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Abstract Background Physical education exercise has a positive effect on adolescents' physical fitness and working memory function, but it has not been found in studies on Uyghur adolescents, an ethnic minority in western China. To this end, this study conducted a randomized controlled trial of physical education exercise for 12 weeks in Uyghur adolescents from Xinjiang, China. The effects of physical education exercise on physical fitness and working memory function of Uyghur adolescents were analyzed. Methods Randomly selected 222 Chinese Xinjiang Uyghur secondary school students were randomly divided into a control group and an exercise intervention group. The physical education exercise was conducted for 12 weeks for the intervention group, and no intervention was conducted for the control group. The subjects were tested on physical fitness items (height, weight, waist circumference, 1000 m/800 m running) and working memory function before and after the intervention. Pre- and post-intervention test results were analyzed using paired-sample t-tests (within-group comparisons). Post-intervention comparisons between intervention and control groups were analyzed using analysis of covariance (between-group comparisons). Results The differences between the pre-intervention and post-intervention physical fitness indicators of Chinese Uyghur adolescents in the intervention group were statistically significant (all P values 0.05). Conclusion The study confirmed that physical education exercise may be one of the effective means to improve the physical fitness and working memory function of Chinese Xinjiang adolescents. However, whether the same intervention effect exists in other groups should be further studied and analyzed. Our study provides reference and help for the government and education department to develop future educational policies to enhance physical education exercise in schools. Trial registration This study adheres to CONSORT guidelines. This study was conducted retrospectively trial registration: ChiCTR2400088822; China Clinical Trial Registration; August 27, 2024.

Abstract Zinc‐bromine flow batteries (ZBFBs) hold promise as energy storage systems for facilitating the efficient utilisation of renewable energy due to their low cost, high energy density, safety features, and long cycle life. However, challenges such as uneven zinc deposition leading to zinc dendrite formation on the negative electrode and parasitic hydrogen evolution reaction during charging pose risks of membrane puncturing and short circuits, thereby limiting energy density improvements. Additionally, the sluggish and non‐reversible Br2/Br− redox reaction hampers battery power density enhancements. Given that electrode properties significantly influence the rate and reversibility of these redox reactions, modifications to the negative and positive electrodes are crucial. While inert carbon‐based electrodes are favoured for their corrosion resistance and conductivity, their hydrophobic nature and low electrochemical activity restrain the performance of ZBFBs. The authors present a comprehensive review of recent advancements in both negative and positive electrode modifications in ZBFBs. It also puts forward future research directions aimed at overcoming existing challenges, with the ultimate objective of promoting the efficient utilisation of ZBFBs.

Abstract The rebound of liquid droplets on solid surfaces exhibits behavior reminiscent of elastic spheres, albeit with distinct contact dynamics. While the rapid detachment of droplets from surfaces holds significant relevance for various applications, previous endeavors relying on engineered surfaces can only reduce the contact time to several milliseconds, primarily due to capillary effects dominating droplet bounce. Here, we present ultrafast rebound by designing heterogeneous core-shell droplets encapsulating a particle (DEP), which achieves an unprecedentedly short contact time of 0.3 ms and 0.05 ms with polydimethylsiloxane and glass particles, respectively. This remarkable contact-time reduction is universally applicable to diverse systems, including both water and oil droplets, elastic and rigid particles, super-repellent and superlyophilic surfaces, and is effective across a wide range of impact velocities. Beyond exhibiting liquid-like dynamics, DEP manifests solid-like behavior owing to asynchronized motions between the particle and the droplet, which effectively breaks down the dominance of capillarity. With systematic experimental and analytical studies, we delineate contact times in three bouncing regimes and identify critical conditions governing regime transitions. DEP amalgamates the bouncing dynamics of both solids and liquids, offering a robust and versatile strategy for tailoring contact time to suit diverse applications involving solid-liquid composite systems.

Abstract Background To introduce a new flange technique (called the Z.S. fixation technique) for 8 − 0 polypropylene suture in scleral fixation of a one-piece intraocular lens (IOL) and evaluate its effectiveness and safety. Methods All surgeries were performed using two strategies. First, the Z.S. fixation technique was used to fix 8 − 0 polypropylene sutures to the sclera and the two haptics of a one-piece IOL, respectively. The one-piece IOL previously implanted in the anterior chamber was then relocated to the posterior chamber. Finally, the suture ends outside the sclera were cauterized into flanges and buried in the sclera. All effectiveness and safety data related to the Z.S. technique were recorded and compared. Results The Z.S. fixation technique was employed in 16 eyes of 13 patients, with a follow-up duration of at least 6 months. Postoperative uncorrected distance visual acuity (UDVA) was greatly improved in most of the operated eyes (11/16). The mean log MAR UDVA after surgery was significantly improved compared with that before surgery (0.93 ± 0.72 vs. 1.53 ± 0.73, P = 0.002). IOLs in the vast majority of operated eyes (15/16) remained stable during half-year follow-up. No severe intra-/post-operative complications were observed in any of the operated eyes. Conclusion The Z.S. fixation technique for 8 − 0 polypropylene suture in scleral fixation of one-piece IOL reduced surgical injuries and had ideal surgical effectiveness and safety.

Aeromonas hydrophila is a significant fish pathogen responsible for substantial economic losses in the global aquaculture industry. To promote bacterial disease resistance during early vaccine immunity in fish, we investigated the regulation of fermentation broth in grass carp (Ctenopharyngodon idella). We focused on leukocyte phagocytosis, the innate immune response, and short-term disease resistance. These investigations were conducted in vitro using C. idella kidney (CIK) cells after exposure to the A. hydrophila vaccine. In this study, we observed that CIK cells exhibited typical phagocytic activity in response to immunostimulation by A. hydrophila. Transcriptome analysis suggested that exposure to inactivated A. hydrophila rapidly activated the host's innate immune defense system, as evidenced by the stimulation of 12 higher-order network correlations among immune-related differentially expressed genes. Moreover, in vivo studies revealed that the fermentation broth of A. hydrophila promoted cytophagocytosis in the blood leukocytes of grass carp by regulating the innate immune response during vaccine-induced immunity. This modulation conferred histopathological protection against early A. hydrophila infection within 7 days post-immunostimulation. These findings provide new insights into the regulatory role of microbial fermentation broth in the early non-specific immune response of fish, highlighting its protective effects against bacterial invasion during the critical period before the establishment of specific immunity.

Magnetic nanoparticles (MNPs) have significant potential in the applications of precision diagnosis and treatment, particularly image monitoring and targeted therapies, owing to their magnetic response and magneto-thermal properties. However, further development of target modulation technologies is required to achieve deep-tissue imaging with high sensitivity. In this paper, we propose an integrated approach combining magnetic modulation of MNPs with magneto-thermo-acoustic imaging. We have designed a three-axis Helmholtz coil and a magneto-thermo-acoustic imaging model, forming the basis of an integrated experimental platform designed for both modulation and imaging. Numerical simulations and experiments have been conducted to examine how various particle characteristics influence outcomes under magnetic fields, and an integrated platform combining a three-axis Helmholtz coil with magneto-thermo-acoustic imaging has been successfully developed. This platform enables, for the first time, real-time monitoring of the regulation of MNPs, and we have carefully validated its effectiveness through experiments. The results demonstrate the advantages of dual-modality in electromagnetic modulation and coupled imaging, highlighting the potential of such a system to enhance the regulation of MNPs under image guidance for precision diagnostic and therapeutic applications.

Systemic sclerosis (SSc) is a perplexing autoimmune disorder, characterized by mysterious causes, high mortality rates, and a lack of effective treatments. The role of abnormal glycosylation in the onset of autoimmune diseases has been recognized for some time. Nonetheless, the intricate details of intact glycopeptides in SSc remain elusive owing to challenges in their detection. In this study, we characterized plasma immunoglobulin G (IgG) intact N-glycopeptides from 30 SSc patients and 30 healthy controls (HCs) via our recently developed intact glycopeptide analysis method GlycoQuant. Through this approach, twelve differentially expressed intact N-glycopeptides were identified. The correlation of specific intact N-glycopeptides with the clinical features of SSc patients was analyzed. The results revealed a notable increase in the levels of 6 intact N-glycopeptides (IgG2-N3H3F1, IgG2-N3H4F1, IgG2-N4H4F1, IgG2-N4H5F1, IgG2-N5H4F1, and IgG2-N5H5F1) and a decrease in the levels of another set of 6 intact N-glycopeptides (IgG1-N4H3F1, IgG2-N3H6F1A1, IgG2-N4H4F1A1, IgG2-N5H3F1, IgG3-N4H3F1, and IgG3-N4H4F1). These changes in the levels of intact N-glycopeptides are associated with various aspects of SSc, including diffuse SSc (dSSc), interstitial lung disease (ILD), disease progression, cardiovascular involvement and C-reactive protein in the peripheral blood. In summary, this study offers a detailed overview of the intact N-glycopeptide profile in the peripheral blood of patients with SSc, providing valuable insights that could propel further research into SSc.

Abstract Graphene films have been applied in the thermal management of electronic devices due to their high thermal conductivity. However, the ever‐increasing power and local heat flux density of electronic chips require graphene films with excellent heat flux carrying capacity. Enhancing the heat flux carrying capacity is highly challenging, and the key is to maintain high thermal conductivity while increasing film thickness. Gases released during film assembly and the resulting catastrophic structural destruction should be responsible for the trade‐off between film thickness and thermal conductivity. Herein, the evolution of the pore structure is investigated during the assembly of graphene films and propose the construction of gas escape channels for the preparation of thick graphene films. The process involves using humidification treatment and freeze‐drying GO films to pre‐construct the ordered flat pore structure. The microstructure optimization of graphene films with more order, fewer wrinkles and defects, and larger grain size is achieved. After optimization, graphene films with ultra‐high thermal conductivity (1781 W m−1 K−1) and a thickness over 100 µm are realized. These films exhibit exceptional heat dissipation and cooling capabilities in high heat flux density (≈2000 W cm−2). This finding holds significant potential for guiding the thermal management of high‐power devices.

Abstract Alzheimer’s disease (AD) is the leading form of dementia, characterized by the accumulation and aggregation of amyloid in brain. Transient receptor potential vanilloid 2 (TRPV2) is an ion channel involved in diverse physiopathological processes, including microglial phagocytosis. Previous studies suggested that cannabidiol (CBD), an activator of TRPV2, improves microglial amyloid-β (Aβ) phagocytosis by TRPV2 modulation. However, the molecular mechanism of TRPV2 in microglial Aβ phagocytosis remains unknown. In this study, we aimed to investigate the involvement of TRPV2 channel in microglial Aβ phagocytosis and the underlying mechanisms. Utilizing human datasets, mouse primary neuron and microglia cultures, and AD model mice, to evaluate TRPV2 expression and microglial Aβ phagocytosis in both in vivo and in vitro. TRPV2 was expressed in cortex, hippocampus, and microglia.Cannabidiol (CBD) could activate and sensitize TRPV2 channel. Short-term CBD (1 week) injection intraperitoneally (i.p.) reduced the expression of neuroinflammation and microglial phagocytic receptors, but long-term CBD (3 week) administration (i.p.) induced neuroinflammation and suppressed the expression of microglial phagocytic receptors in APP/PS1 mice. Furthermore, the hyper-sensitivity of TRPV2 channel was mediated by tyrosine phosphorylation at the molecular sites Tyr(338), Tyr(466), and Tyr(520) by protein tyrosine kinase JAK1, and these sites mutation reduced the microglial Aβ phagocytosis partially dependence on its localization. While TRPV2 was palmitoylated at Cys 277 site and blocking TRPV2 palmitoylation improved microglial Aβ phagocytosis. Moreover, it was demonstrated that TRPV2 palmitoylation was dynamically regulated by ZDHHC21. Overall, our findings elucidated the intricate interplay between TRPV2 channel regulated by tyrosine phosphorylation/dephosphorylation and cysteine palmitoylation/depalmitoylation, which had divergent effects on microglial Aβ phagocytosis. These findings provide valuable insights into the underlying mechanisms linking microglial phagocytosis and TRPV2 sensitivity, and offer potential therapeutic strategies for managing AD.

Abstract Rice is a staple food for over half of the global population, necessitates efficient and cost-effective production methods to ensure food security. However, direct seeding of rice often encounters challenges due to adverse environmental conditions, resulting in increased seeding costs. In this study, we analyzed the germination and physiological data of sixty-six rice varieties under cold and submergence conditions. Our results demonstrate that selecting rice varieties with superior germination capacity in these adverse conditions can improve germination rates by 39.43%. Transcriptomic and metabolomic analyses of two contrasting varieties revealed potential regulatory mechanisms involving hormonal pathways and the glycerophospholipid metabolism pathway. Furthermore, we found that the exogenous application of specific metabolites provides a cost-effective seed enhancement strategy for varieties with poor germination capacity. These findings suggest that combining suitable variety selection with seed enhancement treatments can significantly reduce seeding costs in rice production. This research offers valuable insights for developing resilient rice varieties and cost-effective seeding strategies, potentially contributing to improved rice cultivation practices and enhanced global food security.

Abstract Objective Acute myeloid leukemia (AML) is a malignant clonal proliferative disease with a high mortality rate. The combination therapy of BCL-2 inhibitor Venetoclax (VEN) and hypomethylating agents (HMAs) has significant anti-leukemia activity. Methods We analyzed the efficacy, safety and immune response characteristics of AML patients who were unfit for high-dose chemotherapy and accepted the medication of VEN + HMAs. Results After VEN + HMAs treatment, 31 newly diagnosed AML patients had the morphologic leukemia-free state rate (MLFS%) of 80.6% (25/31), complete response rate (CR%) of 54.8% (17/31), the minimal residual disease negative rate (MRD-%) of 51.6% (16/31), and the median progression-free survival (PFS) of 14 months. After treatment, the proportion of bone marrow primitive cells, the MRD level, white blood cell (WBC) count, fibrinogen (FIB) level and the proportion of B cells were significantly decreased. The red blood cell (RBC) count, hemoglobin (HGB) level, platelet count (PLT) count, activated partial thromboplastin time (APTT), the proportion of total T cells, CD8 + T cells and the IFN-γ level were significantly increased. After VEN + HMAs treatment, 12 relapsed AML patients had a MLFS% of 50% (6/12), CR% of 33.3% (4/12), MRD-% of 25% (3/12), and a median PFS of 7 months. After treatment, the proportion of bone marrow primitive cells and MRD level were slightly decreased, the proportions of CD8 + T cells and NK cells were significantly increased, the proportion of B cells and IL-10 level were significantly decreased. 12 AML patients who receive microtransplantation (MST) treatment using VEN + HMAs as a pretreatment regimen had a PFS of 20.5 months, which was much greater than VEN + HMAs group alone. Hematological recovery was better in the MST group with significantly increased RBC count, HGB level and PLT count. The most common adverse events were myelosuppression, agranulocytosis, infection and cardiovascular toxicity. No fatal adverse events were reported. Conclusion The combination of BCL-2 inhibitors and HMAs had good efficacy and safety in AML patients who were unfit for high-dose chemotherapy, which may improve the immune microenvironment and enhance anti-leukemia immune response.

Abstract Background The pericoronary fat attenuation index (FAI) has emerged as a novel and sensitive biomarker reflecting the degree of coronary artery inflammation. Semaglutide has been demonstrated to exert a cardiovascular protective effect independent of hypoglycemia; however, its impact on coronary artery inflammation remains elusive. This study aimed to investigate the association between semaglutide treatment and coronary artery inflammation based on FAI in patients with type 2 diabetes mellitus (T2DM). Methods This study enrolled 497 T2DM patients who underwent coronary computed tomography angiography (CCTA) at Hebei General Hospital, of whom 93 treated with semaglutide (Sema+) and 404 did not (Sema-). Clinical data, laboratory indicators, and CCTA parameters were collected and compared between the two groups at baseline. Propensity score matching (PSM) was used to adjust for confounders, and pericoronary FAI was compared. Multivariate linear regression models were used to analyze the association between semaglutide treatment and pericoronary FAI. Results Before PSM, pericoronary FAI of the LAD and LCX was lower in patients treated with semaglutide than those without semaglutide treatment. The results of the PSM analysis revealed a lower FAI in all three major coronary arteries in the Sema + group compared to the Sema- group. Multivariate linear regression analyses revealed an independent association between semaglutide treatment and reduced FAI in all three major coronary arteries. This association varied across T2DM patients of differing profiles. Conclusion Semaglutide treatment may be associated with lower coronary artery inflammation in patients with T2DM, which might partially explain its cardiovascular protective mechanism.

Abstract Traumatic dental injuries (TDIs) of teeth occur frequently in children and adolescents. TDIs that impact the periodontal tissues and alveolar tissue can be classified into concussion, subluxation, extrusive luxation, intrusive luxation, lateral luxation, and avulsion. In these TDIs, management of injured soft tissue, mainly periodontal ligament, and dental pulp, is crucial in maintaining the function and longevity of the injured teeth. Factors that need to be considered for management in laxation injuries include the maturation stage of the traumatic teeth, mobility, direction of displacement, distance of displacement, and whether there are alveolar fractures. In avulsion, the maturation stage of the permanent tooth, the out-socket time, storage media/condition of the avulsed tooth, and management of the PDL should also be considered. Especially, in this review, we have subdivided the immature tooth into the adolescent tooth (Nolla stage 9) and the very young tooth (Nolla stage 8 and below). This consensus paper aimed to discuss the impacts of those factors on the trauma management and prognosis of TDI to provide a streamlined guide for clinicians from clinical evaluation, diagnostic process, management plan decision, follow-up, and orthodontic treatment for tooth luxation and avulsion injuries.

The problem of Pb pollution emission from sludge during its combustion has received a widespread attention. The migration and transformation characteristics of Pb during sludge combustion were analyzed by a combination of experimental studies and simulations with the help of inductively coupled plasma mass spectrometry (ICP-MS), specific surface and porosity analyzer (BET), and X-ray diffraction (XRD), etc. The influences of factors such as the addition of CaO, moisture, and acidic gases on the volatilization of Pb and the solid-phase enrichment were investigated, and the activity strength of the adsorption of PbCl2 molecules on different surfaces were revealed with the combination of the density-functional theory. The experimental results showed that the increase of Pb residue to 61.37% after sludge combustion at 900 °C was mainly influenced by the melting effect. The addition of 4% CaO was unfavorable to the enrichment of Pb in the solid-phase product at combustion temperatures of 700−900 °C, while the residual rate of Pb in the solid-phase product increased by 7.82% at 1 000 °C with the addition of 4% CaO. The Pb residual rate was reduced by 28.43% at 20% sludge moisture content compared to burnt dry sludge. The presence of acidic gases favored Pb immobilization, but the promotion varied inconsistently with concentration. CO2 had an obvious promotion effect on the fixation of Pb, and the larger the concentration, the more favorable to the enrichment of Pb, when the simulated flue gas was fed with 30% CO2, the residual rate of Pb increased by 23.37%. While SO2 had a weak promoting effect on Pb immobilization, and with the increase of SO2 concentration, the residual rate of Pb was firstly increased and then decreased, and in the combustion condition with 0.15% SO2, the residual rate of Pb was increased to the best extent, which was only 4.82%. The residual rate of Pb after the combustion of sludge loaded with 4% CaO at 20% H2O/20O2/80N2, 20CO2/20O2/60N2 and 0.15CO2/20O2/79.85N2 increased by −3.61%, 8.77% and 7.65%, respectively. Simulations showed that after the adsorption of PbCl2 molecules on the clean CaO(001) surface, the Pb atoms of Pb molecules underwent orbital hybridization with Osurf atoms, whereas on the surface of CaO(001) with pre-adsorbed CO2, SO2 and H2O, the Pb atoms of PbCl2 molecules would undergo orbital hybridization with OH, OC, and OS atoms, which led to an increase of adsorption energies of PbCl2 molecules after adsorption on the surface of CaO(001) with pre-adsorbed CO2, SO2, and H2O on the surface of CaO(001) with pre-adsorbed CO2, SO2 and OS atoms, which resulted in the increase of adsorption energy after adsorption by 90.069, −13.458 and −55.836 kJ/mol, respectively, compared with that on the clean surface. In summary, controlling the combustion temperature and adding an appropriate amount of CaO can effectively improve the residual rate of Pb, the presence of moisture inhibits the immobilization of Pb, and the CO2 and SO2 atmospheres are favorable for the enrichment of Pb in the solid-phase products.

After desulphurization, the trace amount of SO2 in the tail gas of coal-fired power plant will lead to the deterioration of CO2 adsorption performance of potassium-based adsorbent. Using crystalline aluminum chloride as precursor, the solid adsorbent K2CO3/Al2O3 was prepared by sol-gel method. The adsorption characteristics of CO2 in SO2 (0, 150, 250 and 400 mg/m3) atmosphere were simulated by fixed bed reaction system. Combined with the BET and XRD characterization methods, the pore structure and material composition of the adsorbent were analyzed. The influence of SO2 on the surface adsorption of CO2 by K2CO3/Al2O3(0001) was studied by using the DFT theory. The results showed that in the ideal atmosphere, the cumulative adsorption capacity of CO2 of potassium adsorbent is 1.72 mmol/g. In the presence of 150 mg/m3 SO2 in the reaction atmosphere, the potassium adsorbent reacts with SO2 to form K2SO3, resulting in a 19.77% decrease in adsorption capacity (1.38 mmol/g). When the concentration of SO2 increases to 400 mg/m3, the cumulative adsorption capacity of CO2 of potassium-based adsorbent gradually decreases to 1.26 mmol/g, the adsorption performance of CO2 of the adsorbent is deteriorated. The adsorption capacity of potassium-based adsorbent decreases to 1.1 mmol/g after seven cycles, and the cycle performance is deteriorated. The adsorption sites of CO2 and SO2 on the surface of K2CO3/Al2O3(0001) are Al-O bridge sites, and the H2O molecules are O top sites. The adsorption of SO2 on K2CO3/Al2O3(0001) surface is greater than that on H2O and CO2. When H2O and CO2 are co-adsorbed, the O-s orbitals and H-s orbitals overlap in the CO2 molecules, so that the two can promote each other during surface adsorption. Due to the active p orbitals of S and O atoms, the SO2 molecules preferentially preempt the adsorption site of CO2 and inhibit the adsorption of CO2 on the surface when co-adsorbed with CO2. The catalytic effect of H2O molecules on the adsorption of SO2 on the surface of K2CO3/Al2O3(0001) is greater than that of CO2. The presence of H2O will accelerate the reaction between SO2 and the surface, leading to the deterioration of the adsorption capacity of CO2 on the surface of the adsorbent. When CO2 and H2O are co-adsorbed on K2CO3/Al2O3(0001) surface, the carbonation mechanism is H+ and OH− in H2O molecules, which forms \begin{document}${\mathrm{HCO}}_3^- $\end{document} with \begin{document}${\mathrm{CO}}_3^{2-} $\end{document} and CO2 respectively. The reaction energy barrier is 1.12 eV, and the reaction heat is −1.47 eV.

Abstract As the largest organ in the human body, skeletal muscle is essential for breathing support, movement initiation, and maintenance homeostasis. It has been shown that programmed cell death (PCD), which includes autophagy, apoptosis, and necrosis, is essential for the development of skeletal muscle. A novel form of PCD called ferroptosis is still poorly understood in relation to skeletal muscle. In this study, we observed that the activation of ferroptosis significantly impeded the differentiation of C2C12 myoblasts into myotubes and concurrently suppressed the expression of OTUB1, a crucial deubiquitinating enzyme. OTUB1-silenced C2C12 mouse myoblasts were used to investigate the function of OTUB1 in ferroptosis. The results show that OTUB1 knockdown in vitro significantly increased C2C12 ferroptosis and inhibited myogenesis. Interestingly, the induction of ferroptosis resulting from OTUB1 knockdown was concomitant with the activation of autophagy. Furthermore, OTUB1 interacted with the P62 protein and stabilized its expression by deubiquitinating it, thereby inhibiting autophagy-dependent ferroptosis and promoting myogenesis. All of these findings demonstrate the critical role that OTUB1 plays in controlling ferroptosis, and we suggest that focusing on the OTUB1-P62 axis may be a useful tactic in the treatment and prevention of disorders involving the skeletal muscle.

Abstract DARS, encoding for aspartyl-tRNA synthetase, is implicated in the pathogenesis of various cancers, including renal cell carcinoma, glioblastoma, colon cancer, and gastric cancer. Its role in BCR/ABL1-negative myeloproliferative neoplasms (MPNs), however, remains unexplored. This study aimed to elucidate the expression of DARS in patients with MPNs (PV 23, ET 19, PMF 16) through immunohistochemical analysis and to examine the profiles of circulating immune cells and cytokines using flow cytometry. Our findings indicate a significant overexpression of DARS in all MPNs subtypes at the protein level compared to controls (P

Abstract The rapid development of high-throughput sequencing in recent years has facilitated great progress in the molecular-targeted therapy of hematological malignancies, including leukemia, lymphoma, and multiple myeloma. BCL-2 inhibitors are among the most important molecular-targeted agents. Immunotherapy for hematologic malignancy has rapidly increased in popularity in recent years and has been proven to improve the overall survival rate. However, few clinical studies have investigated combination therapy with BCL-2 inhibitors and immunotherapies, such as immune molecule-targeted drugs or immune cell adoptive therapy. In this review, we discuss the drug discovery process, current clinical application status, and resistance and tolerance issues associated with BCL-2 inhibitors. We emphasize their important role in regulating the immune system and propose that the combination of BCL-2 inhibitors with immunotherapy may be one of the most promising treatment methods for hematologic malignancies.

In this study, the present status of the public health and wellness sector in China is examined. The main objective is to evaluate the financial risk among publicly listed companies in the sector. Despite the significant expansion of the industry, research in this domain remains limited. Moreover, it frequently lacks depth, especially when it comes to financial studies designed especially for publicly traded companies. Current models for assessing corporate financial risk are frequently applied in diverse industries without necessary adjustments. Therefore, this study examines the financial performance and operational health of five publicly listed anonymized companies between 2020 and 2023. Using an efficient methodology that includes reliable data collection and quality assurance, we analyze key performance indicators such as annual revenues, liquidity ratios, and debt-to-equity ratios to assess financial stability and growth potential. Our findings reveal varied revenue trends shaped by external market shocks such as the COVID-19 pandemic. These trends highlight both the resilience of the sector and its vulnerabilities. To evaluate potential financial risks and outliers, the abnormal revenue patterns are also identified using Z-score. Benchmarking is also conducted using industry averages which provides a clearer understanding of competitive positioning. Several suggestions are made in light of the analysis to manage debt, increase liquidity, and leverage digital transformation for long-term growth. Several future directions are also presented to continue research in the domain. Overall, this study offers valuable information for stakeholders navigating the complexities of the public health and wellness industry in China.

Poultry manure is one of the important sources of antibiotic pollution in agricultural soil and groundwater. Recently, the excessive discharge of goat manure has resulted in groundwater environmental challenges and negative impacts. It is of practical significance that such wastes can be converted into functional materials to promote the resource utilization of waste and reduce the risk of antibiotic contamination. In this study, Fe (Ⅱ)-loaded goat manure biochar (Fe-GMC) was prepared by pyrolyzing goat manure and iron salts and used to activate peroxymonosulfate (PMS) for tetracycline (TC) degradation in groundwater. The as-prepared Fe-GMC exhibited good catalytic performance for PMS activation due to its porous surface and rich oxygen-containing groups. Under the conditions of catalyst dosage of 0.2 g/L, PMS dosage of 1.0 mM, and pH of 3.0, TC was removed 81.3% within 60 min. In addition, the TC degradation efficiency was inhibited to different extents by inorganic anions (HCO3−>Cl−>NO3−) in water. Furthermore, the quenching experiments, electron paramagnetic resonance (EPR) experiments, and X-ray photoelectron spectroscopy (XPS) spectra analysis indicated that the generation of hydroxyl radicals (•OH) was responsible for TC degradation. Particularly, Fe-GMC produces a strong oxidizing agent. This study provides an efficient and environmentally friendly tetracycline degradation catalyst, which offers a new theoretical basis for water environmental remediation.

The objective of this retrospective cohort study was to assess the relationship between Corona Disease 2019 (COVID-19) and Secukinumab treatment in patients with Spondylarthritis (SpA) in China during the omicron surge. Researchers retrieved 1018 medical records of Secukinumab-treated patients between January 2020 and January 2023 from the West China Hospital of Sichuan University. Out of these, 190 SpA patients from the rheumatology clinic were selected for the study. Guided phone questionnaires were administered by research staff to collect baseline characteristics, SpA disease status, and COVID-19 clinical outcomes. Cohabitants served as the control group and provided COVID-19 related data. Of the 190 potential SpA patients, 122 (66%) completed the questionnaire via phone, along with 259 cohabitants. 84.4% of SpA patients were diagnosed with Ankylosing Spondylitis (AS), and 15.6% were diagnosed with Psoriatic Arthritis (PsA). The rate of SARS-CoV-2 infection was 83.6% in the Secukinumab group and 88.8% in the cohabitants control group, with no significant difference (OR = 0.684, CI 0.366–1.275). One instance of severe COVID-19 was observed in the Secukinumab group, while two were identified in the cohabitants control group. Patients in the Secukinumab group had less time with fever caused by COVID-19 (p = 0.004). Discontinuing Secukinumab after SARS-CoV-2 infection did not significantly affect the course of COVID-19 or worsen SpA status according to our data. Our study suggests that administering Secukinumab to SpA patients does not increase their susceptibility to contracting SARS-CoV-2, and may have a positive effect on the course of SARS-CoV-2 infection.

Background The Coronavirus disease 2019 (COVID-19) pandemic has brought a heavy burden to the world, interestingly, it shares many clinical symptoms with systemic lupus erythematosus (SLE). It is unclear whether there is a similar pathological process between COVID-9 and SLE. In addition, we don’t know how to treat SLE patients with COVID-19. In this study, we analyse the potential similar pathogenesis between SLE and COVID-19 and explore their possible drug regimens using bioinformatics and systems biology approaches.Methods The common differentially expressed genes (DEGs) were extracted from the COVID-19 datasets and the SLE datasets for functional enrichment, pathway analysis and candidate drug analysis.Result Based on the two transcriptome datasets between COVID-19 and SLE, 325 common DEGs were selected. Hub genes were identified by protein-protein interaction (PPI) analysis. few found a variety of similar functional changes between COVID-19 and SLE, which may be related to the pathogenesis of COVID-19. Besides, we explored the related regulatory networks. Then, through drug target matching, we found many candidate drugs for patients with COVID-19 only or COVID-19 combined with SLE.Conclusion COVID-19 and SLE patients share many common hub genes, related pathways and regulatory networks. Based on these common targets, we found many potential drugs that could be used in treating patient with COVID-19 or COVID-19 combined with SLE.

BackgroundMetabolic disorders are common in individuals with Turner syndrome (TS). Hyperuricemia is associated with metabolic syndrome. This study investigated the serum uric acid (SUA) profile in patients with TS.MethodsA retrospective observational study was conducted with 145 patients with TS. A total of 72 normal girls were in the control group from 2015 to 2024: 86 TS patients were treated with growth hormone (GH), 80 with stanozolol, and 52 with estrogen.ResultsHyperuricemia was present in 33.1% (47/145) of patients with untreated TS and in 16.67% (12/72) of the controls (P < 0.001). Multivariable linear regression analysis showed that BMISDS, fasting serum glucose, and eGFR explained 34.4% (model R2 = 0.344) of the total variation in SUA in the untreated TS group. SUA and SUASDS (SUA standard deviation score) levels generally showed a slow rising tendency with age. SUA increased significantly in the first year of stanozolol initiation (P = 0.032), while adding estrogen and stanozolol improved the lipid profile during the whole assessment period.ConclusionGirls with TS showed a slow rising tendency in SUA and SUASDS with age and had higher SUA and SUASDS levels and incidence of hyperuricemia compared to their healthy female peers. The independent risk factors for hyperuricemia in pediatric patients with TS were BMISDS, HOMA-IR, glucose, and eGFR. The incidence of hyperuricemia increased in the first year of stanozolol treatment.

BackgroundGiven the prevalent utilization of integrated traditional Chinese and western medicine (ITCWM) in the management of acute pancreatitis, the majority of studies have concentrated on severe cases, lacking robust evidence-based medical research. Real-world investigations can provide an objective assessment of the clinical effectiveness of combining traditional Chinese medicine with western medicine. Consequently, relying on real-world research, we intend to evaluate the clinical efficacy and safety of the combined approach in treating mild to moderate acute pancreatitis.MethodsA total of 563 AP patients from Henan Provincial Hospital of Traditional Chinese Medicine were collected from January 2019 to October 2023. A propensity score matching (PSM) analysis was conducted to evaluate the clinical efficacy of traditional Chinese medicine (TCM) in treating mild to moderate acute pancreatitis. Patients were divided into a control group (61 cases) and an integrated traditional Chinese and Western medicine (ITCWM) group (120 cases). To further assess the clinical efficacy of TCM enema in the treatment of mild to moderate acute pancreatitis, PSM analysis was conducted across three groups. The patients were categorized into a control group (n = 49), an oral TCM treatment group (OCM group, n = 274), and an oral TCM plus enema treatment group (OCM+E group, n = 131). Logistic regression was used to analyze factors after treatment in each group, and the Kaplan-Meier method compared symptom duration in each group.ResultsCompared with the control group, the ITCWM group significantly decreased C-reactive protein (CRP, mg/L) (17.8 [1.2–59.5] vs. 8.0 [3.3–33.5], P = 0.022), shortened the duration of abdominal distension, abdominal pain, nausea and bitter taste symptoms (P < 0.05), and shortened the length of hospital stay (median 19.0 and 11.5 days, respectively, P = 0.001); Compared with the other two groups, the neutrophil percentage (NEUT%) was lower (74.1 vs. 61.9 vs. 59.5, P < 0.05) and serum prealbumin (PA, mg/L) was higher (116.0 vs. 184.4 vs. 220.0, P < 0.05), the length of hospitalization (days) was shortened (19.0 vs.12.0 vs.10.0, P < 0.05) in the OCM+E group.ConclusionThe combination of traditional Chinese medicine and modern medicine has been shown to effectively decrease inflammatory indicators in patients with mild to moderate acute pancreatitis, leading to a reduction in symptom duration and hospitalization period, as well as promoting disease recovery. Notably, the use of traditional Chinese medicine in conjunction with enema therapy yields more pronounced benefits.

A mission planning algorithm based on genetic algorithm was designed for LEO satellite IoT constellation with no inter-satellite links, aimed to achieve real-time data communication through multiple ground stations while maximized the resource allocation of satellites and ground stations.Firstly, the objective function to maximized the service duration of satellites in orbit and the constraints on clashed tasks were designed, constructed the mission planning model for LEO satellite IoT constellation.Then, based on genetic algorithm, clashed tasks and early stopping mechanism were introduced, and the mission planning algorithm for the LEO satellite IoT constellation was designed.On this basis, experiments were conducted use a constellation of 18 LEO communication satellites without inter-satellite links and 4 ground stations.In addition, in order to verified the performance of the algorithm, first come first service (FCFS) algorithm was also used for mission planning of the experimental data.The experiments compared with FCFS showed that the designed mission planning algorithm for LEO satellite IoT constellation could significantly improve the scheduling capacity of ground stations for receiving data of communication satellites, addressed the contradiction of insufficient ground stations with a large number of satellites.

Abstract Background Tyrosine kinase inhibitor (TKI) resistance is a significant factor exacerbating the burden on chronic myeloid leukemia (CML) patients and impacting clinical efficacy. The main goal is to offer new insights into overcoming drug resistance in treating CML. Methods Imatinib (IM) resistant K562/IM cells were generated using gradient induction. Responses to IM, lycorine, and autophagy modulators were assessed using CCK-8. Protein expression of Beclin-1, Atg5, LC3, Caspase-3, P62, Bax, Bcl-2, and P-gp was detected using Western blot. Lycorine-induced apoptosis and cell cycle changes were evaluated through flow cytometry, while autophagy alterations were detected using monodansylcadaverine (MDC) staining. In the K562/IM mice model, non-obese diabetic severe combined immunodeficent (NOD-SCID) mice were subcutaneously inoculated with K562/IM cells. After 17 days of lycorine injection, assessments included tumor size, hematoxylin–eosin (HE) staining, and Ki67 expression. Results After 72 h of IM treatment, K562/IM cells showed a 55.86-fold increase in drug resistance compared to K562 cells. Lycorine treatment for 24 h inhibited cell proliferation and induced G0/G1 phase cell cycle arrest and apoptosis in both K562 and K562/IM cells. MDC staining indicated reduced autophagy in K562/IM cells, mitigated by lycorine. In vivo experiments demonstrated reduced tumor size and Ki67 proliferation index in the lycorine treatment group (K562+L, K562/IM+L) compared to the control group, particularly in the drug-resistant group. However, no significant change in Ki67 was observed in the K562 group after lycorine treatment. Conclusion In summary, K562/IM cells displayed heightened autophagy levels compared to K562 cells. Lycorine effectively impeded the proliferation of K562/IM cells through diverse mechanisms, including reduced autophagy, enhanced apoptosis, and induced cell cycle arrest.

Abstract Helicobacter pylori (H. pylori), together with its CagA, has been implicated in causing DNA damage, cell cycle arrest, apoptosis, and the development of gastric cancer. Although lncRNA H19 is abundantly expressed in gastric cancer and functions as a pro-oncogene, it remains unclear whether lncRNA H19 contributes to the oncogenic process of H. pylori CagA. This study investigates the role of H19 in the DNA damage response and malignancy induced by H. pylori. It was observed that cells infected with CagA+ H. pylori strain (GZ7/cagA) showed significantly higher H19 expression, resulting in increased γH2A.X and p-ATM expression and decreased p53 and Rad51 expression. Faster cell migration and invasion was also observed, which was reversed by H19 knockdown in H. pylori. YWHAZ was identified as an H19 target protein, and its expression was increased in H19 knockdown cells. GZ7/cagA infection responded to the increased YWHAZ expression induced by H19 knockdown. In addition, H19 knockdown stimulated cells to enter the G2-phase and attenuated the effect of GZ7/cagA infection on the cellular S-phase barrier. The results suggest that H. pylori CagA can upregulate H19 expression, participate in the DNA damage response and promote cell migration and invasion, and possibly affect cell cycle arrest via regulation of YWHAZ.

Abstract Background Apolipoprotein E4 (ApoE4) allele is the strongest genetic risk factor for late‐onset Alzheimer's disease, and it can aggravate depressive symptoms in non‐AD patients. However, the impact of ApoE4 on AD‐associated depression‐like behaviors and its underlying pathogenic mechanisms remain unclear. Methods This study developed a 5xFAD mouse model overexpressing human ApoE4 (E4FAD). Behavioral assessments and synaptic function tests were conducted to explore the effects of ApoE4 on cognition and depression in 5xFAD mice. Changes in peripheral and central lipid metabolism, as well as the levels of serotonin (5‐HT) and γ‐aminobutyric acid (GABA) neurotransmitters in the prefrontal cortex, were examined. In addition, the protein levels of 24‐dehydrocholesterol reductase/glycogen synthase kinase‐3 beta/mammalian target of rapamycin (DHCR24/GSK3β/mTOR) and postsynaptic density protein 95/calmodulin‐dependent protein kinase II/brain‐derived neurotrophic factor (PSD95/CaMK‐II/BDNF) were measured to investigate the molecular mechanism underlying the effects of ApoE4 on AD mice. Results Compared with 5xFAD mice, E4FAD mice exhibited more severe depression‐like behaviors and cognitive impairments. These mice also exhibited increased amyloid‐beta deposition in the hippocampus, increased astrocyte numbers, and decreased expression of depression‐related neurotransmitters 5‐HT and GABA in the prefrontal cortex. Furthermore, lipid metabolism disorders were observed in E4FAD, manifesting as elevated low‐density lipoprotein cholesterol and reduced high‐density lipoprotein cholesterol in peripheral blood, decreased cholesterol level in the prefrontal cortex, and reduced expression of key enzymes and proteins related to cholesterol synthesis and homeostasis. Abnormal expression of proteins related to the DHCR24/GSK3β/mTOR and PSD95/CaMK‐II/BDNF pathways was also observed. Conclusion This study found that ApoE4 overexpression exacerbates depression‐like behaviors in 5xFAD mice and confirmed that ApoE4 reduces cognitive function in these mice. The mechanism may involve the induction of central and peripheral lipid metabolism disorders. Therefore, modulating ApoE expression or function to restore cellular lipid homeostasis may be a promising therapeutic target for AD comorbid with depression. This study also provided a better animal model for studying AD comorbid with depression.

Abstract Background Kidney transplantation (KT) improves clinical outcomes of patients with end stage renal disease. Little has been reported on the impact of early post-operative surgical complications (SC) on long-term clinical outcomes following KT. We sought to determine the impact of vascular complications, urological complications, surgical site complications, and peri-graft collections within 30 days of transplantation on patient survival, graft function, and hospital readmissions. Methods We conducted a single-centre, observational cohort study examining adult patients (≥ 18 years) who received a kidney transplant from living and deceased donors between January 1st, 2005 and December 31st, 2015 with follow-up until December 31st, 2016 (n = 1,334). Univariable and multivariable analyses were performed with Cox proportional hazards models to analyze the outcomes of SC in the early post-operative period after KT. Results The cumulative probability of SC within 30 days of transplant was 25%, the most common SC being peri-graft collections (66.8%). Multivariable analyses showed significant relationships between Clavien Grade 1 SC and death with graft function (HR 1.78 [95% CI: 1.11, 2.86]), and between Clavien Grades 3 to 4 and hospital readmissions (HR 1.95 [95% CI: 1.37, 2.77]). Conclusions Early SC following KT are common and have a significant influence on long-term patient outcomes.

Abstract Evidence suggests associations between COVID-19 patients or vaccines and glycometabolic dysfunction and an even higher risk of the occurrence of diabetes. Herein, we retrospectively analyzed pancreatic lesions in autopsy tissues from 67 SARS-CoV-2 infected non-human primates (NHPs) models and 121 vaccinated and infected NHPs from 2020 to 2023 and COVID-19 patients. Multi-label immunofluorescence revealed direct infection of both exocrine and endocrine pancreatic cells by the virus in NHPs and humans. Minor and limited phenotypic and histopathological changes were observed in adult models. Systemic proteomics and metabolomics results indicated metabolic disorders, mainly enriched in insulin resistance pathways, in infected adult NHPs, along with elevated fasting C-peptide and C-peptide/glucose ratio levels. Furthermore, in elder COVID-19 NHPs, SARS-CoV-2 infection causes loss of beta (β) cells and lower expressed-insulin in situ characterized by islet amyloidosis and necrosis, activation of α-SMA and aggravated fibrosis consisting of lower collagen in serum, an increase of pancreatic inflammation and stress markers, ICAM-1 and G3BP1, along with more severe glycometabolic dysfunction. In contrast, vaccination maintained glucose homeostasis by activating insulin receptor α and insulin receptor β. Overall, the cumulative risk of diabetes post-COVID-19 is closely tied to age, suggesting more attention should be paid to blood sugar management in elderly COVID-19 patients.

Abstract With advancements in sedation techniques,painless gastrointestinal endoscopy has expanded from a diagnostic role to surgeries. This study aims to explore strategies for enhancing patient satisfaction, improving safety, and reducing complications. Tailoring preoperative assessments beyond American Society of Anesthesiologists classification is crucial, especially for the elderly and pediatric populations. Integration of scales and point-of-care testing (POCT) provides a precise baseline evaluations. Optimizing anesthetic strategies through improved drug selection and enhanced perioperative monitoring follows accurate patient evaluations. While post-procedural follow-up is essential, existing studies in this area are limited. This article outlines current painless gastrointestinal endoscopy technology, emphasizing POCT establishment, personalized monitoring, and optimized anesthesia strategies for a positive impact on patient outcomes.

Abstract Objective In the pathogenesis of myeloproliferative neoplasms (MPN), inflammation plays an important role. However, it is unclear whether there is a causal link between inflammation and MPNs. We used a bidirectional, two-sample Mendelian randomization (MR) approach to investigate the causal relationship between systemic inflammatory cytokines and myeloproliferative neoplasms. Methods A genome-wide association study (GWAS) of 8293 European participants identified genetic instrumental variables for circulating cytokines and growth factors. Summary statistics of MPN were obtained from a GWAS including 1086 cases and 407,155 controls of European ancestry. The inverse-variance-weighted method was mainly used to compute odds ratios (OR) and 95% confidence intervals (Cl). Results Our results showed that higher Interleukin-2 receptor, alpha subunit (IL-2rα) levels, and higher Interferon gamma-induced protein 10 (IP-10) levels were associated with an increased risk of MPN (OR = 1.36,95%CI = 1.03–1.81, P = 0.032; OR = 1.55,95%CI = 1.09–2.22, P = 0.015; respectively).In addition, Genetically predicted MPN promotes expression of the inflammatory cytokines interleukin-10 (IL-10) (BETA = 0.033, 95% CI = 0.003 ~ 0.064, P = 0.032) and monokine induced by interferon-gamma (MIG) (BETA = 0.052, 95% CI = 0.002–0.102, P = 0.043) and, on activation, normal T cells express and secrete RANTES (BETA = 0.055, 95% CI = 0.0090.1, P = 0.018). Conclusion Our findings suggest that cytokines are essential to the pathophysiology of MPN. More research is required if these biomarkers can be used to prevent and treat MPN.

Roots play essential roles in the acquisition of water and minerals from soils in higher plants. However, water or nutrient limitation can alter plant root morphology. To clarify the spatial distribution characteristics of essential nutrients in citrus roots and the influence mechanism of micronutrient deficiency on citrus root morphology and architecture, especially the effects on lateral root (LR) growth and development, two commonly used citrus rootstocks, trifoliate orange (Poncirus trifoliata L. Raf., Ptr) and red tangerine (Citrus reticulata Blanco, Cre), were employed here. The analysis of the mineral nutrient distribution characteristics in different root parts showed that, except for the P concentrations in Ptr, the last two LR levels (second and third LRs) had the highest macronutrient concentrations. All micronutrient concentrations in the second and third LRs of Ptr were higher than those of Cre, except for the Zn concentration in the second LR, which indicates that Ptr requires more micronutrients to maintain normal root system growth and development. Principal component analysis (PCA) showed that B and P were very close in terms of spatial distribution and that Mo, Mn, Cu, and Fe contributed significantly to PC1, while B, Cu, Mo, and Zn contributed significantly to PC2 in both rootstocks. These results suggest that micronutrients are major factors in citrus root growth and development. The analysis of root morphology under micronutrient deficiency showed that root growth was more significantly inhibited in Ptr and Cre under Fe deficiency (FeD) than under other micronutrient deficiencies, while Cre roots exhibited better performance than Ptr roots. From the perspective of micronutrient deficiency, FeD and B deficiency (BD) inhibited all root morphological traits in Ptr and Cre except the average root diameter, while Mn deficiency (MnD) and Zn deficiency (ZnD) had lesser impacts, as well as the morphology of the stem. The mineral nutrient concentrations in Ptr and Cre seedlings under micronutrient deficiency revealed that single micronutrient deficiencies affected both their own concentrations and the concentrations of other mineral nutrients, whether in the roots or in stems and leaves. Dynamic analysis of LR development revealed that there were no significant decreases in either the first or second LR number in Ptr seedlings under BD and ZnD stress. Moreover, the growth rates of first and second LRs in Ptr and Cre did not significantly decrease compared with the control under short-term (10 days) BD stress. Altogether, these results indicate that micronutrients play essential roles in citrus root growth and development. Moreover, citrus alters its root morphology and biological traits as a nutrient acquisition strategy to maintain maximal micronutrient acquisition and growth. The present work on the spatial distribution characteristics and micronutrient deficiency of citrus roots provides a theoretical basis for effective micronutrient fertilization and the diagnosis of micronutrient deficiency in citrus.

The position of makeup air inlets has significant impacts on fire combustion and the smoke spread characteristics. Therefore, influences of makeup air inlets located at different heights on fire combustion and smoke diffusion were discussed through experiments. Experimental results show that when the air inlet was 0.3 m above the ground, the flame width was the largest and the heat release rate (HRR) was the highest. When the height of air inlets was 2.3 m, both the heights of fire flame and smoke layer were the highest. The heights of air inlets were 0.3, 1.3, 2.3 and 3.3 m, the corresponding HRR of the fire was 1.12, 1.06, 0.87 and 0.81 times that of the HRR of the fire natural combustion. There is a logarithmic function relationship between the air inlets height and the HRR, and a polynomial function relationship between the flame height and the air inlets height. When the air inlets was installed at 3.3 m above the ground, the smoke layer height was the lowest, only approximately 1.0 m. Therefore, for rooms with similar dimensions, the makeup air inlets are recommended installed at 1.3–2.3 m above the ground.

Microplastics (MPs) (64.12 %) of detected MPs were