Sensor-Based Multifaceted Feature Extraction and Ensemble Elastic Net Approach for Assessing Fall Risk in Community-Dwelling Older Adults.

Accurate identification of community-dwelling older adults at high fall risk can facilitate timely intervention and significantly reduce fall incidents. Analyzing gait and balance capabilities via feature extraction and modeling through sensor-based motion data has emerged as a viable approach for fall risk assessment. However, the existing approaches for extracting key features related to fall risk lack inclusiveness, with limited consideration of the non-linear characteristics of sensor signals, such as signal complexity, self-similarity, and local stability. In this study, we developed a multifaceted feature extraction scheme employing diverse feature types, including demographic, descriptive statistical, non-linear, spatiotemporal and spectral features, derived from three-axis accelerometers and gyroscope data. This study is the first attempt to investigate non-linear features related to fall risk in multi-task scenarios from a dynamic system perspective. Based on the extracted multifaceted features, we propose an ensemble elastic net (E-E-N) approach for handling imbalanced data and offering high model interpretability. The E-E-N utilizes bootstrap sampling to construct base classifiers and employs a weighting mechanism to aggregate the base classifiers. We conducted a set of validation experiments using real-world data for comprehensive comparative analysis. The results demonstrate that the E-E-N approach exhibits superior predictive performance on fall risk classification. Our proposed approach offers a cost-effective tool for accurately assessing fall risk and alleviating the burden of continuous health monitoring in the long term.

Exploring emission spatiotemporal pattern and potential reduction capacity in China's aviation sector: Flight trajectory optimization perspective.

China's rapid expansion of civil aviation has led to an increase in pollution-related issues, causing adverse health effects on populations near airports and downwind. Accurately quantifying aviation emissions is essential for effective emission management. Here, we developed a high-resolution aviation emissions inventory for China by employing a bottom-up approach that relied on daily flight schedules. By using the Aeronautical Information Publication (AIP) to reproduce real-world flight routes rather than conventional great-circle routes, we improved the accuracy of emissions and investigated the potential for reducing these emissions. Our findings demonstrated substantial variations in domestic civil aviation emissions both spatially and temporally. Emissions peaked in most provinces during Chinese holidays, particularly the Chinese Lunar New Year and summer holidays, highlighting the importance of detailed activity data for accurate emissions calculations. Therefore, we recommend extensive utilization of real-world flight routes, particularly in areas with limited Automatic Dependent Surveillance-Broadcast (ADS-B) coverage since they provide more accurate representations of actual flight trajectories. Our study also identified regions like Shaanxi, Sichuan, Beijing, and their surroundings having considerable potential for emission reduction due to substantial deviations from great-circle routes. This approach can enhance the accuracy and spatiotemporal resolution of aviation emissions at national and global scales throughout the year, without relying on extensive, long-term real-time flight trajectories. Additionally, it provides a unique way to quantify the potential for emission reductions across provinces in civil aviation, ultimately contributing to mitigating pollution-related health impacts from aviation emissions and promoting a more sustainable aviation industry.

External validation of the iScore, ASTRAL score, DRAGON score, and THRIVE score and development of a nomogram to predict outcome in patients with large vessel occlusion-acute ischemic stroke.

OBJECTIVE: This study aimed to validate the iScore, ASTRAL score, DRAGON score, and THRIVE score for assessing large vessel occlusion-acute ischemic stroke (AIS-LVO) and establish a predictive model for AIS-LVO patients that has better performance to guide clinical practice. METHODS: We retrospectively included 439 patients with AIS-LVO and collected baseline data from all of them. External validation of the iScore, ASTRAL score, DRAGON score, and THRIVE score was performed. All variables were compared between groups via univariate analysis, and the results are expressed as ORs and 95 % CIs. Independent variables with P < 0.25 were included in the multivariate logistic analysis, and statistically significant differences (P < 0.05) were identified as risk factors for prognosis in AIS-LVO patients. Receiver operating characteristic (ROC) curve analysis and decision curve analysis (DCA) were used to evaluate the predictive value of our model. RESULTS: Our external validation resulted in an iScore under the curve (AUC) of 0.8475, an ASTRAL AUC of 0.8324, a DRAGON AUC of 0.8196, and a THRIVE AUC of 0.8039. In our research, multivariate Cox regression revealed 8 independent predictors. We used a nomogram to visualize the results of the data analysis. The AUC for the training cohort was 0.8855 (95 % CI, 0.8487-0.9222), and that in the validation cohort was 0.8992 (95 % CI, 0.8496-0. 9488). CONCLUSIONS: In this study, we verified that the above scores have excellent efficacy in predicting the prognosis of AIS-LVO patients. The nomogram we developed was able to predict the prognosis of AIS-LVO more accurately and may contribute to personalized clinical decision-making and treatment for future clinical work.

Immunotherapies targeting the oncogenic fusion gene CLDN18-ARHGAP in gastric cancer.

The CLDN18-ARHGAP fusion gene is an oncogenic driver newly discovered in gastric cancer. It was detected in 9% (8/87) of gastric cancer patients in our center. An immunogenic peptide specifically targeting CLDN18-ARHGAP fusion gene was generated to induce neoantigen-reactive T cells, which was proved to have specific and robust anti-tumor capacity both in in vitro coculture models and in vivo xenograft gastric cancer models. Apart from the immunogenic potential, CLDN18-ARHGAP fusion gene was also found to contribute to immune suppression by inducing a regulatory T (Treg) cell-enriched microenvironment. Mechanistically, gastric cancer cells with CLDN18-ARHGAP fusion activate PI3K/AKT-mTOR-FAS signaling, which enhances free fatty acid production of gastric cancer cells to favor the survival of Treg cells. Furthermore, PI3K inhibition could effectively reverse Treg cells upregulation to enhance anti-tumor cytotoxicity of neoantigen-reactive T cells in vitro and reduce tumor growth in the xenograft gastric cancer model. Our study identified the CLDN18-ARHGAP fusion gene as a critical source of immunogenic neoepitopes, a key regulator of the tumor immune microenvironment, and immunotherapeutic applications specific to this oncogenic fusion.

Degree of joint risk factor control and incident chronic kidney disease among individuals with obesity.

AIM: To investigate the extent to which joint risk factor control might attenuate the excess risk of chronic kidney disease (CKD) in participants with obesity. PATIENTS AND METHODS: We included a total of 97 538 participants who were obese at baseline and matched 97 538 normal weight control participants from the UK Biobank in the analysis. The degree of joint risk factor control was assessed based on six major CKD risk factors, including blood pressure, glycated haemoglobin, low-density lipoprotein cholesterol, albuminuria, smoking and physical activity. The Cox proportional hazards models were used to estimate associations between the degree of risk factor control and risk of CKD, following participants from their baseline assessment until the occurrence of CKD, death, or the end of the follow-up period. RESULTS: Among participants with obesity, joint risk factor control showed an association with a stepwise reduction of incident CKD risk. Each additional risk factor control corresponded to an 11% (hazard ratio: 0.89; 95% confidence interval: 0.86-0.91) reduced risk of CKD among participants with obesity, with the optimal controlling of all six risk factors associated with a 49% (hazard ratio: 0.51; 95% confidence interval: 0.43-0.61) decrease in risk of CKD. Furthermore, in individuals with obesity who jointly controlled all six risk factors, the excess risk of CKD associated with obesity was effectively neutralized compared with normal weight control subjects. Notably, the protective correlations between the degree of joint risk factor control and the incidence of CKD were more pronounced in men compared with women, in individuals with a lower healthy food score versus a higher score, and among diabetes medication users as opposed to non-users (pinteraction = 0.017, 0.033 and 0.014, respectively). CONCLUSION: The joint risk factor control is associated with an inverse association of CKD risk in an accumulative manner among individuals with obesity. Achieving ideal control over risk factors may effectively counterbalance the excessive risk of CKD typically associated with obesity.

Poly I: C Alleviated Duck Intestinal Injury Infected with Duck Viral Enteritis by Inhibiting Apoptosis.

Duck enteritis virus (DEV) may lead to vascular injury, gastrointestinal mucosal erosion, lymphoid organ injury, and Polyinosinic-polycytidylic acid (Poly I:C) has an antiviral effect by inducing low levels of interferon. The purpose of this study was to explore the pathogenesis of DEV-induced intestinal injury in ducks and to verify the therapeutic effects of different concentrations of Poly I:C. In this study, duck enteritis model was established by infecting healthy Pekin ducks with DEV. Duck intestinal tissues were extracted from normal control group, model group, and treatment group with different doses of Poly I:C. In vivo, HE and TUNEL staining were used to observe the morphological changes and apoptosis. In vitro, the proliferation and apoptosis of duck intestinal epithelial cells were evaluated by MTT assay, TUNEL staining, and flow cytometry. The results showed that Poly I:C protected ducks from DEV toxicity by improving intestinal morphology and inhibiting apoptosis. In addition, the antiviral effect of Poly I:C on DEV was found in a dose-dependent manner, with a more relatively obvious effect at a high dose of Poly I:C. All in all, these results demonstrated that Poly I:C played a vital role in the apoptosis induced by DEV in ducks and modest dose of Poly I:C treatment worked well and may provide important reference for the development of new antiviral drugs in the future.

Integrated untargeted and targeted lipidomics discovers LPE 16:0 as a protector against respiratory syncytial virus infection.

Respiratory Syncytial Virus (RSV) is a leading cause of acute lower respiratory infections, imposing a substantial burden on healthcare systems globally. While lipid disorders have been observed in the lungs of infants and young children with RSV pneumonia, the specific characterization of these lipids and their roles in the development and progression of RSV pneumonia remain largely unexplored. To address this tissue, we established a non-targeted high-resolution lipidomics platform using UHPLC-Q-Exactive-MS to analyze lipid profiles in bronchoalveolar lavage fluid (BALF) obtained from mice infected with RSV. Through the lipidomics analysis, a total of 72 lipids species were identified, with 40 lipids were significantly changed. Notably, the primary changes were observed in ether phospholipids and lysophospholipids. Furthermore, a targeted lipidomics analysis utilizing UHPLC-QQQ-MS/MS was developed to specifically assess the levels of lysophospholipids, including lysophosphocholine 16:0 (LPC 16:0), lysophosphoethanolamine 16:0 (LPE 16:0) and lysophosphoglycerol 16:0 (LPG 16:0), in RSV-infected mice compared to control mice. Animal experiments revealed that LPE 16:0, rather than LPC 16:0 or LPG 16:0, provided protection against RSV-induced weight loss, reduced lung viral load, regulated immune cells and mitigated lung injury in mice afflicted with RSV pneumonia. In summary, our findings suggested that the host responses to RSV infection pathology are closely with various lipid metabolic. Additionally, our results elucidated novel biological functions of LPE 16:0 and offering new avenues for drug development against RSV pneumonia.

Hypoxia activates macrophage-NLRP3 inflammasome promoting atherosclerosis via PFKFB3-driven glycolysis.

The onset and progression of atherosclerosis are closely linked to the involvement of macrophages. While the contribution of NLRP3 inflammasome activation to the creation of a local highly inflammatory microenvironment is well recognized, the precise triggers remain unclear. In this study, we aimed to investigate the regulatory mechanism of NLRP3 inflammasome activation in response to hypoxia-induced glycolysis involving PFKFB3 in the development of atherosclerosis. To develop an atherosclerosis model, we selected ApoE knockout mice treated with a high-fat western diet. We then quantified the expression of HIF-1α, PFKFB3, and NLRP3. In addition, we administered the PFKFB3 inhibitor PFK158 during atherosclerosis modeling. The glycolytic activity was subsequently determined through 18F-FDG micro-PET/CT, ex vivo glucose uptake, and ECAR analysis. Furthermore, we employed lipopolysaccharide (LPS) and TNF-α to induce the differentiation of bone marrow-derived macrophages (BMDMs) into M1-like phenotypes under both hypoxic and normoxic conditions. Our histological analyses revealed the accumulation of PFKFB3 in human atherosclerotic plaques, demonstrating colocalization with NLRP3 expression and macrophages. Treatment with PFK158 reduced glycolytic activity and NLRP3 inflammasome activation, thereby mitigating the occurrence of atherosclerosis. Mechanistically, hypoxia promoted glycolytic reprogramming and NLRP3 inflammasome activation in BMDMs. Subsequent blocking of either HIF-1α or PFKFB3 downregulated the NLRP3/Caspase-1/IL-1ß pathway in hypoxic BMDMs. Our study demonstrated that the HIF-1α/PFKFB3/NLRP3 axis serves as a crucial mechanism for macrophage inflammation activation in the emergence of atherosclerosis. The therapeutic potential of PFKFB3 inhibition may represent a promising strategy for atheroprotection.

Frailty Status, Sedentary Behaviors, and Risk of Incident Bone Fractures.

BACKGROUND: The associations of physical pre-frailty and frailty with bone fractures and the modified effect of sedentary lifestyle remain uncertain. This study was performed to explore the association of physical pre-frailty and frailty with risk of incident bone fractures, and test the modification effects of sedentary lifestyle and other risk factors. METHODS: This cohort study included 413 630 participants without bone fractures at baseline in the UK Biobank study between 2006 and 2010 and followed up to 2021. The mean age of the participants was 56.5 years. A total of 224 351 (54.2%) enrolled participants were female and 376 053 (90.9%) included participants were White. Three Cox regression models were constructed to analyze the association of pre-frailty and frailty with total fractures, hip fractures, vertebrae fractures, and other fractures. RESULTS: As compared with the physical nonfrailty group, the multivariate-adjusted hazard ratios were 1.17 (95% confidence interval [CI]: 1.14-1.21) and 1.63 (95% CI: 1.53-1.74) for the physical pre-frailty group and frailty group, respectively (p-trend < .001). In addition, we found that sedentary behavior time significantly accentuated the associations of physical pre-frailty and frailty with total fractures (p-interaction <.001), hip fractures (p-interaction = .013), and other fractures (p-interaction <.001). CONCLUSIONS: Our results indicate that physical pre-frailty and frailty are related to higher risks of bone fractures; such association was more pronounced among those with longer sedentary behavior time.

Predictive Role of Elevated Neutrophil-Lymphocyte Ratio for Bone Metastasis in Esophageal Cancer.

PURPOSE: Research on bone metastasis in esophageal cancer (EC) is relatively limited. Once bone metastasis occurs in patients, their prognosis is poor, and it severely affects their quality of life. Currently, there is a lack of convenient tumor markers for early identification of bone metastasis in EC. Our research aims to explore whether neutrophil-lymphocyte ratio (NLR) can predict bone metastasis in patients with EC. METHODS: Retrospective analysis of clinical indicators was performed on 604 patients with EC. They were divided into groups based on whether or not there was bone metastasis, and the patients' coagulation-related tests, blood routine, tumor markers and other indicators were collected. The receiver operating characteristic curve (ROC) were used to determine the predictive ability of parameters such as NLR for bone metastasis in EC, and univariate and multivariate logistic regression analyses were conducted to determine the impact of each indicator on bone metastasis. Using binary logistic regression to obtain the predictive probability of NLR combined with tumor markers. RESULTS: ROC curves analysis suggested that the area under the curve (AUC) of the NLR was 0.681, with a sensitivity of 79.2% and a specificity of 52.6%, which can be used as a predictive factor for bone metastasis in EC. Multivariate logistic regression analysis showed that high NLR (odds ratio [OR]: 2.608, 95% confidence interval [CI]: 1.395-4.874, P = 0.003) can function as an independent risk factor for bone metastasis in patients with EC. Additionally, high PT, high APTT, high FDP, high CEA, high CA724, low hemoglobin, and low platelet levels can also predict bone metastasis in EC. When NLR was combined with tumor markers, the area under the curve was 0.760 (95% CI: 0.713-0.807, P < 0.001), significantly enhancing the predictability of bone metastasis in EC. CONCLUSION: NLR, as a convenient, non-invasive, and cost-effective inflammatory indicator, could predict bone metastasis in EC. Combining NLR with tumor markers can significantly improve the diagnostic accuracy of bone metastasis in EC.

Sacrificial Additive C60-Assisted Catholyte Buffer Layer for Li1+xAlxTi2-x(PO4)3-Based All-Solid-State High-Voltage Batteries.

All-solid-state batteries with oxide electrolytes and high-nickel layered oxide cathodes (LiNixCoyMnzO2 and LiNixCoyAlzO2, x + y + z = 1, x ≥ 60%) have received widespread attention owing to their high energy density and high safety. However, they generally suffer from interfacial structural instability when coupled with solid-state electrolytes, which strongly diminishes the longevity of the battery. In this work, we propose adding a sacrificial additive C60 to the catholyte buffer layer between Li1.4Al0.4Ti1.6(PO4)3 (LATP) and LiNi0.8Co0.1Mn0.1O2 (NCM811) to enhance the electrochemical stability under high-voltage operating conditions. A uniform and robust cathode-electrolyte interphase (CEI) film enriched with LixPOyFz, LiPxFy, and C60Fn is spontaneously formed on the surface of the cathode particles. In addition, the NCM811/Li solid-state battery delivers a discharge capacity of 150.3 mAh g-1 with a retention of 85% after 200 charge-discharge cycles at 0.5 C. This study offers a practical approach toward realizing LATP-based all-solid-state high-voltage batteries characterized by exceptional cycling stability.

Small Molecule-Induced Post-Translational Acetylation of Catalytic Lysine of Kinases in Mammalian Cells.

Reversible lysine acetylation is an important post-translational modification (PTM). This process in cells is typically carried out enzymatically by lysine acetyltransferases and deacetylases. The catalytic lysine in the human kinome is highly conserved and ligandable. Small-molecule strategies that enable post-translational acetylation of the catalytic lysine on kinases in a target-selective manner therefore provide tremendous potential in kinase biology. Herein, we report the first small molecule-induced chemical strategy capable of global acetylation of the catalytic lysine on kinases from mammalian cells. By surveying various lysine-acetylating agents installed on a promiscuous kinase-binding scaffold, Ac4 was identified and shown to effectively acetylate the catalytic lysine of >100 different protein kinases from live Jurkat/K562 cells. In order to demonstrate that this strategy was capable of target-selective and reversible chemical acetylation of protein kinases, we further developed six acetylating compounds on the basis of VX-680 (a noncovalent inhibitor of AURKA). Among them, Ac13/Ac14, while displaying excellent in vitro potency and sustained cellular activity against AURKA, showed robust acetylation of its catalytic lysine (K162) in a target-selective manner, leading to irreversible inhibition of endogenous kinase activity. The reversibility of this chemical acetylation was confirmed on Ac14-treated recombinant AURKA protein, followed by deacetylation with SIRT3 (a lysine deacetylase). Finally, the reversible Ac13-induced acetylation of endogenous AURKA was demonstrated in SIRT3-transfected HCT116 cells. By disclosing the first cell-active acetylating compounds capable of both global and target-selective post-translational acetylation of the catalytic lysine on kinases, our strategy could provide a useful chemical tool in kinase biology and drug discovery.

Preparation for practice: What are students learning for?

BACKGROUND: Junior doctors often feel inadequately prepared for clinical practice. Current approaches to optimising the pre-clinical to clinical transition generally overlook intrinsic factors, yet motivation and emotional engagement are likely to be important in building clinical competence. To address this gap, we explored the attitudes of medical undergraduates and clinicians towards learning and how these attitudes seemed to affect learning motivation. METHODS: We conducted semi-structured individual or group interviews with 22 medical undergraduates and eight clinicians. Interviews were transcribed and thematically analysed. RESULTS: Students and clinicians had differing perspectives on the content and context of learning, as well as divergent attitudes towards learning. Students focused on factual knowledge and examination performance, preferably with simple, clear-cut answers, privileged book learning, and equated medical knowledge with clinical competence. Conversely, clinicians focused on soft skills and clinical reasoning, emphasised learning through observation and experience, assessments that acknowledged complexity and context, and saw knowledge as a foundation for practice. Further, clinicians mostly felt that the pre-clinical curriculum over-emphasised factual recall of knowledge that was neither useful nor relevant for clinical practice. CONCLUSION: We found that students tended to be extrinsically motivated by examination performance, which led to adopting surface learning approaches. This in turn led to a mismatch between the pre-clinical emphasis on factual recall and the higher-order skills necessary for clinical practice. We propose that a shift away from content overload and high-stakes assessment towards patient-centric teaching approaches may help re-orientate students towards intrinsic motivation and more effective learning methods.

Predominance of hyperprogression in mucosal melanoma during anti-PD-1 monotherapy treatment.

BACKGROUND: A minority subset of immunotherapy patients manifests hyperprogressive disease (HPD), with the disparity in melanoma subtypes yet to be reported. This study aimed to delineate the proportion and prognosis of HPD in patients receiving anti-PD-1 monotherapy and to identify patient with HPD clinical characteristics across melanoma subtypes to inform clinical decision making. METHODS: Utilizing 4 established HPD definitions, the incidence of HPD in patients with advanced melanoma on anti-PD-1 monotherapy was determined. The incidence rates and prognostic abilities of various HPD definitions were compared to elect the most effective one. This facilitated a comparative analysis of subtypes and clinical features between patients with HPD and traditional progression. RESULTS: A total of 262 patients with advanced melanoma treated with anti-PD-1 monotherapy from 5 prospectively registered clinical trials were included in the study. The objective response rate (ORR) and disease control rate (DCR) was 21% and 58%, respectively, with 42% showcasing progression disease. The HPD incidences by 4 definitions were 13.2%, 16.8%, 10.8%, and 28.2%. All definitions effectively segregated HPD patients, with significantly poorer outcome than other progressive patients. The Delta TGR > 100 definition was the most indicative of a reduced overall survival, corroborated by the highest hazard ratio and statistical significance. The number of metastatic organs over 2 is a risk factor for HPD (OR = 4.18, P = .0103). Mucosal melanoma was the HPD prevalent subtype (OR = 3.13, P = .0489) in multivariable analysis, which is also indicated by RECIST criteria (P = .005). CONCLUSION: A delta TGR exceeding 100 best identified HPD patients in the advanced melanoma population treated with anti-PD-1 monotherapy. Hyperprogression was notably prevalent in mucosal melanoma patients with multiple metastatic organs. Caution against HPD is warranted when applying anti-PD-1 monotherapy in mucosal subtype.

Model Attention Expansion for Few-Shot Class-Incremental Learning.

Few-Shot Class-Incremental Learning (FSCIL) aims at incrementally learning new knowledge from limited training examples without forgetting previous knowledge. However, we observe that existing methods face a challenge known as supervision collapse, where the model disproportionately emphasizes class-specific features of base classes at the detriment of novel class representations, leading to restricted cognitive capabilities. To alleviate this issue, we propose a new framework, Model aTtention Expansion for Few-Shot Class-Incremental Learning (MTE-FSCIL), aimed at expanding the model attention fields to improve transferability without compromising the discriminative capability for base classes. Specifically, the framework adopts a dual-stage training strategy, comprising pre-training and meta-training stages. In the pre-training stage, we present a new regularization technique, named the Reserver (RS) loss, to expand the global perception and reduce over-reliance on class-specific features by amplifying feature map activations. During the meta-training stage, we introduce the Repeller (RP) loss, a novel pair-based loss that promotes variation in representations and improves the model's recognition of sample uniqueness by scattering intra-class samples within the embedding space. Furthermore, we propose a Transformational Adaptation (TA) strategy to enable continuous incorporation of new knowledge from downstream tasks, thus facilitating cross-task knowledge transfer. Extensive experimental results on mini-ImageNet, CIFAR100, and CUB200 datasets demonstrate that our proposed framework consistently outperforms the state-of-the-art methods.

The Impact of Hydrogen Sulfide in the Paraventricular Nucleus on the MAPK Pathway in High Salt-Induced Hypertension.

The hypothalamic paraventricular nucleus (PVN) plays a central role in regulating cardiovascular activity and blood pressure (BP). We administered hydroxylamine hydrochloride (HA), a cystathionine-ß-synthase (CBS) inhibitor, into the PVN to suppress endogenous hydrogen sulfide (H2S) and investigate its effects on the mitogen-activated protein kinase (MAPK) pathway in high salt-induced hypertension. We randomly divided 40 male Dahl salt-sensitive rats into 4 groups: the NS+PVN vehicle group, the NS+PVN HA group, the HS+PVN vehicle group, and the HS+PVN HA group, with 10 rats in each group. The rats in the NS (normal salt) groups were fed a normal-salt diet containing 0.3% NaCl, while the HS (high salt) groups were fed a high-salt diet containing 8% NaCl. The mean arterial pressure (MAP) was calculated after noninvasive measurement using an automatic sphygmomanometer to occlude the tail cuff once a week. HA or vehicle was infused into the bilateral PVN using Alzet osmotic mini-pumps for 6 weeks after the hypertension model was successfully established. We measured the levels of H2S in the PVN and plasma norepinephrine (NE) using ELISA. Additionally, we assessed the parameters of the MAPK pathway, inflammation, and oxidative stress through western blotting, immunohistochemical analysis, or real-time PCR. In the current study, we discovered that decreased levels of endogenous hydrogen sulfide in the PVN contributed to the onset of high salt-induced hypertension. This was linked to the activation of the MAPK signaling pathway, proinflammatory cytokines, and oxidative stress in the PVN, as well as the activation of the sympathetic nervous system.

Nonlinear association between the triglyceride-glucose index and diabetes mellitus in overweight and obese individuals: a cross-sectional retrospective analysis.

BACKGROUND: The triglyceride-glucose (TyG) index is linked to both the development and progression of diabetes, while obesity remains a significant risk factor for this disease. However, the relationship between the TyG index and overweight or obese diabetes remains unclear. METHODS: This study was a cross-sectional analysis of data from 40,633 participants with body mass index (BMI) ≥ 24 kg/m2 who were screened from January 2018 to December 2023 at Henan Provincial People's Hospital. Participants were divided into groups of overweight or obese individuals with diabetes and those without diabetes according to the diabetes diagnostic criteria. The TyG index, the dependent variable, was determined using the equation ln [fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2]. We explored the association between TyG index and diabetes in overweight or obese individuals through multivariate logistic regression, subgroup analysis, generalized additive models, smoothed curve fitting, and analysis of threshold effects. RESULTS: Patients who were overweight or obese and had diabetes had higher TyG index levels than those without diabetes. After adjusting for confounders, our findings indicated a significant association between the TyG index and the risk of diabetes in overweight or obese individuals [odds ratio (OR) = 7.38, 95% confidence interval (CI): 6.98-7.81]. There was a J-shaped nonlinear association between TyG index and diabetes. When TyG index was > 4.46, the risk of diabetes increased sharply. Notably, a high baseline TyG index (Q4 group) correlated with a notably greater risk of diabetes than did the Q1 group, with an OR of 22.72 (95% CI: 20.52-25.16). Subgroup analysis revealed that the association between TyG and diabetes was stronger in females than in males (OR = 7.57, 95% CI: 6.76-8.48,), more significant in individuals with a BMI of 24-28 kg/m2 than in those with a BMI ≥ 28 kg/m2 (OR = 8.40, 95% CI: 7.83-9.02), and increased with age (OR = 8.15, 95% CI: 7.25-9.17) (all P for interaction < 0.001). CONCLUSION: Among overweight or obese individuals, a higher TyG index is associated with an elevated risk of diabetes, especially when TyG is > 4.46. Furthermore, factors such as sex, age, and BMI significantly influence the risk of diabetes in overweight or obese individuals. Specifically, older women with a BMI of 24-28 kg/m2 are at a greater risk of diabetes under similar TyG index conditions.

Robot-assisted radical nephroureterectomy using the KangDuo Surgical Robot-01 Sys-tem versus the da Vinci System: a multicenter prospective randomized controlled trial.

INTRODUCTION: We aim to compare the safety and effectiveness of the KangDuo (KD)-Surgical Robot-01 (KD-SR-01) system and the da Vinci (DV) system for robot-assisted radical nephroureterectomy (RARNU). MATERIALS AND METHODS: This multicenter prospective randomized controlled trial was conducted between March 2022 and September 2023. Group 1 included 29 patients undergoing KD-RARNU. Group 2 included 29 patients undergoing DV-RARNU. Patient demographic and clinical characteristics, perioperative data, and follow-up outcomes were collected prospectively and compared between the two groups. RESULTS: There were no significant differences in patient baseline demographic and preoperative characteristics between the two groups. The success rates in both groups were 100% without conversion to open or laparoscopic surgery or positive surgical margins. No significant difference was observed in docking time [242 (120-951) s vs 253 (62-498) s, P = 0.780], console time [137 (55-290) min vs 105 (62-220) min, P = 0.114], operative time [207 (121-460) min vs 185 (96-305) min, P = 0.091], EBL [50 (10-600) mL vs 50 (10-700) mL, P = 0.507], National Aeronautics and Space Administration Task Load Index scores, and postoperative serum creatinine levels between the two groups. None of the patients showed evidence of distant metastasis, local recurrence, or equipment-related adverse events during the four-week follow-up. One (3.4%) patient in Group 2 experienced postoperative enterovaginal and enterovesical fistulas (Clavien-Dindo grade III). CONCLUSIONS: The KD-SR-01 system is safe and effective for RARNU compared to the DV Si or Xi system. Further randomized controlled studies with larger sample sizes and longer durations are required.

Characterization of bZIP Transcription Factors in Transcriptome of Chrysanthemum mongolicum and Roles of CmbZIP9 in Drought Stress Resistance.

bZIP transcription factors play important roles in regulating plant development and stress responses. Although bZIPs have been identified in many plant species, there is little information on the bZIPs in Chrysanthemum. In this study, bZIP TFs were identified from the leaf transcriptome of C. mongolicum, a plant naturally tolerant to drought. A total of 28 full-length bZIP family members were identified from the leaf transcriptome of C. mongolicum and were divided into five subfamilies based on their phylogenetic relationships with the bZIPs from Arabidopsis. Ten conserved motifs were detected among the bZIP proteins of C. mongolicum. Subcellular localization assays revealed that most of the CmbZIPs were predicted to be localized in the nucleus. A novel bZIP gene, designated as CmbZIP9, was cloned based on a sequence of the data of the C. mongolicum transcriptome and was overexpressed in tobacco. The results indicated that the overexpression of CmbZIP9 reduced the malondialdehyde (MDA) content and increased the peroxidase (POD) and superoxide dismutase (SOD) activities as well as the expression levels of stress-related genes under drought stress, thus enhancing the drought tolerance of transgenic tobacco lines. These results provide a theoretical basis for further exploring the functions of the bZIP family genes and lay a foundation for stress resistance improvement in chrysanthemums in the future.

Self-Assembly of Three-Dimensional Hyperbranched Magnetic Composites and Application in High-Turbidity Water Treatment.

In order to improve dispersibility, polymerization characteristics, chemical stability, and magnetic flocculation performance, magnetic Fe3O4 is often assembled with multifarious polymers to realize a functionalization process. Herein, a typical three-dimensional configuration of hyperbranched amino acid polymer (HAAP) was employed to assemble it with Fe3O4, in which we obtained three-dimensional hyperbranched magnetic amino acid composites (Fe3O4@HAAP). The characterization of the Fe3O4@HAAP composites was analyzed, for instance, their size, morphology, structure, configuration, chemical composition, charged characteristics, and magnetic properties. The magnetic flocculation of kaolin suspensions was conducted under different Fe3O4@HAAP dosages, pHs, and kaolin concentrations. The embedded assembly of HAAP with Fe3O4 was constructed by the N-O bond according to an X-ray photoelectron energy spectrum (XPS) analysis. The characteristic peaks of -OH (3420 cm-1), C=O (1728 cm-1), Fe-O (563 cm-1), and N-H (1622 cm-1) were observed in the Fourier transform infrared spectrometer (FTIR) spectra of Fe3O4@HAAP successfully. In a field emission scanning electron microscope (FE-SEM) observation, Fe3O4@HAAP exhibited a lotus-leaf-like morphological structure. A vibrating sample magnetometer (VSM) showed that Fe3O4@HAAP had a relatively low magnetization (Ms) and magnetic induction (Mr); nevertheless, the ferromagnetic Fe3O4@HAAP could also quickly respond to an external magnetic field. The isoelectric point of Fe3O4@HAAP was at 8.5. Fe3O4@HAAP could not only achieve a 98.5% removal efficiency of kaolin suspensions, but could also overcome the obstacles induced by high-concentration suspensions (4500 NTU), high pHs, and low fields. The results showed that the magnetic flocculation of kaolin with Fe3O4@HAAP was a rapid process with a 91.96% removal efficiency at 0.25 h. In an interaction energy analysis, both the UDLVO and UEDLVO showed electrostatic repulsion between the kaolin particles in the condition of a flocculation distance of <30 nm, and this changed to electrostatic attraction when the separation distance was >30 nm. As Fe3O4@ HAAP was employed, kaolin particles could cross the energy barrier more easily; thus, the fine flocs and particles were destabilized and aggregated further. Rapid magnetic separation was realized under the action of an external magnetic field.