Frailty in Patients on Dialysis.

Frailty is a condition that is frequently observed among patients performing dialysis. It is characterised by a decline in both physiological and cognitive state, leading to a combination of symptoms such as weight loss, exhaustion, low physical activity, weakness, and slow walking speed. Frail patients not only experience a poor quality of life, but they are also at a higher risk of hospitalization, infection, cardiovascular events, dialysis-associated complications, and death. Frailty occurs as a result of a combination and interaction of various medical issues in patients who are on dialysis. Unfortunately, there is no cure for frailty. To address frailty, a multifaceted approach is necessary, involving coordinated efforts from nephrologists, geriatricians, nurses, allied health practitioners, and family members. Strategies such as optimizing nutrition and CKD-related complications, reducing polypharmacy by deprescription, personalized dialysis prescription and considering home-based or assisted dialysis may help slow the decline of physical function over time in subjects with frailty. This review discusses the underlying causes of frailty in patients on dialysis and examines the methods and difficulties involved in managing frailty among this group.

High-dose Vitamin C injection ameliorates against sepsis-induced myocardial injury by anti-apoptosis, anti-inflammatory and pro-autophagy through regulating MAPK, NF-κB and PI3K/AKT/mTOR signaling pathways in rats.

AIMS: This study aimed to evaluate the effects of VC on SIMI in rats. METHODS: In this study, the survival rate of high dose VC for SIMI was evaluated within 7 days. Rats were randomly assigned to three groups: Sham group, CLP group, and high dose VC (500 mg/kg i.v.) group. The animals in each group were treated with drugs for 1 day, 3 days or 5 days, respectively. Echocardiography, myocardial enzymes and HE were used to detect cardiac function. IL-1ß, IL-6, IL-10 and TNF-α) in serum were measured using ELISA kits. Western blot was used to detect proteins related to apoptosis, inflammation, autophagy, MAPK, NF-κB and PI3K/Akt/mTOR signaling pathways. RESULTS: High dose VC improved the survival rate of SIMI within 7 days. Echocardiography, HE staining and myocardial enzymes showed that high-dose VC relieved SIMI in rats in a time-dependent manner. And compared with CLP group, high-dose VC decreased the expressions of pro-apoptotic proteins, while increased the expression of anti-apoptotic protein. And compared with CLP group, high dose VC decreased phosphorylation levels of Erk1/2, P38, JNK, NF-κB and IKK α/ß in SIMI rats. High dose VC increased the expression of the protein Beclin-1 and LC3-II/LC3-I ratio, whereas decreased the expression of P62 in SIMI rats. Finally, high dose VC attenuated phosphorylation of PI3K, AKT and mTOR compared with the CLP group. SIGNIFICANCE: Our results showed that high dose VC has a good protective effect on SIMI after continuous treatment, which may be mediated by inhibiting apoptosis and inflammatory, and promoting autophagy through regulating MAPK, NF-κB and PI3K/AKT/mTOR pathway.

Precision Prediction for Dengue Fever in Singapore: A Machine Learning Approach Incorporating Meteorological Data.

OBJECTIVE: This study aimed to improve dengue fever predictions in Singapore using a machine learning model that incorporates meteorological data, addressing the current methodological limitations by examining the intricate relationships between weather changes and dengue transmission. METHOD: Using weekly dengue case and meteorological data from 2012 to 2022, the data was preprocessed and analyzed using various machine learning algorithms, including General Linear Model (GLM), Support Vector Machine (SVM), Gradient Boosting Machine (GBM), Decision Tree (DT), Random Forest (RF), and eXtreme Gradient Boosting (XGBoost) algorithms. Performance metrics such as Mean Absolute Error (MAE), Root Mean Square Error (RMSE), and R-squared (R2) were employed. RESULTS: From 2012 to 2022, there was a total of 164,333 cases of dengue fever. Singapore witnessed a fluctuating number of dengue cases, peaking notably in 2020 and revealing a strong seasonality between March and July. An analysis of meteorological data points highlighted connections between certain climate variables and dengue fever outbreaks. The correlation analyses suggested significant associations between dengue cases and specific weather factors such as solar radiation, solar energy, and UV index. For disease predictions, the XGBoost model showed the best performance with an MAE = 89.12, RMSE = 156.07, and R2 = 0.83, identifying time as the primary factor, while 19 key predictors showed non-linear associations with dengue transmission. This underscores the significant role of environmental conditions, including cloud cover and rainfall, in dengue propagation. CONCLUSION: In the last decade, meteorological factors have significantly influenced dengue transmission in Singapore. This research, using the XGBoost model, highlights the key predictors like time and cloud cover in understanding dengue's complex dynamics. By employing advanced algorithms, our study offers insights into dengue predictive models and the importance of careful model selection. These results can inform public health strategies, aiming to improve dengue control in Singapore and comparable regions.

Iridoids modulate inflammation in diabetic kidney disease: A review.

In recent years, preclinical research on diabetic kidney disease (DKD) has surged to the forefront of scientific and clinical attention. DKD has become a pervasive complication of type 2 diabetes. Given the complexity of its etiology and pathological mechanisms, current interventions, including drugs, dietary modifications, exercise, hypoglycemic treatments and lipid-lowering methods, often fall short in achieving desired therapeutic outcomes. Iridoids, primarily derived from the potent components of traditional herbs, have been the subject of long-standing research. Preclinical data suggest that iridoids possess notable renal protective properties; however, there has been no summary of the research on their efficacy in the management and treatment of DKD. This article consolidates findings from in vivo and in vitro research on iridoids in the context of DKD and highlights their shared anti-inflammatory activities in treating this condition. Additionally, it explores how certain iridoid components modify their chemical structures through the regulation of intestinal flora, potentially bolstering their therapeutic effects. This review provides a focused examination of the mechanisms through which iridoids may prevent or treat DKD, offering valuable insights for future research endeavors. Please cite this article as: Zhou TY, Tian N, Li L, Yu R. Iridoids modulate inflammation in diabetic kidney disease: A review. J Integr Med. 2024; Epub ahead of print.

Isolation and usage of exosomes in central nervous system diseases.

BACKGROUND: Exosomes are vesicles secreted by all types of mammalian cells. They are characterized by a double-layered lipid membrane structure. They serve as carriers for a plethora of signal molecules, including DNA, RNA, proteins, and lipids. Their unique capability of effortlessly crossing the blood-brain barrier underscores their critical role in the progression of various neurological disorders. This includes, but is not limited to, diseases such as Alzheimer's, Parkinson's, and ischemic stroke. Establishing stable and mature methods for isolating exosomes is a prerequisite for the study of exosomes and their biomedical significance. The extraction technologies of exosomes include differential centrifugation, density gradient centrifugation, size exclusion chromatography, ultrafiltration, polymer coprecipitation, immunoaffinity capture, microfluidic, and so forth. Each extraction technology has its own advantages and disadvantages, and the extraction standards of exosomes have not been unified internationally. AIMS: This review aimed to showcase the recent advancements in exosome isolation techniques and thoroughly compare the advantages and disadvantages of different methods. Furthermore, the significant research progress made in using exosomes for diagnosing and treating central nervous system (CNS) diseases has been emphasized. CONCLUSION: The varying isolation methods result in differences in the concentration, purity, and size of exosomes. The efficient separation of exosomes facilitates their widespread application, particularly in the diagnosis and treatment of CNS diseases.

Identifying key antioxidative stress factors regulating Nrf2 in the genioglossus with human umbilical cord mesenchymal stem-cell therapy.

Intermittent hypoxia in patients with obstructive sleep apnea (OSA) hypopnea syndrome (OSAHS) is associated with pharyngeal cavity collapse during sleep. The effect of human umbilical cord mesenchymal stem cells (HUCMSCs) on OSA-induced oxidative damage in the genioglossus and whether nuclear factor erythroid 2-related factor 2 (Nrf2) or its upstream genes play a key role in this process remains unclear. This study aimed to identify the key factors responsible for oxidative damage during OSAHS through Nrf2 analysis and hypothesize the mechanism of HUCMSC therapy. We simulated OSA using an intermittent hypoxia model, observed the oxidative damage in the genioglossus and changes in Nrf2 expression during intermittent hypoxia, and administered HUCMSCs therapy. Nrf2 initially increased, then decreased, aggravating the oxidative damage in the genioglossus; Nrf2 protein content decreased during hypoxia. Using transcriptomics, we identified seven possible factors in HUCMSCs involved in ameliorating oxidative stress by Nrf2, of which DJ-1 and MEF2A, showing trends similar to Nrf2, were selected by polymerase chain reaction. HUCMSCs may reduce oxidative stress induced by intermittent hypoxia through Nrf2, and the possible upstream target genes in this process are MEF2A and DJ-1. Further studies are needed to verify these findings.

Why is HSO5- so effective against bacteria? Insights into the mechanisms of Escherichia coli disinfection by unactivated peroxymonosulfate.

This study examined the antimicrobial efficacy of peroxymonosulfate (PMS) against bacteria, using Escherichia coli (E. coli) as a model organism. Our investigation delineates the complex mechanisms exerted by unactivated PMS. Thus, an initial redox reaction between PMS and the target biomolecules of bacteria generates SO4•- as the pivotal reactive species for bacterial inactivation; to a lesser extent, •OH, 1O2, or O2•- may also participate. Damage generated during oxidation was identified using an array of biochemical techniques. Specifically, redox processes are promoted by PMS and SO4•- targets and disrupt various components of bacterial cells, predominantly causing extracellular damage as well as intracellular lesions. Among these, external events are the key to cell death. Finally, by employing gene knockout mutants, we uncovered the role of specific gene responses in the intracellular damage induced by radical pathways. The findings of this study not only expand the understanding of PMS-mediated bacterial inactivation but also explain the ten-fold higher effectiveness of PMS than that reported for H2O2. Hence, we provide clear evidence that unactivated PMS solutions generate SO4•- in the presence of bacteria, and consequently, should be considered an effective disinfection method.

Development of a CT-based radiomics-clinical model to diagnose acute pancreatitis on nonobvious findings on CT in children with pancreaticobiliary maljunction.

OBJECTIVES: Since neither abdominal pain nor pancreatic enzyme elevation is specific for acute pancreatitis (AP), the diagnosis of AP in patients with pancreaticobiliary maljunction (PBM) may be challenging when the pancreas appears normal or nonobvious on CT. This study aimed to develop a quantitative radiomics-based nomogram of pancreatic CT for identifying AP in children with PBM who have nonobvious findings on CT. METHODS: PBM patients with a diagnosis of AP evaluated at the Children's Hospital of Soochow University from June 2015 to October 2022 were retrospectively reviewed. The radiological features and clinical factors associated with AP were evaluated. Based on the selected variables, multivariate logistic regression was used to construct clinical, radiomics, and combined models. RESULTS: Two clinical parameters and 6 radiomics characteristics were chosen based on their significant association with AP, as demonstrated in the training (area under curve [AUC]: 0.767, 0.892) and validation (AUC: 0.757, 0.836) datasets. The radiomics-clinical nomogram demonstrated superior performance in both the training (AUC, 0.938) and validation (AUC, 0.864) datasets, exhibiting satisfactory calibration (P > .05). CONCLUSIONS: Our radiomics-based nomogram is an accurate, noninvasive diagnostic technique that can identify AP in children with PBM even when CT presentation is not obvious. ADVANCES IN KNOWLEDGE: This study extracted imaging features of nonobvious pancreatitis. Then it developed and evaluated a combined model with these features.

Recent advances in microfluidic technology of arterial thrombosis investigations.

Microfluidic technology has emerged as a powerful tool in studying arterial thrombosis, allowing researchers to construct artificial blood vessels and replicate the hemodynamics of blood flow. This technology has led to significant advancements in understanding thrombosis and platelet adhesion and aggregation. Microfluidic models have various types and functions, and by studying the fabrication methods and working principles of microfluidic chips, applicable methods can be selected according to specific needs. The rapid development of microfluidic integrated system and modular microfluidic system makes arterial thrombosis research more diversified and automated, but its standardization still needs to be solved urgently. One key advantage of microfluidic technology is the ability to precisely control fluid flow in microchannels and to analyze platelet behavior under different shear forces and flow rates. This allows researchers to study the physiological and pathological processes of blood flow, shedding light on the underlying mechanisms of arterial thrombosis. In conclusion, microfluidic technology has revolutionized the study of arterial thrombosis by enabling the construction of artificial blood vessels and accurately reproducing hemodynamics. In the future, microfluidics will place greater emphasis on versatility and automation, holding great promise for advancing antithrombotic therapeutic and prophylactic measures.

What is the context? To study the mechanism of arterial thrombosis, including the platelet adhesion and aggregation behavior and the coagulation process.Microfluidic technology is commonly used to study thrombosis. Microfluidic technology can simulate the real physiological environment on the microscopic scale in vitro, with high throughput, low cost, and fast speed.As an innovative experimental platform, microfluidic technology has made remarkable progress and has found applications in the fields of biology and medicine.What is new? This review summarizes the different fabrication methods of microfluidics and compares the advantages and disadvantages of these methods. Recent developments in microfluidic integrated systems and modular microfluidic systems have led to more diversified and automated microfluidic chips in the future.The different types and functions of microfluidic models are summarized. Platelet adhesion aggregation and coagulation processes, as well as arterial thrombus-related shear force changes and mechanical behaviors, were investigated by constructing artificial blood vessels and reproducing hemodynamics.Microfluidics can provide a basis for the development of personalized thrombosis treatment strategies. By analyzing the mechanism of action of existing drugs, using microfluidic technology for high-throughput screening of drugs and evaluating drug efficacy, more drug therapy possibilities can be developed.What is the impact?This review utilizes microfluidics to further advance the study of arterial thrombosis, and microfluidics is also expected to play a greater role in the biomedical field in the future.

miR828a-CsMYB114 Module Negatively Regulates the Biosynthesis of Theobromine in Camellia sinensis.

Theobromine is an important quality component in tea plants (Camellia sinensis), which is produced from 7-methylxanthine by theobromine synthase (CsTbS), the key rate-limiting enzyme in theobromine biosynthetic pathway. Our transcriptomics and widely targeted metabolomics analyses suggested that CsMYB114 acted as a potential hub gene involved in the regulation of theobromine biosynthesis. The inhibition of CsMYB114 expression using antisense oligonucleotides (ASO) led to a 70.21% reduction of theobromine level in leaves of the tea plant, which verified the involvement of CsMYB114 in theobromine biosynthesis. Furthermore, we found that CsMYB114 was located in the nucleus of the cells and showed the characteristic of a transcription factor. The dual luciferase analysis, a yeast one-hybrid assay, and an electrophoretic mobility shift assay (EMSA) showed that CsMYB114 activated the transcription of CsTbS, through binding to CsTbS promoter. In addition, a microRNA, miR828a, was identified that directly cleaved the mRNA of CsMYB114. Therefore, we conclude that CsMYB114, as a transcription factor of CsTbS, promotes the production of theobromine, which is inhibited by miR828a through cleaving the mRNA of CsMYB114.

Implanting oxophilic metal in PtRu nanowires for hydrogen oxidation catalysis.

Bimetallic PtRu are promising electrocatalysts for hydrogen oxidation reaction in anion exchange membrane fuel cell, where the activity and stability are still unsatisfying. Here, PtRu nanowires were implanted with a series of oxophilic metal atoms (named as i-M-PR), significantly enhancing alkaline hydrogen oxidation reaction (HOR) activity and stability. With the dual doping of In and Zn atoms, the i-ZnIn-PR/C shows mass activity of 10.2 A mgPt+Ru-1 at 50 mV, largely surpassing that of commercial Pt/C (0.27 A mgPt-1) and PtRu/C (1.24 A mgPt+Ru-1). More importantly, the peak power density and specific power density are as high as 1.84 W cm-2 and 18.4 W mgPt+Ru-1 with a low loading (0.1 mg cm-2) anion exchange membrane fuel cell. Advanced experimental characterizations and theoretical calculations collectively suggest that dual doping with In and Zn atoms optimizes the binding strengths of intermediates and promotes CO oxidation, enhancing the HOR performances. This work deepens the understanding of developing novel alloy catalysts, which will attract immediate interest in materials, chemistry, energy and beyond.

Calycosin enhances Treg differentiation for alleviating skin inflammation in atopic dermatitis.

ETHNOPHARMACOLOGICAL RELEVANCE: Atopic dermatitis (AD) is a prevalent chronic inflammatory skin disorder that poses a significant global health challenge. There is a lack of safe and effective medications to treat AD. Astragalus membranaceous is a traditional Chinese medicine widely used in clinical treatment of skin diseases. Calycosin (CA), derived from the root of Astragalus membranaceous, exhibits dual attributes of anti-inflammatory and antioxidant properties, suggesting its promise for addressing cutaneous inflammation. Nonetheless, the precise mechanisms underlying CA's therapeutic actions in AD remain elusive. AIM OF THE STUDY: This study aimed to evaluate the efficacy and safety of CA in treating AD while also delving into the mechanistic underpinnings of CA's action in AD. MATERIALS AND METHODS: The cell viability and anti-inflammatory impacts of CA in vitro were first gauged using CCK-8 and RT-qPCR. The potential mechanisms of CA were then probed using modular pharmacology. Flow cytometry was employed to ascertain the differentiation of Treg and Th17 cells derived from naïve T cells, as well as the proportions and mean fluorescence intensity (MFI) of human iTreg cells. The expressions of IL-10 and TGF-ß1 were measured and Treg suppression assay was performed. The in vivo therapeutic efficacy of topical CA application was assessed using a calcipotriol (MC903)-induced AD mouse model. The expression metrics of inflammatory cytokines, IL-17A, FOXP3, and RORγt were authenticated via immunohistochemistry, RT-qPCR, Western blot, and ELISA. RESULTS: CA exhibited a favorable safety profile and reduced the mRNA expressions of Th2 inflammatory cytokines in HaCaT cells. Modular pharmacology analysis pinpointed Th17 differentiation as the pivotal mechanism behind CA's therapeutic effect on AD. In vitro, CA fostered the differentiation of naïve T cells into Tregs while inhibiting their differentiation into Th17 cells. Furthermore, CA augmented the proliferation of human iTregs. In vivo, CA alleviated skin manifestations and decreased the levels of inflammatory mediators (IL-4, IL-5, IL-13, TSLP, and NF-κB related cytokines) in AD-like mouse models. Simultaneously, it regulated Treg/Th17 balance through suppressing IL-17A and RORγt expressions and bolstering FOXP3 expression. CONCLUSIONS: The study provides insights into the mechanistic pathways through which CA exerts its anti-inflammatory effects, particularly through promoting Treg cell differentiation and inhibiting Th17 cell differentiation. Furthermore, CA emerges as an alternative or adjunctive treatment strategy for managing AD.

High-Sensitivity C-Reactive Protein Is Associated With Heart Failure Hospitalization in Patients With Metabolic Dysfunction-Associated Fatty Liver Disease and Normal Left Ventricular Ejection Fraction Undergoing Coronary Angiography.

BACKGROUND: Systemic chronic inflammation plays a role in the pathophysiology of both heart failure with preserved ejection fraction (HFpEF) and metabolic dysfunction-associated fatty liver disease. This study aimed to investigate whether serum hs-CRP (high-sensitivity C-reactive protein) levels were associated with the future risk of heart failure (HF) hospitalization in patients with metabolic dysfunction-associated fatty liver disease and a normal left ventricular ejection fraction. METHODS AND RESULTS: The study enrolled consecutive individuals with metabolic dysfunction-associated fatty liver disease and normal left ventricular ejection fraction who underwent coronary angiography for suspected coronary heart disease. The study population was subdivided into non-HF, pre-HFpEF, and HFpEF groups at baseline. The study outcome was time to the first hospitalization for HF. In 10 019 middle-aged individuals (mean age, 63.3±10.6 years; 38.5% women), the prevalence rates of HFpEF and pre-HFpEF were 34.2% and 34.5%, with a median serum hs-CRP level of 4.5 mg/L (interquartile range, 1.9-10 mg/L) and 5.0 mg/L (interquartile range, 2.1-10.1 mg/L), respectively. Serum hs-CRP levels were significantly higher in the pre-HFpEF and HFpEF groups than in the non-HF group. HF hospitalizations occurred in 1942 (19.4%) patients over a median of 3.2 years, with rates of 3.7% in non-HF, 20.8% in pre-HFpEF, and 32.1% in HFpEF, respectively. Cox regression analyses showed that patients in the highest hs-CRP quartile had a ≈4.5-fold increased risk of being hospitalized for HF compared with those in the lowest hs-CRP quartile (adjusted-hazard ratio, 4.42 [95% CI, 3.72-5.25]). CONCLUSIONS: There was a high prevalence of baseline pre-HFpEF and HFpEF in patients with metabolic dysfunction-associated fatty liver disease and suspected coronary heart disease. There was an increased risk of HF hospitalization in those with elevated hs-CRP levels.

From Bench to Clinic: A Nitroreductase Rv3368c-Responsive Cyanine-Based Probe for the Specific Detection of Live Mycobacterium tuberculosis.

Tuberculosis (TB), characterized by high mortality and low diagnosis, is caused by a single pathogen, Mycobacterium tuberculosis (Mtb). Imaging tools that can be used to track Mtb without pre-labeling and to diagnose live Mtb in clinical samples can shorten the gap between bench and clinic, fuel the development of novel anti-TB drugs, strengthen TB prevention, and improve patient treatment. In this study, we report an unprecedented novel nitroreductase-responsive cyanine-based fluorescent probe (Cy3-NO2-tre) that rapidly and specifically labels Mtb and detects it in clinical samples. Cy3-NO2-tre generated fluorescence after activation by a specific nitroreductase, Rv3368c, which is conserved in the Mycobacteriaceae. Cy3-NO2-tre effectively imaged mycobacteria within infected host cells, tracked the infection process, and visualized Mycobacterium smegmatis being endocytosed by macrophages. Cy3-NO2-tre also detected Mtb in the sputum of patients with TB and exhibited excellent photostability. Furthermore, the Cy3-NO2-tre/auramine O percentage change within 7 ± 2 days post drug treatment in the sputum of inpatients was closely correlated with the reexamination results of the chest computed tomography, strongly demonstrating the clinical application of Cy3-NO2-tre as a prognostic indicator in monitoring the therapeutic efficacy of anti-TB drugs in the early patient care stage.

PCSK6 exacerbates Alzheimer's disease pathogenesis by promoting MT5-MMP maturation.

Proprotein convertase subtilisin/kexin type 6 (PCSK6) is a calcium-dependent serine proteinase that regulates the proteolytic activity of various precursor proteins and facilitates protein maturation. Dysregulation of PCSK6 expression or function has been implicated in several pathological processes including nervous system diseases. However, whether and how PCSK6 is involved in the pathogenesis of Alzheimer's disease (AD) remains unclear. In this study, we reported that the expression of PCSK6 was significantly increased in the brain tissues of postmortem AD patients and APP23/PS45 transgenic AD model mice, as well as N2AAPP cells. Genetic knockdown of PCSK6 reduced amyloidogenic processing of APP in N2AAPP cells by suppressing the activation of membrane-type 5-matrix metalloproteinase (MT5-MMP), referred to as η-secretase. We further found that PCSK6 cleaved and activated MT5-MMP by recognizing the RRRNKR sequence in its N-terminal propeptide domain in N2A cells. The mutation or knockout of this cleavage motif prevented PCSK6 from interacting with MT5-MMP and performing cleavage. Importantly, genetic knockdown of PCSK6 with adeno-associated virus (AAV) reduced Aß production and ameliorated hippocampal long-term potentiation (LTP) and long-term spatial learning and memory in APP23/PS45 transgenic mice. Taken together, these results demonstrate that genetic knockdown of PCSK6 effectively alleviate AD-related pathology and cognitive impairments by inactivating MT5-MMP, highlighting its potential as a novel therapeutic target for AD treatment.

Association of albumin to non-high-density lipoprotein cholesterol ratio with mortality in peritoneal dialysis patients.

OBJECTIVE: Malnutrition and inflammation are associated with mortality in peritoneal dialysis (PD) patients. Serum albumin and non-high-density lipoprotein cholesterol (non-HDL-C) are independently associated with mortality in PD patients. Combining albumin and non-HDL-C with mortality may be more plausible in clinical practice. METHODS: This retrospective cohort study included 1954 Chinese PD patients from 1 January 2009 to 31 December 2016. Kaplan-Meier curve was used to determine the relationship between albumin to non-HDL-C ratio and all-cause mortality. Cox regression analysis was applied to assess the independent predictive value while adjusting for confounding factors. Competitive risk analysis was used to examine the effects of other outcomes on all-cause mortality prognosis. RESULTS: In the 33-month follow-up period, there were 538 all-cause deaths. Kaplan-Meier analysis presented significant differences in all-cause mortality. Multivariate Cox regression showed that the risk of all-cause mortality was lower in the moderate group (9.36-12.79) (HR, 0.731; 95% CI, 0.593-0.902, p = 0.004) and the highest group (>12.79) (HR, 0.705; 95% CI, 0.565-0.879, p = 0.002) compared to the lowest group (≤9.36). Competitive risk analysis revealed significant differences for all-cause mortality (p < 0.001), while there was no statistical significance for other competing events. CONCLUSIONS: Low albumin to non-HDL-C ratio was associated with a high risk of all-cause mortality in PD patients. It may serve as a potential prognostic biomarker in PD patients.

CSTB accelerates the progression of hepatocellular carcinoma via the ERK/AKT/mTOR signaling pathway.

Hepatocellular carcinoma (HCC) is a significant contributor to global cancer-related deaths, leading to high mortality rates. However, the pathogenesis of HCC remains unclear. In this research, by the bioinformatics data analysis, we found that elevated CSTB expression correlated with advanced disease and predicted diminished overall survival (OS) in HCC patients. We subsequently verified the oncogenic role of CSTB as well as the potential underlying mechanisms in HCC through a series of in vitro experiments, such as CCK-8 assays, cloning assays, flow cytometry, Transwell assays, and western blotting. Our findings illustrated that the silencing of CSTB effectively suppressed cellular proliferation by inducing cell cycle arrest in the G2 phase and impaired HCC cell invasion and migration by stimulating epithelial-mesenchymal transition (EMT). Additionally, we analyzed the pathways enriched in HCC using RNA sequencing and found that the ERK/AKT/mTOR signaling pathway was related to increased CSTB expression in HCC. Finally, we confirmed the tumorigenic role of CSTB via in vivo experiments. Thus, our findings revealed that silencing CSTB inhibited the HCC progression via the ERK/AKT/mTOR signaling pathway, highlighting new perspectives for investigating the mechanisms of HCC.

Comprehensive mining of information in Weakly Supervised Semantic Segmentation: Saliency semantics and edge semantics.

In the studies of Weakly Supervised Semantic Segmentation (WSSS) with image-level labels, there is an issue of incomplete semantic information, which we summarize as insufficient saliency semantic mining and neglected edge semantics. We proposes a two-stage framework, Saliency Semantic Full Mining-Edge Semantic Mining (SSFM-ESM), which views WSSS from the perspective of comprehensive information mining. In the first stage, we rely on SSFM to address the insufficient saliency semantic mining. The network learns feature representations consistent with salient regions via the proposed pixel-level class-agnostic distance loss. Then, the full saliency semantic information is mined by explicitly receiving pixel-level feedback. The initial pseudo-label with complete saliency semantic information can be obtained after the first stage. In the second stage, we focus on the mining of edge semantic information through the proposed edge semantic mining module. Specifically, we guide the initial pseudo-label avoid learning about false semantic information and obtain high-confidence edge semantics. The self-correction ability of the segmentation network is also fully utilized to obtain more edge semantic information. Extensive experiments are conducted on the PASCAL VOC 2012 and MS COCO 2014 datasets to verify the feasibility and superiority of this approach.

Associations of Blood Absolute Neutrophil Count and Cytokines With Cognitive Function in Dementia-Free Participants: A Population-Based Cohort Study.

BACKGROUND: The relationships of neutrophils and cytokines with cognitive dysfunction are poorly defined. We aimed to investigate the association of peripheral blood absolute neutrophil count (ANC) with cognitive function in older adults and to further explore the mediating role of serum cytokines in this association. METHODS: This population-based cohort study included 1 666 dementia-free participants (age ≥60 years) derived from baseline examinations (March-September 2018) of the Multimodal Intervention to Delay Dementia and Disability in Rural China (MIND-China); of these, 1 087 participants completed follow-up examinations in October-December 2019. We used a neuropsychological test battery to assess episodic memory, verbal fluency, attention, and executive function at the baseline and follow-up examinations. We used Mindray BC-6800 automated hematology analyzer to measure ANC and Meso Scale Discovery to measure serum interleukin-6 (IL-6) and eotaxin-3. RESULTS: The linear regression analysis of cross-sectional data at baseline (n = 1 666) suggested that increased ANC was significantly associated with a lower episodic memory z score (ß coefficient: -0.149, 95% CI: -0.274 to -0.023) and lower long-delayed free recall z score (-0.216, -0.361 to -0.070). Serum IL-6 and eotaxin-3 could mediate 16.16% to 20.21% and 7.55% to 9.35%, respectively, of these associations. The analysis of longitudinal data (n = 1 087) showed a J-shaped relationship of ANC with decline in episodic memory z score (p for nonlinear = .049), and a U-shaped relationship between ANC and decline in long-delayed free recall z score (p for nonlinear = .043). CONCLUSIONS: Increased neutrophils are associated with poor cognitive performance and accelerated decline in episodic memory, and the cross-sectional association is partly mediated by serum cytokines.