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This study investigates the influence of Cu content on the microstructure and properties of AlCuxCrTiV (x = 0.4, 1.0, 1.7) high-entropy alloys (HEAs) fabricated via vacuum arc melting. Advanced characterization techniques were used to analyze the alloy's composition, microstructure, mechanical performance, and corrosion resistance. The results show that the alloys primarily consist of BCC, FCC, and HCP phases. With increasing Cu content, the HCP phase volume fraction increases, while grain size decreases. Mechanical testing reveals a slight reduction in hardness but significant improvements in strength and fracture strain. The AlCu1.7CrTiV alloy achieves a compressive strength of 1688 MPa, a yield strength of 1443 MPa, and a fracture strain of 17%. Electrochemical tests demonstrate that higher Cu content reduces corrosion current density, increases corrosion potential, and enhances charge transfer resistance, thereby improving corrosion resistance. Overall, Cu promotes HCP phase formation, optimizes the soft-hard phase balance, and enhances ductility while maintaining high strength. Furthermore, Cu bonding strength significantly impacts corrosion resistance. These findings provide valuable insights for the optimization and practical application of AlCuxCrTiV HEAs.

Abstract Aberrant vascular systems are significant indicators of cancer and play pivotal roles in tumor immunomodulation. However, the role of PD-L1 expressed on vascular endothelial cells (VECs) in the tumor immune microenvironment of nasopharyngeal carcinoma (NPC), as well as its correlation with patient prognosis, remains unclear. According to in vitro experiments conducted in our research, NPC tumor supernatants could upregulate PD-L1 expression on HUVECs, and the upregulated PD-L1 could bind to PD-1 on T cells leading to diminished T cell killing. The results of animal experiments similarly showed that elevated levels of PD-L1 on tumor VECs hindered the anti-tumor effectiveness of T cells, resulting in immune evasion and tumor progression. Furthermore, PD-L1 expression on tumor VECs served as a valuable prognostic marker, with heightened expression linked to poorer prognosis in NPC patients. Mechanistically, we discovered that the interaction between NF-κB and STAT3 signaling pathways may contribute significantly to the up-regulation of PD-L1 on VECs in NPC. Together, our work provides novel insights into identifying prognostic markers and strategies for reversing immune evasion mechanisms in NPC.

Abstract A primary behavioral pathology in drug addiction is the overpowering motivational strength and decreased ability to control the desire to obtain drugs, which shows some variation between different individuals. Here, using a morphine-induced conditioned place preference (CPP) model with footshock, we found that mice exhibited significant individual differences in morphine-induced addiction. Despite the consequences of footshock, a small percentage of mice (24%) still showed stable morphine preference, demonstrating resistant to punishment. The majority of mice (76%) were relatively sensitive to punishment and showed termination of morphine preference. As a region of advanced cognitive function in the mammalian brain, the medial prefrontal cortex (mPFC) is involved in regulating drug-induced addictive behaviors. We found that activating the pyramidal neurons in the prelimbic cortex (PrL) could effectively reverse morphine-induced CPP in resistant mice, and inhibiting pyramidal neurons in the PrL could promote morphine-induced CPP in sensitive mice. To further explore the differences between resistant and sensitive mice, we analyzed the differences in gene expression in their PrL regions through RNA-seq analysis. The results showed that compared to sensitive mice, the significantly downregulated differentially expressed genes (DEGs), such as Panx2, Tcf7l2, Htr2c, Htr5a, Orai3, Slc24a4 and Cacnb2, in resistant mice were mainly involved in synaptic formation and neurodevelopment. We speculated that there may be defects in the neuronal system of resistant mice, and caused they are more prone to morphine-induced CPP. These findings are likely to contribute to research in gene therapy, and they may also serve as potential therapeutic targets for drug addiction.

Abstract Background Tuberculous pleural effusion (TPE) is a challenging extrapulmonary manifestation of tuberculosis, with traditional diagnostic methods often involving invasive surgery and being time-consuming. While various machine learning and statistical models have been proposed for TPE diagnosis, these methods are typically limited by complexities in data processing and difficulties in feature integration. Therefore, this study aims to develop a diagnostic model for TPE using ChatGPT-4, a large language model (LLM), and compare its performance with traditional logistic regression and machine learning models. By highlighting the advantages of LLMs in handling complex clinical data, identifying interrelationships between features, and improving diagnostic accuracy, this study seeks to provide a more efficient and precise solution for the early diagnosis of TPE. Methods We conducted a cross-sectional study, collecting clinical data from 109 TPE and 54 non-TPE patients for analysis, selecting 73 features from over 600 initial variables. The performance of the LLM was compared with logistic regression and machine learning models (k-Nearest Neighbors, Random Forest, Support Vector Machines) using metrics like area under the curve (AUC), F1 score, sensitivity, and specificity. Results The LLM showed comparable performance to machine learning models, outperforming logistic regression in sensitivity, specificity, and overall diagnostic accuracy. Key features such as adenosine deaminase (ADA) levels and monocyte percentage were effectively integrated into the model. We also developed a Python package ( https://pypi.org/project/tpeai/ ) for rapid TPE diagnosis based on clinical data. Conclusions The LLM-based model offers a non-surgical, accurate, and cost-effective method for early TPE diagnosis. The Python package provides a user-friendly tool for clinicians, with potential for broader use. Further validation in larger datasets is needed to optimize the model for clinical application.

Abstract Background Depressive symptoms are highly prevalent among adolescents with a history of parent-child separation. This study investigates whether self-perceived pleasure in social interactions mediates the relationship between early parent-child separation and depressive symptoms among Chinese adolescents. Methods 1250 teenagers (mean age = 12.95 years, SD = 1.55; 54.6% male) completed self-report surveys assessing early parent-child separation, self-perceived pleasure in social interactions, and depressive symptoms. Mediation analysis was conducted using the bootstrap method. Results Early parent-child separation increased the risk for depressive symptoms in adolescents by 1.743 times (95% CI, 1.348–2.253). Self-perceived pleasure in social interaction partially mediated the association between early parent-child separation and adolescent depressive symptoms, after adjusting for age and gender (β = 0.095; 95%CI, 0.032–0.168). The mediating effect was significant and accounted for 19.87% of the total effect. Conclusions This study highlights the impact of self-perceived pleasure from social interactions on adolescent depressive symptoms. Improving perceived pleasure from social interactions may help reduce the negative effects of parent-child separation on depressive symptoms.

Abstract Background Glioma is a brain tumor and glioblastoma represents its most common type, accounting for almost 40% of primary tumors of the central nervous system, and is associated with the worst prognosis. Glioblastoma remains one of the major challenges in neurooncology. Recently, the Food and Drug Administration (FDA) has approved tumor treating fields (TTF) for the treatment of glioblastoma. In this analysis, we aimed to systematically assess the adverse outcomes associated with TTF when combined to temozolamide versus temozolamide alone for the treatment of glioblastoma. Methods MEDLINE (subset PubMed), EMBASE, Web of Science, Cochrane databases, Google scholar, and http://www.ClinicalTrials.gov were searched for publications comparing TTF in combination with temozolomide versus temozolomide alone for the treatment of glioblastoma. The adverse outcomes were considered as the endpoints in this analysis. The statistical analysis was carried out by the latest version of the RevMan software (version 5.4). Risk ratios (RR) with 95% confidence intervals (CI) were used to represent the data following assessment. A random effect model was used during the statistical analysis. Results A total number of 994 participants were included in this analysis whereby 572 participants were assigned to TTF + temozolomide, whereas 422 participants were assigned to temozolomide alone. All the studies were randomized trials. The majority of the participants were males (68.0–75.0%) with a mean age of the varying from 54.0 to 69.0 years. Results of this analysis showed that TTF in combination with temozolomide was not associated with significantly higher adverse outcomes related to blood and lymphatic system disorders (RR:0.87, 95% CI 0.30–2.48; P = 0.79), gastrointestinal disorders (RR: 0.83, 95% CI 0.14–4.72; P = 0.83), general deterioration and malaise (RR: 1.43, 95% CI 0.90–2.25; P = 0.13), infections and infestations (RR: 1.21, 95% CI 0.33–4.45; P = 0.78), injury/poison and procedural complications (RR: 1.78, 95% CI 0.88–3.61; P = 0.11), metabolic and nutritional disorders (RR: 0.61, 95% CI 0.34–1.08; P = 0.09), central nervous system disorders (RR: 1.14, 95% CI 0.89–1.46; P = 0.31), musculoskeletal and connective tissue disorders (RR: 0.99, 95% CI 0.48–2.07; P = 0.99), respiratory/thoracic/mediastinal disorders (RR: 0.85, 95% CI 0.44–1.62; P = 0.62), and psychiatric disorders (RR: 1.27, 95% CI 0.42–3.79; P = 0.67). Similar adverse effects were observed. Conclusion TTF in combination with temozolomide was not associated with significantly worse adverse outcomes for the treatment of patients with glioblastoma. Hence, future trials should focus on the cost-effectiveness of TTF for the treatment of glioblastoma.

Abstract Rotavirus (RV) is a leading pathogen causing diarrhea in children. In this study, a total of 51 fecal samples from children with RV enteritis, 29 post-treatment fecal samples, and 38 fecal samples from age-matched healthy controls were collected. Microbial DNA was isolated from the samples followed by high throughput Illumina sequencing targeting 16 S rRNA gene. Compared to the healthy group, the RV-infected group exhibited reduced microbial diversity. Both groups shared Firmicutes as the dominant phylum. Additionally, the abundance of Proteobacteria increased significantly in the RV-infected group. At the genus level, among the top 50 most abundant genera, 34 showed significant differences, with these differential genera correlating with certain clinical indicators such as dehydration levels and C-reactive protein (CRP). Notably, there were no significant differences in the microbiota before and after treatment in RV-infected children. Only 8.82% (3/34) of the differential genera in the post-treatment group showed a recovery trend towards the healthy state. This study enhances the understanding of how RV infection alters the gut microbiota structure in children and provides a scientific basis for improving clinical diagnosis and treatment strategies.

We assessed Cordyceps sinensis mycelium culture extract (Cs4) for alleviating long COVID symptoms. In this randomized trial 110 participants were assigned to receive Cs4 (55 participants) or were waitlisted (55 participants) for 12 weeks. The primary outcome was the change in long COVID symptom severity at 12 weeks, as measured by the modified COVID-19 Yorkshire Rehabilitation Scale. The secondary outcomes included changes in the Brief Fatigue Inventory Form, Insomnia Severity Index, Hospital Anxiety and Depression Scale, St. George’s Respiratory Questionnaire, and the Short Form 12 health survey at 12 weeks. Participants receiving Cs4 showed improvement in long COVID symptoms compared to the waitlist control group (MD, −10.1; 95% CI, −14.1 to −6.1; P < 0.001) at 12 weeks. Cs4 recipients also experienced improvement in fatigue (MD, −8.1; 95% CI, −14.2 to −2.0; P = 0.011), insomnia (MD, −2.9; 95% CI, −4.6 to −1.2; P = 0.001), and respiratory symptoms (MD, −6.3; 95% CI, −11.4 to −1.2; P = 0.018). Cs4 also improved the quality of life (physical component MD, 7.0; 95% CI, 4.2–9.8; P < 0.001; mental component MD, 6.8; 95% CI, 2.9–10.7; P < 0.001). No severe adverse events were reported. Cs4 may be a beneficial treatment for patients with long COVID symptoms.

In aquatic environments, natural iron minerals are a prevalent form of iron, which alter substance speciation through adsorption and redox reactions. Their abiotic migration and transformation processes are pivotal for maintaining aquatic ecosystem stability, particularly in nitrogen and organic carbon dynamics. Recent studies have been revealed that the generation of reactive oxygen species at iron mineral-redox fluctuation interfaces can change the transformations of pollutants and organic carbon. This article provides a concise introduction to the characteristics, extraction, and characterization of natural iron minerals in aquatic environments, and summarizes their predominant abiotic processes. These conclusions are expected to provide new insights into a deeper understanding of water dynamics that are influenced by natural iron minerals.

Abstract To update the efficacy and safety of different drugs for the treatment of patients with hyperphosphatemia in chronic kidney disease, we conducted a network meta-analysis of 22 therapies for the treatment of uncontrolled hyperphosphatemia in patients with chronic kidney disease (CKD). All randomized controlled trials on hyperphosphatemia published from January 2013 to November 2023 were searched from CNKI, VIP database, Wanfang database, PubMed, Scopus, and Cochrane databases. Meta-analysis was used to evaluate the serum phosphorus, calcium levels, total effective rate and adverse events of patients with chronic kidney disease (CKD). Data collection and quality evaluation were carried out by three evaluators, RevMan (5.5.3) and Stata (1.3.0). A total of 71 RCTs, and 22 treatment strategies were included in this NMA. The results showed that all treatment strategies were effective in improving patients’ blood phosphorus levels. Among them, SL + CT, CA + CC, SL and TCM had higher overall efficacy, RT, TCM and SL + CT had lower blood phosphorus levels, SL + CT, SL and NAM had lower blood calcium levels, and OAC, CC, NAM and SL had higher safety. Among them, SL + CT seems to be the most recommended treatment strategy. In addition, multidrug combination strategies usually have a higher efficacy and safety profile.

The water content of cut flowers is a significant factor in their post-harvest quality. In this study, we examine the efficacy of silver nanoparticles (NS) on the longevity of cut gladiolus, with a focus on water state and distribution. We used Low-field nuclear magnetic resonance (LF-NMR) technology to identify three water fractions with different transverse relaxation times (T2) values: bound water T21 (10 ms). During the opening process, T23 increased at stages 2 and 3 and then decreased, T22 decreased slowly, and T21 remained unchanged. Free water values were consistently higher than bound water and immobilized water and reached their maximum from stage 2 until stage 4, when the petals were extended and began to wilt. The vascular bundles responsible for transporting water had higher water content, as detected by proton density-weighted magnetic resonance imaging (MRI). Bound water and free water with NS pretreatments in bracts were initially lower but then two days later the signal amplitude of each water state exceeded those of the control, indicating that the treatment enhanced the water-holding capacity over time. Furthermore, NS pretreatments reduced the free water mobility of the cut flowers and inhibited stem decay. Additionally, we found that NS can enter the stem and are primarily transported upward along the xylem with water using scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDS) technology. Overall, our findings indicate that NS pretreatment reduces free water in gladiolus cut flowers, enhancing their water retention and prolonging their vase life.

Abstract CITE-seq provides a powerful method for simultaneously measuring RNA and protein expression at the single-cell level. The integrated analysis of RNA and protein expression in identical cells is crucial for revealing cellular heterogeneity. However, the high experimental costs associated with CITE-seq limit its widespread application. In this paper, we propose scTEL, a deep learning framework based on Transformer encoder layers, to establish a mapping from sequenced RNA expression to unobserved protein expression in the same cells. This computation-based approach significantly reduces the experimental costs of protein expression sequencing. We are now able to predict protein expression using single-cell RNA sequencing (scRNA-seq) data, which is well-established and available at a lower cost. Moreover, our scTEL model offers a unified framework for integrating multiple CITE-seq datasets, addressing the challenge posed by the partial overlap of protein panels across different datasets. Empirical validation on public CITE-seq datasets demonstrates scTEL significantly outperforms existing methods.

Background: COVID-19 infection has a lasting impact on human health, which is known as post-COVID-19 conditions. Fatigue is one of the most commonly reported post-COVID-19 conditions. Management of fatigue in the post-COVID-19 era is necessary and emerging. The use of medicinal plants may provide a strategy for the management of post-COVID-19 fatigue. Methods: A literature search has been conducted by using PubMed, Embase and Cochrane library databases is performed for studies published up to March 2024. Keywords, such as “post-COVID-19 conditions, persistent COVID-19 symptoms, chronic COVID-19, long-term sequelae, fatigue, post-COVID-19 fatigue, herbal plants, medicinal herbs, traditional Chinese medicine, pharmacological mechanisms, pharmacological actions” are thoroughly searched in Englsih and Chinese. This study reviews the pathophysiology of post-COVID-19 fatigue and potential herbal plants for managing post-COVID-19 fatigue. Results and conclusion: Representative medicinal plants that have been extensively investigated by previous studies are presented in the study. Three common mechanisms among the most extensively studied for post-COVID-19 fatigue, with each mechanism having medicinal plants as an example. The latest clinical studies concerning the management of post-COVID-19 fatigue using medicinal plants have also been summarized. The study shows the potential for improving post-COVID-19 fatigue by consuming medicinal plants.

Lymphocyte antigen 6 complex, locus K (LY6K) is a putative oncogene in various human cancers, including colorectal cancer, where elevated expression is associated with poor prognosis. This study investigates the antitumor effects of LY6K in colon cancer stem cells (CCSCs) both in vitro and in vivo. EpCAM and CD44 surface markers were used to isolate CCSCs from HCT116 cells, and the expression of LY6K in CCSCs was analyzed by real-time PCR. RNA interference was used to silence LY6K to evaluate its potential role of LY6K on the proliferation, migration, invasion, and cell cycle of CCSCs. Functional assays, including MTS assays, flow cytometric analyses, Transwell migration and invasion assays, and a xenograft model, were used for analysis. The results revealed that LY6K was highly expressed in CCSCs. siRNA-mediated LY6K-silencing in CCSCs inhibited cell proliferation by inducing G1 phase cell cycle arrest and suppressed migration and invasion. In vivo, LY6K silencing effectively reduced tumor growth and extended survival in a mouse model. These findings suggest LY6K as a promising therapeutic target for eradicating CCSCs in colorectal cancer treatment.

Abstract For patients with necrotizing cervical tuberculous lymphadenitis (CTL) who have formed abscesses and are unwilling to undergo surgery, early and accurate assessment of drug therapy should be performed to guide subsequent clinical adjustments. This study investigated 22 patients with necrotizing CTL who underwent chemotherapy at our hospital from February 2020 to December 2022. They were diagnosed based on the positive results of pathogen detection methods (acid-fast bacillus smear, mycobacteria culture, Gene X-pert, and next-generation sequencing). Based on the 6-month treatment outcomes, the relationship among prechemotherapy ultrasound features, pus Mycobacterium tuberculosis (MTB) load, and treatment efficacy was assessed. In this study, the maximum lymph node (LN) area, maximum necrotic area, and pus MTB load in patients with necrotizing CTL were associated with poor prognosis and showed significant differences between the effective and ineffective groups (P 0.05). The maximum necrotic area of the LNs was not associated with the pus MTB load. Furthermore, maximum LN area, maximum necrotic area, and pus bacterial load may be potential radiological markers for predicting the therapeutic response of CTL.

Abstract The antioxidant protein sulfiredoxin-1 (SRX) is an oncogenic factor that promotes tumor progression, but the regulatory mechanism underlying SRX degradation remains to be understood. Herein, we report that Keap1, the substrate-specific adapter of CRL3 complex, specifically binds and promotes the ubiquitin-mediated degradation of SRX at residue K61. Keap1 knockdown accumulates SRX, which in turn facilitates colorectal cancer (CRC) metastasis by activating the activator protein-1/matrix metalloproteinase 9 (AP-1/MMP9) pathway. CRC-associated Keap1 mutants within the BACK domain lose the capability to ubiquitinate SRX and instead promote CRC metastasis. Moreover, inactivation of Keap1 facilitates CRC tumorigenesis and metastasis in mouse models of tumor xenograft due to SRX accumulation. Clinical sample analysis reveals that Keap1 is downregulated while SRX is overexpressed in CRC, which correlates with poor prognosis. Our findings elucidate a mechanism by which CRL3Keap1 ubiquitin ligase degrades SRX to suppress CRC progression, indicating that the Keap1-SRX axis will guide the targeted therapy towards CRC.

Groundwater is an important part of Beijing’s water supply, excessive ferric and manganese in groundwater will limit the development and utilization of water resources. The spatial distribution, geochemical characteristics, and sources of ferric and manganese in groundwater were analyzed based on X-ray fluorescence spectrometry, iron and manganese step extraction method, geological statistical analysis, and GIS spatial feature analysis. Results show that the iron concentration in groundwater in the study area ranged from 0.02 to 26.7 mg/L, with an average of 0.76 mg/L, and the manganese concentration ranged from 0.01 to 5.24 mg/L, with an average of 0.21 mg/L. The distributions of iron and manganese in groundwater were basically consistent, showing a trend of gradually increasing along the groundwater flow direction (from northwest to southeast) and gradually decreasing with the increase of sampling depth. The mass ratio of iron in the deposits ranged from 9.25 to 52.18 g/kg, with an average of 19.90 g/kg, while the mass ratio of manganese ranged from 0.12 to 7.26 g/kg, with an average of 0.50 g/kg. The mass ratios of iron and manganese in the sediments in the whole city did not show a distribution pattern similar to that in groundwater. However, there were positive correlations between the proportion of active component iron and the iron in groundwater (R=0.66, P>0.05), and between the content of active component manganese and the manganese concentration in groundwater (R=0.84, P

The interaction and feedback between soil and vegetation will promote the restoration of damaged mine ecosystems towards a virtuous cycle, especially in surface mine dump site reclamation areas. However, the lack of understanding of the correlation and mutual feedback mechanism between vegetation restoration and soil functions limits the scientific formulation of vegetation reconstruction strategies for surface mine dump sites. This study aims to reveal the trade-off and synergistic relationship between vegetation succession and soil system functions during the vegetation restoration process. Using methods such as field surveys, high-throughput sequencing, and resilience assessment models, four reclamation areas with different reclamation timings were selected in the Heidaigou surface coal mine on the Loess Plateau, and a resilience assessment model and trade-off synergy were constructed for five plant restoration types: grassland, shrub, coniferous forest, broad-leaved forest and mixed forest. The results show that: ① compared with bare land, the recovery degree of soil indicators is 30%−80% and the vegetation index recovery degree is 20%−75% after 8−30 a of restoration. ② The recovery rate of soil nutrient conservation and ecological carbon sink functions of grassland and shrubs peaked at 15 a, and the recovery rate of coniferous forest, broadleaf forest and mixed forest peaked at 25 a. The recovery degree of the soil system is mixed forest > grassland > coniferous forest > broadleaf forest > shrubs, and the vegetation system recovery is mixed forest > broadleaf forest > coniferous forest > grassland > shrubs. ③ In terms of the overall trend, the functional resilience of grassland, shrub and broad-leaved forest vegetation and soil systems is mainly in a trade-off relationship, while coniferous forest and mixed forest are mainly in a synergistic relationship. It concludes that the vegetation restoration significantly improves the physical, chemical, biological properties and vegetation community characteristics of the reclaimed soil, the reclamation years significantly affects the recovery elasticity and rate of the soil-vegetation system in the surface mine area of the Loess Plateau, China. As the reclamation years increase, there is a trade-off relationship between soil-vegetation system indicators. The research results confirm that different vegetation types have temporal characteristics in improving the resilience of the soil-vegetation system. Therefore, it is recommended to appropriately adjust the vegetation clustering strategy, allocate vegetation types in a timely manner, and fully coordinate the relationship between various soil functions to optimize the surface mine ecology of the Loess Plateau. The study provides a scientific basis for the restoration planning and management of disturbed surface mine.

Abstract Background The World Health Organization certified China malaria-free in 2021. Consequently, preventing the risk of malaria re-introduction caused by imported malaria has now become a major challenge. This study aims to characterize the dynamics and predict the risk of malaria importation in Jiangsu Province, where the number of imported malaria cases ranks among the highest in China. Methods The annual number of cases with imported malaria in Jiangsu Province, the annual number of travelers from sub-Saharan Africa (SSA) to Jiangsu Province (both Chinese and international travelers), and the annual number of Chinese migrant workers from Jiangsu Province who stayed abroad between 2013 and 2020 were assessed. The spatio-temporal dynamics of malaria importation was characterized with ArcGIS 10.8. A negative binomial model was applied to model malaria importation to Jiangsu Province, China. Results A total of 2,221 of imported malaria cases were reported from January 1, 2013, until December 31, 2020. Imported malaria cases into China were mainly from SSA (98%) and P. falciparum (78%), the most common species. A seasonal pattern was observed, with the most cases occurring from December to February. The negative binomial model, which incorporates the number of Chinese migrant workers from Jiangsu Province who stayed abroad as an independent variable, demonstrated better performance (AIC: 96.495, BIC: 94.230) compared to the model based solely on travelers from SSA to Jiangsu Province. The model indicated an estimated 139% increase in imported cases for a 10% increase in Chinese migrant workers from Jiangsu Province who stayed abroad. Conclusion In conclusion, our study underscores the importance of incorporating data on Chinese migrant workers who have stayed abroad when predicting malaria importation risks. By integrating both international travel patterns and migrant worker data, our findings offer a more robust framework for assessing and managing malaria risk in Jiangsu Province. This approach provides valuable insights for public health officials, enabling more effective resource allocation and targeted interventions to prevent the re-introduction of malaria and improve overall disease management.

Abstract Purpose This study aimed to develop postsurgical progression/hyperprogression recurrence (type III-IV recurrence) prediction models for hepatocellular carcinoma (HCC) patients with macroscopic vascular invasion (MaVI) and to guide treatment strategies in the accurate healthcare era. Patients and methods 393 HCC patients with MaVI from two central hospitals made up the entire study population. In developmental (290 patients) and validation (103 patients) cohorts, all patients were randomized into one or the other. Two prediction models for type III-IV recurrence were developed, based on the findings of univariate and multivariate analysis in the development cohort, and multidimensional verification was carried out in both cohorts. Results The postoperative recurrence rate of type III-IV in 393 HCC patients with MaVI was 70.9%. Young age, large tumor size (≥ 10 cm), node number, incomplete tumor capsule, postoperative complications, and high Ki67 index were the independent risk factors for relapse of type III-IV. In the development cohort, two nomograms (pre- and postoperative) had the Area Under the ROC curve (AUC) of 0.827 and 0.891, respectively. The two nomograms performed well, according to multidimensional verification methods such as clinical impact curves, decision curve analysis (DCA), and calibration curves. The validation cohort saw similar encouraging results. Both nomograms could separate patients into two distinct prognosis subgroups with ideal cutoff values of 170.3 presurgery and 175.0 postsurgery (both P

Abstract Background Recent studies have identified a correlation between insulin resistance (IR) and depression. This study aims to explore the correlation between estimated glucose disposal rate (eGDR), a practical and noninvasive measure for assessing IR, and depression in the general population. Methods In this population-based cross-sectional study, data from 28,444 adults aged 18 years old or older in the NHANES during the period from 1999 to 2018 were analyzed. The correlation between eGDR and depression was examined through multivariate logistic regression analyses, subgroup analyses, restricted cubic spline, and interaction tests. Furthermore, a mediation analysis was conducted to elucidate the role of the atherogenic index of plasma (AIP) in mediating the effect of eGDR on depression. Results Multivariate logistic regression analysis and restricted cubic splines analysis indicated that eGDR can exhibit a linearly correlation with depression (OR = 0.913; 95% CI: 0.875, 0.953). Subjects in eGDR6-8 and eGDR > 8 groups had a decrease risk of depression as 25.4% and 41.5% than those in the eGDR

Abstract Reversing the hypoxic microenvironment of tumors is an important method to enhance the synergistic effect of tumor treatment. In this work, we developed the nanoparticles called Ce6@HGMOF, which consists of a photosensitizer (Ce6), glucose oxidase (GOX), chemotherapy drugs (HCPT) and an iron-based metal-organic framework (MOF). Ce6@HGMOF can consume glucose in tumor cells through “starvation therapy”, cut off their nutrition source, and produce gluconic acid and hydrogen peroxide (H2O2). Utilizing this feature, Ce6@HGMOF can produce oxygen through catalase-like catalytic activity, thereby reversing the hypoxic microenvironment of tumors. This strategy of changing the hypoxic environment can help to slow down the growth of tumor blood vessels and improve the drug-resistant microenvironment to some extent. Meanwhile, increasing the supply of oxygen can enhance the effect of photodynamic therapy (PDT) and enhance the oxidative stress damage caused by reactive oxygen species (ROS) in tumor cells. On the other hand, cancer cells usually produce higher levels of glutathione (GSH) to adapt to high oxidative stress and protect themselves. The Ce6@HGMOF we designed can also consume GSH and induce ferroptosis of tumor cells through Fenton reaction with H2O2, while enhancing the effect of PDT. This innovative synergistic strategy, the combination of PDT/ferroptosis /starvation therapy, can complement each other and enhance each other. It has great potential as a powerful new anti-tumor paradigm in the future.

Infected wounds pose a significant clinical challenge due to bacterial resistance, recurrent infections, and impaired healing. Reactive oxygen species (ROS)-based strategies have shown promise in eradicating bacterial infections. However, the excess ROS in the infection site after treatments may cause irreversible damage to healthy tissues. To address this issue, we developed bovine serum albumin-iridium oxide nanoclusters (BSA-IrOx NCs) which enable photo-regulated ROS generation and scavenging using near infrared (NIR) laser. Upon NIR laser irradiation, BSA-IrOx NCs exhibit enhanced photodynamic therapy, destroying biofilms and killing bacteria. When the NIR laser is off, the nanoclusters' antioxidant enzyme-like activities prevent inflammation and repair damaged tissue through ROS clearance. Transcriptomic and metabolomic analyses revealed that BSA-IrOx NCs inhibit bacterial nitric oxide synthase, blocking bacterial growth and biofilm formation. Furthermore, the nanoclusters repair impaired skin by strengthening cell junctions and reducing mitochondrial damage in a fibroblast model. In vivo studies using rat infected wound models confirmed the efficacy of BSA-IrOx NCs. This study presents a promising strategy for treating biofilm-induced infected wounds by regulating the ROS microenvironment, addressing the challenges associated with current ROS-based antibacterial approaches.

Abstract Background The production of β-lactamases is the most prevalent resistance mechanism for β-lactam antibiotics in Gram-negative bacteria. Presently, over 4900 β-lactamases have been discovered, and they are categorized into hundreds of families. In each enzyme family, amino acid substitutions result in subtle changes to enzyme hydrolysis profiles; in contrast, certain conserved sequences retained by all of the family members can serve as important markers for enzyme family identification. Results The SHV family was chosen as the study object. First, a unique 10-mer peptide was identified as SHV family's epitope by an approach of protein fingerprint analysis. Then, an SHV-specific magnetic epitope-imprinted gel polymer (MEI-GP) was prepared by an epitope surface imprinting technique, and its sorption behavior and recognition mechanism for template epitope and SHV were both elaborated. Finally, the MEI-GP was successfully applied to selectively extract SHV from bacteria, and the extracted SHV was submitted to MALDI-TOF MS for specific determination. By following this strategy, other β-lactamase families can also be specifically detected. According to the molecular weight displayed in mass spectra, the kind of β-lactamase and its associated hydrolysis profile on β-lactams can be easily identified. Based on this, an initial drug option scheme can be quickly formulated for antimicrobial therapy. From protein extraction to medication guidance reporting, the mean time to detection (MTTD) was less than 2 h, which is much faster than conventional phenotype-based methods (at least 16–20 h) and gene-based techniques (usually about 8 h). Conclusions This enzyme-specific detection strategy combined the specificity of epitope imprinting with the sensitivity of mass spectrometry, enabling β-lactamase to be selectively extracted from bacteria and clearly presented in mass spectra. Compared with other drug resistance detection methods, this technique has good specificity, high sensitivity (≤ 15 mg of bacteria), a short MTTD (less than 2 h), and simple operation, and therefore has a broad application prospect in clinical medicine. Graphical Abstract

Abstract This study aimed to identify predictive factors for the prognosis of acute-on-chronic liver disease (AoCLD) due to both hepatitis B virus (HBV) and alcohol and to develop prognostic models to improve treatment management. AoCLD patients with HBV and alcohol as etiological factors were selected from two multicenter prospective cohorts (NCT02457637,NCT03641872) and included in separate training and validation cohorts (n = 180 and n = 148). In the training cohort, the CATCH-LIFE A nomogram (based on age, bilirubin, international normalized ratio, serum sodium, and hepatic encephalopathy score) and CATCH-LIFE B nomogram (based on age, bilirubin, international normalized ratio, serum albumin, white blood cell, platelet count, and hepatic encephalopathy score) had discriminatory ability for predicting 28-day (c-indexes of 0.910 and 0.899) and 90-day mortality (c-indexes of 0.878 and 0.887, respectively). The area under the curve values for 28-day and 90-day mortality prediction by the CATCH-LIFE A nomogram were 0.922 (95% CI : 0.874, 0.971) and 0.905 (0.856, 0.956), respectively, while those for the CATCH-LIFE B nomogram were 0.916(0.861,0.972) and 0.915 (0.866,0.964), respectively. Similar performance results were observed in the validation cohort. Optimal cut-off scores for each nomogram could be used for patient stratification in high- and low-risk groups, and the high-risk groups showed shorter survival times than the low-risk groups in both the training and validation cohorts. Two nomograms constructed from the first short-term follow-up data from patients with AoCLD due to combined HBV infection and alcohol exposure showed good predictive performance for 28-day and 90-day mortality and might be used to guide clinical management.

Abstract Rice (Oryza sativa L.) endosperm is essential to provide nutrients for seed germination and determine grain yield. RNA editing, a post-transcriptional modification essential for plant development, unfortunately, is not fully characterized during rice endosperm development. Here, we perform systematic analyses to characterize RNA editome during rice endosperm development. We find that most editing sites are C-to-U CDS-recoding in mitochondria, leading to increased hydrophobic amino acids and changed structures of mitochondrial proteins. Comparative analysis of RNA editome reveals that CDS-recoding sites present higher editing frequencies with lower variabilities and their resultant recoded amino acids tend to exhibit stronger evolutionary conservation across many land plants. Furthermore, we classify mitochondrial genes into three groups, presenting distinct patterns in terms of CDS-recoding events. Besides, we conduct genome-wide screening to detect pentatricopeptide repeat (PPR) proteins and construct PPR-RNA binding profiles, yielding candidate PPR editing factors related to rice endosperm development. Taken together, our findings provide valuable insights for deciphering fundamental mechanisms of rice endosperm development underlying RNA editing machinery.

IntroductionBlastocystis hominis (B. hominis), a protozoan parasite often found in the human intestinal tract, is typically identified through fecal examination. Its presence in ascitic fluid is quite uncommon, making such a detection significant in the context of medical diagnosis.Case presentationIn this case report, we describe a 53-year-old female patient who presented with a 6-month history of recurrent diarrhea and fecal incontinence subsequent to the diagnosis of rectal signet ring cell carcinoma. The patient was discovered to have a severe abdominal infection, with B. hominis identified in both the abdominal cavity and the intestinal tract. Marked improvement in diarrheal symptoms was achieved following peritoneal lavage with metronidazole.ConclusionThis case underscores the significance of detecting B. hominis infection in the ascitic fluid of a patient afflicted with rectal signet ring cell carcinoma. B. hominis, a prevalent opportunistic pathogen, often exploits the compromised immune states and nutritional deficiencies prevalent in cancer patients, rendering them more susceptible to such infections. It is imperative to enhance diagnostic accuracy and mitigate the risk of misdiagnosis to subsequently improve the clinical outcomes and overall quality of life for individuals battling cancer.

Introduction: Chronic heart failure (CHF) is considered to be the last battlefield of cardiovascular disease. Jinxinkang granule (JXK) is an integrated traditional Chinese medicine formula for treating CHF. Our previous clinical study showed that JXK could increase the left ventricular ejection fraction and reduce concomitant symptoms in patients with CHF. However, the molecular mechanism underlying the action of JXK on CHF has yet to be fully illustrated. Methods: Sprague-Dawley (SD) rats under left anterior descending artery ligation model, C57BL/6 mice subcutaneously injected isoproterenol (ISO) model in vivo and H9c2 cells under oxygen glucose deprivation (OGD) in vitro were used to evaluate the effect of JXK against CHF. Cardiac function and morphology assessment using M-mode echocardiography, H&E/Masson/WGA staining, western blotting analysis, real-time PCR detection, ATP and cAMP assays were used to explore the mechanism of JXK against CHF. Results: JXK improved cardiac function and ameliorated cardiac fibrosis in both LAD-induced CHF rats and ISO-induced CHF mice, and protected cardiomyocytes from OGD injury in H9c2 cells. Moreover, JXK increased the level of ATP content and enhanced fatty acid oxidation by increasing CD36, CPT1A and ACADM expression. Mechanism study showed that JXK increased the GPER expression and cAMP level, promoted AMPK phosphorylation and PGC-1α expression. Additionally, molecular docking analysis showed that dihydroisotanshinone I has a high binding affinity with GPER at -8.5 kcal/mol, which has the similar binding sites with G-1, a GPER agonist. Importantly, after using the inhibitor of GPER (G15), the cardioprotective effect of JXK and the enhancing effect on the fatty acid oxidation were blocked. Conclusion: JXK effectively activated GPER/AMPK/PGC-1α signaling pathway to enhance the oxidation of fatty acid, thereby promoting cardiac energy metabolism production to ameliorate CHF.

Herein, we present a case of serious protein-energy malnutrition in an elderly critically ill patient with situs inversus totalis. It was difficult to implement enteral nutrition in this patient for more than 2 months of hospitalisation in another hospital, and we applied electromagnetic navigation guidance to implement enteral nutrition after successful placement of nasojejunal tubes. We reviewed the management of enteral nutrition support.

ObjectiveAutoimmune diseases (ADs) result from an aberrant immune response, in which the body mistakenly targets its own tissues. The association between TGF-β1 gene polymorphisms and risk of developing autoimmune diseases remains to be established. This meta-analysis aimed to reassess the relationship between TGF-β1 T869C gene polymorphisms and susceptibility to autoimmune diseases.MethodsWe conducted a comprehensive search of seven electronic databases for case-control studies investigating the TGF-β1 T869C polymorphism in relation to autoimmune diseases, including rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, Sjögren’s syndrome, and juvenile idiopathic arthritis. The search encompassed publications published up to June 2024. Studies were categorized by ethnicity into three groups: Asian, Caucasian, and mixed-ethnicity groups. Five different genetic models were assessed, and the quality of the included studies was evaluated using the Newcastle-Ottawa Scale (NOS). Statistical analyses were performed using Stata 14.0, by calculating the odds ratio (OR) and 95% confidence interval (CI).ResultsA total of 32 case-control studies (31 articles), comprising 4,304 cases and 4,664 controls, were included in this meta-analysis. The overall analysis indicated no significant association between TGF-β1 T869C gene polymorphism and susceptibility to autoimmune diseases. However, subgroup analyses based on race and disease status revealed significant associations. Ethnic subgroup analysis showed that the TGF-β1 T869C allele model (T vs C: OR = 1.422, 95% CI = 1.109–1.824, P = 0.006), homozygous model (TT vs CC: OR = 1.923, 95% CI = 1.232–3.004, P = 0.004), and dominant model (TT + TC vs CC: OR = 1.599, 95% CI = 1.164–2.196, P = 0.004) were associated with autoimmune disease susceptibility in Asians. In the disease subgroup analysis, the results showed that the TGF-β1 T869C allele model (T vs C: OR = 1.468, 95% CI = 1.210–1.781, P = 0.000), recessive model (TT vs TC + CC: OR = 1.418, 95% CI = 1.097–1.832, P = 0.008), dominant model (TT + TC vs CC: OR = 1.747, 95% CI = 1.330–2.295, P = 0.000), homozygous model (TT vs CC: OR = 1.937, 95% CI = 1.373–2.734, P = 0.000), and heterozygous model (TC vs CC: OR = 1.555, 95% CI = 1.199–2.016, P = 0.001) were associated with rheumatoid arthritis susceptibility.ConclusionThe findings of this meta-analysis suggest that carrying the T allele of the TGF-β1 T869C polymorphism increases the risk of autoimmune diseases in Asian populations. Moreover, individuals carrying the T allele are at higher risk of developing rheumatoid arthritis.

IntroductionCognitive decline is common in Parkinson’s disease (PD). Reliance on neuropsychological testing alone can lead to delayed identification, and an objective and comprehensive approach is needed in clinical practice. We assessed brain functional connectivity during PD-MCI (mild cognitive impairment) and PD-NC (normal cognition) patients, and healthy controls (HC) completing the Stroop color-word test (SCWT) using functional near-infrared spectroscopy (fNIRS), and explored the predictive value of combining relevant brain function and behavioral information for general cognitive decline in PD.MethodsNineteen patients with PD-MCI, 21 with PD-NC and 33 age-matched HC were recruited. Group differences in executive performance and prefrontal functional connectivity were analyzed. Receiver operating characteristic analysis was used to measure the value of combining brain functional connectivity with executive and motor function in predicting PD-MCI.ResultsDuring the color-word incongruent test, PD-MCI patients had significantly lower correct rate than HC and PD-NC patients. Meanwhile, PD-MCI patients exhibited significantly increased regional strength of the left and right prefrontal cortex (RSl, RSr), and global efficiency than HC, and compared with PD-NC, PD-MCI patients showed significantly higher RSr. For PD patients, MMSE score and correct rate during the color-word incongruent test were negatively associated with the RSr after adjusting for education level and age. After combined the RSr, correct rate and MDS-UPDRS III score, diagnostic sensitivity and specificity of PD-MCI reached 0.737 and 0.810, respectively, with an area under the curve of 0.830.ConclusionWe proposed a signature combining brain functional connectivity with executive and motor function for general cognitive decline in PD, which could provide new insights into early detection and intervention of this problem.

Phosphorus (P) pollution from livestock farming poses significant environmental challenges, necessitating efficient P utilization. This study systematically investigated the effects of varying dietary P levels on growth, slaughter performance, nutrient digestion, and metabolism in Yunnan Semi-fine Wool Sheep during the growth phase. Forty-five sheep (30.33 ± 0.56 kg) were randomly assigned to five dietary P levels (0.40, 0.51, 0.68, 0.82, and 0.97%) over a 44-day trial, including a 14-day pre-feeding and 30-day formal trial period. Digestibility trials were conducted on days 22–27, and selected sheep were slaughtered for detailed analysis. Results showed no significant effects of dietary P on daily weight gain, feed-to-gain ratio, or organ indices (p > 0.05). However, dry matter intake, liver, and lung weights decreased linearly with increasing P levels (p

Functional near-infrared spectroscopy (fNIRS) is a widely-used transcranial brain imaging technique in neuroscience research. Nevertheless, the lack of anatomical information from recordings poses challenges for designing appropriate optode montages and for localizing fNIRS signals to underlying anatomical regions. The photon measurement density function (PMDF) is often employed to address these issues, as it accurately measures the sensitivity of an fNIRS channel to perturbations of absorption coefficients at any brain location. However, existing PMDF-based localization methods have two limitations: (1) limited channel space, and (2) estimation based on a single standard head model, which usually differ anatomically from individuals. To overcome these limitations, this study proposes a continuous standard channel space for fNIRS and constructs a PMDF-based transcranial brain atlas (PMDF-TBA) by calculating PMDFs using MRI data from 48 adults. The PMDF-TBA contains group-averaged sensitivities of channels to gray matter and brain regions as defined in 3 atlases: Brodmann, AAL2, and LPBA40. We evaluated the prediction ability of PMDF-TBA for sensitivity of unseen individuals. The results show that it outperformed PMDFs based on single standard head models, making PMDF-TBA a more generalizable fNIRS spatial localization tool. Therefore, in the absence of individual sMRI data, PMDF-TBA can optimize optode montage design, enhance channel sensitivity in target brain regions, and assist in source localization for fNIRS data, thereby facilitating the application of fNIRS in neuroscience research.

IntroductionThe multi-targeted ligands (MTDL) strategy has been recognized as a promising Approach for the development of effective treatments against Alzheimer’s disease (AD), due to the presence of multiple pathological mechanisms in AD. In this study, a series of bis(7)-harmine derivatives were designed and synthesized as multifunctional drugs for the treatment of AD.MethodsThe derivatives were synthesized by chemical methods and their structure was confirmed by nuclear magnetic resonance (NMR). The Ellman’s assay was utilized to assess the inhibitory potential of derivatives against hAChE and hBuChE. The inhibitory activity of these derivatives on both hMAO-A and hMAO-B was assessed using a fluorescence-based method. The thioflavin T (Th-T) fluorescence assay was used to assess the inhibition of Aβ1−42 self-aggregation. The cytotoxicity was evaluated using the MTT assay. The Surflex-Dock program in Sybyl-X2.0 Software was employed for molecular docking.ResultsIn vitro studies revealed that numerous synthesized compounds exhibited potent inhibitory activity against hAChE, and hMAO-B (IC50 < 1 μM), as well as Aβ1−42 aggregation (IC50 < 20 μM). Importantly, the multitarget compounds 6d, 8c, and 8d exhibited remarkable efficacy in simultaneously mitigating Aβ-induced toxicity in SH−SY5Y cells while demonstrating minimal cytotoxicity. Furthermore, predicted ADMET results suggested that 6d, 8c, and 8d possessed favorable pharmacokinetic properties and demonstrated low toxicity levels. Additionally, molecular docking studies of 6d within the activesites of hAChE, hMAO-B, and Aβ1−42 elucidated the inhibition mechanism.Discussion and conclusionBased on these findings, it is evident that 6d, 8c, and 8d hold potential as promising multi-functional drugs for AD treatment.

The Han River, a key water source for China’s South-to-North Water Diversion Project, faces ecological challenges due to urbanization-driven heavy metal pollution and eutrophication. This study analyzed microbial communities in sediment samples from 15 sites using 16S rDNA sequencing. Our findings revealed a significant decrease in α-diversity with increasing copper (Cu) concentration, with the downstream region (group L) exhibiting higher diversity compared to the upstream region (group U). Group U was dominated by Alphaproteobacteria, while Clostridia prevailed in groups M and L. Analysis of β-nearest taxon index (βNTI) indicated that stochastic processes primarily shaped community assembly. Redundancy analysis (RDA) identified Cu, Fe, and Cr as key environmental factors influencing bacterial community composition in group U, while COD, Chl_a, pH, TN, and TP affected groups M and L. The study emphasizes the importance of addressing heavy metal pollution in eutrophic waters to protect microbial community diversity.

Over the last decade, hip-hop pedagogy has received a lot of attention in the field of education because of its significance in improving students’ learning effects. This review articulates the current understanding of the positive impact of hip-hop pedagogy on students’ learning effects within publications, an under-researched area. Based on a review of previous studies, this review innovatively examines six major elements of hip-hop pedagogy (DJ, MC, cypher, breakdance, knowledge, and graffiti) and concludes that the six major elements of hip-hop pedagogy can, in terms of the four dimensions of learning motivation, engagement, learning and memorization, and critical thinking, improve students’ learning effects. Hip-hop pedagogy is an all-encompassing pedagogy that is popular with youth and deserves more in-depth research by hip-hop educators in the future.

Echinococcosis is a zoonotic parasitic disease caused by the larvae of echinococcus tapeworms infesting the human body. Drug combination therapy is highly valued for the treatment of echinococcosis because of its potential to overcome resistance and enhance the response to existing drugs. Traditional methods of identifying drug combinations via biological experimentation is costly and time-consuming. Besides, the scarcity of existing drug combinations for echinococcosis hinders the development of computational methods. In this study, we propose a transfer learning-based model, namely TransferBAN-Syn, to identify synergistic drug combinations against echinococcosis based on abundant information of drug combinations against parasitic diseases. To the best of our knowledge, this is the first work that leverages transfer learning to improve prediction accuracy with limited drug combination data in echinococcosis treatment. Specifically, TransferBAN-Syn contains a drug interaction feature representation module, a disease feature representation module, and a prediction module, where the bilinear attention network is employed in the drug interaction feature representation module to deeply extract the fusion feature of drug combinations. Besides, we construct a special dataset with multi-source information and drug combinations for parasitic diseases, including 21 parasitic diseases and echinococcosis. TransferBAN-Syn is designed and initially trained on the abundant data from the 21 parasitic diseases, which serves as the source domain. The parameters in the feature representation modules of drug interactions and diseases are preserved from this source domain, and those in the prediction module are then fine-tuned to specifically identify the synergistic drug combinations for echinococcosis in the target domain. Comparison experiments have shown that TransferBAN-Syn not only improves the accuracy of predicting echinococcosis drug combinations but also enhances generalizability. Furthermore, TransferBAN-Syn identifies potential drug combinations that hold promise in the treatment of echinococcosis. TransferBAN-Syn not only offers new synergistic drug combinations for echinococcosis but also provides a novel approach for predicting potential drug pairs for diseases with limited combination data.

BackgroundConditional survival (CS) analysis can estimate further survival probabilities based on the time already survived, providing dynamic updates for prognostic information. This study aimed to develop a CS-nomogram to promote individualized disease management for stage III non-small cell lung cancer (NSCLC).MethodsThis study included patients diagnosed with stage III NSCLC in the Surveillance, Epidemiology, and End Results database from 2010 to 2017 (N = 3,512). The CS was calculated as CS(y|x) = OS(y + x)/OS(x), where OS(y + x) and OS(x) were the overall survival (OS) in the year (y + x) and year x, respectively, calculated by the Kaplan–Meier method. We used the least absolute shrinkage and selection operator (LASSO) regression to identify predictors and developed the CS-nomogram based on these predictors and the CS formula.ResultsThe CS analysis provided real-time updates on survival, with 5-year OS improving dynamically from 14.4 to 29.9%, 47.9, 66.0, and 80.8% (after 1–4 years of survival). Six independent predictors (age, tumor size, N status, surgery, radiotherapy and chemotherapy) were identified for the development of the CS-nomogram and its web version (https://dynapp.shinyapps.io/NSCLC/). The model performed with an excellent concordance index (C-index) of 0.71 (95% CI: 0.70–0.72), and a median time-dependent AUC of 0.71–0.73 from 200 iterations 5-fold cross-validation.ConclusionThe study demonstrated the improvement in real-time OS over time in stage III NSCLC survivors and developed the novel CS-nomogram to provide patients with updated survival data. It provided novel insights into clinical decisions in follow-up and treatment for survivors, offering a convenient tool for optimize resource allocation.

AimThis study aimed to explore the association between the ratio of 4-pyridoxine (4-PA) to pyridoxal 5′-phosphate (PLP) (4-PA/PLP) and diabetic retinopathy (DR) and further assess the mediating effect of Endothelial Activation and Stress Index (EASIX) on the association between 4-PA/PLP and DR.MethodsIn this cross-sectional study, 1,698 patients with diabetes from the National Health and Nutrition Examination Survey were included. According to the median, 4-PA/PLP was categorized into a high-level group (≥0.89) and a low-level group (

Objective: To investigate the effect and mechanism of Nup50 on radiation-induced DNA damage repair to radiation and explore the potential role of Nup50 as radioprotective target. Methods: The Nup50 gene was knocked down in HUVEC cells using lentiviruses. Colony formation, CCK-8, and flow cytometry were performed to determine the viability, proliferation and apoptosis of HUVEC cells treated with γ-rays，respectively. The extent of DNA damage was evaluated by using comet assay and immunofluorescence staining against γ-H2AX. In addition, we explored the role of Nup50 in DNA damage response (DDR) pathways through western blotting assay. Finally, nuclear and chromatin fractionation were performed to determine the potential molecular mechanism underlying the radiation protection function of Nup50 knockdown. Results: Nup50 knockdown increased the cellular resistance to ionizing radiation. The CCK-8 data showed that cell viability was significantly increased in the Nup50 knockdown group after radiation (t ​= ​4.23, P ​

Abstract 2-dimensional (2D) piezoelectric materials have gained significant attention due to their potential applications in flexible energy harvesting and storage devices. Recently, niobium oxide dihalides NbOI2 stands out as a multifunctional anisotropic semiconductor family with an exceptionally high lateral piezoelectric constant (~21.8 pm/V), making it a promising candidate for energy conversion applications. Here we report the experimental observation of anisotropic in-plane piezoelectricity in multilayer NbOI2. Current-voltage relationships reveal a significant piezotronic effect in two typical crystalline orientations. Additionally, cyclic tensile and release experiments demonstrate an intrinsic current output of up to 140 pA when subjected to a tensile strain of 0.51%. A flexible piezoelectric nanogenerator prototype is demonstrated on the human finger and wrist, which opens up new avenues for the development of wearable electronic devices and provides valuable insights for further exploration in this field.

Abstract During bacterial cytokinesis, polymers of the bacterial tubulin FtsZ coalesce into the Z ring to orchestrate divisome assembly and septal cell wall synthesis. Previous studies have found that Z ring condensation and stability is critical for successful cell division. However, how FtsZ filaments condense into a Z ring remains enigmatic and whether septal cell wall synthesis can feedback to the Z ring has not been investigated. Here, we show that FtsZ-associated proteins (Zaps) play important roles in Z ring condensation and stability, and discover septal cell wall synthesis as a novel player for Z ring condensation and stabilization in Escherichia coli and Caulobacter crescentus. Moreover, we find that the interaction between the Z ring membrane anchor, FtsA, and components of the septal cell wall synthetic complex are critical for septal cell wall synthesis-mediated Z ring condensation. Altogether, these findings suggest that the divisome is a self-enhancing machine in these two gram-negative bacteria, where the Z ring and the septal cell wall synthetic complex communicate with and reinforce each other to ensure robustness of cell division.

Abstract Background The cGAS-STING pathway is an important component of the innate immune system and plays significant role in acetaminophen-induced liver injury (AILI). Pentagalloylglucose (PGG) is a natural polyphenolic compound with various beneficial effects, including anti-cancer, antioxidant, anti-inflammatory, and liver-protective properties; however, whether it can be used for the treatment of AILI and the specific mechanism remain unclear. Materials and methods A cell culture model was created to study the effect of PGG on cGAS-STING pathway activation using various techniques including western blotting (WB), real-time quantitative polymerase chain reaction (RT-qPCR), immunofluorescence (IF), and immunoprecipitation (IP). The effect of PGG was investigated in vivo by establishing a dimethylxanthenone acetic acid (DMXAA)-mediated activation model. An AILI model was used to evaluate the hepatoprotective and therapeutic effects of PGG by detecting liver function indicators, liver histopathology, and cGAS-STING pathway-related indicators in mice with AILI. Results PGG blocked cGAS-STING pathway activation in bone marrow-derived macrophages (BMDMs), THP-1 cells, and peripheral blood mononuclear cells (PBMCs) in vitro. Furthermore, PGG inhibited the generation of type I interferons (IFN-I) and the secretion of inflammatory factors in DMXAA-induced in vivo experiments. In addition, PGG also reduced serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP), improved liver tissue damage and apoptosis, and inhibited the cGAS-STING pathway activation caused by acetaminophen. In terms of the mechanism, PGG disrupted the connection between STING and TBK1. Conclusions PGG exerts a protective effect against AILI by blocking the cGAS-STING pathway, offering a promising treatment strategy.

Abstract There are no nationwide surveys on antihypertensive drugs in China. In order to assess the current status of antihypertensive drug therapy in patients with hypertension and analyzed factors that may affect combination therapy, using convenience sampling, we recruited 305,624 patients with hypertension from the Chinese Cardiovascular Association Database‐Hypertension Center between January 2019 and December 2021. Chi‐squared test was performed to analyze the administered antihypertensive drug types and their combinations in different hospital settings. Logistic regression was used to assess the factors influencing combination therapy. We found around 33.1% of the participants had stage 2 and above hypertension, of which 67.9% were treated with combination therapy. In community or general hospitals, the most common monotherapy was calcium channel blockers (CCB), angiotensin‐converting enzyme inhibitor/angiotensin II receptor inhibitor (ACEI/ARB) and diuretic were the main single‐pill combinations (SPCs), and ACEI/ARB and CCB were the main free combination. From 2019 to 2021, the rates of combination therapy increased (58.8%–64.1%) with SPCs from 25.9% to 31.0% and free combination from 31.9% to 32.6%. Patients aged

Abstract Optic disc (OD) and optic cup (OC) segmentation is an important task in ophthalmic medicine and is crucial for aiding glaucoma screening. With the development of smart healthcare and the increase of large datasets, there is an increasing number of research efforts targeting OD and OC segmentation, making it particularly important to provide a systematic review of the latest advances in the field. This paper presents a systematic review of commonly used datasets, evaluation metrics, and related research results in the field of OD and OC segmentation. The advantages and disadvantages of segmentation techniques based on traditional and deep learning methods are comparatively analysed. In addition, this study emphasizes the importance of OD and OC segmentation efforts in smart healthcare. Despite the technological advances, the lack of generalization capability is still a major obstacle limiting its clinical application. To address this issue, this study explores unsupervised domain adaptation methods to enhance the generalization performance of segmentation techniques and provide new strategies for clinical diagnosis. Finally, this paper discusses the challenges and future research directions faced by OD and OC segmentation when applied in the medical field to help readers comprehensively grasp the research dynamics in this area.

Abstract Background The quality of low-light endoscopic images involves applications in medical disciplines such as physiology and anatomy for the identification and judgement of tissue structures. Due to the use of point light sources and the constraints of narrow physiological structures, medical endoscopic images display uneven brightness, low contrast, and a lack of texture information, presenting diagnostic challenges for physicians. Methods In this paper, a nonlinear brightness enhancement and denoising network based on Retinex theory is designed to improve the brightness and details of low-light endoscopic images. The nonlinear luminance enhancement module uses higher-order curvilinear functions to improve overall brightness; the dual-attention denoising module captures detailed features of anatomical structures; and the color loss function mitigates color distortion. Results Experimental results on the Endo4IE dataset demonstrate that the proposed method outperforms existing state-of-the-art methods in terms of Peak Signal-to-Noise Ratio (PSNR), Structural Similarity (SSIM), and Learned Perceptual Image Patch Similarity (LPIPS). The PSNR is 27.2202, SSIM is 0.8342, and the LPIPS is 0.1492. It provides a method to enhance image quality in clinical diagnosis and treatment. Conclusions It offers an efficient method to enhance images captured by endoscopes and offers valuable insights into intricate human physiological structures, which can effectively assist clinical diagnosis and treatment.

Abstrac t Prior research has explored the effects of engaging with real or virtual natural landscapes and listening to music during aerobic exercise on short-term affect, however, the specific differences in the improvement of short-term affect by different combinations of Virtual Reality (VR) and music rhythm require further investigation. The objective of this study is to investigate the effects of various combinations of VR and music on short-term mood, thereby providing a reference for future research on public fitness. This study recruited 132 valid participants (mean age 24.0 ± 0.9 years), with a gender distribution of 68 males and 64 females. Participants were randomly assigned to one of four groups: Visual-Music (V-M), Music-Visual (M-V), Visual-only (V), and Music-only (M). The exercise mode was 15 min of aerobic power cycling with 2 min of low-intensity power cycling intervals in the middle. After the exercise, the participants were asked to sit and then performed either a VR intervention or a music intervention for 15 min. The collected indicators included blood pressure, positive/negative affect, and heart rate variability indicators (RMSSD, SDNN, LF/HF). Data analysis included descriptive statistics, repeated measures ANOVA, and multifactor ANOVA. The effect of different VR and Music combined with exercise interventions on the improvement of short-term affect was analyzed based on the effect size (ɳp2) and combined with the significance p-value. Intra-group results showed that DBP, positive and negative affect, SDNN, RMSSD indicators in V-M group were significant differences (p 0.05). Aerobic exercise with consistent intensity and the combined visual-auditory interventions (M-V and V-M) significantly improved blood pressure, and the short-term affect of physiological responses (LF/HF, SDNN, RMSSD), along with subjective affect measures, compared to other groups. These findings suggest that incorporating VR and music with exercise can effectively enhance short-term affect, recommending an integrated approach to aerobic exercise and relaxation through music and visual exposure to natural environments.

Abstract Background Imbalances in gut microbiota (GM) have been proposed as a potential contributing factor to diabetic complications; however, the causal relationship remains incompletely understood. Methods Summary statistics were obtained from genome-wide association studies (GWAS) of 196 gut microbial taxa, including 9 phyla, 16 classes, 20 orders, 32 families, and 119 genera. These data were then analyzed using mediation Mendelian randomization (MR) analyses to explore the potential mediating effect of diabetes complications risk factors on the relationship between gut microbiota and specific diabetic complications such as diabetic kidney disease (DKD), ketoacidosis, and diabetic retinopathy (DR). Results In our Mendelian analysis, we observed negative associations between Bifidobacterial order and Actinomycete phylum with DKD in type 1 diabetes (T1D) as well as early DKD in T1D. Conversely, these taxa showed positive associations with ketoacidosis in type 2 diabetes (T2D). In reverse Mendelian analysis, we found that DR in both T1D and T2D as well as ketoacidosis in T2D affected the abundance of Eubacterium fissicaten genus and LachnospiraceaeUCG010 family within the gut microbiota. Conclusions Our findings provide compelling evidence for causal relationships between specific GM taxa and various diabetes complications. These insights contribute valuable knowledge for developing treatments targeting diabetes-related complications.