Search

Abstract Background Non-muscle-invasive bladder cancer (NMIBC) is renowned for its high recurrence, invasiveness, and poor prognosis. Consequently, developing new biomarkers for risk assessment and investigating innovative therapeutic targets postoperative in NMIBC patients are crucial to aid in treatment planning. Approaches Differential gene expression analysis was performed using multiple Gene Expression Omnibus (GEO) datasets to identify differentially expressed genes (DEGs) between NMIBC and normal tissue, as well as between NMIBC and muscle-invasive bladder cancer (MIBC). Functional enrichment analysis was conducted based on the DEGs identified. Subsequently, prognosis-related genes were selected using Kaplan–Meier (KM) analysis and Cox regression analysis. The Boruta algorithm was utilized to further screen for core DEGs related to postoperative progression in NMIBC based on the aforementioned prognosis-related genes. Single-cell and clinical correlation studies were performed to verify their expression across various stages of bladder cancer. To investigate the link between core genes and the immune microenvironment, single-sample gene set enrichment analysis (ssGSEA) was utilized, and Receiver Operating Characteristic (ROC) and KM analyses were performed to confirm predictive power for immune therapy outcomes. Machine learning (ML) models were constructed using the DepMap dataset to predict the efficacy of core gene inhibitors in treating bladder cancers. The prognostic performance of the core genes was evaluated using ROC curve analysis. An online prediction tool was developed based on the core genes to provide prognostic predictions. Finally, RT-qPCR, CCK-8, and Transwell assays were used to verify the pro-tumor effects of the GINS2 in bladder cancer. Results A total of 70 DEGs were identified, among which 11 prognostic genes were obtained through KM analysis, and an additional 8 prognostic genes were obtained through COX analysis. The Boruta algorithm selected AURKB, GINS2, and UHRF1 as the three core DEGs. Single-cell and clinical variable correlation analyses indicated that the core genes promoted the progression of bladder cancer. The analysis of immune infiltration revealed a strong positive association between the core genes and both activated CD4 T cells and Type 2 helper T cells. Two random forest (RF) models were constructed to effectively predict the treatment effect of bladder cancer after targeted inhibition of AURKB and GINS2. In addition, an online nomogram tool was developed to effectively predict the risk of postoperative progression in NMIBC patients undergoing TURBT. Finally, RT-qPCR, CCK8, and Transwell assays showed that GINS2 promoted the growth and progression of bladder cancer. Conclusion AURKB, GINS2, and UHRF1 have the potential to enhance postoperative management of NMIBC patients undergoing transurethral resection of bladder tumor (TURBT) and can predict immunotherapy response, establishing them as promising therapeutic targets.

Abstract Background Research on low-protein-level diets has indicated that even though the profiles of essential amino acids (EAAs) follow the recommendation for a normal-protein-level diet, broilers fed low-protein diets failed to achieve productive performance compared to those fed normal diets. Therefore, it is imperative to reassess the optimum profile of EAAs in low-protein diets and establish a new ideal pattern for amino acid balance. Furthermore, identifying novel sensitive biomarkers for assessing amino acid balance will greatly facilitate the development of amino acid nutrition and application technology. In this study, 12 dietary treatments [Con(+), Con(-), L&A(-), L&A(+), M&C(-), M&C(+), BCAA (-), BCAA(+), Thr(-), Thr(+), Trp(-) and Trp(+)] were established by combining different EAAs including lysine and arginine, methionine and cysteine, branched-chain amino acid (BCAA), threonine, and tryptophan to observe the growth and development of the broiler chickens fed with low-protein-level diets. Based on the biochemical parameters and untargeted metabolomic analysis of animals subjected to different treatments, biomarkers associated with optimal and suboptimal amino acid balance were identified. Results Growth performance, carcass characteristics, hepatic enzyme activity, serum biochemical parameters, and breast muscle mRNA expression differed significantly between male and female broilers under different dietary amino acid patterns. Male broilers exhibited higher sensitivity to the adjustment of amino acid patterns than female broilers. For the low-protein diet, the dietary concentrations of lysine, arginine, and tryptophan, but not of methionine, cystine, or threonine, needed to be increased. Therefore, further research on individual BCAA is required. For untargeted metabolomic analysis, Con(+) was selected as a normal diet (NP) while Con(-) represented a low-protein diet (LP). L&A(+) denotes a low-protein amino acid balanced diet (LPAB) and Thr(+) represents a low-protein amino acid imbalance diet (LPAI). The metabolites oxypurinol, pantothenic acid, and D-octopine in birds were significantly influenced by different dietary amino acid patterns. Conclusion Adjusting the amino acid profile of low-protein diets is required to achieve normal growth performance in broiler chickens fed normal-protein diets. Oxypurinol, pantothenic acid, and D-octopine have been identified as potentially sensitive biomarkers for assessing amino acid balance.

Abstract Background Owing to their unique physiochemical properties, low toxicity, antipathogenic effects and tunability, fluorescent carbon quantum dots (CQDs) represent a new generation of carbon-based nanomaterials. Despite the mounting research on the efficacy of CQDs against resilient plant pathogens, their potential ability to mitigate viral pathogens and the underlying molecular mechanism(s) remain understudied. In this study, we optimized the CQDs to maximize their antiviral effects against a highly pathogenic Begomovirus (cotton leaf curl Multan virus, CLCuMuV) and elucidated the mechanistic pathways associated with CQDs-mediated viral inhibition. To fine-tune the CQDs-induced antiviral effects against CLCuMuV and investigate the underlying molecular mechanisms,we used HR-TEM, XRD, FT-IR, XPS, and UV‒Vis spectrophotometry to characterize the CQDs. SPAD and FluorCam were used for physiological and photosynthetic performance analysis. Transcriptome, RT‒qPCR, integrated bioinformatics and molecular biology were employed to investigate gene expression, viral quantification and data validation. Results The application of fluorescent, hexagonal crystalline, UV-absorptive and water-soluble CQDs (0.01 mg/ml) significantly reduced the CLCuMuV titer and mitigated viral symptoms in N. benthamiana at the early (5 dpi) and late (20 dpi) stages of infection. CQDs significantly increased the morphophysiological properties, relative chlorophyll contents and photosynthetic (Fv/Fm, QY_max, NPQ and Rfd) performance of the CLCuMuV-infected plants. While CLCuMuV infection disrupted plant immunity, the CQDs improved the antiviral defense response by regulating important immunity-related genes involved in endocytosis/necroptosis, Tam3-transposase, the ABC transporter/sphingolipid signaling pathway and serine/threonine protein kinase activities. CQDs potentially triggered TSS and TTS alternative splicing events in CLCuMuV-infected plants. Conclusions Overall, these findings underscore the antiviral potential of CQDs, their impact on plant resilience, and their ability to modulate gene expression in response to viral stress. This study’s molecular insights provide a foundation for further research on nanomaterial applications in plant virology and crop protection, emphasizing the promising role of CQDs in enhancing plant health and combating viral infections. Graphical Abstract

Abstract Lung adenocarcinoma (LUAD) is the major subtype of lung cancer. The poor prognosis of LUAD patients is attributed primarily to metastasis. ADAMTS16 is a crucial member of the ADAMTS family and is involved in tumor progression. However, its role and regulatory mechanism in LUAD remain unexplored. In this study, ADAMTS16 was identified as a crucial oncogene and survival predictor in LUAD via analyses of public datasets. Clinical specimens and tissue microarrays confirmed the differential expression and prognostic value of ADAMTS16 in LUAD patients. Transcriptome data and in vitro experiments demonstrated that ADAMTS16 was positively associated with epithelial-mesenchymal transition (EMT) and the migration abilities of LUAD cells. Knockdown of ADAMTS16 attenuated lung and pleural metastasis in an animal model. Mechanistically, the results of the enzyme-linked immunosorbent assay (ELISA) and western blot (WB) suggested that ADAMTS16 activated the TGF-β signaling pathway by facilitating the conversion of LAP-TGF-β1 to active TGF-β1. Co-Immunoprecipitation (co-IP) indicated an interaction between ADAMTS16 and LAP-TGF-β1. Inhibition of ADAMTS16 impaired EMT and aggressiveness of LUAD cells, while treatment with recombinant TGF-β1 reversed this inhibition. Chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assays indicated that SOX4 acted as a transcriptional activator of ADAMTS16 and that TGF-β1 regulated the expression of ADAMTS16 by increasing the binding of SOX4 to the promoter of ADAMTS16. Suppressing the TGF-β signaling pathway inhibited ADAMTS16 expression, EMT, and lung metastasis, whereas overexpressing SOX4 reversed this inhibition. Therefore, ADAMTS16 forms a positive feedback loop with the TGF-β1/SOX4 axis to regulate EMT and metastasis, and disruption of this feedback loop inhibits tumor progression. These findings underscore the potential of ADAMTS16 as a prognostic biomarker and therapeutic target in LUAD and offer novel insight into the mechanism of EMT and metastasis.

Abstract The night-time temperature-related injury risks and burdens were unclear. Using 11,512,467 non-fatal injury cases in 243 surveillance hospitals across China from 2006-2021, we estimated the associations between daytime or night-time temperature and injury by a time-stratified case-crossover study, and compared their injury burden during 1990s–2010s. We found the excess risk (ER) for per 1°C rise in night-time temperature (ER = 1.21%, 95%CI:1.03%,1.39%) was greater than that in daytime (ER = 0.86%, 95%CI:0.72%,1.00%). Compared with the 1980s, the attributable fractions (AFs) for daytime and night-time temperature change during the 1990s–2010s were 0.59% (95%eCI:0.54%,0.67%) and 0.73% (95%eCI:0.69%,0.77%), respectively. Spatially, the higher AFs of night-time temperature were more widely distributed than daytime temperature. The non-fatal injury risk attributed to night-time temperature was stronger than daytime temperature, and increased night-time temperatures posed a heavier injury burden compared with daytime temperature in China. Our findings indicate that high night-time temperature is an important injury risk in the context of climate change.

Abstract Hydro-viscous clutch has become an inevitable choice for special vehicle transmissions. As a nonlinear dynamic system with large lagging link, its timing performance is affected by input rotational speed, lubricating oil temperature and pressure and other factors. However, from the control perspective, the speed regulation law, formation mechanism control characteristics, global model of hydro-viscous speed control system (HSCS) are unclear. To solve these problems, this paper presents a comprehensive analysis of the Hydro-viscous Speed Control System (HSCS), focusing on its steady-state and dynamic speed control characteristics. A data-driven model is established to describe the relationship between input rotational speed, output speed, control oil pressure, and lubricating oil temperature. The findings provide a foundation for optimizing HSCS structure and parameters, enhancing the performance and reliability of such systems in special vehicle transmissions and establishing a temperature-speed control system for special vehicle transmissions.

Abstract To ensure that the discrete element model of the coal wall accurately reflects the actual cutting process of coal and rock during virtual prototype simulation of mining equipment, this study aims to expedite the development of intelligent mining machinery. Using coal samples from the 4602 working face of Yangcun Coal Mine, operated by Yanzhou Coal Mining Group, we conducted coal rock packing experiments and uniaxial compression tests to obtain the packing angle and compressive strength of the coal samples. Based on the experimental results, we designed Plackett–Burman experiments (PB experiments), steepest ascent experiments, and Box-Behnken experiments to study the influence of particle contact mechanics parameters and bonding mechanics parameters on the packing angle and compressive strength, using the packing angle and compressive strength as response variables. Our objective is to minimize the relative error between the simulated packing angle and the measured packing angle. We solved and optimized the parameter calibration model and conducted simulation calibration experiments based on the optimization results. A comparative analysis with the actual test results revealed that the maximum relative errors between the simulated and measured values for the packing angle and compressive strength were only 2.9% and 5.0%, respectively. Additionally, a discrete element model of a typical working face coal wall was established based on the parameters obtained from this calibration method. A bidirectional coupling model of the cutting process between the coal and rock was created using EDEM-RecurDyn to simulate the rigid-flexible coupling of the coal cutter. An experimental coal wall model was constructed based on similarity theory, and both simulation and physical experiments were conducted. The evaluation metrics for comparison were the time-domain and frequency-domain characteristics of the drum’s vibration signals. The maximum relative error for the time-domain signal characteristics between the two experimental setups was only 4.19%, while the maximum relative error for the frequency-domain signal characteristics was 3.75%. This validates the feasibility of the proposed calibration method for the discrete element coal wall model and the accuracy of the calibration results. Furthermore, it demonstrates that the constructed discrete element coal wall accurately represents the actual coal and rock properties. The virtual simulation based on this model effectively replicates the interaction process between mining machinery and coal, providing a safe, efficient, and low-cost technological approach for performance analysis of mining equipment and intelligent control of supporting devices.

Abstract The rockeries of classical Chinese gardens are masterpieces of classical Chinese garden art and form a key element of garden heritage. Consequently, a quantitative study of “rockery shadows” is of considerable importance to the study of “rockery forms.” In this study, we selected the representative North Rockery in Zhanyuan Garden of Nanjing and Ruiyunfeng, Guanyunfeng, and Yulinglong as the objects of the study. This study aims to explore the shadow images of rockeries using image extraction and targeted quantitative analysis methods. Macroscopically, the overall shape of rockery shadows was described using fractal dimensions; microscopically, the aspect ratio, angle, and refinement indexes of each shadow based on each observation angle of the rockery were measured using the PAT-GEOM plug-in in ImageJ software. SPSS Statistics was used for the normal distribution test of the angular distribution data. Consequently, the shadow data of the North Rockery in Zhanyuan Garden and Ruiyunfeng, Guanyunfeng, and Yulinglong, respectively, were analyzed and compared, and four rockery-shadow laws were derived. Finally, the results were applied to the design of the rockery morphological translation based on quantitative analysis of the shadows. The approach presented here will enhance landscape design, support environmental planning, and preserve cultural heritage.

ObjectiveThis paper investigates the synchronization control problem for supply and supplied ships during underway replenishment in a constantly time-varying ocean environment while considering the ocean environmental disturbances induced by wind, waves and currents, and the interaction effects between ships and their soft connections. It then proposes an event-triggered synchronization anti-disturbance control method based on disturbance estimation and compensation.MethodThe first-order Markov process is used to describe the ocean environmental disturbances induced by waves, wind and currents that affect the supply ship, as well as the unmodeled dynamics. The interaction effects between the ships and their soft connections are included in the unmodeled dynamics. The online disturbance observer estimates time-varying unknown bounded disturbances which are compensated for in the control design using disturbance estimates. The auxiliary dynamic system helps to reduce the control saturation effects on anti-disturbance control. The event-triggered mechanism reduces the execution frequencies of control signals to avoid the excessive wear of the thrusters.ResultsA simulation of a supply ship using the event-triggered control method shows the existence of a minimum sampling interval greater than 0 and the inability to trigger infinitely in a finite time. The controller can achieve synchronous navigation between supply and supplied ships while ensuring the global uniform ultimate boundedness of all closed-loop control signals.ConclusionThe simulation results validate the effectiveness of the proposed event-triggered disturbance estimation and compensation control method.

Abstract Postoperative cognitive dysfunction, a common neurological complication in the perioperative period, seriously affects patient survival and prognosis. Its high incidence has made the study of postoperative cognitive dysfunction challenging. Whether the clinical application of dexmedetomidine, a potential neuroprotective drug, can reduce the incidence of postoperative cognitive dysfunction is controversial, although several potential mechanisms by which dexmedetomidine improves postoperative cognitive dysfunction have been identified; therefore, this remains an area in need of further exploration.

Abstract Indoor localization using Wi-Fi fingerprinting based on Received Signal Strength (RSS) has gained widespread attention due to its immunity to external factors and ability to penetrate obstacles. The localization process involves an offline phase for building a radio map and an online phase for matching location queries. Existing matching algorithms often prioritize enhancing online phase accuracy, overlooking the importance of offline data preprocessing, which can negatively impact overall performance. This study introduces a novel approach called Fingerprint Dictionary Preprocessing (FDP) that employs Convolutional Dictionary Learning (CDL) to process radio map data. CDL learns a set of kernels capturing site characteristics, representing RSS values from Access Points (APs) in a sparse manner. The proposed FDP system compresses data through feature learning, reducing storage requirements for data transmission. In the online phase, CDL is utilized for assisting matching fingerprints against the learned dictionary, accurately locating users. The contributions of the FDP system presenting a cost-effective and practical solution for indoor localization, addressing the challenges associated with large data collection and multi-dimensional data requirements, making it a promising approach for real-world applications. We conducted experiments in two real indoor environments, and the results indicated that the proposed FDP system, whether applied to the original radio map or the preprocessed fingerprint database, led to improved localization accuracy and reduced localization time.

Abstract The objective of this study is to investigate the effects of various doses of esketamine on the median effective concentration (EC50) of propofol required for inhibiting body movement during hysteroscopy. Additionally, this research aims to explore the pharmacodynamic interactions between esketamine and propofol. Prospective, double-blind, up-down sequential allocation study. Operating room, post-anesthesia care unit (PACU), and general ward. A total of 90 patients were allocated into three groups in a randomized, double-blinded manner as follows: 0.1 mg/kg esketamine combined with propofol intravenous injection (EP0.1) group, 0.2 mg/kg esketamine combined with propofol intravenous injection (EP0.2) group, 0.3 mg/kg esketamine combined with propofol of intravenous injection (EP0.3) group. For the initial patient in each group, the starting effector target concentration of propofol was set at 4 µg/ml. Each patient received an initial intravenous injection of 0.04 mg/kg midazolam, followed by the administration of the appropriate dose of esketamine. Ten seconds after the esketamine injection, propofol was administered intravenously to achieve the target concentration. In accordance with the sequential method principle, the concentration of propofol for the subsequent patient was adjusted based on the response of the previous patient. Effective inhibition of body movement was defined as the absence of any involuntary body movements throughout the entire surgical process. If the previous patient exhibited body movements, the propofol concentration for the next patient was increased by 0.5 µg/ml; conversely, if no movements were observed, it was decreased by 0.5 µg/ml. The up-down sequential allocation method and probit regression were used to calculate the EC50 of propofol. Hospital Anxiety and Depression Scale-Anxiety (HADS-A) and Depression (HADS-D) score, adverse events, hemodynamic changes, demographic data and clinical characteristics. The EC50 of propofol was 3.849 μg/ml (95% CI: 3.419–4.281) in the EP0.1 group, 3.641 μg/ml (95% CI: 2.807−4.200) in the EP0.2 group, and 3.417 μg/ml (95% CI: 2.845–3.852) in the EP0.3 group. These findings suggest that esketamine can dose-dependently reduce the EC50 of propofol. Esketamine can dose-dependently reduce the EC50 of propofol in hysteroscopy, while concurrently lowering patients’ HADS-A and HADS-D scores 24 h post-operation. It is concluded that the optimal dose of esketamine, when combined with propofol for hysteroscopy, is 0.3 mg/kg.

Abstract Oxidative stress (OS) is strongly implicated in the pathophysiology of major depressive disorder (MDD) but the molecular mechanisms remain largely unknown. The purpose of this study is to identify genes related to both OS and MDD, and further to evaluate the utility of these genes as diagnostic markers and potential treatment targets. We searched datasets related to MDD from the Gene Expression Omnibus (GEO) database for differentially expressed genes (DEGs) also related to OS according to GeneCards. Bioinformatics analyses and machine learning algorithms were used to identify hub genes mediating OS–MDD interactions. A summary data-based Mendelian randomization (SMR) approach was employed to identify possible causal genes for MDD from blood tissue eQLT data. These investigations identified 32 genes mediating OS–MDD interactions, while SMR analysis identified KCNE1 (OR = 1.057, 95%CI = 1.013–1.102, P value = 0.010), MAPK3 (OR = 1.023, 95%CI = 1.004–1.043, P value = 0.020), and STIP1 (OR = 0.792, 95%CI = 0.641–0.979, P value = 0.031) as OS-related causal genes for MDD. These genes may thus serve as useful diagnostic markers and potential therapeutic targets.

Abstract Astragalus membranaceus (AM) roots are a well-known homologous medicine and food in China. AM stems, which are discarded and not used effectively, also contain many active compounds and exhibit beneficial effects. It has the potential to be explored as antibiotic alternative. Fermentation combined with enzymatic hydrolysis (FEH) is an effective strategy for extracting polyphenol and improving the usage of AM stems. Therefore, in this study, the conditions of FEH and extraction for polyphenol in AM stems were screened. The antioxidant activity of extract from AM stems without and with FEH (AMSE and FAMSE) was evaluated. The metabolite profiles of phenolic acids and flavonoids in AMSE and FAMSE were characterized by ultra-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry (UPLC–ESI-MS/MS). The results showed that the highest polyphenol content from AM stems was obtained with cellulase and pectinase (1:1, 2000 U/g), moisture content 43%, fermentation temperature 30 °C, and fermentation time 7 days. Selected extraction conditions of polyphenol were ethanol concentration 50%, ultrasonic power 500 W, extraction temperature 35 °C, and extraction time 40 min. On this condition, compared with AMSE, the polyphenol and flavonoid contents in FAMSE were significantly higher. FAMSE exhibited stronger DPPH, hydroxyl radical scavenging rate and reducing power than AMSE. The relative content of 3-(4-hydroxyphenyl)-propionic acid, dihydroferulic acid, isoferulic acid, 4-hydroxybenzoic acid, 4-hydroxyphenyllactic acid, ferulic acid, vanillic acid, syringic acid, gentisic acid, sinapic acid, apigenin, tricin, acacetin, daidzein, genistein, formononetin, prunetin, pratensein, rhamnocitrin and galangin were significantly upregulated in FAMSE. Graphical Abstract

Glioma is the most prevalent primary malignant tumor in the central nervous system (CNS). It represents a diverse group of brain malignancies characterized by the presence of various cancer cell types as well as an array of noncancerous cells, which together form the intricate glioma tumor microenvironment (TME). Understanding the interactions between glioma cells/glioma stem cells (GSCs) and these noncancerous cells is crucial for exploring the pathogenesis and development of glioma. To invesigate these interactions requires in vitro co-culture models that closely mirror the actual TME in vivo. In this review, we summarize the two- and three-dimensional in vitro co-culture model systems for glioma-TME interactions currently available. Furthermore, we explore common glioma-TME cell interactions based on these models, including interactions of glioma cells/GSCs with endothelial cells/pericytes, microglia/macrophages, T cells, astrocytes, neurons, or other multi-cellular interactions. Together, this review provides an update on the glioma-TME interactions, offering insights into glioma pathogenesis.

Abstract Oats (Avena sativa L.) are rich in nutrients and bioactive compounds, serving as a roughage source for ruminants. This study investigated the impact of lactic acid bacteria (LAB), cellulase (M), and their combinations (LM) on the fermentation quality and metabolic compounds of oat silage. Results demonstrated that all additive treatments significantly increased lactic acid content compared to the control group (P

Abstract Retinol is widely used to treat skin ageing because of its effect on cell differentiation, proliferation and apoptosis. However, its potential benefits appear to be limited by its skin permeability. Herein, we investigated the transcutaneous behavior of retinol in semisolid cosmetics, in both in vitro and in vivo experiments. In vitro experiments used the modified Franz diffusion cell combined with Raman spectroscopy. In in vivo experiments, the content of retinol in rat skin and plasma was detected with HPLC. Retinol in semisolid cosmetics was mainly concentrated in the stratum corneum in the skin of the three animal models tested, and in any case did not cross the skin barrier after a 24 h dermatologic topical treatment in Franz diffusion cells tests. Similar results were obtained in live mice and rats, where retinol did not cross the skin barrier and did not enter the blood circulation. Raman spectroscopy was used to test the penetration depth of retinol in skin, which reached 16 μm out of 34 μm in pig skin, whereas the skin of mouse and rat showed too strong bakground interference. To explore epidermal transport mechanism and intradermal residence, skin transcriptomics was performed in rats, which identified 126 genes upregulated related to retinol transport and metabolism, relevant to the search terms “retinoid metabolic process” and “transporter activity”. The identity of these upregulated genes suggests that the mechanism of retinol action is linked to epidermis, skin, tissue and epithelium development.

Leaves are the main organ for photosynthesis and organic synthesis in cotton. Leaf shape has important effects on photosynthetic efficiency and canopy formation, thereby affecting cotton yield. Previous studies have shown that LMI1 (LATE MERISTEM IDENTITY1) is the main gene regulating leaf shape. In this study, the LMI1 gene was inserted into the 35S promoter expression vector, and cotton plants overexpressing LMI1 (OE) were obtained through genetic transformation. Statistical analysis of the biological traits of the T1 and T2 populations showed that compared to the wild type (WT), OE plants had significantly larger leaves, thicker stems and significantly greater dry weight. Furthermore, plant sections of the main vein and petiole showed that the numbers of cells in those tissues of OE plants were significantly greater. In addition, RNA-seq analysis revealed the differential expression of genes related to gibberellin synthesis and NAC gene family (genes containing the NAC domain) between the OE and WT plants, suggesting that LMI1 is involved in secondary wall formation and cell proliferation, which promotes stem thickening. Moreover, Gene Ontology (GO) analysis revealed enrichment in the terms of calcium ion binding, and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed enrichment in the terms of fatty acid degradation, phosphatidylinositol signal transduction system, and cAMP (cyclic adenosine monophosphate) signal pathway. These results suggested that LMI1 OE plants are responsive to gibberellin hormone signals, and have altered messenger signals (cAMP, Ca2+) which amplify this function, to promote stronger aboveground vegetative growth. This study found the LMI1 greatly increased the vegetative growth in cotton, which is the basic requirement for higher yield.

Abstract Viral encephalitis is characterized by inflammation of the brain parenchyma caused by a variety of viruses, among which the Japanese encephalitis (JE) virus (JEV) is a typical representative arbovirus. Neuronal death, neuroinflammation, and breakdown of the blood brain barrier (BBB) constitute vicious circles of JE progression. Currently, there is no effective therapy to prevent this damage. Growth arrest specific gene 6 (GAS6) is a secreted growth factor that binds to the TYRO3, AXL, and MERTK (TAM) family of receptor tyrosine kinases and has been demonstrated to participate in neuroprotection and suppression of inflammation in many central nervous system (CNS) diseases which has great potential for JE intervention. In this study, we found that GAS6 expression in the brain was decreased and was reversely correlated with viral load and neuronal loss. Mice with GAS6/TAM signalling deficiency showed higher mortality and accelerated neuroinflammation during peripheral JEV infection, accompanied by BBB breakdown. GAS6 directly promoted the expression of tight junction proteins in bEnd.3 cells and strengthened BBB integrity, partly via AXL. Mice administered GAS6 were more resistant to JEV infection due to increased BBB integrity, as well as decreased viral load and neuroinflammation. Thus, targeted GAS6 delivery may represent a strategy for the prevention and treatment of JE especially in patients with impaired BBB.

Abstract Porcine circoviruses, particularly porcine circovirus type 2 (PCV2) and porcine circovirus type 3 (PCV3), significantly impact the global pig industry due to their high prevalence and pathogenicity. Conversely, porcine circovirus type 1 (PCV1) and porcine circovirus type 4 (PCV4) currently have low positivity rates. This study aimed to characterize the distribution and epidemiology of porcine circoviruses in Xinjiang, while also analyzing the genetic diversity and evolution of PCV2 and PCV3, which pose the greatest threats to the industry. In this study, we collected blood and tissue samples from 453 deceased pigs across eight regions in Xinjiang Province from 2022 to 2024. We utilized real-time PCR to detect the presence of PCV1, PCV2, PCV3, and PCV4. The positive rates were 15%, 71%, 25%, and 17%, respectively. Genetic analysis showed 9 PCV2 sequences and 12 PCV3 sequences. The capsid protein of PCV2 showed significant variability. In contrast, the amino acid sequences of capsid in PCV3 were relatively stable. Moreover, we predicted antigenic epitopes for PCV3 capsid using IEDB and ElliPro. The findings from this study provide valuable epidemiological data on PCV coinfection in the Xinjiang region and enhance the understanding of virus diversity nationwide. This research may serve as an important reference for the development of strategies to prevent and control porcine circovirus infections.

To address the requirements for safety enhancement, weight reduction, and emission reduction, a novel transformation-induced plasticity-assisted bainitic ferrite (TBF) steel was processed by involving a pre-quenching (PQ) process. This steel was designed with varying PQ temperatures to achieve different fractions of intercritical ferrite and bainite, and its influence on mechanical properties of TBF steels was thoroughly investigated through tensile tests and hole expansion tests. The results demonstrated that the introduction of high-temperature PQ treatment before heat treatment can dramatically accelerate the formation of austenite during the secondary annealing process, thereby facilitating a more sufficient bainitic transformation in the subsequent isothermal process. With the increase of PQ temperature from 750 to 900 °C, abundant intercritical ferrite was replaced by lathy bainite. In comparison with conventional specimens, the high-temperature PQ treatment could reduce the fraction of intercritical ferrite and martensite-austenite (M-A) islands, in favor of delaying the initiation of microvoid and microcrack and improving local formability. In summary, the P-900 specimen exhibited optimal comprehensive mechanical properties, with the highest yield strength of 657 MPa, ultimate tensile strength of 1081 MPa, elongation of 28.7%, and hole expansion ratio of 35.1%.

Plastic pollution is widely present in terrestrial and aquatic ecosystems, and microplastics (MPs) can be detected in organisms. In situ detection methods for MPs in organisms have attracted widespread attention. Traditional imaging characterization methods of MPs, including stereo microscopes and fluorescence microscopy, are typically used to image artificially added microsphere standards under laboratory conditions. However, they cannot specifically identify MPs in biological samples. Thus, there is a need for a detection technique that can provide spatial distribution information of MPs in biological samples as well as measure their quality and quantity. In this perspective, to obtain high-resolution images with chemical composition analysis, we compared ion sources for ionizing plastic macromolecules and mass analyzers for analyzing macromolecules. Matrix-assisted laser desorption/ionization (MALDI) is suitable for imaging characterization, while time-of-flight (TOF) and Orbitrap mass spectrometry are suitable for polymer mass spectrometry analysis. Furthermore, we propose a technique that combines MALDI with TOF or Orbitrap, which holds promise for the in situ imaging of MPs in biological samples.

Through-thickness corrosion homogeneity of stabilized AA5083 alloy thick plate was investigated. For the as-received stabilized plates, no differences in corrosion behavior are evident in the specimens from different sampling positions along the thickness direction. However, in the plates after sensitization, the specimen from the surface position (T/10, SP) exhibits the highest degree of sensitization (DoS) and stress corrosion cracking (SCC) susceptibility, indicating the through-thickness corrosion inhomogeneity. Compared with interlayer position (3T/10, IP) and center position (T/2, CP), the higher grain stored energy and richer high angle grain boundaries (HAGBs) in SP specimens promote the formation of β phases (Al3Mg2) during the sensitization process. It results in a high coverage of β phases in the SP specimen and therefore induces severe corrosion.

Abstract Culter alburnus is extensively distributed in various rivers and lakes across China. As a widely adaptive fish species, it has significant economic values and special ecological roles. To meet research demands and provide better genomic resources, in this research, a chromosome-level genome assembly was constructed using HiFi long-reads and Hi-C sequencing data. Compared with the published versions, our genome assembly is of higher quality with only 31 gaps and closer to its true structure and sequence. The genome size was 1.052 Gb, with a contig N50 of 32.92 Mb and a scaffold N50 of 43.09 Mb. 55 contigs were anchored to 24 chromosomes on the basis of Hi-C data. A total of 598.23 Mb of repetitive sequences were annotated and 28,228 protein-coding genes were predicted. Additionally, BUSCO assessment indicated assembly and annotation scores of 98.3% and 99.2%, respectively. This high-quality genome will provide scientific support for excavating the species characteristics of C. alburnus and exploring its molecular mechanisms in response to environmental changes and stress.

Abstract Paternal genome elimination (PGE) is an intriguing but poorly understood reproductive strategy in which females are typically diploid, but males lose paternal genomes. Paternal genome heterochromatin (PGH) occurs in arthropods with germline PGE, such as the mealybug, coffee borer beetles, and booklice. Here, we present evidence that PGH initially occurs during early embryo development at around 15 h post-mating (hpm) in the cotton mealybug, Phenacoccus solenopsis Tinsley. Transcriptome analysis followed by qPCR validation indicated that six histone lysine methyltransferase (KMT) genes are predominantly expressed in adult females. We knocked down these five genes through dsRNA microinjection. We found that downregulation of two KMT genes, PsEZH2-X1 and PsEHMT1, resulted in a decrease of heterochromatin-related methylations, including H3K27me1, H3K27me3, and H3K9me3 in the ovaries, fewer PGH male embryos, and reduced male offspring. For further confirmation, we obtained two strains of transgenic tobacco highly expressing dsRNA targeting PsEZH2-X1 and PsEHMT1, respectively. Similarly, fewer PGH embryos and fewer male offspring were observed when feeding on these transgenic tobacco plants. Overall, we present evidence that PsEZH2-X1 and PsEHMT1 have essential roles in male embryo survival by regulating PGH formation in cotton mealybugs.

Abstract Background Methyl methacrylate (MMA) is a key precursor of polymethyl methacrylate, extensively used as a transparent thermoplastic in various industries. Conventional MMA production poses health and environmental risks; hence, citramalate serves as an alternative bacterial compound precursor for MMA production. The highest citramalate titer was previously achieved by Escherichia coli BW25113. However, studies on further improving citramalate production through metabolic engineering are limited, and phage contamination is a persistent problem in E. coli fermentation. Results This study aimed to construct a phage-resistant E. coli BW25113 strain capable of producing high citramalate titers from glucose. First, promoters and heterologous cimA genes were screened, and an effective biosynthetic pathway for citramalate was established by overexpressing MjcimA3.7, a mutated cimA gene from Methanococcus jannaschii, regulated by the BBa_J23100 promoter in E. coli. Subsequently, a phage-resistant E. coli strain was engineered by integrating the Ssp defense system into the genome and mutating key components of the phage infection cycle. Then, the strain was engineered to include the non-oxidative glycolysis pathway while removing the acetate synthesis pathway to enhance the supply of acetyl-CoA. Furthermore, glucose utilization by the strain improved, thereby increasing citramalate production. Ultimately, 110.2 g/L of citramalate was obtained after 80 h fed-batch fermentation. The citramalate yield from glucose and productivity were 0.4 g/g glucose and 1.4 g/(L·h), respectively. Conclusion This is the highest reported citramalate titer and productivity in E. coli without the addition of expensive yeast extract and additional induction in fed-bath fermentation, emphasizing its potential for practical applications in producing citramalate and its derivatives.

Abstract Background The objective of this study is to illustrate the changes in the choroidal vasculature in individuals with diffuse chorioretinal atrophy (DCA, early-stage myopic maculopathy) and investigate the association between them. Methods This study included 1418 highly myopic eyes from 720 participants aged 18 − 60 years from the Wenzhou High Myopia Cohort Study. These participants underwent comprehensive ophthalmic assessments. Myopic maculopathy classification followed the Meta-PM system, with pathological myopia defined as myopic maculopathy of DCA or severer. Eyes with myopic maculopathy categorized as no macular lesions (C0), tessellated fundus (C1), and DCA (C2) were enrolled in the analysis. Choroidal images were obtained from swept-source optical coherence tomography (SS-OCT), and the images were processed with a deep learning-based automatic segmentation algorithm and the Niblack auto-local threshold algorithm. Results DCA was detected in 247 eyes (17.4%). In comparison to eyes with C0, those with C2 exhibited significant reductions in choroidal thickness (ChT), luminal area (LA), and stromal area (SA) across all evaluated regions (all P

Abstract Glycyrrhiza stems and leaves (GSL) are waste products of Glycyrrhiza; however, it has been considered a potential source of flavonoid compounds. In this study, GSL was processed by solid-state fermentation (SSF) to improve the flavonoid content and antioxidant activity. Firstly, a near-infrared (NIR) prediction model for flavonoid content in fermented Glycyrrhiza stems and leaves (FGSL) was established. Next, the effects of SSF on the antioxidant activity and metabolite profile of GSL were investigated. Finally, the possible mechanism of ferment release of flavonoids was explored based on enzyme activity, thermogravimetric analysis, and FTIR spectroscopy. The results revealed that NIR spectroscopy can efficiently analyze flavonoid contents in GSL, with predicted determination coefficient (Rp2) and root mean square error (RMSEP) of 0.9874 and 0.125, respectively. SSF significantly increased the levels of flavonoids, and enhanced the scavenging activities of DPPH radical and hydroxyl radical and reducing power of FGSL. Widely targeted metabolomic analysis showed the detection of 461 differential metabolites were identified after SSF, with 141 metabolites remarkably up-regulated and 320 metabolites of FGSL down-regulated during fermentation. The main types of differential metabolites were phenolic acids and flavonoids, and the destruction of cellulose by SFF was crucial to the release of flavonoids. In conclusion, our study revealed that SSF remarkably improved the phytochemical components of FGSL by increasing enzyme activity and destroying cellulose structure, thereby contributing to the enhancement of antioxidant activity. This study provided a scientific basis for the production of high-value flavonoids from plant materials and offered a novel approach to elucidate the release and conversion of flavonoids. Graphical Abstract

Abstract Background To investigate the value of 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) semi-quantitative parameters, including the lesion diameter, maximum standardized uptake value (SUVmax), maximum standardized uptake value corrected for lean body mass (SULmax), metabolic lesion volume (MLV), and total lesion glycolysis (TLG), for classifying hepatic echinococcosis. Methods In total, 20 patients with 36 hepatic echinococcosis lesions were included in the study. Overall, these lesions were categorized as hepatic cystic echinococcosis (HCE) or hepatic alveolar echinococcosis (HAE) according to the pathological results. Multiple semi-parameters including the maximum diameter, SUVmax, SULmax, MLV, and TLG were measured to classify HCE and HAE compared with the pathological results. The receiver operator characteristic curve and area under the curve (AUC) of each quantitative parameter were calculated. The Mann–Whitney U test was used to compare data between the two groups. Results In total, 12 cystic lesions and 24 alveolar lesions were identified after surgery. There were significant differences in SUV max, SUL max, MLV, and TLG between the HAE and HCE groups (Z = − 4.70, − 4.77, − 3.36, and − 4.23, respectively, all P 0.05). The best cutoffs of SUV max, SUL max, MLV, and TLG for the differential diagnosis of HAE and HCE were 2.09, 2.67, 27.12, and 18.79, respectively. The AUCs of the four parameters were 0.99, 0.99, 0.85, and 0.94, respectively. The sensitivities were 91.7%, 87.5%, 66.7%, and 85.6%, respectively, and the specificities were 90.1%, 91.7%, 83.3%, and 90.9%, respectively. Conclusion 18F-FDG PET/CT semi-quantitative parameters had significant clinical value in the diagnosis and pathological classification of hepatic echinococcosis and evaluation of clinical treatment.

Abstract Chenopodium album L. (CAL) has many bioactive compounds and pharmacological activities. Fermentation is the preferred modification method of releasing target bioactive. We prepared two crude polysaccharides: SLC (the polysaccharide from the unfermented stem and leaves of CAL) and FSLC (the polysaccharide from the fermented stem and leaves of CAL). In vitro antioxidant and composition of SLC and FSLC were compared, and the effects of FSLC on antioxidant activity in the IPEC-J2 cells model and development-promoting activity in the zebrafish model were evaluated. The results revealed that FSLC possesses stronger DPPH, hydroxyl radical scavenging, and reducing power than SLC. The levels of total polysaccharide, polyphenol, and flavonoid, as well as the molar ratio of glucuronic acid increased in FSLC. Compared with SLC, the relative contents of protocatechuic acid, protocatechualdehyde, gentisic acid, vanillic acid, p-coumaric acid, quercetin, ferulic acid methyl ester, hispidulin, diosmetin, cinnamic acid, isorhamnetin, syringic acid and kaempferol in FSLC increased. In IPEC-J2 cells, antioxidant enzyme activities and GSH levels were significantly increased, while the MDA level was reduced by treatment with 0.25 mg/mL FSLC. In the zebrafish model, treatment with 25 ~ 300 μg/mL of FSLC had no harmful impact on the morphology and viability of embryos at 12 ~72 hpf. At 48 and 60 hpf, treatment with 100 ~ 300 μg/mL FSLC increased the hatching rate of embryos. At 72hpf, treatment with 100 ~ 300 μg/mL FSLC could relieve morphological abnormalities caused by LPS in zebrafish and improve the hatching rate of embryos. Together, these results provide useful information on the potential for applying polysaccharides from the stems and leaves of CAL as natural feed additives to exert its antioxidant and development-promoting functions. Graphical Abstract

Abstract Background Step width is a spatial variable in the frontal plane, defined as the mediolateral distance between the heel (forefoot during sprinting) of bilateral feet at initial contact. Variations in step width may impact the lower limb biomechanics. This systematic review aimed to synthesize the published findings to determine the influence of acute changes in step width on locomotion biomechanics and provide implications for injury prevention and enhanced sports performance. Methods Literature was identified, selected, and appraised in accordance with the methods of a systematic review. Four electronic databases (Web of Science, MEDLINE via PubMed, Scopus, and ScienceDirect) were searched up until May 2023 with the development of inclusion criteria based on the PICO model. Study quality was assessed using the Downs and Black checklist and the measured parameters were summarized. Results Twenty-three articles and 399 participants were included in the systematic review. The average quality score of the 23 studies included was 9.39 (out of 14). Step width changed the kinematics and kinetics in the sagittal, frontal, and transverse planes of the lower limb, such as peak rearfoot eversion angle and moment, peak hip adduction angle and moment, knee flexion moment, peak knee internal rotation angle, as well as knee external rotation moment. Alteration of step width has the potential to change the stability and posture during locomotion, and evidence exists for the immediate biomechanical effects of variations in step width to alter proximal kinematics and cues to impact loading variables. Conclusion Short-term changes in step width during walking, running, and sprinting influenced multiple lower extremity biomechanics. Narrower step width may result in poor balance and higher impact loading on the lower extremities during walking and running and may limit an athlete’s sprint performance. Increasing step width may be beneficial for injury rehabilitation, i.e., for patients with patellofemoral pain syndrome, iliotibial band syndrome or tibial bone stress injury. Wider steps increase the supporting base and typically enhance balance control, which in turn could reduce the risks of falling during daily activities. Altering the step width is thus proposed as a simple and non-invasive treatment method in clinical practice.

Abstract Background Depression is a common mental disorder with a much higher prevalence in women than in men. Although there has been a gradual increase in research on the association between reproductive health and depression, there is still some inconsistency in the evidence of the relationship between pregnancy loss and depression. This study aimed to investigate the relationship between pregnancy loss and depressive symptoms. Methods We analyzed data from the 2007–2020 National Health and Nutrition Examination Survey (NHANES), which included female participants aged 20 to 80 years. Pregnancy loss was determined based on participants’ self-reported number of pregnancies and pregnancy outcomes. Depressive symptoms were measured using the Patient Health Questionnaire (PHQ-9, score ≥ 10). Multivariate logistic regression, smoothed curve fitting, and generalized additive modeling were used to examine the association between pregnancy loss and depression. We also performed sensitivity analyses and subgroup analyses to verify the robustness and specificity of the findings. Results A total of 12,873 female participants were included in our study, of which 1,595 (12.39%) were categorized as depressed. Multivariate logistic regression results indicated that experiencing a pregnancy loss increased the risk of prevalence of depression in women (for 1 loss: OR = 1.31, 95% CI 1.15,1.50; for 2 or more losses: OR = 1.58, 95% CI 1.38, 1.81). When sensitivity analyses were performed, an association between pregnancy loss and depression was found in both multivariate linear regressions with PHQ-9 scores as a continuous variable and multivariate logistic regressions with a threshold of 5 PHQ-9 scores. The association between pregnancy loss and depression remained stable across subgroups. Conclusion Pregnancy loss correlated with elevated PHQ-9 scores and a heightened risk of depression in adult women across the United States. Focusing on the incidence of adverse pregnancy events in the female population may help prevent or early recognize the onset of depression.

AlCoCrFeMo0.05Ni2 high-entropy alloy (HEA) has great potential for high-temperature applications. However, its FCC matrix will decompose during annealing, which seriously limits its high-temperature applications. Here, the lattice distortion, Gibbs free energy change, phonon spectra, density of states, and bond length distribution of the FCC matrix were calculated by first-principles calculations. The findings indicate that the primary barrier to the formation of a single homogeneous solid solution in the alloy is more closely associated with Gibbs free energy rather than the degree of lattice distortion. The vibration frequency of Al is not in sync with the overall structure, making it prone to desolvation at elevated temperatures. Furthermore, an analysis of bond lengths reveals that the Al–Ni bond length is significantly shorter than the theoretical value, facilitating the formation of a (Ni, Al)-rich phase. In contrast, the longer bond lengths of Al–Cr and Al–Mo facilitate the detachment of Cr and Mo from the (Ni, Al)-rich phase, resulting in the formation of (Cr, Mo)-rich phase. This in-depth investigation sheds light on the phase decomposition mechanism of high-entropy alloys, offering valuable insights for future research in this field.

Abstract In traditional Chinese rockery stacking, the peculiarity of the materials and reliance on the personal experience of artisans during the construction process make it challenging to scientifically quantify the structural stress and use scientific methods to ensure the stability of rockery structures and the safety of the construction process. Therefore, the intangible cultural heritage of rockery stacking technology faces the problem of scientific structural inspection and risk estimation during the construction process. This study uses a finite element analysis to evaluate the structural stress of the rockery-stacking site to contribute to the sustainable development and protection of this intangible cultural heritage. After establishing a three-dimensional digital model, mechanical calculations are carried out for the overall structure of the rockery and its different parts. The analysis identifies three types of structural factors in artificial rockeries: contact, structure, and load. It also effectively and intuitively identifies the weak points in the rockery structures and provides an assessment of risks, offering valuable insights for risk prevention and for the construction and maintenance of the structures. These results contribute to the structural safety inspection of traditional Chinese rockery stacking and the structural evaluation of existing rockery heritage.

Abstract Immune checkpoint inhibitors, particularly PD-1/PD-L1 blockades, have been approved for unresectable hepatocellular carcinoma (HCC). However, high resistance rates still limit their efficacy, highlighting the urgent need to understand the underlying mechanisms and develop strategies for overcoming the resistance. In this study, tankyrasel binding protein 1 (TNKS1BP1) was found to interact with tripartite motif containing 21 (TRIM21) and mediated the ubiquitination of CCR4-NOT transcription complex subunit 4 (CNOT4) at the K239 residue via K48 and K6 linkage, which was essential for its tumorigenesis function. Autophagy and lipid reprogramming were identified as two possible mechanisms underlying the pro-tumor effect of TNKS1BP1. Upregulated TNKS1BP1 inhibited autophagy while induced lipid accumulation by inhibiting the JAK2/STAT3 pathway upon the degradation of CNOT4 in HCC. Importantly, knocking down TNKS1BP1 synergized with anti-PD-L1 treatment by upregulating PD-L1 expression on tumor cells via the JAK2/STAT3 pathway, and remodeling the tumor microenvironment by increasing infiltration of tumor-infiltrating lymphocytes as well as augmenting the effect of cytotoxic T lymphocytes. In conclusion, this study identified TNKS1BP1 as a predictive biomarker for patient prognosis and a promising therapeutic target to overcome anti-PD-L1 resistance in HCC.

Abstract Accumulating evidence supports the concept that DNA damage response targeted therapies can improve antitumor immune response by increasing the immunogenicity of tumor cells and improving the tumor immune microenvironment. Ataxia telangiectasia mutated (ATM) is a core component of the DNA repair system. Although the ATM gene has a significant mutation rate in many human cancers, including colorectal, prostate, lung, and breast, it remains understudied compared with other DDR-involved molecules such as PARP and ATR. Here, we found that either gene knockout or drug intervention, ATM inhibition activated the cGAS/STING pathway and augmented MHC class I in CRC cells, and these effects could be amplified by radiation. Furthermore, we found that MHC class I upregulation induced by ATM inhibition is dependent on the activation of the NFκB/IRF1/NLRC5 pathway and independent of STING. Animal experiments have shown increasing infiltration and cytotoxic function of T cells and better survival in ATM-deficient tumors. This work indicated that ATM nonsense mutation predicted the clinical benefits of radiotherapy combined with immune checkpoint blockade for patients with CRC. It also provides a molecular mechanism rationale for ATM-targeted agents for patients with CRC.

Abstract Objectives The geographical environment and military activities in the plateau area pose potential work-related stressors for military personnel, leading to burnout which is an external manifestation of internal energy exhaustion caused by stress. Without countermeasures, this can result in serious military problems. This study aims to examine the association between burnout and occupational stressors among military personnel stationed in the plateau area of China. Material and methods A stratified randomized cluster sampling survey was conducted among 2026 military personnel from 6 different troops stationed in the plateau area of China. The Chinese Maslach Burnout Inventory-General Survey(MBI-GS in Chinese) was administered from March 2022 to December 2023, and data were analyzed using SPSS version 25. Results A total of 2026 military personnel participated in the survey. The mean overall burnout score was 3.37 ± 0.73, with emotional exhaustion at 2.69 ± 0.89, depersonalization at 3.58 ± 0.92, and professional achievement at 3.81 ± 0.85 levels respectively reported by participants on average scale scores ranging from zero to six. Severe level of burnout was reported by 43.2% of participants while medium level of burnout was reported by 54 .3%. Age, education level, length of military service, and household income were identified as important factors influencing burnout. Conclusion This study highlights a relatively high prevalence of burnout among military personnel stationed in plateau areas necessitating attention towards their occupational health particularly focusing on working hours and economic aspects so as to formulate effective policies and implement intervention measures that strengthen career development for soldiers deployed in such regions.

Abstract Objective To investigate the characteristics of eye movement in children with anisometropic amblyopia, and to compare those characteristics with eye movement in a control group. Methods 31 children in the anisometropic amblyopia group (31 amblyopic eyes in group A, 31 contralateral eyes in group B) and 24 children in the control group (48 eyes in group C). Group A was subdivided into groups Aa (severe amblyopia) and Ab (mild-moderate amblyopia). The overall age range was 6–12 years (mean, 7.83 ± 1.79 years). All children underwent ophthalmic examinations; eye movement parameters including saccade latency and amplitude were evaluated using an Eyelink1000 eye tracker. Data Viewer and MATLAB software were used for data analysis. Results Mean and maximum saccade latencies, as well as mean and maximum saccade amplitudes, were significantly greater in group A than in groups B and C before and after treatment (P

Abstract Behçet’s disease (BD) is a multifaceted autoimmune disorder affecting multiple organ systems. Vascular complications, such as venous thromboembolism (VTE), are highly prevalent, affecting around 50% of individuals diagnosed with BD. This study aimed to identify potential biomarkers for VTE in BD patients. Three microarray datasets (GSE209567, GSE48000, GSE19151) were retrieved for analysis. Differentially expressed genes (DEGs) associated with VTE in BD were identified using the Limma package and weighted gene co-expression network analysis (WGCNA). Subsequently, potential diagnostic genes were explored through protein–protein interaction (PPI) network analysis and machine learning algorithms. A receiver operating characteristic (ROC) curve and a nomogram were constructed to evaluate the diagnostic performance for VTE in BD patients. Furthermore, immune cell infiltration analyses and single-sample gene set enrichment analysis (ssGSEA) were performed to investigate potential underlying mechanisms. Finally, the efficacy of listed drugs was assessed based on the identified signature genes. The limma package and WGCNA identified 117 DEGs related to VTE in BD. A PPI network analysis then selected 23 candidate hub genes. Four DEGs (E2F1, GATA3, HDAC5, and MSH2) were identified by intersecting gene sets from three machine learning algorithms. ROC analysis and nomogram construction demonstrated high diagnostic accuracy for these four genes (AUC: 0.816, 95% CI: 0.723–0.909). Immune cell infiltration analysis revealed a positive correlation between dysregulated immune cells and the four hub genes. ssGSEA provided insights into potential mechanisms underlying VTE development and progression in BD patients. Additionally, therapeutic agent screening identified potential drugs targeting the four hub genes. This study employed a systematic approach to identify four potential hub genes (E2F1, GATA3, HDAC5, and MSH2) and construct a nomogram for VTE diagnosis in BD. Immune cell infiltration analysis revealed dysregulation, suggesting potential macrophage involvement in VTE development. ssGSEA provided insights into potential mechanisms underlying BD-induced VTE, and potential therapeutic agents were identified.

Abstract A climatology of stratospheric gravity waves (SGWs) induced by tropical cyclones (TC-SGWs) is necessary for stratospheric aviation safety and accurate numerical weather prediction. Few previous works have characterized the climatology of TC-SGWs, and the relative importance of the source and background wind for TC-SGWs has not been clearly established. Here we present the distribution of TC-SGWs formed over the northwest Pacific Ocean based on 30 years of ERA5 reanalysis data. Using explainable artificial intelligence, we found the background wind in the lower stratosphere to be more important than TCs in controlling the distribution pattern of TC-SGWs. The background wind shear can influence the direction of TC-SGW propagation by refraction and filtering, which influences the distribution pattern of the TC-SGWs. The TC intensity only influences the TC-SGW intensity. Our results provide information on TC-SGW hotspots and suggest the importance of the background wind shear.

Objective For precise and minimally invasive treatment of ossification of the posterior longitudinal ligament of the cervical spine, the lifting segment is minimized, anterior controllable antedisplacement and fusion (ACAF) was refined and improved. In addition, the development of appropriate surgical procedures for the ossification of each segment was rarely reported. Therefore, this study aimed to compare the efficacy and safety of hybrid anterior controlled antedisplacement fusion (Hybrid ACAF) with laminoplasty for multilevel ossification of the posterior longitudinal ligament (OPLL). Methods Between May 2018 and May 2021, 70 patients with multilevel OPLL were divided into a hybrid ACAF group and a laminoplasty group according to surgical methods. All patients were followed up for at least 1 year. Japanese Orthopaedic Association (JOA) score and recovery rate (JOARR), (VAS, NDI) score and C2–C7 Cobb angle, the sagittal vertical axis of the neck (SVA), and complications (cerebrospinal fluid leakage, C5 paralysis, etc.) were compared between the two groups by t test or non‐parametric test. Results The operation time of hybrid ACAF was longer. C5 paralysis and axial pain were more common in the laminoplasty group, while dysphagia and hoarseness were more common in the hybrid ACAF group. At the last follow‐up, the hybrid ACAF group had better recovery and maintenance of cervical lordosis and sagittal plane balance and a higher JOA score and recovery rate than the laminoplasty group. Conclusions Hybrid ACAF can reduce the number of vertebral bodies and expand the decompression range, which is safe, effective, and tailored to local conditions. Compared with laminoplasty, hybrid ACAF is a precise alternative for patients with OPLL.

Abstract Background EEG reactivity is a predictor for neurological outcome in comatose patients after cardiac arrest (CA); however, its application is limited by variability in stimulus types and visual assessment. We aimed to evaluate the prognostic value of the quantitative analysis of EEG reactivity induced by standardized electrical stimulation and for early prognostication in this population. Methods This prospective observational study recruited post-CA comatose patients in Xuanwu Hospital, Capital Medical University (Beijing, China) between January 2016 and June 2023. EEG reactivity to electrical or traditional pain stimulation was randomly performed via visual and quantitative analysis. Neurological outcome within 6 months was dichotomized as good (Cerebral Performance Categories, CPC 1–2) or poor (CPC 3–5). Results Fifty-eight post-CA comatose patients were admitted, and 52 patients were included in the final analysis, of which 19 (36.5%) had good outcomes. EEG reactivity induced with the electrical stimulation had superior performance to the traditional pain stimulation for good outcome prediction (quantitative analysis: AUC 0.932 vs. 0.849, p = 0.048). When using the electrical stimulation, the AUC of EEG reactivity to predict good outcome by visual analysis was 0.838, increasing to 0.932 by quantitative analysis (p = 0.039). Comparing to the traditional pain stimulation by visual analysis, the AUC of EEG reactivity for good prognostication by the electrical stimulation with quantitative analysis was significantly improved (0.932 vs. 0.770, p = 0.004). Conclusions EEG reactivity induced by the standardized electrical stimulation in combination with quantitative analysis is a promising formula for post-CA comatose patients, with increased predictive accuracy.

Abstract Tree-based machine learning algorithms, such as random forest, have emerged as effective tools for estimating fine particulate matter (PM2.5) from satellite observations. However, they typically have unchanged model structures and configurations over time and space, and thus may not fully capture the spatiotemporal variations in the relationship between PM2.5 and predictors, resulting in limited accuracy. Here, we propose geographically and temporally weighted tree-based models (GTW-Tree) for remote sensing of surface PM2.5. Unlike traditional tree-based models, GTW-Tree models vary by time and space to simulate the variability in PM2.5 estimation, and they can output variable importance for every location for the deeper understanding of PM2.5 determinants. Experiments in China demonstrate that GTW-Tree models significantly outperform the conventional tree-based models with predictive error reduced by >21%. The GTW-Tree-derived time-location-specific variable importance reveals spatiotemporally varying impacts of predictors on PM2.5. Aerosol optical depth (AOD) contributes largely to PM2.5 estimation, particularly in central China. The proposed models are valuable for spatiotemporal modeling and interpretation of PM2.5 and other various fields of environmental remote sensing.

Abstract Over the years, obesity has become more commonplace and has had a substantial impact on several medical specialties, including reproductive medicine. The potential correlation between the visceral adiposity index (VAI) and infertility has yet to be determined. Women between the ages of 18 and 45 were included in this cross-sectional study, which was conducted as part of the National Health and Nutrition Examination Survey (NHANES) between 2015 and 2020. Three tertiles were used to group VAI levels. Subgroup analysis and weighted binary logistic regression were employed to investigate the independent relationship between VAI and infertility. Smooth curve fitting was used to explore nonlinear relationships. This cross-sectional study followed the criteria of the STROBE guidelines. Of the 1231 participants, 127 were infertile women aged 18–45 years. A higher VAI was associated with a higher prevalence of infertility (OR = 1.22, 95% CI:1.03–1.45), which remained consistent across all subgroups (p > 0.05 for all interactions). We demonstrated a positive nonlinear association between VAI and infertility using a smooth curve fit. A higher visceral adiposity index level is positively correlated with a higher incidence of infertility among women in the United States. Women who are infertile can be identified using the visceral obesity index, and controlling visceral obesity may help lower the chances of becoming infertile.

Abstract Liver cancer is one of the most common malignant tumors worldwide. Although some progress has been made in the diagnosis and treatment of Hepatocellular carcinoma (HCC), the diagnosis and treatment of HCC is still facing great challenges because of the high mortality rate and poor prognosis of HCC. The purpose of this study was to explore the relationship between adhesion-regulating molecule1 (ADRM1), and liver cancer, and the relationship between prognoses. ADRM1 is highly expressed in tumors and is closely associated with the prognosis of patients with liver cancer. In our previous study, we found that ADRM1 was highly expressed in HCC and was closely related to tumor immune and immune checkpoint levels in HCC. We validated the immune expression of ADRM1 in liver cancer cells using flow cytometry. In hepatocellular carcinoma tissues, miR-891a-5p regulates ADRM1. Upregulation of miR-891a-5p upregulates ADRM1, and downregulation of miR-891a-5p downregulates ADRM1. It is suggested that ADRM1 plays a key role in the occurrence and development of hepatocellular carcinoma. This study is expected to provide new ideas for the research and development of anti-HCC drugs targeting miR-891a-5p/ADRM1. However, further trials are needed to confirm these results and explore the actual results in patients with HCC.

Abstract With the high incidence of urogenital tumors worldwide, urinary system tumors are among the top 10 most common tumors in men, with prostate cancer ranking first and bladder cancer fourth. Patients with resistant urogenital tumors often have poor prognosis. In recent years, researchers have discovered numerous specific cancer antigens, which has led to the development of several new anti-cancer drugs. Using protein analysis techniques, researchers developed immune checkpoint inhibitors (ICIs) and antibody-conjugated drugs (ADCs) for the treatment of advanced urogenital tumors. However, tumor resistance often leads to the failure of monotherapy. Therefore, clinical trials of the combination of ICIs and ADCs have been carried out in numerous centers around the world. This article reviewed phase 2 and 3 clinical studies of ICIs, ADCs, and their combination in the treatment of urogenital tumors to highlight safe and effective methods for selecting individualized therapeutic strategies for patients. ICIs activate the immune system, whereas ADCs link monoclonal antibodies to toxins, which can achieve a synergistic effect when the two drugs are combined. This synergistic effect provides multiple advantages for the treatment of urogenital tumors.

Abstract Background With the rapid development of perinatal medicine and neonatal resuscitation technology, neonatal mortality gradually reduces, but sepsis is still a neonatal critical illness and an important cause of death. The onset of sepsis in premature infants is insidious, and the clinical symptoms lack of specificity. The available laboratory tests exhibit limited sensitivity and specificity for diagnosis, and there is a certain degree of time lag. Therefore, it is particularly important to find a method for early detection of severe infection in premature infants. Main body Sepsis is the third leading cause of death with poor prognosis in infants. Early and accurate identification of sepsis are particularly important. Heart rate variability may present before clinical symptoms of sepsis. The study is to summarize the available data on the relationship between heart rate variability and development of sepsis in early infants. We searched six database, PubMed, Web of Science, Embase, Cochrane Library, Wanfang, and CNKI, using the following terms for our search strategy (Infants, Newborn) OR (Newborn Infant) OR (Newborn Infants) OR (Newborns) OR (Newborn) OR (Neonate) OR (Neonates) AND (Sepsis) OR (Bloodstream Infection) OR (Bloodstream Infections) OR (Pyemia) OR (Pyemias) OR (Pyohemia) OR (Pyohemias) OR (Pyaemia) OR (Pyaemias) OR (Septicemia) OR (Septicemias) OR (Blood Poisoning) OR (Blood Poisonings) OR (Severe Sepsis) OR (Sepsis, Severe) AND (Heart Rate Variability). Premature infants would experience the reduction in heart rate variability before clinical symptoms of sepsis present. Conclusion The application of heart rate variability, a noninvasive monitoring method, to the identification and diagnosis of sepsis in premature infants can enable clinicians to identify, diagnose, and treat children with sepsis early, thereby reducing the mortality of premature infants and neurological damage.

ABSTRACT Lung cancer accounts for the large majority of cancer incidence and mortality worldwide for decades. The dysbiotic microbiome and its metabolite secretions in the gut have been regarded as the dominant biological factors in oncogenesis, development, and progression, adding probiotic components of which have come to be potential therapeutic regimes. However, there still exists little knowledge about whether probiotic microorganisms in lower airways inhibit lung cancer by lung microenvironment remodulation. In this study, we performed bioinformatics analysis from previous sequencing data and specific microbiome databases to identify the potent protective microbes in lower airways, followed by bacterial cultivation and morphological verifications in vitro. We found that Paenibacillus odorifer was correlated closely with the anti-tumorous by-product acetic acid in lower respiratory tract. Additionally, the enrichment of this microorganism in the health, rather than in lung neoplasms from public data sets, further confirmed its protective activity in preserving pulmonary homeostasis. Colony cultivation of this strain and targeted metabolite analysis indicated that Paenibacillus odorifer proliferation was weakened at 37°C but lasted longer than it did at the optimal temperature. And performing as a candidate origin of acetic acid, this strain was liable to inhibit the growth of lung cancer cells in time- and dose-dependent approaches which was validated by colony formation assays. These results suggested that Paenibacillus odorifer functions as a candidate probiotic in lower airways to restrict lung cancer cell growth by releasing protective molecules, indicating a potential preventive microbial strategy.IMPORTANCEVarious types of microorganisms in lower respiratory tracts protect local homeostasis against oncogenesis. Although extensive efforts engaged in gut microbiome-mediated pulmonary carcinogenesis, emerging evidence suggested the crucial role of microbial metabolites from respiratory tracts in modulating carcinogenesis-related host inflammation and DNA damage in lung cancer, which was still not fully understood in lower respiratory tract microbes and its metabolite-mediated microecological environment homeostasis in preventing or alleviating lung cancer. In this study, we analyzed the lower respiratory tract microbiome and SCFAs expression among different lung segments from the same participants, further identifying that Paenibacillus odorifer was correlated closely with anti-tumorous by-product, acetate acid in lower respiratory tract by multi-omics analysis. And previous experiments showed this strain could inhibit the growth of lung cancer cells in vitro. These findings indicated that Paenibacillus odorifer in lower respiratory tracts might perform as a candidate probiotic against lung carcinogenesis by releasing protective factor acetate, which further presented a promising diagnostic and interventional approach in clinical settings of lung cancer.

Summary: Background: Accurate staging of liver fibrosis (LF) is essential for clinical management in chronic liver disease. While non-contrast MRI (NC-MRI) yields valuable information for liver assessment, its effectiveness in predicting LF remains underexplored. This study aimed to develop and validate artificial intelligence (AI)-powered models utilizing NC-MRI for staging LF. Methods: A total of 1726 patients from Shengjing Hospital of China Medical University, registered between October 2003 and October 2022, were retrospectively collected, and divided into development (n = 1208) and internal test (n = 518) cohorts. An external test cohort consisting of 337 individuals from six centers, registered between June 2015 and November 2022, were also included. All participants underwent NC-MRI (T1-weighted imaging, T1WI; and T2-fat-suppressed imaging, T2FS) and liver biopsies. Two classification models (CMs), named T1 and T2FS, were trained on respective image types using 3D contextual transformer networks and evaluated on both test cohorts. Additionally, three CMs—Clinic, Image, and Fusion—were developed using clinical features, T1 and T2FS scores, and their integration via logistic regression. Classification effectiveness of CMs was assessed using the area under the receiver operating characteristic curve (AUC). A comparison was conducted between the optimal models (OMs) with highest AUC and other methods (transient elastography, five serum biomarkers, and six radiologists). Findings: Fusion models (i.e., OM) yielded the highest AUC among the CMs, achieving AUCs of 0.810 for significant fibrosis, 0.881 for advanced fibrosis, and 0.918 for cirrhosis in the internal test cohort, and 0.808, 0.868, and 0.925, respectively, in the external test cohort. The OMs demonstrated superior performance in AUC, significantly surpassing transient elastography (only for staging ≥ F2 and ≥ F3 grades), serum biomarkers, and three junior radiologists for staging LF. Radiologists, with the aid of the OMs, can achieve a higher AUC in LF assessment. Interpretation: AI-powered models utilizing NC-MRI, including T1WI and T2FS, accurately stage LF. Funding: National Natural Science Foundation of China (No. 82071885); General Program of the Liaoning Provincial Department of Education (LJKMZ20221160); Liaoning Province Science and Technology Joint Plan (2023JH2/101700127); the Leading Young Talent Program of Xingliao Yingcai in Liaoning Province (XLYC2203037).

Distributed optical fiber sensors with the capability of dynamic temperature and strain discrimination can be used for various applications, including perimeter security, structural health monitoring, and seismic sensing, as they can access the tolerance of the structures and sites to natural hazards, such as earthquakes, fires, and overflows. Here, we propose a hybrid Brillouin/Rayleigh sensing system that combines distributed phase matching measurement via Brillouin dynamic grating and inhomogeneity-induced Rayleigh scatting in polarization-maintaining fiber. Due to the high birefringence of polarization-maintaining fibers imposed by the stress-rods, the detection of Brillouin dynamic gratings results in opposite signs of spectral shifts under the changed temperature and strain, giving a high discrimination accuracy. In addition, the usage of a single chirped probe pulse signal allows a single end detection system for Rayleigh of the probe wave and idler wave from stimulated Brillouin scattering enhanced four-wave mixing, which simplified the sensing system significantly. Driven by the high spatial resolution ability of distributed phase matching measurement without phonon lifetime limitation, an intensity-based analysis approach for Rayleigh traces is carried out to resolve the external perturbation applied in a short section that is smaller than the spatial distinctness associated pulse width. In the proof-of-concept experiments, a simultaneous strain and temperature variation within a 40 cm fiber section are successfully discriminated with noise equivalent discrimination errors for strain and temperature of 112.2 nɛ and 10.9 m °C. The spatial resolution here is 2 m, and the maximum system’s sampling rate is up to 100 kHz without average, corresponding to the sensing distance of 1 km.