INTRODUCTION:Long-term exposure to air pollution has been associated with incident hypertension; however, its role in the progression and prognosis of subsequent comorbidities remains poorly understood. METHODS:Using data from the UK Biobank (participants enrolled between 2006 and 2010), this study used a multistate model to examine the effects of fine particulate matter, inhalable particulate matter, nitrogen oxides, and nitrogen dioxide on hypertension progression trajectories and to investigate potential mediators. Comorbidities included ischemic heart disease, atherosclerosis, heart failure, arrhythmia, hypertensive heart and kidney disease, cardiac arrest, aneurysm and aortic dissection, stroke, dementia, depression, glaucoma, retinal vascular occlusion, and chronic kidney disease. Data were analyzed in 2024. RESULTS:A total of 272,245 participants free of hypertension and related comorbidities were included at baseline. During a median follow-up of 14.8 years, 33,021 individuals were diagnosed with hypertension; 7,494 developed hypertension comorbidities; and 1,141 died after experiencing comorbidities. An IQR increase in annual levels of fine particulate matter, nitrogen dioxide, and nitrogen oxides was associated with an increased risk of hypertension progression trajectories (from baseline to hypertension, hypertension to comorbidities, and comorbidities to death), with hazard ratios ranging from 1.03 to 1.09, from 1.07 to 1.19, and from 1.05 to 1.10, respectively. Pollution promoted the progression of hypertension to cardiovascular and renal comorbidities, particularly ischemic heart disease, atherosclerosis, and chronic kidney disease, ultimately contributing to an increased risk of mortality. BMI and lung function mediated 7.7%-25.3% of the associations between nitrogen oxides and both the onset of hypertension and its progression to comorbidities. CONCLUSIONS:This study offers actionable insights for the targeted prevention and management of hypertension, underscoring the need for clean air policies and the imperative to monitor hypertension as a dynamic continuum.

BACKGROUND:The 2019 European Society of Cardiology and European Association for the Study of Diabetes (ESC/EASD) recommendations classified cardiovascular disease (CVD) risk in diabetes mellitus (DM) patients. The assessment and stratification of CVD risk were essential for identifying individuals with a very high risk of cardiovascular disease (CVD) and implementing glycemic control regimen with clear cardiovascular benefits. This research aim to evaluate the ratio of very high CV risk among patients with type 1 diabetes mellitus (T1DM) in mainland China. METHODS:This was a cross-sectional screening study from Jan 01, 2020 to Dec 30, 2022. Basic information such as disease duration, body mass index (BMI), target organ damage (including atherosclerotic heart disease, impaired renal function, left ventricular hypertrophy, and retinopathy) were collected from outpatients by trained physicians. According to the 2019 ESC/EASD guidelines, we identify T1DM individuals with a "very high CVD risk" and others were categorized into the "else" group. RESULTS:A total of 38,260 participants from 1,669 hospitals in mainland China were enrolled from 2020 to 2022, of which 54.81 % of T1DM patients were at very high CV risk category. The proportions of very high CVD risk in T1DM patients were highest in the Northeast region (72.70 %), followed by the Southwest region (69.99 %), and the Central region (54.41 %), while it was the lowest proportion in the Southern region (47.03 %). The proportion of very high CVD risk among T1DM patients increased with age and BMI, with 33.61 % in those under 35 years old, 59.57 % in those between 35 and 65 years old, and 70.80 % in those over 65 years old (P < 0.0001). Males and smokers showed an increased proportion of very high CVD risk in T1DM patients (P < 0.0001). CONCLUSIONS:This was the largest cross-sectional screening study to assess the CVD risk in T1DM patients in mainland China. The CVD risk among Chinese DM patients has reached a critical level which may necessitate the comprehensive strategies for the control and management of CV-related risk factors, such as blood pressure, BMI, and lipids in DM patients, to effectively reduce the incidence of CVD events and death.

Histone methylation, a common form of chromatin remodeling, has been found to be associated with various neurological and cognitive disorders. However, little is known about how this mechanism contributes to the onset and progression of Alzheimer's disease (AD). Here, we found that lysine demethylase 5C (KDM5C), a histone H3 lysine 4 di- and tri-methyl (H3K4me2/3)-specific demethylase encoded by an X-linked mental retardation-related gene, displayed a progressive increase in the hippocampus with age in 3 × Tg-AD mice. Suppression of KDM5C partially mitigated the cognitive decline according to water maze, Y maze, and novel object recognition tests. In addition, significantly decreased amyloid plaques, enhanced long-term potentiation (LTP), and up-regulated expression of synaptic proteins were observed in KDM5C knockdown 3 × Tg-AD mice. Mechanistically, suppression of KDM5C could promote the expression of brain-derived neurotrophic factor (BDNF) to partially protect hippocampal neurons from beta-amyloid damage. In the promoter region of Bdnf, KDM5C was bound to the repressor element-1 (RE-1) motif to reduce the nearby H3K4me3 level and inhibit gene transcription. Mutations in the RE-1 motif reversed the inhibitory effect of KDM5C. Our results emphasize that KDM5C excess is one of the reasons for the onset and progression of AD and that suppression of KDM5C in the hippocampus should be considered a potential therapeutic target to ameliorate cognitive impairment and pathological symptoms in AD.

ObjectiveTo investigate the dynamic distribution characteristics of microbial concentrations and particulate matter （PM） particle size in the air of hospital intensive care units （ICU） and their associated factors.MethodsA convenience sampling method was used to select a multi-bed open ICU in a tertiary hospital in Xi'an as the sampling site.The TSI 9 360 laser dust particle counter was used to sample six particle sizes with aerodynamic equivalent diameters （AED） greater than 0.3， 0.5， 1.0， 2.5， 5.0，and 10.0 µm within the ICU.ResultsIn actual conditions， the microbial concentrations and number of particulate matter in the ICU showed fluctuating trends. Microbial concentrations were negatively correlated with indoor temperature and humidity， and positively correlated with the number of staff， number of aerosol-generating procedures （AGP）， and patient occupancy rate. The number of particulate matter was negatively correlated with indoor humidity and positively correlated with the number of staff and number of AGP.ConclusionWithin a certain range， microbial concentrations in the ICU decrease as temperature and humidity increase， but increase with the number of fixed and active individuals in the hall， total number of staff， patient occupancy rate，and number of AGP.The number of particulate matter decreases within a certain range as indoor humidity increases， but increases with the number of fixed and active individuals in the hall， total number of staff， and number of AGP.The main source of indoor particulate matter is nebulization procedures.

PM2.5 (fine particulate matter) has become a significant contributor to global health risks. Emerging evidence links PM2.5 exposure to chronic diseases via gut-mediated pathways, including systemic inflammation and oxidative stress. These processes disrupt intestinal barrier integrity (e.g., reducing occluding and ZO-1 expression) and increase intestinal permeability, facilitating harmful substance translocation within the organism. Crucially, PM2.5 exposure significantly alters gut microbiota composition: increasing Lactobacillus, Parabacteroides, Firmicutes and Akkermansia abundance, while decreasing Bacteroidetes and short-chain fatty acid (SCFA)-producing bacteria (e.g., Prevotella). Concomitant metabolite disturbances feature impaired SCFA synthesis and phosphatidylcholine metabolic dysregulation. These microbiota and metabolite shift collectively impair gut-brain axis function. Therefore, enhanced PM2.5 pollution control is vital for gut health maintenance and disease prevention. This review summarizes the impact of PM2.5 on gut structure, microbiota, metabolites and their mechanistic links to systemic health.

Although a few studies have explored the impact of greenness on neurodegenerative diseases, little is known about the association between greenness and Parkinson’s disease (PD) prevalence, especially in developing countries. We aimed to investigate the association between greenness and PD prevalence in China. This cross-sectional study utilized data from the 2020 wave of the China Health and Retirement Longitudinal Study (CHARLS), involving a sample of 17 029 individuals. PD diagnoses were ascertained through medical professionals and records in questionnaires. To assess greenness exposure, Normalized Difference Vegetation Index (NDVI) was calculated as annual population-weighted for 2020 (NDVI ^2020 ) and a two-year average population-weighted for the period of 2019 and 2020 (NDVI ^2019−2020 ), respectively. Logistic regression models were employed to analyze the association between greenness and PD prevalence at city scale, and stratified analyses were further performed to identify potential modifiers of the association between greenness and PD prevalence. In the fully-adjusted models, a 0.1 increase in NDVI ^2020 was associated with 14.0% [odds ratio (OR) 0.860, 95% confidence interval (CI): 0.750, 0.987] lower odds of prevalent PD. Similarly, a 0.1 increase in NDVI ^2019−2020 was associated with 13.9% (OR 0.861, 95% CI: 0.744, 0.997) reduction in the odds of prevalent PD. This conclusion remained robust in the sensitivity analyses. Moreover, significant protective effects of greenness on PD prevalence were identified among females, the elderly, those living alone, and those with healthier habits. This national cross-sectional study found that exposure to higher greenness was associated with reduced odds of prevalent PD. Greenness may serve as a readily accessible environmental intervention for lowering prevalent PD in the future.

Prospective evidence on the relationship of greenness with cardiovascular disease (CVD) incidence is limited in low- and middle-income countries. In 512,691 participants of the China Kadoorie Biobank cohort across 10 regions in China, we calculated the levels of greenness exposure based on satellite-retrieved Normalized Difference Vegetation Index (NDVI) data. Annual maximum NDVI (NDVImax) values were estimated within 500 ​m and 1000 ​m buffers around the locations for the participants during the follow-up periods. Record linkages to healthcare databases provided incidence data of total CVD, ischemic heart disease and stroke during 2005-2017. Time-varying Cox proportional hazards regression was used to assess the associations between greenness exposure and CVD incidence. After 5.08 million person-years of follow-up, 148,032 incident CVD events were recorded. The overall average level of NDVImax was 0.543 for all participants. We observed significant inverse associations of greenness with the incidence of CVD and its subtypes. Specifically, the hazard ratio for total CVD incidence was 0.976 (95% confidence interval: 0.958, 0.994) per 0.1 increase in NDVImax within a 500 ​m buffer. As the 5 rural regions have achieved the WHO recommended greenness goal values, we compared the greenness levels in the 5 urban regions with the WHO's goal for greenness and found that, on average, 3.81% of total CVD incidence might be averted if the recommended greenness values could be achieved. Exposure to a higher level of greenness was associated with a lower risk of CVD incidence in Chinese adults.

The Sterile alpha motif domain-containing protein 4 (SAMD4) family consists of two evolutionarily conserved and highly homologous RNA-binding proteins, SAMD4A and SAMD4B. Previous studies have established SAMD4A as a tumor suppressor that is downregulated in breast cancer, while the function of SAMD4B in tumorigenesis remains poorly defined. In this study, we observed that SAMD4B expression is upregulated in breast cancer. Functional assays demonstrated that SAMD4B facilitated breast cancer cell proliferation, migration, and invasion by inducing epithelial–mesenchymal transition (EMT). Furthermore, SAMD4B accelerated G1-to-S phase cell cycle progression by modulating p53 expression, collectively supporting an oncogenic function of SAMD4B in breast cancer. Mechanistically, we found that SAMD4B enhanced TCF/LEF transcriptional activity and upregulated the expression of β-catenin, Cyclin D1, c-Myc, and Axin2. Further investigations confirmed that SAMD4B activated the Wnt/β-catenin pathway by stabilizing β-catenin mRNA and increasing β-catenin protein expression level. Importantly, treatment with XAV-939, a specific Wnt/β-catenin pathway inhibitor, abrogated the pro-oncogenic effects of SAMD4B overexpression, including Wnt/β-catenin pathway activation, enhanced proliferation, and increased metastatic capacity. These results confirm that SAMD4B promotes the malignant phenotypes of breast cancer cells in a manner dependent on the Wnt/β-catenin pathway. In summary, our findings clarify that SAMD4B exerts an oncogenic role in breast cancer progression by activating the Wnt/β-catenin pathway. These data identify SAMD4B as a potential therapeutic target in breast cancer, although further in vivo investigations are required to validate its clinical relevance.

BACKGROUND AND PURPOSE:Autophagy-lysosomal pathway dysfunction leads to postoperative cognitive dysfunction (POCD). Dexmedetomidine (Dex) improves POCD, and we probed the effects of Dex on autophagy-lysosomal pathway dysfunction in a POCD model. EXPERIMENTAL APPROACH:A POCD mouse model was established and intraperitoneally injected with Dex. Cognitive function was evaluated by Morris water maze/open field test/novel object recognition assay. Levels of neurotransmitters/inflammatory cytokines in hippocampus, and NLRP3/ASC/Cleaved Caspase-1 proteins were determined by ELISA/Western blot. NLRP3 inflammasome-mediated microglial activation/astrocyte A1 differentiation in the hippocampal CA1 region were assessed by immunofluorescence assay. BV-2 cells were treated with lipopolysaccharide (LPS) and Dex and/or the NLRP3 inflammasome activator Nigericin, and transfected with si-TFEB for co-culture with primary reactive astrocytes (RAs) to verify the function of Dex in vitro. KEY RESULTS:Dex alleviated cognitive dysfunction in POCD mice and repressed NLRP3 inflammasome-mediated microglial activation and astrocyte A1 differentiation. NLRP3 inflammasome activation partially reversed the protective effect of Dex on the POCD condition. In vitro experiments verified the inhibitory properties of Dex on microglial activation and astrocyte A1 differentiation. Dex induces TFEB nuclear translocation, microglial autophagy and lysosomal biogenesis. By activating the autophagy-lysosome pathway, Dex regulated NLRP3 inflammasome-mediated microglial activation, inhibited astrocyte A1 differentiation and alleviated POCD in vivo. CONCLUSION AND IMPLICATIONS:Dex regulates NLRP3 inflammasome-mediated hippocampal microglial activation by promoting TFEB nuclear translocation and activating the autophagy-lysosome pathway and inhibits astrocyte A1 differentiation, thereby alleviating POCD.

Exposure to high ambient temperatures can cause significant damage to the gastrointestinal tract; however, the therapeutic potential of fecal microbiota transplantation (FMT) in this context remains largely unexplored. We investigated whether FMT could alleviate heat-induced colonic injury in C57BL/6J mice. Mice were randomly divided into four groups: normal control (22°C only), normal-FMT (NF, 22 °C+ FMT), heat exposure (HE, 39°C only), and HE-FMT (HF, 39°C + FMT). The HE and HF groups were exposed to 39°C for 2 hours daily over 15 consecutive days. FMT (100 µL/day) was administered by oral gavage to the NF and HF groups for 15 days, starting after the first HE. Our results showed that FMT significantly modulated gut microbiota composition, increasing the relative abundance of Alistipes, Citrobacter, Parasutterella, Bifidobacterium, Lachnospiraceae_UCG-001, Raoultella, Woeseia, Prevotellaceae_UCG-001, and Christensenellaceae, while decreasing Clostridium_sensu_stricto_1, Eubacterium_xylanophilum_group, Clostridioides, Bilophila, GCA-900066575, and Peptococcus. Notably, FMT markedly restored epithelial integrity and enhanced mucus production, as shown by hematoxylin-eosin and periodic acid-Schiff staining. Moreover, FMT attenuated heat-induced epithelial cell apoptosis, evidenced by reduced apoptotic cells and downregulation of mitochondrial apoptotic markers, including Bax, Bak, cleaved Caspase-3, cleaved Caspase-9, and the phospho-P53/P53 ratio. In addition, FMT mitigated oxidative stress induced by HE, indicated by decreased 3-nitrotyrosine levels and normalization of antioxidant-related proteins, such as Nrf2, Sod1, Cat, and Gpx4. Collectively, these findings demonstrate that FMT alleviates heat-induced colonic injury by restoring mucosal barrier integrity, inhibiting apoptosis, and reducing oxidative stress, highlighting its potential as a promising therapeutic strategy for heat-related gastrointestinal disorders. IMPORTANCE:This study is the first to demonstrate the protective role of fecal microbiota transplantation (FMT) against heat-induced colonic injury in a mouse model. We show that FMT mitigates colonic damage by restoring gut microbiota balance, preserving mucosal barrier integrity, inhibiting epithelial cell apoptosis, and reducing oxidative stress. These findings underscore the essential role of the gut microbiota in maintaining intestinal homeostasis under heat stress and highlight the therapeutic potential of microbiota-targeted strategies, such as FMT, in preventing or treating heat-related intestinal injury.

AbstractFine particulate matter (PM2.5) is suggested to pose a severe risk to the kidneys by inducing functional degradation and chronic kidney diseases (CKD). This study aims to explore the nephrotoxicity of PM2.5 exposure and the underlying mechanism. Herein, based on the UK Biobank, it is found that per interquartile range (IQR) increase in PM2.5 is associated with a 6% (95% CI: 1%–11%), 7% (95% CI: 3%–11%), 9% (95% CI: 4%–13%), 11% (95% CI: 9%–13%), and 10% (95% CI: 8%–12%) increase in the risk of nephritis, hydronephrosis, kidney stone, acute renal failure, and CKD, respectively. In experimental study, noticeable kidney injury, which is the initiation of kidney diseases, is observed with PM2.5 exposure in C57BL/6N mice (n = 8), accompanied with oxidative stress, autophagy and pyroptosis. In vitro, HK‐2 cells with PM2.5‐stimulation exhibit tubulopathy, increased reactive oxygen species (ROS) generation and activated pyroptosis and autophagy. All changes are abolished by ROS scavenger of N‐acetyl‐L‐cysteine (NAC) both in vivo and in vitro. In conclusion, the study provides evidence showing that PM2.5 exposure is associated with 5 kinds of kidney diseases by directly inducing nephrotoxicity, in which ROS may be the potential target by triggering autophagy and pyroptosis.

Circular RNAs (circRNAs) play crucial roles in the immune and inflammatory responses of many diseases by acting as competing endogenous RNAs (ceRNAs). However, the role of circRNAs as ceRNAs in the immune and inflammatory processes of coronary atherosclerosis heart disease (CHD) remains unclear. This study aimed to identify and validate the potential immune-related circRNAs as biomarkers for CHD. Firstly, we constructed a ceRNA regulatory network including 14 circRNAs, 24 miRNAs, and 15 genes through bioinformatics analysis. Four hub genes were identified and five candidate immune-related circRNAs were screened. Subsequently, the expression levels of these candidate circRNAs were detected by qRT-PCR. Notably, hsa_circRNA_101069 and hsa_circRNA_406053 showed significant up-regulation in CHD patients (p < 0.001). The value of these circRNAs as biomarkers for CHD was evaluated by the area under the ROC curve (AUC), net reclassification improvement (NRI), and integrated discrimination improvement (IDI) indexes. Adding circRNAs to a traditional CHD model significantly enhanced classification performance, with an IDI of 0.058 and an NRI of 0.280 for hsa_circRNA_101069 and an IDI of 0.051 and an NRI of 0.480 for hsa_circRNA_406053. Furthermore, hsa_circRNA_101069 was up-regulated in ox-LDL-induced THP-1 macrophages, and silencing hsa_circRNA_101069 significantly inhibited the apoptosis rates and the inflammatory cytokines levels. This study constructed an immune-related circRNA-miRNA-mRNA network and identified two circRNAs as biomarkers for CHD, with hsa_circRNA_101069 potentially contributing to the pathological basis of CHD.

BACKGROUND:The role of circular RNAs (circRNAs) as biomarkers of coronary artery disease (CAD) remains poorly explored. This study aimed to identify and validate potential circulating circRNAs as biomarkers for the diagnosis of CAD. METHODS:The expression profile of circRNAs associated with CAD was obtained from Gene Expression Omnibus (GEO) database. Differential expression analysis, weighted gene co-expression network analysis (WGCNA) and least absolute shrinkage and selection operation (LASSO) were employed to identify CAD-related hub circRNAs. The expression levels of these hub circRNAs were validated using qRT-PCR in blood samples from 100 CAD patients and 100 controls. The diagnostic performance of these circRNAs was evaluated through logistic regression analysis, receiver operator characteristic (ROC) analysis, integrated discrimination improvement (IDI), and net reclassification improvement (NRI). Functional enrichment analyses were performed to predict the possible mechanisms of circRNAs in CAD. RESULTS:A total of ten CAD-related hub circRNAs were identified through WGCNA and LASSO analysis. Among them, hsa_circ_0069972 and hsa_circ_0021509 were highly expressed in blood samples of CAD patients, and they were identified as independent predictors after adjustment for relevant confounders. The area under the ROC curve for hsa_circ_0069972 and hsa_circ_0021509 was 0.760 and 0.717, respectively. The classification of patients was improved with the incorporation of circRNAs into the clinical model composed of conventional cardiovascular risk factors, showing an IDI of 0.131 and NRI of 0.170 for hsa_circ_0069972, and an IDI of 0.111 and NRI of 0.150 for hsa_circ_0021509. Functional enrichment analyses revealed that the hsa_circ_0069972-miRNA-mRNA network was enriched in TGF-β、FoxO and Hippo signaling pathways, while the hsa_circ_0021509-miRNA-mRNA network was enriched in PI3K/Akt and MAPK signaling pathways. CONCLUSION:Hsa_circ_0069972 and hsa_circ_0021509 were identified by integrated analysis, and they are highly expressed in CAD patients. They may serve as novel biomarkers for CAD.

To investigate the prognostic and immune values of ferredoxin 1 (FDX1) in brain lower grade glioma (LGG). Data from the Cancer Gene Atlas Database and the Genotype and Gene Expression Correlation Database were collected to compare the expression difference of FDX1 between glioma tissues and normal tissues, along with immunohistochemical method. Cox regression analysis was used to evaluate the relationship between FDX1 expression and survival indicators. The Kaplanu2013Meier method was used to assess independent risk of FDX1 in LGG survival probability. The Tumor Immune Estimation Resource database was used to evaluate the correlation between FDX1 expression and immune cell infiltration. FDX1 was overexpressed in LGG than normal tissues. The Kaplanu2013Meier analysis showed high FDX1 expression was significantly correlated with poor overall survival, disease specific survival and progress free interval (P u0026lt; 0.001). A positive correlation was found between FDX1 expression and infiltration of B cells, CD4+ T cells, CD8+ T cells, macrophages, neutrophils and dendritic cells. FDX1 was positively correlated with immune checkpoints in LGG. FDX1 may serve as a specific prognostic and therapeutic biomarker for LGG.

Abstract Background The associations between short- and long-term exposure to ambient fine particulate matter with an aerodynamic diameter ≤ 2.5 µm (PM2.5) and allergic symptoms in middle-aged and elderly populations remain unclear, particularly in China, where most cities have severe air pollution. Methods Participants (n = 10,142; age = 40–75 years) were recruited from ten regions in China from 2018 to 2021 for the Predictive Value of Inflammatory Biomarkers and Forced Expiratory Volume in 1 s (FEV1) for Chronic Obstructive Pulmonary Disease (PIFCOPD) study. Short-term (lag0 and lag0–7 day) and long-term (1-, 3- and 5-year) PM2.5 concentrations at residences were extracted from the air pollutant database known as Tracking Air Pollution (TAP) in China. Multivariate logistic regression models were used to estimate associations for short- and long-term PM2.5 exposure concentrations and long-term exposure models were additionally adjusted for short-term deviations. Results A 10 µg/m3 increase in PM2.5 on the day the allergic symptoms questionnaire was administered (lag0 day) was associated with higher odds of allergic nasal (1.09, 95% CI 1.05, 1.12) and eye symptoms (1.08, 95% CI 1.05, 1.11), worsening dyspnea caused by allergens (1.06, 95% CI 1.02, 1.10), and ≥ 2 allergic symptoms (1.07, 95% CI 1.03, 1.11), which was similar in the lag0–7 day concentrations. A 10 µg/m3 increase in the 1-year average PM2.5 concentration was associated with an increase of 23% for allergic nasal symptoms, 22% for eye symptoms, 20% for worsening dyspnea caused by allergens, and 21% for ≥ 2 allergic symptoms, similar to the 3- and 5-year average PM2.5 concentrations. These associations between long-term PM2.5 concentration and allergic symptoms were generally unchanged after adjustment for short-term deviations. Conclusions Short- and long-term exposure to ambient PM2.5 was associated with an increased risk of allergic nasal and eye symptoms, worsening dyspnea caused by allergens, and ≥ 2 allergic symptoms. Trial registration Clinical trial ID: NCT03532893 (29 Mar 2018).

The term cardiomyopathy refers to a group of heart diseases that cause severe heart failure over time. Cardiomyopathies have been proven to be associated with ferroptosis, a non-apoptotic form of cell death. It has been shown that some small molecule drugs and active ingredients of herbal medicine can regulate ferroptosis, thereby alleviating the development of cardiomyopathy. This article reviews recent discoveries about ferroptosis, its role in the pathogenesis of cardiomyopathy, and the therapeutic options for treating ferroptosis-associated cardiomyopathy. The article aims to provide insights into the basic mechanisms of ferroptosis and its treatment to prevent cardiomyopathy and related diseases.

Long non-coding RNAs (lncRNAs) are strongly associated with cellular physiological mechanisms and implicated in the numerous diseases. By exploring the subcellular localizations of lncRNAs, we can not only gain crucial insights into the molecular mechanisms of lncRNA-related biological processes but also make valuable contributions towards the diagnosis, prevention, and treatment of various human diseases. However, conventional experimental techniques tend to be laborious and time-intensive. In this context, computational methods are in increased demand. The focus of this paper is the development of an innovative ensemble method that incorporates hybrid features to accurately predict the subcellular localizations of lncRNAs. To address the issue of incomplete reflection of inherent correlation with the intended target using singular source features, the utilization of heterogeneous multi-source features is implemented by introducing information on sequence composition, physicochemical properties, and structure. To address the issue of the imbalance classes in the benchmark dataset, the Synthetic Minority Over-sampling Technique (SMOTE) is employed. Finally, the resulting predictor termed lncSLPre is developed by integrating the outputs of the individual classifiers. Experimental findings suggest that the complementarity of multi-source heterogeneous features improves prediction performance. Additionally, it is demonstrated that the application of SMOTE is effective in mitigating the issue of the imbalanced dataset, while the feature selection approach is critical in eliminating extraneous and redundant features. Compared with existing advanced methods, lncSLPre achieves better performance with an overall accuracy improvement of 13.13%, 2.15%, and 3.23%, respectively, indicating that lncSLPre can effectively predict lncRNA subcellular localizations.

Abstract The control strategy is important for variable refrigerant flow (VRF) air conditioning system to realize energy saving and stable operation. In this work, the super‐heating degree (SHD) responsive control strategy was developed to dynamically adjust the respective SHD target value (ΔTe,tar) of indoor units so as to adapt to the variable cooling load. The capacity code (Ecode) is introduced into the control model to quantify the reference target value of SHD. To responsively adapt to variable cooling load, the correction target values of SHD based on discharge temperature and deviation of the outlet air temperature are introduced in the SHD model for operation protection of the compressor and the consistency of refrigerant distribution. The enthalpy difference analogy method is developed to estimate the performance of the VRF system including cooling capacity, electric power, and energy efficiency ratio (EER). The performance was tested under the conditions of different ΔTe,tar. Experimental results demonstrate that the ΔTe,tar is an important factor to determine the operation frequency, which affects cooling capacity, power, EER, and operation status of the system. The cooling capacity and electric power at the ΔTe,tar of 9°C was about 55.2% and 63.5% lower than those at the ΔTe,tar of 1°C, and the corresponding EER was improved by 22.6%. To further verify the SHD control strategy, the VRF system was tested by the responsive control model under the condition that Ecode and ΔTe,tar were constantly automatically adjusted and changed with the actual indoor ambient temperature. Experimental results demonstrate that the VRF system can achieve a good and uniform cooling effect and realize energy saving and stable operation according to the responsive super‐heating degree control.

Aberrant lysosomal alkalization is associated with various biological processes, such as oxidative stress, cell apoptosis, ferroptosis, etc. Herein, we developed a novel aminofluorene-based fluorescence probe named FAN to monitor the lysosomal alkalization-related biological processes by its migration from lysosome to nucleus. FAN possessed NIR emission, large Stokes shift, high pH stability, and high photostability, making it suitable for real-time and long-term bioimaging. As a lysosomotropic molecule, FAN can accumulate in lysosomes first and then migrate to the nucleus by right of its binding capability to DNA after lysosomal alkalization. In this manner, FAN was successfully used to monitor these physiological processes which triggered lysosomal alkalization in living cells, including oxidative stress, cell apoptosis, and ferroptosis. More importantly, at higher concentrations, FAN could also serve as a stable nucleus dye for the fluorescence imaging of the nucleus in living cells and tissues. This novel multifunctional fluorescence probe shows great promise for application in lysosomal alkalization-related visual research and nucleus imaging.

OBJECTIVE:Diabetic retinopathy (DR) is a leading cause of vision impairment and blindness among diabetics. We aimed to explore whether long-term exposure to residential greenness was beneficial to DR. RESEARCH DESIGN AND METHODS:We used data from a large-scale, cross-sectional screening survey conducted in 129 cities of 27 provincial regions of China from 2018 to 2021 among patients with diabetes. We measured residential greenness exposure as the 3-year average of annual maximum Normalized Difference Vegetation Index (NDVI) at a spatial resolution of 250 m. DR was assessed by ophthalmologists based on fundus photographs. The primary outcome was DR, and secondary outcome included DR severity status (i.e., nonproliferative and proliferative), hallmarks of retinal lesions and macular oedema. RESULTS:A total of 484,380 adult participants with diabetes were included in the current analysis, and 15.7% of them were diagnosed with DR. NDVI was inversely and linearly associated with DR prevalence, and an increment of 0.1 NDVI was associated with a 10% (9%-10%) decrease in DR prevalence. Significant and inverse associations were further found for nonproliferative and proliferative DR, hallmarks of lesions and macular oedema. The association between greenness and DR was stronger among participants who were older, obese, lived in the south, had longer duration of diabetes or did not take antidiabetic medications. CONCLUSIONS:This large-scale nationwide study provides the first-hand epidemiological evidence on the associations of residential greenness with DR. Our findings highlight the importance of residential greenness in alleviating DR risk especially in an era of aging and urbanization.