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Abstract Background Manipulation under anesthesia (MUA) has been recommended for refractory arthrofibrosis after anterior cruciate ligament (ACL) reconstruction. However, the effectiveness of MUA to restore normal kinematics of the arthrofibrotic knee is still unclear. The objective of this study was to evaluate tibiofemoral and patellofemoral kinematics in six degrees-of-freedom (6DOF) in patients with arthrofibrosis before and after MUA. Methods Computed tomography and dual fluoroscopic imaging system were used to assess in vivo knee kinematics. Ten patients (6 women and 4 men; 32.6 ± 6.5y, 168.4 ± 7.8 cm, 61.8 ± 13.2 kg) were included in this study. The tibiofemoral and patellofemoral kinematics in 6DOF were collected before and one year after MUA. A simple analysis of variance was used to evaluate kinematic data of preoperative arthrofibrotic knee, postoperative arthrofibrotic knee, and the contralateral knee. Results The patella in the postoperative arthrofibrotic knee shifted significantly more inferiorly compared to the preoperative knee at 45° (P = 0.010), 60° (P = 0.008), and 75° (P = 0.049) of flexion. The patellar flexion in the postoperative arthrofibrotic knee significantly increased at 45° (P = 0.048), 60° (P = 0.037), and 75° (P = 0.006) of flexion compared to the preoperative arthrofibrotic knee. The patellar tilt was significantly decreased at 60° (P = 0.006) and at 75° (P = 0.037) of knee flexion in the postoperative arthrofibrotic knee compared to the contralateral knee. MUA significantly increased tibial internal rotation angle in the arthrofibrotic knee at 45° (P = 0.047), at 60° (P = 0.033), and at 75° (P = 0.021) of knee flexion. Conclusions MUA could restore normal patellar inferior shift, flexion, and tibial rotation compared to the contralateral side. However, the MUA could not restore normal patellar tilt of the arthrofibrotic knee. This indicated that improvement of patellar tilt should be emphasized in postoperative rehabilitation.

Abstract Background Childhood maltreatment (CM) is closely linked to internet addiction (IA), especially in adolescents with Major Depressive Disorder (MDD). Previous studies have shown that adolescents who experience CM are more likely to develop IA and other psychological problems. This study aims to explore the complex relationship between CM and IA through network analysis, particularly identifying the core symptoms and bridge symptoms to better understand the development of IA in these adolescents. Methods A cross-sectional study was conducted in seven hospitals in Anhui Province, China, involving 332 adolescents diagnosed with MDD using DSM-5 criteria. The Childhood Trauma Questionnaire - Short Form (CTQ-SF) and the Internet Addiction Test (IAT) were used to assess CM and IA symptoms, respectively. Gender-based network analysis was also performed. Results Network analysis constructed a CM-IA network and identified core and bridge symptoms. “Depress/moody/nervous being offline”, “Request an extension for longer time”, “Sleep loss due to late-night logins”, and “emotional abuse” emerged as central symptoms within the CM-IA network. Additionally, “emotional abuse”, “sexual abuse”, and “complaints about online time” were identified as key bridge symptoms linking CM and IA. These symptoms demonstrated significant connectivity, underscoring their critical role in linking CM and IA. Conclusion The findings highlight the complex relationship between CM and IA in adolescents with MDD. Specific symptoms, such as emotional abuse and online-related symptoms, play important roles in understanding and intervening in adolescent IA. Future interventions should target these core and bridge symptoms for more effective prevention and treatment.

Hard X-ray microscopes with 20–30 nm spatial resolution ranges are an advanced tool for the inspection of materials at the nanoscale. However, the limited efficiency of the focusing optics, for example, a Fresnel zone plate (ZP) lens, can significantly reduce the power of a nanoprobe. Despite several reports on ZP lenses that focus hard X-rays with 20 nm resolution – mainly constructed by zone-doubling techniques – a systematic investigation into the limiting factors has not been reported. We report the structural effects on the focusing and imaging efficiency of 20–30 nm-resolution ZPs, employing a modified beam-propagation method. The zone width and the duty cycle (zone width/ring pitch) were optimized to achieve maximum efficiency, and a comparative analysis of the zone materials was conducted. The optimized zone structures were used in the fabrication of Pt-hydrogen silsesquioxane (HSQ) ZPs. The highest focusing efficiency of the Pt-HSQ-ZP with a resolution of 30 nm was 10% at 7 keV and >5% in the range 6–10 keV, whereas the highest efficiency of the Pt-HSQ-ZP with a resolution of 20 nm was realized at 7 keV with an efficiency of 7.6%. Optical characterization conducted at X-ray beamlines demonstrated significant enhancement of the focusing and imaging efficiency in a broader range of hard X-rays from 5 keV to 10 keV, demonstrating the potential application in hard X-ray focusing and imaging.

Abstract Background The Interleukin-6 (IL-6)-signal transducer and activator of transcription 3 (STAT3) pathway, along with the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway, are critical contributors to neuroinflammation in Alzheimer’s disease (AD). Although previous research outside the context of AD has indicated that the IL-6-STAT3 pathway may regulate the cGAS-STING pathway, the exact molecular mechanisms through which IL-6-STAT3 influences cGAS-STING in AD are still not well understood. Methods The activation of the IL-6-STAT3 and cGAS-STING pathways in the hippocampus of 5×FAD and WT mice was analyzed using WB and qRT-PCR. To explore the effects of IL-6 deficiency, Il6 +/− mice were crossed with 5×FAD mice, and the subsequent impact on hippocampal STAT3 pathway activity, cGAS-STING pathway activation, amyloid pathology, neuroinflammation, and cognitive function was evaluated through WB, qRT-PCR, immunohistochemistry, ThS staining, ELISA, and behavioral tests. The regulatory role of STAT3 in the transcription of the Cgas and Sting genes was further validated using ChIP-seq and ChIP-qPCR on hippocampal tissue from 5×FAD and Il6 −/− : 5×FAD mice. Additionally, in the BV2 microglial cell line, the impact of STAT3 activation on the transcriptional regulation of Cgas and Sting genes, as well as the production of inflammatory mediators, was examined through WB and qRT-PCR. Results We observed marked activation of the IL-6-STAT3 and cGAS-STING pathways in the hippocampus of AD mice, which was attenuated in the absence of IL-6. IL-6 deficiency reduced beta-amyloid deposition and neuroinflammation in the hippocampus of AD mice, contributing to cognitive improvements. Further analysis revealed that STAT3 directly regulates the transcription of both the Cgas and Sting genes. These findings suggest a potential mechanism involving the STAT3-cGAS-STING pathway, wherein IL-6 deficiency mitigates neuroinflammation in AD mice by modulating this pathway. Conclusion These findings indicate that the STAT3-cGAS-STING pathway is critical in mediating neuroinflammation associated with AD and may represent a potential therapeutic target for modulating this inflammatory process in AD.

The correlation of prior austenite grain (PAG) size, mechanical properties, and the variant selection in martensite transformation of a 2 GPa grade automobile steel has been systematically investigated by using a combination of scaning electron microscopy (SEM), electron backscatter diffraction (EBSD), and uniaxial tesile tests. As the austenitizing temperature decreases from 970 °C to 870 °C, the as-quenched microstructure of the studied steel is fully lath martensite. Meanwhile, the average size of PAG is refined from 7.2 ± 3.9 μm to 2.1 ± 1.2 μm, and the volume fraction of high angle grain boundaries (HAGB) is increased from 59.8% to 72.3%, accompanied with an increased number fraction of grains belonging to closely spaced planes (CP) group. With the refinement of the PAGs, the martensitic variant selectivity becomes strong, and the Bain group variant selection discretely transites to the CP group, resulting in a dominate CP group. Consequently, a tensile strength of 2014 ± 33 MPa, a tensile elongtation of 12.9 ± 0.5% and a maximum strength × ductility production of 26.0 ± 1.4 GPa·%, are obtained when the austenitization temperature is at 920 °C.

Abstract Objective To analyze the clinical efficacy of autologous platelet rich plasma (PRP) injection in the treatment of knee osteoarthritis (KOA) and its influence on related biomarkers such as interleukin-1 beta (IL-1β), tumor necrosis factor-alpha (TNF-α), and high-sensitivity C-reactive protein (hs-CRP). Method 150 study subjects are randomly selected from KOA patients received treatment in the Third Hospital of Bethune Hospital from January 2022 to January 2023. After enrollment, patients are randomly numbered 1–100. 75 patients with odd and even numbers are included in the control group and the observation group, respectively. The former is cured with etocoxib, while the latter is treated with autologous PRP injection based on this. The clinical efficacy, relevant biomarkers (IL-1β, TNF-α, hs-CRP), and Lysholm knee score scale and Fugl Meyer assessment (FMA) scores are compared and analyzed. Results The total effective rate of 94.67% (71/75) in the observation group was higher than 84.00% (63/75) in the other one group (P 0.05. When the treatment period is at 1 and 2 months, the IL-1β, TNF-α, hs-CRP levels within the group were lower than before treatment, while the Lysholm knee joint score and FMA scale score were higher than before treatment (P

Abstract Burnout, depression, anxiety, and stress negatively impact the well-being and retention of healthcare professionals. The interplay of these symptoms is understudied. Utilizing network analysis, this study examined the interrelationships among these symptom clusters in clinical therapists in China. An anonymous survey was conducted among clinical therapists from 41 tertiary psychiatric hospitals in China. Burnout was assessed using the Maslach Burnout Inventory-Human Service Survey (MBI-HSS), while symptoms of depression, anxiety, and stress were assessed via the Depression, Anxiety, and Stress Scale-21 (DASS-21). Analyses were performed to identify central symptoms and bridge symptoms of this network. A total of 419 participants were included in this survey. The prevalence rate for burnout, depression, anxiety, and stress was 19.8%, 22.2%, 17.9%, and 8.6%, respectively. Network analysis indicated that stress symptoms had the highest expected influence values, closely followed by emotional exhaustion from MBI-HSS. Notably, emotional exhaustion emerged as the strongest bridge of expected influence. The stability of the expected influence and bridge expected influence was robust, with coefficients at 0.75. The study’s findings underscore the importance of recognizing the central symptoms and bridge symptoms, which could lead to more effective early detection and intervention for burnout, depression, anxiety, and stress among clinical therapists.

Abstract Duck plague virus (DPV) causes the highly pathogenic duck plague, and the envelope glycoprotein I (gI), as one of the key virulence genes, has not yet had its critical virulence sites identified through screening. This study used reverse genetics technology to target the gI, specifically within the DPV genome. Four DPV mutants with gI N-glycosylation site mutations were designed and constructed, and these mutant strains were successfully rescued. Our results confirmed that three asparagine residues of gI (N69, N78, and N265) are N-glycosylation sites, and western blot analysis substantiated that glycosylation at each predicted N-glycosylation site was compromised. The deglycosylation of gI leads to the protein misfolding and subsequent retention in the endoplasmic reticulum (ER). The subsequent deglycosylated gI is carried into the Golgi apparatus (GM130) in the interaction of gE. Compared to the parental virus, the mutated virus shows a 66.3% reduction in intercellular transmission capability. In ducks, the deglycosylation of gI significantly reduces DPV replication in vivo, thereby weakening the virulence of DPV. This study represents the first successful creation of a weak DPV virus strain by specific mutation at the N-glycosylation site. The findings provide a foundational understanding of DPV pathogenesis and form the basis for developing live attenuated vaccines against the disease.

Abstract Objective Given the lack of global consensus on anesthesia selection for peritoneal dialysis catheter (PDC) placement via open surgery, this study investigates the safety and efficacy of combining local infiltration anesthesia (LIA) with monitored anesthesia care (MAC) in patients with end-stage renal disease (ESRD). Methods This retrospective analysis of ESRD patients who underwent open surgical placement of PDC in the Department of Nephrology, the First Affiliated Hospital of the Army Medical University from 1 August 2020 to 31 May 2022. Patients were categorized into two groups based on anesthesia method: LIA group and LIA + MA group. MA was defined as preoperative sedation (0.2–0.7 µg/kg/h) with dexmedetomidine injection (Huidrican trade name, DEX), and intraoperative analgesia with dexrazoxane injection (Garonin trade name, DEZ) as appropriate according to the patients’ pain scores. We compared the general clinical data of the two groups of patients, the changes in blood pressure and heart rate during the whole operation, the intraoperative and postoperative pain, the total duration of the operation and the immediate postoperative complications. Results The study included 123 patients (59 in the LIA + MAC group and 64 in the LIA group). The LIA + MA group exhibited lower pain scores measured by Visual Analogue Scale(VAS) during surgery (skin incision, subcutaneous adipose tissue dissection, anterior fascia, muscle traction, posterior fascia, peritoneum, and catheterization) compared to the LIA group(p

Abstract Background With the rapid aging of the global population, identifying lifestyle patterns that effectively delay aging and reduce mortality risk is of paramount importance. This study utilizes the UK Biobank to analyze the associations of the Dietary Inflammatory Index, physical activity, and sleep on biological aging and all-cause mortality. Methods A prospective cohort study was conducted using data from over half a million UK Biobank participants. Two datasets were created by subjective and objective measurements of physical activity: the Subjective Physical Activity (SPA) and Objective Physical Activity (OPA) datasets. Lifestyle patterns, including diet habits, exercise levels, and sleep quality, were assessed within these datasets. Biological aging was quantified using validated methods, including Homeostatic Dysregulation, Klemera-Doubal Method Biological Age, Phenotypic Age, and Telomere Length. All-cause mortality data were obtained from the National Health Service. Statistical analyses included weighted linear regression and Cox proportional hazard models, adjusted for a range of covariates. Results The findings indicate that, in most cases, maintaining an anti-inflammatory diet, engaging in at least moderate physical activity, and ensuring healthy sleep conditions are associated with delayed physiological aging (Cohen’s d ranging from 0.274 to 0.633) and significantly reduced risk of all-cause mortality (HR-SPA: 0.690, 95% CI: 0.538, 0.884; HR-OPA: 0.493, 95% CI: 0.293, 0.828). These effects are particularly pronounced in individuals under 60 years of age and in women. However, it was observed that the level of physical activity recommended by the World Health Organization (600 MET-minutes/week) does not achieve the optimal effect in delaying biological aging. The best effect in decelerating biological aging was seen in the high-level physical activity group (≥ 3000 MET-minutes/week). The study also highlights the potential of biological age acceleration and telomere length as biomarkers for predicting the risk of mortality. Conclusions Choosing healthy lifestyle patterns, especially an anti-inflammatory diet, at least moderate physical activity, and healthy sleep patterns, is crucial for delaying aging and reducing mortality risk. These findings support the development of targeted interventions to improve public health outcomes. Future research should focus on objective assessments of lifestyle to further validate these associations.

Abstract Homozygous familial hypercholesterolemia (HoFH), is a rare genetic disorder characterized by dual mutations in the low-density lipoprotein receptor (LDLR) gene, leading to dysfunctional or absent LDLRs, often accompanied by severe premature Atherosclerotic Cardiovascular Disease (ASCVD) and exhibiting refractoriness to aggressive pharmacological interventions. Double filtration plasmapheresis (DFPP), a form of lipoprotein apheresis (LA), has been effectively utilized as an adjunctive treatment modality to reduce serum LDL-C levels in refractory cases of HoFH. Here, we report a case of a 36-year-old female with HoFH who developed xanthomas on her limbs and waist at age 7. Despite maximum-tolerated doses of statins from age 32, combined with ezetimibe and evolocumab, her LDL-C levels remained critically elevated at 12–14 mmol/L. Her genetic testing confirmed a homozygous LDLR mutation. At 35 years old, she experienced exertional chest pain, and percutaneous coronary intervention revealed severe calcific left main stenosis, necessitating stent implantation. Subsequently, she initiated once every 1–2 months DFPP. Pre-DFPP, her LDL-C and total cholesterol (TC) levels were 13.82 ± 3.28 and 15.45 ± 0.78 mmol/L, respectively. Post-DFPP, her LDL-C and TC levels significantly decreased to 2.43 ± 0.33 mmol/L (81.76 ± 4.11% reduction) and 3.59 ± 0.41 mmol/L (76.76 ± 2.75% reduction), respectively. Lipoprotein (a) and triglycerides also decreased by 89.10 ± 1.39% and 42.29 ± 15.68%,respectively. Two years later, there was no progression of coronary artery disease, and her symptoms and xanthomas regressed significantly. Collectively, DFPP effectively reduces LDL-C levels in refractory cases of HoFH and contributes to delaying ASCVD progression, representing an efficacious adjunctive therapeutic modality.

Abstract Suicidal ideation (SI) is a significant precursor and risk marker for suicide behaviors in major depressive disorder (MDD). Exploration of SI trajectory from a longitudinal framework are essential for treatment guidelines and clinical management of suicide risk. This study sought to explore SI trajectories and its associated clinical, sociodemographic characteristics, and initial treatment among patients with MDD. We used data from a non-interventional, national multi-centered prospective cohort study. 1 461 patients with MDD were included in the growth mixture modeling using SI at baseline, 2 weeks, 4 weeks, 8 weeks, 12 weeks, and 6 months, 9 months, and 12 months as the indicator. A multinomial regression was employed with SI trajectory as the outcome and anhedonia, depressive symptoms, atypical depressive symptoms, pharmacological treatments, and other covariates as the predictors. Four distinct SI trajectories were identified: a consistently low SI trajectory(50.7%), a persistently mild SI trajectory(20.6%), a fast declined SI trajectory(8.9%), and a slowly declined trajectory(19.8%). Compared to those with a consistently low SI trajectory, a higher score of anhedonia was associated with an increased risk of experiencing persistently mild (RRR = 1.20, 95%CI: 1.05, 1.38) and slowly declined SI (1.54, 95%CI: 1.32, 1.80). Severity of depressive symptom was also positively associated with the risk of experiencing persistently mild (1.15, 95%CI: 1.13, 1.18) and slowly declined SI (1.17, 95%CI: 1.14, 1.21). And the risk of experiencing slowly declined SI was higher for those use SSRI(1.49, 95%CI: 1.02, 2.31), and for those use antidepressant and antipsychotic/mood stabilizer combined therapy (3.78, 95%CI: 1.48, 9.61). The findings of this study are potentially useful for clinical practice as critical indicators of profiles and interventions for prognosis among patients with MDD. Further research is warranted to explore potential modifiable factors and the association between SI trajectories and suicide behavior.

Gliomas are the most prevalent primary malignant brain tumors worldwide, with glioblastoma (GBM) being the most common and aggressive type. The standard therapy for GBM has remained unchanged for nearly two decades, with no significant improvement in survival outcomes. Despite several barriers such as the tumor microenvironment (TME) and blood–brain barrier, immunotherapies bring new hope for the treatment of GBM. To better understand the development and progress of immunotherapies in GBM, we made this scientometric analysis of this field. A total of 3753 documents were obtained from the Web of Science Core Collection, with publication years ranging from 1999 to 2022. The Web of Science platform, CiteSpace, and VOS viewer were used to conduct the scientometric analysis. The results of scientometric analysis showed that this field has recently become a popular topic of interest. The United States had the most publications among 89 countries or regions. Keyword analysis indicated significant areas in the field of immunotherapies for GBM, especially TME, immune checkpoint blockades (ICBs), chimeric antigen receptor T (CAR-T) cells, vaccines, and oncolytic viruses (OVs). Overall, we hope that this scientometric analysis can provide insights for researchers and promote the development of this field.

Abstract The tight sandstone reservoris are important exploration and production target in the Xujiahe Formation in Xinchang area of Western Sichuan. Due to the various lithofacies and diagenetic alteration in distributary channel belt sandstones, the reservoirs exhibit strong heterogeneity. The strong heterogeneity makes the identification of petrologically superior sandbodies a great challenge. In order to better understand reservoir quality, this study constructs a model between diagenetic alterations and reservoir quality within distributary channel belts. 73 plug samples were taken from 17 wells located in the channel belt. An integration of thin sections, X-ray diffraction, carbon and oxygen isotope ratios, cathodoluminescence, and micro-CT were analysed for the genesis and distribution of reservoir quality. The results show that subaqueous distributary channels are formed under various hydrodynamics, resulting in different lithofacies. The thicknesses of channels can be divided into less than 2 m, 2–6 m, and more than 6 m. The diagenetic alteration in lithofacies were identified. Coarse-grained sandstones with low content of rock fragments are relatively weakly compacted with less calcite and chlorite cementation. Fine-grained sandstones with high content of rock fragments are strongly compacted with calcite cementation during early diagenesis. The dissolution pores are related to the soluble mineral content and the distribution of mudstones. The subaqueous distributary channels formed in high-energy, moderate-energy, and low-energy hydrodynamic settings have experienced different diagenetic intensities. Additionally, fractures can effectively improve the reservoir properties. The distribution of good quality reservoirs is controlled by the combined influence of diagenetic heterogeneity and fractures. This would help to promote better understanding of reservoir quality within the subaqueous distributary channel belts in braided-river delta front.

Abstract Evaluating Community-Acquired Pneumonia (CAP) is crucial for determining appropriate treatment methods. In this study, we established a machine learning model using radiomics and clinical features to rapidly and accurately identify Severe Community-Acquired Pneumonia (SCAP). A total of 174 CAP patients were included in the study, with 64 cases classified as SCAP. Radiomic features were extracted from chest CT scans using radiomics techniques, and screened to remove irrelevant features. Additionally, clinical indicators of patients were similarly screened and constituted the clinical feature set. Subsequently, eight common machine learning models were employed to complete the SCAP identification task. Specifically, interpretability analysis was conducted on the models. In the end, we screened out 15 radiomic features (such as LeastAxisLength, Maximum2DDiameterColumn and ZonePercentage) and two clinical features: Lymphocyte (p = 0.041) and Albumin (p = 0.044). Using radiomic features as inputs in model predictions yielded the highest AUC of 0.85 on the test set. When using the clinical feature set as model inputs, the AUC was 0.82. Combining the two sets of features as model inputs, Ada Boost achieved the best performance with an AUC of 0.89. Our study demonstrates that combining radiomics and clinical data using machine learning methods can more accurately identify SCAP patients.

Abstract This study aimed to create a reduced‐salt version of Chaozhou beef meatballs (CBMs) by employing ultrasound treatment (0 and 30 min) combined with sodium bicarbonate (0%, 0.15%, and 0.3%). The ultrasound‐assisted sodium bicarbonate treatment significantly enhanced pH, salt‐soluble protein solubility (SSP), water‐holding capacity (WHC), and storage modulus (G′) of the CBMs (p

Abstract Mathematical problem posing, generally defined as the process of interpreting given situations and formulating meaningful mathematical problems, is academically important, and thus several interventions have been used to enhance this competence among students and teachers. Yet little is known about the interventions’ various components and their relative or combined effectiveness. In this meta-analysis of 26 intervention studies in mathematics, we identified nine intervention components and found that the interventions had a medium, positive, and significant mean weighted effect size. A stepwise meta-regression analysis revealed that intervention efficacy varied by moderators relevant to the research design, sample characteristics, and intervention characteristics. The findings obtained from this meta-analysis are expected to serve as a foundation for future efforts to design and implement (more) effective interventions to improve mathematical problem posing competence.

Abstract Background Amelogenesis imperfecta (AI) is a group of genetic disorders characterized by tooth discoloration and enamel defects. Patients with AI always exhibit generalized attrition and defective tooth structure, leading to the loss of occlusal vertical dimension (OVD). Appropriate rehabilitation is challenging and essential to improve patients’ aesthetics and function. Case presentation This case report presents a comprehensive management of a 30-year-old woman with hypoplastic AI. A 52-month follow-up revealed satisfactory full-mouth rehabilitation performances of lithium disilicate ceramic crowns after clinical crown lengthening, with increased vertical dimension. Conclusions Patients with severe hypoplastic AI require proper full-mouth rehabilitation. Using full-crown lithium disilicate restorations to increase the OVD by 2‒4 mm is a safe and predictable recommendation for such cases. In addition, patients with AI require complex and comprehensive management. The long-term effects of full-mouth rehabilitation with lithium disilicate ceramic crowns still necessitate further follow-ups.

PURPOSE: Systemic inflammation and body composition are associated with survival outcomes of cancer patients. This study aimed to examine the combined prognostic value of systemic inflammatory markers and body composition parameters in patients with locally advanced cervical cancer (LACC). METHODS: Patients who underwent concurrent chemoradiotherapy (CCRT) for LACC at a tertiary referral teaching hospital between January 2010 and January 2018 were enrolled. A predictive model was established based on systemic immune-inflammation index (SII) and computer tomography-derived visceral fat-to-muscle ratio (vFMR). Overall survival (OS) and progression-free survival (PFS) were assessed using the Kaplan–Meier method and Cox regression models. The model performance was assessed using discrimination, calibration, and clinical usefulness. RESULTS: In total, 212 patients were enrolled. The SII and vFMR were closely related, and both independently predicted survival (P < 0.05). A predictive model was established based on the above biomarkers and included three subgroups: high-risk [both high SII (>828) and high vFMR (>1.1)], middle-risk (either high SII or high vFMR), and low-risk (neither high SII nor high vFMR). The 3-year OS (PFS) rates for low-, middle-, and high-risk patients were 90.5% (86.0%), 73.9% (58.4%), and 46.8% (36.1%), respectively (P < 0.05). This model demonstrated satisfactory predictive accuracy (area under the curve values for predicting 3-year OS and PFS were 0.704 and 0.718, respectively), good fit (Hosmer–Lemeshow tests: P > 0.05), and clinical usefulness. CONCLUSION: Systemic inflammatory markers combined with body composition parameters could independently predict the prognosis of patients with LACC, highlighting the utilization of commonly collected indicators in decision-making processes. CLINICAL SIGNIFICANCE: The SII and vFMR, as well as their composite indices, were promising prognostic factors in patients with LACC who received definitive CCRT. Future studies are needed to explore novel therapies to improve the outcomes in high-risk patients.

Introduction: Lecithin cholesterol acyltransferase (LCAT) plays a crucial role in acyl-esterifying cholesterol in plasma, which is essential for reverse cholesterol transport (RCT). Previous studies indicated that its activity on both α and β lipoproteins interpret its effects on lipoproteins for many controversial investigations of atherosclerosis. Objectives: To better understand the relationship between LCAT, diet-induced dyslipidemia and atherosclerosis, we developed a double knockout (LCAT−/−&LDLR−/−, DKO) hamster model to evaluate the specific role of LCAT independent of LDL clearance effects. Methods: Plasma triglyceride (TG), total cholesterol (TC), high-density lipoprotein-cholesterol (HDL-C), and free cholesterol (FC) levels were measured using biochemical reagent kits. FPLC was performed to analyze the components of lipoproteins. Apolipoprotein content was assessed using western blotting (WB). The hamsters were fed a high cholesterol/high fat diet (HCHFD) to induce atherosclerosis. Oil Red O staining was employed to detect plaque formation. Peritoneal macrophages were studied to investigate the effects of LCAT on cholesterol uptake and efflux. Results: On HCHFD, DKO hamsters exhibited significantly elevated levels of TG and FC, while HDL-C was nearly undetectable without affecting TC levels, as compared to low-density lipoprotein receptor (LDLR)-deficient (LDLR−/−, LKO) hamsters. Lipoprotein profiling revealed a marked increase in plasma chylomicron/very low-density lipoprotein (CM/VLDL) fractions, along with an unexpected reduction in LDL fraction in DKO hamsters. Furthermore, DKO hamsters displayed aggravated atherosclerotic lesions in the aorta, aortic root, and coronary artery relative to LKO hamsters, attributed to a pro-atherogenic lipoprotein profile and impaired cholesterol efflux in macrophages. Conclusions: Our study demonstrates the beneficial role of LCAT in inhibiting atherosclerotic development and highlights the distinctive lipid metabolism characteristics in hamsters with familial hypercholesterolemia.

Understanding stakeholders’ differences in perceptions of ecosystem services (ES) is crucial for guiding ecological conservation and planning. However, the variations of ES perception amongst different types of residents in urbanizing areas along an urban-rural gradient are still poorly understood. Combining a questionnaire-based survey, redundancy analysis, and statistical tests, we delineated the urban-rural gradient according to local residents’ socio-economic characteristics, and investigated the differences in local residents’ perceptions of ES and potential factors affecting them in the Guanting Reservoir basin, a rapidly urbanizing basin in China. The results showed that residents living in urban-rural transitional areas attached great importance to provisioning services of providing food and domestic water, regulating services of carbon sequestration and air purification, and cultural services of providing education and training, which were 0.7%–13.1%, 0.7%–9.1% and 2.5%–21.2% higher than that of residents in other areas, respectively. Age and occupation were major factors affecting residents’ perceptions. In terms of land-use types that deliver ES, the difference in perceptions of ES delivered by grassland was the greatest amongst residents. Our results support recommendations for policymakers to take into account the stakeholders’ diverse perceptions, thus promoting residents’ sense of gain on ES.

Ischemic stroke is a leading cause of death and disability worldwide, with an increasing trend and tendency for onset at a younger age. China, in particular, bears a high burden of stroke cases. In recent years, the inflammatory response after stroke has become a research hotspot: understanding the role of inflammatory response in tissue damage and repair following ischemic stroke is an important direction for its treatment. This review summarizes several major cells involved in the inflammatory response following ischemic stroke, including microglia, neutrophils, monocytes, lymphocytes, and astrocytes. Additionally, we have also highlighted the recent progress in various treatments for ischemic stroke, particularly in the field of stem cell therapy. Overall, understanding the complex interactions between inflammation and ischemic stroke can provide valuable insights for developing treatment strategies and improving patient outcomes. Stem cell therapy may potentially become an important component of ischemic stroke treatment.

The development and application of nuclear energy is often considered as a potential solution to meet the increasing energy demand. However, it is important to acknowledge that the utilization of nuclear energy resources and the treatment of nuclear waste pollution pose significant challenges that require careful consideration and management. Therefore, it is crucial to address the challenges of uranium pollution treatment and uranium resource recovery to ensure the sustainable development of nuclear energy. The technology of photocatalytic reduction has been found to have a synergistic adsorption reduction ability, which allows it to overcome the thermodynamic limitations of single adsorption removal. As a result, photocatalytic reduction technology is widely recognized as having great potential in the removal and recycling of uranium in nuclear waste liquid. One of the key factors for the effective application of this technology is the acquisition of a catalyst with high photocatalytic reduction ability. Nitride carbon materials are considered an ideal photocatalyst for photocatalytic reduction of U（Ⅵ） due to their excellent photochemical properties, excellent physicochemical adjustability, and good chemical stability. However, the pure g-C3N4 photocatalyst still suffers from its low separation efficiency of photogenerated charge carriers, which results in unsatisfactory photocatalytic activity. In recent years, research on modifying and applying carbon nitride has provided in-depth insights into the reduction of uranium through photocatalysis. Discussing the strategy of modifying C3N4, constructing heterojunction nanostructures, and utilizing them for the photocatalytic reduction of uranium, along with the mechanisms involved. This review summarizes the recent significant progress on the design of g-C3N4-based heterostructure photocatalysts and their special separation/transfer mechanisms of photogenerated charge carriers. On the one hand, according to the key steps of photocatalytic uranium reduction, modification strategies using g-C3N4 photocatalysts can be classified into the following groups: morphology modification, band-structure regulation, and heterostructure construction. Moreover, according to the different transfer mechanisms of photogenerated charge carriers between g-C3N4 and the coupled components, the g-C3N4-based heterostructure photocatalysts can be divided into the following categories: g-C3N4-based conventional Type-Ⅱ heterojunction, g-C3N4-based Z-scheme heterojunction, g-C3N4-based S-scheme heterojunction, and g-C3N4/metal heterostructure. We also focused on the structure-activity relationship between the modification of photocatalytic materials based on carbon nitride and their photocatalytic reduction performance for U（Ⅵ）, as well as the mechanism of their catalytic reduction removal. Finally, this section offers concluding remarks and prospects for exploring the challenges and opportunities faced by advanced carbon nitride-based photocatalytic materials in the removal of uranium pollution and the recovery of uranium resources. It also provides directions for future breakthroughs.

Abstract Background Data on long-term cancer survivors treated with apatinib are lacking. This study aimed to describe the characteristics of long-term cancer survivors after apatinib-based therapy, and to know about their satisfaction degree with apatinib and severity of depression and insomnia. Methods Patients with solid tumors who had received apatinib-based therapy for at least 5 years were invited to complete an online questionnaire. Characteristics of patients and treatment, knowledge of apatinib, satisfaction degree, and severity of depression and insomnia assessed by Patient Health Questionnaire-9 and Insomnia Severity Index were collected. Results Between December 8, 2023 and March 1, 2024, a total of 436 patients completed the online questionnaire. Most patients were satisfied with the efficacy (96.6%) and safety (93.1%) of apatinib, were willing to continue apatinib treatment (99.5%), and would recommend apatinib to other patients (93.3%). Continuous apatinib treatment resulted in significant negative impact on daily life, work, or study in only two (0.5%) patients. Almost all patients currently had no or mild depression (97.0%) and insomnia (97.9%) problems. The most common patient-reported adverse events were hand-foot syndrome (21.3%) and hypertension (18.3%). Conclusions Our survey showed a high satisfaction degree with apatinib in long-term cancer survivors. Long-term apatinib treatment resulted in almost no negative impact on patient’s quality of life.

This paper investigates the optimal reinsurance-investment strategy for an insurer whose premium is subject to extrapolative bias. In other words, the insurance premium is dynamically updated by a weighted average of prior claims and the initial estimation of claims. The insurer's surplus follows a diffusion approximation process. He purchases proportional reinsurance or acquires new business to manage insurance risk, and invests his surplus in the financial market, containing a risk-free asset and a risky asset (stock). The price of the risky asset is described by a constant elasticity of variance (CEV) model. The insurer is uncertain about the models of claims and risky asset. In order to derive robust optimal reinsurance-investment strategies, we establish an optimal control problem by maximizing the insurer's expected exponential utility of terminal wealth and solve the optimization problem explicitly. Finally, we present several numerical examples to illustrate our theoretical results.

Abstract Epstein-Barr virus (EBV) related post-transplant lymphoproliferative disorder (EBV-PTLD) is a life-threatening complication after hematopoietic stem cell transplantation (HSCT) or solid organ transplantation (SOT), for which no standard therapeutic means have been developed. Significant increase expression of natural killer group 2 member D ligands (NKG2DLs) was observed on B-lymphoblastoid cells of EBV-PTLD, indicating NKG2DLs as potential therapeutic targets for treatment of EBV-PTLD. In this study, the recombinant constructs of NKG2D CAR and IL-15/IL-15Rα-NKG2D CAR were generated with a retroviral vector and then transduced to human T cells to produce NKG2D CAR-T and IL-15/IL-15Rα-NKG2D CAR-T cells, respectively. B-lymphoblastoid cell lines (B-LCLs) and the xenografted mouse models were established to evaluate the efficacy of these CAR-T cells. IL-15/IL-15Rα-NKG2D CAR-T cells exhibited superior proliferation and antigen-specific cytotoxic effect compared to NKG2D CAR-T, as IL-15/IL-15Rα signaling promoted the expansion of less differentiated central memory T cells (TCM) and increased expression of CD107a and IFN-γ. Moreover, EBV DNA load was dramatically reduced, and 80% B-LCL cells were eliminated by IL-15/IL-15Rα-NKG2D CAR-T cells after co-culturing. In-vivo study confirmed that IL-15/IL-15Rα-NKG2D CAR-T cell therapy significantly enhanced antiviral efficacy in mice, as the serum load of EBV after IL-15/IL-15Rα-NKG2D CAR-T cell infusion was 1500 times lower than the untreated control (P

Abstract Objectives To investigate the effect of neutral 10-methacryloyloxydecyl dihydrogen phosphate salt (MDP-Na) on the dentin bond strength and remineralization potential of etch-&-rinse adhesive. Methods Two experimental etch-&-rinse adhesives were formulated by incorporating 0 wt% (E0) or 20 wt% (E20) neutral MDP-Na into a basic primer. A commercial adhesive, Adper Single Bond 2 (SB, 3 M ESPE), served as the control. Sixty prepared teeth were randomly allocated into three groups (n = 20) and bonded using either one of the experimental adhesives or SB. Following 24 h of water storage, the bonded specimens were sectioned into resin-dentin sticks, with four resin-dentin sticks obtained from each tooth for microtensile bond strength (MTBS) test. Half of the sticks from each group were immediately subjected to tensile loading using a microtensile tester at a crosshead speed of 1 mm/min, while the other half underwent tensile loading after 6-month incubation in artificial saliva (AS). The degree of conversion (DC) of both the control and experimental adhesives (n = 6 in each group) and the adsorption properties of MDP-Na on the dentin organic matrix (n = 5 in each group) were determined using Fourier-transform infrared spectrometry. Furthermore, the effectiveness of neutral MDP-Na in promoting the mineralization of two-dimensional collagen fibrils and the adhesive-dentin interface was explored using transmission electron microscopy and selected-area electron diffraction. Two- and one-way ANOVA was employed to assess the impact of adhesive type and water storage on dentin bond strength and the DC (α = 0.05). Results The addition of MDP-Na into the primer increased both the short- and long-term MTBS of the experimental adhesives (p = 0.00). No difference was noted in the DC between the control, E0 and E20 groups (p = 0.366). The MDP-Na remained absorbed on the demineralized dentin even after thorough rinsing. The intra- and extra-fibrillar mineralization of the two-dimensional collagen fibril and dentin bond hybrid layer was confirmed by transmission electron microscopy and selected-area electron diffraction when the primer was added with MDP-Na. Conclusions The use of neutral MDP-Na results in high-quality hybrid layer that increase the dentin bond strength of etch-&-rinse adhesive and provides the adhesive with remineralizing capability. This approach may represent a suitable bonding strategy for improving the dentin bond strength and durability of etch-&-rinse adhesive.

The control strategy of rehabilitation robots should not only adapt to patients with different levels of motor function but also encourage patients to participate voluntarily in rehabilitation training. However, existing control strategies usually consider only one of these aspects. This study proposes a voluntary and adaptive control strategy that solves both questions. Firstly, the controller switched to the corresponding working modes (including challenge, free, assistant, and robot-dominant modes) based on the trajectory tracking error of human-robot cooperative movement. To encourage patient participation, a musculoskeletal model was used to estimate the patient’s active torque. The robot’s output torque was designed as the product of the active torque and a coefficient, with the coefficient adaptively changing according to the working mode. Experiments were conducted on two healthy subjects and four hemiplegic patients using an ankle rehabilitation robot. The results showed that this controller not only provided adaptive the robot’s output torque based on the movement performance of patients but also encouraged patients to complete movement tasks themselves. Therefore, the control strategy has high application value in the field of rehabilitation.

Abstract Background Bipolar depression (BPD) is often misdiagnosed as a major depressive disorder (MDD) in clinical practice, which may be attributed to a lack of robust biomarkers indicative of differentiated diagnosis. This study analysed the differences in various hormones and inflammatory markers to explore peripheral biomarkers that differentiate BPD from MDD patients. Methods A total of 2,048 BPD and MDD patients were included. A panel of blood tests was performed to determine the levels of sex hormones, stress hormones, and immune-related indicators. Propensity score matching (PSM) was used to control for the effect of potential confounders between two groups and further a receiver operating characteristic (ROC) curve was used to analyse the potential biomarkers for differentiating BPD from MDD. Results Compared to patients with MDD, patients with BPD expressed a longer duration of illness, more hospitalisations within five years, and an earlier age of onset, along with fewer comorbid psychotic symptoms. In terms of biochemical parameters, MDD patients presented higher IgA and IgM levels, while BPD patients featured more elevated neutrophil and monocyte counts. ROC analysis suggested that combined biological indicators and clinical features could moderately distinguish between BPD and MDD. In addition, different biological features exist in BPD and MDD patients of different ages and sexes. Conclusions Differential peripheral biological parameters were observed between BPD and MDD, which may be age-sex specific, and a combined diagnostic model that integrates clinical characteristics and biochemical indicators has a moderate accuracy in distinguishing BPD from MDD.

Abstract Light serves as a crucial external zeitgeber for maintaining and restoring physiological homeostasis in most organisms. Disrupting of light rhythms often leads to abnormal immune function, characterized by excessive inflammatory responses. However, the underlying regulatory mechanisms behind this phenomenon remain unclear. To address this concern, we use in vivo imaging to establish inflammation models in zebrafish, allowing us to investigate the effects and underlying mechanisms of light disruption on neutrophil recruitment. Our findings reveal that under sustained light conditions (LL), neutrophil recruitment in response to caudal fin injury and otic vesicle inflammation is significantly increased. This is accompanied by elevated levels of histone (H3K18) lactylation and reactive oxygen species (ROS) content. Through ChIP-sequencing and ChIP‒qPCR analysis, we discover that H3K18 lactylation regulates the transcriptional activation of the duox gene, leading to ROS production. In turn, ROS further promote H3K18 lactylation, forming a positive feedback loop. This loop, driven by H3K18 lactylation-ROS, ultimately results in the over recruitment of neutrophils to inflammatory sites in LL conditions. Collectively, our study provides evidence of a mutual loop between histone lactylation and ROS, exacerbating neutrophil recruitment in light disorder conditions, emphasizing the significance of maintaining a proper light-dark cycle to optimize immune function.

Abstract This study aimed to elucidate the influence of miR-483-3p on human renal tubular epithelial cells (HK-2) under high glucose conditions and to understand its mechanism. Human proximal tubular epithelial cells (HK-2) were exposed to 50 mmol/L glucose for 48 h to establish a renal tubular epithelial cell injury model, denoted as the high glucose group (HG group). Cells were also cultured for 48 h in a medium containing 5.5 mmol/L glucose, serving as the low glucose group. Transfection was performed in various groups: HK-2 + low glucose (control group), high glucose (50 mM) (HG group), high glucose + miR-483-3p mimics (HG + mimics group), high glucose +miR-483-3p inhibitor (HG + inhibitor group), and corresponding negative controls. Real-time quantitative polymerase chain reaction (qPCR) assessed the mRNA expression of miR-483-3p, bax, bcl-2, and caspase-3. Western blot determined the corresponding protein levels. Proliferation was assessed using the CCK-8 assay, and cell apoptosis was analyzed using the fluorescence TUNEL method. Western blot and Masson’s staining were conducted to observe alterations in cell fibrosis post miR-483-3p transfection. Furthermore, a dual-luciferase assay investigated the targeting relationship between miR-483-3p and IGF-1. The CCK8 assay demonstrated that the HG + mimics group inhibited HK-2 cell proliferation, while the fluorescent TUNEL method revealed induced cell apoptosis in this group. Conversely, the HG + inhibitor group promoted cell proliferation and suppressed cell apoptosis. The HG + mimics group upregulated mRNA and protein expression of pro-apoptotic markers (bax and caspase-3), while downregulating anti-apoptotic marker (bcl-2) expression. In contrast, the HG + inhibitor group showed opposite effects. Collagen I and FN protein levels were significantly elevated in the HG + mimics group compared to controls (P

Abstract Zinc (Zn) is an essential micronutrient but can be cytotoxic when present in excess. Plants have evolved mechanisms to tolerate Zn toxicity. To identify genetic loci responsible for natural variation of plant tolerance to Zn toxicity, we conduct genome-wide association studies for root growth responses to high Zn and identify 21 significant associated loci. Among these loci, we identify Trichome Birefringence (TBR) allelic variation determining root growth variation in high Zn conditions. Natural alleles of TBR determine TBR transcript and protein levels which affect pectin methylesterification in root cell walls. Together with previously published data showing that pectin methylesterification increase goes along with decreased Zn binding to cell walls in TBR mutants, our findings lead to a model in which TBR allelic variation enables Zn tolerance through modulating root cell wall pectin methylesterification. The role of TBR in Zn tolerance is conserved across dicot and monocot plant species.

Abstract This study aims to provide a comprehensive summary of the status and trends of Two-Dimensional Nano Black Phosphorus (2D nano BP) in cancer research from 2015 to 2023, offering insights for future studies. To achieve this, articles from the Web of Science database published between 2015 and 2023 were analyzed using R and VOSviewer software. The analysis included 446 articles, revealing a consistent increase in publication rates, especially between 2017 and 2019. China emerged as a leader in both publication volume and international collaborations. Prominent journals in this field included ACS Applied Materials & Interfaces and Advanced Materials, while key researchers were identified as Zhang Han, Tao Wei, and Yu Xuefeng. The analysis highlighted common keywords such as drug delivery, photothermal therapy, photodynamic therapy, and immunotherapy, indicating the major research focuses. The findings suggest that 2D nano BP holds significant promise in cancer treatment research, with a growing global interest. This study thus serves as a valuable reference for future investigations, providing a detailed analysis of the current state and emerging trends in this promising field.

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 The second-order nonlinear Hall effect (NLHE) in non-centrosymmetric materials has recently drawn intense interest, since its inherent rectification could enable various device applications such as energy harvesting and wireless charging. However, previously reported NLHE systems normally suffer from relatively small Hall voltage outputs and/or low working temperatures. In this study, we report the observation of a pronounced NLHE in tellurium (Te) thin flakes at room temperature. Benefiting from the semiconductor nature of Te, the obtained nonlinear response can be readily enhanced through electrostatic gating, leading to a second-harmonic output at 300 K up to 2.8 mV. By utilizing such a giant NLHE, we further demonstrate the potential of Te as a wireless Hall rectifier within the radiofrequency range, which is manifested by the remarkable and tunable rectification effect also at room temperature. Extrinsic scattering is then revealed to be the dominant mechanism for the NLHE in Te, with symmetry breaking on the surface playing a key role. As a simple elemental semiconductor, Te provides an appealing platform to advance our understanding of nonlinear transport in solids and to develop NLHE-based electronic devices.

Abstract Background Most patients with acute myeloid leukemia (AML) eventually develop drug resistance, leading to a poor prognosis. Dysregulated long gene non coding RNAs (lincRNAs) have been implicated in chemoresistance in AML. Unfortunately, the effects of lincRNAs which participate in regulating the Adriamycin (ADR) resistance in AML cells remain unclear. Thus, the purpose of this study is to determine LINC00987 function in ADR-resistant AML. Methods In this study, ADR-resistant cells were constructed. LINC00987, miRNAs, and HMGA2 mRNA expression were measured by qRT-PCR. P-GP, BCRP, and HMGA2 protein were measured by Western blot. The proliferation was analyzed by MTS and calculated IC50. Soft agar colony formation assay and TUNEL staining were used to analyze cell colony formation and apoptosis. Xenograft tumor experiment was used to analyze the xenograft tumor growth of ADR-resistant AML. Results We found that higher expression of LINC00987 was observed in AML patients and associated with poor overall survival in AML patients. LINC00987 expression was increased in ADR-resistant AML cells, including ADR/MOLM13 and ADR/HL-60 cells. LINC00987 downregulation reduces ADR resistance in ADR/MOLM13 and ADR/HL-60 cells in vitro and in vivo, while LINC00987 overexpression enhanced ADR resistance in MOLM13 and HL-60 cells. Additionally, LINC00987 functions as a competing endogenous RNA for miR-4458 to affect ADR resistance in ADR/MOLM13 and ADR/HL-60 cells. HMGA2 is a target of miR-4458. LINC00987 knockdown and miR-4458 overexpression reduced HMGA2 expression. HMGA2 overexpression enhanced ADR resistance, which reversed the function of LINC00987 silencing in suppressing ADR resistance of ADR/MOLM13 and ADR/HL-60 cells. Conclusions Downregulation of LINC00987 weakens ADR resistance by releasing miR-4458 to deplete HMGA2 in ADR/MOLM13 and ADR/HL-60. Therefore, LINC00987 may act as the therapeutic target for treating chemoresistant AML.

Abstract Effects of short-term exposure to ambient air pollution on systemic immunological and inflammatory biomarkers in rural population have not been adequately characterized. From May to July 2021, 5816 participants in rural villages of northern Henan Province, China, participated in this cross-sectional study. Blood biomarkers of systemic inflammation were determined including peripheral white blood cells (WBC), eosinophils (EOS), basophils (BAS), monocytes (MON), lymphocytes (LYM), neutrophils (NEU), neutrophil-lymphocyte ratio (NLR), and serum high-sensitivity C-reactive protein (hs-CRP). The concentrations of ambient fine particulate matter (PM2.5), PM10, nitrogen dioxide (NO2), carbon monoxide (CO), and ozone (O3) were assessed up to 7 days prior to the blood draw. A generalized linear model was used to analyze the associations between air pollution exposure and the above-mentioned blood biomarkers. Significantly positive associations were revealed between PM2.5, CO and WBC; CO, O3 and LYM; PM2.5, PM10, SO2, CO and NEU; PM2.5, PM10, SO2, CO and NLR; PM2.5, PM10, SO2, NO2, CO, O3 and hs-CRP. Meanwhile, negative associations were found between SO2 and WBC; PM2.5, PM10, NO2, CO, or O3 and EOS; PM2.5, SO2, or CO and BAS; SO2, NO2 or O3 and MON; PM2.5, PM10, SO2, or NO2 and LYM. Moreover, men, individuals with normal body mass index (BMI), current smokers, and those older than 60 years were found vulnerable to air pollution effects. Taken together, short-term exposure to air pollution was associated with systemic inflammatory responses, providing insight into the potential mechanisms for air pollution-induced detrimental systemic effects in rural residents.

Abstract Background Salt sensitivity of blood pressure (SSBP) is an intermediate phenotype of hypertension and is a predictor of long-term cardiovascular events and death. However, the genetic structures of SSBP are uncertain, and it is difficult to precisely diagnose SSBP in population. So, we aimed to identify genes related to susceptibility to the SSBP, construct a risk evaluation model, and explore the potential functions of these genes. Methods and results A genome-wide association study of the systemic epidemiology of salt sensitivity (EpiSS) cohort was performed to obtain summary statistics for SSBP. Then, we conducted a transcriptome-wide association study (TWAS) of 12 tissues using FUSION software to predict the genes associated with SSBP and verified the genes with an mRNA microarray. The potential roles of the genes were explored. Risk evaluation models of SSBP were constructed based on the serial P value thresholds of polygenetic risk scores (PRSs), polygenic transcriptome risk scores (PTRSs) and their combinations of the identified genes and genetic variants from the TWAS. The TWAS revealed that 2605 genes were significantly associated with SSBP. Among these genes, 69 were differentially expressed according to the microarray analysis. The functional analysis showed that the genes identified in the TWAS were enriched in metabolic process pathways. The PRSs were correlated with PTRSs in the heart atrial appendage, adrenal gland, EBV-transformed lymphocytes, pituitary, artery coronary, artery tibial and whole blood. Multiple logistic regression models revealed that a PRS of P

Abstract Background Acute myeloid leukemia (AML) is a hematopoietic malignancy with poor outcomes, especially in older AML patients. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is considered a promising anticancer drug because it selectively induces the extrinsic apoptosis of tumor cells without affecting normal cells. However, clinical trials have shown that the responses of patients to TRAIL are significantly heterogeneous. It is necessary to explore predictable biomarkers for the preselection of AML patients with better responsiveness to TRAIL. Here, we investigated the critical role of tumor protein p53 inducible nuclear protein 2 (TP53INP2) in the AML cell response to TRAIL treatment. Methods First, the relationship between TP53INP2 and the sensitivity of AML cells to TRAIL was determined by bioinformatics analysis of Cancer Cell Line Encyclopedia datasets, Cell Counting Kit-8 assays, flow cytometry (FCM) and cell line-derived xenograft (CDX) mouse models. Second, the mechanisms by which TP53INP2 participates in the response to TRAIL were analyzed by Western blot, ubiquitination, coimmunoprecipitation and immunofluorescence assays. Finally, the effect of TRAIL alone or in combination with the BCL-2 inhibitor venetoclax (VEN) on cell survival was explored using colony formation and FCM assays, and the effect on leukemogenesis was further investigated in a patient-derived xenograft (PDX) mouse model. Results AML cells with high TP53INP2 expression were more sensitive to TRAIL in vitro and in vivo. Gain- and loss-of-function studies demonstrated that TP53INP2 significantly enhanced TRAIL-induced apoptosis, especially in AML cells with nucleophosmin 1 (NPM1) mutations. Mechanistically, cytoplasmic TP53INP2 maintained by mutant NPM1 functions as a scaffold bridging the ubiquitin ligase TRAF6 to caspase-8 (CASP 8), thereby promoting the ubiquitination and activation of the CASP 8 pathway. More importantly, simultaneously stimulating extrinsic and intrinsic apoptosis signaling pathways with TRAIL and VEN showed strong synergistic antileukemic activity in AML cells with high levels of TP53INP2. Conclusion Our findings revealed that TP53INP2 is a predictor of responsiveness to TRAIL treatment and supported a potentially individualized therapeutic strategy for TP53INP2-positive AML patients.

Abstract Background YTHDC1, a key m(6)A nuclear reader, plays a crucial role in regulating mRNA splicing, export, and stability. However, the functional significance and regulatory mechanisms of YTHDC1 in inflammatory bowel disease (IBD) remain to be explored. Methods We established a dextran sulfate sodium (DSS)-induced murine colitis model in vivo and LPS/IFN-γ-stimulated macrophage inflammation in vitro. The expression of YTHDC1 was determined. Colocalization of YTHDC1 and macrophages was assayed by immunofluorescence staining. LV-YTHDC1 or shYTHDC1 lentiviruses were applied for YTHDC1 overexpression or inhibition. For NF-κB inhibition, JSH-23 was utilized. The interaction of YTHDC1 and Beclin1 mRNA was determined by RIP, and the m6A modification of Beclin1 was confirmed by MeRIP. Results In DSS-induced colitis and LPS/IFN-γ-treated RAW264.7 macrophages, we observed a significant downregulation of YTHDC1. Overexpression of YTHDC1 resulted in decreased levels of iNOS, CD86, and IL-6 mRNA, along with inhibited NF-κB activation in LPS/IFN-γ-treated RAW264.7 cells. Conversely, downregulation of YTHDC1 promoted iNOS expression and inhibited autophagy. Additionally, the effect of YTHDC1 knockdown on CD86 and IL-6 mRNA induced by LPS/IFN-γ was abolished by the NF-κB inhibitor JSH-23. Mechanistically, YTHDC1 interacted with Beclin1 mRNA, thereby stabilizing Beclin1 mRNA and enhancing Beclin1 expression and autophagy. These effects ultimately led to the inhibition of NF-κB signaling in LPS/IFN-γ-challenged macrophages. Conclusions YTHDC1 inhibited the macrophage-mediated inflammatory response by stabilizing Beclin1 mRNA, which may be a potential therapeutic target for the treatment of IBD.

Abstract Background Body weight and its changes have been associated with cancer outcomes. However, the associations of short‐term peridiagnosis weight dynamics in standardized, clinically operational time frames with cancer survival remain largely unknown. This study aimed to screen for and evaluate the optimal indicator of short‐term peridiagnosis weight dynamics to predict overall survival (OS) in patients with cancer. Methods This multicentre cohort study prospectively collected data from 7460 patients pathologically diagnosed with cancer between 2013 and 2019. Body weight data were recorded 1 month before, at the time of and 1 month following diagnosis. By permuting different types (point value in kg, point height‐adjusted value in kg/m2, absolute change in kg or relative change in percentage) and time frames (prediagnosis, postdiagnosis or peridiagnosis), we generated 12 different weight‐related indicators and compared their prognostic performance using Harrell's C‐index, integrated discrimination improvement, continuous net reclassification improvement and time‐dependent C‐index. We analysed associations of peridiagnosis relative weight change (RWC) with OS using restricted cubic spine (RCS), Kaplan–Meier analysis and multivariable‐adjusted Cox regression models. Results The study enrolled 5012 males and 2448 females, with a median age of 59 years. During a median follow‐up of 37 months, 1026 deaths occurred. Peridiagnosis (1 month before diagnosis to 1 month following diagnosis) RWC showed higher prognostic performance (Harrell's C‐index = 0.601, 95% confidence interval [CI] = [0.583, 0.619]) than other types of indicators including body mass index (BMI), absolute weight change, absolute BMI change, prediagnosis RWC and postdiagnosis RWC in the study population (all P 10%, hazard ratio [HR] = 0.530, 95% CI = [0.413, 0.680]) and moderate (gain 5–10%, HR = 0.588, 95% CI = [0.422, 0.819]) weight gain groups were both associated with improved OS. In contrast, the moderate (loss 5–10%, HR = 1.219, 95% CI = [1.029, 1.443]) and significant (loss >10%, HR = 1.280, 95% CI = [1.095, 1.497]) weight loss groups were both associated with poorer OS. Conclusions The prognostic performance of peridiagnosis RWC is superior to other weight‐related indicators in patients with cancer. The findings underscore the importance of expanding the surveillance of body weight from at diagnosis to both past and future, and conducting it within clinically operational time frames, in order to identify and intervene with patients who are at risk of weight change‐related premature deaths.

Abstract Global warming will lead to significantly increased temperatures on earth. Plants respond to high ambient temperature with altered developmental and growth programs, termed thermomorphogenesis. Here we show that thermomorphogenesis is conserved in Arabidopsis, soybean, and rice and that it is linked to a decrease in the levels of the two macronutrients nitrogen and phosphorus. We also find that low external levels of these nutrients abolish root growth responses to high ambient temperature. We show that in Arabidopsis, this suppression is due to the function of the transcription factor ELONGATED HYPOCOTYL 5 (HY5) and its transcriptional regulation of the transceptor NITRATE TRANSPORTER 1.1 (NRT1.1). Soybean and Rice homologs of these genes are expressed consistently with a conserved role in regulating temperature responses in a nitrogen and phosphorus level dependent manner. Overall, our data show that root thermomorphogenesis is a conserved feature in species of the two major groups of angiosperms, monocots and dicots, that it leads to a reduction of nutrient levels in the plant, and that it is dependent on environmental nitrogen and phosphorus supply, a regulatory process mediated by the HY5-NRT1.1 module.

During the Omicron pandemic in late 2022, this study surveyed Chinese students via an online questionnaire to assess their mental health status, prevalence of psychological symptoms, and associated factors. A nationwide cross-sectional survey of 4254 participants was conducted in seven regions of China from January 5 to February 9, 2023. Scales were utilized respectively to measure depressive symptoms, anxiety symptoms, post-traumatic stress disorder (PTSD) symptoms, and perceived social support. Descriptive, univariate, and multivariable analyses were performed to identify associated factors. Protective factors against depressive symptoms include regular exercise and robust social support networks, while risk factors involve excessive alcohol consumption, comorbidities, Omicron infection, and irregular sleep patterns. Risk factors for anxiety symptoms include comorbidities, Omicron infection, living alone, and irregular sleep patterns, while social support emerges as a protective factor. For PTSD symptoms, regular exercise and strong social support systems are identified as protective measures, with risks associated with comorbidities, Omicron infection, and poor sleep quality. Students are particularly vulnerable during the pandemic due to their lifestyle and academic pressures. It's essential to bolster their social support and promote healthier habits.

Postoperative dry eye is a common complication following femtosecond laser-assisted cataract surgery, and the patient interface (PI) used during the procedure may play a significant role in its occurrence. This study, utilizing a meticulous scientific search strategy, identified seven relevant articles through literature search engines. Most of these studies employed contact-type PI during surgeries, while one researcher used a non-contact PI. All studies assessed dry eye symptoms at various postoperative periods using metrics such as the Ocular Surface Disease Index (OSDI), tear Break-Up Time (BUT), Schirmer I test (SIt), and so on. However, the findings were inconsistent. On this basis, this comprehensive review delves into the potential impact of different patient interfaces on corneal nerve damage and conjunctival goblet cell injury, possibly contributing to an increased risk of postoperative dry eye. The review also explores various preventive and solution strategies, including improving PI design, reducing surgical time, and utilizing tear protective agents. The findings highlight the importance of optimizing the PI to minimize the risk of postoperative dry eye in femtosecond laser-assisted cataract surgery.

Hydrochlorothiazide (HCTZ) is a widely utilized diuretic for the treatment of hypertension. The photosensitivity of HCTZ has been recognized for six decades, with UVA being considered the primary culprit. However, the precise molecular mechanism of HCTZ sensitizing skin to UV radiation remains unknown. In this study, we demonstrate that HCTZ exacerbates UVB-induced photosensitivity in normal skin by disrupting the DNA damage response, a crucial network responsible for maintaining epidermal homeostasis. Here, we found that HCTZ aggravates UVB-induced mouse skin damage. Through transcriptomic and proteomic profiling, we have found that the cell cycle and p53 signaling pathway may contribute to the photosensitivity caused by HCTZ. In keratinocytes, HCTZ promotes the transition from G1 to S phase and inhibits the p53 signaling pathway after exposure to UV radiation. We have found that HCTZ enhances the accumulation of DNA damage induced by UVB and impairs nucleotide excision repair (NER), which is responsible for repairing UVB-induced DNA lesions, by inhibiting the expression of NER-related genes and shortening the duration of G1 phase. Furthermore, pharmacologically inducing G1 arrest eliminates HCTZ-induced accumulation of damaged DNA. These findings unveil an unknown mechanism through which HCTZ impairs NER and interferes with UVB-induced cell cycle arrest, ultimately leading to improper response towards DNA damage and increased skin sensitivity.

Abiotic stressors such as salt stress restrict plant development and output, which lowers agricultural profitability. In this study, alfalfa (Medicago sativa L.) varieties with different levels of salt tolerance were examined using high-throughput RNA sequencing (RNA-Seq) and Tandem Mass Tags (TMT) technologies to study the reactions of the root systems to salt stress, from transcriptomics and proteomics perspectives. The varieties Atlantic (AT) and Zhongmu-1 (ZM-1) were selected and evaluated after 2 h and 6 h of treatment with 150 mM NaCl. The results showed that under salt stress for 2 h, 1810 differentially expressed genes (DEGs) and 160 differentially expressed proteins (DEPs) in AT were screened, while 9341 DEGs and 193 DEPs were screened in ZM-1. Under salt stress for 6 h, 7536 DEGs and 118 DEPs were screened in AT, while 11,754 DEGs and 190 DEPs were screened in ZM-1. Functional annotation and pathway enrichment analyses indicated that the DEGS and DEPs were mainly involved in the glutathione metabolism, biosynthesis of secondary metabolites, glycolysis/gluconeogenesis, carbon fixation in photosynthetic organisms, and photosynthesis pathways. A series of genes related to salt tolerance were also identified, including GSTL3 and GSTU3 of the GST gene family, PER5 and PER10, of the PER gene family, and proteins such as APR and COMT, which are involved in biosynthesis of secondary metabolites. This study provides insights into salt resistance mechanisms in plants, and the related genes and metabolic pathways identified may be helpful for alfalfa breeding in the future.

Abstract Asynchronous nuclear and cytoplasmic maturation in human oocytes is believed to cause morphological anomalies after controlled ovarian hyperstimulation. Vacuolar protein sorting 34 (VPS34) is renowned for its pivotal role in regulating autophagy and endocytic trafficking. To investigate its impact on oocyte development, oocyte‐specific knockout mice (ZcKO) are generated, and these mice are completely found infertile, with embryonic development halted at 2‐ to 4‐cell stage. This infertility is related with a disruption on autophagic/mitophagic flux in ZcKO oocytes, leading to subsequent failure of zygotic genome activation (ZGA) in derived 2‐cell embryos. The findings further elucidated the regulation of VPS34 on the activity and subcellular translocation of RAS‐related GTP‐binding protein 7 (RAB7), which is critical not only for the maturation of late endosomes and lysosomes, but also for initiating mitophagy via retrograde trafficking. VPS34 binds directly with RAB7 and facilitates its activity conversion through TBC1 domain family member 5 (TBC1D5). Consistent with the cytoplasmic vacuolation observed in ZcKO oocytes, defects in multiple vesicle trafficking systems are also identified in vacuolated human oocytes. Furthermore, activating VPS34 with corynoxin B (CB) treatment improved oocyte quality in aged mice. Hence, VPS34 activation may represent a novel approach to enhance oocyte quality in human artificial reproduction.