Search

Abstract Clear cell renal cell carcinoma is a prevalent urological malignancy, imposing substantial burdens on both patients and society. In our study, we used bioinformatics methods to select four putative target genes associated with EMT and prognosis and developed a nomogram model which could accurately predicting 5-year patient survival rates. We further analyzed proteome and single-cell data and selected PLCG2 and TMEM38A for the following experiments. Overexpression models of PLCG2 and TMEM38A were generated in Caki-1 and 786-O cell lines using plasmids. The in vitro experiments demonstrated that both of them exerted pro-apoptotic effects on Caki-1 and 786-O cells, inducing G2/M phase arrest, inhibiting proliferation, and suppressing EMT. In summary, we identified potential tumor suppressor factors and stratified ccRCC patients into high-risk and low-risk groups based on these factors. Furthermore, we elucidated the impact of PLCG2 and TMEM38A in Caki-1 and 786-O cell lines, offering novel avenues for therapeutic target exploration.

Abstract Background Bacterial pathogens frequently encounter host-derived metabolites during their colonization and invasion processes, which can serve as nutrients, antimicrobial agents, or signaling molecules for the pathogens. The essential nutrient choline (Cho) is widely known to be utilized by a diverse range of bacteria and may undergo conversion into the disease-associated metabolite trimethylamine (TMA). However, the impact of choline metabolism on bacterial physiology and virulence remains largely unexplored. Methods Here, we employed an in vitro infection model to investigate the role of Cho in intracellular survival and virulence of Pseudomonas aeruginosa (P. aeruginosa). Additionally, a comprehensive RNA-seq based transcriptomic analysis and various phenotypic assays were performed to elucidate the impacts of Cho on P. aeruginosa. Results We observed that the Cho metabolite glycine betaine (GB) effectively reduced intracellular levels of cyclic-di-GMP (c-di-GMP). Supplementation of Cho or GB in P. aeruginosa had thus affected c-di-GMP regulated phenotypes, such as pyoverdine production, biofilm formation, and mobility. Depletion of Cho metabolism through knockout of the betAB operon resulted in compromised intracellular survival of P. aeruginosa. Notably, the P. aeruginosa betAB mutant elicited a more robust protective inflammatory response compared to the wild-type strain. Conclusion Our study showed that P. aeruginosa Cho metabolism not only interferes host nutritional immunity, but also directly affect multiple virulence phenotypes through modulation of c-di-GMP signaling.

Abstract Cancer stem cells (CSCs) represent a small yet pivotal subset of tumor cells endowed with self-renewal capabilities. These cells are intricately linked to tumor progression and are central to drug resistance, metastasis, and recurrence. The tumor microenvironment (TME) encompasses the cancer cells and their surrounding milieu, including immune and inflammatory cells, cancer-associated fibroblasts, adjacent stromal tissues, tumor vasculature, and a variety of cytokines and chemokines. Within the TME, cells such as immune and inflammatory cells, endothelial cells, adipocytes, and fibroblasts release growth factors, cytokines, chemokines, and exosomes, which can either sustain or disrupt CSCs, thereby influencing tumor progression. Conversely, CSCs can also secrete cytokines, chemokines, and exosomes, affecting various components of the TME. Exosomes, a subset of extracellular vesicles (EVs), carry a complex cargo of nucleic acids, proteins, and lipids, playing a crucial role in the communication between CSCs and the TME. This review primarily focuses on the impact of exosomes secreted by CSCs (CSC-exo) on tumor progression, including their roles in maintaining stemness, promoting angiogenesis, facilitating metastasis, inducing immune suppression, and contributing to drug resistance. Additionally, we discuss how exosomes secreted by different cells within the TME affect CSCs. Finally, we explore the potential of utilizing exosomes to mitigate the detrimental effects of CSCs or to target and eliminate them. A thorough understanding of the exosome-mediated crosstalk between CSCs and the TME could provide valuable insights for developing targeted therapies against CSCs.

Abstract The complexity of tumors and the challenges associated with treatment often stem from the limitations of existing models in accurately replicating authentic tumors. Recently, organoid technology has emerged as an innovative platform for tumor research. This bioengineering approach enables researchers to simulate, in vitro, the interactions between tumors and their microenvironment, thereby enhancing the intricate interplay between tumor cells and their surroundings. Organoids also integrate multidimensional data, providing a novel paradigm for understanding tumor development and progression while facilitating precision therapy. Furthermore, advancements in imaging and genetic editing techniques have significantly augmented the potential of organoids in tumor research. This review explores the application of organoid technology for more precise tumor simulations and its specific contributions to cancer research advancements. Additionally, we discuss the challenges and evolving trends in developing comprehensive tumor models utilizing organoid technology.

A lightweight human pose recognition model based on OpenPose improvement is proposed to address the difficulty of intelligent supervision of abnormal behaviors of coal mine workers. The backbone network of original model is replaced with MobileNet-v3, and the original 7×7 convolutional kernels is replaced with a smaller convolutional kernel to improve model detection speed and reduce resource consumption. In addition, due to the limited shooting range of the working face camera, it is difficult to meet the needs of panoramic visualization of the working face. This article adopts the SIFT image stitching algorithm to fuse multiple monitoring perspectives and achieve real-time synchronization of full scene monitoring of the working face. After algorithm experiments, the improved human posture recognition model has an accuracy of 81.5%, occupies 42% of the memory of the original model, and the detection speed is 1.59 times that of the original model. The improved human posture recognition model not only reduces the memory consumption, but also greatly improves the speed of model detection and maintains a high accuracy. Combining human posture recognition and image stitching algorithm can realize real-time monitoring of workers’ behaviors.

Abstract In recent years, ischemic preconditioning (IPC) has garnered significant attention in sports research. While IPC has demonstrated positive effects in high-intensity sports such as judo and swimming, its potential benefits for enhancing the performance of Taekwondo athletes have not been extensively studied. This study aimed to investigate the effects of IPC on taekwondo performance and to observe the metabolic characteristics associated with enhancing sports performance via LC‒MS/MS-based plasma metabolomics. Seventeen participants underwent the repeated frequency speed of kick test (FSKT) after IPC, along with pre- and post-exercise plasma metabolite analysis. Differential abundance metabolite analysis, enriched pathway analysis, and weighted gene coexpression network analysis (WGNCA) were employed to delve into metabolic characteristics. The findings highlighted a significant enhancement in FSKT performance in the experimental group. Metabolomic analysis revealed 109 differentially abundant metabolites, including Dl-lactate, hypoxanthine, acetylcarnitine, and acetylsalicylic acid. Enriched pathway analysis revealed pathways such as pentose and glucuronic acid interconversion, ascorbic acid and aldonic acid metabolism, the pentose phosphate pathway (PPP), and the Warburg effect. In conclusion, IPC can significantly increase the specific athletic abilities of Taekwondo athletes, with enhancements linked to anaerobic metabolism, PPP utilization, the Warburg effect for energy production, redox system stability, reduced muscle fatigue, and pain alleviation.

Abstract Tobacco bacterial wilt is a major limiting factor for tobacco production and development, and it is more likely to occur under perennial single cropping of tobacco. In recent years, the rotation of tobacco-radish has gradually become popular. Therefore, we studied the effects of years of tobacco–radish rotation on tobacco bacterial wilt occurrence and rhizosphere microorganisms. The results indicated that both SY and TY could significantly reduce the risk of tobacco bacterial wilt occurrence, and SY had the lowest disease index. The rotation of radish plants significantly increased the soil pH but decreased the contents of alkali-hydrolysed nitrogen and organic matter in the soil. Alkali-hydrolysed nitrogen and pH are the key factors affecting the composition of the bacterial community. Furthermore, radish rotation changed the composition of the soil microbial community, increased the diversity of the bacterial community, and significantly altered the bacterial community structure. At the genus level, the abundance of Sphingomonas species negatively correlated with Ralstonia increased significantly, while the relative abundance of Rhodanobacter species positively correlated with Ralstonia decreased significantly. Disease index, pH and available phosphorus were the main factors affecting the variation in different bacterial genera. The network analysis results showed that Ralstonia was less connected in the network than in the CK group, and the SY treatment group had a more complex bacterial network structure. Overall, 2 years of tobacco and radish rotation improved the bacterial community structure of the rhizosphere soil and alleviated the harm caused by tobacco bacterial wilt, which is highly important for the stability and health of the rhizosphere soil ecosystem.

Abstract Objective The purpose of the study is to develop a prognosis nomogram for esophageal squamous cell carcinoma (ESCC) patients with radical resection and to identify patients who may benefit from postoperative adjuvant radiotherapy/chemoradiotherapy through survival risk stratification. Methods We retrospectively enrolled patients who underwent esophagectomy in the First Affiliated Hospital of Nanjing Medical University from July 2015 to June 2017. Patients with stage I-III esophageal squamous cell carcinoma who received radical R0 resection with or without postoperative adjuvant radiotherapy/chemoradiotherapy were included. Further, patients were randomly allocated into two groups (training and validation cohorts) with a distribution ratio of 7:3. The prognosis nomogram was constructed based on independent factors determined by univariate and multivariate Cox analyses. The area under the receiver operating characteristic curve (AUC) and calibration curve were adopted to evaluate the discriminative ability and reliability of the nomogram. The accuracy and clinical practicability were respectively assessed by C-index values and decision curve analysis (DCA), and further contrasted the nomogram model and the eighth edition of the American Joint Committee on Cancer (AJCC) TNM staging system. In addition, survival risk stratification was further performed according to the nomogram, and the effect of postoperative adjuvant therapy on each risk group was appraised by the Kaplan-Meier survival analysis. Results A total of 399 patients with esophageal squamous cell carcinoma were recruited in this study, including the training cohort (n = 280) and the validation cohort (n = 119). The nomogram-related AUC values ​​for 1, 3, and 5-year OS were 0.900, 0.795, and 0.802, respectively, and 0.800, 0.865, 0.829 in the validation cohort, respectively. The slope of the calibration curve for both cohorts was close to 1, indicating good consistency. The C-index value of the nomogram was 0.769, which was higher than that of the AJCC 8th TNM staging system by 0.061 (p

In this study, we analyzed the performance of an Unmanned Aerial Vehicle (UAV)-based mixed Underwater Power Line Communication-Radio Frequency (UPLC-RF) network. In this network, a buoy located at the sea is used as a relay to transmit signals from the underwater signal source to the UAV through the PLC link. We assume that the UPLC channel obeys a log-normal distribution and that the RF link follows the Rician distribution. Using this model, we obtained the closed-form expressions for the Outage Probability (OP), Average Bit-error-rate (ABER), and Average Channel Capacity (ACC). In addition, the asymptotic analysis of the OP and ABER was performed, and an upper bound for the average capacity was obtained. Finally, the analytical results were verified by Monte Carlo simulation thereby demonstrating the effect of impulse noise and the altitude of the UAV on network performance.

Abstract Pseudomonas aeruginosa is a widespread nosocomial pathogen with a significant to cause both severe planktonic acute and biofilm-related chronic infections. Small RNAs (sRNAs) are noncoding regulatory molecules that are stabilized by the RNA chaperone Hfq to trigger various virulence-related signaling pathways. Here, we identified an Hfq-binding sRNA in P. aeruginosa PAO1, PqsS, which promotes bacterial pathogenicity and pseudomonas quinolone signal quorum sensing (pqs QS) system. Specifically, PqsS enhanced acute bacterial infections by inducing host cell death and promoting rhamnolipid-regulated swarming motility. Meanwhile, PqsS reduced chronic infection traits including biofilm formation and antibiotic resistance. Moreover, PqsS repressed pqsL transcript, increasing PQS levels for pqs QS. A PQS-rich environment promoted PqsS expression, thus forming a positive feedback loop. Furthermore, we demonstrated that the PqsS interacts and destabilizes the pqsL mRNA by recruiting RNase E to drive degradation. These findings provide insights for future research on P. aeruginosa pathogenesis and targeted treatment.

Abstract Gliomas are aggressive brain tumors associated with poor prognosis and limited treatment options due to their invasive nature and resistance to current therapeutic modalities. Research suggests that exosomal microRNAs have emerged as key players in intercellular communication within the tumor microenvironment, influencing tumor progression and therapeutic responses. Exosomal microRNAs (miRNAs), small non-coding RNAs, are crucial in glioma development, invasion, metastasis, angiogenesis, and immune evasion by binding to target genes. This comprehensive review examines the clinical relevance and implications of exosomal miRNAs in gliomas, highlighting their potential as diagnostic biomarkers, therapeutic targets and prognosis biomarker. Additionally, we also discuss the limitations of current exsomal miRNA treatments and address challenges and propose future directions for leveraging exosomal miRNAs in precision oncology for glioma management.

IntroductionThis study examines the effects of steam-flaked corn starter on pre-weaned Simmental calves' growth, immunity, and metabolism. Despite benefits shown in adult cattle, research on calves is limited. The goal is to optimize calf feeding for better growth, health, and nutrient use.MethodsThirty-two Simmental bull calves (avg. wt: 50.50 ± 4.50 kg, avg. age: 21 ± 7 days) were divided into four groups of eight. The 127-day study included a 7-day pretest and a 120-day trial. Calves had unlimited access to starter feed, alfalfa hay, and water. Groups received starter diets with 0% (CK, control), 33% (SFC33, low), 66% (SFC66, medium), or 100% (SFC100, high) steam-flaked corn replacing regular corn. Other conditions were consistent.ResultsFeeding 33% steam-flaked corn to pre-weaned Simmental calves led to highest daily weight gain (0.80 kg/d), significantly boosting serum globulin, cholesterol, urea nitrogen, glucose, immunoglobulins, GH, INS, and IGF-1 (P < 0.05). Compared to control, 31 metabolites differed in SFC33 group, mostly up-regulated, including glycerophospholipids, linoleic/arachidonic acid metabolism, cholesterol pathway molecules, L-glutamine in multiple pathways, and mannose in fructose/mannose metabolism.DiscussionIn summary, feeding 33% steam-flaked corn-based starter can improve the growth performance, enhance immunity, and improve sugars, lipids, and proteins metabolism of pre-weaned Simmental calves.

Here, we report a SERS based VFA using PNC as a sensing substrate for highly sensitive multiplex mycotoxins detection. The PNC was fabricated by filtration-based self-assembled monodisperse SiO2 NPs on a filter membrane as a template, and the obtained PNC had an ordered complementary inverse opal structure. In parallel, three kinds of Raman dyes encoding Au@NBAAg, Au@4-MBAAg and Au@DNTBAg SERS nanotags were synthesized for the detection of OTA, AFB1 and ZON. In the immunoassay, because of the slow-photon effect of the PNC substrate, which facilitates the light coupling with SERS nanotags, the SERS signal was highly enhanced. The LODs of 8.2, 13.7 and 47.6 fg mL−1 were achieved for simultaneous detection of OTA, AFB1 and ZON, respectively, which were lower than the tolerable cutoff values recommended by the EC. Therefore, this proposed PNC based SERS VFA is expected to be a powerful method for multiplex mycotoxins detection.

Summary: Benign prostatic hyperplasia (BPH) is a common condition in aging males, but its underlying pathogenesis remains unclear. Sphingosine-1-phosphate (S1P) and its receptors (S1PRs) play important roles in various diseases, while less studied in prostate. Current study attempts to clarify the expression and functional activities of S1P/S1PRs in the prostate. We discovered that S1P/S1PRs were richly expressed in the prostate, with S1PR1/2/3 localized in the epithelial/stromal compartments, while S1PR4/5 were less expressed. In vitro, S1P/S1PR1/S1PR3 promoted cell proliferation via AKT and ERK1/2 pathways, S1P/S1PR2/S1PR3 enhanced contraction of WPMY-1 cells and human prostate via RhoA/ROCK pathway, while S1P/S1PR1/S1PR2/S1PR3 alleviated the inflammation response via STAT3 pathway. In vivo, S1P and S1PR1/3 agonists (SEW2871, CYM5541) led to prostate enlargement in rats, while S1PR1/3 antagonists (W-146, TY-52156) suppressed testosterone-induced BPH. Overall, this study suggests that S1P/S1PRs play a critical role in the development of BPH and may be a promising therapeutic target for BPH treatment.

ABSTRACTHepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths worldwide, and emerging evidence suggests that the gut microbiota may play a role in its development and progression. In this study, the association between B. thetaiotaomicron, a gut microbiota species, and HCC recurrence, as well as patient clinical outcomes, was investigated. It was observed that B. thetaiotaomicron-derived acetic acid has the potential to modulate the polarization of pro-pro-inflammatory macrophagess, which promotes the function of cytotoxic CD8+ T cells. The increased biosynthesis of fatty acids was implicated in the modulation of pro-inflammatory macrophages polarization by B. thetaiotaomicron-derived acetic acid. Furthermore, B. thetaiotaomicron-derived acetic acid was found to facilitate the transcription of ACC1, a key enzyme involved in fatty acid biosynthesis, through histone acetylation modification in the ACC1 promoter region. Curcumin, an acetylation modification inhibitor, significantly blocked the inhibitory effects of B. thetaiotaomicron and acetic acid on HCC tumor growth. These findings highlight the potential role of gut microbiota-derived acetic acid in HCC recurrence and patient clinical outcomes, and suggest a complex interplay between gut microbiota, immune modulation, fatty acid metabolism, and epigenetic regulation in the context of HCC development. Further research in this area may provide insights into novel strategies for HCC prevention and treatment by targeting the gut microbiota and its metabolites.

Exhaust sound quality is an important part of vehicle performance. In this paper, the sporty exhaust sound quality of an economical vehicle equipped with a 4-cylinder and 4-stroke engine is evaluated, analyzed, and improved under acceleration. Firstly, a sporty feeling evaluation method with engine speed divided is proposed, and the influence of exhaust sound order components on sporty exhaust sound is analyzed. The results show that while the A-weighted sound pressure level (ASPL) of Order 2 is lower and the ASPLs of Orders 4 and 6 are higher, the exhaust sound is sportier. Then, a hybrid predicted model of vehicle sporty exhaust sound under acceleration is established based on convolutional neural network (CNN) and support vector regression (SVR) algorithm. The relative errors between the predicted results of CNN-SVR hybrid model and the subjective evaluation results are limited within 2%, which indicates that the CNN-SVR hybrid prediction model achieves a high accuracy in assessing the sporty feeling of exhaust sound. Finally, considering the frequency ranges corresponding with the above order components under the practical accelerating condition, a strategy is proposed to enhance the sporty feeling of exhaust sound by reducing the sound energy within 100 Hz and increasing the sound energy within 100–450 Hz. Based on this strategy, a muffler with different structure is selected and installed on the economical vehicle, and the sporty feeling of exhaust sound is 0.63 points higher than before.

The advent of cancer immunotherapy has imparted a transformative impact on cancer treatment paradigms by harnessing the power of the immune system. However, the challenge of practical and precise targeting of malignant cells persists. To address this, engineered nanoparticles (NPs) have emerged as a promising solution for enhancing targeted drug delivery in immunotherapeutic interventions, owing to their small size, low immunogenicity, and ease of surface modification. This comprehensive review delves into contemporary research at the nexus of NP engineering and immunotherapy, encompassing an extensive spectrum of NP morphologies and strategies tailored toward optimizing tumor targeting and augmenting therapeutic effectiveness. Moreover, it underscores the mechanisms that NPs leverage to bypass the numerous obstacles encountered in immunotherapeutic regimens and probes into the combined potential of NPs when co-administered with both established and novel immunotherapeutic modalities. Finally, the review evaluates the existing limitations of NPs as drug delivery platforms in immunotherapy, which could shape the path for future advancements in this promising field.

On September 17, 2020, a landslide occurred in Hongzhai Village, Jichang Town, Qinglong County, Guizhou Province, resulting in serious damage to 134 houses and emergency evacuation of 569 people from 127 households. Investigation revealed that the Hongzhai landslide is a deep-seated large-scale landslide with a volume of approximately 6.25×106 m3. Although surface buildings and infrastructure were severely damaged, the overall movement distance of the landslide was extremely short. Through comprehensive analysis including terrain geomorphology, rock and soil structure and material composition analysis, assessment of hydrological changes, and disclosure of multiple slip surfaces through borehole drilling, it was concluded that the Hongzhai landslide is a resurrected ancient landslide along bedding planes. In order to analyze and study the deformation characteristics and resurrection causes of the landslide, methods including UAV aerial survey, engineering geological survey, rock and soil mass investigation, and geophysical exploration were employed to obtain detailed data on disaster development characteristics, influencing factors, and identification features of ancient landslides. The results show that the Hongzhai landslide can be divided into four zones (A, B, C, D) based on deformation and stress transfer direction, with zone B further divided into subzones B1 and B2 based on relative displacement. The deformation and resurrection of the landslide occurred under the joint effects of steep terrain, complex rock mass structures, weak engineering rock masses, and continuous surface infiltration. Various features such as the arm-chair shaped topography at the back edge of the landslide, material differences between the slide body and surrounding rock and soil masses, fault-cutting front edges, and changes in hydrological sedimentation verify the existence of the ancient landslide.

Abstract Background Previous studies have identified the hemoglobin (Hb) to red blood cell distribution width (RDW) ratio (HRR) is associated with the prognosis of a variety of malignant tumors. However, the relationship between HRR and pancreatic ductal adenocarcinoma (PDAC) prognosis remains unexplored. This study aims to ascertain the prognostic significance of HRR in PDAC patients. Methods In a retrospective analysis, 128 PDAC patients undergoing initial surgical resection at Ningbo Medical Center Lihuili Hospital between January 2016 and September 2021 were included. Based on receiver operating characteristic curve-derived cut-off values, participants were categorized into low and high HRR groups. The correlation between HRR and patient prognosis was subsequently examined. Results Significant disparities in age, Hb levels, RDW, tumor locality, surgical intervention, and postoperative chemotherapy were observed between the two groups (P

Abstract Malignant tumors remain a primary cause of human mortality. Among the various treatment modalities for neoplasms, tumor vaccines have consistently shown efficacy and promising potential. These vaccines offer advantages such as specificity, safety, and tolerability, with mRNA vaccines representing promising platforms. By introducing exogenous mRNAs encoding antigens into somatic cells and subsequently synthesizing antigens through gene expression systems, mRNA vaccines can effectively induce immune responses. Katalin Karikó and Drew Weissman were awarded the 2023 Nobel Prize in Physiology or Medicine for their great contributions to mRNA vaccine research. Compared with traditional tumor vaccines, mRNA vaccines have several advantages, including rapid preparation, reduced contamination, nonintegrability, and high biodegradability. Tumor-targeted therapy is an innovative treatment modality that enables precise targeting of tumor cells, minimizes damage to normal tissues, is safe at high doses, and demonstrates great efficacy. Currently, targeted therapy has become an important treatment option for malignant tumors. The application of mRNA vaccines in tumor-targeted therapy is expanding, with numerous clinical trials underway. We systematically outline the targeted delivery mechanism of mRNA vaccines and the mechanism by which mRNA vaccines induce anti-tumor immune responses, describe the current research and clinical applications of mRNA vaccines in tumor-targeted therapy, and forecast the future development trends of mRNA vaccine application in tumor-targeted therapy.

Abstract Staphylococcus aureus (SA) poses a serious risk to human and animal health, necessitating a low-cost and high-performance analytical platform for point-of-care diagnostics. Cellulose paper-based field-effect transistors (FETs) with RNA-cleaving DNAzymes (RCDs) can fulfill the low-cost requirements, however, its high hydrophilicity and lipophilicity hinder biochemical modification and result in low sensitivity, poor mechanical stability and poor fouling performance. Herein, we proposed a controllable self-cleaning FET to simplify biochemical modification and improve mechanical stability and antifouling performance. Then, we constructed an RCD-based DNA nanotree to significantly enhance the sensitivity for SA detection. For controllable self-cleaning FET, 1 H,1 H,2 H,2 H-perfluorodecyltrimethoxysilane based-polymeric nanoparticles were synthesized to decorate cellulose paper and whole carbon nanofilm wires. O2 plasma was applied to regulate to reduce fluorocarbon chain density, and then control the hydrophobic-oleophobic property in sensitive areas. Because negatively charged DNA affected the sensitivity of semiconducting FETs, three Y-shaped branches with low-cost were designed and applied to synthesize an RCD-based DNA-Nanotree based on similar DNA-origami technology, which further improved the sensitivity. The trunk of DNA-Nanotree was composed of RCD, and the canopy was self-assembled using multiple Y-shaped branches. The controllable self-cleaning FET biosensor was applied for SA detection without cultivation, which had a wide linear range from 1 to 105 CFU/mL and could detect a low value of 1 CFU/mL.

The fabrication of high quality copper alloys using laser powder bed fusion (LPBF) technology remains challenging due to their low laser absorption and high thermal conductivity. LPBF often involves intrinsic defects, such as rough surface and internal pores, which largely deteriorate the performance of as-built copper alloy components. Here we studied the effect of scanning speed on the evolution of surface morphologies and internal pores of LPBF-fabricated CuSn10 alloy. The melt flow behaviors were studied by both experiments and in situ observations where combined a high-speed camera with an infrared thermal imager. With increasing the scanning speed, the morphology of melt track evolves from a continuous track to a discontinuous one, whereas the internal defects change from a great number of spherical pores to many irregular pores. A higher scanning speed decreases the peak temperature of the melt pool and causes less overlaps between neighboring melt tracks, thus deteriorating wetting behaviors. It is expected that the obtained results are beneficial for guiding the additive manufacturing of copper alloy parts with high metallurgical quality and thus promoting their industrial applications.

Mastitis affects almost all mammals including humans and dairy cows. In the dairy industry, bovine mastitis is a disease with a persistently high incidence, causing serious losses to the health of cows, the quality of dairy products, and the economy of dairy farms. Although local udder infection caused by the invasion of exogenous pathogens into the mammary gland was considered the main cause of mastitis, evidence has been established and continues to grow, showing that nutrition factors and gastrointestinal microbiome (GM) as well as their metabolites are also involved in the development of mammary inflammatory response. Suboptimal nutrition is recognized as a risk factor for increased susceptibility to mastitis in cattle, in particular the negative energy balance. The majority of data regarding nutrition and bovine mastitis involves micronutrients. In addition, the dysbiotic GM can directly trigger or aggravate mastitis through entero-mammary gland pathway. The decreased beneficial commensal bacteria, lowered bacterial diversity, and increased pathogens as well as proinflammatory metabolites are found in both the milk and gastrointestinal tract of mastitic dairy cows. This review discussed the relationship between the nutrition (energy and micronutrient levels) and mastitis, summarized the role of GM and metabolites in regulating mastitis. Meanwhile, several non-antibiotics strategies were provided for the prevention and alleviation of mastitis, including micronutrients, probiotics, short-chain fatty acids, high-fiber diet, inulin, and aryl hydrocarbon receptor.

PurposeIn recent years, ischemic preconditioning (IPC) has emerged as an effective strategy to increase tissue resistance against long-term ischemic damage and has been increasingly integrated into exercise regimens. However, further research is needed to explore the impact of IPC-mediated metabolic alterations from an exercise standpoint to conduct a comprehensive exploration of metabolic alterations and their exercise-related mechanisms during acute IPC.MethodsNontarget metabolomics was performed on blood samples obtained from 8 male athletes both before and after IPC. The studies included the identification of differentially abundant metabolites, analysis of receiver operating characteristic (ROC) curves, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis for differentially abundant metabolites, and metabolite set enrichment analysis (MSEA).ResultsNineteen differentially abundant metabolites were identified, with increasing levels of five metabolites, such as O-desmethyltramadol and D-gluconate, whereas 14 metabolites, including 9-hydroxy-10e, 12z-octadecadienoic acid (9-HODE), tetradione, 2-hexenal, (2,4-dichlorophenoxy)acetic acid (2,4-D), and phosphatidylserine (PS), decreased. ROC curve analysis revealed an AUC of 0.9375 for D-gluconate. Both KEGG enrichment analysis and MSEA revealed enrichment in the pentose phosphate pathway (PPP).ConclusionThis study revealed that PPP, D-gluconate, O-desmethyltramadol, and D-2-aminobutyric acid could be upregulated within 5 min after acute IPC, whereas 2,4-D, PS, 9-HODE, 2-hexenal, and tetradinone could be downregulated. These identified metabolites show promise for improving physical functional status and could be harnessed to enhance athletic performance.

ObjectiveTo investigate whether the combination of acupuncture and mirror therapy can improve motor impairment in stroke patients.DesignA systematic review and meta-analysis of randomised controlled trials.Data sourcesCNKI, Wanfang, PubMed, Embase, Vip, web of since, Cochrane database and CBM database.Eligibility criteria for selecting studiesThe included randomized controlled trials compared the efficacy of acupuncture therapy (AT) combined with mirror therapy (MT) against AT, MT, and conventional rehabilitation therapy on limb motor impairment in stroke patients, with independent data extraction and study quality assessment conducted. A META analysis using fixed-effect and random-effect models was performed to calculate the mean difference (MD) in motor scores and the Total effective rate RR (Risk ratio) between the AT combined with MT group and the control group.Main outcome measuresThe Fugl-Meyer Assessment (FMA) for motor function includes the FMA-T (total FMA), FMA-UE (upper extremity FMA), and FMA-L (lower extremity FMA).ResultsA total of 42 randomized controlled trials were included, involving 3,340 patients with post-stroke motor impairment. AT combined with MT was more favorable for FMA-UE (mean difference [MD] = 6.67, 95% CI [5.60–7.93], Z = 11.42, P

Early-onset epilepsy following ischemic stroke is a severe neurological condition, the pathogenesis of which remains incompletely understood. Recent studies suggest that Neural stem/progenitor cells (NSPCs) play a crucial role in the disease process, yet the precise molecular mechanisms regulating NSPCs have not been thoroughly investigated. This study utilized single-cell transcriptome sequencing and bioinformatics analysis to identify disease-related genes, which were subsequently validated in both in vitro and in vivo experiments. The findings revealed that Hsp90aa1 (heat shock protein 90 kDa alpha, class A member 1), Jun proto-oncogene (JUN), and CC Motif Ligation 2 (Ccl2) constitute an important regulatory axis influencing the migration and differentiation of NSPCs, potentially impacting the onset and progression of early-onset epilepsy post-ischemic stroke. Additionally, the expression of Hsp90aa1 was found to influence the likelihood of seizure occurrence and the severity of brain ischemia.

BackgroundModerately differentiated gastric adenocarcinoma (MDGA) has a high risk of metastasis and individual variation, which strongly affects patient prognosis. Using large-scale datasets and machine learning algorithms for prediction can improve individualized treatment. The specific efficacy of several lymph node indicators in predicting distant metastasis (DM) and patient prognosis in MDGA remains obscure.MethodsWe collected data from MDGA patients from the SEER database from 2010 to 2019. Additionally, we collected data from MDGA patients in China. We used nine machine learning algorithms to predict DM. Subsequently, we used Cox regression analysis to determine the risk factors affecting overall survival (OS) and cancer-specific survival (CSS) in DM patients and constructed nomograms. Furthermore, we used logistic regression and Cox regression analyses to assess the specific impact of six lymph node indicators on DM incidence and patient prognosis.ResultsWe collected data from 5,377 MDGA patients from the SEER database and 109 MDGC patients from hospitals. T stage, N stage, tumor size, primary site, number of positive lymph nodes, and chemotherapy were identified as independent risk factors for DM. The random forest prediction model had the best overall predictive performance (AUC = 0.919). T stage, primary site, chemotherapy, and the number of regional lymph nodes were identified as prognostic factors for OS. Moreover, T stage, number of regional lymph nodes, primary site, and chemotherapy were also influential factors for CSS. The nomograms showed good predictive value and stability in predicting the 1-, 3-, and 5-year OS and CSS in DM patients. Additionally, the log odds of a metastatic lymph node and the number of negative lymph nodes may be risk factors for DM, while the regional lymph node ratio and the number of regional lymph nodes are prognostic factors for OS.ConclusionThe random forest prediction model accurately identified high-risk populations, and we established OS and CSS survival prediction models for MDGA patients with DM. Our hospital samples demonstrated different characteristics of lymph node indicators in terms of distant metastasis and prognosis.

Objective Bedding deep cutting slopes containing weak interlayers are commonly found in slope engineering, whose stability is influenced by two key factors: The strength of the sliding zone soil and the reserved thickness of the base (the distance from the base of an excavated slope to the weak interlayer). Methods In this research, taking the K42 cutting slope of the Yang-Xuan Expressway as an example, the evolution process of slope deformation was analyzed, especially the characteristics of basal heave deformation. The properties of the deep sliding zone soil in the slope were revealed by ring shear tests, which are suitable for studying the shear strength of soil that has experienced large shear displacements. Moreover, the residual strength parameters of the saturated sliding zone soil were applied to analyze the reserved thickness of the base. Results The results show that sliding zone soils exhibit obvious strain softening characteristics, which become more evident as the normal stress decreases. As the soil shear strength transitions from peak strength to residual strength, both the cohesion force and internal friction angle decrease, with the cohesion force decreasing to a greater extent than the internal friction angle. The residual cohesion force of sliding zone soil varies slightly with the shear rate, while the relationship between the residual internal friction angle and shear rate varies as a logarithmic function. When the shear rate is less than 2 mm/min, the residual shear strength parameter of sliding zone soil is more sensitive to the shear rate and vice versa. Conclusion Furthermore, according to the regression equations of the critical states of slope stability, the reserved thickness of the base under different slope rates was divided into four zones: A (extremely unstable zone), B (unstable zone), C (basically stable zone) and D (stable zone), and based on this, the criterion and early warning model of the reserved thickness of the base for slope excavation were established.

Abstract Background Bronchial arterial embolization (BAE) has been accepted as an effective treatment for bronchiectasis-related hemoptysis. However, rare clinical trials compare different sizes of specific embolic agents. This study aims to evaluate whether different Embosphere microsphere sizes change the outcome of BAE. Methods A retrospective review was conducted on consecutive patients with bronchiectatic hemoptysis who were scheduled to undergo BAE treatment during a period from January 2018 to December 2022. The patients received BAE using microspheres of different sizes: group A patients were treated with 500–750 μm microspheres, and group B patients were treated with 700–900 μm microspheres. The cost of embolic microspheres (Chinese Yuan, CNY), duration of hospitalization, complications, and hemoptysis-free survival were compared between patients in group A and those in group B. A Cox proportional hazards regression model was used to identify predictors of recurrent hemoptysis. Results Median follow-up was 30.2 months (range, 20.3–56.5 months). The final analysis included a total of 112 patients (49–77 years of age; 45 men). The patients were divided into two groups: group A (N = 68), which received 500–750 μm Embosphere microspheres, and group B (N = 44), which received 700–900 μm Embosphere microspheres. Except for the cost of embolic microspheres(group A,5314.8 + 1301.5 CNY; group B, 3644.5 + 1192.3 CNY; p = 0.042), there were no statistically significant differences in duration of hospitalization (group A,7.2 + 1.4 days; group B, 8 + 2.4days; p = 0.550), hemoptysis-free survival (group A, 1-year, 2-year, 3-year, 85.9%, 75.8%, 62.9%; group B, 1-year, 2-year, 3-year, 88.4%, 81.2%,59.4%;P = 0.060), and complications(group A,26.5%; group B, 38.6%; p = 0.175) between the two groups. No major complications were observed. The multivariate analysis results revealed that the presence of cystic bronchiectasis (OR 1.61, 95% CI 1.12–2.83; P = 0.001) and systemic arterial-pulmonary shunts (SPSs) (OR 1.52, 95% CI 1.10–2.72; P = 0.028) were independent risk factors for recurrent bleeding. Conclusions For the treatment of BAE in patients with bronchiectasis-related hemoptysis, 500–750 μm diameter Embosphere microspheres have a similar efficacy and safety profile compared to 700–900 μm diameter Embosphere microspheres, especially for those without SPSs or cystic bronchiectasis. Furthermore, the utilization of large-sized (700–900 μm) Embosphere microspheres is associated with the reduced cost of an embolic agent.

Objectives: We characterized the population structure and features of clinical Streptococcus pneumoniae isolates associated with invasive pneumococcal disease (IPD) from 2009 to 2017 in a Chinese metropolitan city using a whole-genome sequencing approach. Methods: Seventy-nine pneumococcal strains, including 60 serogroup-19 strains from children enduring IPD from a paediatric hospital in Shenzhen, were subjected to whole-genome sequencing. Population structure was characterized through phylogenetic analysis, sequence typing, serotyping, virulence factor, and antimicrobial drug resistance (AMR) gene profiling, combining the publicly available related WGS data. Clinical demography and antibiotic susceptibility profiles were compared among different populations to emphasize the higher-risk populations. Genetic regions associated with AMR gene mobilization were identified through comparative genomics. Results: These IPD strains mainly belonged to clonal complex 320 (CC320) and were composed of serotypes 19A and 19F. In addition to sporadic possible importation-related isolates (ST320), we identified an independent clade, CC320_SZpop (ST271), that predominantly circulated in Shenzhen and possibly expanded its range. Clinical features and antibiotic susceptibility analysis revealed that CC320_SZpop might manifest much higher pathogenicity and tolerance to β-lactams. Specific virulence factors in Shenzhen isolates of CC320_SZpop were identified. Furthermore, an ca. 40 kb hotspot genomic region enduring frequent recombination was identified, possibly associated with the divergence of S. pneumoniae strains. Conclusion: A novel pneumococcal clade, CC320_SZpop, circulating in Shenzhen and other regions in China, possibly under expansion, was found and deserves more study and surveillance. Our study also emphasizes the importance of continuous genomic surveillance of clinical S. pneumoniae isolates, especially IPD isolates.

Under the trend of deep mining of coal resources, the problem of high temperature heat damage in mines is becoming increasingly serious, the heat source that causes high temperature heat damage in mines is actually sustainably used geothermal energy, extracting and utilizing geothermal energy from deep mines while mining coal is an innovative way to build green mines and reduce mine carbon dioxide emission. This paper summarizes the current situation of deep mineral and geothermal energy collaborative exploration at China and abroad, analyzes the feasibility in terms of processes and key equipment and finally proposes a system of coal-geothermal collaborative exploration. The system adopts closed cycle mode, including ground heat utilization system and underground extracting system, drilling horizontal holes and installing coaxial casing heat exchangers at the coal to extract the heat, and utilization of the extracted low-grade geothermal energy through the heat pump on ground. Adhering to the principle of “mining heat first and then mining” in terms of time and space coordination, the thermal mining face is divided in front of the mining work in advance, and two modes of sequential and alternating thermal mining are proposed to ensure that the thermal mining process does not interfere with the coal mining process. Analyzed key technologies including spatial collaborative design, coal seam drilling, efficient heat extraction, and intelligent monitoring and control. Conducted underground spatial collaborative design for coal mining and geothermal energy extraction, proposed a coaxial casing heat exchanger layout process based on coal seam water injection. Multiple combinations of quick assembly coaxial casing heat exchangers can be used to achieve efficient heat extraction. Building an intelligent monitoring and control platform and proposed relevant optimization models, building a heat extraction calculation model and propose an intelligent control heat extraction method. Simplify the heat transfer process of coal formations, construct a heat transfer model for heat extraction from coal to calculate and evaluate the heat capacity of the mining face based on its actual situation and the outlet airflow parameters. According to the heat transfer model, the initial temperature of coal, the coal transportation volume, and the outlet air flow temperature through mining face are the key parameters that determine the heat extraction from the coal. The heat extraction is the maximum when the moisture content of the air flow of the working face remains unchanged and the equivalent temperature of the air flow at the outlet of the working face is not higher than 28 ℃. The application of this system will converting heat damage of deep mine to useful resources, which not only solves the problem of heat damage of coal mining, but also realizes the comprehensive utilization of geothermal energy in deep mine.

Pseudomonas aeruginosa and Mycobacterium abscessus are opportunistic pathogens that cause severe infections in hospitals, and their co-infections are increasingly reported. The interspecies interactions between these two bacterial species and their potential impacts on infections are largely unexplored. In this study, we first demonstrated that P. aeruginosa inhibits the growth of M. abscessus by iron chelating via pqs quorum sensing. Next, through proteomic analysis, we discovered that the PQS molecule significantly changed a large amount of protein expression in M. abscessus, including proteins involved in the type VII secretion system and iron homeostasis. Furthermore, we revealed that PQS significantly enhanced the production of bacterial membrane vesicles (MVs) by M. abscessus. Our study suggests that the P. aeruginosa PQS can serve as an interspecies signaling molecule to communicate with Mycobacterium and affect their physiology and virulence.

In flowering plants, MADS-box genes play regulatory roles in flower induction, floral initiation, and floral morphogenesis. Isatis indigotica (I. indigotica) is a traditional Chinese medicinal plant. However, available information concerning MADS-box genes in I. indigotica is insufficient. Based on the sequencing data of the I. indigotica transcriptome, we identified MADS-box gene-encoding transcription factors that have been shown to play critical roles in developmental processes. In this study, 102 I. indigotica MADS-box genes were identified and categorized into type I (Mα, Mβ, and Mγ) and type II (MIKCC and MIKC*) subfamilies. IiMADS proteins in the same cluster had similar motifs and gene structures. In total, 102 IiMADS-box genes were unevenly distributed across seven chromosomes. APETALA1 (AP1) encodes a MADS-box transcription factor which plays a pivotal role in determining floral meristem identity and also modulates developmental processes within the perianth. We then selected IiAP1 for functional studies and found that it is localized to the nucleus and highly expressed in inflorescence, sepals, and petals. The ectopic expression of IiAP1 in Arabidopsis resulted in early flowering and abnormal development of floral organs. Taken together, this research study carried out a systematic identification of MADS-box genes in I. indigotica and demonstrated that IiAP1 takes part in the regulation of floral transition and formation.

Neutrinoless double beta decay (0νββ) provides a way to probe physics beyond the Standard Model of particle physics. The upcoming nEXO experiment will search for 0νββ decay in 136Xe with a projected half-life sensitivity exceeding 1028 years at the 90% confidence level using a liquid xenon (LXe) Time Projection Chamber (TPC) filled with 5 tonnes of Xe enriched to ∼90% in the ββ-decaying isotope 136Xe. In parallel, a potential future upgrade to nEXO is being investigated with the aim to further suppress radioactive backgrounds and to confirm ββ-decay events. This technique, known as Ba-tagging, comprises extracting and identifying the ββ-decay daughter 136Ba ion. One tagging approach being pursued involves extracting a small volume of LXe in the vicinity of a potential ββ-decay using a capillary tube and facilitating a liquid-to-gas phase transition by heating the capillary exit. The Ba ion is then separated from the accompanying Xe gas using a radio-frequency (RF) carpet and RF funnel, conclusively identifying the ion as 136Ba via laser-fluorescence spectroscopy and mass spectrometry. Simultaneously, an accelerator-driven Ba ion source is being developed to validate and optimize this technique. The motivation for the project, the development of the different aspects, along with the current status and results, are discussed here.

In natural language processing (NLP) tasks, computing semantic textual similarity (STS) is crucial for capturing nuanced semantic differences in text. Traditional word vector methods, such as Word2Vec and GloVe, as well as deep learning models like BERT, face limitations in handling context dependency and polysemy and present challenges in computational resources and real-time processing. To address these issues, this paper introduces two novel methods. First, a sentence embedding generation method based on Kullback–Leibler Divergence (KLD) optimization is proposed, which enhances semantic differentiation between sentence vectors, thereby improving the accuracy of textual similarity computation. Second, this study proposes a framework incorporating RoBERTa knowledge distillation, which integrates the deep semantic insights of the RoBERTa model with prior methodologies to enhance sentence embeddings while preserving computational efficiency. Additionally, the study extends its contributions to sentiment analysis tasks by leveraging the enhanced embeddings for classification. The sentiment analysis experiments, conducted using a Stochastic Gradient Descent (SGD) classifier on the ACL IMDB dataset, demonstrate the effectiveness of the proposed methods, achieving high precision, recall, and F1 score metrics. To further augment model accuracy and efficacy, a feature selection approach is introduced, specifically through the Dynamic Principal Component Selection (DPCS) algorithm. The DPCS method autonomously identifies and prioritizes critical features, thus enriching the expressive capacity of sentence vectors and significantly advancing the accuracy of similarity computations. Experimental results demonstrate that our method outperforms existing methods in semantic similarity computation on the SemEval-2016 dataset. When evaluated using cosine similarity of average vectors, our model achieved a Pearson correlation coefficient (τ) of 0.470, a Spearman correlation coefficient (ρ) of 0.481, and a mean absolute error (MAE) of 2.100. Compared to traditional methods such as Word2Vec, GloVe, and FastText, our method significantly enhances similarity computation accuracy. Using TF-IDF-weighted cosine similarity evaluation, our model achieved a τ of 0.528, ρ of 0.518, and an MAE of 1.343. Additionally, in the cosine similarity assessment leveraging the Dynamic Principal Component Smoothing (DPCS) algorithm, our model achieved a τ of 0.530, ρ of 0.518, and an MAE of 1.320, further demonstrating the method’s effectiveness and precision in handling semantic similarity. These results indicate that our proposed method has high relevance and low error in semantic textual similarity tasks, thereby better capturing subtle semantic differences between texts.

Abstract Extracellular matrix (ECM) remodeling is strongly linked to Alzheimer's disease (AD) risk; however, the underlying mechanisms are not fully understood. Here, it is found that the injection of chondroitinase ABC (ChABC), mimicking ECM remodeling, into the medial prefrontal cortex (mPFC) reversed short‐term memory loss and reduced amyloid‐beta (Aβ) deposition in 5xFAD mice. ECM remodeling also reactivated astrocytes, reduced the levels of aggrecan in Aβ plaques, and enhanced astrocyte recruitment to surrounding plaques. Importantly, ECM remodeling enhanced the autophagy‐lysosome pathway in astrocytes, thereby mediating Aβ clearance and alleviating AD pathology. ECM remodeling also promoted Aβ plaque phagocytosis by astrocytes by activating the astrocytic phagocytosis receptor MERTK and promoting astrocytic vesicle circulation. The study identified a cellular mechanism in which ECM remodeling activates the astrocytic autophagy‐lysosomal pathway and alleviates AD pathology. Targeting ECM remodeling may represent a potential therapeutic strategy for AD and serve as a reference for the treatment of this disease.

BackgroundReactivate the T cell immunity by PD-1/PD-L1 checkpoint blockade is widely used in non-small cell lung cancer (NSCLC) patients, while the post-translational modification of Programmed death ligand-1 (PD-L1) is commonly existed in various cancer cells, thus increases the complexity and difficulty in therapy development. Ginsenoside Rg3 is an active component of traditional Chinese herb Ginseng with multiple pharmacological effects including immune regulation. However, the effect on the glycosylation of PD-L1 is unknown.MethodsNSCLC cell lines were tested for glycosylation of PD-L1, and the potential mechanisms were investigated. Tumor cell-T cell coculture experiment was conducted and the activation of T cells and cytotoxicity were measured by flow cytometry. In vivo xenograft mouse tumor model was used to investigate the effects of Rg3 on PD-L1-mediated immunosuppression and tumor growth.ResultsHere, we identified PD-L1 is widely N-linked glycosylated in NSCLC cell lines, while Rg3 could inhibit the glycosylation of PD-L1 by downregulating the EGFR signaling and further activate GSK3b-mediated degradation, thus resulted in reduced PD-L1 expression. Moreover, the inhibition of PD-L1 glycosylation promoted the activation and cytotoxicity of T cells under coculture condition. In addition, Rg3 could decrease the tumor volume and enhance anti-tumor T cell immunity as evidence by the upregulated expression of Granzyme B and perforin in CD8+T cells, along with elevated serum IL-2, IFN-g and TNF-a level in Rg3-treated mice.ConclusionsThese results suggest that Rg3 inhibits PD-L1 glycosylation and thus enhance anti-tumor immunity, which provide new therapeutic insight into drug discovery.

The bacterial membrane vesicles (MVs) are non-replicative, nanoscale structures that carry specific cargos and play multiple roles in microbe–host interactions. An appropriate MV isolation method that mimics complex pathogen infections in vivo is needed. After bacterial MVs extraction, flagella or pili can be frequently observed along with MVs by transmission electron microscope (TEM). Recently, MVs from Pseudomonas aeruginosa were found to coexist with Pf4 phages, and this MV–phages complex exhibited a different impact on host cell innate immunity compared with MVs or phages solely. The presence of this MVs–phages complex simulates the real condition of complex pathogen infections within the host. This protocol outlines the extraction of the MVs and Pf4 phages complex of P. aeruginosa PAO1, including the respective isolation and qualification approaches. Our step-by-step bacterial MVs–phages complex extraction protocol provides valuable insights for further studying microbe–host cell interactions and the development of novel phage therapies.

In this paper, the effects of drywet cycling and salt erosion on the unconfined compressive strength (UCS), relative dynamic elastic modulus and mass of cemented tailings backfill (CTB) were investigated, and the mechanism for CTB deterioration was explored with scanning electron microscopy-energy dispersive spectroscopy, X-ray diffraction and Fourier transform infrared spectroscopy. The reliability lifespan of CTB was predicted with the Wiener stochastic process. The results showed that with the increases in the number of drywet cycles, the damage to the CTB deepened continuously, including skin peeling, corner damage, and aggregate exposure; the UCS, relative dynamic elastic modulus and mass of CTB immersed in a sodium chloride solution, a sodium sulfate solution, and a solution of both first increased and then decreased; and the UCS, relative dynamic elastic modulus and mass of CTB immersed in a magnesium chloride solution, a magnesium sulfate solution, and a solution of both showed a decreasing trend. Cl- inhibited the erosion of CTB by SO42- but did not inhibit erosion by Mg2+. Cl- and SO42- invaded the CTB to produce calcium hydroxide, gypsum, Friedel's salt, ettringite, C-S-H and other products. The reliable lifetime predicted with the relative dynamic elastic modulus used as the degradation index was the longest, followed by the UCS, and the lifetime predicted with the mass was the shortest.

To solve the problems of large storage requirements for iron and steel solid waste piles, environmental pollution, and low utilization, an alkali-activated ground granulated blast furnace slag (GGBFS)-steel slag (SS) grouting material (AAGM) was prepared, quicklime was used as an additive, and the activity of SS and GGBFS was activated by NaOH and water glass. Through a full factor analysis test, the effects of alkali content (AC), GGBFS/SS, and quicklime content (QC) on the fluidity, initial setting time (IST), and final setting time (FST) of AAGM were investigated. The strength formation mechanism of AAGM was analyzed using mechanical property testing, X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM). These studies showed that the fluidity of the slurry decreased with increasing QC, AC, and GGBFS/SS, and the IST and FST of the slurry continuously shorten with increasing QC, increasing AC, and decreasing GGBFS/SS. The 28-day unconfined compressive strength (UCS) of AAGM decreased with decreasing QC and increasing AC, and first increased and then decreased with increasing GGBFS/SS. As the age increased, the hydration reaction inside the specimen was sufficient and the compactness was stronger, reducing the porosity inside the specimen; the hydration products inside AAGM were mainly plate-like crystals (anhydrite, calcite), a small amount of columnar crystals (ettringite), and a large amount of gel-like substances (C-S-H/C-A-S-H) attached to its surface. When the GGBFS/SS ratio was 1:1.3, the QC was 3 %, the AC was 13 %, the water glass modulus was 1.6, and the water/cement ratio was 0.6; additionally, the fluidity, IST, FST, and 28-day UCS of AAGM were 137 mm, 255 min, 280 min, and 27.07 MPa, respectively, which can meet various performance indicators required for engineering grouting.

ObjectivePulmonary artery sarcoma (PAS) is an exceedingly rare and insufficiently investigated disease, leading to uncertain in its optimal management. This study aims to present our institutional experience and the outcomes of pulmonary endarterectomy for PAS.MethodsWe gathered clinical characteristics, intraoperative data, postoperative outcomes, and prognosis information from PAS patients who underwent surgical treatment at our institution between December 2016 and September 2023.ResultsA total of 20 patients with PAS underwent pulmonary endarterectomy. The median age of the patients was 52 (IQR 45, 57) years, with 12 patients (60%) being female. Intimal sarcoma was confirmed in 19 patients, while the remaining one was diagnosed with large cell neuroendocrine carcinoma. The perioperative mortality rate was three cases (15%). Follow-up was conducted for a median duration of 14 months (range: 1–61). During the follow-up period, 11 patients experienced recurrence or metastasis, and 5 patients succumbed to the disease. The estimated cumulative survival rates at 1 and 2 years for all 20 patients were 66.4% and 55.3%, respectively.ConclusionPulmonary endarterectomy emerges as a palliative but effective approach for managing PAS, particularly when complemented with postoperative therapies such as chemotherapy and targeted therapy, which collectively contribute to achieving favorable long-term survival outcomes.

Summary: Thymocyte development requires precise control of PI3K-Akt signaling to promote proliferation and prevent leukemia and autoimmune disorders. Here, we show that ablating individual clusters of the miR-17∼92 family has a negligible effect on thymocyte development, while deleting the entire family severely impairs thymocyte proliferation and reduces thymic cellularity, phenocopying genetic deletion of Dicer. Mechanistically, miR-17∼92 expression is induced by Myc-mediated pre-T cell receptor (TCR) signaling, and miR-17∼92 promotes thymocyte proliferation by suppressing the translation of Pten. Retroviral expression of miR-17∼92 restores the proliferation and differentiation of Myc-deficient thymocytes. Conversely, partial deletion of the miR-17∼92 family significantly delays Myc-driven leukemogenesis. Intriguingly, thymocyte-specific transgenic miR-17∼92 expression does not cause leukemia or lymphoma but instead aggravates skin inflammation, while ablation of the miR-17∼92 family ameliorates skin inflammation. This study reveals intricate roles of the miR-17∼92 family in balancing thymocyte development, leukemogenesis, and autoimmunity and identifies those microRNAs (miRNAs) as potential therapeutic targets for leukemia and autoimmune diseases.

Abstract DNA methylation serves as the primary mode of epigenetic regulation in prokaryotes, particularly through transcriptional regulation. With the rapid implementation of third‐generation sequencing technology, we are currently experiencing a golden age of bacterial epigenomics. However, there has been a lack of comprehensive research exploring the versatility and consequential impact of bacterial DNA methylome on cellular and physiological functions. There is a critical need for a user‐friendly bioinformatics tool that can effectively characterize DNA methylation modification features and predict the regulation patterns. To address this gap, the current study introduces Bacmethy, an innovative tool that utilizes SMRT‐seq data and offers a range of analytical modules. First, the tool classifies methylation sites in the genome, highlighting the distinct regulations present under varying modification fractions and location enrichment. Furthermore, this tool enables us to identify regulatory region methylation and potential cis and trans interactions between methylation sites and regulatory effectors. Using benchmark data sets and our data, we show that our tool facilitates the understanding of the distinctive traits of DNA methylation modifications and predicts transcriptional regulation effects on important physiological and pathological functions. Bacmethy code is freely available, and the Docker image is downloadable. Bacmethy has been made available as a user‐friendly web server interface at https://bacmethy.med.sustech.edu.cn.

This paper aimed to explore the correlation between the physical and chemical indicators of sauce-flavor Daqu with different sensory characteristics and the community of molds, six physical and chemical indicators of WQ, YQ and BQ were tested, the mold of Daqu were separated and identified, the correlation between the physical and chemical indicators and mold community in three kinds of Daqu were analyzed by redundancy analysis. The results showed that the liquefaction power of YQ was higher, and YQ and BQ showed the higher fermentation power and esterification power, respectively: 1.56 U, 22.63 U and 1.51 U, 22.48 U. A total of 78 strains of 13 species of molds belonging to 6 genera were isolated and identified from three kinds of Daqu, including 7 species in WQ, namely Paecilomyces subglobosus, Paecilomyces variotii, Lichtheimia corymbifera, Lichtheimia ornata, Penicillium tardochrysogenum, Penicillium chrysogenum, Epicoccum endophytica. 6 Species were isolated from YQ, namely Lichtheimia ramosa, Lichtheimia corymbifera, Paecilomyces variotii, Lichtheimia hongkongensis, Lichtheimia ornata, Aspergillus intermedius. 7 Species were isolated from BQ, namely Paecilomyces variotii, Paecilomyces subglobosus, Lichtheimia ramosa, Scopulariopsis brevicaulis, Lichtheimia corymbifera, Aspergillus sydowii, Aspergillus quadrilineatus. Through redundancy analysis, it was concluded that Lichtheimia was the main strain affecting the saccharification and esterification of Daqu. This study provides a basis for the research and application of molds in sauce-flavored Daqu and provides data support for improving the fermentation performance of sauce-flavored Daqu.

Abstract Chronic wounds are often infected with biofilm bacteria and characterized by high oxidative stress. Current dressings that promote chronic wound healing either require additional processes such as photothermal irradiation or leave behind gross amounts of undesirable residues. We report a dual-functionality hydrogel dressing with intrinsic antibiofilm and antioxidative properties that are synergistic and low-leaching. The hydrogel is a crosslinked network with tethered antibacterial cationic polyimidazolium and antioxidative N-acetylcysteine. In a murine diabetic wound model, the hydrogel accelerates the closure of wounds infected with methicillin-resistant Staphylococcus aureus or carbapenem-resistant Pseudomonas aeruginosa biofilm. Furthermore, a three-dimensional ex vivo human skin equivalent model shows that N-acetylcysteine promotes the keratinocyte differentiation and accelerates the re-epithelialization process. Our hydrogel dressing can be made into different formats for the healing of both flat and deep infected chronic wounds without contamination of the wound or needing other modalities such as photothermal irradiation.

Abstract After undergoing metabolic reprogramming, tumor cells consume additional glutamine to produce amino acids, nucleotides, fatty acids, and other substances to facilitate their unlimited proliferation. As such, the metabolism of glutamine is intricately linked to the survival and progression of cancer cells. Consequently, targeting the glutamine metabolism presents a promising strategy to inhibit growth of tumor cell and cancer development. This review describes glutamine uptake, metabolism, and transport in tumor cells and its pivotal role in biosynthesis of amino acids, fatty acids, nucleotides, and more. Furthermore, we have also summarized the impact of oncogenes like C-MYC, KRAS, HIF, and p53 on the regulation of glutamine metabolism and the mechanisms through which glutamine triggers mTORC1 activation. In addition, role of different anti-cancer agents in targeting glutamine metabolism has been described and their prospective applications are assessed.

Abstract Aims Diabetic cardiomyopathy (DCM) is a major cause of mortality in patients with diabetes, and the potential strategies for treating DCM are insufficient. Melatonin (Mel) has been shown to attenuate DCM, however, the underlying mechanism remains unclear. The role of vascular endothelial growth factor-B (VEGF-B) in DCM is little known. In present study, we aimed to investigate whether Mel alleviated DCM via regulation of VEGF-B and explored its underlying mechanisms. Methods and results We found that Mel significantly alleviated cardiac dysfunction and improved autophagy of cardiomyocytes in type 1 diabetes mellitus (T1DM) induced cardiomyopathy mice. VEGF-B was highly expressed in DCM mice in comparison with normal mice, and its expression was markedly reduced after Mel treatment. Mel treatment diminished the interaction of VEGF-B and Glucose-regulated protein 78 (GRP78) and reduced the interaction of GRP78 and protein kinase RNA -like ER kinase (PERK). Furthermore, Mel increased phosphorylation of PERK and eIF2α, then up-regulated the expression of ATF4. VEGF-B−/− mice imitated the effect of Mel on wild type diabetic mice. Interestingly, injection with Recombinant adeno-associated virus serotype 9 (AAV9)-VEGF-B or administration of GSK2656157 (GSK), an inhibitor of phosphorylated PERK abolished the protective effect of Mel on DCM. Furthermore, rapamycin, an autophagy agonist displayed similar effect with Mel treatment; while 3-Methyladenine (3-MA), an autophagy inhibitor neutralized the effect of Mel on high glucose-treated neonatal rat ventricular myocytes. Conclusions These results demonstrated that Mel attenuated DCM via increasing autophagy of cardiomyocytes, and this cardio-protective effect of Mel was dependent on VEGF-B/GRP78/PERK signaling pathway.

Abstract Background Deletion of haploinsufficient genes or duplication of triplosensitive ones results in phenotypic effects in a concentration-dependent manner, and the mechanisms underlying these dosage-sensitive effects remain elusive. Phase separation drives functional compartmentalization of biomolecules in a concentration-dependent manner as well, which suggests a potential link between these two processes, and warrants further systematic investigation. Results Here we provide bioinformatic and experimental evidence to show a close link between phase separation and dosage sensitivity. We first demonstrate that haploinsufficient or triplosensitive gene products exhibit a higher tendency to undergo phase separation. Assessing the well-established dosage-sensitive genes HNRNPK, PAX6, and PQBP1 with experiments, we show that these proteins undergo phase separation. Critically, pathogenic variations in dosage-sensitive genes disturb the phase separation process either through reduced protein levels, or loss of phase-separation-prone regions. Analysis of multi-omics data further demonstrates that loss-of-function genetic perturbations on phase-separating genes cause similar dysfunction phenotypes as dosage-sensitive gene perturbations. In addition, dosage-sensitive scores derived from population genetics data predict phase-separating proteins with much better performance than available sequence-based predictors, further illustrating close ties between these two parameters. Conclusions Together, our study shows that phase separation is functionally linked to dosage sensitivity and provides novel insights for phase-separating protein prediction from the perspective of population genetics data.

Abstract Aging in mammals is accompanied by an imbalance of intestinal homeostasis and accumulation of mitochondrial DNA (mtDNA) mutations. However, little is known about how accumulated mtDNA mutations modulate intestinal homeostasis. We observe the accumulation of mtDNA mutations in the small intestine of aged male mice, suggesting an association with physiological intestinal aging. Using polymerase gamma (POLG) mutator mice and wild-type mice, we generate male mice with progressive mtDNA mutation burdens. Investigation utilizing organoid technology and in vivo intestinal stem cell labeling reveals decreased colony formation efficiency of intestinal crypts and LGR5-expressing intestinal stem cells in response to a threshold mtDNA mutation burden. Mechanistically, increased mtDNA mutation burden exacerbates the aging phenotype of the small intestine through ATF5 dependent mitochondrial unfolded protein response (UPRmt) activation. This aging phenotype is reversed by supplementation with the NAD+ precursor, NMN. Thus, we uncover a NAD+ dependent UPRmt triggered by mtDNA mutations that regulates the intestinal aging.

Sarcasm is a sophisticated speech act that is intended to express contempt or ridicule on social communities such as Twitter. In recent years, the prevalence of sarcasm on the social media has become highly disruptive to sentiment analysis systems due to not only its tendency of polarity flipping but also usage of figurative language. It is observed that sarcastic texts often convey a humorous effect. Thus, determining the humor in texts can be pertinent to the successful detection of sarcasm, and vice versa. However, current works always regard sarcasm detection and humor identification as separate tasks. In this paper, we argue that these tasks should be treated as a joint, collaborative, effort, considering the semantic connections between sarcasm and humor expressed in texts. Enlightened by the multi-task learning strategy, we present a joint architecture that settles two highly pertinent tasks, sarcasm detection and humor identification. As the basic of deep neural networks, we learn both tasks jointly exploring weight sharing to capture the task-specific features for each task and task-cross features between the two tasks. Extensive experiments on real-world datasets demonstrate that our presented model consistently enhances both sarcasm detection and humor identification tasks consistently with the help of the strong semantic relationships, achieving much better performance than state-of-the-art baselines.