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Abstract Gut bacteria might play an important role in male reproductive disorders, such as male infertility and sperm abnormalities; however, their causal role is unclear. Herein, Mendelian randomization (MR)-Egger, weighted median, inverse variance weighting, Simple mode, and Weighted mode were used to test the causal relationship between gut microbes and male reproductive diseases. The MR results were validated using various metrics. The MR results were also consolidated using reverse causality speculation, conducted using two-way MR analysis and Steiger filtering. Biological function was analysed using enrichment analyses. The results suggested that eight intestinal microflorae were causally associated with male infertility. The Eubacterium oxidoreducens group was associated with an increased risk of male infertility, while the family Bacteroidaceae was negatively associated with male reproductive diseases. Eight intestinal microflorae were causally associated with abnormal spermatozoa. The family Streptococcaceae was associated with a high risk of abnormal spermatozoa, whereas the family Porphyromonadaceae was associated with a low risk of abnormal spermatozoa. No pleiotropy was observed, this study identified a high correlation between the gut flora and the likelihood of male reproductive diseases. Future research will attempt to advance microbial-focused treatments for such diseases.

Abstract Background Neoadjuvant therapy (NT) has increased survival rates for patients with locally advanced esophageal cancer (EC), but estimating the impact of NT treatment prior to surgery is still very difficult. Methods A retrospective study of the clinical information of 150 patients with locally advanced EC who got NT at Qilu Hospital of Shandong University between June 2018 and June 2023. Patients were randomized into training and internal validation groups at a 3:1 ratio. Furthermore, an external validation cohort comprised 38 patients who underwent neoadjuvant therapy at Qianfoshan Hospital in the Shandong Province between June 2021 and June 2023. Independent risk factors were identified using univariate and multivariate logistic regression (forward stepwise regression). Predictive models and dynamic web nomograms were developed by integrating these risk factors. Results A total of 188 patients with locally advanced EC were enrolled, of whom 118 achieved stage I of neoadjuvant pathologic TNM (ypTNM) after receiving NT and 129 achieved grades 0-1 in the tumor regression grade (TRG). Logistic regression analysis identified five independent predictors of TRG grades 0-1: pulmonary function tests (PFT), prognostic nutritional index (PNI), triglyceride (TG) levels, squamous cell carcinoma antigen (SCC-Ag) levels, and combination immunotherapy. The areas under the receiver operating characteristic (ROC) curves for the training, internal validation, and external validation groups were 0.87, 0.75, and 0.80, respectively. Meanwhile, two independent predictors of stage I of ypTNM were identified: prealbumin (PA) and SCC antigen. The areas under the ROC curves for the training, internal validation, and external validation groups were 0.78, 0.67, and 0.70, respectively. The Hosmer-Lemeshow test for both predictive models showed excellent calibration, with well-fitted calibration curves. Decision curve analysis (DCA) and clinical impact curves (CIC) have demonstrated that nomograms are of clinical utility. Conclusion The nomograms performed well in predicting the likelihood of stage I of ypTNM and TRG grade 0-1 after NT in patients with locally advanced EC. It helps thoracic surgeons to predict the sensitivity of patients to NT before surgery, which enables precise treatment of patients with locally advanced EC.

Abstract Background Non-small cell lung cancer (NSCLC) is the primary reason for cancer-related deaths globally. Tertiary lymphoid structure (TLS) is an organized collection of immune cells acquired in non-physiological, non-lymphoid tissues. High expression of TLS in tumor tissues is generally associated with better prognosis. This research aimed to investigate the prognostic and clinicopathological significance of TLS in patients with NSCLC. Methods A comprehensive literature search was conducted based on Pubmed, EMBASE, and Cochrane Library databases to identify eligible studies published up to December 8, 2023. The prognostic significance and clinicopathological value of TLS in NSCLC were evaluated by calculating the combined hazard ratios (HRs) and odds ratios (ORs) and their 95% confidence intervals (CIs). Following that, additional analyses, including subgroup analysis and sensitivity analysis, were conducted. Results This meta-analysis evaluated the prognostic and clinicopathological significance of TLS in 10 studies involving 1,451 patients with NSCLC. The results revealed that the high levels of TLS were strongly associated with better overall survival (OS) (HR = 0.48, 95% CI: 0.35–0.66, p

Abstract. Background:. Acute respiratory distress syndrome (ARDS) is a common cause of respiratory failure in many critically ill patients. Although inflammasome activation plays an important role in the induction of acute lung injury (ALI) and ARDS, the regulatory mechanism of this process is still unclear. When cells are stimulated by inflammation, the integrity and physiological function of mitochondria play a crucial part in pyroptosis. However, the underlying mechanisms and function of mitochondrial proteins in the process of pyroptosis are largely not yet known. Here, we identified the 18-kDa translocator protein (TSPO), a mitochondrial outer membrane protein, as an important mediator regulating nucleotide-binding domain, leucine-rich repeat, and pyrin domain-containing protein 3 (NLRP3) inflammasome activation in macrophages during ALI. Methods:. TSPO gene knockout (KO) and lipopolysaccharide (LPS)-induced ALI/ARDS mouse models were employed to investigate the biological role of TSPO in the pathogenesis of ARDS. Murine macrophages were used to further characterize the effect of TSPO on the NLRP3 inflammasome pathway. Activation of NLRP3 inflammasome was preformed through LPS + adenosine triphosphate (ATP) co-stimulation, followed by detection of mitochondrial membrane potential, reactive oxygen species (ROS) production, and cell death to evaluate the potential biological function of TSPO. Comparisons between two groups were performed with a two-sided unpaired t-test. Results:. TSPO-KO mice exhibited more severe pulmonary inflammation in response to LPS-induced ALI. TSPO deficiency resulted in enhanced activation of the NLRP3 inflammasome pathway, promoting more proinflammatory cytokine production of macrophages in LPS-injured lung tissue, including interleukin (IL)-1β, IL-18, and macrophage inflammatory protein (MIP)-2. Mitochondria in TSPO-KO macrophages tended to depolarize in response to cellular stress. The increased production of mitochondrial damage-associated molecular pattern led to enhanced mitochondrial membrane depolarization and pyroptosis in TSPO-KO cells. Conclusion:. TSPO may be the key regulator of cellular pyroptosis, and it plays a vital protective role in ARDS occurrence and development.

The acid water-soluble fraction of the 95% EtOH extract of Leonurus japonicus exhibited significant anti-inflammatory activity by suppressing the p-ERK/ERK ratio and iNOS expression. A further phytochemical investigation of this acid water-soluble fraction led to the isolation of three previously undescribed sesquineolignan glycosides, leolignosides A–C (1–3), and their planar structures were elucidated using HR-ESI-MS and 1D and 2D NMR. To determine the complicated absolute configuration of sesquineolignan glycosides, coupling constants, NOESY data, empirical rules, enzymatic hydrolysis, and ECD data were comprehensively used. These isolated compounds were also screened for anti-inflammatory activity. Encouragingly, leolignosides A–C all suppressed LPS-induced NO overproduction in RAW 264.7 macrophages. The aglycone (3a) of leolignoside C was chosen for further investigation for its activity and the available amount. Similar to the acid water-soluble fraction, compound 3a inhibited NO overproduction and decreased the p-ERK/ERK and p-NF-κB/NF-κB ratios, indicating that 3a may exert anti-inflammatory effects through the ERK/NF-κB signaling pathway.

Boron (B), an essential micronutrient for fruit development, also plays a crucial role in maintaining the shelf life of strawberries (Fragaria ananassa Duch.) by affecting cell wall structure and components. We investigated the distribution pattern of B within cells and cell walls in strawberry fruits under different B levels and revealed the relationship between the B distribution in cell walls and fruit firmness after harvesting. Foliar spraying of 0.1% H3BO3 promoted the growth of strawberry seedlings and improved fruit yield and flesh firmness by 45.7% and 25.6%. During the fruit softening and decay process, the content of bound B and cell wall-B decreased while more B was allocated to the protoplast and apoplast. The changes in B distribution in cells were attributed to cell damage during fruit decay, and B extended the freshness period of the fruits by alleviating the decrease of B distribution in cell walls. After leaving the fruits at room temperature for 10 h, the B content in different cell wall components significantly decreased, while foliar spraying of B alleviated the reduction of B content in covalently bound pectin (CBP), cellulose, and hemicellulose. Meanwhile, B spraying on fruit decreased the activity of cell wall degradation enzymes, including polygalacturonase (PG) and pectin lyase (PL), by 20.2% and 38.1%, while enhancing the demethylation of pectin by increasing pectin methylesterase (PME) activity from 21.6 U/g to 25.7 U/g. Thus, foliar spraying of 0.1% H3BO3 enhances the cross-linking of B with cell wall components and maintains cell wall structure, thereby prolonging the shelf life of strawberry fruits.

Unveiling the potential application of psychrophilic polymerases as candidates for polymerase-nanopore long-read sequencing presents a departure from conventional choices such as thermophilic Bacillus stearothermophilus (Bst) renowned for its limitation in temperature and mesophilic Bacillus subtilis phage (phi29) polymerases for limitations in strong exonuclease activity and weak salt tolerance. Exploiting the PB-Bst fusion DNA polymerases from Psychrobacillus (PB) and Bacillus stearothermophilus (Bst), our structural and biochemical analysis reveal a remarkable enhancement in salt tolerance and a concurrent reduction in exonuclease activity, achieved through targeted substitution of a pivotal functional domain. The sulfolobus 7-kDa protein (Sso7d) emerges as a standout fusion domain, imparting significant improvements in PB-Bst processivity. Notably, this study elucidates additional functional sites regulating exonuclease activity (Asp43 and Glu45) and processivity using artificial nucleotides (Glu266, Gln283, Leu334, Glu335, Ser426, and Asp430). By disclosing the intricate dynamics in exonuclease activity, strand displacement, and artificial nucleotide-based processivity at specific functional sites, our findings not only advance the fundamental understanding of psychrophilic polymerases but also provide novel insights into polymerase engineering.

BackgroundThis study aimed to construct a clinical prediction model and nomogram to differentiate invasive from non-invasive pulmonary adenocarcinoma in solitary pulmonary nodules (SPNs).MethodWe analyzed computed tomography and clinical features as well as preoperative biomarkers in 1,106 patients with SPN who underwent pulmonary resection with definite pathology at Qilu Hospital of Shandong University between January 2020 and December 2021. Clinical parameters and imaging characteristics were analyzed using univariate and multivariate logistic regression analyses. Predictive models and nomograms were developed and their recognition abilities were evaluated using receiver operating characteristic (ROC) curves. The clinical utility of the nomogram was evaluated using decision curve analysis (DCA).ResultThe final regression analysis selected age, carcinoembryonic antigen, bronchus sign, lobulation, pleural adhesion, maximum diameter, and the consolidation-to-tumor ratio as associated factors. The areas under the ROC curves were 0.844 (95% confidence interval [CI], 0.817–0.871) and 0.812 (95% CI, 0.766–0.857) for patients in the training and validation cohorts, respectively. The predictive model calibration curve revealed good calibration for both cohorts. The DCA results confirmed that the clinical prediction model was useful in clinical practice. Bias-corrected C-indices for the training and validation cohorts were 0.844 and 0.814, respectively.ConclusionOur predictive model and nomogram might be useful for guiding clinical decisions regarding personalized surgical intervention and treatment options.

Abstract Objectives In this study, we aimed to develop a multiparameter prediction model to improve the diagnostic accuracy of invasive adenocarcinoma in pulmonary pure glass nodules. Method We included patients with pulmonary pure glass nodules who underwent lung resection and had a clear pathology between January 2020 and January 2022 at the Qilu Hospital of Shandong University. We collected data on the clinical characteristics of the patients as well as their preoperative biomarker results and computed tomography features. Thereafter, we performed univariate and multivariate logistic regression analyses to identify independent risk factors, which were then used to develop a prediction model and nomogram. We then evaluated the recognition ability of the model via receiver operating characteristic (ROC) curve analysis and assessed its calibration ability using the Hosmer-Lemeshow test and calibration curves. Further, to assess the clinical utility of the nomogram, we performed decision curve analysis. Result We included 563 patients, comprising 174 and 389 cases of invasive and non-invasive adenocarcinoma, respectively, and identified seven independent risk factors, namely, maximum tumor diameter, age, serum amyloid level, pleural effusion sign, bronchial sign, tumor location, and lobulation. The area under the ROC curve was 0.839 (95% CI: 0.798–0.879) for the training cohort and 0.782 (95% CI: 0.706–0.858) for the validation cohort, indicating a relatively high predictive accuracy for the nomogram. Calibration curves for the prediction model also showed good calibration for both cohorts, and decision curve analysis showed that the clinical prediction model has clinical utility. Conclusion The novel nomogram thus constructed for identifying invasive adenocarcinoma in patients with isolated pulmonary pure glass nodules exhibited excellent discriminatory power, calibration capacity, and clinical utility.

Abstract The role of Basic leucine zipper and W2 domains 2 (BZW2) in the advancement of different types of tumors is noteworthy, but its involvement and molecular mechanisms in lung adenocarcinoma (LUAD) remain uncertain. Through this investigation, it was found that the upregulation of BZW2 was observed in LUAD tissues, which was associated with an unfavorable prognosis for individuals diagnosed with LUAD, as indicated by data from Gene Expression Omnibus and The Cancer Genome Atlas databases. Based on the clinicopathologic characteristics of LUAD patients from the tissue microarray, both univariate and multivariate analyses indicated that BZW2 functioned as an independent prognostic factor for LUAD. In terms of mechanism, BZW2 interacted with glycogen synthase kinase-3 beta (GSK3β) and enhanced the ubiquitination-mediated degradation of GSK3β through slowing down of the dissociation of the ubiquitin ligase complex, which consists of GSK3β and TNF receptor-associated factor 6. Moreover, BZW2 stimulated Wnt/β-catenin signaling pathway through GSK3β, thereby facilitating the advancement of LUAD. In conclusion, BZW2 was a significant promoter of LUAD. The research we conducted identified a promising diagnostic and therapeutic target for LUAD.

Abstract Conventional RGB‐T salient object detection treats RGB and thermal modalities equally to locate the common salient regions. However, the authors observed that the rich colour and texture information of the RGB modality makes the objects more prominent compared to the background; and the thermal modality records the temperature difference of the scene, so the objects usually contain clear and continuous edge information. In this work, a novel mirror‐complementary Transformer network (MCNet) is proposed for RGB‐T SOD, which supervise the two modalities separately with a complementary set of saliency labels under a symmetrical structure. Moreover, the attention‐based feature interaction and serial multiscale dilated convolution (SDC)‐based feature fusion modules are introduced to make the two modalities complement and adjust each other flexibly. When one modality fails, the proposed model can still accurately segment the salient regions. To demonstrate the robustness of the proposed model under challenging scenes in real world, the authors build a novel RGB‐T SOD dataset VT723 based on a large public semantic segmentation RGB‐T dataset used in the autonomous driving domain. Extensive experiments on benchmark and VT723 datasets show that the proposed method outperforms state‐of‐the‐art approaches, including CNN‐based and Transformer‐based methods. The code and dataset can be found at https://github.com/jxr326/SwinMCNet.

Abstract Background The prognostic significance of adjuvant chemotherapy (ACT) for patients with stage IA micropapillary non-predominant (MPNP) lung adenocarcinoma (LUAD) remains unknown. This study aimed to investigate the effects of postoperative ACT in patients with stage IA MPNP-LUAD. Methods A total of 149 patients with pathological stage IA MPNP-LUAD who underwent surgery at our center were retrospectively analyzed. Propensity score matching (PSM) analysis was conducted to reduce potential selection bias. Kaplan–Meier analyses were used to assess the impact of ACT on recurrence-free survival (RFS), overall survival (OS), and disease-specific survival (DSS). Subgroup analyses were performed for the survival outcomes based on the percentage of micropapillary components. Cox proportional hazards regression analyses were applied to identify risk factors associated with survival. Results The receipt or non-receipt of postoperative ACT had no significant effect on RFS, OS, and DSS among all enrolled patients with stage IA MPNP-LUAD (P > 0.05). For patients with a micropapillary component > 5%, the 5-year rates of RFS, OS, and DSS were significantly higher in the ACT group compared to the observation group, both before and after PSM (P 0.05). The resection range (HR = 0.071; 95% CI: 0.020–0.251; P

Abstract Background Identifying lymph node metastasis areas during surgery for early invasive lung adenocarcinoma remains challenging. The aim of this study was to develop a nomogram mathematical model before the end of surgery for predicting lymph node metastasis in patients with early invasive lung adenocarcinoma. Methods In this study, we included patients with invasive lung adenocarcinoma measuring ≤ 2 cm who underwent pulmonary resection with definite pathology at Qilu Hospital of Shandong University from January 2020 to January 2022. Preoperative biomarker results, clinical features, and computed tomography characteristics were collected. The enrolled patients were randomized into a training cohort and a validation cohort in a 7:3 ratio. The training cohort was used to construct the predictive model, while the validation cohort was used to test the model independently. Univariate and multivariate logistic regression analyses were performed to identify independent risk factors. The prediction model and nomogram were established based on the independent risk factors. Recipient operating characteristic (ROC) curves were used to assess the discrimination ability of the model. Calibration capability was assessed using the Hosmer–Lemeshow test and calibration curves. The clinical utility of the nomogram was assessed using decision curve analysis (DCA). Results The overall incidence of lymph node metastasis was 13.23% (61/461). Six indicators were finally determined to be independently associated with lymph node metastasis. These six indicators were: age (P

Fragment reassembly is widely used in fields such as archaeology and forensics. This paper introduces an algorithm for reassembling irregular fragments, enabling the reconstruction of arbitrarily segmented irregular fragments without any prerequisites. The reassembly procedure encompasses feature extraction, local pairwise matching, and global composition. We design a classification network to assess the compatibility of fragment pairings. In order to alleviate the impact of unavoidable errors in the local matching phase, we put forth an error assessment criterion calculated from the contour differences at the junctions, a two-stage reassembly strategy involving both initial and candidate phases, and a region completeness evaluation standard based on the size of the background region to gauge the ultimate composition outcomes. Additionally, due to the limited availability of publicly shared datasets at present, we created a dataset comprising 1000 sets of randomly divided irregular fragments for training and testing. The experimental results show the excellent performance of this algorithm in terms of accuracy and completeness in fragment reassembly for both public and self-constructed datasets.

Background: This study clarified the expression of cicrTLK1 in non-small cell lung cancer (NSCLC) and explored its role in cancer growth, metastasis and immune escape, providing a potential molecular target and theoretical basis for NSCLC treatment. Methods: The expression levels of circTLK1, miR-876-3p and SRSF7 were determined by RT-qPCR assay. The localization of circTLK1 in NSCLC cells was determined by FISH assay. EdU and cell plate clone formation assay were applied to explore cell proliferation. Wound healing test and Transwell assay were applied to measure the migration and invasion ability. Cell apoptosis rate was detected by FCM assay. Western blotting assay was adopted to measure the protein expression of SRSF7. Dual-luciferase reporter gene assay was applied to assess the interaction between miR-876-3p and circTLK1, and between miR-876-3p and SRSF7. The ability of cirTLK1 to regulate tumor formation in vivo was examined by tumor transplantation experiments in nude mice. Results: The relative expression of circTLK1 was increased in NSCLC cell lines. Knockdown of circTLK1 prohibited the proliferation, migration, and invasion, and promoted apoptosis rate, but miR-876-3p inhibitor reversed the effects of circTLK1 knockdown. In addition, silencing of circTLK1 overtly restrained the growth of transplanted tumors in vivo, and inhibited immune escape. In addition, circTLK1 interacted with miR-876-3p, and SRSF7 was concluded to be the target gene of miR-876-3p. Conclusion: In this study, we researched the inhibitory effect of circTLK1knockdown on NSCLC progression and immune escape, and further elucidated the potential regulatory mechanism of circTLK1/miR876-3p/SRSF7 axis.

Abstract Lithium‐ion batteries (LIBs) have gained widespread attention due to their numerous advantages, including high energy density, prolonged cycle life, and environmental friendliness. Nevertheless, their electrochemical performance deteriorates rapidly under extreme temperature conditions, accompanied by a series of safety issues. Electrolyte optimization has emerged as a crucial and feasible strategy to expand the operational temperature range of LIBs. This review comprehensively summarizes the challenges, advances, and characterization methodologies of electrolytes at both subzero and elevated temperatures. Initially, it discusses the degradation mechanisms of different types of electrolytes at extreme temperatures, integrates recent advances, and offers insights into future research directions. Subsequently, various experimental techniques are systematically presented to evaluate the fundamental physical properties, stability, and dynamic behaviors of electrolytes in non‐ambient environments. Finally, it also provides relevant computational methods across the electronic, molecular, and macroscopic scales, and explores the application of high‐throughput techniques in this field. This review offers valuable guidance for breaking the working temperature limits of electrolytes and promoting the development of next‐generation LIBs.

ObjectiveInvestigate the impact of combined computerized cognitive training and occupational therapy on individuals with mild cognitive impairment (MCI).MethodsWe randomly assigned 118 MCI patients into two groups: a combined intervention group (n = 37) and a control group (n = 81), the latter receiving standard nursing care. The intervention group additionally underwent 12 weeks of computerized cognitive training and occupational therapy. Blind assessors evaluated cognitive performance, anxiety, depression, and daily living activities before the intervention, post-intervention, and at a 3-month follow-up.ResultsRepeated-measures analysis of variance showed that the sMoCA scores, HAMA scores, and ADL scores of the experimental group at T2 (post-intervention) and T3 (3-month follow-up) were higher than those of the control group, and the difference was statistically significant (p

BackgroundAs an important mathematical model, the finite state machine (FSM) has been used in many fields, such as manufacturing system, health care, and so on. This paper analyzes the current development status of FSMs. It is pointed out that the traditional methods are often inconvenient for analysis and design, or encounter high computational complexity problems when studying FSMs.MethodThe deep Q-network (DQN) technique, which is a model-free optimization method, is introduced to solve the stabilization problem of probabilistic finite state machines (PFSMs). In order to better understand the technique, some preliminaries, including Markov decision process, ϵ-greedy strategy, DQN, and so on, are recalled.ResultsFirst, a necessary and sufficient stabilizability condition for PFSMs is derived. Next, the feedback stabilization problem of PFSMs is transformed into an optimization problem. Finally, by using the stabilizability condition and deep Q-network, an algorithm for solving the optimization problem (equivalently, computing a state feedback stabilizer) is provided.DiscussionCompared with the traditional Q learning, DQN avoids the limited capacity problem. So our method can deal with high-dimensional complex systems efficiently. The effectiveness of our method is further demonstrated through an illustrative example.

Abstract Background Lymphocyte-activation gene 3 (LAG3) is a recently discovered immune checkpoint molecule that has been linked to immunosuppression and the advancement of cancer in different types of solid tumors. This study aimed to evaluate the prognostic importance of LAG3 and its role in the immune system within solid tumors. Methods Extensive literature searches were conducted using the Pubmed, EMBASE, and Cochrane Library databases to identify relevant studies exploring the effect of LAG3 on survival outcomes. Pooled hazard ratios (HRs) with its 95% confidence intervals (CIs) were calculated to evaluate the prognostic values of LAG3. Afterwards, subgroup analysis and sensitivity analysis were conducted. Pan-cancer analysis investigated the possible relationships between LAG3 expression and genetic alterations, RNA methylation modification-related genes, genomic instability, immune checkpoint genes, and infiltration of immune cells. Results A total of 43 studies with 7,118 patients were included in this analysis. Higher expression of LAG3 was associated with worse overall survival (HR = 1.10, 95% CI 1.01–1.19, P = 0.023), but not disease-free survival (HR = 1.41, 95% CI 0.96–2.07, P = 0.078), progression-free survival (HR = 1.12, 95% CI 0.90–1.39, P = 0.317) or recurrence-free survival (HR = 0.98, 95% CI 0.81–1.19, P = 0.871). Subgroup analysis showed that LAG3 might play different prognostic roles in different solid tumors. LAG3 expression was positively associated with immune cell infiltration and immune checkpoint genes in all of the cancers included. LAG3 expression was also found to be associated with microsatellite instability (MSI), copy number variation (CNV), simple nucleoside variation (SNV), tumor mutation burden (TMB), and neoantigen in various types of cancers. Conclusions Elevated expression of LAG3 is linked to poorer prognosis among patients diagnosed with solid cancers. LAG3 might play varying prognostic roles in different types of solid tumors. Given its substantial involvement in cancer immunity and tumorigenesis, LAG3 has garnered attention as a promising prognostic biomarker and a potential target for immunotherapy.

Abstract Background DARS2 expression is upregulated in lung adenocarcinoma (LUAD) which correlates with tumor patient stage and prognosis. The mechanism of DARS2 involvement in LUAD still needs to be further explored. Methods In this study, we found that DARS2 expression in LUAD tissue was significantly higher than that in normal tissue. At the same time, the Kaplan–Meier curve showed that the survival prognosis of LUAD patients with high expression of DARS2 was significantly worse than low expression of DARS2. The expression of DARS2 was detected in LUAD and adjacent normal tissues by IHC staining, histochemical scoring and a survival curve was generated. In addition, we demonstrated that the knockdown and overexpression of DARS2 significantly affected the proliferation, invasion, and migration of LUAD cells in vitro and in vivo. Finally, western blot and rescue assay were performed on LUAD cells to further explore and verify the signaling pathway. Results DARS2 expression was significantly upregulated in LUAD tissues and cell lines. What is more, the increased expression of DARS2 was closely related to proliferation, invasion and metastasis. The tumorigenic assay in nude mice further showed that the tumorigenic ability of nude mice was significantly improved with the increase in DARS2 expression. Finally, we determined that DARS2 plays its role in LUAD by targeting the ERK/c‐Myc signaling pathway. Conclusion Our data revealed the oncogenic role of DARS2 in LUAD, indicating that DARS2 may be a predictive biomarker and novel therapeutic target for LUAD.

Abstract Background Chronic obstructive pulmonary disease (COPD) is a serious health burden worldwide with high mortality. LncRNA plasmacytoma variant translocation 1 (PVT1) has been illustrated to serve as a biomarker for COPD progression. Nonetheless, its specific functions and mechanisms in COPD are unclarified. Methods Cigarette smoke extract (CSE) was utilized to stimulate 16HBE cells, and cigarette smoke combining with lipopolysaccharide (LPS) was employed to induce COPD in rats. Western blotting and RT-qPCR were utilized for measuring protein and RNA levels. Flow cytometry was implemented for detecting cell apoptosis. Concentrations of inflammatory factors TNF-α and IFN-γ were examined using ELISA. Luciferase reporter assay was utilized for verifying the interaction between molecules. Hematoxylin–eosin staining was performed for histological analysis of rat lung tissues. Results PVT1 was highly expressed in CSE-stimulated 16HBE cells and the lungs of COPD rats. PVT1 depletion restored the viability, restrained apoptosis and hindered inflammatory cytokine production in 16HBE cells under CSE treatment and alleviated pathological damages in COPD rats. PVT1 bound to miR-30b-5p and miR-30b-5p targeted BCL2 like 11 (BCL2L11). Overexpressing BCL2L11 offset the above effects mediated by PVT1 in CSE-triggered 16HBE cells. Conclusion PVT1 enhances apoptosis and inflammation of 16HBE cells under CSE stimulation by modulating miR-30b-5p/BCL2L11 axis.

This paper investigates the use of loaded Co/BETA molecular sieve catalysts for the selective oligomerization of isobutylene. The physicochemical properties of Co/BETA molecular sieves were characterized using XRD, BET, NH3-TPD, FT-IR, XPS, and Py-FTIR. The effects of different active component loadings, reaction temperatures, and reaction air velocities on the selective oligomerization of isobutylene were investigated in a fixed-bed reactor. The results showed that the catalytic effect was optimal when the Co loading was 6%, the reaction temperature was 60 °C, the reaction pressure was 1 MPa, and the reaction air speed was 1 h−1. The isobutylene conversion was greater than 74%, the C8= selectivity was approximately 70%, and the C8= yield reached 51.69% with minimal loss of n-butene, providing good catalytic capacity and efficiency.

2,4-dinitrophenol (2,4-DNP) is a new kind of pollutant that is highly toxic and difficult to be biodegraded. In this study, the feasibility of using exogenous growth regulator salicylic acid (SA) to improve the purification ability of Salix matsudana (S. matsudana) seedlings to 2,4-DNP stress was investigated by a hydroponic simulation experiment. The main research results are as follows: (1) After adding exogenous SA, a high concentration of SA (1000 mg·L−1) inhibited the photosynthetic process and the normal physiological process of the chlorophyll fluorescence system of S. matsudana seedlings to a certain extent. When adding a low concentration of SA (10 mg·L−1) to treat S. matsudana seedlings, all exogenous treatment groups could alleviate the stress of 2,4-DNP on the photosynthetic system and chlorophyll fluorescence system of S. matsudana seedlings, and 10 mg·L−1 SA (DNP + S1) was the best. (2) The addition of exogenous SA could alleviate the damage of 2,4-DNP to S. matsudana seedlings by enhancing the activity of its antioxidant enzymes to remove excess reactive oxygen species (ROS) in the body and reducing the level of membrane lipid peroxidation and the size of membrane damage. The treatment with 10 mg·L−1 SA had the best effect. (3) Exogenous low concentration of SA (10 mg·L−1) could alleviate the decline of biomass index of S. matsudana seedlings under 2,4-DNP stress, but a high concentration of SA (1000 mg·L−1) could not alleviate the 2,4-DNP toxicity of S. matsudana seedlings leaves. Exogenous SA could effectively alleviate the growth damage caused by 2,4-DNP stress on S. matsudana seedlings and increase the tolerance threshold range of S. matsudana seedlings to 2,4-DNP (8.81–33.78 mg·L−1). (4) Exogenous addition of SA could increase the removal percentage of 2,4-DNP in Salix matsudana seedlings. Among them, the removal percentage of Salix matsudana was the highest at 10 mg·L−1 SA, which was 1.46 times (5 days) and 1.19 times (10 days) higher than that of the DNP treatment group, respectively. Overall, when SA reached 10 mg·L−1, the photosynthetic productivity of S. matsudana was the highest, and S. matsudana had the best purification effect on 2,4-DNP in wastewater.

A good intelligent learning model is the key to complete recognition of scene information and accurate recognition of specific targets in intelligent unmanned system. This study proposes a new associative memory model based on the semi-tensor product (STP) of matrices, to address the problems of information storage capacity and association. First, some preliminaries are introduced to facilitate modeling, and the problem of information storage capacity in the application of discrete Hopfield neural network (DHNN) to associative memory is pointed out. Second, learning modes are equivalently converted into their algebraic forms by using STP. A memory matrix is constructed to accurately remember these learning modes. Furthermore, an algorithm for updating the memory matrix is developed to improve the association ability of the model. And another algorithm is provided to show how our model learns and associates. Finally, some examples are given to demonstrate the effectiveness and advantages of our results. Compared with mainstream DHNNs, our model can remember learning modes more accurately with fewer nodes.

Background and aims To explore the incidence of alcohol-related hepatocellular carcinoma (HCC), evaluate possible synergisms between alcohol and well-known risk factors associated with HCC and establish a nomogram to predict alcohol-associated liver disease (ALD)-related HCC risk.Methods A database of 136 571 inpatients in the Fifth Medical Center of Chinese PLA General Hospital from 2002 to 2018 with chronic liver disease was established. Data were collected by medical records review. Multivariate logistic regression was used to identify the independent high-risk factors associated with HCC, and then were incorporated into a novel nomogram. Afterward, the new established model was validated using external cohort by receiver operating characteristic curves analysis. For external cohort, 1646 patients with ALD admitted to our hospital from 2019 to 2021 were included. ALD was diagnosed on the basis of a history of sustained heavy alcohol intake greater than 40 g/day for men and 20 g/day for women for >5 years, clinical evidence of liver disease and supporting laboratory abnormalities.Results Over the last 17 years, trends showed obviously increases in ALD. ALD-related HCC experienced a significant increase from 5.8% to 30.7%, whereas hepatitis B virus (HBV)-related HCC declined from 77.6% to 52.0%. In patients with ALD-related HCC (5119), 3816 (74.54%) cases had HBV infection, 493 (9.63%) cases had hepatitis C virus (HCV) infection, 71 (1.39%) cases were coinfected with both HBV and HCV, and 739 (14.44%) cases had neither HBV nor HCV infection. Drinking years (OR 1.009, 95% CI (1.000 to 1.017)), age (OR 1.060, 95% CI (1.051 to 1.069)), diabetes mellitus (OR 1.314, 95% CI (1.123 to 1.538)), HBV infection (OR 4.905, 95% CI (4.242 to 5.671)), liver cirrhosis (OR 4.922, 95% CI (3.887 to 6.232)) and male sex (OR 17.011, 95%CI (2.296 to 126.013)) were associated with increased risk of HCC in patients with ALD. A nomogram had a concordance index of 0.786 (95% CI 0.773 to 0.799) and had well-fitted calibration curves. These results were successfully validated both in the internal cohort and external cohort.Conclusion The prevalence of ALD and ALD-related HCC has been increased dramatically. The nomogram model established here with its high accuracy and easy-to-use features achieved an optimal prediction of HCC development in patients with ALD, which can help clinicians to develop an individualised and precise treatment strategy.

Tobacco is an important cash crop in China, but the low potassium (K) content and high ratio of total sugar to nicotine in tobacco leaves have seriously affected the quality of tobacco leaves. As a fertilizer synergist, polyaspartic acid (PASP) can improve the K content in tobacco leaves, but it is unknown how it affects the K content in different parts of tobacco leaves, and how PASP affects the ratio of total sugar to nicotine in tobacco leaves has not been reported. Therefore, “Zhongyan 100” was selected for pot experiments with 5 different PASP addition levels: CK (0.0 %), P1 (0.1 %), P2 (0.2 %), P3 (0.4 %) and P4 (0.6 %), to reveal the effects of PASP on tobacco growth, K content, sugar content, nicotine content and the ratio of total sugar to nicotine in different tobacco parts, and determine the optimal PASP dosage for regulating the K content and the ratio of total sugar to nicotine in tobacco. The results showed that P1 (0.1 %) and P2 (0.2 %) only had slighter effects on tobacco growth and quality, while P3 (0.4 %) and P4 (0.6 %)treatments significantly promoted dry matter accumulation, increased K and nicotine content in leaves, decreased reducing sugar and total soluble sugar content in leaves, thereby reducing the ratio of total sugar to nicotine in tobacco leaves, especially in upper leaves. Considering the economic cost savings, 0.4% PASP was determined as the best application level to improve the growth and quality of tobacco. Thus, proper application of PASP is beneficial to improve tobacco leaf quality and reduce chemical K fertilizer application, thereby decreasing agricultural environmental risks of chemical fertilizer and alleviating the rapid depletion of potash in the world.

Limax maximus, or great gray slug, is a common agriculture pest. The pest infests crops during their growth phase, creating holes in vegetable leaves, particularly in seedlings and tender leaves. A study was conducted to assess the insecticidal activity of Ageratina adenophora extract against these slugs. Factors such as fecundity, growth, hatching rate, offspring survival rate, protective enzyme activity, and detoxifying enzyme activity were examined in slugs exposed to the extract's sublethal concentration (LC50) for two different durations (24 and 48 h). The phytochemical variability of the extracts was also studied. The LC50 value of the A. adenophora extract against L. maximus was 35.9 mg/mL. This extract significantly reduced the hatching rate of eggs and the survival rate of offspring hatched from exposed eggs compared with the control. The lowest rates were observed in those exposed for 48 h. The survival, growth, protective enzyme, and detoxification activity of newly hatched and 40-day-old slugs decreased. The A. adenophora extract contained tannins, flavonoids, and saponins, possibly contributing to their biological effects. These results suggest that the extract could be used as an alternative treatment for slug extermination, effectively controlling this species.

Fan-spine magnetic structure, as a fundamental three-dimensional topology in magnetic reconnection theory, plays a crucial role in producing solar jets. However, how fan-spine configurations form in the solar atmosphere remains elusive. Using the Chinese H α Solar Explorer (CHASE) and the Solar Dynamics Observatory, we present a case study on the complete buildup of fan-spine topology driven by flux emergence and the subsequent jet production. Two fan-spine structures and the two associated null points are present. Variations in null-point heights and locations were tracked over time during flux emergence. The north fan-spine structure is found to be created through magnetic reconnection between the newly emerged flux and the background field. Gentle reconnection persistently occurs after formation of the north fan-spine structure, resulting in weak plasma outflows. Subsequently, as flux emergence and magnetic helicity injection continue, the formation and eruption of minifilaments after reconnection at the quasi-separatrix layer between the two nulls trigger three homologous jets. The CHASE observations reveal that the circular flare ribbon, inner bright patch, and remote brightening all exhibit redshifted signatures during these jet ejections. This work unveils the key role of flux emergence in the formation of fan-spine topology, and highlights the importance of minifilaments for subsequent jet production.

BackgroundEsophagectomy is the gold standard treatment for resectable esophageal cancer; however, there is insufficient evidence to indicate potential advantages over standard minimally invasive esophagectomy (MIE) in treating thoracic esophageal cancer. Robot-assisted minimally invasive esophagectomy (RAMIE) bridges the gap between open and minimally invasive surgery. In this single-center retrospective review, we compare the clinical outcomes of EC patients treated with MIE and RAMIE.MethodWe retrospectively reviewed the clinical data of patients with esophageal cancer who underwent surgery at Qilu Hospital between August 2020 and August 2022, including 159 patients who underwent MIE and 35 patients who received RAMIE. The intraoperative, postoperative, and preoperative patient characteristics in both groups were evaluated.ResultsExcept for height, the MIE and RAMIE groups showed no significant differences in preoperative features (P>0.05). Further, there were no significant differences in intraoperative indices, including TNM stage of the resected tumor, tumor tissue type, or ASA score, between the two groups. However, statistically significant differences were found in some factors; the RAMIE group had a shorter operative time, less intraoperative bleeding, and more lymph nodes removed compared to the MIE group. Patients in the RAMIE group reported less discomfort and greater chest drainage on the first postoperative day than patients in the MIE group; however, there were no differences in other features between the two datasets.ConclusionBy comparing the clinical characteristics and outcomes of RAMIE with MIE, this study verified the feasibility and safety of RAMIE for esophageal cancer. Overall, RAMIE resulted in more complete lymph node clearance, shorter operating time, reduced surgical hemorrhage, reduced postoperative discomfort, and chest drainage alleviation in patients. To investigate the function of RAMIE in esophageal cancer, we propose undertaking a future clinical trial with long-term follow-up to analyze tumor clearance, recurrence, and survival after RAMIE.

Background: This study presents the initial case of phlegmonous enteritis following endoscopic submucosal dissection (ESD), a rare and potentially fatal complication. Additionally, a comprehensive review of relevant literature is provided. Case report: A 66-year-old female patient, diagnosed with Hashimoto's thyroiditis and thrombocytopenia, underwent ESD to address a laterally spreading tumor located in the ascending colon. After the procedure, the patient manifested abdominal pain and a high fever, was diagnosed with peritonitis, necessitating an emergency exploratory laparotomy and right hemicolectomy. Subsequent histological examination indicated a significant presence of neutrophil infiltration across all layers of the intestines. The ascites culture yielded the growth of Escherichia coli. Literature review: A search was conducted in the PubMed database to identify case reports conforming to the definition of phlegmonous enteritis proposed by Rokitansky et al. We retrieved about 30 studies regarding phlegmonous enteritis from 1951 to 2022, with around 39 cases. Among these, only 28 patients had comprehensive medical data available. Subsequently, an examination of the literature was undertaken to explore the pathogenesis, prevention, and treatment of phlegmonous enteritis. Conclusion: The possibility of phlegmonous enteritis should be taken into consideration in cases of unexplained acute abdomen, particularly in patients with compromised immunity, in order to provide active surgical and antibiotic interventions.

Micro-milling, widely employed across various fields, faces significant challenges due to the small diameter and limited stiffness of its tools, making the process highly susceptible to cutting chatter and premature tool breakage. Ensuring stable and safe cutting processes necessitates the prediction of chatter by considering the tool breakage. Crucially, the modal parameters of the spindle–holder–tool system are important prerequisites for such stability prediction. In this paper, the frequency response functions (FRFs) of the micro-milling tool are calculated by direct FRFs of the micro-milling cutter and cross FRFs between a point on the shank and one on the tool tip. Additionally, by utilizing a cutting force model specific to micro-milling, the bending stress experienced by the tool is computed, and the tool breakage curve is subsequently determined based on the material’s permissible maximum allowable stress. The FRFs of the micro-milling tool, alongside the tool breakage curve, are then integrated to generate the final stability lobe diagrams (SLDs). The effectiveness and reliability of the proposed methodology are confirmed through a comprehensive series of numerical and experimental validations.

Hybrid rocket motors have great development potential due to their outstanding thrust adjustment flexibility and long-term operation ability. However, nozzle erosion during the motor operation can cause an increase in the throat area of the nozzle, which leads to a decrease in combustion chamber pressure and nozzle efficiency. Therefore, a performance prediction model for hybrid rocket motors considering nozzle erosion has become a key technology that must be addressed when developing hybrid rocket motors. This study uses dynamic grid technology to simulate the regression of the combustion surface and nozzle erosion, which fits well with experimental values. The behavior of high-energy particles in the combustion chamber is simulated through a discrete phase model. Notably, distinctive behavior is observed in Al and Mg droplets, with Al droplets exhibiting incomplete vaporization in the combustion chamber while Mg droplets completely vaporize. A ground firing test using the Φ336 mm hybrid rocket motor lasting 200 s is conducted. The results show that the dynamic numerical simulation, accounting for nozzle erosion, substantially enhances performance prediction accuracy. The average deviation in motor thrust remains below 1.8%, and the combustion chamber pressure deviation stays under 2.6%, confirming the precision of the model. Ultimately, both simulation and experimental outcomes indicate a gradual decrease in specific impulse and characteristic velocity over the long-term operation, attributed to the gradual deviation of the oxygen-fuel ratio. This research provides valuable insights for guiding hybrid rocket motor design and optimizing design parameters to improve overall performance. This model can achieve long-duration and high-precision performance predictions for hybrid rocket motors.

Abstract Gut microbiota is closely related to human health and disease because, together with their metabolites, gut microbiota maintain normal intestinal peristalsis. The use of antibiotics or opioid anesthetics, or both, during surgical procedures can lead to dysbiosis and affect intestinal motility; however, the underlying mechanisms are not fully known. This review aims to discuss the effect of gut microbiota and their metabolites on postoperative intestinal motility, focusing on regulating the enteric nervous system, 5-hydroxytryptamine neurotransmitter, and aryl hydrocarbon receptor.

Abstract Background Effective targeted therapy for lung adenocarcinoma (LUAD), the number one cancer killer worldwide, continues to be a difficult problem because of the limitation of number of applicable patients and acquired resistance. Identifying more promising drug targets for LUAD treatment holds immense clinical significance. Recent studies have revealed that the U2 auxiliary factor (U2AF) homology motif kinase 1 (UHMK1) is a robust pro‐oncogenic factor in many cancers. However, its biological functions and the underlying molecular mechanisms in LUAD have not been investigated. Methods The UHMK1 expression in LUAD cells and tissues was evaluated by bioinformatics analysis, immunohistochemistry (IHC), western blotting (WB), and real time quantitative polymerase chain reaction (RT‐qPCR) assays. A series of gain‐ and loss‐of‐function experiments for UHMK1 were carried out to investigate its biological functions in LUAD in vitro and in vivo. The mechanisms underlying UHMK1's effects in LUAD were analyzed by transcriptome sequencing and WB assays. Results UHMK1 expression was aberrantly elevated in LUAD tumors and cell lines and positively correlated with tumor size and unfavorable patient prognosis. Functionally, UHMK1 displayed robust pro‐oncogenic capacity in LUAD and mechanistically exerted its biological effects via the phosphoinositide 3‐kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway. Conclusion UHMK1 is a potent oncogene in LUAD. Targeting UHMK1 may significantly improve the effect of LUAD treatment via inhibiting multiple biological ways of LUAD progression.

Abstract Objective This study aims to explore the effect of an extract of Atractylodes lancea (A. lancea) on antibiotics-induced intestinal tract disorder and the probable therapeutic mechanisms employed by this extract to ameliorate these disorders. Methods Three days after acclimatization, nine male and nine female specific-pathogen-free (SPF) mice were randomly assigned into three groups: Group C (normal saline), Group M (antibiotic: cefradine + gentamicin), and Group T (antibiotic + A. lancea extract). Each mouse in Groups M and T received intragastric (i.g.) gavage antibiotics containing cefradine and gentamicin sulfate (0.02 ml/g−1/D−1) for 7 days. A. lancea extract (0.02 ml/g−1/D−1) was administered by i.g. gavage to Group T mice for 7 days following the cessation of antibiotic therapy. Group M received an equivalent volume of normal saline for 7 days, while Group C received an equivalent volume of normal saline for 14 days. Afterwards, we collected mouse feces to assess changes in intestinal microbiota by 16S ribosomal ribonucleic acid (rRNA) sequencing and metabolomics. In addition, serum samples were gathered and analyzed using liquid chromatography–mass spectrometry (LS-MS). Finally, we performed a correlation analysis between intestinal microbiota and metabolites. Results After treatment with antibiotic, the richness and diversity of the flora, numbers of wall-breaking bacteria and Bacteroidetes, and the numbers of beneficial bacteria decreased, while the numbers of harmful bacteria increased. After i.g. administration of A. lancea extract, the imbalance of microbial flora began to recover. Antibiotics primarily influence the metabolism of lipids, steroids, peptides, organic acids, and carbohydrates, with lipid compounds ranking first. Arachidonic acid (AA), arginine, and proline have relatively strong effects on the metabolisms of antibiotic-stressed mice. Our findings revealed that A. lancea extract might restore the metabolism of AA and L-methionine. The content of differential metabolites detected in the serum of Group T mice was comparable to that in the serum of Group C mice, but significantly different from that of Group M mice. Compared to putative biomarkers in the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, it was found that altered metabolites, such as amino acids, glycerol, and phospholipids, were primarily associated with the metabolism. Conclusions The effective mechanisms of A. lancea extract in regulating the disorder of intestinal flora in mice are related to the mechanisms of A. lancea. It could relate to lipid metabolism, bile acid metabolism, and amino acid metabolism. These results will provide a basis for further explaining the mechanism by which A. lancea regulats intestinal flora.

BackgroundThe progression of early stage non-small cell lung cancer (NSCLC) is closely related to epidermal growth factor receptor (EGFR) mutation status. The purpose of this study was to systematically investigate the relationship between EGFR mutation status and demographic, imaging, and ultimately pathologic features in patients with NSCLC.MethodsA complete literature search was conducted using the PubMed, Web of Science, EMBASE, and Cochrane Library databases to discover articles published by May 15, 2023 that were eligible. The relationship between EGFR mutation status and specific demographic, imaging, and ultimately pathologic features in patients with NSCLC was evaluated using pooled odds ratios (ORs) and their 95% confidence intervals (CIs). The standardized mean difference (SMD) with 95% CIs was the appropriate statistic to summarize standard deviations (SDs) means for continuous variables.ResultsA total of 9 studies with 1789 patients were included in this analysis. The final findings suggested that patients with a greater age, female gender, and non-smoking status would have a relatively higher incidence of EGFR mutations. Additionally, the risk of EGFR mutations increased with larger tumor diameter, tumor imaging presentation of mixed ground glass opacity (mGGO), and tumor pathological findings of minimally invasive adenocarcinoma (MIA) or invasive adenocarcinoma (IAC). Significantly, malignancies presenting as MIA are more likely to contain L858R point mutations (OR = 1.80; 95% CI: 1.04–3.13; p = 0.04) rather than exon 19 deletions (OR = 1.81; 95% CI: 0.95–3.44; p = 0.07).ConclusionThis meta-analysis showed that imaging parameters and histological classifications of pulmonary nodules may be able to predict stage IA NSCLC genetic changes.

In order to assess the heavy metal pollution features, ecological dangers, and health risk status posed to human beings by soils in the Ankang Basin, a study was conducted. This involved the collection of 38 surface soil samples, followed by the determination of elemental levels of arsenic, mercury, copper, cadmium, lead, chromium, nickel, and zinc. The concentrations of arsenic, mercury, copper, cadmium, lead, chromium, nickel, and zinc were quantified through the collection of 38 surface soil samples. The data obtained from the study was subjected to analysis and evaluation utilizing various academic methodologies, including the geo-accumulation index method, potential ecological risk assessment method, human health risk assessment model, and Monte Carlo simulation method. The findings indicated that the concentrations of the eight heavy metals in the soil above the background levels, with only Cadmium (Cd) marginally surpassing the threshold set for controlling soil pollution risks. The ground accumulation index revealed a higher degree of soil pollution with mercury, cadmium, copper, and zinc components. According to the possible ecological risk index, the presence of mercury and cadmium elements poses significant ecological hazards. The geographical distribution analysis suggests that these risks mostly stem from the combined impacts of human activities and the topographical and geomorphological characteristics of the river valley. The findings of the human health risk assessment indicated that the non-carcinogenic risk fell within acceptable limits. Additionally, it was observed that the carcinogenic risk associated with arsenic, mercury, cadmium, and nickel was comparatively greater for children as compared to adults. The results of the Monte Carlo simulations indicate that the non-carcinogenic hazards have a negligible effect on human health. However, it was seen that arsenic and nickel have a greater likelihood of presenting a substantial carcinogenic risk to humans, particularly in relation to the pediatric population, hence exerting a more pronounced impact on their health. In general, it is observed that conventional deterministic risk assessments tend to overstate the potential health risks associated with a given situation. Conversely, the utilization of Monte Carlo simulations has been found to effectively mitigate uncertainties in health risk assessments. It has been observed that children exhibit a higher vulnerability to both carcinogenic and non-carcinogenic health impacts resulting from exposure to heavy metals present in soil, in comparison to adults. It is recommended that residents prioritize the surveillance of soil heavy metals in relation to potential impacts on human health.

A large amount of nitrogen (N) fertilizer is applied to maintain a stable yield because of the low N utilization efficiency (NUtE) in rapeseed (Brassica napus L.), which increases production costs and has a negative impact on the environment. Abscisic acid (ABA) has been reported to have crosstalk with nitrate. In this study, exogenous ABA treatment and RNA-seq were used to explore the response patterns of rapeseed with contrasting NUtE to ABA signals. Our results showed that ABA application on leaf promoted the N allocation from vegetative organs to grain and increased the number of seeds per silique, grain yield, N harvest index (NHI), and the NUtE in N-efficient rapeseed. Transcriptome analysis showed the DEGs were mainly enriched in N metabolism, ABC transporters, and MAPK signaling pathways. Among them, the Glutamate dehydrogenase (GS) genes and the Glutamine synthetase gene were more highly expressed in the N-efficient genotype leaf than the N-inefficient genotype after ABA treatment. In contrast, the opposite expression level was observed in seven genes, including nitrate transporter 2.1, Nitrate Reductase genes, and GS genes in the root. In conclusion, the shoot and root of rapeseed may have different response mechanisms to ABA stimulation, and N-efficient rapeseed is more sensitive to ABA treatment, which may be one of the reasons for the difference in NUtE

In Phi29-α–hemolysin (α-HL) nanopore sequencing systems, a strong electrochemical signal is dependent on a high concentration of salt. However, high salt concentrations adversely affect polymerase activity. Sequencing by synthesis (SBS) requires the use of phi29 polymerase without exonuclease activity to prevent the degradation of modified nucleotide tags; however, the lack of exonuclease activity also affects polymerase processivity. This study aimed to optimize phi29 polymerase for improved salt tolerance and processivity while maintaining its lack of exonuclease activity to meet the requirements of nanopore sequencing. Using salt tolerance compartmentalized self-replication (stCSR) and a microfluidic platform, we obtained 11 mutant sites with enhanced salt tolerance attributes. Sequencing and biochemical analyses revealed that the substitution of conserved amino acids such as G197D, Y369E, T372N, and I378R plays a critical role in maintaining the processivity of exonuclease-deficient phi29 polymerase under high salt conditions. Furthermore, Y369E and T372N have been identified as important determinants of DNA polymerase binding affinity. This study provides insights into optimizing polymerase processability under high-salt conditions for real-time polymerase nanopore sequencing, paving the way for improved performance and applications in nanopore sequencing technologies.

Abstract The presence of grand minima, characterized by significantly reduced solar and stellar activity, brings a challenge to the understanding of solar and stellar dynamo. The Maunder Minimum (1645–1715 AD) is a representative grand solar minimum. The cyclic variation of solar activity, especially the cycle length during this period, is critical to understand the solar dynamo but remains unknown. By analyzing the variations in solar activity‐related equatorial auroras recorded in Korean historical books in the vicinity of a low‐intensity paleo‐West Pacific geomagnetic anomaly, we find clear evidence of an 8‐year solar cycle rather than the normal 11‐year cycle during the Maunder Minimum. This result provides a key constraint on solar dynamo models and the generation mechanism of grand solar minima.

Abstract Background A Phase II study was undertaken to evaluate the safety and efficacy of the neoadjuvant socazolimab, a novel PD-L1 inhibitor, in combination with nab-paclitaxel and cisplatin for locally advanced esophageal squamous cell carcinoma (ESCC). Methods Sixty-four patients were randomly divided between the Socazolimab + nab-paclitaxel + cisplatin (TP) arm (n = 32) and the control arm (n = 32), receiving either socazolimab (5 mg/kg intravenously (IV), day 1) or a placebo with nab-paclitaxel (125 mg/m2 IV, day 1/8) and cisplatin (75 mg/m2 IV, day 1) repeated every 21 days for four cycles before surgery. The primary endpoint was major pathological response (MPR), and the secondary endpoints were pathological complete response (pCR), R0 resection rate, event-free survival (EFS), overall survival (OS), and safety. Results A total of 29 (90.6%) patients in each arm underwent surgery, and 29 (100%) and 28 (98.6%) patients underwent R0 resection in the Socazolimab + TP and Placebo + TP arms, respectively. The MPR rates were 69.0 and 62.1% (95% Confidence Interval (CI): 49.1–84.0% vs. 42.4–78.7%, P = 0.509), and the pCR rates were 41.4 and 27.6% (95% CI: 24.1–60.9% vs. 13.5–47.5%, P = 0.311) in the Socazolimab + TP and Placebo + TP arms, respectively. Significantly higher incidence rates of ypT0 (37.9% vs. 3.5%; P = 0.001) and T downstaging were observed in the Socazolimab + TP arm than in the Placebo + TP arm. The EFS and OS outcomes were not mature. Conclusions The neoadjuvant socazolimab combined with chemotherapy demonstrated promising MPR and pCR rates and significant T downstaging in locally advanced ESCC without increasing surgical complication rates. Trial registration Registration name (on clinicaltrials.gov): A Study of Anti-PD-L1 Antibody in Neoadjuvant Chemotherapy of Esophageal Squamous Cell Carcinoma. Registration number: NCT04460066.

Myocardial substrate metabolism in cardiac hypertrophy or heart failure shifts from fatty acid oxidation to a greater reliance on glycolysis. Here, the authors show that KLF7 can simultaneously regulate key enzymes in glycolysis and fatty acid oxidation to mitigate metabolic imbalance during cardiac hypertrophy.

Abstract Crohn's disease (CD) is a complex autoimmune disorder presumed to be driven by complex interactions of genetic, immune, microbial and even environmental factors. Intrinsic molecular mechanisms in CD, however, remain poorly understood. The identification of novel biomarkers in CD cases based on larger samples through machine learning approaches may inform the diagnosis and treatment of diseases. A comprehensive analysis was conducted on all CD datasets of Gene Expression Omnibus (GEO); our team then used the robust rank aggregation (RRA) method to identify differentially expressed genes (DEGs) between controls and CD patients. PPI (protein‒protein interaction) network and functional enrichment analyses were performed to investigate the potential functions of the DEGs, with molecular complex detection (MCODE) identifying some important functional modules from the PPI network. Three machine learning algorithms, support vector machine-recursive feature elimination (SVM-RFE), random forest (RF), and least absolute shrinkage and selection operator (LASSO), were applied to determine characteristic genes, which were verified by ROC curve analysis and immunohistochemistry (IHC) using clinical samples. Univariable and multivariable logistic regression were used to establish a machine learning score for diagnosis. Single-sample GSEA (ssGSEA) was performed to examine the correlation between immune infiltration and biomarkers. In total, 5 datasets met the inclusion criteria: GSE75214, GSE95095, GSE126124, GSE179285, and GSE186582. Based on RRA integrated analysis, 203 significant DEGs were identified (120 upregulated genes and 83 downregulated genes), and MCODE revealed some important functional modules in the PPI network. Machine learning identified LCN2, REG1A, AQP9, CCL2, GIP, PROK2, DEFA5, CXCL9, and NAMPT; AQP9, PROK2, LCN2, and NAMPT were further verified by ROC curves and IHC in the external cohort. The final machine learning score was defined as [Expression level of AQP9 × (2.644)] + [Expression level of LCN2 × (0.958)] + [Expression level of NAMPT × (1.115)]. ssGSEA showed markedly elevated levels of dendritic cells and innate immune cells, such as macrophages and NK cells, in CD, consistent with the gene enrichment results that the DEGs are mainly involved in the IL-17 signaling pathway and humoral immune response. The selected biomarkers analyzed by the RRA method and machine learning are highly reliable. These findings improve our understanding of the molecular mechanisms of CD pathogenesis.

Abstract Background The Mesenchymal epithelial transition factor (MET) gene encodes a receptor tyrosine kinase with pleiotropic functions in cancer. MET exon 14 skipping alterations and high-level MET amplification are oncogenic and targetable genetic changes in patients with non-small-cell lung cancer (NSCLC). Resistance to tyrosine kinase inhibitors (TKIs) has been a major challenge for targeted therapies that impairs their clinical efficacies. Methods Eighty-six NSCLC patients were categorized into three cohorts based on the time of detecting MET tyrosine kinase domain (TKD) mutations (cohort 1: at baseline; cohort 2: after MET-TKI treatment; cohort 3: after EGFR-TKI treatment). Baseline and paired TKI treatment samples were analyzed by targeted next-generation sequencing. Results MET TKD mutations were highly prevalent in METex14-positive NSCLC patients after MET-TKI treatment, including L1195V, D1228N/H/Y/E, Y1230C/H/N/S, and a double-mutant within codons D1228 and M1229. Missense mutations in MET TKD were also identified at baseline and in post-EGFR-TKI treatment samples, which showed different distribution patterns than those in post-MET-TKI treatment samples. Remarkably, H1094Y and L1195F, absent from MET-TKI-treated patients, were the predominant type of MET TKD mutations in patients after EGFR-TKI treatment. D1228H, which was not found in treatment-naïve patients, also accounted for 14.3% of all MET TKD mutations in EGFR-TKI-treated samples. Two patients with baseline EGFR-sensitizing mutations who acquired MET-V1092I or MET-H1094Y after first-line EGFR-TKI treatment experienced an overall improvement in their clinical symptoms, followed by targeted therapy with MET-TKIs. Conclusions MET TKD mutations were identified in both baseline and patients treated with TKIs. MET-H1094Y might play an oncogenic role in NSCLC and may confer acquired resistance to EGFR-TKIs. Preliminary data indicates that EGFR-mutated NSCLC patients who acquired MET-V1092I or MET-H1094Y may benefit from combinatorial therapy with EGFR-TKI and MET-TKI, providing insights into personalized medical treatment.

Abstract Circular RNAs play important roles in many cancers, including esophageal squamous cell carcinoma (ESCC), but the precise functions of most circular RNAs are poorly understood. Here we detected significant downregulation of circTRPS1-2 in ESCC based on high-throughput sequencing of three pairs of ESCC tissue and adjacent normal tissue, followed by PCR validation with another 30 tissue pairs. Patients with ESCC whose circTRPS1-2 expression was below the median level for the sample showed significantly shorter median overall survival (13 months) than patients whose circTRPS1-2 expression was above the median (36 months). Overexpressing circTRPS1-2 in the human ESCC cell lines K150 and E109, which express low endogenous levels of circTRPS1-2, inhibited cell proliferation and migration. Conversely, knocking down circTRPS1-2 using short interfering RNA promoted cell proliferation and migration. Similar results were observed in mice bearing K150 xenografts in which circTRPS1-2 was overexpressed or knocked down. Several ribosomal proteins co-immunoprecipitated with circTRPS1-2 from K150 cells in culture, and K150 cells overexpressing circTRPS1-2 showed reduced numbers of ribosomes by A260 absorbance measure and electron microscopy. Our results suggest that circTRPS1-2 can inhibit ESCC proliferation and migration by reducing the production of ribosomes, establishing its potential usefulness in ESCC treatment and prediction of prognosis.

The hopper is an important piece of basic equipment used for storing and transporting materials in the agricultural, grain, chemical engineering, coal mine and pharmaceutical industries. The discharging performance of hoppers is mainly affected by material properties and hopper structure. In this work, the flow capacity of cylindrical pellets in the hopper with the unloading paddle is studied. A series of numerical simulation analyses with the aid of the discrete element method (DEM) platform are carried out. Then, the discharging process is illustrated, and the flow capacity of pellets in the hopper is analyzed by the mass flow index (MFI), the dynamic discharging angle (DDA) formed in the discharging process and porosity among pellets. Furthermore, the effect of parameters such as hopper half angle, rotation speed of the unloading paddle and outlet diameter of the hopper is investigated. The results show that MFI increases with an increase in hopper half angle or outlet diameter and a decrease in rotation speed. Meanwhile, DDA and porosity decrease with the increase in the hopper half angle or outlet diameter and the decrease in the rotation speed. Finally, the MFI ~0.24 is identified as the criterion to distinguish the mass flow from the funnel flow for the hopper with an unloading paddle, and the optimization results are decided as follows: hopper half angle greater than 60°, outlet diameter greater than 60 mm and rotation speed between 45 rpm and 60 rpm. These results should be useful for providing a theoretical reference for the optimization design of feeding devices for swine feeders.

Coronal mass ejections (CMEs) on stars can change the stars’ magnetic field configurations and mass-loss rates during the eruption and propagation and therefore, may affect the stars’ rotation properties on long timescales. The dynamics of stellar CMEs and their influence on the stellar angular momentum loss rate are not yet well understood. In order to start investigating these CME-related aspects on other stars, we conducted a series of magnetohydrodynamic simulations of CMEs on a solar-type star of moderate activity levels. The propagation and evolution of the CMEs were traced in the three-dimensional outputs and the temporal evolution of their dynamic properties (such as masses, velocities, and kinetic energies) were determined. The simulated stellar CMEs are more massive and energetic than their solar analog, which is a result of the stronger magnetic field on the surface of the simulated star than that of the Sun. The simulated CMEs display masses ranging from ∼10 ^16 to ∼10 ^18 g and kinetic energies from ∼10 ^31 to ∼10 ^33 erg. We also investigated the instantaneous influence of the CMEs on the star’s angular momentum loss rate. Our results suggest that angular momentum can either be added to or removed from the star during the evolution of CME events. We found a positive correlation between the amplitude of the angular momentum loss rate variation and the CME’s kinetic energy as well as mass, suggesting that more energetic/massive CMEs have a higher possibility to add angular momentum to the star.

Filament eruptions often lead to coronal mass ejections (CMEs) on the Sun and are one of the most energetic eruptive phenomena in the atmospheres of other late-type stars. However, the detection of filament eruptions and CMEs on stars beyond the solar system is challenging. Here, we present six filament eruption cases on the Sun and show that filament material obscuring part of the solar disk can cause detectable dimming signatures in Sun-as-a-star flux curves of He ii 304 Å. Those filament eruptions have similar morphological features, originating from small filaments inside active regions and subsequently strongly expanding to obscure large areas of the solar disk or the bright flare regions. We have tracked the detailed evolution of six obscuration dimmings and estimated the dimming properties, such as dimming depths, dimming areas, and duration. The largest dimming depth among the six events under study is 6.2% accompanied by the largest dimming area of 5.6% of the solar disk area. Other events have maximum dimming depths in a range of around 1%–3%, with maximum areas varying between about 3%–4% of the solar disk area. The duration of the dimming spans from around 0.4–7.0 hr for the six events under study. A positive correlation was found between the dimming depth and area, which may help to set constraints on the filament sizes in stellar observations.