is analyzed. Analysis theory of different subgrade construction schemes and grouting treatment process on goaf is established. Response characteristics of displacement and equivalent stress and strain of goaf in multilayer inclined coal seam are obtained. A new method for analyzing the characteristics of the stress and deformation of the rock strata before and after grouting in the goaf under the conditions of different foundation schemes on the surface is provided in this research.

Abstract Objective Thyroid cancer is one of the most frequently reported endocrine system malignancies. It is difficult to distinguish follicular thyroid cancer (FTC) from follicular thyroid adenoma (FTA) during pathological diagnosis in patients without lymph nodes or distant metastases. Therefore, we conducted a retrospective study to investigate the significance of SLC5A8 methylation and expression in the diagnosis and prognosis of FTC. Methods We used 165 tissue samples, including FTC (n = 58), thyroid tumors of uncertain malignant potential (TT-UMP, n = 40), and FTA (n = 67), to explore the differences in SLC5A8 methylation and mRNA transcription in different pathological types. Survival analysis was conducted to evaluate the recurrence rate at a 5-year follow-up. Results The SLC5A8 methylation positive rate was higher in patients with thyroglobulin ≥ 40 μg/l and Chol ≥ 5.17 mmol/l, and it was higher in patients with FTC (n = 42, 72.4%) than those with FTA (n = 27, 40.3%) and TT-UMP (n = 23, 57.5%). The relative concentration of SLC5A8 mRNA was lower in patients with FTC than in those with FTA (p

Brake pads play a vital role in controlling the operation of high-speed trains with over 300 km/h. Currently the copper-based composites produced by powder metallurgy techniques have been proved as one of the ideal materials. However，the braking performance is strongly influenced by the chemical composition, production, microstructure as well as the working conditions. The intrinsic mechanism of the thermal fade and wear loss under thermal and mechanical coupled influence has not yet been fully revealed. As of late, machine learning algorithms have attracted widespread attention and extraordinary results has been accomplished in materials science and engineering. In this study the algorithms for predicting the braking performance of copper-based brake pads are developed. A new PM copper-based alloy, was designed via the models of the coefficient of friction (COF) and wear loss. The braking test results of this alloy show that the average COF was 0.37 at stable stage I and thermal recession decrease only 0.012 at stage II when under 350 km/h/0.48 MPa continuous braking for 10 times. And the total wear loss is only 1.30 g when under braking from 200 km/h to 350 km/h with pressure from 0.31 MPa to 0.48 MPa. Compared with the commercial brake pads, our designed alloy exhibits excellent braking performance with COF for thermal fade reduced to 21% and the total wear loss reduced to 20%.

Abstract Introduction A pan-genotypic and effective treatment regimen for patients with chronic hepatitis C virus (HCV) infection remains an unmet medical need in China. Alfosbuvir is a novel potent HCV NS5B polymerase inhibitor in development for the treatment of chronic HCV infection. We conducted a phase 3 study to evaluate the efficacy and safety of alfosbuvir in combination with daclatasvir in Chinese patients with HCV infection. Methods All patients received 600 mg alfosbuvir tablets plus 60 mg daclatasvir tablets once daily for 12 weeks. The primary endpoint was sustained virological response 12 weeks after the end of treatment (SVR12). A follow-up visit was done at week 4 and 12, and those who achieved SVR12 were followed up at post-treatment week 24. Results Of the 326 patients who received at least one dose of the study drug, 320 (98.2% [95% confidence interval (CI): 96.5%–99.5%]) achieved sustained virological response at post-treatment week 12 (SVR12), which was superior to the historical SVR12 rate of 88% (p

Background/Aims: To investigate the autoantibody against fumarate hydratase (FH), which is a specific liver failure-associated antigen (LFAA) and determine whether it can be used as a biomarker to evaluate the prognosis of acute-on-chronic liver failure (ACLF). Methods: An immunoproteomic approach was applied to screen specific LFAAs related to differential prognosis of ACLF (n=60). Enzyme-linked immunosorbent assay (ELISA) technology was employed for the validation of the frequency and titer of autoantibodies against FH in ACLF patients with different prognoses (n=82). Moreover, we clarified the expression of autoantibodies against FH in patients with chronic hepatitis B (n=60) and hepatitis B virus-related liver cirrhosis (n=60). The dynamic changes in the titers of autoantibodies against FH were analyzed by sample collection at multiple time points during the clinical course of eight ACLF patients with different prognoses. Results: Ultimately, 15 LFAAs were screened and identified by the immunoproteomic approach. Based on ELISA-based verification, anti-FH/Fumarate hydratase protein autoantibody was chosen to verify its expression in ACLF patients. ACLF patients had a much higher anti-FH autoantibody frequency (76.8%) than patients with liver cirrhosis (10%, p=0.000), patients with chronic hepatitis B (6.7%, p=0.022), and normal humans (0%, p=0.000). More importantly, the frequency and titer of anti-FH protein autoantibodies in the serum of ACLF patients with a good prognosis were much higher than that of patients with a poor prognosis (83.9% vs 61.5%, p=0.019; 1.41±0.85 vs 0.94±0.56, p=0.017, respectively). The titer of anti-FH autoantibodies showed dynamic changes in the clinical course of ACLF. Conclusions: The anti-FH autoantibody in serum may be a potential biomarker for predicting the prognosis of ACLF.

With the increase of the depth of the blast hole, the rock clamping effect at the bottom of the blast hole is enhanced, resulting in low rock breaking efficiency and blast hole utilization. The past continuous charging method can not solve the above problems. On this basis, this paper studies the rock roadway deep hole segmented charging cut blasting technology to improve the cut blasting efficiency. Using the smooth particle hydrodynamics-finite element method (SPH-FEM), a single-hole cut blasting model with different segmented charge structures was established, and the blasting speed of rock particles in the rock, the number of rock blasting and the characteristics of blasting cavity were analyzed in the blasting process under different models. The results show that different charge structures affect the damage range of the rock near the blast hole, and the damage area of the traditional continuous charge structure in the direction of the blast hole is larger than that of the segmented charge structure. In addition, the continuous charge structure makes the energy distribution of the explosive uneven because the explosive is concentrated at the bottom of the blast hole, resulting in poor blasting effect. The segmented charge structure can increase the number of rock fragments and optimize the blasting cavity, and the rock particles accelerate twice in the process of flying. The large or small proportion of the first segment charge obviously causes the unreasonable use of explosive energy and the poor effect of blasting cavity. Under the conditions of blast hole length, rock parameters and explosive performance set in the simulation, when the first stage charge ratio is 0.4, deep-hole rock tunnel excavation and blasting can make full use of explosive energy to achieve better cut blasting effect. The optimal subsection ratio obtained by numerical simulation was applied to the blasting construction of roadway excavation, and the delay initiation of two explosives in the cut hole was realized by using digital electronic detonator. The field test results show that the segmented charging can create good blasting effect and improve the utilization rate of blast holes in deep hole cut blasting.

To investigate the dynamic damage evolution characteristics of bank slopes with serrated structural planes, the shaking table model test and the numerical simulation were utilized. The main findings indicate that under continuous seismic loads, the deformation of the bank slope increased, particularly around the hydro-fluctuation belt, accompanying by the pore water pressure rising. The soil pressure increased and then decreased showed dynamic variation characteristics. As the undulation angle of the serrated structural planes increased (30°, 45°, and 60°), the failure modes were climbing, climbing-gnawing, and gnawing respectively. The first-order natural frequency was used to calculate the damage degree (Dd) of the bank slope. During microseisms and small earthquakes, it was discovered that the evolution of Dd followed the “S” shape, which was fitted by a logic function. Additionally, the quadratic function was used to fit the Dd during moderately strong earthquakes. Through the numerical simulation, the variation characteristics of safety factors (Sf) for slopes with serrated structural planes and slopes with straight structural planes were compared. Under continuous seismic loads, the Sf of slopes with straight structural planes reduce stalely, whereas the Sf for slopes with serrated structural planes was greater than the former and the reduction rate was increasing.

Abstract Background Pulmonary vein perforation is an uncommon complication during cardiac intervention. We present a rare case of pulmonary vein perforation into the respiratory tract with systemic air embolism during left atrial appendage closure (LAAC). Case presentation A 77-year-old man with persistent nonvalvular atrial fibrillation was referred for percutaneous LAAC under local anaesthesia (CHA2DS2-VASc score of 4, HAS-BLED score of 3, and prior ischaemic stroke). During the procedure, after delivering a super-stiff guidewire into the left superior pulmonary vein (LSPV), the patient suddenly developed a severe cough with haemoptysis upon advancement of a delivery sheath along the guidewire. Fluoroscopy showed signs of blood entering the left main bronchus, and fast transthoracic echocardiography revealed bubbles in the left heart without pericardial effusion. The procedure was terminated because of a major complication indicated by the repeated haemoptysis and headache, and haemostatic drugs were immediately administered. Subsequent chest computed tomography angiography (CTA) revealed a filling defect in the LSPV branches and bubbles in the aorta. The patient was transferred to the critical care unit for haemostasis and antibacterial treatment. Transthoracic echocardiography later that day showed no bubbles in the heart. The headache and haemoptysis significantly abated the following day. The bubbles in the aorta disappeared on chest CTA 7 days later. Conclusions Interventional cardiologists should pay attention to anatomical variations of the pulmonary vein, which are associated with a high risk of complications of pulmonary vein perforation during LAAC. Preoperative CTA examination and intraoperative transoesophageal echocardiography might be helpful to avoid this complication.

Abstract Genome-wide association studies have identified numerous variants associated with human complex traits, most of which reside in the non-coding regions, but biological mechanisms remain unclear. However, assigning function to the non-coding elements is still challenging. Here we apply Activity-by-Contact (ABC) model to evaluate enhancer-gene regulation effect by integrating multi-omics data and identified 544,849 connections across 20 cancer types. ABC model outperforms previous approaches in linking regulatory variants to target genes. Furthermore, we identify over 30,000 enhancer-gene connections in colorectal cancer (CRC) tissues. By integrating large-scale population cohorts (23,813 cases and 29,973 controls) and multipronged functional assays, we demonstrate an ABC regulatory variant rs4810856 associated with CRC risk (Odds Ratio = 1.11, 95%CI = 1.05–1.16, P = 4.02 × 10−5) by acting as an allele-specific enhancer to distally facilitate PREX1, CSE1L and STAU1 expression, which synergistically activate p-AKT signaling. Our study provides comprehensive regulation maps and illuminates a single variant regulating multiple genes, providing insights into cancer etiology.

Abstract Background Whether pretreatment with gonadotropin-releasing hormone agonist (GnRHa) can improve the pregnancy outcomes in frozen-thawed embryo transfer (FET) cycles is controversial. The inconsistencies in the results of different studies would be related to the characteristics of the included patients and the protocol of GnRHa use. In this study, we investigated the efficacy of pretreatment with a long-acting GnRH agonist in the early follicular phase of FET cycles and determined which population was suitable for the protocol. Results We retrospectively included 630 and 1141 patients in the GnRHa FET and hormone replacement treatment (HRT) FET without GnRHa groups respectively, between October 2017 and March 2019 at a university-affiliated in vitro fertilization center. On the second or third day of menstruation, 3.75 mg of leuprorelin was administered. After 14 days, HRT was initiated for endometrial preparation. No significant differences were observed between the two groups in terms of patient characteristics. However, the GnRHa FET group showed a higher percentage of endometrium with a triple line pattern (94.8% vs 89.6%, p

Abstract Background The prevalence of human immunodeficiency virus (HIV) is becoming more common among college students in China. However, latest data on the prevalence and correlates of HIV testing among sexually experienced college students is rarely. Methods An online survey was conducted among college students aged 18 years or older using multistage stratified cluster sampling from 16 colleges. Data on socio-demographic, HIV testing, HIV-related awareness, attitudes, sexual education and behaviors were collected. Propensity score matching (PSM) and logistic regression model were used to identify factors associated with HIV testing. Result A total of 108,987 students participated the survey, of which 13,201 sexually experienced college students were included in this study. 1,939 (14.69%) college students with sexual experience reported uptake of HIV testing in the preceding year. The uptake of HIV testing increased for college students with a rising HIV knowledge score and sexual health knowledge. Being awareness of HIV-related knowledge (aOR = 1.15, 95%CI: 1.01–1.30), accepting one-night stands (aOR = 1.16, 95%CI:1.03–1.32), obtaining satisfactory sexual interpretation from parent(s) (aOR = 1.24, 95%CI: 1.07–1.43), ever had unintended pregnancy (aOR = 1.78, 95%CI: 1.32–2.38), ever had received HIV-related preventive service(s) (aOR = 1.37, 95%CI: 1.10–1.70), ever had participated HIV-related preventive services (aOR = 3.76, 95%CI: 2.99–4.75) and ever had anal sex (aOR = 2.66, 95%CI: 2.11–3.34) were positively associated with uptake of HIV testing. However, accepting premarital sex (aOR = 0.76, 95%CI: 0.66–0.88), accepting cohabitation (aOR = 0.75, 95%CI: 0.61–0.92), occasionally discussing sex with parent(s) (aOR = 0.68, 95%CI: 0.50–0.91), and being with moderate satisfaction of school sex courses (aOR = 0.74, 95%CI: 0.58–0.95) were negatively associated with uptake of HIV testing. Conclusion The prevalence of HIV testing was relatively low. Participation in HIV-related services and high-risk sexual behaviors were important enablers for testing. Improving sex education for students, increasing HIV preventive services on campus, and improving family sex education are necessary to increase HIV testing among college sexually experienced students.

This study investigates the underlying causes of Variable Polarity Plasma Arc Welding (VPPAW) spatial positional instability and its adverse impact on weld seam quality. Microstructural analysis reveals that the primary cause of poor transverse mechanical properties is the asymmetric distribution of grains. Through the study of heat and mass transfer in the molten pool, it was found that the asymmetric flow of molten metal under the influence of gravity is the main factor leading to uneven temperature distribution and asymmetric grain distribution in the weld pool. A novel approach based on a predefined temperature field is proposed to regulate the weld pool's stability and welding quality. The implementation of the predefined temperature field effectively improves VPPAW weld pool flow, leading to enhanced temperature distribution and grain size and distribution. These findings provide a theoretical foundation and valuable engineering recommendations for achieving high-quality spatial position welding in VPPAW.

Abstract Background Laparoscopic common bile duct exploration with primary closure (LCBDE‐PC) exhibits more benefits than other surgeries for patients with choledocholithiasis. It remains unclear whether it is feasible for and beneficial to elderly individuals. This study aimed to clarify and stratify elderly patients who would benefit from LCBDE‐PC. Methods A retrospective study of 1240 patients with choledocholithiasis who underwent laparoscopic procedures between 2011 and 2019 was conducted. Patients were divided into the young group (

Abstract Background Thin endometrium is considered suboptimal for embryo implantation, leading to compromised pregnancy rates without effective therapies. While some studies have reported promoted endometrial growth after a period of hyperbaric oxygen therapy (HBOT) in patients with intrauterine adhesion, there have been no reports in patients with resistant thin endometrium. The purpose of this study was to investigate the impact of HBOT on endometrium growth and pregnancy outcomes in patients with resistant thin endometrium during frozen embryo transfer (FET) treatments. Methods This prospective pre-post cohort study was conducted at a university-affiliated assisted reproductive medical center between October 2021 and December 2022. Patients who had experienced at least one canceled transfer cycle due to a thin endometrium(

The abnormal activation of epidermal growth factor receptor (EGFR) drives the development of non-small cell lung cancer (NSCLC). The EGFR-targeting tyrosine kinase inhibitor osimertinib is frequently used to clinically treat NSCLC and exhibits marked efficacy in patients with NSCLC who have an EGFR mutation. However, free osimertinib administration exhibits an inadequate response in vivo, with only ∼3% patients demonstrating a complete clinical response. Consequently, we designed a biomimetic nanoparticle (CMNP@Osi) comprising a polymeric nanoparticle core and tumor cell-derived membrane-coated shell that combines membrane-mediated homologous and molecular targeting for targeted drug delivery, thereby supporting a dual-target strategy for enhancing osimertinib efficacy. After intravenous injection, CMNP@Osi accumulates at tumor sites and displays enhanced uptake into cancer cells based on homologous targeting. Osimertinib is subsequently released into the cytoplasm, where it suppresses the phosphorylation of upstream EGFR and the downstream AKT signaling pathway and inhibits the proliferation of NSCLC cells. Thus, this dual-targeting strategy using a biomimetic nanocarrier can enhance molecular-targeted drug delivery and improve clinical efficacy.

Metal halide perovskites have shown unique advantages compared with traditional optoelectronic materials. Currently, perovskite films are commonly produced by either multi-step spin coating or vapor deposition techniques. However, both methods face challenges regarding large-scale production. Herein, we propose a straightforward in situ growth method for the fabrication of CsPbBr3 nanocrystal films. The films cover an area over 5.5 cm × 5.5 cm, with precise thickness control of a few microns and decent uniformity. Moreover, we demonstrate that the incorporation of magnesium ions into the perovskite enhances crystallization and effectively passivates surface defects, thereby further enhancing luminous efficiency. By integrating this approach with a silicon photodiode detector, we observe an increase in responsivity from 1.68 × 10−2 A/W to 3.72 × 10−2 A/W at a 365 nm ultraviolet wavelength.