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Abstract Background Environmental pollution seriously endangers people’s physical and mental health, especially the health of middle-aged and elderly people. Environmental pollution, trade openness, and population health are interconnected. Environmental pollution may have a nonlinear impact on health, and the impact of trade openness on the health effects of environmental pollution may not be a simple strengthening or weakening effect. However, few studies have used threshold effects model to explore the nonlinear mechanisms of environmental pollution’s impact on health in China. As a result, this study incorporates trade openness into the research framework on the health effects of environmental pollution, aiming to study the mechanism of environmental pollution on health. Methods Using the China Health and Retirement Longitudinal Study (CHARLS) data from 2013 to 2020 and the data of 111 prefecture-level cities in China, we combine two-way fixed-effects models and threshold models to explore the effects of environmental pollution on the health of middle-aged and elderly people and the role of trade openness in the path of environmental pollution affecting health. Results Environmental pollution impairs the health of middle-aged and elderly people, and there is a single threshold effect and regional heterogeneity in this negative impact. Trade openness has the effect of first weakening and then strengthening in the inhibitory effect of environmental pollution on health. Conclusion The negative impact of environmental pollution on health has regional heterogeneity, and there is a nonlinear relationship between environmental pollution and the health of middle-aged and elderly people. The health effect of environmental pollution is mainly long-term effect, and trade openness has a threshold effect on the impact of environmental pollution on health. Therefore, instead of adopting a one-size-fits-all policy, environmental and economic policies should be customized according to the degree of environmental pollution, trade openness, and regional variations, so as to safeguard the health of middle-aged and elderly individuals through effective environmental governance.

Abstract Background With global climate change, the health threats of ambient high temperature have received widespread attention. However, latest spatio-temporal patterns of the non-communicable diseases (NCDs) burden attributable to high temperature have not been systematically reported. We aimed to analyze vulnerable areas and populations based on a detailed profile for the NCDs burden attributable to high temperature globally. Methods We obtained data from the Global Burden of Diseases (GBD) Study (2019) to describe the temporal and spatial patterns of NCDs burden attributable to high temperature globally from 1990–2019. Then we analyzed the differences by region, sex, and socio-demographic index (SDI). Finally, the age‑period‑cohort (APC) model was utilized to explore the age, period, and cohort effects of NCDs mortality caused by high temperature. Results In 2019, the number of deaths and Disability-adjusted life years (DALYs) from high-temperature-related NCDs was about 150,000 and 3.4 million globally, of which about 70% were in South Asia and North Africa and Middle East, and the burden was higher in men. Among 204 countries and territories, the highest age-standardized mortality rate (ASMR) and age-standardized DALY rate (ASDR) were observed in Oman and United Arab Emirates, respectively. The global burden showed an upward trend from 1990 to 2019, with an EAPC of 3.66 (95%CI: 3.14–4.18) for ASMR and 3.68 (95%CI: 3.16-4.21) for ASDR. Cardiovascular diseases were the main contributors to the global burden of high-temperature-related NCDs in 2019. The age and period effect in APC model showed an increasing trend globally. There was a significant negative correlation between SDI and both ASMR (r = -0.17) and ASDR (r = -0.20) from 1990 to 2019. Conclusion There was an increasing trend of the global burden of high-temperature-related NCDs. The burden was likely to be higher in males and the elderly, as well as in countries and regions with less economically and socially developed and in tropical climates. Surveillance and prevention measures should be implemented with a focus on these vulnerable areas and susceptible populations.

Abstract Background Sepsis remains a leading cause of mortality in intensive care units, and rapid and accurate pathogen detection is crucial for effective treatment. This study evaluated the clinical application of multi-site metagenomic next-generation sequencing (mNGS) for the diagnosis of sepsis, comparing its performance against conventional methods. Methods A retrospective analysis was conducted on 69 patients with sepsis consecutively admitted to the Department of Intensive Care Medicine, Meizhou People’s Hospital. Samples of peripheral blood and infection sites were collected for mNGS and conventional method tests to compare the positive rate of mNGS and traditional pathogen detection methods and the distribution of pathogens. The methods used in this study included a comprehensive analysis of pathogen consistency between peripheral blood and infection site samples. Additionally, the correlation between the pathogens detected and clinical outcomes was investigated. Results Of the patients with sepsis, 57.97% experienced dyspnea, and 65.2% had underlying diseases, with hypertension being the most common. mNGS demonstrated a significantly higher pathogen detection rate (88%) compared to the conventional method tests (26%). The pathogen consistency rate was 60% between plasma and bronchoalveolar lavage fluid samples, and that of plasma and local body fluid samples was 63%. The most frequently detected pathogens were gram-negative bacteria, and Klebsiella pneumonia. There were no significant differences in the clinical features between the pathogens. Conclusion mNGS is significantly superior to conventional methods in pathogen detection. There was a notable high pathogen consistency detection between blood and local body fluid samples, supporting the clinical relevance of mNGS. This study highlights the superiority of mNGS in detecting a broad spectrum of pathogens quickly and accurately. Trial registration Not applicable.

Abstract Objective This study aimed to identify the incidence, risk factors, and outcomes of permanent pacemaker (PPM) implantation after transcatheter aortic valve implantation (TAVI) procedures. Methods A retrospective analysis was conducted on 70 patients who underwent TAVI at the Department of Cardiology, Fujian Provincial Hospital, from January 2018 to March 2022. Based on whether a new PPM was implanted after TAVI, all patients were divided into two groups: NEW PPM and NO PPM. Baseline characteristics and clinical data were compared between the two groups. Univariate analysis was used to analyze different variables between the two groups. A binary logistic regression analysis was used to evaluate independent correlates for PPM implantation after TAVI. Results The mean age of the 70 patients was 73.1 ± 8.8 years. The incidence of PPM implantation was 17.1%. Patients with diabetes and chronic kidney disease were more likely to require PPM (50% vs. 20.7%, p = 0.042, 25% vs. 5.2%, p = 0.042). Our study did not identify any significant differences in the incidence of electrocardiographic conduction disturbances except for the previous right bundle branch block (RBBB) (NO PPM 6.9% vs. NEW PPM 33.3%, p

Abstract Background Malnutrition is linked to a higher risk of unfavorable outcomes in various illnesses. The present investigation explored the correlation between inadequate nutritional condition and outcomes in older individuals diagnosed with hyperlipidemia. Methods The geriatric nutritional risk index (GNRI) was used to evaluate the nutritional status. All patients were divided into two groups according to GNRI. A Kaplan-Meier analysis was used to assess the survival rates of different groups at risk of malnutrition. In addition, GNRI was used in COX proportional risk regression models to evaluate its predictive effect on both overall mortality and cardiovascular mortality among patients with hyperlipidemia. Furthermore, the study employed restricted cubic splines (RCS) to examine the nonlinear correlation between GNRI and mortality. Results The study included 4,532 elderly individuals diagnosed with hyperlipidemia. During a median follow-up duration of 139 months, a total of 1498 deaths from all causes and 410 deaths from cardiovascular causes occurred. The Kaplan-Meier analysis demonstrated significantly poorer survival among individuals at risk of malnutrition, as indicated by the GNRI. In the malnutrition risk group, the modified COX proportional hazards model revealed that a decrease in GNRI was associated with a higher risk of all-cause mortality (HR=1.686, 95% CI 1.212-2.347) and cardiovascular mortality (HR=3.041, 95% CI 1.797-5.147). Furthermore, the restricted cubic splines revealed a non-linear association between GNRI and both all-cause mortality and cardiovascular mortality (p-value for non-linearity = 0.0039, p-value for non-linearity=0.0386). Conclusions In older patients with hyperlipidemia, lower levels of GNRI are associated with mortality. The GNRI could potentially be used to predict all-cause mortality and cardiovascular mortality.

Abstract Background Acute kidney injury (AKI) is a common and serious condition, particularly among elderly patients. It is associated with high morbidity and mortality rates, further compounded by the need for continuous renal replacement therapy in severe cases. To improve clinical decision-making and patient management, there is a need for accurate prediction models that can identify patients at a high risk of mortality. Methods Data were extracted from the Dryad Digital Repository. Multivariate analysis was performed using least absolute shrinkage and selection operator (LASSO) logistic regression analysis to identify independent risk factors and construct a predictive nomogram for mortality within 28 days after continuous renal replacement therapy in elderly patients with acute kidney injury. The discrimination of the model was evaluated in the validation cohort using the area under the receiver operating characteristic curve (AUC), and calibration was evaluated using a calibration curve. The clinical utility of the model was assessed using decision curve analysis (DCA). Results A total of 606 participants were enrolled and randomly divided into two groups: a training cohort (n = 424) and a validation cohort (n = 182) in a 7:3 proportion. A risk prediction model was developed to identify independent predictors of 28-day mortality in elderly patients with AKI. The predictors included age, systolic blood pressure, creatinine, albumin, phosphorus, age-adjusted Charlson Comorbidity Index (CCI), Acute Physiology and Chronic Health Evaluation II (APACHE II) score, and sequential organ failure assessment (SOFA) score. These predictors were incorporated into a logistic model and presented in a user-friendly nomogram. In the validation cohort, the model demonstrated good predictive performance with an AUC of 0.799. The calibration curve showed that the model was well calibrated. Additionally, DCA revealed significant net benefits of the nomogram for clinical application. Conclusion The development of a nomogram for predicting 28-day mortality in elderly patients with AKI receiving continuous renal replacement therapy has the potential to improve prognostic accuracy and assist in clinical decision-making.

Abstract Background To explore the application effect of 3D printing surgical training models in the preoperative assessment of robot-assisted partial nephrectomy. Methods Eighty patients who underwent robot-assisted partial nephrectomy surgery between January 2022 and December 2023 were selected and divided into two groups according to the chronological order. The control group (n = 40) received preoperative assessment with verbal and video education from January 2022 to December 2022, while the observation group (n = 40) received preoperative assessment with 3D printing surgical training models combined with verbal and video education from January 2023 to December 2023. The preoperative anxiety, information demand score, and surgical awareness were compared between the two groups. The physiological stress indicators, including interleukin-6 (IL-6), angiotensin II (AT II), adrenocorticotropic hormone (ACTH), cortisol (Cor), mean arterial pressure (MAP), and heart rate (HR), were also measured at different time points before and after surgery.They were 6:00 am on the day before surgery (T0), 6:00 am on the day of the operation (T1), 6:00 am on the first day after the operation (T2), and 6:00 am on the third day after the operation (T3).The preparation rate before surgery was compared between the two groups. Results The anxiety and surgical information demand scores were lower in the observation group than in the control group before anesthesia induction, and the difference was statistically significant (P

Abstract Precious metals are core assets for the development of modern technologies in various fields. Their scarcity poses the question of their cost, life cycle and reuse. Recently, an emerging catalysis employing contact-electrification (CE) at water-solid interfaces to drive redox reaction, called contact-electro-catalysis (CEC), has been used to develop metal free mechano-catalytic methods to efficiently degrade refractory organic compounds, produce hydrogen peroxide, or leach metals from spent Li-Ion batteries. Here, we show ultrasonic CEC can successfully drive the reduction of Ag(ac), Rh3+, [PtCl4]2-, Ag+, Hg2+, Pd2+, [AuCl4]-, and Ir3+, in both anaerobic and aerobic conditions. The effect of oxygen on the reaction is studied by electron paramagnetic resonance (EPR) spectroscopy and ab-initio simulation. Combining measurements of charge transfers during water-solid CE, EPR spectroscopy and gold extraction experiments help show the link between CE and CEC. What’s more, this method based on water-solid CE is capable of extracting gold from synthetic solutions with concentrations ranging from as low as 0.196 ppm up to 196 ppm, reaching in 3 h extraction capacities ranging from 0.756 to 722.5 mg g−1 in 3 h. Finally, we showed CEC is employed to design a metal-free, selective, and recyclable catalytic gold extraction methods from e-waste aqueous leachates.

Abstract Background Adolescents with depression who engage in non-suicidal self harming behaviors are more likely to adopt negative coping strategies when faced with negative events. Therefore, these patients should be introduced to positive coping strategies. Evidences have showed that mindfulness-based interventions can positively impact the psychology of patients with mental disorders. This study was to explore the impact of a combination of mindfulness therapy and mentalization-based family therapy (MBFT) on suicidal ideation in adolescents with depressive disorder. Methods Eighty adolescent patients with depression and suicidal ideation admitted to our hospital from September 2021 to February 2022 were selected as subjects. They were divided into a control group and a study group using the random number table method, with each group comprising 40 subjects. The control group received MBFT, whereas the study group received both mindfulness therapy and MBFT. The psychological status and suicidal ideations of the two groups were compared before and after the intervention. Results The psychological health scores of both groups of patients were lower after the intervention, with the scores of the study group being lower than those of the control group (P

Bladder cancer (BC) is the most common malignancy of the urinary system and often recurs after tumor removal and/or is resistant to chemotherapy. In cancer cells, the activity of the signaling pathway changes significantly, affecting a wide range of cell activities from growth and proliferation to apoptosis, invasion and metastasis. Nrf2 is a transcription factor that plays an important role in cellular defense responses to a variety of cellular stresses. There is increasing evidence that Nrf2 acts as a tumor driver and that it is involved in the maintenance of malignant cell phenotypes. Abnormal expression of Nrf2 has been found to be common in a variety of tumors, including bladder cancer. Over-activation of Nrf2 can lead to DNA damage and the development of bladder cancer, and is also associated with various pathological phenomena of bladder cancer, such as metastasis, angiogenesis, and reduced toxicity and efficacy of therapeutic anticancer drugs to provide cell protection for cancer cells. However, the above process can be effectively inhibited or reversed by inhibiting Nrf2. Therefore, Nrf2 signaling may be a potential targeting pathway for bladder cancer. In this review, we will characterize this signaling pathway and summarize the effects of Nrf2 and crosstalk with other signaling pathways on bladder cancer progression. The focus will be on the impact of Nrf2 activation on bladder cancer progression and current therapeutic strategies aimed at blocking the effects of Nrf2. To better determine how to promote new chemotherapy agents, develop new therapeutic agents, and potential therapeutic targets.

Summary: Apolipoprotein E (apoE) plays a crucial role in the pathogenesis of Alzheimer’s disease (AD). Microglia exhibit a substantial upregulation of apoE in AD-associated circumstances, despite astrocytes being the primary source of apoE expression and secretion in the brain. Although the role of astrocytic apoE in the brain has been extensively investigated, it remains unclear that whether and how apoE particles generated from astrocytes and microglia differ in biological characteristic and function. Here, we demonstrate the differences in size between apoE particles generated from microglia and astrocytes. Microglial apoE particles impair neurite growth and synapses, and promote neuronal senescence, whereas depletion of GPNMB (glycoprotein non-metastatic melanoma protein B) in microglial apoE particles mitigated these deleterious effects. In addition, human APOE4-expressing microglia are more neurotoxic than APOE3-bearing microglia. For the first time, these results offer concrete evidence that apoE particles produced by microglia are involved in neuronal senescence and toxicity.

Abstract Background This study aims to assess the efficacy and safety of Qingpeng ointment (QPO), a Tibetan medicine for alleviating symptoms in individuals with acute gouty arthritis (AGA). Methods This study was a randomized, double-blind, placebo-controlled trial that involved individuals with AGA whose joint pain, as measured on a visual analog scale (VAS) from 0 to 10, was equal to or greater than 3. The participants were randomly assigned to either the QPO or the placebo group and received their respective treatments twice daily for seven consecutive days. In case of intolerable pain, the participants were allowed to use diclofenac sodium sustained-release tablets as a rescue medicine. The primary outcomes measured were joint pain and swelling, while the secondary outcomes included joint mobility, redness, serum uric acid levels, C-reactive protein levels, and the amount of remaining rescue medicine. Any adverse events that occurred during the trial were also recorded. Results A total of 203 cases were divided into two groups, with balanced baselines: 102 in the QPO group and 101 in the placebo group. For joint pain, differences between the groups were notable in the VAS scores [1.75 (0, 3.00) versus 2.00 (1.00, 3.50); P = 0.038], changes in VAS [5.00 (3.00, 6.00) versus 4.00 (2.00, 6.00); P = 0.036], and disappearance rate [26.47% compared to 15.84%; P = 0.046] after treatment. Concerning joint swelling, significant between-group differences were observed in the VAS scores [1.00 (0, 2.30) versus 2.00 (0.70, 3.00); P = 0.032] and disappearance rate [33.33% compared to 21.78%; P = 0.046] at treatment completion. The QPO group exhibited a statistically significant mobility improvement compared to the placebo group (P = 0.004). No significant differences were found in other secondary outcomes. Five patients, four from the QPO group and one from the other, encountered mild adverse events, primarily skin irritation. All of these cases were resolved after dosage reduction or discontinuation of the medication. Conclusions Compared to the placebo, QPO exhibits positive effects on AGA by alleviating pain, reducing swelling, and enhancing joint mobility, without causing significant adverse effects. Trial Registration ISRCTN34355813. Registered on 25/01/2021.

Abstract Antimicrobial resistance is a global public health threat, and the World Health Organization (WHO) has announced a priority list of the most threatening pathogens against which novel antibiotics need to be developed. The discovery and introduction of novel antibiotics are time-consuming and expensive. According to WHO’s report of antibacterial agents in clinical development, only 18 novel antibiotics have been approved since 2014. Therefore, novel antibiotics are critically needed. Artificial intelligence (AI) has been rapidly applied to drug development since its recent technical breakthrough and has dramatically improved the efficiency of the discovery of novel antibiotics. Here, we first summarized recently marketed novel antibiotics, and antibiotic candidates in clinical development. In addition, we systematically reviewed the involvement of AI in antibacterial drug development and utilization, including small molecules, antimicrobial peptides, phage therapy, essential oils, as well as resistance mechanism prediction, and antibiotic stewardship.

Abstract Ball milling is a representative mechanochemical strategy that uses the mechanical agitation-induced effects, defects, or extreme conditions to activate substrates. Here, we demonstrate that ball grinding could bring about contact-electro-catalysis (CEC) by using inert and conventional triboelectric materials. Exemplified by a liquid-assisted-grinding setup involving polytetrafluoroethylene (PTFE), reactive oxygen species (ROS) are produced, despite PTFE being generally considered as catalytically inert. The formation of ROS occurs with various polymers, such as polydimethylsiloxane (PDMS) and polypropylene (PP), and the amount of generated ROS aligns well with the polymers’ contact-electrification abilities. It is suggested that mechanical collision not only maximizes the overlap in electron wave functions across the interface, but also excites phonons that provide the energy for electron transition. We expect the utilization of triboelectric materials and their derived CEC could lead to a field of ball milling-assisted mechanochemistry using any universal triboelectric materials under mild conditions.

Abstract Purpose To explore the potential role of signal transducer and activator of transcription 5A (STAT5A) in the metastasis of breast cancer, and its mechanism of regulation underlying. Methods and results TCGA datasets were used to evaluate the expression of STAT5A in normal and different cancerous tissues through TIMER2.0, indicating that STAT5A level was decreased in breast cancer tissues compared with normal ones. Gene Set Enrichment Analysis predicted that STAT5A was associated with the activation of immune cells and cell cycle process. We further demonstrated that the infiltration of immune cells was positively associated with STAT5A level. Influorescence staining revealed the expression and distribution of F-actin was regulated by STAT5A, while colony formation assay, wound healing and transwell assays predicted the inhibitory role of STAT5A in the colony formation, migratory and invasive abilities in breast cancer cells. In addition, overexpression of the Notch3 intracellular domain (N3ICD), the active form of Notch3, resulted in the increased expression of STAT5A. Conversely, silencing of Notch3 expression by siNotch3 decreased STAT5A expression, supporting that STAT5A expression is positively associated with Notch3 in human breast cancer cell lines and breast cancer tissues. Mechanistically, chromatin immunoprecipitation showed that Notch3 was directly bound to the STAT5A promoter and induced the expression of STAT5A. Moreover, overexpressing STAT5A partially reversed the enhanced mobility of breast cancer cells following Notch3 silencing. Low expression of Notch3 and STAT5A predicted poorer prognosis of patients with breast cancer. Conclusion The present study demonstrates that Notch3 inhibits metastasis in breast cancer through inducing transcriptionally STAT5A, which was associated with tumor-infiltrating immune cells, providing a novel strategy to treat breast cancer.

The Asian honey bee (Apis cerana) plays a crucial role in providing abundant bee products and in maintaining ecological balance. Despite the availability of the genomic sequence of the Asian honey bee, its transcriptomic information remains largely incomplete. To address this issue, here we constructed three pooled RNA samples from the queen, drone, and worker bees of A. cerana and performed full-length RNA sequencing using Nanopore single-molecule sequencing technology. Ultimately, we obtained 160,811 full-length transcript sequences from 19,859 genes, with 141,189 being novel transcripts, of which 130,367 were functionally annotated. We detected 520, 324, and 1823 specifically expressed transcripts in the queen, worker, and drone bees, respectively. Furthermore, we identified 38,799 alternative splicing (AS) events from 5710 genes, 44,243 alternative polyadenylation (APA) sites from 1649 gene loci, 88,187 simple sequence repeats (SSRs), and 17,387 long noncoding RNAs (lncRNAs). Leveraging these transcripts as references, we identified 6672, 7795, and 6804 differentially expressed transcripts (DETs) in comparisons of queen ovaries vs drone testes, worker ovaries vs drone testes, and worker ovaries vs queen ovaries, respectively. Our research results provide a comprehensive set of reference transcript datasets for Apis cerana, offering important sequence information for further exploration of its gene functions.