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Abstract Background Insulin resistance (IR) is linked to an increased risk of frailty, yet it remains unclear whether the non-insulin-based IR indicators are associated with frailty trajectories and physical function decline. It aimed to examine the associations of triglyceride-glucose (TyG) index, metabolic score for insulin resistance (METS-IR), estimated glucose disposal rate (eGDR) and with long-term deficit-accumulation frailty trajectories and physical function decline. Methods Data from 6722 participants in the China Health and Retirement Longitudinal Study (CHARLS) were analyzed. Baseline TyG index, METS-IR, eGDR, along with the frailty index (FI) over nine years, were calculated. FI trajectories were assessed using group-based trajectory model (GBTM). Logistic regression models were used to analyze the associations between IR indicators with FI trajectory and frailty risk. Restricted cubic splines (RCS) models were utilized to detect potential dose-response associations. Linear mixed-effects model was used to evaluate associations with FI development speed. Age, gender, educational level, marital status, smoking status, drinking status, life satisfaction, social activity and sleep duration were adjusted. Additionally, a two-sample Mendelian randomization (MR) was performed to assess the causality of observed associations. Results Three FI trajectories including low-stable frailty, moderate-increasing frailty, and accelerated rising frailty were identified. Regarding the frail risk, each SD increment in TyG index was associated with a 16.1% increase in the risk of frailty (OR = 1.161; 95%CI: 1.092, 1.235). An inverse association was observed for eGDR with the OR (95%CI) being 0.741 (0.696, 0.788). A linear relationship was observed between baseline TyG index and frailty risk (P nonlinear = 0.696), but nonlinear association patterns for eGDR (P nonlinearity

Abstract Background Magnolia officinalis (M. officinalis) thrives in temperate, elevated regions, and its desiccated bark comprises medicinal monolignol. Both abiotic and biotic factors can influence the pharmacodynamic compounds of M. officinalis, which display a variety of capabilities. It was the goal of this study to find the main bioclimatic factors that impact the amount of helpful compounds in M. officinalis and to show how these bioclimatic factors influence the metabolic pathways of magnolol and honokiol through actions on transcripts and molecules. We assessed the amounts of medicinal compounds in M. officinalis from Baoxing (BX), Nanjiang (NJ), Xuanhan (XH), and Beichuan (BC) in Sichuan Province. After that, the bioclimatic factors were gathered and put together that affected the growth and used the transcriptome and metabolome to label the M. officinalis data. The associated metabolic pathways were analyzed based on significant alterations in bioclimatic factors. Results Temperature and precipitation influence the accumulation of bioactive compounds in M. officinalis, as well as the metabolism of monolignol, amino acids, flavonoids, α-linolenic acid, and arachidonic acids. Moreover, temperature was negatively related to the mounts of phenylalanine ammonia-lyase (PAL), 4-coumarate-CoA ligase (4CL), and cinnamoyl-CoA reductase (CCR) in the monolignol biosynthetic pathway, as well as to the amounts of cinnamyl alcohol and 4-coumaryl alcohol that were made. Conclusions Moderate temperatures and appropriate precipitation enhanced the metabolism of monolignols in M. officinalis, ascribed to elevated levels of effective enzyme that correlated with the temperature and precipitation modulation of PAL, 4CL, and CCR activity. Furthermore, this study discovered that cinnamonyl alcohol and 4-coumaryl alcohol were critical precursors for the production of magnolol and honokiol, indicating potential strategies for improving M. officinalis' pharmacodynamic characteristics.

Abstract Background Preoperative smoking cessation may reduce postoperative complications in patients with lung cancer. However, the optimal duration of short-term preoperative smoking cessation remains unclear. Methods Three databases, PubMed, Embase, and the Cochrane Library, were searched for studies published up to April 5, 2024. The Newcastle–Ottawa scale was used to assess the risk of bias. The included studies compared the incidence of postoperative complications between patients with different preoperative smoking cessation times and those with persistent preoperative smoking. A meta-analysis of postoperative complications and events such as pneumonia was performed in patients with lung cancer. Results Fourteen studies met the inclusion criteria and included a total of 50,741 patients who had undergone pulmonary resection. The meta-analysis showed that preoperative smoking cessation of > 2 weeks and 1 month was effective in reducing the incidence of postoperative complications (OR 0.72; 95% CI 0.63–0.83; P 1 month is effective in reducing complications and pneumonia after pulmonary resection in patients with lung cancer, especially as video-assisted thoracoscopic surgery (VATS) and robotic-assisted surgery become more common.

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 Objectives This study aimed to analyze lymph node metastasis (LNM) distribution in superficial esophageal squamous cell carcinoma (ESCC) and its impact factors on survival. Methods We reviewed 241 pT1N+ ESCC cases between February 2012 and April 2022 from 10 Chinese hospitals with a high volume of esophageal cancer (EC). We analyzed clinicopathological data to identify overall survival (OS) risk factors and LNM distribution in relation to tumor invasion depth. Results Of the 241 patients, 26 (10.8%) had pT1a cancer and 215 (89.2%) had pT1b cancer. We showed that N3 stage, ≤ 28 lymphadenectomies, and nerve infiltration (NI) were negative factors for OS in superficial pN+ ESCC, whereas the OS was not definitively affected by the tumor depth and the choice of adjuvant therapy. In general, the LNM rates of the 193 pT1N+ ESCC cases can be ranked in the following order: station 106recR > station 106recL > station 1 > station 7 > station 2. With deeper tumor invasion, the higher LNM rate was observed near the bilateral recurrent laryngeal nerves (RLN), but there was no statistically significant difference. Conclusions In superficial ESCC, LNM was frequently observed along the 106recR (35.8%) and 106recL (25.6%) stations. Advanced N‐staging (N3) was a major negative impact factor in prognosis, and adequate lymph nodes dissected (LND) (N > 28) improved OS of pT1N+ ESCC. However, in superficial ESCC, tumor infiltration depth did not affect patients' OS or the distribution of positive LNs. The optimal adjuvant treatment that favors survival for these patients required further investigation.

We report the detection of an extreme stellar prominence eruption on the M dwarf Large Sky Area Multi-Object Fiber Spectroscopic Telescope (LAMOST) J044431.62+235627.9, observed through time-domain H α spectroscopy with the LAMOST. This prominence eruption was accompanied by a superflare lasting over 160.4 minutes. The H α line profile exhibits significant blue-wing enhancement during the impulsive phase and near the flare peak, with a projected bulk blueshift velocity of −228 ± 11 km s ^−1 and a maximum blueshift velocity reaching −605 ± 15 km s ^−1 . Velocity analysis of the eruptive prominence at various heights above the stellar surface indicates that some of the projected ejection velocities along the line of sight exceed the corresponding escape velocities, suggesting a potential coronal mass ejection (CME). The equivalent width (EW) of the H α blue-wing enhancement in this eruption appears to be the largest observed to date and is comparable to the EW of the H α line profile during the quiescent phase of the host star. We performed a two-cloud modeling for the prominence and the associated flare, which suggests that the eruptive prominence has a mass ranging from 1.6 × 10 ^19 to 7.2 × 10 ^19 g. More importantly, the mass ratio of the erupting prominence to its host star is the largest among all reported stellar prominence eruptions/CMEs.

Abstract 1,3‐Dioxolane (DOL), with its broad liquid phase temperature window and low Li+‐solvent binding energy, stands out as an ideal solvent candidate for the wide‐temperature and high‐rate electrolytes. Unfortunately, DOL is susceptible to undergo ring‐opening polymerization under common lithium salts, which markedly retards the reaction kinetics. This work introduces the organic basic additive 1,8‐Diazabicyclo[5.4.0]undec‐7‐ene (DBU) to effectively suppress the polymerization, thus achieving compatibility between LiFSI, LiDFOB lithium salts, and DOL. Furthermore, density functional theory (DFT) calculations are utilized to elucidate the underlying mechanisms of DOL polymerization and to clarify how DBU inhibits its polymerization. The resulting electrolyte, devoid of polymer chain formation, forms a weak solvation structure rich in anions, which demonstrates rapid ion transport kinetics in the bulk electrolyte and excellent electrochemical stability at the electrolyte–electrode interfaces (EEIs) simultaneously. When applied to the LiFePO4||graphite full cell, it exhibits exceptional wide‐temperature and high‐rate performance, with specific capacities reaching 101.2 mAh g −1 at room temperature (20 C), 36.9 mAh g−1 at −40 °C (0.5 C), and 118.0 mAh g−1 at 60 °C (20 C). This study significantly guides the development of wide‐temperature, high‐rate electrolytes.

The properties of DNA polymerases isolated from thermophilic and mesophilic microorganisms, such as the thermophilic Geobacillus stearothermophilus (Bst) and mesophilic Bacillus subtilis phage (Phi29), have been widely researched. However, DNA polymerases in psychrophilic microorganisms remain poorly understood. In this study, we present for the first time the expression and functional characterization of DNA polymerases PWT-WT and FWT-WT from Psychrobacillus sp. BL-248-WT-3 and FJAT-21963. Enzymatic activity assays revealed that FWT-WT possessed strand displacement but lacked exonuclease activity and high ionic strength tolerance, whereas PWT-WT lacked all these properties. Further protein engineering and biochemical analysis identified D423 and S490 as critical mutation sites for improving strand displacement and tolerance to high ionic strength, specifically in the presence of 0–0.3 M potassium chloride (KCl), sodium chloride (NaCl), and potassium acetate (KAc). Three-dimensional structural analysis demonstrated that the size and the electric charge of the single-stranded DNA (ssDNA) encapsulation entrance were pivotal factors in the binding of the ssDNA template.

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.

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 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.

Surface mining is an important way of mining mineral resources. The state and local governments have put forward higher requirements for surface mining in China. Therefore, it is particularly urgent to take surface mining as a science to carry out systematic research, reveal the laws of mining process and phenomenon occurred, and make scientific explanations. First of all, the major technical achievements in the field of surface mining of solid mineral resources in China in the past 40 years were summarized from three aspects: the basic theory of surface mining, the development of key complete sets of equipment and blasting engineering technology. Then, the modern scientific metrology and information metrology technologies were used to conduct a multivariate dynamic analysis of 7128 papers and reports in the past 40 years, and a multi-dimensional quantitative description of the development and evolution process of the main research topics, including the time dimension, was carried out by the cluster analysis. It is found that the evolution of research topics is the result of the coupling effect of many factors, such as technological development, mining status, policy environment, etc. Based on the sorting of the existing major scientific and technological achievements and the objective literature measurement results, it is pointed out that the goal of the future surface mining science is to form a systematic and comprehensive safe, green, efficient and intelligent surface mining technology system, and the realization path is given, that is, to form a hot research topic of surface mining technology system and major equipment, and to strengthen the deep cross integration between the existing hot research and surface mining technology system and major equipment. It also provides some useful suggestions on how to jointly tackle major scientific and technological problems with the advantageous resources of various themes inside and outside the industry to achieve a substantial collaborative innovation among multiple themes. Finally, from the perspective of energy and ecology, the paper looks forward to the development direction of major basic theories and technologies of the future surface mining science from seven aspects: mining area planning theory, intelligent mining design principle, intelligent cluster scheduling theory, safe and efficient mining technology of coal mining in spontaneous combustion prone extra thick coal seams, high slope stability control technology, efficient belt conveyor transportation technology under complex working conditions, and intelligent surface mine system engineering. The development direction of the future surface mining equipment is prospected from five aspects: high efficiency mobile crushing equipment, modular semi-fixed crushing equipment, continuous mining process system equipment, large inclination transportation equipment and large dump machine. It is expected that the study can be used as a reference for scientists and engineers in the surface mining field.

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.

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 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.

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.

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.

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 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

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.

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

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.

Drought stress is a primary abiotic stress that causes significant losses to forestry and agricultural production. Therefore, exploring drought-responsive genes and their regulatory mechanism is crucial for plant molecular breeding for forestry and agriculture production safety. Small auxin-up RNA (SAUR) proteins are essential in plant growth and development but show functional diversity in stress response. In this study, the transcriptome sequencing data of Ammopiptanthus nanus seedlings revealed that the expression of AnSAUR50 was continuously downregulated under drought stress. Hence, the AnSAUR50 gene was cloned and functionally analyzed in drought response. The results showed that the coding sequence of AnSAUR50 was 315 bp in length and encoded 104 amino acids. The AnSAUR50 protein showed high conservation, possessed a SAUR-specific domain, and localized in the nucleus and cell membrane. The heterologous expression of the AnSAUR50 gene enhanced the drought sensitivity of the transgenic Arabidopsis with a lower survival rate, biomass, and higher malondialdehyde content and relative electrolyte leakage. Moreover, transgenic plants showed shorter root lengths and bigger stomatal apertures, resulting in facilitating water loss under drought stress. The study indicates that AnSAUR50 negatively regulates drought tolerance by inhibiting root growth and stomatal closure, which provides insights into the underlying function and regulatory mechanism of SAURs in plant stress response.

Screening the edible parts of low-cadmium (Cd) and high-nutrient crop cultivars is an effective method for reducing Cd intake and enhancing the absorption of beneficial elements for humans. In a hydroponic experiment with Cd toxicity treatment (5 μmol/L CdCl2), we analyzed the differences in the absorption and transport characteristics of Cd and mineral nutrients in 30 rapeseed (Brassica napus L.) cultivars during the seedling stage, as well as the correlations between various elements. Firstly, Pearson correlation analysis indicated that Cd content in the shoot parts of 30 rapeseed cultivars was not correlated with the Cd uptake ability of the roots and was obviously positively correlated with the Cd translocation coefficient from root to shoot (r = 0.452 *, p < 0.05). Hierarchical clustering selected 26 cultivars with lower Cd content in the shoots, and correlation analysis of Cd and other nutrient element contents in the shoots of the 26 cultivars revealed significant negative correlations (r = −0.40 *, p < 0.05; r = −0.45 *, p < 0.05) between iron (Fe) and magnesium (Mg) content and Cd content, while potassium (K), calcium (Ca), manganese (Mn), and zinc (Zn) content had no correlation with Cd content. Then, hierarchical clustering screened 19 cultivars with higher dry weight, 4 cultivars with higher K content, 1 cultivar with higher Ca content, 8 cultivars with higher Mn content, and 3 cultivars with higher Zn content. Finally, a Venn diagram identified four superior rapeseed cultivars with lower Cd and higher nutrients in the shoots, namely, OJ114 (lower Cd, higher Mn and K content), BN365 (lower Cd, higher Mn, Fe, and Zn content), BN275 (lower Cd, higher Ca, Zn, Mn, and Fe content), and BN112 (lower Cd, higher K, Mg, Fe, and Mn content).

Cracks are the most typical faults of concrete structures, and their extension can lead to structural fracture. However, when cracks develop inside a structure, the most important depth information is invisible and difficult to measure. The tracer electromagnetic method is an effective technique for detecting the depth of concrete cracks, but since concrete is a multiphase stochastic composite material, its complex internal structure often interferes with the radar detection results, making the conventional radar interpretation technique difficult. In this study, the detection results for concrete crack depth detection based on the tracer electromagnetic method were comprehensively analyzed by combining the complex signal analysis technique, using transient information such as amplitude, phase, and frequency in order to improve the precision and accuracy of radar signal interpretation. In this study, a numerical model was established to determine whether typical cracks such as vertical cracks and diagonal cracks contain indicators or not, and the ground-penetrating radar forward simulation software was used to perform forward simulation of the numerical model and analyze the forward results. The complex signal analysis technique was used to obtain the response characteristics of typical cracks when they did and did not contain the indicator, and the complex signal was finally analyzed by combining it with the actual crack depth detection data. The results show that the tracer electromagnetic method can significantly improve the crack bottom’s reflection ability for radar signals, and when the crack bottom contains an indicator, the amplitude of the reflected signal at the bottom of the crack is enhanced, the phase is reversed, and the frequency is reduced. The distribution of the crack morphology and the location of the crack bottom can be analyzed more conveniently by using the complex signal analysis technique.

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.

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.

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.

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.

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.

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.

Accurate and high coverage genome assemblies are the basis for downstream analysis of metagenomic studies. Long-read sequencing technology is an ideal tool to facilitate the assemblies of metagenome, except for the drawback of usually producing reads with high sequencing error rate. Many polishing tools were developed to correct the sequencing error, but most are designed on the ground of one or two species. Considering the complexity and uneven depth of metagenomic study, we present a novel deep-learning polishing tool named MetaCONNET for polishing metagenomic assemblies. We evaluate MetaCONNET against Medaka, CONNET and NextPolish in accuracy, coverage, contiguity and resource consumption. Our results demonstrate that MetaCONNET provides a valuable polishing tool and can be applied to many metagenomic studies.

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.

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.

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

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.

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 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.

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.