Human-induced pluripotent stem cell-derived neural stem cell exosomes improve blood-brain barrier function after intracerebral hemorrhage by activating astrocytes via PI3K/AKT/MCP-1 axis.

JOURNAL/nrgr/04.03/01300535-202502000-00029/figure1/v/2024-05-28T214302Z/r/image-tiff Cerebral edema caused by blood-brain barrier injury after intracerebral hemorrhage is an important factor leading to poor prognosis. Human-induced pluripotent stem cell-derived neural stem cell exosomes (hiPSC-NSC-Exos) have shown potential for brain injury repair in central nervous system diseases. In this study, we explored the impact of hiPSC-NSC-Exos on blood-brain barrier preservation and the underlying mechanism. Our results indicated that intranasal delivery of hiPSC-NSC-Exos mitigated neurological deficits, enhanced blood-brain barrier integrity, and reduced leukocyte infiltration in a mouse model of intracerebral hemorrhage. Additionally, hiPSC-NSC-Exos decreased immune cell infiltration, activated astrocytes, and decreased the secretion of inflammatory cytokines like monocyte chemoattractant protein-1, macrophage inflammatory protein-1α, and tumor necrosis factor-α post-intracerebral hemorrhage, thereby improving the inflammatory microenvironment. RNA sequencing indicated that hiPSC-NSC-Exo activated the PI3K/AKT signaling pathway in astrocytes and decreased monocyte chemoattractant protein-1 secretion, thereby improving blood-brain barrier integrity. Treatment with the PI3K/AKT inhibitor LY294002 or the monocyte chemoattractant protein-1 neutralizing agent C1142 abolished these effects. In summary, our findings suggest that hiPSC-NSC-Exos maintains blood-brain barrier integrity, in part by downregulating monocyte chemoattractant protein-1 secretion through activation of the PI3K/AKT signaling pathway in astrocytes.

Effect of aerobic exercise on the improvement of executive function in children with attention deficit hyperactivity disorder: a systematic review and meta-analysis.

Objective: Aerobic exercise (AE) interventions are beginning to be used as an emerging adjunctive treatment modality in the treatment of children with Attention Deficit Hyperactivity Disorder (ADHD). However, to date, there is no substantial evidence to support the improved effects of aerobic exercise intervention in children with ADHD aged 6-12 years. This study aims to investigate the effect of aerobic exercise therapy on executive function in children with attention deficit hyperactivity disorder aged 6-12 years. Method: We conducted a systematic review and meta-analysis using PubMed and Web of Science. The cut-off date was June 1, 2023. The aim was to assess the impact of aerobic exercise interventions on children with ADHD and all randomized controlled trials eligible for aerobic exercise interventions for children with ADHD were included. Nine randomized controlled trials were screened for eligibility for systematic evaluation, and the nine studies were assessed for risk of bias using the PEDro score and the GRADE Quality of Evidence Evaluation System for quality grading of outcome indicators. After testing for heterogeneity, a random-effects model was selected for analysis. Finally, meta-analyses and regression analyses were performed on the core functions (inhibitory control, cognitive flexibility, and working memory) and subgroups of the nine studies on executive function using Revman 5.4 and Stata 16.0. Results: The risk of bias evaluation showed a mean PEDro score of 7.78, and of the nine studies, two were rated as having excellent methodological quality, while the remaining seven had a good level of evidence, and the GRADE evidence evaluation showed that the outcome indicators were all of moderate quality. Inhibitory control [SMD = 0.83,95% CI (0.37-1.29), Z = 3.51, p = 0.0005], cognitive flexibility [SMD = 0.65,95% CI (0.37-0.93), Z = 4.58, p < 0.00001], and working memory [SMD = 0.48,95% CI (0.02-0.95), Z = 2.03, p = 0.04] were statistically significant, with effect sizes of moderate or higher; furthermore, in subgroup analyses type of intervention, duration, intensity, and medication use had different effects on inhibitory control and cognitive flexibility, and the combined IC, CF statistic found that a single category of aerobic exercise ( ß = 0.867, p < 0.001), moderate intensity ( ß = 0.928, p < 0.001), 6-12 weeks (ß = 0.804, p < 0.001), 60-90 min ( ß = 0.894, p < 0.001), and the use of medication ( ß = 1.202, p = 0.002) were better for overall improvement in EF. Conclusion: Aerobic exercise therapy significantly improved executive functioning in children with ADHD, showing above moderate effect sizes especially in inhibitory control, cognitive flexibility, and working memory. Aerobic exercise therapy can be used as a reference in improving executive function in children with ADHD, but given the limitations of this study, it should be used with caution when applied in clinical settings.

Analysis on the pathogenesis and treatment progress of NRG1 fusion-positive non-small cell lung cancer.

Lung cancer persistently leads as the primary cause of morbidity and mortality among malignancies. A notable increase in the prevalence of lung adenocarcinoma has become evident in recent years. Although targeted therapies have shown in treating certain subsets of non-small cell lung cancers (NSCLC), a significant proportion of patients still face suboptimal therapeutic outcomes. Neuregulin-1 (NRG1), a critical member of the NRG gene family, initially drew interest due to its distribution within the nascent ventricular endocardium, showcasing an exclusive presence in the endocardium and myocardial microvessels. Recent research has highlighted NRG1's pivotal role in the genesis and progression across a spectrum of tumors, influencing molecular perturbations across various tumor-associated signaling pathways. This review provides a concise overview of NRG1, including its expression patterns, configuration, and fusion partners. Additionally, we explore the unique features and potential therapeutic strategies for NRG1 fusion-positive occurrences within the context of NSCLC.

Genetic and recombination heterogeneity of Canine Bufaviruses detected in diarrheal dogs in China.

Bufavirus (BuV) was first identified in feces from children with acute diarrhea, and a genetically related Canine bufavirus (CBuV) was first reported in Italy in 2018. In this study, through the investigation of CBuV in 622 anal swabs from dogs with diarrhea symptoms collected from various provinces in northern, central and eastern China during 2018-2022, 14 samples were detected to be positive. And 5 samples were from dogs co-infected with other canine diarrhea related viruses, which consist of CPV-2, CDV and CCoV. The complete genome sequences (4219 nt) of the fourteen strains were amplified and sequenced. Through comparative analysis with 51 reference BuV strains, six strains might recombinate from the CBuV strains (HUN/2012/22, CaBuV/9AS/2005/ITA and CaBuV/35/2016/ITA) in Hungary and Italy as the parents, and two genetic recombination events from various parents were predicted to occur on the BUV-422 strain. Combined analyzing the phylogenetic tree and sequence alignment, it was found that these CBuVs are highly conserved in the nonstructural protein NS1, but indeed various amino acid mutation sites in the capsid protein VP2, and even some amino acid sites coincide with putative protein plastic regions and potential epitopes. The BUV-422 and BUV-512 strains show sequential mutation sites identical to the divergent strains of CaBuV/9AS/2005/ITA and CaBuV/35/2016/ITA. This study would enrich the molecular data of CBuV in China and provide essential reference for the epidemiological research and vaccine development of CBuV in the future.

Dynamic look-ahead feedrate scheduling method based on sliding mode velocity control.

In the feedrate scheduling of complex curve direct interpolation, dynamic constraints such as axis acceleration and jerk are related to the actual state of the tool. Most existing methods convert dynamic constraints to velocity constraints at sampling points. However, it cannot guarantee the dynamic constraints are satisfied between sampling points. Addressing the issue, this paper proposes a dynamic look-ahead feedrate scheduling method based on sliding mode velocity control, which generates the motion command considering dynamic constraints in every interpolation cycle. To dynamically generate commands based on the current tool state, the acceleration and deceleration method based on sliding mode velocity control has been proposed, which can control tool state to transition to the command state with any initial state. To ensure sufficient distance for acceleration and deceleration, this paper uses braking distance to dynamically estimate the look-ahead distance. Then the minimum value within the look-ahead interval is selected as the command velocity for this scheduling cycle and the actual motion command is determined based on the dynamic constraints of each axis. Simulation and experiment results prove that compared with the existing method, this method effectively reduces the overshoot of dynamic constraints without significantly increasing the machining time. The analysis of real-time computation time has demonstrated the potential of the method proposed in this paper for real-time applications.

The impact of the Drug Marketing Authorization Holder system on sustainable improvement of innovation quality in the pharmaceutical manufacturing industry in China-An empirical study using synthetic control methods.

BACKGROUND: In November 2015, China launched a pilot program for its Drug Marketing Authorization Holder (MAH) system, aiming to integrate production and research and development resources to spur drug innovation. While many scholars have examined the theoretical relationship between the MAH system and pharmaceutical manufacturing innovation, empirical studies have been scarce. METHODS: This study uses inter-provincial panel data on China's pharmaceutical manufacturing industry from 2009 to 2019, along with synthetic control methods, to offer a robust analysis of the impact of the MAH paradigm on innovation quality in pilot provinces. We treat the 2015 MAH system implementation in ten provinces as a natural experiment and account for the mediating effects of R&D investments, allowing us to discern the underlying mechanisms. RESULTS: Our findings demonstrate a significant positive effect of China's MAH system on innovation quality in the pharmaceutical manufacturing industry. Specifically, the system is most effective in Jiangsu, Guangdong, and Shandong provinces. We also identify R&D investments as playing a mediating role in facilitating the favorable impact of the MAH system on innovation quality. CONCLUSION: Our study highlights the crucial importance of the MAH system in promoting innovation quality in China's pharmaceutical manufacturing industry, providing vital empirical support for its adoption and further enhancement. This research also offers practical insights for policymakers and R&D decision-makers in the pharmaceutical sector.

Steric Hindrance Engineering to Modulate the Closed Pores Formation of Polymer-Derived Hard Carbon for High-Performance Sodium-Ion Batteries.

The closed pores play a critical role in improving the sodium storage capacity of hard carbon (HC) anode, however, their formation mechanism as well as the efficient modulation strategy at molecular level in the polymer-derived HCs is still lacking. In this work, the steric hindrance effect has been proposed to create closed pores in the polymer-derived HCs for the first time through grafting the aromatic rings within and between the main chains in the precursor. The experimental data and theoretical calculation demonstrate that steric-hindrance effect from the aromatic ring side group can increase backbone rigidity and the internal free volumes in the polymer precursor, which can prevent the over graphitization and facilitate the formation of closed pores during the carbonization process. As a result, the as-prepared HC anode exhibits a remarkably enhanced discharge capacity of 340.3 mAh/g at 0.1 C, improved rate performance (210.7 mAh/g at 5 C) as well as boosted cycling stability (86.4% over 1000 cycles at 2C). This work provides a new insight into the formation mechanisms of closed pores via steric hindrance engineering, which can shed light on the development of high-performance polymer-derived HC anode for sodium-ion batteries.

The impact of sleep quality on visual working memory varied with the duration of maintenance.

Objective: Sleep quality can affect the performance of visual working memory. However, the effect of sleep quality on the maintenance stage, which is the key to maintain the quality and efficiency of visual working memory representation, remains unclear. This study is the first to explore the effect of sleep quality on the maintenance of visual working memory information. Method: 60 healthy college students completed the Pittsburgh Sleep Quality Index (PSQI) and color recall task of visual working memory. A mixed experimental design of sleep quality (high or low) and delay duration (1, 4, or 6 s) was used to assess the effect of sleep quality on the maintenance phase of visual working memory. Results: The main effects of sleep quality were significant on visual working memory quantity, precision and offset indexes. Among the quantity index, the interaction between sleep quality and delay duration was also significant. This suggests that prolonging the delay time in the maintenance phase leads to difficulty in maintaining attention to the task for those with lower sleep quality, which results in poorer working memory quantitative representations. Conclusion: Increases in the delay duration of the maintenance phase in visual working memory intensify the impact of sleep quality on task performance. Our study provides evidence to reveal the relationship between sleep quality and visual working memory and offers recommendations for improving sleep quality and cognitive functioning in individuals.

Three-year results of central corneal stromal thickness reduction in small-incision lenticule extraction for high myopia correction.

BACKGROUND: To investigate the long-term corneal stromal remodeling and central stromal thickness (CST) reduction accuracy after small-incision lenticule extraction (SMILE) for high myopia correction. METHODS: This prospective study included 30 patients (50 eyes) who had undergone SMILE. Measurements of CST reduction using optical coherence tomography were performed at 1 month, 6 months, 1 year, and 3 years after surgery. Correlations were performed between planned and achieved CST reductions. RESULTS: The study enrolled 50 eyes of 30 patients. The mean spherical equivalent was -9.25±1.52 D(diopters). The postoperative CST increased in the first month after surgery and remained stable for a year. Thereafter, it remained stable during follow-up from 1 to 3 years postoperatively. The predicted CST reduction was 146.4±10.3 µm. The achieved CST reductions at 1 month, 6 months, 1 year, and 3 years after surgery were 135.3±12.1 µm, 130.8±10.6 µm, 125.9±9.4 µm, and 122.2±10.6 µm, respectively. An overestimation of CST reduction was observed three years after surgery. Correlation analysis revealed a strong correlation between planned and achieved CST reductions; however, no correlation was found between CST reductions predicted error and the planned CST reductions. CONCLUSION: During long-term follow-up, our findings revealed a significant stromal remodeling following SMILE in patients with high myopia. Therefore, clinicians should consider it when screening patients with high myopia for SMILE.

CCT6A promotes cell proliferation in colon cancer by targeting BIRC5 associated with p53 status.

Chaperonin-containing TCP1 (CCT) is a multi-subunit complex, known to participate the correct folding of many proteins. Currently, the mechanism underlying CCT subunits in cancer progression is incompletely understood. Based on data analysis, the expression of CCT subunit 6 A (CCT6A) is found higher than the other subunits of CCT and correlated with an unfavorable prognosis in colon cancer. Here, we find CCT6A silencing suppresses colon cancer proliferation and survival phenotype in vitro and in vivo. CCT6A plays a role in cellular process, including the cell cycle, p53, and apoptosis signaling pathways. Further investigations have shown direct binding between CCT6A and both Wtp53 and Mutp53, and BIRC5 is found to act downstream of CCT6A. The highlight is that CCT6A inhibition significantly reduces BIRC5 expression independent of Wtp53 levels in Wtp53 cells. Conversely, in Mutp53 cells, downregulation of BIRC5 by CCT6A inhibition mainly depends on Mutp53 levels. Additionally, combined CCT6A inhibition and Wtp53 overexpression in Mutp53 cell lines effectively suppresses cell proliferation. It is concluded CCT6A is a potential oncogene that influences BIRC5 through distinct pathways in Wtp53 and Mutp53 cells.

Economic and technical analysis of an HRES (Hybrid Renewabl e Energy System) comprising wind, PV, and fuel cells using an improved subtraction-average-based optimizer.

HRES (Hybrid Renewable Energy Systems) has been designed because of the increasing demand for environmentally friendly and sustainable energy. In this study, an Improved Subtraction-Average-Based Optimizer (ISABO) is presented for optimizing the HRES system by wind power, fuel cells, and solar energy. The suggested approach, by introducing adaptive mechanisms and enhancing processes, improves the performance of the traditional subtraction-average-based optimization. Optimization aims to provide reliable and efficient energy while lowering system expenses. The efficacy of ISABO is evaluated for this goal and compared with other optimization techniques. According to the findings, The ISABO algorithm, when equipped with adaptive mechanisms, surpasses conventional optimization techniques by achieving a 12 % decrease in Net Present Cost (NPC) and Levelized Cost of Electricity (LCOE) along with a 45 % cost reduction in electrolyzers. Through simulations, it has been shown that the ISABO algorithm ensures the lowest average NPC at $1,357,018.15 while also upholding system reliability with just a 0.8 % decline in Load Point Supply Probability (LPSP) in the event of a PV unit failure. This research validates that hybrid PV/wind/fuel cell systems present superior cost-effectiveness and reliability, thereby opening doors for more economical renewable energy solutions. The study reveals hybrid PV/wind/fuel cell systems are more cost-effective than purely wind, PV, or fuel cell systems. This advancement in HRES design and optimization techniques will enable more cost-effective renewable energy options.

Developing the Additive Systems of Stand Basal Area Model for Broad-Leaved Mixed Forests.

Stand basal area (SBA) is an important variable in the prediction of forest growth and harvest yield. However, achieving the additivity of SBA models for multiple tree species in the complex structure of broad-leaved mixed forests is an urgent scientific issue in the study of accurately predicting the SBA of mixed forests. This study used data from 58 sample plots (30 m × 30 m) for Populus davidiana × Betula platyphylla broad-leaved mixed forests to construct the SBA basic model based on nonlinear least squares regression (NLS). Adjustment in proportion (AP) and nonlinear seemingly unrelated regression (NSUR) were used to construct a multi-species additive basal area prediction model. The results identified the Richards model (M6) and Korf model (M1) as optimal for predicting the SBA of P. davidiana and B. platyphylla, respectively. The SBA models incorporate site quality, stand density index, and age at 1.3 m above ground level, which improves the prediction accuracy of basal area. Compared to AP, NSUR is an effective method for addressing the additivity of basal area in multi-species mixed forests. The results of this study can provide a scientific basis for optimizing stand structure and accurately predicting SBA in multi-species mixed forests.

The Biosynthesis Pattern and Transcriptome Analysis of Sapindus saponaria Oil.

The Sapindus saponaria (soapberry) kernel is rich in oil that has antibacterial, anti-inflammatory, and antioxidant properties, promotes cell proliferation, cell migration, and stimulates skin wound-healing effects. S. saponaria oil has excellent lubricating properties and is a high-quality raw material for biodiesel and premium lubricants, showing great potential in industrial and medical applications. Metabolite and transcriptome analysis revealed patterns of oil accumulation and composition and differentially expressed genes (DEGs) during seed development. Morphological observations of soapberry fruits at different developmental stages were conducted, and the oil content and fatty acid composition of the kernels were determined. Transcriptome sequencing was performed on kernels at 70, 100, and 130 days after flowering (DAF). The oil content of soapberry kernels was lowest at 60 DAF (5%) and peaked at 130 DAF (31%). Following soapberry fruit-ripening, the primary fatty acids in the kernels were C18:1 (oleic acid) and C18:3 (linolenic acid), accounting for an average proportion of 62% and 18%, respectively. The average contents of unsaturated fatty acids and saturated fatty acids in the kernel were 86% and 14%, respectively. Through the dynamic changes in fatty acid composition and DEGs analysis of soapberry kernels, FATA, KCR1, ECR, FAD2 and FAD3 were identified as candidate genes contributing to a high proportion of C18:1 and C18:3, while DGAT3 emerged as a key candidate gene for TAG biosynthesis. The combined analysis of transcriptome and metabolism unveiled the molecular mechanism of oil accumulation, leading to the creation of a metabolic pathway pattern diagram for oil biosynthesis in S. saponaria kernels. The study of soapberry fruit development, kernel oil accumulation, and the molecular mechanism of oil biosynthesis holds great significance in increasing oil yield and improving oil quality.

Global burden and cross-country inequalities in stroke and subtypes attributable to diet from 1990 to 2019.

DATA SOURCES: The Global Burden of Diseases, Injuries, and Risk Factors study (GBD) 2019. BACKGROUND: To describe burden, and to explore cross-country inequalities according to socio-demographic index (SDI) for stroke and subtypes attributable to diet. METHODS: Death and years lived with disability (YLDs) data and corresponding estimated annual percentage changes (EAPCs) were estimated by year, age, gender, location and SDI. Pearson correlation analysis was performed to evaluate the connections between age-standardized rates (ASRs) of death, YLDs, their EAPCs and SDI. We used ARIMA model to predict the trend. Slope index of inequality (SII) and relative concentration index (RCI) were utilized to quantify the distributive inequalities in the burden of stroke. RESULTS: A total of 1.74 million deaths (56.17% male) and 5.52 million YLDs (55.27% female) attributable to diet were included in the analysis in 2019.Between 1990 and 2019, the number of global stroke deaths and YLDs related to poor diet increased by 25.96% and 74.76% while ASRs for death and YLDs decreased by 42.29% and 11.34% respectively. The disease burden generally increased with age. The trends varied among stroke subtypes, with ischemic stroke (IS) being the primary cause of YLDs and intracerebral hemorrhage (ICH) being the leading cause of death. Mortality is inversely proportional to SDI (R = -0.45, p < 0.001). In terms of YLDs, countries with different SDIs exhibited no significant difference (p = 0.15), but the SII changed from 38.35 in 1990 to 45.18 in 2019 and the RCI showed 18.27 in 1990 and 24.98 in 2019 for stroke. The highest ASRs for death and YLDs appeared in Mongolia and Vanuatu while the lowest of them appeared in Israel and Belize, respectively. High sodium diets, high red meat consumption, and low fruit diets were the top three contributors to stroke YLDs in 2019. DISCUSSION: The burden of diet-related stroke and subtypes varied significantly concerning year, age, gender, location and SDI. Countries with higher SDIs exhibited a disproportionately greater burden of stroke and its subtypes in terms of YLDs, and these disparities were found to intensify over time. To reduce disease burden, it is critical to enforce improved dietary practices, with a special emphasis on mortality drop in lower SDI countries and incidence decline in higher SDI countries.

Tumor-infiltrating T lymphocytes: A promising immunotherapeutic target for preventing immune escape in cholangiocarcinoma.

Cholangiocarcinoma (CCA) is becoming more common and deadly worldwide. Tumor-infiltrating T cell subtypes make distinct contributions to the immune system; collectively, they constitute a significant portion of the tumor microenvironment (TME) in CCA. By secreting cytokines and other chemicals, regulatory T cells (Tregs) decrease activated T cell responses, acting as immunosuppressors. Reduced CD8+ T cell activation results in stimulating programmed death-1 (PD-1), which undermines the immunological homeostasis of T lymphocytes. On the other hand, cancer cells are eliminated by activated cytotoxic T lymphocyte (CTL) through the perforin-granzyme or Fas-FasL pathways. Th1 and CTL immune cell infiltration into the malignant tumor is also facilitated by γδ T cells. A higher prognosis is typically implied by CD8+ T cell infiltration, and survival is inversely associated with Treg cell density. Immune checkpoint inhibitors, either singly or in combination, provide novel therapeutic strategies for CCA immunotherapy. Furthermore, it is anticipated that immunotherapeutic strategies-such as the identification of new immune targets, combination treatments involving several immune checkpoint inhibitors, and chimeric antigen receptor-T therapies (CAR-T)-will optimize the effectiveness of anti-CCA treatments while reducing adverse effects.

Destructive Cryptococcal Osteomyelitis Mimicking Tuberculous Spondylitis.

BACKGROUND Cryptococcosis is an opportunistic fungal infection that typically occurs in patients with compromised immune systems, primarily affecting the respiratory and central nervous systems. However, cryptococcal osteomyelitis is a rare manifestation of cryptococcal infection, characterized by nonspecific clinical features. Here, we present a case of vertebral cryptococcal osteomyelitis in a middle-aged woman and discuss diagnostic approaches. CASE REPORT A 56-year-old woman presented with lower back pain and limited mobility, without fever, and with a history of pulmonary tuberculosis. Physical examination revealed enlarged lymph nodes and tenderness in the thoracic vertebrae. A computed tomography-guided biopsy confirmed granulomatous inflammation caused by Cryptococcus, with abundant 10 µm spherical microbial spores. After 4 weeks of treatment with amphotericin B and fluconazole, symptoms and lesions improved. Upon discharge, the patient was prescribed oral fluconazole. Follow-up examinations showed a stable condition and a negative serum cryptococcal capsular polysaccharide antigen test. CONCLUSIONS Given the rarity and lack of specificity of clinical features of cryptococcal spondylitis, clinicians encountering similar presentations should consider tuberculous spondylitis and spinal tumors as differential diagnoses. Additionally, tissue biopsy of the affected vertebral bodies should be performed early to establish the type of vertebral infection, aiding in diagnosis, treatment, and prognosis.

The prognostic value and its relationship with immune infiltration of ACLY in clear cell renal cell carcinoma.

ATP citrate lyase (ACLY) is activated in various cancers, but its role in clear cell renal cell carcinoma (ccRCC) remains poorly understood. Herein, we investigated the prognostic role and potential mechanism of ACLY in ccRCC. The expression profile of ACLY in ccRCC was explored using Gene Expression Profiling Interactive Analysis 2 (GEPIA2), Gene Expression Omnibus (GEO), UALCAN and western blotting assays. The prognosis was investigated using immunohistochemistry (IHC) and Kaplan-Meier plotter assays. The relationship with immune infiltration was further evaluated using Tumor Immune Estimation Resource 2 (TIMER2) and Tumor Immune System Interactions and DrugBank (TISIDB) databases, respectively. Further biological function of ACLY in ccRCC pathogenesis was explored using in vitro experiments. ACLY level was higher in ccRCC than adjacent kidney tissues, and Kaplan-Meier survival analysis showed ACLY mRNA or protein were predictors of poor prognosis in ccRCC patients. Importantly, we reported for the first time that ACLY gene expression was significantly correlated with numerous immune cells and immune inhibitors in ccRCC. ACLY inhibition significantly impaired cell proliferation, induced cell apoptosis, attenuated cell migration, decreased lipid droplets formation, and suppressed epithelial-mesenchymal transition (EMT) of ccRCC. Moreover, these effects might be acted through mammalian target of rapamycin complex 1 (mTORC1) pathway. Collectively, ACLY was not only implicated in ccRCC tumorigenesis and progression, but also potentially interacted with immune infiltration and mTORC1 pathway. Our findings may provide a novel therapeutic strategy by targeting ACLY for ccRCC treatment.

A new dicyanophenanthrene-based thermally activated delayed fluorophore: Design, synthesis, photophysical study, and electroluminescence application.

A novel thermally activated delayed fluorescence (TADF) emitter, DCNP-SCF, is developed based on a dicyanophenanthrene acceptor. DCNP-SCF is prepared by a simple C-N coupling reaction. Its thermal, theoretical, photophysical, and electroluminescent properties are investigated, emphasizing its potential in organic electroluminescence devices. DCNP-SCF demonstrates highly distorted donor-acceptor conformation, facilitating significant TADF for efficient triplet harvesting in electroluminescence devices. Additionally, due to the moderate electron push-pull effect, DCNP-SCF exhibits appropriate intramolecular charge transfer for considerable photoluminescence quantum yield for electroluminescence applications.

TG/HDL-C ratio is positively associated with risk and severity of CHD among NAFLD patients: a case control study.

Objective: This study aimed to explore the association between the triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio and the risk and severity of CHD among NAFLD patients. Methods: This retrospective study included 278 patients with NAFLD and chest pain. The TG/HDL-C ratio was calculated and coronary angiography performed. All individuals were divided into NAFLD + CHD and NAFLD groups. The severity of coronary artery stenosis is quantified using the Gensini score based on angiographic results. In NAFLD patients, the association between the TG/HDL-C ratio and the risk and severity of CHD was explored. Results: CHD was detected in 139 of 278 patients. Compared to NAFLD group, multivariate logistic regression showed that TG/HDL-C ratio was a risk factor for CHD among NAFLD patients after adjustment for confounding factors with the odds ratio (OR 1.791, 95% CI 1.344-2.386, P<0.001). Further analysis using multivariate logistic regression based on tertiles revealed that, after adjusting for confounding factors, compared to the T1 group, the risk of CHD in the T2 group was 2.17-fold higher (OR, 2.17; 95% CI, 1.07-4.38; P = 0.031). Similarly, the risk of CHD in the T3 group increased by 2.84-fold (OR, 2.84; 95% CI, 1.36-5.94; P = 0.005). The multifactor linear regression analysis showed each 1-unit increase in TG/HDL-C ratio in the NAFLD + CHD group was associated with a 7.75-point increase in Gensini score (ß=7.75, 95% CI 5.35-10.15, P<0.001). Conclusion: The TG/HDL-C ratio was positively correlated with CHD risk and reflected coronary atherosclerosis severity in NAFLD patients.

The interaction between physical activity and ambient particulate matters on cognitive function among Chinese community-dwelling older adults.

BACKGROUND: The interaction between physical activity (PA) and ambient particulate matters (PMs) on cognition is rarely investigated. Our study aimed to assess the interactions of PA and PMs on cognitive function in older adults. METHODS: Our study comprised 3937 Chinese community-dwelling older adults. Cognition was evaluated using the Mini-Mental State Examination. PA information was gathered using the International Physical Activity Questionnaire. The data of PMs were obtained from China High Air Pollutants (CHAP). Linear regressions model and interaction plots were applied to assess and visualize the interaction of PA and PMs on cognition, respectively. Bayesian kernel machine regression (BKMR) method was employed to visualize discernible thresholds for the interaction. RESULTS: PMs were negatively associated with MMSE scores (PM1: ß = -0.40, 95 % CI: -0.58, -0.28; PM2.5: ß = -0.46, 95 % CI: -0.64, -0.29; PM10: ß = -0.44, 95 % CI: -0.61, -0.26), and PA was positively affiliated with MMSE scores (ß = 0.18, 95 % CI: -0.01, 0.38). Interaction plots and BKMR demonstrated that adverse connotations of PMs with MMSE increased with the elevated PA levels, and the positive associations of PA with MMSE scores were attenuated by increased PMs (all Pinteraction < 0.20). Discernible thresholds for the interaction between PMs and PA on MMSE were found. CONCLUSIONS: Our findings suggest that PA should not be taken at higher PMs concentrations, and that low level of PA could be performed in PMs polluted environment to improve cognitive function. Further experimental and cohort researches are required to reproduce our discovery.