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Articular cartilage has limited self-healing ability, resulting in injuries often evolving into osteoarthritis (OA), which poses a significant challenge in the medical field. Although some treatments exist to reduce pain and damage, there is a lack of effective means to promote cartilage regeneration. Reactive Oxygen Species (ROS) have been found to increase significantly in the OA micro-environment. They play a key role in biological systems by participating in cell signaling and maintaining cellular homeostasis. Abnormal ROS expression, caused by internal and external stimuli and tissue damage, leads to elevated levels of oxidative stress, inflammatory responses, cell damage, and impaired tissue repair. To prevent excessive ROS accumulation at injury sites, biological materials can be engineered to respond to the damaged microenvironment, release active components in an orderly manner, regulate ROS levels, reduce oxidative stress, and promote tissue regeneration. Hydrogels have garnered significant attention due to their excellent biocompatibility, tunable physicochemical properties, and drug delivery capabilities. Numerous antioxidant hydrogels have been developed and proven effective in alleviating oxidative stress. This paper discusses a comprehensive treatment strategy that combines antioxidant hydrogels with existing treatments for OA and explores the potential applications of antioxidant hydrogels in cartilage tissue engineering.

Chimeric antigen receptor T (CAR-T) cell therapy is a new treatment for cancers, but reports on curing immune-related skin diseases are limited. We report a case of successful CAR-T-cell therapy in a patient with refractory/relapsed diffuse large B-cell lymphoma (R/R DLBCL) who was incidentally cured of chronic generalized plaque psoriasis. The patient, a 65-year-old male who had a known history of psoriasis for 45 years, did not receive immunotherapy for psoriasis during this period. Imaging, molecular biology and immunology diagnostics confirmed DLBCL. After several weeks of standard-dose R-CHOP chemotherapy, the patient achieved partial remission, but according to CT, the patient relapsed, and there was no significant improvement in her psoriasis symptoms. Subsequently, the patient was enrolled in the CD19 CAR-T-cell therapy group. Four weeks after CAR-T-cell infusion, the patient’s abdominal pain disappeared, and there was a significant improvement in overall skin lesions. One year later, follow-up results indicated complete remission of R/R DLBCL (confirmed by PET-CT), with only minimal residual psoriatic skin lesions limited to the patient’s neck. The results of using CAR-T-cell therapy to achieve an incidental cure for psoriasis highlight the potential for exploring cell-based therapies for complex autoinflammatory skin diseases.

The present study investigated the effects of water extracts of Artemisia annua L. (WEAA) on rumen immune and antioxidative indexes, fermentation parameters and microbial diversity in lambs. A total of 32 3-month-old Dorper × Han female lambs having comparable body weights (24±0.09 kg) were selected and were randomly assigned to four treatments, with eight repetitions for each treatment. The basal diet, consisting of 45% concentrate and 55% forage, was solely provided to the control group. For the other treatment groups, the basal diet was supplemented with WEAA at dosages of 500, 1000, and 1500 mg/kg diet, respectively. Rumen tissue samples were collected for the analysis of immune and antioxidative parameters, as well as related gene expression. Rumen fluid samples were collected to assess rumen fermentation parameters on days 30 and 60 and to evaluate the microbiota on day 60. Results showed that WEAA supplementation linearly or quadratically increased the content of sIgA, IL-4, IL-2 and the gene expression level of MyD88, IκB-α, IL-4, COX-2, iNOS in rumen tissue (p < 0.05), as well as the bacteria negatively associated with IL-6 (g_ [Eubacterium]_cellulosolvens_group). Furthermore, the addition of WEAA linearly or quadratically increased rumen T-SOD, GSH-Px (p < 0.05) and the gene expression level of Nrf2, SOD2, GSH-Px, HO-1 (p < 0.05), and decreased the rumen concentration of malondialdehyde (MDA) and gene expression level of Keap1 (p < 0.05), as well as the bacteria positively associated with T-AOC, T-SOD and GSH-Px (g_Lachnospiraceae_NK3A20_group, g_Saccharofermentans, g__Marvinbryantia, g_unclassified_f_Eggerthellaceae). The supplementation of WEAA caused the concentration of microprotein (MCP), total volatile fatty acids (TVFA), propionate to increase either linearly or quadratically, while reducing the concentration of NH3-N and the acetate/propionate ratio (A:P) in rumen fluid (p < 0.05). The addition of WEAA linearly or quadratically increased the abundance of Actinobacteriota, Cyanobacteria and Lachnospiraceae_NK3A20_group (p < 0.10), and g__Lachnospiraceae_NK3A20_group, g_Saccharofermentans, g_Marvinbryantia, g_Bifidobacterium were significantly abundant as specific microflora in the 1000 mg/kg WEAA supplementation group. In conclusion, dietary inclusion of 1000 mg/kg WEAA improved the rumen immune function, antioxidant status, rumen fermentation, and composition of rumen microbes in lambs.

IntroductionThis cross-sectional study examined the mechanisms underlying adolescent math achievement by investigating the relationship between parents’ rearing styles (including different dimensions of rearing style) and adolescent self-control, math anxiety, and math achievement based on the ecological systems theory.MethodA total of 584 junior high school students (M age = 12.52) completed the Parenting Style Questionnaire, Self-control Scale, and Math Anxiety Rating Scale and provided their math test scores.ResultsThe rearing styles of both fathers and mothers directly predicted adolescents’ math achievement. Maternal rearing style indirectly predicted adolescents’ math achievement through their self-control and math anxiety; however, the indirect effect of paternal rearing style on adolescents’ math achievement was not significant. After distinguishing the three dimensions of rearing styles, we found that paternal emotional warmth can increase adolescents’ self-control, while maternal emotional warmth can reduce adolescents’ self-control. Further, paternal overprotectiveness can directly and positively predict adolescents’ math achievement, while maternal rejection and overprotectiveness can positively predict adolescents’ math achievement. None of the three dimensions of rearing styles can predict math achievement through adolescents’ self-control; however, they can predict math achievement indirectly through adolescents’ math anxiety and the chain-mediation of adolescents’ self-control and math anxiety.DiscussionOur results suggest both commonalities and differences in how paternal and maternal rearing styles, along with their three dimensions (emotional warmth, rejection, overprotection), predict adolescent math achievement. These findings highlight the importance of paternal and maternal rearing styles on adolescents’ math achievement and underscore the need to examine them separately to better understand their impact.

Gibberellin 20-oxidases (GA20oxs) are multifunctional enzymes involved in regulating gibberellin (GA) biosynthesis and controlling plant growth. We identified and characterized the GA20ox1 gene in a plant height mutant of Sophora davidii, referred to as SdGA20ox1. This gene was expressed in root, stem, and leaf tissues of the adult S. davidii plant height mutant, with the highest expression observed in the stem. The expression of SdGA20ox1 was regulated by various exogenous hormones. Overexpression of SdGA20ox1 in Arabidopsis resulted in significant elongation of hypocotyl and root length in seedlings, earlier flowering, smaller leaves, reduced leaf chlorophyll content, lighter leaf color, a significant increase in adult plant height, and other phenotypes. Additionally, transgenic plants exhibited a substantial increase in biologically active endogenous GAs (GA1, GA3, and GA4) content, indicating that overexpression of SdGA20ox1 accelerates plant growth and development. Using a yeast two-hybrid (Y2H) screen, we identified two SdGA20ox1-interacting proteins: the ethylene receptor EIN4 (11430582) and the rbcS (11416005) protein. These interactions suggest a potential regulatory mechanism for S. davidii growth. Our findings provide new insights into the role of SdGA20ox1 and its interacting proteins in regulating the growth and development of S. davidii.

Soil nematodes are the most abundant soil metazoans, occupying multiple trophic levels in the soil food web and playing an important role in soil function. Research on the biogeographic distribution patterns of soil nematode communities and their drivers has received greater attention. However, the distribution characteristics of soil nematode communities along the elevational gradient in the arid and semi-arid regions of Northwest China remain unclear. In this study, four elevational gradients (1750–1900, 1900–2100, 2100–2350 and 2350–2560 m) were established on Luoshan Mountain, Ningxia, an arid and semi-arid region in Northwest China, and soil nematodes in the soil layers of 0–10, 10–20 and 20–40 cm were investigated using the improved Baermann funnel method. The results revealed a monotonically decreasing trend in the total number of soil nematodes along the elevational gradient and soil layer depth, decreasing by 63.32% to 79.94% and 73.59% to 86.90%, respectively, while the interactions were not obvious. A total of 1487 soil nematodes belonging to 27 families and 32 genera were identified across the elevational gradient, with Helicotylenchus as the dominant genus, accounting for 10.43% of the total number of nematodes, and bacterivore nematodes as the main trophic groups, accounting for 32.39% to 52.55% of the relative abundance at each elevation, which increased with increasing elevation. Soil nematode community diversity, richness and maturity indices were relatively low at high elevation and decreased by 44.62%, 48% and 54.74%, respectively, with increasing soil layer depth at high elevations. Compared to low elevations, high-elevation soils experienced greater disturbance, reduced structural complexity and nutrient enrichment of the soil food web, and a shift in soil organic matter decomposition from bacterial to fungal pathways as elevation increased. Finally, redundancy analysis showed that soil pH, bulk density, soil moisture, soil organic carbon, available nitrogen, available phosphorus and available potassium were the main soil factors affecting the composition of soil nematode communities, which well explained the differences in nematode communities at different elevations and soil depths. This study can be used as basic information for further research on soil biota in this mountainous region, expanding our further understanding of the spatial ecology of soil nematodes in the arid and semi-arid mountain ecosystems.

The wound healing process involves communication among growth factors, cytokines, signaling pathways, and cells in the extracellular matrix, with growth factors acting as key regulators. Although stem cells can promote wound healing by secreting diverse growth factors, their therapeutic potential is hindered by poor survival and engraftment. Mimicking the stem cell-matrix interactions can improve stem cell survival, regulate their fate, and even enhance their paracrine effects. This study investigated the use of composite RGDmix hydrogel, which can support the survival and proliferation of human amniotic mesenchymal stem cells (hAMSCs), and effectively increase the expression of various growth factors, thereby promoting wound re-epithelialization, angiogenesis, and epidermal maturation. At last, the specific role of integrin αv and PI3K/AKT signaling pathways in the secretion of growth factors were examined by silencing them in vitro and in vivo. Results suggested that the RGDmix hydrogel improved the secretion of growth factors by hAMSCs through the RGDSP/integrin αv/PI3K/AKT axis, thereby enhancing the therapeutic effect in wound healing.

BackgroundAn increasing number of studies have turned their lens to the application of Artificial Intelligence (AI) in the diagnosis and treatment of colorectal cancer (CRC).ObjectiveTo clarify and visualize the basic situation, research hotspots, and development trends of AI in the diagnosis and treatment of CRC, and provide clues for research in the future.MethodsOn January 31, 2024, the Web of Science Core Collection (WoSCC) database was searched to screen and export the relevant research published during 2004-2023, and Cite Space, VoSviewer, Bibliometrix were used to visualize the number of publications, countries (regions), institutions, journals, authors, citations, keywords, etc.ResultsA total of 2715 pieces of literature were included. The number of publications grew slowly until the end of 2016, but rapidly after 2017, till to the peak of 798 in 2023. A total of 92 countries, 3997 organizations, and 15,667 authors were involved in this research. Chinese scholars released the highest number of publications, and the U.S. contributed the highest number of total citations. As to authors, MORI, YUICHI had the highest number of publications, and WANG, PU had the highest number of total citations. According to the analysis of citations and keywords, the current research hotspots are mainly related to “Colonoscopy”, “Polyp Segmentation”, “Digital Pathology”, “Radiomics”, “prognosis”.ConclusionResearch on the application of AI in the diagnosis and treatment of CRC has made significant progress and is flourishing across the world. Current research hotspots include AI-assisted early screening and diagnosis, pathology, and staging, and prognosis assessment, and future research is predicted to put weight on multimodal data fusion, personalized treatment, and drug development.

BackgroundWe conducted a large-scale epidemiological analysis to investigate the associations between systemic inflammation markers and heart failure (HF). Our aim is to identify potential biomarkers for early detection of HF.MethodsA cross-sectional study was conducted using data from the National Health and Nutrition Examination Survey. We investigated the associations between five systemic inflammation markers (neutrophil to lymphocyte ratio [NLR], platelet to lymphocyte ratio [PLR], systemic immune inflammation index [SII], system inflammation response index [SIRI], and aggregate index of systemic inflammation [AISI]) and the risk of HF.ResultsThe prevalence rates of HF exhibited a gradual increase across increasing logNLR, logPLR, logSII, logSIRI, and logAISI tertiles. Compared to those in the highest tertiles of logNLR, logSII, logSIRI, and logAISI had a 1.579-fold, 1.341-fold, 1.956-fold, and 1.499-fold increased risk of HF compared to those in the lowest tertile respectively. Conversely, there was no significant correlation between logPLR and HF risk among subjects in the highest tertile. The restricted cubic splines (RCS) analysis revealed a non-linear relationship between the elevation of systemic inflammation markers and HF prevalence. Specifically, a per standard deviation increase in any of these variables is associated with a respective 45%, 29%, 28%, 44% and 29% increase in HF prevalence. The receiver operating characteristic (ROC) analysis demonstrated favorable sensitivity and specificity of these systemic inflammation markers in detecting the presence of HF.ConclusionOur cross-sectional study demonstrates significant positive correlations between the NLR, PLR, SII, SIRI, and AISI with the incidence of HF.

IntroductionRecently, a novel type of metabolic-regulated cell demise titled disulfidptosis has been discovered. Studies have demonstrated its importance in immune responses against cancer and its impact on the proliferation of cancer cells. Nonetheless, the precise mechanism and roles of disulfidptosis are not fully understood, particularly regarding the prognosis for individuals with uterine corpus endometrial carcinoma (UCEC).MethodsIn this research, a distinctive disulfidptosis pattern was developed in UCEC, and by utilizing Non-negative Matrix Factorization (NMF) on 23 disulfidptosis related genes within the TCGA database, 3 distinct subgroups were distinguished. To collect data, we acquired gene expression profiles, somatic mutation information, copy number variation data, and corresponding clinical data from the TCGA and GEO database, specifically from UCEC patients. Cell line experiments and immunohistochemical (IHC) staining were conducted to validate the role of the LRPPRC in proliferation, migration and invasion.ResultsThe genetic features and immune microenvironment of these subgroups were examined. It is worth mentioning that these subgroups offer important insights into comprehending the tumor microenvironment (TME) and the response of patients to immunotherapy and chemotherapy. Moreover, a disulfidptosis model was developed and validated, demonstrating a high level of accuracy in predicting the prognosis and outcomes of immunotherapy in UCEC patients. Additionally, a novel biomarker, LRPPRC, was identified, which can server as a promising predictor for forecasting prognosis in UCEC patients, with validation through tissue microarray staining and cell line experiments.DiscussionThis study has designed a classification system and a disulfidptosis model for UCEC, in addition to identifying a new biomarker, LRPPRC, for UCEC. These advancements serve as reliable and positive indicators for predicting outcomes and the efficacy of immunotherapy for each UCEC patient.

ObjectiveTo investigate the effects of Plyometric Training (PT) on the athletic performance of youth basketball players (age 5–17.99) and to provide a theoretical basis for applying PT in basketball training practice.MethodPubMed, Web of Science, Cochrane Library, EBSCO and other data platforms were searched, and Meta-analysis was performed using STATA 16.0 software.ResultA total of 24 studies were included, with a sample size of 738 participants. The results showed that PT improved jumping, linear sprinting, change of direction (COD) speed, and balance in youth basketball players (p < 0.05) but did not significantly improve lower limb strength (p > 0.05). The results of subgroup analyses showed that:1) Regarding the effect of PT on different aspects of athletic performance, enhancements were found for vertical jump, 5–10 m, 20–30 m sprinting ability, velocity-oriented and force-oriented COD speed, and dynamic balance ability of youth basketball players. 2) When analyzing different participant subgroups, basketball players aged 5 to 10.99 and 11–14.99 years appeared to improve their jump, sprinting ability, and COD speed through PT training, whereas no improvements in sprinting ability and COD speed were found for players aged 15 to 17.99. Male and female youth basketball players could improve their jumping through PT, in contrast, straight-line sprinting ability and COD speed were significantly improved only by male youth basketball players, and balance ability was significantly improved only by female youth basketball players. 3) Regarding different training protocols, high-frequency PT (>2 times/week) with a low-volume (jumping ≤150 times/week) and Single-type PT (one specific movement) improved only jumping ability. In contrast, low-frequency PT (1–2 times/week) with a high-volume (jumping >150 times/week) and mixed-type PT (varied jumping drills) protocols significantly improved jumping, linear sprinting, COD speed, and balancing abilities.ConclusionPT can enhance the jumping, linear sprinting, COD speed, and balance of youth basketball players, but it does not affect lower limb strength. It is recommended that coaches make full use of the training-sensitive periods of young athletes by incorporating low-frequency, high-volume, and mixed-type PT into their regular training routines over the long term.

BackgroundIn this retrospective study, we aimed to identify key risk factors and establish an interpretable model for HCC with a diameter ≥ 5 cm using Lasso regression for effective risk stratification and clinical decision-making.MethodsIn this study, 843 patients with advanced hepatocellular carcinoma (HCC) and tumor diameter ≥ 5 cm were included. Using Lasso regression to screen multiple characteristic variables, cox proportional hazard regression and random survival forest models (RSF) were established. By comparing the area under the curve (AUC), the optimal model was selected. The model was visualized, and the order of interpretable importance was determined. Finally, risk stratification was established to identify patients at high risk.ResultLasso regression identified 8 factors as characteristic risk factors. Subsequent analysis revealed that the lasso-cox model had AUC values of 0.773, 0.758, and 0.799, while the lasso-RSF model had AUC values of 0.734, 0.695, and 0.741, respectively. Based on these results, the lasso-cox model was chosen as the superior model. Interpretability assessments using SHAP values indicated that the most significant characteristic risk factors, in descending order of importance, were tumor number, BCLC stage, alkaline phosphatase (ALP), ascites, albumin (ALB), and aspartate aminotransferase (AST). Additionally, through risk score stratification and subgroup analysis, it was observed that the median OS of the low-risk group was significantly better than that of the middle- and high-risk groups.ConclusionWe have developed an interpretable predictive model for middle and late HCC with tumor diameter ≥ 5 cm using lasso-cox regression analysis. This model demonstrates excellent prediction performance and can be utilized for risk stratification.

ObjectiveThis study aimed to investigate the efficacy, long-term prognosis and safety of combining chemotherapy with regorafenib and immune checkpoint inhibitors as first-line treatment for patients with advanced biliary tract carcinoma (BTC).MethodsIn this single arm phase II trial, twenty-nine patients with advanced BTC were included, all of whom received gemcitabine-based chemotherapy combined with regorafenib and immune checkpoint inhibitors as the first-line treatment. And the study analyzed anti-tumor efficacy, long-term prognosis, and adverse reactions.ResultsAmong the patients, 0 patient achieved complete response, 18 patients (62.1%) achieved partial response, 8 patients (27.6%) had stable disease, and 3 patients (10.3%) experienced progressive disease. The corresponding objective response rate (ORR) was 18/29 (62.1%), and the disease control rate (DCR) was 26/29 (89.7%). The median overall survival (OS) was 16.9 months (95% confidence interval [CI]: 12.0 -21.8) and the median progress free survival (PFS) was 10.2 months (95% CI: 7.8- 12.6). The 1-year OS and PFS were 65% (95% CI: 0.479-0.864) and 41% (95% CI: 0.234-0.656), respectively. The incidence of adverse reactions was 27/29 (93.1%), and the incidence of grade III/IV adverse reactions was 5/29 (17.2%).ConclusionThe combination of chemotherapy, regorafenib, and immune checkpoint inhibitors as a first-line treatment for patients with advanced BTC may has good anti-tumor efficacy without causing serious adverse reactions, and can significantly improve the long-term prognosis.

Glucocorticoids (GCs) are steroid hormones fundamental to the body’s normal physiological functions and are pivotal in fetal growth and development. During gestation, the mother’s cortisol concentration (active GCs) escalates to accommodate the requirements of fetal organ development and maturation. A natural placental GCs barrier, primarily facilitated by 11β hydroxysteroid dehydrogenase 2, exists between the mother and fetus. This enzyme transforms biologically active cortisol into biologically inactive corticosterone, thereby mitigating fetal GCs exposure. However, during pregnancy, the mother may be vulnerable to adverse factor exposures such as stress, hypoxia, caffeine, and synthetic GCs use. In these instances, maternal serum GCs levels may surge beyond the protective capacity of the placental GCs barrier. Moreover, these adverse factors could directly compromise the placental GCs barrier, resulting in excessive fetal exposure to GCs. It is well-documented that prenatal GCs exposure can detrimentally impact the offspring’s cardiovascular system, particularly in relation to blood pressure, vascular function, and heart function. In this review, we succinctly delineate the alterations in GCs levels during pregnancy and the potential mechanisms driving these changes, and also analyze the possible causes of prenatal GCs exposure. Furthermore, we summarize the current advancements in understanding the adverse effects and mechanisms of prenatal GCs exposure on the offspring’s cardiovascular system.

This paper presents an innovative approach for achieving rapid synchronization between two memristor chaotic circuits (MCCs), both with and without noise perturbations. The proposed adaptive control strategy effectively handles the uncertainty in control gains by adhering to predesigned update law. Additionally, this protocol is non-chattering and differentiable, avoiding the use of conventional discontinuous functions such as signum and absolute value functions. This method successfully mitigates the tremors caused by discontinuous functions. We derive two sufficient criteria using finite-time Lyapunov and stochastic finite-time Lyapunov stability methods. Numerical results validate the theoretical analysis and demonstrate the influence of noise intensity on convergence speed. Furthermore, the results have an application in image encryption transmission.

Dahongpao mother tree (Camellia sinensis (L.) O. Ktze) is a representative of Wuyi rock tea. Whether there is a difference in rhizosphere soil microbial diversity and function between asexually propagated cuttings of Dahongpao (PD) and the parent Dahongpao mother tree (MD) has not been reported. In this study, high throughput sequencing technology was used to analyze rhizosphere soil microbial diversity, functions and their relationship with soil available nutrients and enzyme activities in MD and PD. The results showed that available nitrogen, phosphorus and potassium contents and urease, protease, acid phosphatase and sucrase activities of rhizosphere soils in MD were significantly higher than those in PD. Both bacterial and fungal diversity were higher in rhizosphere soils in MD than in PD, and secondly, the bacterial community structure was less stable while the fungal community structure was more stable in PD compared to MD. There were significant differences between MD and PD tea tree rhizosphere soils in 6 genera of characteristic bacteria and 4 genera of characteristic fungi. The results of function and interaction effect analysis showed that the rhizosphere soil available nutrient content and enzyme activities in MD were significantly higher than those in PD, and their contributions mainly originated from Pirellula and Acidisphaera of characteristic bacteria and Alatospora of characteristic fungi. Secondly, MD maybe had a stronger ability to inhibit soil pathogens than PD, with the main contribution coming from Scopulariopsis and Tolypocladium of characteristic fungi. Overall, compared with PD, soil texture in MD was relatively better, and its soil nutrient cycling-related enzyme activities were stronger, which was more favorable to soil nutrient cycling and increased the available nutrient content of the soil, which in turn promoted the growth of tea trees. This study provides an important reference for the planting and management of tea tree cuttings and microbial regulation of tea tree growth.

IntroductionShortage and high turnover intention rate of physicians are concerning problems in China. Professional identity has been shown as an influential factor for physicians’ turnover intention. Enhancing physicians’ professional identity in their early phase of career, standardized residency training program (SRTP), may help reduce the turnover rate. This study aimed to investigate the current status of professional identity and explore its associated psychosocial factors among Chinese SRTP trainees, hoping to provide evidence in strengthening the available medical human resources in China.MethodsThe final sample was comprised of 2,267 Chinese SRTP trainees in this cross-sectional survey conducted from 9 March to 20 March in 2023. Descriptive statistics were calculated. Bivariate analyses and hierarchical multiple linear regression were used to analyze potential associated factors of Chinese SRTP trainees’ professional identity.ResultsThe average score of respondents’ professional identity was 47.68 (standard deviation, SD = 8.61). Results from hierarchical multiple linear regression analysis showed that being married (β = 0.066, p

IntroductionThe aboveground carbon storage (AGC) in forests serves as a crucial metric for evaluating both the composition of the forest ecosystem and the quality of the forest. It also plays a significant role in assessing the quality of regional ecosystems. However, current technical limitations introduce a degree of uncertainty in estimating forest AGC at a regional scale. Despite these challenges, remote sensing technology provides an accurate means of monitoring forest AGC. Furthermore, the implementation of machine learning algorithms can enhance the precision of AGC estimates. Lishui City, with its rich forest resources and an approximate forest coverage rate of 80%, serves as a representative example of the typical subtropical forest distribution in Zhejiang Province.MethodsTherefore, this study uses Landsat remote sensing images, employing backpropagation neural network (BPNN), random forest (RF), and categorical boosting (CatBoost) to model the forest AGC of Lishui City, selecting the best model to estimate and analyze its forest AGC spatiotemporal dynamics over the past 30 years (1989–2019).ResultsThe study shows that: (1) The texture information calculated based on 9×9 and 11×11 windows is an important variable in constructing the remote sensing estimation model of the forest AGC in Lishui City; (2) All three machine learning techniques are capable of estimating forest AGC in Lishui City with high precision. Notably, the CatBoost algorithm outperforms the others in terms of accuracy, achieving a model training accuracy and testing accuracy R2 of 0.95 and 0.83, and RMSE of 2.98 Mg C ha-1 and 4.93 Mg C ha-1, respectively. (3) Spatially, the central and southwestern regions of Lishui City exhibit high levels of forest AGC, whereas the eastern and northeastern regions display comparatively lower levels. Over time, there has been a consistent increase in the total forest AGC in Lishui City over the past three decades, escalating from 1.36×107 Mg C in 1989 to 6.16×107 Mg C in 2019.DiscussionThis study provided a set of effective hyperparameters and model of machine learning suitable for subtropical forests and a reference data for improving carbon sequestration capacity of subtropical forests in Lishui City.

With the introduction of China’s “Carbon Peaking Action Plan Before 2030,” the transformation of the power industry has released huge opportunities and potential. The DC distribution network can well-coordinate the contradiction between distributed power and grid access, fully develop the benefits of distributed energy, and become a new direction for the development of the power industry. However, the current traditional DC–DC converters have problems such as single-topology structure and low power density, which can only complete one-way transmission of energy; hence, the distributed energy cannot be fully utilized. Addressing the problem of distributed energy transfer, this paper is based on a three-port DC–DC converter for a low-voltage DC distribution network to realize energy transfer between the DC distribution network, distributed energy, and low-voltage load. First, the energy transfer modes of the three-port DC–DC converter are introduced. Combined with the converter topology and energy transfer mode, a simplified equivalent model of the converter is established. The voltage gain characteristics and frequency characteristics of this converter are studied. Furthermore, the effects of the excitation inductance to primary resonance inductance ratio parameter k and quality factor Q on the voltage gain characteristics of the converter are discussed. On this basis, the resonant cavity design of the converter is based on the optimal selection of parameters k and Q so that the converter can meet the voltage gain requirements in both forward and reverse operations. The simulation results under different loads verify the reasonableness of the resonant cavity component selection.

Background and aimsTranscatheter tricuspid valve replacement (TTVR) has recently emerged as a novel therapeutic approach for managing severe tricuspid regurgitation (TR). However, surgical tricuspid valve replacement (STVR) continues to be the predominant treatment modality. There are limited comparative data on both procedures. This study aimed to compare clinical and echocardiographic outcomes between patients who underwent mini-thoracotomy transatrial LuX-Valve TTVR and those who underwent STVR.MethodsThis study prospectively collected patients with severe TR who underwent TTVR (n = 29) or isolated STVR (n = 59) at Wuhan Union Hospital from 2019 to 2022. All TTVR patients received the LuX-Valve via a mini-thoracotomy and transatrial approach. The clinical and echocardiographic outcomes were compared at 30-day and one-year follow-ups.ResultsAt baseline, patients with LuX-Valve TTVR had higher surgical risk scores and a greater proportion of right ventricular dysfunction compared with STVR. In the early postoperative period, the STVR group had a greater decrease in right ventricular function. Hospital length of stay (LOS), intensive care unit LOS, total procedure time, and tracheal intubation time were shorter in the TTVR than in the STVR group. The incidence of postoperative paravalvular leaks was higher among patients who underwent TTVR. Compared to the STVR group, the pacemaker implantation rate was lower in the TTVR group. During follow-up, the peak tricuspid valve velocity and mean gradient in the TTVR group were consistently lower than those in the STVR group. There was similar mortality between TTVR and STVR at 30-day and one-year follow-ups.ConclusionsThe mini-thoracotomy transatria LuX-Valve TTVR has a higher incidence of paravalvular leaks and a lower rate of pacemaker implantation than STVR, with similar 30-day and one-year mortality rates. In some respects, mini-thoracotomy transatrial LuX-Valve TTVR may be a feasible and safe treatment option for specific populations, or it could potentially serve as an alternative therapy to supplement conventional STVR. Further follow-up is required to assess differences in long-term clinical outcomes and valve durability.

IntroductionSince their identification in 1974, circoviruses have caused clinicopathological diseases in various animal species, including humans. However, their origin, transmission, and genetic evolution remain poorly understood.MethodsIn this study, the genome sequences of circovirus were obtained from GenBank, and the Bayesian stochastic search variable selection algorithm was employed to analyzed the evolution and origin of circovirus.ResultsHere, the evolutionary origin, mode of transmission, and genetic recombination of the circovirus were determined based on the available circovirus genome sequences. The origin of circoviruses can be traced back to fish circovirus, which might derive from fish genome, and human contributes to transmission of fish circovirus to other species. Furthermore, mosquitos, ticks, bats, and/or rodents might play a role as intermediate hosts in circovirus intra- and inter-species transmission. Two major lineages (A and B) of circoviruses are identified, and frequent recombination events accelerate their variation and spread. The time to the most recent common ancestor of circoviruses can be traced back to around A.D. 600 and has been evolving at a rate of 10-4 substitutions site-1 year-1 for a long time.DiscussionThese comprehensive findings shed light on the evolutionary origin, population dynamics, transmission model, and genetic recombination of the circovirus providing valuable insights for the development of prevention and control strategies against circovirus infections.

The transformation of energy structure has brought about new changes in the power system, and the environmentally friendly gas switchgear with the goal of low carbon and environmental protection has been widely spread and applied, but due to its short application time and the accumulation of related research, it continues to carry out life prediction to improve the related operation and maintenance system. The article proposes the environmental protection gas switchgear data processing technology based on data enhancement technology, proposes the environmental protection gas switchgear life prediction technology based on approximate dynamic planning, and verifies the algorithm through case analysis, which proves the effectiveness and accuracy of the proposed method.

Aerospace breeding is a breeding technique that utilizes a spacecraft to position plants in a space environment for mutagenesis, which is conducive to rapid mutagenesis for the screening of superior plant varieties. In this study, tea trees with aviation mutagenesis (TM) and those without aviation mutagenesis (CK) were selected as research subjects to analyze the effects of aviation mutagenesis on the growth, physiological properties, and hormone metabolism of tea trees, and to further screen the characteristic hormones and validate their functions. The results showed that the leaf length, leaf width, and leaf area of TM tea trees were significantly larger than those of CK. The growth indexes, the photosynthetic physiological indexes (i.e., chlorophyll content, intercellular CO2 concentration, stomatal conductance, transpiration rate, and photosynthetic rate), and the resistance physiological indexes (i.e., superoxide dismutase, peroxidase, catalase, and soluble sugar) were significantly higher in TM than in CK. Hormone metabolome analysis showed that four characteristic hormones distinguished CK from TM, namely, l-tryptophan, indole, salicylic acid, and salicylic acid 2-O-β-glucoside, all of which were significantly more abundant in TM than in CK. These four characteristic hormones were significantly and positively correlated with the growth indexes, tea yield, and the photosynthetic and resistance physiological indexes of tea trees. The leaf area, chlorophyll content, photosynthetic rate, and superoxide dismutase activity of tea tree seedlings after spraying with the four characteristic hormones were significantly increased, in which salicylic acid and salicylic acid 2-O-β-glucoside were more favorable to increase the leaf area and superoxide dismutase activity, while l-tryptophan and indole were more favorable to increase the leaf chlorophyll content and photosynthetic rate. It can be observed that aviation mutagenesis improves the accumulation of the characteristic hormones of tea trees, enhances their photosynthetic capacity, improves their resistance, promotes their growth, and then improves the tea yield.

BackgroundClinical studies have indicated a comorbidity between sepsis and kidney diseases. Individuals with specific mutations that predispose them to kidney conditions are also at an elevated risk for developing sepsis, and vice versa. This suggests a potential shared genetic etiology that has not been fully elucidated.MethodsSummary statistics data on exposure and outcomes were obtained from genome-wide association meta-analysis studies. We utilized these data to assess genetic correlations, employing a pleiotropy analysis method under the composite null hypothesis to identify pleiotropic loci. After mapping the loci to their corresponding genes, we conducted pathway analysis using Generalized Gene-Set Analysis of GWAS Data (MAGMA). Additionally, we utilized MAGMA gene-test and eQTL information (whole blood tissue) for further determination of gene involvement. Further investigation involved stratified LD score regression, using diverse immune cell data, to study the enrichment of SNP heritability in kidney-related diseases and sepsis. Furthermore, we employed Mendelian Randomization (MR) analysis to investigate the causality between kidney diseases and sepsis.ResultsIn our genetic correlation analysis, we identified significant correlations among BUN, creatinine, UACR, serum urate, kidney stones, and sepsis. The PLACO analysis method identified 24 pleiotropic loci, pinpointing a total of 28 nearby genes. MAGMA gene-set enrichment analysis revealed a total of 50 pathways, and tissue-specific analysis indicated significant enrichment of five pairs of pleiotropic results in kidney tissue. MAGMA gene test and eQTL information (whole blood tissue) identified 33 and 76 pleiotropic genes, respectively. Notably, genes PPP2R3A for BUN, VAMP8 for UACR, DOCK7 for creatinine, and HIBADH for kidney stones were identified as shared risk genes by all three methods. In a series of immune cell-type-specific enrichment analyses of pleiotropy, we identified a total of 37 immune cells. However, MR analysis did not reveal any causal relationships among them.ConclusionsThis study lays the groundwork for shared etiological factors between kidney and sepsis. The confirmed pleiotropic loci, shared pathogenic genes, and enriched pathways and immune cells have enhanced our understanding of the multifaceted relationships among these diseases. This provides insights for early disease intervention and effective treatment, paving the way for further research in this field.

Numerous tripartite motif (TRIM) proteins, identified as E3 ubiquitin ligases, participate in various viral infections through ubiquitylation, ISGylation, and SUMOylation processes. Respiratory viruses, particularly influenza A virus (IAV) and respiratory coronaviruses (CoVs), have severely threatened public health with high morbidity and mortality, causing incalculable losses. Research on the regulation of TRIM proteins in respiratory virus infections is crucial for disease prevention and control. This review introduces TRIM proteins, summarizes recent discoveries regarding their roles and molecular mechanisms in IAV and CoVs infections, discusses current research gaps, and explores potential future trends in this rapidly developing field. It aims to enhance understanding of virus–host interactions and inform the development of new molecularly targeted therapies.

PurposeTo evaluate organ at risk (OAR) auto-segmentation in the head and neck region of computed tomography images using two different commercially available deep-learning-based auto-segmentation (DLAS) tools in a single institutional clinical applications.MethodsTwenty-two OARs were manually contoured by clinicians according to published guidelines on planning computed tomography (pCT) images for 40 clinical head and neck cancer (HNC) cases. Automatic contours were generated for each patient using two deep-learning-based auto-segmentation models—Manteia AccuContour and MIM ProtégéAI. The accuracy and integrity of autocontours (ACs) were then compared to expert contours (ECs) using the Sørensen-Dice similarity coefficient (DSC) and Mean Distance (MD) metrics.ResultsACs were generated for 22 OARs using AccuContour and 17 OARs using ProtégéAI with average contour generation time of 1 min/patient and 5 min/patient respectively. EC and AC agreement was highest for the mandible (DSC 0.90 ± 0.16) and (DSC 0.91 ± 0.03), and lowest for the chiasm (DSC 0.28 ± 0.14) and (DSC 0.30 ± 0.14) for AccuContour and ProtégéAI respectively. Using AccuContour, the average MD was

BackgroundMajor depressive disorder (MDD) pathogenesis may involve metalloids in a significant way. The aim of our study was to identify potential links between MDD and metalloid elements [boron (B), germanium (Ge), arsenic (As), antimony (Sb)].MethodsA total of 72 MDD cases and 75 healthy controls (HCs) were recruited from Zhumadian Second People’s Hospital in Henan Province, China. The levels of four metallic elements (B, Ge, As, and Sb) in the serum and urine were measured using inductively coupled plasma mass spectrometry (ICP-MS).ResultsIn comparison to the HCs, the B, As, and Sb levels were considerably lower in the MDD group (p < 0.05) in the serum; the MDD group had significantly higher (p < 0.05) and significantly lower (p < 0.001) B and Sb levels in the urine. After adjusting for potential confounders, serum B (OR = 0.120; 95% CI, 0.048, 0.300; p < 0.001) and Sb (OR = 0.133; 95% CI, 0.055, 0.322; p < 0.001) showed a negative correlation with MDD. Urine B had a negative correlation (OR = 0.393; 95% CI, 0.193, 0.801; p = 0.01) with MDD, while urine Sb had a positive correlation (OR = 3.335; 95% CI, 1.654, 6.726; p = 0.001) with MDD. ConclusionOur current research offers insightful hints for future investigation into the function of metalloids in connection to MDD processes.

Myasthenia gravis with positive MuSK antibody often involves the bulbar muscles and is usually refractory to acetylcholinesterase inhibitors. For MuSK-MG patients who experience acute exacerbations and do not respond to conventional treatments, there is an urgent need to find more suitable treatment options. With the advent of biologic agents, efgartigimod has shown promising results in the treatment of MG. We report a 65-year-old MuSK-MG patient who presented with impaired eye movements initially, and the symptoms rapidly worsened within a week, affecting the limbs and neck muscles, and had difficulties in chewing and swallowing. Lymphoplasmapheresis did not achieve satisfactory results, but after a cycle of efgartigimod treatment, the patient’s symptoms gradually improved and remained in a good clinical state for several months.

Epigenetics refers to the mechanisms such as DNA methylation and histone modification that influence gene expression without altering the DNA sequence. These epigenetic modifications can regulate gene transcription, splicing, and stability, thereby impacting cell differentiation, development, and disease occurrence. The formation of dentin is intrinsically linked to the odontogenic differentiation of dental pulp stem cells (DPSCs), which are recognized as the optimal cell source for dentin-pulp regeneration due to their varied odontogenic potential, strong proliferative and angiogenic characteristics, and ready accessibility Numerous studies have demonstrated the critical role of epigenetic regulation in DPSCs differentiation into specific cell types. This review thus provides a comprehensive review of the mechanisms by which epigenetic regulation controls the odontogenesis fate of DPSCs.

BackgroundInflammatory bowel disease (IBD) is a group of diseases characterized by chronic and recurrent inflammation of the gastrointestinal tract. The etiology of IBD remains multifaceted and poorly understood, resulting in limited treatment options that primarily target disease induction and remission maintenance. Thus, the exploration of novel therapeutic options for IBD among existing medications is advantageous. Mendelian randomization analysis (MR) serves as a valuable tool in investigating the relationship between drugs and diseases. In this study, MR analysis was employed to investigate the potential causal relationship between 23 approved drugs for the treatment of various diseases and IBD.MethodWe performed a two-sample MR analysis using publicly available genome-wide association study (GWAS) statistics. The inverse variance weighting (IVW) method was used as the main analysis method, supplemented by the remaining four methods (weighted median, MR Egger regression, simple and weighted models), and Meta-analysis was performed to expand the sample size to obtain a more reliable composite causal effect. Finally, Cochran’s Q statistic and the MR-Egger test for directed pleiotropy were applied to determine whether significant heterogeneity or directed pleiotropy existed.ResultsIn the main MR analysis (IVW), drugs with a negative causal association with the risk of IBD were immunosuppressant {OR (95% CI) = 0.7389 [0.6311–0.8651], p = 0.0046} and diabetes drugs {OR (95% CI) = 0.9266 [0.8876–0.9674], p = 0.0058}. A positive causal association with the risk of IBD was found for salicylic acid and derivatives {OR (95% CI) = 1.2737 [1.0778–1.5053], p = 0.0345}. Negative causal associations with UC risk were identified for immunosuppressants {OR (95% CI) = 0.6660 [0.5133–0.8640], p = 0.0169} and diabetes medications {OR (95% CI) = 0.9020 [0.8508–0.9551], p = 0.0046}; positive causal associations with UC risk were found for β-receptor blockers {OR (95% CI) = 1.1893 [1.0823–1.3070], p = 0.0046}. A negative causal association with the risk of CD was found for immunosuppressants {OR (95% CI) = 0.6957 [0.5803–0.8341], p = 0.0023}. There was no statistically significant association between the remaining 19 drugs and IBD and subtypes.ConclusionThis MR study provides evidence suggesting that immunosuppressants have a mitigating effect on the risk of IBD and demonstrate consistent efficacy in subtypes of ulcerative colitis (UC) and Crohn’s disease (CD). Additionally, diabetes medications show potential in reducing the risk of IBD, particularly in cases of UC, while β-blockers may elevate the risk of UC. Conversely, salicylic acid and its derivatives may increase the risk of IBD, although this effect is not consistently observed in the subtypes of the disease. These findings offer new insights into the prevention and management of IBD.

BackgroundSintilimab plus chemotherapy has proven effective as a combination immunotherapy for patients with advanced gastric and gastroesophageal junction adenocarcinoma (GC/GEJC). A multi-center study conducted in China revealed a median progression-free survival (PFS) of 7.1 months. However, the prediction of response duration to this immunotherapy has not been thoroughly investigated. Additionally, the potential of baseline laboratory features in predicting PFS remains largely unexplored. Therefore, we developed an interpretable machine learning (ML) framework, iPFS-SC, aimed at predicting PFS using baseline (pre-treatment) laboratory features and providing interpretations of the predictions.Materials and methodsA cohort of 146 patients with advanced GC/GEJC, along with their baseline laboratory features, was included in the iPFS-SC framework. Through a forward feature selection process, predictive baseline features were identified, and four ML algorithms were developed to categorize PFS duration based on a threshold of 7.1 months. Furthermore, we employed explainable artificial intelligence (XAI) methodologies to elucidate the relationship between features and model predictions.ResultsThe findings demonstrated that LightGBM achieved an accuracy of 0.70 in predicting PFS for advanced GC/GEJC patients. Furthermore, an F1-score of 0.77 was attained for identifying patients with PFS durations shorter than 7.1 months. Through the feature selection process, we identified 11 predictive features. Additionally, our framework facilitated the discovery of relationships between laboratory features and PFS.ConclusionA ML-based framework was developed to predict Sintilimab plus chemotherapy response duration with high accuracy. The suggested predictive features are easily accessible through routine laboratory tests. Furthermore, XAI techniques offer comprehensive explanations, both at the global and individual level, regarding PFS predictions. This framework enables patients to better understand their treatment plans, while clinicians can customize therapeutic approaches based on the explanations provided by the model.

Part-set cuing facilitation and impairment effects are rarely found in spatial memory, which is a challenge to the theories of part-set cuing effects based on lexical stimulus. This study aims to investigate whether there part-set cuing facilitation and impairment effects are present in spatial memory by constructing two types of memory scenes with high and low degrees of interitem associations, achieved by manipulating the presentation of miniatures. This study examined the effects of different part-set cues on free recall, recognition, and reconstruction tasks. The results of two experiments revealed that matrix cues impaired the performance of three recall tasks in memory scenes with a high degree of interitem associations, and scene cues facilitated the reconstruction performance (Experiment 1). Conversely, in memory scenes with a low degree of interitem associations, the impairment effect of matrix cues was not observed in the three recall tasks, but scene cues still facilitated the reconstruction performance (Experiment 2). These findings supported the retrieval strategy disruption hypothesis, the two-mechanism and the multi-mechanism accounts, demonstrating the significance of interitem associations in spatial memory. Furthermore, the results provided direct evidence for the importance of the encoding-retrieval strategy matching principle in spatial memory tasks.

Existing studies on soil-pipe interaction due to tunneling mainly focus on short-term responses. However, in areas with high water tables and low permeability soil, long-term ground movement and associated pipe responses may occur due to dissipation of excess pore pressure generated during tunnel construction. In this paper, a Winkler solution with time-varying subgrade modulus and the corresponding greenfield soil displacement formula are developed to investigate the tunneling effects on existing pipelines. The pipe is considered as an infinite Euler beam of finite width resting on a poroelastic half-space, and adhesion and drainage effects between the pipe and soil are considered using bounding techniques. The greenfield consolidation settlement is evaluated using a modified Gaussian curve. The findings indicate that the subgrade modulus decreases while greenfield soil displacement increases during the consolidation process. The time-dependent behavior of the subgrade modulus is governed by the drainage condition at the pipe-soil interface, whereas the greenfield soil displacement is primarily influenced by the drainage condition at the tunnel-soil interface. The study reveals that the bonded contact condition, hydraulic boundary condition, and displacement constraint conditions all influence the bending moment of the pipe.

Poly-ether-ether-ketone (PEEK) is a biomedical plastic that can be used for orthopedic implants, but it offers poor antibacterial properties and bioactivity. In this study, PEEK was sulfonated with the obtained porous structure adsorbing graphene oxide (GO). The surface microstructures and properties of the original PEEK, sulfonated PEEK (SPEEK), and GO-grafted PEEK (GO-SPEEK) were characterized. The results revealed that the GO-SPEEK surface is a 3D porous structure exhibiting superior hydrophilicity to the original PEEK. Although SPEEK was shown to possess antimicrobial properties against both Escherichia coli and Staphylococcus aureus, the bactericidal effect was even more significant for GO-SPEEK, at about 86% and 94%, respectively. In addition, the in vitro simulated-body-fluid immersion and cell experiments indicated that GO-SPEEK had much better hydroxyapatite (HA)-precipitation induction capacity and cell–material interactions (e.g., cell adhesion, proliferation, osteodifferentiation, and extracellular matrix mineralization. The tensile test revealed that the mechanical properties of PEEK were maintained after surface modification, as GO-SPEEK has comparable values of elastic modulus and tensile strength to PEEK. Our investigation sought a method to simultaneously endow PEEK with both good antimicrobial properties and bioactivity as well as mechanical properties, providing a theoretical basis for developing high-performance orthopedic implants in the clinic.

With the development of global social economy and the deepening of the aging population, diseases related to aging have received increasing attention. The pathogenesis of many respiratory diseases remains unclear, and lung aging is an independent risk factor for respiratory diseases. The aging mechanism of the lung may be involved in the occurrence and development of respiratory diseases. Aging-induced immune, oxidative stress, inflammation, and telomere changes can directly induce and promote the occurrence and development of lung aging. Meanwhile, the occurrence of lung aging also further aggravates the immune stress and inflammatory response of respiratory diseases; the two mutually affect each other and promote the development of respiratory diseases. Explaining the mechanism and treatment direction of these respiratory diseases from the perspective of lung aging will be a new idea and research field. This review summarizes the changes in pulmonary microenvironment, metabolic mechanisms, and the progression of respiratory diseases associated with aging.

With the high intensification of poultry breeding, a series of diseases caused by pathogenic bacteria threaten the health of poultry and human. Among them, poultry diseases induced by Escherichia coli cause significant economic loss every year. The aim of this study was to investigate the effects of dietary supplementation with Artemisia annua L. polysaccharide (AAP) on the growth performance and intestinal barrier function of broilers with Escherichia coli (E. coli) challenge. A total of 256 one-day-old chicks were randomly assigned to four treatment groups: control group (fed basal diet), AAP group (fed basal diet supplemented with AAP), E. coli group (fed basal diet and orally administered E. coli), AAP + E. coli group (fed basal diet supplemented with AAP and orally administered E. coli). Dietary AAP supplementation elevated the BW, ADG and ADFI in non-challenged broilers. AAP also increased the apparent metabolic rate of EE and Ca in E. coli-challenged broilers. Moreover, AAP not only enhanced the serum IgA content but also decreased the serum and jejunum content of IL-6, as well as the jejunum level of IL-1β in non-challenged broilers. AAP also down-regulates the mRNA level of inflammatory factors (IL-1β, IL-6, and TNF-α) by inhibiting the mRNA expression of TLR4 and MyD88 in intestinal NF-κB signaling pathway of E. coli-challenged broilers. Meanwhile, AAP up-regulates the activity and mRNA level CAT by down-regulating the mRNA level of Keap1 in intestinal Nrf2 signaling pathway of E. coli-challenged broilers, and decreased serum MDA concentration. AAP significantly elevated the mRNA level of CAT, SOD and Nrf2 in jejunal of non-challenged broilers. Interestingly, AAP can improve intestinal physical barrier by down-regulating serum ET content, increasing the jejunal villus height/crypt depth (VH/CD) and ZO-1 mRNA level in broilers challenged by E. coli. AAP also elevated the VH/CD and the mRNA level of Occludin, ZO-1, Mucin-2 in non-challenged broilers. Importantly, AAP reshaped the balance of jejunum microbiota in E. coli-challenged broilers by altering α diversity and community composition. In summary, AAP ameliorated the loss of growth performance in broilers challenged with E. coli, probably by regulating the intestinal permeability and mucosa morphology, immune function, antioxidant ability, and microbiota.

Introduction: TT-01025-CL is an oral, irreversible small molecule that potently inhibits vascular adhesion protein-1 (VAP-1) for the treatment of inflammation associated with non-alcoholic steatohepatitis (NASH). The objectives of this study were to evaluate the safety/tolerability, pharmacokinetics, and pharmacodynamics of TT-01025-CL, a VAP-1 inhibitor, in healthy Chinese volunteers.Methods: Double-blind, placebo-controlled, dose-escalation studies were conducted in subjects randomized to receive oral once-daily TT-01025-CL (ranges: 10–300 mg [single dose]; 20–100 mg for 7 days [multiple doses]) or placebo under fasting conditions. Safety and tolerability were monitored throughout the study. Pharmacokinetic (PK) parameters were determined using non-compartment analysis. The activity of semicarbazide-sensitive amine oxidase (SSAO)-specific amine oxidase and the accumulation of methylamine in plasma were evaluated as pharmacodynamic (PD) biomarkers.Results: A total of 36 (single-dose group) and 24 (multiple-dose group) subjects were enrolled in the study. No serious adverse events (AEs) were reported, and no subject discontinued due to an AE. All treatment-emergent adverse events (TEAEs) were mild and moderate in intensity. No dose-dependent increase in the intensity or frequency of events was observed. TT-01025-CL was rapidly absorbed after administration. In the single-ascending dose (SAD) study, median Tmax ranged from 0.5 to 2 h and mean t1/2z ranged from 2.09 to 4.39 h. PK was linear in the range of 100–300 mg. The mean Emax of methylamine ranged from 19.167 to 124.970 ng/mL, with mean TEmax ranging from 13.5 to 28.0 h. The complete inhibition (>90%) of SSAO activity was observed at 0.25–0.5 h post-dose and was maintained 48–168 h post-dose. In the multiple-ascending dose (MAD) study, a steady state was reached by day 5 in the 40 mg and 100 mg dose groups. Negligible accumulation was observed after repeated dosing. PK was linear in the range of 20–100 mg. Plasma methylamine appeared to plateau at doses of 20 mg and above, with mean Emax ranging from 124.142 to 156.070 ng/mL and mean TEmax ranging from 14.2 to 22.0 h on day 7. SSAO activity in plasma was persistently inhibited throughout the treatment period. No evident change in methylamine and SSAO activity was observed in the placebo groups.Conclusion: TT-01025-CL was safe and well-tolerated at a single dose of up to 300 mg and multiple doses of up to 100 mg once daily for 7 consecutive days. Absorption and elimination occurred rapidly in healthy volunteers. Linearity in plasma exposure was observed. TT-01025-CL inhibited SSAO activity rapidly and persistently in humans. The profile of TT-01025-CL demonstrates its suitability for further clinical development.

Non-coding RNAs (ncRNAs) play essential regulatory functions in various physiological and pathological processes in the brain. To systematically characterize the ncRNA profile in cortical cells, we downloaded single-cell SMART-Seq v4 data of mouse cerebral cortex. Our results revealed that the ncRNAs alone are sufficient to define the identity of most cortical cell types. We identified 1,600 ncRNAs that exhibited cell type specificity, even yielding to distinguish microglia from perivascular macrophages with ncRNA. Moreover, we characterized cortical layer and region specific ncRNAs, in line with the results by spatial transcriptome (ST) data. By constructing a co-expression network of ncRNAs and protein-coding genes, we predicted the function of ncRNAs. By integrating with genome-wide association studies data, we established associations between cell type-specific ncRNAs and traits related to neurological disorders. Collectively, our study identified differentially expressed ncRNAs at multiple levels and provided the valuable resource to explore the functions and dysfunctions of ncRNAs in cortical cells.

Nocardia seriolae is the primary pathogen causing nocardiosis in various fish species, leads to significant economic losses in the aquaculture industry. In this study, 10 bacterial strains isolated from Micropterus salmoides and Channa argus infected with nocardiosis, were identified as N. seriolae by physiological and biochemical identification, as well as 16S rDNA sequencing. Moreover, the key virulence-related genes such as ESX-1, T7SS-2, T7SS-3, EspG1, sodC, sod2 and ESAT6 were all positive, and showing high homology among different strains. Pathogenicity testing revealed mortality rates ranging from 70 to 100%, accompanied by the presence of white nodules in the viscera of deceased fish. The drug sensitivity test demonstrated that LY21811, the most lethal strain, exhibited high sensitivity to nine types of antibiotics, including azithromycin, doxycycline, florfenicol and compound sulfamethoxazole, yet showed complete resistance to β-lactam antibiotics. Additionally, the tannic acid also demonstrated potent inhibitory effects against LY21811, with a minimum inhibitory concentration of 0.0625 mg/mL. These results showed that N. seriolae originated from M. salmoides and C. argus in Zhejiang Province were highly conserved, demonstrating a high homogeneity in genetic characteristics, pathogenicity and antimicrobial susceptibilities. These results provide a foundation for further research on the pathogenic characteristics and disease prevention of N. seriolae infections.

IDH wild-type glioblastoma (GBM) intrinsic subtypes have been linked to different molecular landscapes and outcomes. Accurate prediction of molecular subtypes of GBM is very important to guide clinical diagnosis and treatment. Leveraging machine learning technology to improve the subtype classification was considered a robust strategy. Several single machine learning models have been developed to predict survival or stratify patients. An ensemble learning strategy combines several basic learners to boost model performance. However, it still lacked a robust stacking ensemble learning model with high accuracy in clinical practice. Here, we developed a novel integrative stacking ensemble model framework (ecGBMsub) for improving IDH wild-type GBM molecular subtype classification. In the framework, nine single models with the best hyperparameters were fitted based on extrachromosomal circular DNA (eccDNA) molecular profiling. Then, the top five optimal single models were selected as base models. By randomly combining the five optimal base models, 26 different combinations were finally generated. Nine different meta-models with the best hyperparameters were fitted based on the prediction results of 26 different combinations, resulting in 234 different stacked ensemble models. All models in ecGBMsub were comprehensively evaluated and compared. Finally, the stacking ensemble model named “XGBoost.Enet-stacking-Enet” was chosen as the optimal model in the ecGBMsub framework. A user-friendly web tool was developed to facilitate accessibility to the XGBoost.Enet-stacking-Enet models (https://lizesheng20190820.shinyapps.io/ecGBMsub/).

The impact of climate warming on soil microbial communities can significantly influence the global carbon cycle. Coastal wetlands, in particular, are susceptible to changes in soil microbial community structure due to climate warming and the presence of invasive plant species. However, there is limited knowledge about how native and invasive plant wetland soil microbes differ in their response to warming. In this study, we investigated the temporal dynamics of soil microbes (prokaryotes and fungi) under experimental warming in two coastal wetlands dominated by native Phragmites australis (P. australis) and invasive Spartina alterniflora (S. alterniflora). Our research indicated that short-term warming had minimal effects on microbial abundance, diversity, and composition. However, it did accelerate the succession of soil microbial communities, with potentially greater impacts on fungi than prokaryotes. Furthermore, in the S. alterniflora wetland, experimental warming notably increased the complexity and connectivity of the microbial networks. While in the P. australis wetland, it decreased these factors. Analysis of robustness showed that experimental warming stabilized the co-occurrence network of the microbial community in the P. australis wetland, but destabilized it in the S. alterniflora wetland. Additionally, the functional prediction analysis using the Faprotax and FunGuild databases revealed that the S. alterniflora wetland had a higher proportion of saprotrophic fungi and prokaryotic OTUs involved in carbon degradation (p

Chromobacterium violaceum (C. violaceum) is a gram-negative bacillus that is widespread in tropical and subtropical areas. Although C. violaceum rarely infects humans, it can cause critical illness with a mortality rate above 50%. Here, we report the successful treatment of a 15-year-old male who presented with bloodstream infection of C. violaceum along with sepsis, specific skin lesions, and liver abscesses. Cardiogenic shock induced by sepsis was reversed by venoarterial extracorporeal membrane oxygenation (VA ECMO). Moreover, C. violaceum-related purpura fulminans, which is reported herein for the first time, was ameliorated after treatment. This case report demonstrates the virulence of C. violaceum with the aim of raising clinical awareness of this disease.

CO2, used as an environmentally friendly fracturing fluid, has encountered a bottleneck in development in recent years. Despite great efforts in research work, limited progress has been made in field applications. In this study, an extensive literature review of research work and field cases was performed to summarize the technical issues and challenges of CO2 fracturing. The key issues of CO2 fracturing were analyzed to reveal the gap between fundamental research and field operations. The effects of CO2 properties on fracture creation and proppant transport were synthetically analyzed to extract new common research orientations, with the aim of improving the efficiency of CO2 injection. The hydraulic parameters of CO2 fracturing were compared with those of water-based fracturing fluids, which revealed a theory-practice gap. By studying the developing trends and successful experiences of conventional fluids, new strategies for CO2 fracturing were proposed. We identified that the major theory-practice gap in CO2 fracturing exists in pump rate and operation scale. Consequently, the friction reducer, effects of flow loss (due to leak-off) and distribution (within fracture networks), and shear viscosity of thickened CO2 are key factors in improving both fracture propagation and proppant transport. By increasing the scale of injected CO2, the CO2 fracturing technique can be enhanced, making it an essential option for carbon capture, utilization, and storage (CCUS) to reduce carbon emissions and mitigate climate change.

Background: The transfer of the anterior tibiofibular ligament distal fascicle (ATiFL-DF) for the augmentation repair of the anterior talofibular ligament (ATFL) shows potential as a surgical technique. However, evidences on the benefits and disadvantages of this method in relation to ankle joint function are lacking.Purpose: This study aimed to provide comprehensive experimental data to validate the feasibility of ATiFL-DF transfer augmentation repair of the ATFL.Methods: This study included 50 embalmed ankle specimens to measure various morphological features, such as length, width, thickness, and angle, for evaluating similarities between the ATiFL-DF and ATFL. Furthermore, 24 fresh-frozen ankle specimens were examined for biomechanical testing of the ATiFL-DF transfer augmented repair of the ATFL. Finally, 12 pairs of ATiFL-DF and ATFL tissues from fresh-frozen ankle specimens were treated with gold chloride staining to analyze mechanoreceptor densities.Results: Anatomical studies found that the lengths and thicknesses of the ATFL and ATiFL-DF are similar. Biomechanical outcomes showed that performing ATiFL-DF transfer for ATFL repair can improve the stability of the talus and ankle joints. This is evident from the results of the anterior drawer, axial load, and ultimate failure load tests. However, performing ATiFL-DF transfer may compromise the stability of the distal tibiofibular joint, based on the Cotton and axial load tests at an external rotation of 5°. Analysis of the histological findings revealed that mechanoreceptor densities for four types of mechanoreceptors were comparable between the ATiFL-DF and ATFL groups.Conclusion: ATiFL-DF transfer is a viable method for augmenting ATFL repair. This technique helps to improve the stability of the talus and ankle joints while compensating for proprioception loss. Although ATiFL-DF transfer augmented repair of the ATFL may negatively affect the stability of the distal tibiofibular joint, this procedure can enhance the stability of the talus and ankle joints.

Introduction: Bone tissue engineering is considered the ideal approach for bone repair. Mesoporous bioactive glass (MBG) possesses the characteristics of high drug-loading capacity and bioactivity. Low-intensity pulsed ultrasound contributes to promoting fracture healing and bone defect repair, and dimethyloxalyl glycine (DMOG) is a small molecular inhibitor that can suppress prolyl hydroxylase, reducing the degradation of hypoxia-inducible factor.Methods: In this study, we proposed to prepare DMOG-loaded MBG/poly(D,L-lactide) composite scaffolds (DMOG-MBG/PDLLA) for promoting bone repair. The effects of ultrasound stimulation and DMOG release on the cell responses of rat bone marrow mesenchymal stem cells (BMSCs) and human umbilical vein endothelial cells (HUVECs) and bone repair in vivo were investigated.Results and Discussion: The results showed that both ultrasound stimulation and DMOG release could promote the proliferation, adhesion and differentiation of BMSCs and HUVECs, respectively. After the implantation of scaffolds in rat cranial bone defect model for 8 weeks, the results indicated that the combined ultrasound stimulation and DMOG release contributed to the highest ability for promoting bone repair. Hence, the DMOG-MBG/PDLLA scaffolds with ultrasound stimulation are promising for application in bone repair.

BackgroundRight ventricular systolic dysfunction (RVSD) in patients with sepsis is an area of growing interest, but its prognostic significance remains unclear and additional tools are needed to improve our understanding. Right ventricular free wall strain (RV-FWS) is a relatively new parameter to assess RV function. This study aimed to investigate the potential correlation between impaired RV-FWS and prognostic outcomes in patients with sepsis.MethodsWe prospectively assessed right ventricular function in patients with sepsis within the initial 24 h of their hospital admission. RV-FWS, right ventricular global strain (RV-GS), fractional area change (FAC), and tricuspid annular plane systolic excursion (TAPSE) were examined. RVSD was defined as impaired RV-FWS. Moreover, the association between RVSD and 30-day mortality rate was assessed.ResultsThis study included 89 patients. Among them, 27 (30.3%) succumbed to their illness within 30 days. The nonsurviving patients demonstrated significantly lower absolute RV-FWS (−19.7% ± 2.4% vs. −21.1% ± 2.1%, P = 0.008) and RV-GS (−17.7% ± 1.2% vs. −18.4% ± 1.4%, P = 0.032) values than the surviving patients. However, TAPSE and FAC values were not significantly different between the two groups. The optimal cutoff values for RV-FWS, RV-GS, FAC, and TAPSE were −19.0%, −17.9%, 36.5%, and 1.55 cm, respectively. Kaplan–Meier survival curves revealed that patients with impaired RV-FWS and RV-GS demonstrated lower 30-day survival rates, and the predictive performance of RV-FWS (hazard ratio [HR]: 3.97, 95% confidence interval [CI]: 1.85–8.51, P