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Abstract Background Spinal cord injury (SCI) is a common neurological condition marked by damage to the spinal cord. In the field of neurological rehabilitation, virtual reality (VR) is increasingly employed for evaluating and addressing the physical limitations caused by SCI. This study aimed to describe and calculate the effect sizes of virtual reality intervention (VR) on the functional performance of SCI. Methods We searched PubMed, Embase, Web of Science, and Cochrane Library to identify articles published before October 30, 2023, that addressed the intervention of SCI using virtual reality technology. We excluded from the meta-analysis articles that did not provide enough data to evaluate the association between virtual reality intervention and spinal cord injury. The RevMan 5.4 statistical software was used for data analysis. Results We included 16 articles in the systematic review and pooled 9 for the meta-analysis, which were 5 randomized controlled trials (RCTs) and 4 non-RCTs, including 248 subjects. The outcome measure of the walking index for spinal cord injury, limits of stability testing and berg balance scale scores improved in non-RCTs. Conclusion VR has shown promise in enhancing walking ability and balance function in individuals with SCI. However, the existing evidence for VR interventions in SCI patients remains limited, highlighting the necessity for future studies in this area.

Abstract Background Polymyxins have been revived as a last-line therapeutic option for multi-drug resistant bacteria and continue to account for a significant proportion of global antibiotic usage. However, kidney injury is often a treatment limiting event with kidney failure rates ranging from 5 to 13%. The mechanisms underlying polymyxin-induced nephrotoxicity are currently unclear. Researches of polymyxin-associated acute kidney injury (AKI) models need to be more standardized, which is crucial for obtaining consistent and robust mechanistic results. Methods In this study, male C57BL/6 mice received different doses of polymyxin B (PB) and polymyxin E (PE, also known as colistin) by different routes once daily (QD), twice daily (BID), and thrice daily (TID) for 3 days. We continuously monitored the glomerular filtration rate (GFR) and the AKI biomarkers, including serum creatinine (Scr), blood urea nitrogen (BUN), neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule-1 (KIM-1). We also performed histopathological examinations to assess the extent of kidney injury. Results Mice receiving PB (35 mg/kg/day subcutaneously) once daily exhibited a significant decrease in GFR and a notable increase in KIM-1 two hours after the first dose. Changes in GFR and KIM-1 at 24, 48 and 72 h were consistent and demonstrated the occurrence of kidney injury. Histopathological assessments showed a positive correlation between the severity of kidney injury and the changes in GFR and KIM-1 (Spearman’s rho = 0.3167, P = 0.0264). The other groups of mice injected with PB and PE did not show significant changes in GFR and AKI biomarkers compared to the control group. Conclusion The group receiving PB (35 mg/kg/day subcutaneously) once daily consistently developed AKI at 2 h after the first dose. Establishing an early and stable AKI model facilitates researches into the mechanisms of early-stage kidney injury. In addition, our results indicated that PE had less toxicity than PB and mice receiving the same dose of PB in the QD group exhibited more severe kidney injury than the BID and TID groups.

Stress is a nonspecific response that occurs when the body is stimulated by internal and external stimuli. When the stress levels exceed the body´s tolerance threshold, physiological and biochemical changes occur that affect homeostasis within the internal environment. Takifugu fasciatus is an important cultured fish species in China, and its demand in the aquatic market has increased in recent years. Stress is extremely harmful to T. fasciatus farming, and cortisol is considered an essential marker for determining the stress response of fish, as it changes significantly within the organism under stress. The intestine is a contact medium between fish and the external environment and can respond to physiological stress levels. Although the study of fish intestinal responses to stress is a global research focus, the role of the T. fasciatus intestinal tract in response to stress remains unclear. In this study, intestinal epithelial cells of T. fasciatus were cultured using four different methods: Trypsin (0.25%) with DMEM, trypsin (0.25%) with RPMI 1640, typeⅠcollagenase (1 mg/mL) in DMEM, and typeⅠcollagenase (1 mg/mL) in RPMI 1640 to establish an in vitro culture method for primary intestinal epithelial cells of T. fasciatus. The effects of different concentrations of cortisol on oxidative stress, apoptosis, and lipid metabolism were investigated. The study methodology involved disinfecting of T. fasciatus with 75% alcohol and subsequently anesthetizing with MS-222. Furthermore, the intestines were removed and cleansed using PBS containing 100 IU/mL penicillin and 100 μg/mL streptomycin. The intestines were then sectioned into 1.5 mL centrifuge tubes with digestive solutions and digested at 28 ℃ for 30 min. Cells were subsequently centrifuged at 1 000 r/min for 5 min at 4 ℃, and resuspended in a new complete medium (DMEM containing 20% fetal bovine serum, 100 IU/mL penicillin, and 100 μg/mL streptomycin). The proliferation rate of intestinal epithelial cells under the four culture methods was determined within 5 d using the CCK-8 method, and cell growth was observed under a microscope after 24 h of culture. Cortisol solutions at varying concentrations were diluted with complete medium, and the cell viability of T. fasciatus was measured using the CCK-8 method after cortisol treatment (0, 100, 1 000, 2 000, 3 000, and 5 000 nmol/L) for 24 h. The morphological structure of intracellular mitochondria was observed through transmission electron microscopy after cortisol treatment (0, 10, 100, and 1 000 nmol/L) for 24 h. After cortisol treatment (0, 10, 100, and 1 000 nmol/L) for 3, 6, 12, and 24 h, the expression patterns of oxidative stress-related genes, apoptosis-related genes, and lipid metabolism-related genes in intestinal epithelial cells were measured by real-time fluorescence-based quantitative PCR (qRT-PCR). Cell apoptosis was measured using the Annexin V-FITC/PI method, and the contents of triglycerides, total cholesterol, and free fatty acids were measured using kits from Nanjing Jiancheng Co. The results showed that the intestinal epithelial cells cultured with trypsin (0.25%) digestion and DMEM had the highest cell proliferation rate among the four culture methods, with predominantly fibroblast-like cell morphology and the best apposition. At a cortisol concentration of 1 000 nmol/L, the intestinal epithelial cell viability was 0.8 times that of the control group, with no significant difference between the 1 000 nmol/L cortisol-treated group and the 2 000 nmol/L cortisol-treated group. However, the cell viability significantly decreased when the cortisol concentration exceeded 2 000 nmol/L (P < 0.05). Thus, 1 000 nmol/L or lower was selected for cortisol treatment. Transmission electron microscopy revealed that the mitochondrial structure of intestinal epithelial cells was altered in all the cortisol-treated groups, with an increase in the number of mitochondria. The expression of oxidative stress-related genes (sod, cat, and gsh-px) and apoptotic index significantly increased with increasing cortisol treatment concentration and time. Pro-apoptotic genes (caspase-3, caspase-7, caspase-9, bax and p53) increased significantly, while anti-apoptotic gene bcl-2 expression decreased significantly with the increase of cortisol treatment concentration (P < 0.05). The expression of lipid synthesis-related genes (g6pd, 6gpd, pparγ, fas and acc) decreased significantly and lipolysis-related genes (hsl, pparα, lpl and cpt-1) increased significantly with increasing cortisol treatment concentration (P < 0.05). Triglyceride and total cholesterol contents decreased significantly, whereas the free fatty acids content increased significantly with increasing cortisol treatment concentration and time (P < 0.05). These results indicate that trypsin (0.25%) digestion with DMEM is optimal for culture of primary intestinal epithelial cells of T. fasciatus. Cortisol promotes oxidative stress, apoptosis, and lipid decomposition but suppresses lipid synthesis in intestinal epithelial cells of T. fasciatus. This study established the optimal isolation and culture method for primary intestinal epithelial cells of T. fasciatus and investigated the mechanism of the intestinal response to cortisol stress in T. fasciatus, thus providing a theoretical basis for the subsequent anti-stress culture of fish.

Abstract In this study, we dynamically monitored the glomerular filtration rate and other assessment of renal function and markers of injury in various mice models of acute kidney injury. Male C57BL/6 mice were utilized to establish acute kidney injury models of sepsis, ischemia reperfusion, cisplatin, folic acid, aristolochic acid and antibiotic. In addition to the real time glomerular filtration rate, renal LCN-2 and HAVCR-1 mRNA expression levels, and serum creatinine, urea nitrogen and cystatin c levels were also used to evaluate renal function. In addition, the protein levels of LCN-2 and HAVCR-1 in renal, serum and urine were measured. Our results demonstrated that the changes in biomarkers always lagged the real time glomerular filtration rate during the progression and recovery of renal injury. Cystatin-c can reflect renal injury earlier than other markers, but it remains higher in the recovery stage. Perhaps the glomerular filtration rate does not reflect the greater injury caused by vancomycin plus piperacillin.

Abstract The minimal clinically important difference (MCID) is an important concept with big appeal in a field struggling to interpret quality of life (QOL) and other patient-reported outcomes (PRO), is also a bridge between statistics and clinical medicine. This study uses the ROC curve to formulate the MCID value of the Quality of Life Instruments for Chronic Diseases of Systemic lupus erythematosus (QLICD-SLE V2.0) scale. Using the representative item “In general, would you say your health is” of the MOS item short form health survey(SF-36) as an anchor, the questionnaire of QLICD-SLE V2.0 and the anchor item were used to investigate the patients on the first day of hospitalization, and the day before the patient was discharged. 279 patients with lupus erythematosus were participated in this longitudinal follow-up study. The ROC curve was constructed by using the classification based on the anchor item as the gold standard and the difference score of the scale as the test variable. The cut-off point corresponding to the maximum value of the Youden index in the ROC curve is taken as the minimum clinical importance difference (MCID) value of the QLICD-SLE (V2.0) scale. The Results showed that the MCID of physical domain, psychological domain, social domain, general module, specific module and QLICD-SLE (V2.0) total scale are 8.3, 2.3, 2.5, 2.7, 9.2 and 3.2, respectively. Area under the ROC curve of QLICD-SLE (V2.0) is 0.898, P (Area = 0.5)

Abstract Transport accessibility is crucial for defining urban clusters and evaluating a region's centrality and connectivity. To foster equitable growth in urban conglomerates, it is crucial to understand the relationship between transport accessibility and regional development. This study introduces the concept of 'regional efficiency'—the effectiveness of converting regional inputs into outputs—determined via the super-efficiency Data Envelopment Analysis methodology, to assess the progression of regional development. Employing a combination of bivariate spatial autocorrelation and spatial regression analysis, this research elucidates the spatial dynamics between transport accessibility and regional efficiency, both at macro and micro levels. A binary Logit model identifies the factors affecting the Moran's I correlation between regional efficiency and transport accessibility. Based on the diverse urban characteristics within a single conglomerate, tailored development strategies are suggested. Focusing on the Yangtze River Delta Urban Agglomeration in China as a case study, four distinct spatial clusters—High–High (HH), Low–Low (LL), High–Low (HL), and Low–High (LH)—are identified, based on the local correlation between regional efficiency and transport accessibility. The findings reveal that regions with a High–High Moran's I correlation between road accessibility and regional efficiency predominantly located in the eastern sectors of the Yangtze River Delta, exhibiting effective regional efficiency. These regions are characterized by superior road accessibility, aligning well with their regional efficiency metrics. For air accessibility, cities classified under the HH category, including Shanghai and its neighboring cities, demonstrate a significant spatial correlation with regional efficiency. Population density and urban tier are key predictors of the significance of the Moran's I correlation between road accessibility and regional efficiency. In contrast, for air accessibility, these factors assume an inverse role. The identified cluster types (HH, LL, LH, and HL) are proposed as predictive indicators for the significance of the Moran's I relationship between air accessibility and regional efficiency.

Abstract Introduction Persons with diabetes are at risk for developing a cardiomyopathy through several pathophysiological mechanisms independent of traditional risk factors for heart failure. Among those with diabetic cardiomyopathy (DbCM), the relationship between natriuretic peptides, cardiac structural abnormalities and functional capacity is largely unknown. Methods In this prespecified subgroup analysis of the Aldose Reductase Inhibition for Stabilization of Exercise Capacity in Heart Failure (ARISE-HF) trial, 685 participants with asymptomatic DbCM underwent baseline echocardiography data, laboratory investigations, and functional assessments. Participants were stratified by N-terminal pro-B type natriuretic peptide (NT-proBNP) quartiles, and correlation with echocardiographic and functional parameters were assessed using Spearman correlation test. Results The median NT-proBNP was 71 (Q1, Q3: 33, 135) ng/L. No association was observed between NT-proBNP concentrations and echocardiographic parameters of either diastolic or systolic dysfunction including global longitudinal strain, left ventricular ejection fraction, left ventricular mass index, left atrial volume index, E/E’, or right ventricular systolic pressure. In contrast, NT-proBNP was significantly correlated with overall Kansas City Cardiomyopathy Questionnaire score (rho = − 0.10; p = 0.007), the Physical Activity Scale in the Elderly (rho = − 0.12; p = 0.004), duration of cardiopulmonary exercise testing (rho = − 0.28; p 95 for females or > 115 for males or E/e’ >13 or left atrial volume index > 34. †Normal ECHO is defined as the absence of these abnormalities. Low NT-proBNP is defined as

Volatile organic compounds (VOCs) have boiling points ranging from 50 ℃ to 260 ℃ at room temperature. These compounds are emitted from complex sources, including automobile manufacturing, fine chemicals, the pharmaceutical industry, interior decoration, and the plastics industry. VOCs serve as important precursors of secondary organic aerosols and ozone. However, some VOCs discharged into the atmosphere undergo photochemical reactions, resulting in the formation of photochemical smog. This byproduct is irritating, teratogenic, and carcinogenic, causing considerable harm to human health and posing a serious threat to the environment. Among VOCs, aromatic hydrocarbons originate from a wide range of sources relevant to human life. These compounds have been a constant hot spot in the field of VOC removal due to their unique aromatic ring structure, highly toxic effects, and challenging treatment. VOC removal mainly comprises source reduction, process management, and end–to–end treatment. End–to–end treatment methods involve adsorption, photocatalytic, plasma decomposition, membrane separation, and catalytic oxidation. Catalytic oxidation can effectively convert VOCs into carbon dioxide and water at relatively low temperatures, making it one of the most effective methods for VOC treatment. Efficient catalyst development is the key point for catalytic oxidation methods. This review highlights progress in catalyst development for the catalytic oxidation of toluene, focusing on the characteristics of noble-metal catalysts, such as noble-metal species, particle size, alloying systems, and support properties. While transition-metal oxide catalysts are abundant and inexpensive, they exhibit low catalytic performance for toluene oxidation. Therefore, discussions on transition-metal oxide catalysts include synthesis or calcination temperature, atomic substitution (isovalent and heterovalent substitutions), surface modification (noble- and transition-metal doping), and in situ surface treatment (chemical etching and surface modification). Although studies on toluene degradation using spinel- and perovskite-type oxide catalysts and metal-organic framework-based catalysts are limited, a brief summary of their characteristics during catalytic oxidation of toluene is provided, focusing on the relationship between the catalyst microstructure and performance. Furthermore, the kinetic model for the catalytic oxidation of toluene was briefly evaluated, and the corresponding reaction mechanism and kinetics were analyzed. This review aims to contribute to the development of efficient catalysts for the complete or selective oxidation of toluene.

Developing the alternative supported noble metal catalysts with low cost, high catalytic efficiency, and good resistance toward carbon dioxide and water vapor is critically demanded for the oxidative removal of volatile organic compounds (VOCs). In this work, we prepared the mesoporous chromia-supported bimetallic Co and Ni single-atom (Co1Ni1/meso-Cr2O3) and bimetallic Co and Ni nanoparticle (CoNPNiNP/meso-Cr2O3) catalysts adopting the one-pot polyvinyl pyrrolidone (PVP)- and polyvinyl alcohol (PVA)-protecting approaches, respectively. The results indicate that the Co1Ni1/meso-Cr2O3 catalyst exhibited the best catalytic activity for n-hexane (C6H14) combustion (T50% and T90% were 239 and 263 °C at a space velocity of 40,000 mL g−1 h−1; apparent activation energy and specific reaction rate at 260 °C were 54.7 kJ mol−1 and 4.3 × 10−7 mol gcat−1 s−1, respectively), which was associated with its higher (Cr5+ + Cr6+) amount, large n-hexane adsorption capacity, and good lattice oxygen mobility that could enhance the deep oxidation of n-hexane, in which Ni1 was beneficial for the enhancements in surface lattice oxygen mobility and low-temperature reducibility, while Co1 preferred to generate higher contents of the high-valence states of chromium and surface oxygen species as well as adsorption and activation of n-hexane. n-Hexane combustion takes place via the Mars−van Krevelen (MvK) mechanism, and its reaction pathways are as follows: n-hexane → olefins or 3-hexyl hydroperoxide → 3-hexanone, 2-hexanone or 2,5-dimethyltetrahydrofuran → 2-methyloxirane or 2-ethyl-oxetane → acrylic acid → COx → CO2 and H2O.

The endoplasmic reticulum (ER) plays a pivotal role in protein folding and secretion, Ca2+ storage, and lipid synthesis in eukaryotic cells. When the burden of protein synthesis and folding required to be handled exceeds the processing capacity of the ER, the accumulation of misfolded/unfolded proteins triggers ER stress. In response to short-term ER stress, the unfolded protein response (UPR) is activated to allow cells to survive. When ER stress is severe and sustained, it typically provokes cell death through multiple approaches. It is well documented that ER stress and metabolic deregulation are functionally intertwined, both are considered contributing factors to the pathogenesis of liver diseases, including non-alcoholic fatty liver disease (NAFLD), alcoholic liver disease (ALD), ischemia/reperfusion (I/R) injury, viral hepatitis, liver fibrosis, and hepatocellular carcinoma (HCC). Hepatocytes are rich in smooth and rough ER, which harbor metabolic enzymes that are capable of sensing alterations in various nutritional status and external stimuli. Extensive research has focused on the molecular mechanism linking ER stress with metabolic enzymes. The purpose of this review is to summarize the current knowledge regarding the effects of ER stress on metabolic enzymes in various liver diseases and to provide potential therapeutic strategies for chronic liver diseases via targeting UPR.

Abstract Background Anxiety disorders can cause serious physical and psychological damage, so many anxiety scales have been developed internationally to measure anxiety disorders, but due to the cultural differences and cultural dependence of quality of life between Chinese and Western cultures, it is difficult to reflect the main characteristics of Chinese patients. Therefore, we developed a scale suitable for Chinese patients with anxiety disorders: the Anxiety Disorders Scale of the Quality of Life Instruments for Chronic Diseases (QLICD-AD), hoping to achieve satisfactory QOL assessments for anxiety disorders. Objectives Items from the Anxiety Disorders Scale of the Quality of Life in Chronic Disease Instrument QLICD-AD system were analyzed using CTT and IRT to lay the groundwork for further refinement of the scale to accurately measure anxiety disorders. Methods 120 patients with anxiety disorder were assessed using the QLICD-AD (V2.0). Descriptive statistics, variability method, correlation coefficient method, factor analysis and Cronbach’s coefficient of CTT, and graded response model (GRM) of item response theory were used to analyze the items of the scale. Result CTT analysis showed that the standard deviation of each item was between 0.928 and 1.466; Pearson correlation coefficients of item-to-domain were generally greater than 0.5 and also greater than that of item-to-other domain; the Cronbach ‘s of the total scale was 0.931, α of each domain was between 0.706 and 0.865. IRT analysis showed that the discrimination was between 1.14 and 1.44. The difficulty parameter of all items increased with the increase of grade. But some items (GPH6,GPH8,GPS3,GSO2-GSO4,AD2,AD5) difficulty parameters were less than 4 or greater than 4. The average of information amount was between 0.022 and 0.910. Conclusion Based on CTT and IRT analysis, most items of the QLICD-AD (V2.0) scale have good performance and good differentiation, but a few items still need further revision. Suggests that the QLICD-AD (V2.0) appears to be a valid measure of anxiety disorders. It may effectively improve the diagnosticity of anxiety disorders, but due to the limitations of the current sample, further validation is needed in a broader population extrapolation trial.

Abstract Background Deep learning (DL), a specialized form of machine learning (ML), is valuable for forecasting survival in various diseases. Its clinical applicability in real-world patients with gastric cancer (GC) has yet to be extensively validated. Methods A combined cohort of 11,414 GC patients from the Surveillance, Epidemiology and End Results (SEER) database and 2,846 patients from a Chinese dataset were utilized. The internal validation of different algorithms, including DL model, traditional ML models, and American Joint Committee on Cancer (AJCC) stage model, was conducted by training and testing sets on the SEER database, followed by external validation on the Chinese dataset. The performance of the algorithms was assessed using the area under the receiver operating characteristic curve, decision curve, and calibration curve. Results DL model demonstrated superior performance in terms of the area under the curve (AUC) at 1, 3, and, 5 years post-surgery across both datasets, surpassing other ML models and AJCC stage model, with AUCs of 0.77, 0.80, and 0.82 in the SEER dataset and 0.77, 0.76, and 0.75 in the Chinese dataset, respectively. Furthermore, decision curve analysis revealed that the DL model yielded greater net gains at 3 years than other ML models and AJCC stage model, and calibration plots at 3 years indicated a favorable level of consistency between the ML and actual observations during external validation. Conclusions DL-based model was established to accurately predict the survival rate of postoperative patients with GC.

Bile acids (BAs) undergo extensive microbial metabolism in the gut and exert hormone-like functions on physiological processes underlying metabolic risk. However, the extent to which gut BA profiles predict cardiometabolic risk and explain individual responses to dietary interventions in humans is still unclear. In the DIRECT-PLUS Trial, we conducted a multi-omics analysis of 284 participants randomized into three groups: healthy dietary guidelines and two Mediterranean diet (MedDiet) groups. We longitudinally measured 44 fecal BAs using liquid chromatography-mass spectrometry, the gut microbiome through shotgun metagenomic sequencing, and body adiposity and serum lipids at baseline, 6, and 18 months. Fecal levels of 14 BAs, such as lithocholic acid and ursodeoxycholic acid, were prospectively associated with body mass index (BMI) and serum lipid profiles (false discovery rate [q]

IntroductionTertiary lymphoid structures (TLSs) are analogues of secondary lymphoid organs that contain various immune cells. The spatial distribution, maturation and composition of TLSs have differential effects on prognosis, and the roles of TLSs in gastric adenocarcinoma (GA) have not been revealed.MethodsThus, we evaluated the prognostic value of TLSs in GA through analysis of bulk RNA sequencing(RNA-seq) data from public databases and validated our findings in tumour samples from the Fudan University Shanghai Cancer Center (FUSCC) cohort. The spatial distribution,maturation, and composition of TLSs in GA were analysed by reviewing H&E-stained sections and by multiplex immunofluorescence (mIF) staining.ResultsWe found that TLSs, especially TLSs with germinal centres (GCs) and TLSs located in the invasive margin (IM), were correlated with prolonged overall survival (OS). Second, analysis of public RNA-seq data showed that high dendritic cell (DC) scores were a favourable prognostic factor in GA patients with high scores for both TLSs and GCs. In the FUSCC cohort, DC-LAMP+ DCs weresignificantly enriched in IM-TLSs with GCs, suggesting a potential correlation between the tumour immune activation milieu and the DC abundance. Third, compared to that in TLSs without GCs, the proportion of FOXP3+CD8+ Treg cells was significantly decreased in IM-TLSs with GCs, and the percentage of PD1+CD20+ B cells was significantly increased in TLSs with GCs.DiscussionOur results demonstrate that the spatial arrangement and maturation of TLSs significantly affect prognosis and indicate that TLSs could be a new additional factor for histopathological evaluation.

The roles of lipoprotein(a) [Lp(a)] and related oxidized phospholipids (OxPLs) in the development and progression of coronary disease is known, but their influence on extracoronary vascular disease is not well-established. We sought to evaluate associations between Lp(a), OxPL apolipoprotein B (OxPL-apoB), and apolipoprotein(a) (OxPL-apo(a)) with angiographic extracoronary vascular disease and incident major adverse limb events (MALEs). Four hundred forty-six participants who underwent coronary and/or peripheral angiography were followed up for a median of 3.7 years. Lp(a) and OxPLs were measured before angiography. Elevated Lp(a) was defined as ≥150 nmol/L. Elevated OxPL-apoB and OxPL-apo(a) were defined as greater than or equal to the 75th percentile (OxPL-apoB ≥8.2 nmol/L and OxPL-apo(a) ≥35.8 nmol/L, respectively). Elevated Lp(a) had a stronger association with the presence of extracoronary vascular disease compared to OxPLs and was minimally improved with the addition of OxPLs in multivariable models. Compared to participants with normal Lp(a) and OxPL concentrations, participants with elevated Lp(a) levels were twice as likely to experience a MALE (odds ratio: 2.14, 95% confidence interval: 1.03, 4.44), and the strength of the association as well as the C statistic of 0.82 was largely unchanged with the addition of OxPL-apoB and OxPL-apo(a). Elevated Lp(a) and OxPLs are risk factors for progression and complications of extracoronary vascular disease. However, the addition of OxPLs to Lp(a) does not provide additional information about risk of extracoronary vascular disease. Therefore, Lp(a) alone captures the risk profile of Lp(a), OxPL-apoB, and OxPL-apo(a) in the development and progression of atherosclerotic plaque in peripheral arteries.

Background: The Juan-Bi decoction (JBD) is a classic traditional Chinese medicines (TCMs) prescription for the treatment of rheumatoid arthritis (RA). However, the active compounds of the JBD in RA treatment remain unclear.Aim: The aim of this study is to screen effective compounds in the JBD for RA treatment using systems pharmacology and experimental approaches.Method: Botanical drugs and compounds in the JBD were acquired from multiple public TCM databases. All compounds were initially screened using absorption, distribution, metabolism, excretion, and toxicity (ADMET) and physicochemical properties, and then a target prediction was performed. RA pathological genes were acquired from the DisGeNet database. Potential active compounds were screened by constructing a compound–target–pathogenic gene (C-T-P) network and calculating the cumulative interaction intensity of the compounds on pathogenic genes. The effectiveness of the compounds was verified using lipopolysaccharide (LPS)-induced RAW.264.7 cells and collagen-induced arthritis (CIA) mouse models.Results: We screened 15 potentially active compounds in the JBD for RA treatment. These compounds primarily act on multiple metabolic pathways, immune pathways, and signaling transduction pathways. Furthermore, in vivo and in vitro experiments showed that bornyl acetate (BAC) alleviated joint damage, and inflammatory cells infiltrated and facilitated a smooth cartilage surface via the suppression of the steroid hormone biosynthesis.Conclusion: We screened potential compounds in the JBD for the treatment of RA using systems pharmacology approaches. In particular, BAC had an anti-rheumatic effect, and future studies are required to elucidate the underlying mechanisms.

Background Higher lipoprotein(a) and oxidized phospholipid concentrations are associated with increased risk for coronary artery disease and valvular heart disease. The role of lipoprotein(a) or oxidized phospholipid as a risk factor for incident heart failure (HF) or its complications remains uncertain. Methods and Results A total of 1251 individuals referred for coronary angiography in the Catheter Sampled Blood Archive in Cardiovascular Diseases (CASABLANCA) study were stratified on the basis of universal definition of HF stage; those in stage A/B (N=714) were followed up for an average 3.7 years for incident stage C/D HF or the composite of HF/cardiovascular death. During follow‐up, 105 (14.7%) study participants in stage A/B progressed to symptomatic HF and 57 (8.0%) had cardiovascular death. In models adjusted for multiple HF risk factors, including severe coronary artery disease and aortic stenosis, individuals with lipoprotein(a) ≥150 nmol/L were at higher risk for progression to symptomatic HF (hazard ratio [HR], 1.90 [95% CI, 1.15–3.13]; P=0.01) or the composite of HF/cardiovascular death (HR, 1.71 [95% CI, 1.10–2.67]; P=0.02). These results remained significant after further adjustment of the model to include prior myocardial infarction (HF: HR, 1.89, P=0.01; HF/cardiovascular death: HR, 1.68, P=0.02). Elevated oxidized phospholipid concentrations were similarly associated with risk, particularly when added to higher lipoprotein(a). In Kaplan‐Meier analyses, individuals with stage A/B HF and elevated lipoprotein(a) had shorter time to progression to stage C/D HF or HF/cardiovascular death (both log‐rank P

During aging, the brain is subject to greater oxidative stress (OS), which is thought to play a critical role in cognitive impairment. Glutathione (GSH), as a major antioxidant in the brain, can be used to combat OS. However, how brain GSH levels vary with age and their associations with cognitive function is unclear. In this study, we combined point-resolved spectroscopy and edited spectroscopy sequences to investigate extended and closed forms GSH levels in the anterior cingulate cortex (ACC), posterior cingulate cortex (PCC), and occipital cortex (OC) of 276 healthy participants (extended form, 166 females, age range 20–70 years) and 15 healthy participants (closed form, 7 females, age range 26–56 years), and examined their relationships with age and cognitive function. The results revealed decreased extended form GSH levels with age in the PCC among 276 participants. Notably, the timecourse of extended form GSH level changes in the PCC and ACC differed between males and females. Additionally, positive correlations were observed between extended form GSH levels in the PCC and OC and visuospatial memory. Additionally, a decreased trend of closed form GSH levels with age was also observed in the PCC among 15 participants. Taken together, these findings enhance our understanding of the brain both closed and extended form GSH time course during normal aging and associations with sex and memory, which is an essential first step for understanding the neurochemical underpinnings of healthy aging.

Abstract Background Diabetic cardiomyopathy (DbCM) is a form of Stage B heart failure (HF) at high risk for progression to overt disease. Using baseline characteristics of study participants from the Aldose Reductase Inhibition for Stabilization of Exercise Capacity in Heart Failure (ARISE-HF) Trial we sought to characterize clinical characteristics of individuals with findings consistent with DbCM. Methods Among study participants meeting inclusion criteria, clinical characteristics, laboratory testing, imaging, Kansas City Cardiomyopathy Questionnaire (KCCQ), Physical Activity Scale of the Elderly (PASE) and cardiopulmonary exercise testing (CPET) results were tabulated. Cluster phenogroups were identified. Results Among 691 study participants (mean age 67.4 years; 50% were female), mean duration of type 2 diabetes mellitus (T2DM) was 14.5 years. The median (Q1, Q3) N-terminal pro-B type natriuretic peptide and high sensitivity cardiac troponin T were 71 (35, 135) ng/L and 9 [6, 12] ng/L. The most common echocardiographic abnormalities were reduced global longitudinal strain in 25.3% and impaired diastolic relaxation in 17.7%. Despite rather well-preserved KCCQ scores the average PASE score was markedly impaired at 155 accompanied by an average maximal oxygen consumption of 15.7 mL/Kg/minute on CPET. In K-means clustering, 4 phenogroups were identified including a higher-risk group with more advanced age, greater elevation of cardiac biomarkers, and more prevalent evidence for diastolic dysfunction and left ventricular hypertrophy. Conclusions Baseline data from the ARISE-HF Trial provide clinical characterization of individuals with T2DM and features of stage B HF, and may help clarify the diagnosis of DbCM. Trial Registration ARISE-HF, NCT04083339.

A slow-wave half-mode substrate integrated waveguide with a spoof surface plasmon polariton (SW-HMSIW-SSPP) transmission line structure is proposed, analyzed, and demonstrated. Results show longitudinal and lateral size reductions of more than 80% and 73%, respectively, as compared with an equivalent SIW at the same cutoff frequency while maintaining a low attenuation constant of 0.02 dB/mm. By altering the geometric parameters of the SW-HMSIW-SSPP the dispersion curve can be tailored. The dispersion and electromagnetic (EM) field distribution characteristics of the proposed SW-HMSIW-SSPP unit cell and overall structure are analyzed by HFSS simulations and an equivalent circuit, and pertinent performance parameters are compared to those of SW-HMSIW and HMSIW-SSPP structures. A proof-of-concept PCB SW-HMSIW-SSPP sample was fabricated, and measurement results showing a band-pass of 4.8-11.5 GHz are found consistent with simulation results. The SW-HMSIW-SSPP structure has applications in the design of miniaturized microwave circuits.

To clarify the preferences of employees seeking influenza vaccination, a discrete choice experiment aims to understand the essential factors that close the gap between intention and behavior. A total of 866 employees with vaccination willingness willing to participated in a discrete choice experiment (DCE) between October 31st and December 6th, 2022 in China including the following attributes: price, vaccination setting, appointment mode, and service time. The data was analyzed using mixed logit models. Employees from smaller enterprises were more likely to get vaccinated collectively. For employees willing to get the influenza vaccine, 95.08 % of their choice was dominated by price. Employees’ behavior varied according to their socioeconomic characteristics. Only female employees strongly favored work-site-based vaccination. Price was the primary factor considered by employees for getting the influenza vaccine. DCE would help to develop influenza vaccination intervention targeted at different groups in future studies.

Accounting for over 40% of the total energy consumption, the global building sector is pivotal for achieving carbon peak and neutrality objectives. The intricate nature of building carbon emissions, influenced by spatial, temporal, and multifactor coupling, poses challenges on implementing carbon-neutral technologies and conservation strategies. This study focuses on nearly zero energy buildings in China and employs system dynamics to predict energy consumption and carbon emissions according to various scenarios, unveiling influencing patterns and viable emission reduction pathways. The results highlight the substantial impact of enhancing energy conservation awareness as this leads to a 36.4% reduction in energy consumption and a 44.2% reduction in carbon emissions. To attain energy efficiency and carbon reduction goals, a comprehensive approach is essential, encompassing improved building performance, heightened resident energy awareness, increased renewable energy use, and energy landscape adjustments. These findings inform future building energy and carbon emission regulations and offer valuable policy insights.

Abstract Objective The present study is aimed to develop and validate a quality of life scale for systemic lupus erythematosus (SLE) patients with Chinese cultural background, QLICD-SLE (V2.0). Methods The QLICD-SLE (V2.0) was developed using a systematic approach that involved focus groups, nominal discussions, and pilot testing. A total of 428 SLE patients participated in the scale's assessment. Validity was examined through qualitative analysis, item domain correlation, multidimensional scaling, and factor analysis. Reliability was assessed using Pearson's correlation and Cronbach's alpha coefficients. To evaluate responsiveness, paired T-tests were conducted to compare pre- and post-treatment measurements with the standardised response mean (SRM) being calculated. Results Correlation and factor analyses demonstrated strong construct validity. When using SF-36 as criteria, the correlation between various domains of QLICD-SLE and SF-36 ranged from 0.55 to 0.70. Test–retest correlation coefficients exceeded 0.71, and Cronbach’s alpha coefficients for both measurements in each domain were greater than or equal to 0.75. T-test results showed that both the overall score and most facet scores within each domain showed statistically significant changes after treatment (P

Abstract Aims Serial assessment of natriuretic peptides is widely utilized in heart failure clinics. Uncertainty exists regarding the value of multiple natriuretic peptide measurements and how they might be best interpreted. Methods and results Six hundred thirty‐two patients with heart failure with reduced ejection fraction ( 0.1). However, among those with higher baseline NT‐proBNP, those with lower subsequent AUC had a greater improvement in cardiac remodelling indices (P‐value

With the rapid development of the civil aviation industry, the number of flights has increased rapidly. However, the availability of flight slot resources remains limited, and how to allocate flight slot resources effectively has been a hot research topic in recent years. A comprehensive flight slot optimization method can significantly enhance the rationality of the allocation results. The effective allocation of flight slot is the key to improving the operational efficiency of the multi-airport system. We will optimize the flight schedule of the entire multi-airport system considering the fairness of each airport in it. The optimization results will provide an important reference for the reasonable allocation of flight slot within the multi-airport system. Based on the operation characteristics of the multi-airport system, we have established a multi-objective flight slot allocation optimization model. In this model, we set the airport capacity limit, shared waypoint capacity limit and aircraft turnaround time limit as the constraints. The optimization goal of the model is to minimize total flight schedule displacement and the maximum deviation of fairness from the absolute fairness. Gurobi solver is used to solve the model. We have innovatively incorporated the rolling capacity constraint method into our model to ensure more accurate flight slot allocation results. The Beijing-Tianjin-Hebei regional multi-airport system is selected as an example to verify the above model, and the flight slot optimization results have successfully met the fairness goal. The comparative analysis has demonstrated that the rolling capacity constraint method significantly improves the accuracy of solution results, leading to more stable flight slot allocation. The results also prove that the flight slot allocation method of multi-airport system based on absolute fairness of peak demand can improve the fairness of the allocation results. To achieve a higher level of fairness, we have found that the peak-demand based fairness method requires a smaller slot displacement compared to the non-peak demand-based method. Through the optimization of flight slot of the multi-airport system, the coordination between airports can be significantly improved. It can provide a new solution for the efficient operation of the multi-airport system.

Abstract Breast cancer is the most common cancer and the leading cause of cancer death among females worldwide. During the past 15 years, quality of life (QOL) has become an important aspect of breast cancer treatment. The purpose of this study was to evaluate QOL of breast cancer patients in China, and investigate its associations with sociodemographic and clinical variables. A cross-sectional study was conducted in 246 breast cancer patients in China. Recruited patients were surveyed for QOL using the QOL instruments for cancer patients-breast cancer QLICP-BR (V2.0). We assessed the associations between potential influencing factors and QOL using multiple linear regression models. The general mean QOL score for our population was 70.24 with SD = 8.70. Results indicated that medical insurance, drinking history, alkaline phosphatase, serum chloride ion level, serum calcium ion level, serum phosphorus ion level, mean corpuscular volume, mean corpuscular hemoglobin, red cell volume distribution width and platelet had significant associations with QOL of breast cancer patients. Our results emphasized that many factors are affecting QOL of breast cancer patients, which may provide a reference for targeted management or intervention strategies of breast cancer patients to improve their QOL.

Microstructure and corrosion behavior of welded joints between super duplex stainless steel 2507 and low alloy steel E690 were characterized herein. The joints are composed of base metal and heat affected zone (HAZ) of the two steels, weld metal, and dilution zone at the interface between weld metal and HAZ of E690 steel. Concentration gradients of Fe, Ni, Cr, and Mo exist between fusion boundary and Type-II boundary, and martensite band with a high hardness is formed. The changes of microstructure, element diffusion in different regions, and local acidification in E690 HAZ lead to heterogeneous corrosion attacks on the welded joints in artificial seawater. After long-term exposure, a corrosion groove is generated at the HAZ of E690 adjacent to the interface, where high stress corrosion cracking vulnerability is expected.

The present study proposed novel prefabricated composite RC shear walls with a concrete-filled steel tube frame (CCRCSW-CFST) because of the superior seismic performance of shear walls incorporating CFSTs as boundary-restrained members. One cast-in-place reinforced concrete shear wall (RCSW) and seven CRCSW-CFSTs, each varying in axial compression ratios, concrete strengths, and shear span ratios, were designed for experimental analysis. Cyclic loading tests were performed on these specimens, yielding the following results: (1) Compared to reinforced concrete shear walls, CCRCSW-CFSTs demonstrated superior seismic performance, with 14.2% increased ductility and 47.5% greater energy dissipation capacity. (2) Elevating the axial compression ratio in CCRCSW-CFSTs resulted in increased yield strength, peak strength, and stiffness. Conversely, this adjustment also expedited the degradation of stiffness with displacement and decreased both ductility and ultimate deformation. (3) The peak displacement and ultimate displacement of CCRCSW-CFSTs were both increased with an increase in concrete strength. Increasing the axial compression ratio enhanced the initial stiffness of CCRCSW-CFSTs and mitigated the rate at which stiffness deteriorated with increasing displacement. (4) The stiffness, peak and ultimate displacements, peak and ultimate loads, and shear span ratio of CCRCSW-CFSTs were significantly reduced as the shear span ratio was increased. (5) The minor slip between the reinforced concrete panel of the precast slab and the encasing C-shaped steel contributed to an increase in early-stage energy dissipation of the CCRCSW-CFSTs.

Abstract The purpose of the present study is to develop and validate the hypertension scale of the Quality of Life Instruments (QoL) for Chronic Diseases system, QLICD-HY (V2.0). The QLICD-HY (V2.0) was developed via a programmed decision method with several focus groups, nominal discussions and pilot testing. The data was collected from 370 hypertensive inpatients and measured their QoL three times before and after treatment. Using correlation, factor analyses, as well as t-tests, the psychometric properties of the scale were assessed with regard to validity, reliability and responsiveness. Correlation and factor analysis supported good construct validity and criterion-related validity when using Short Form 36 as a criterion. Test–retest reliability coefficients for the overall scale score and all domains, with the exception of the psychological and social domain (0.77, 0.78), were greater than 0.80, with a range of 0.77–0.92. The internal consistency for all domains was higher than 0.70. With the exception of the psychological domain and social domain, the overall score and scores for the majority of aspects within each domain underwent statistically significant changes (t-tests) after the treatment. The QLICD-HY (V2.0) has good validity, reliability and responsiveness and can be used as a QoL measure for hypertensive patients.

Abstract Background The insulin-like growth factors (IGF) play a crucial role in regulating cellular proliferation, apoptosis, and key metabolic pathways. The ratio of IGF-1 to IGF binding protein-3 (IGFBP-3) is an important factor in determining IGF-1 bioactivity. We sought to investigate the association of IGF-1 and IGFBP-3 with cardio-renal outcomes among persons with type 2 diabetes. Methods Samples were available from 2627 individuals with type 2 diabetes and chronic kidney disease that were randomized to receive canagliflozin or placebo and were followed up for incident cardio-renal events. Primary outcome was defined as a composite of end-stage kidney disease, doubling of the serum creatinine level, or renal/cardiovascular death. IGF-1 and IGFBP-3 were measured at baseline, Year-1 and Year-3. Elevated IGF-1 level was defined according to age-specific cutoffs. Cox proportional hazard regression was used to investigate the association between IGF-1 level, IGFBP-3, and the ratio of IGF-1/IGFBP-3 with clinical outcomes. Results Elevated IGF-1 was associated with lower glomerular filtration rate at baseline. Treatment with canagliflozin did not significantly change IGF-1 and IGFBP-3 concentrations by 3 years (p-value > 0.05). In multivariable models, elevated IGF-1 (above vs below age-specific cutoffs) was associated with the primary composite outcome (incidence rate:17.8% vs. 12.7% with a hazard ratio [HR]: 1.52; 95% confidence interval CI 1.09–2.13;P: 0.01), renal composite outcome (HR: 1.65; 95% CI 1.14–2.41; P: 0.01), and all-cause mortality (HR: 1.52; 95% CI 1.00–2.32; P; 0.05). Elevations in log IGFBP-3 did not associate with any clinical outcomes. Increase in log IGF-1/IGFBP-3 ratio was also associated with a higher risk of the primary composite outcome (HR per unit increase: 1.57; 95% CI 1.09–2.26; P; 0.01). Conclusions These results further suggest potential importance of IGF biology in the risk for cardio-renal outcomes in type 2 diabetes. SGLT2 inhibition has no impact on the biology of IGF despite its significant influence on outcomes. Trial registration: CREDENCE; ClinicalTrials.gov Identifier: NCT02065791.

Abstract Objectives To investigate the correlation between serum angiopoietin‐like protein 4 (ANGPTL4) levels, white matter hyperintensity (WMH), and cognitive impairment (CI) in patients with cerebral small vessel disease (CSVD). Methods This cross‐sectional study enrolled 171 patients with CSVD who attended the First Affiliated Hospital of Xinxiang Medical University from December 2021 to July 2022. All subjects underwent a 3.0T head magnetic resonance imaging, neuropsychology assessment, and blood sampling. Serum ANGPTL4 levels were detected by enzyme‐linked immunosorbent assay and the severity of WMH was assessed by the Fazekas scale. According to the Montreal Cognitive Assessment (MoCA) scale, subjects were divided into normal cognition group (NC, n = 80) and CI group (n = 91). According to the total Fazekas scores, subjects were divided into a mild WMH group (n = 84), a moderate WMH group (n = 70), and a severe WMH group (n = 17). Results Serum ANGPTL4 levels were significantly higher in the CI group than in the NC group (p

This field experiment aimed to investigate the effects of different ratios of organic and inorganic fertilizers with maintaining equal nitrogen application rates on the yield, quality, and nitrogen uptake efficiency of Dioscorea polystachya (yam). Six treatments were set, including a control without fertilizer (CK), sole application of chemical fertilizer (CF), sole application of organic fertilizer (OM), 25% organic fertilizer + 75% chemical fertilizer (25%OM + 75%CF), 50% organic fertilizer + 50% chemical fertilizer (50%OM + 50%CF), and 75% organic fertilizer + 25% chemical fertilizer (75%OM + 25%CF). The experiment followed a randomized complete block design with three replications. Various yield parameters, morphology, quality indicators, and nitrogen utilization were analyzed to assess the differences among treatments. The results indicated that all fertilizer treatments significantly increased the yield, morphology, quality indicators, and nitrogen utilization efficiency compared to the control. Specifically, 25%OM + 75%CF achieved the highest yield of 31.96 t hm-2, which was not significantly different from CF (30.18 t hm-2). 25%OM + 75%CF exhibited the highest values at 69.23 cm in tuber length and 75.86% in commodity rate, 3.14% and 1.57% higher than CF respectively. Tuber thickness and fresh weight of 25%OM + 75%CF showed no significant differences from CF, while OM and 50%OM+50%CF exhibited varying degrees of reduction compared to CF. Applying fertilizer significantly enhanced total sugar, starch, crude protein, total amino acid, and ash contents of D. polystachya (except ash content between CK and OM). Applying organic fertilizer increased the total sugar, starch, crude protein, total amino acid, and ash contents in varying degrees when compared with CF. The treatment with 25%OM+75%CF exhibited the highest increases of 6.31%, 3.78%, 18.40%, 29.70%, and 10%, respectively. Nitrogen content in different plant parts followed the sequence of tuber > leaves > stems > aerial stem, with the highest nitrogen accumulation observed in 25%OM + 75%CF treatment. Nitrogen harvest index did not show significant differences among treatments, fluctuating between 0.69 and 0.74. The nitrogen apparent utilization efficiency was highest in 25%OM + 75%CF (9.89%), followed by CF (9.09%), both significantly higher than OM (5.32%) and 50%OM + 50%CF (6.69%). The nitrogen agronomic efficiency varied significantly among treatments, with 25%OM + 75%CF (33.93 kg kg-1) being the highest, followed by CF (29.68 kg kg-1), 50%OM + 50%CF (21.82 kg kg-1), and OM (11.85 kg kg-1). Nitrogen partial factor productivity was highest in 25%OM + 75%CF treatment (76.37 kg kg-1), followed by CF (72.11 kg kg-1), both significantly higher than 50%OM + 50%CF (64.25 kg kg-1) and OM (54.29 kg kg-1), with OM exhibiting significantly lower values compared to other treatments. In conclusion, the combined application of organic and inorganic fertilizers can effectively enhance the yield, quality, and nitrogen utilization efficiency of D. polystachya. Particularly, the treatment with 25% organic fertilizer and 75% chemical fertilizer showed the most promising results.

This study examines the influence of lag fertilization techniques on Pakistani wheat production, highlighting the need to understand and mitigate the environmental impacts of farming methods. The basic purpose of this study is to investigate the impact of CO2 emission from fertilization and other factors on wheat production in Pakistan, using a time series of data from 1990 to 2020. CO2 emission from fertilization (CO2EF) is estimated using the default values provided by the IPCC guidelines. The ARDL approach analyses the short-run and long-run effects of CO2EF, technology level, energy use, agricultural land, and agricultural labor on wheat production. The results show that all factors have significantly impacted wheat production in Pakistan at levels of 1% and 5% significance, both in the short and long run. These findings suggest that reducing CO2EF, technology level, energy use, agricultural land, and agricultural labor on wheat production can help to increase wheat production in Pakistan. The study also highlights the importance of adopting sustainable and efficient fertilization practices, exploring alternative fertilizers, and using crop rotation systems to mitigate the adverse effects of carbon emissions from nitrogen fertilization, energy use, and the use of technology. These measures can contribute to a more sustainable and climate-resilient agriculture sector in Pakistan.

Abstract Background Although mesenchymal stem cells (MSCs) have been effective in tendinopathy, the mechanisms by which MSCs promote tendon healing have not been fully elucidated. In this study, we tested the hypothesis that MSCs transfer mitochondria to injured tenocytes in vitro and in vivo to protect against Achilles tendinopathy (AT). Methods Bone marrow MSCs and H2O2-injured tenocytes were co-cultured, and mitochondrial transfer was visualized by MitoTracker dye staining. Mitochondrial function, including mitochondrial membrane potential, oxygen consumption rate, and adenosine triphosphate content, was quantified in sorted tenocytes. Tenocyte proliferation, apoptosis, oxidative stress, and inflammation were analyzed. Furthermore, a collagenase type I-induced rat AT model was used to detect mitochondrial transfer in tissues and evaluate Achilles tendon healing. Results MSCs successfully donated healthy mitochondria to in vitro and in vivo damaged tenocytes. Interestingly, mitochondrial transfer was almost completely blocked by co-treatment with cytochalasin B. Transfer of MSC-derived mitochondria decreased apoptosis, promoted proliferation, and restored mitochondrial function in H2O2-induced tenocytes. A decrease in reactive oxygen species and pro-inflammatory cytokine levels (interleukin-6 and -1β) was observed. In vivo, mitochondrial transfer from MSCs improved the expression of tendon-specific markers (scleraxis, tenascin C, and tenomodulin) and decreased the infiltration of inflammatory cells into the tendon. In addition, the fibers of the tendon tissue were neatly arranged and the structure of the tendon was remodeled. Inhibition of mitochondrial transfer by cytochalasin B abrogated the therapeutic efficacy of MSCs in tenocytes and tendon tissues. Conclusions MSCs rescued distressed tenocytes from apoptosis by transferring mitochondria. This provides evidence that mitochondrial transfer is one mechanism by which MSCs exert their therapeutic effects on damaged tenocytes.

Abstract Expression of the long non-coding RNA (lncRNA) keratin-7 antisense (KRT7-AS) is downregulated in various types of cancer; however, the impact of KRT7-AS deficiency on tumorigenesis and apoptosis is enigmatic. We aim to explore the influence of KRT7-AS in carcinogenesis and apoptosis. We found that KRT7-AS was deficient in breast and lung cancers, and low levels of KRT7-AS were a poor prognostic factor in breast cancer. Cellular studies showed that silencing of KRT7-AS in lung cancer cells increased oncogenic Keratin-7 levels and enhanced tumorigenesis, but diminished cancer apoptosis of the cancer cells; by contrast, overexpression of KRT7-AS inhibited lung cancer cell tumorigenesis. Additionally, KRT7-AS sensitized cancer cells to the anti-cancer drug cisplatin, consequently enhancing cancer cell apoptosis. In vivo, KRT7-AS overexpression significantly suppressed tumor growth in xenograft mice, while silencing of KRT7-AS promoted tumor growth. Mechanistically, KRT7-AS reduced the levels of oncogenic Keratin-7 and significantly elevated amounts of the key tumor suppressor PTEN in cancer cells through directly binding to PTEN protein via its core nucleic acid motif GGCAAUGGCGG. This inhibited the ubiquitination-proteasomal degradation of PTEN protein, therefore elevating PTEN levels in cancer cells. We also found that KRT7-AS gene transcription was driven by the transcription factor RXRα; intriguingly, the small molecule berberine enhanced KRT7-AS expression, reduced tumorigenesis, and promoted apoptosis of cancer cells. Collectively, KRT7-AS functions as a new tumor suppressor and an apoptosis enhancer in lung and breast cancers, and we unraveled that the RXRα-KRT7-AS-PTEN signaling axis controls carcinogenesis and apoptosis. Our findings highlight a tumor suppressive role of endogenous KRT7-AS in cancers and an important effect the RXRα-KRT7-AS-PTEN axis on control of cancer cell tumorigenesis and apoptosis, and offer a new platform for developing novel therapeutics against cancers.

Abstract Exposure to fine particulate matter (PM2.5) is linked to lung cancer incidence and mortality. However, the impact of PM2.5 exposure on lung cancer patients after lobectomy, which remains the primary treatment for early-stage lung cancer, is unknown. Therefore, we investigated the correlation between PM2.5 exposure and the survival of lung cancer patients after lobectomy. This study included 3,327 patients with lung cancer who underwent lobectomy procedures. We converted residential addresses into coordinates and estimated individual patients' daily PM2.5 and O3 exposure levels. A Cox multivariate regression model was used to analyze the specific monthly association between PM2.5 exposure and lung cancer survival. Every 10 μg/m3 increase in monthly PM2.5 concentration in the first and second months after lobectomy increased the risk of death (hazard ratio [HR]: 1.043, 95% confidence interval [CI]: 1.019–1.067 and HR: 1.036, 95% CI: 1.013–1.060, respectively). Non-smokers, younger patients, and patients with longer hospitalization durations had worse survival rates when exposed to greater concentrations of PM2.5. High postoperative PM2.5 exposure immediately after lobectomy reduced the survival of patients with lung cancer. Patients living in areas with high PM2.5 should be offered the opportunity to transfer to areas with better air quality after undergoing lobectomies, to prolong their survival times.

IntroductionThe study explored the relationship between subjective well-being and the quality of life among older adults. It highlights the importance of understanding how these factors are interconnected in the context of an aging population.MethodsDescriptive statistics were used to analyze the scores of general demographic characteristics, subjective wellbeing and quality of life. Simple correlation analysis and canonical correlation analysis were employed to analyze the relationship between subjective wellbeing and quality of life among older adults.ResultsData from 892 older adults were collected. Canonical correlation analysis revealed four pairs of canonical variables, with the first four pairs of canonical correlation coefficients all being statistically significant (0.695, 0.179, 0.147, 0.121) (p < 0.05), and the first pair of canonical variables explaining 93.03% of the information content. From the canonical loading coefficients, Vitality and mental health contributed the most to the quality of life (U1) canonical variable. The canonical variable V1, which corresponded to subjective wellbeing, was reflected by a combination of positive affect, negative affect, positive experience and negative experience. X1 (physical functioning), X2 (role-physical), X3 (bodily pain), X4 (general health), X5 (vitality), X6 (social functioning), X7 (role-emotional) and X8 (mental health) were positively correlated with Y1 (positive affect) and Y3 (positive experience), negatively correlated with Y2 (negative affect) and Y4 (negative experience). Cross-loadings revealed that physical functioning, bodily pain, general health, vitality, social functioning and mental health were the main factors reflecting the subjective wellbeing of older adults.DiscussionAs quality of life among older adults was highly correlated with subjective wellbeing, appropriate measures should be taken to account for individual characteristics of older adults, and various factors should be integrated to improve their subjective wellbeing.

Abstract Background Combination of chemotherapy and immune checkpoint inhibitor therapy has greatly improved the anticancer effect on multiple malignancies. However, the efficiency on triple-negative breast cancer (TNBC) is limited, since most patients bear “cold” tumors with low tumor immunogenicity. Doxorubicin (DOX), one of the most effective chemotherapy agents, can induce immunogenic cell death (ICD) and thus initiating immune response. Methods In this study, to maximize the ICD effect induced by DOX, chitosan and cell-penetrating peptide (R6F3)-modified nanoparticles (PNPs) loaded with ginsenoside Rg3 (Rg3) were fabricated using the self-assembly technique, followed by co-encapsulation with DOX based on thermo-sensitive hydrogel. Orthotopic tumor model and contralateral tumor model were established to observe the antitumor efficacy of the thermo-sensitive hydrogel combined with anti-PD-L1 immunotherapy, besides, the biocompatibility was also evaluated by histopathological. Results Rg3-PNPs strengthened the immunogenic cell death (ICD) effect induced by DOX. Moreover, the hydrogel co-loading Rg3-PNPs and DOX provoked stronger immune response in originally nonimmunogenic 4T1 tumors than DOX monotherapy. Following combination with PD-L1 blocking, substantial antitumor effect was achieved due to the recruitment of memory T cells and the decline of adaptive PD-L1 enrichment. Conclusion The hydrogel encapsulating DOX and highly permeable Rg3-PNPs provided an efficient strategy for remodeling immunosuppressive tumor microenvironment and converting immune “cold” 4T1 into “hot” tumors.

Abstract. Background:. Dermatophagoides pteronyssinus is a common allergen causing allergic diseases in China. The aim of this study was to evaluate the efficacy and safety of D. pteronyssinus extracts produced by Peking Union Medical College Hospital (PUMCH) for the skin prick test (SPT) in the diagnosis of D. pteronyssinus allergy. Methods:. A total of 910 subjects with allergic diseases were prescribed D. pteronyssinus SPT and specific sIgE (sIgE) test among the Outpatients of Department of Allergy, PUMCH from August 10, 2015 to August 30, 2017. Receiver operating characteristic curve (ROC) analysis was performed according to the results of D. pteronyssinus-sIgE detection. The accuracy of D. pteronyssinus extracts used for SPT in the diagnosis of D. pteronyssinus allergy was evaluated under different cutoff values. Adverse events after SPT were recorded to evaluate safety. Results:. There were 796 and 618 subjects in the full analysis set (FAS) and the per protocol set (PPS), respectively. The areas under the curve of FAS and PPS were 0.871 and 0.873, respectively. According to the ROC of PPS, the optimal and 95% specificity diagnostic cutoff values of D. pteronyssinus SPT mean wheal diameter were 3.25 and 3.75 mm, respectively. No adverse events occurred. Conclusion:. The extracts of D. pteronyssinus for SPT were simple, highly accurate, and safe and should be considered for recommendation in the clinical diagnosis of D. pteronyssinus allergy.

Abstract Background Breast parenchymal texture features, including grayscale variation (V), capture the patterns of texture variation on a mammogram and are associated with breast cancer risk, independent of mammographic density (MD). However, our knowledge on the genetic basis of these texture features is limited. Methods We conducted a genome-wide association study of V in 7040 European-ancestry women. V assessments were generated from digitized film mammograms. We used linear regression to test the single-nucleotide polymorphism (SNP)-phenotype associations adjusting for age, body mass index (BMI), MD phenotypes, and the top four genetic principal components. We further calculated genetic correlations and performed SNP-set tests of V with MD, breast cancer risk, and other breast cancer risk factors. Results We identified three genome-wide significant loci associated with V: rs138141444 (6q24.1) in ECT2L, rs79670367 (8q24.22) in LINC01591, and rs113174754 (12q22) near PGAM1P5. 6q24.1 and 8q24.22 have not previously been associated with MD phenotypes or breast cancer risk, while 12q22 is a known locus for both MD and breast cancer risk. Among known MD and breast cancer risk SNPs, we identified four variants that were associated with V at the Bonferroni-corrected thresholds accounting for the number of SNPs tested: rs335189 (5q23.2) in PRDM6, rs13256025 (8p21.2) in EBF2, rs11836164 (12p12.1) near SSPN, and rs17817449 (16q12.2) in FTO. We observed significant genetic correlations between V and mammographic dense area (r g = 0.79, P = 5.91 × 10−5), percent density (r g = 0.73, P = 1.00 × 10−4), and adult BMI (r g = − 0.36, P = 3.88 × 10−7). Additional significant relationships were observed for non-dense area (z = − 4.14, P = 3.42 × 10−5), estrogen receptor-positive breast cancer (z = 3.41, P = 6.41 × 10−4), and childhood body fatness (z = − 4.91, P = 9.05 × 10−7) from the SNP-set tests. Conclusions These findings provide new insights into the genetic basis of mammographic texture variation and their associations with MD, breast cancer risk, and other breast cancer risk factors.

Abstract Background A short instrument would enhance the viability of a study. Therefore, we aimed to shorten the specific module (SPD-10) of the Quality of Life Instrument for Chronic Diseases - Chronic Renal Failure (QLICD-CRF) for assessing the quality of life of patients with chronic renal failure. Methods The 10-item SPD-10 was self-administered to 164 patients with chronic renal failure. A shortened form was first obtained by a tandem use of the classical test theory (CTT), the generalizability theory (GT), and the item response theory (IRT). In addition, we also shortened the SPD-10 by the Optimal Test Assembly (OTA). Results Both the tandem use of GT, CTT and IRT, and the OTA derived the same 7-item shortened version (SPD-7). It included items CRF1, CRF2, CRF3, CRF4, CRF6, CRF8, and CRF9 of the SPD-10. The SPD-7 had a Cronbach alpha of 0.78. The correlation coefficients of its total and factor scores with those of the SPD-10 were 0.96 and 0.98, respectively. Confirmatory factor analysis confirmed the unidimensional structure of the SPD-7, with the comparative fit index=0.96, the Tucker-Lewis index=0.94, and the root mean square error of approximation=0.09. Conclusion The short-form SPD-7 is reliable and valid for assessing the impact of clinical symptoms and side effects on the quality of life of patients with chronic renal failure. It is an efficient option without compromising the measurement performance of the SPD-10.

Abstract It is found that the osteon is composed of thin and thick lamellae which are periodic and approximately concentric, every 5 lamellae is a cycle, the periodic helix angle of mineralized collagen fibers in two adjacent sub-lamellae is 30°. Four bionic composite models with different fiber helix angles were established and fabricated according to the microstructure of mineralized collagen fibers in osteon. Based on the impact analysis of four kinds of bionic composite models, the effects of the fiber periodic spiral structure on the impact resistance and energy dissipation of multi-layer bionic composite were investigated. The analysis results show that the fiber helix angle affects the impact damage resistance and energy dissipation of multi-layer fiber reinforced composites. Among the 4 kinds of multi-layer composite models, the composite model with helix angle of 30° has better comprehensive ability to resist impact damage. The test results show that the impact damage area of the specimen with 30° helix angle is smallest among the 4 types of bionic specimens, which is consistent with the results of finite-element impact analysis. Furthermore, in the case of without impact damage, the smaller the fiber helix angle is, the more uniform the stress distribution is and more energy is dissipated in the impact process. The periodic spiral structure of mineralized collagen fibers in osteon are the result of natural selection of biological evolution. This structure can effectively improve the ability of cortical bone to resist external impact. The research results can provide useful guidance for the design and manufacture of high-performance and strong impact resistant bionic composites. Graphical Abstract

BackgroundStatin therapy has been shown to reduce mortality in a wide range of cancer types and overall stages. Still, there is uncertainty about its efficacy in increasing survival among advanced cancer patients.MethodsWe conducted a meta-analysis with data from all studies that compared the hazard ratio of overall survival, cancer-specific survival, and progression-free survival in patients with advanced-stage cancer who receive statin therapy. Studies were selected from the PubMed, Embase, and Web of Science databases from their inception to December 31, 2022. Cancer types are limited to those rarely screened during the annual examination and more likely to develop into advanced stages, such as lung, pancreatic and ovarian cancers. This resulted in 27 studies eligible for meta-analysis.ResultsStatin therapy was associated with a 26% decreased risk of overall survival (HR, 0.74; 95% CI, 0.67, 0.81), 26% decreased risk of cancer-specific survival (HR, 0.74; 95% CI, 0.61-0.88), and 24% decreased risk of progression-free survival (HR, 0.76; 95% CI, 0.65-0.87) for advanced-stage cancer patients. The associations were not attenuated or reinforced by study design, study regions, cancer types, or other medical care. Concomitant use of other anticancer medications did not result in confounding effects.ConclusionsStatin therapy produces significant benefits on overall survival and cancer-specific survival. Although the benefits might be lower than the approved immunotherapy medications, its cost-effectiveness could lead to dramatic health consequences. Concomitant use of statin drugs as cancer treatments is highly recommended in future clinical trials.

The tumor microenvironment (TME) is a crucial driving factor for tumor progression and it can hinder the body’s immune response by altering the metabolic activity of immune cells. Both tumor and immune cells maintain their proliferative characteristics and physiological functions through transporter-mediated regulation of nutrient acquisition and metabolite efflux. Transporters also play an important role in modulating immune responses in the TME. In this review, we outline the metabolic characteristics of the TME and systematically elaborate on the effects of abundant metabolites on immune cell function and transporter expression. We also discuss the mechanism of tumor immune escape due to transporter dysfunction. Finally, we introduce some transporter-targeted antitumor therapeutic strategies, with the aim of providing new insights into the development of antitumor drugs and rational drug usage for clinical cancer therapy.

Abstract Background Drug abuse has many negative effects not only on individuals but also on society. Nowadays, researchers pay a lot of attention to quality of life of drug addicts. However, there are few scales available to measure quality of life of drug addicts. The scale QLICD-DA (quality of life instrument for chronic diseases-drug addition) developed by modular approach could be used to measure quality of life of drug addicts with good validity, reliability and sensitivity. Objective This study is aimed to understand the quality of life status and influencing factors in drug addicts by suitable sensitively scale, with the hypothesis of the quality of life in drug addicts being different from that of other peoples and possibly being influenced by many factors. Methods By cluster random sampling method, 192 drug addicts at Kunming compulsory drug rehabilitation center were recruited to take part in the investigation. All participants completed the general information questionnaire and the scale QLICD-DA. We used a t-test to compare the scores of the quality of life of the participants with the norm (QOL scores from 1953 patients of 10 chronic diseases). A stepwise regression method was applied to explore the influencing factors of the quality of life in drug addicts. Results 192 participants ranged in age from 19 to 59 with an average age of 34.86. Most of them were male (70.3%), high school education level (67.7%) and of Han nationality (82.8%). The quality of life of drug addicts was lower than the norm in the physical domain, psychological domain, social domain, and general module, and the differences were statistically significant (p

Abstract Autophagy classically functions as a physiological process to degrade cytoplasmic components, protein aggregates, and/or organelles, as a mechanism for nutrient breakdown, and as a regulator of cellular architecture. Its biological functions include metabolic stress adaptation, stem cell differentiation, immunomodulation and diseases regulation, and so on. Current researches have proved that autophagy dysfunction may contribute to the pathogenesis of some myopathies through impairment of myofibres regeneration. Studies of autophagy inhibition also indicate the importance of autophagy in muscle regeneration, while activation of autophagy can restore muscle function in some myopathies. In this review, we aim to report the mechanisms of action of autophagy on muscle regeneration to provide relevant references for the treatment of regenerating defective myopathies by regulating autophagy. Results have shown that one key mechanism of autophagy regulating the muscle regeneration is to affect the differentiation fate of muscle stem cells (MuSCs), including quiescence maintenance, activation and differentiation. The roles of autophagy (organelle/protein degradation, energy facilitation, and/or other) vary at different myogenic stages of the repair process. When the muscle is in homeostasis, basal autophagy can maintain the quiescence state and stemness of MuSCs by renewing organelle and protein. After injury, the increased autophagy flux contributes to meet biological energy demand of MuSCs during activation and proliferation. By mitochondrial remodelling, autophagy during differentiation can promote the metabolic transformation and balance mitochondrial‐mediated apoptosis signals in myoblasts. Autophagy in mature myofibres is also essential for the degradation of necrotic myofibres, and may affect the dynamics of MuSCs by affecting the secretion spectrum of myofibres or the recruitment of supporting cells. Except for myogenic cells, autophagy also plays an important role in regulating the function of non‐myogenic cells in the muscle microenvironment, which is also essential for successful muscle recovery. Autophagy can regulate the immune microenvironment during muscle regeneration through the recruitment and polarization of macrophages, while autophagy in endothelial cells can regulate muscle regeneration in an angiogenic or angiogenesis‐independent manner. Drug or nutrition targeted autophagy has been preliminarily proved to restore muscle function in myopathies by promoting muscle regeneration, and further understanding the role and mechanism of autophagy in various cell types during muscle regeneration will enable more effective combinatorial therapeutic strategies.

IntroductionInternet addiction (IA) is becoming a significant public health issue that requires urgent attention, especially for adolescents. Previous studies mainly focused on the risk factors of Internet addiction and drawn some conclusions. The purpose of this study is to investigate the Internet addiction status and concurrent psychological problems in adolescent groups, and explore the differences in the relationship between IA and psychological problems in adolescents from gender and grade.MethodsA cross-sectional study was conducted among students of junior and senior high school in 21 prefecture-level cities of Guangdong Province. The Young Diagnostic Questionnaire (YDQ) and the validated Chinese version of the Depression Anxiety Stress Scale-21 (DASS-21) were used to assess participants’ Internet addiction and psychological status. Two-way ANOVA was used to verify the interaction between gender and Internet addiction, grade and Internet addiction on psychological problems. When the interaction was statistically significant, simple effect analysis was further carried out.ResultsThe prevalence of problematic Internet use (PIU), depression, anxiety, and stress symptoms among adolescents were 16.32%, 30.16%, 35.97% and 18.80% respectively. Although the prevalence of PIU among boys (17.89%) was higher than that of girls (14.86%), girls in PIU group had the highest scores of depression, anxiety and stress. Similarly, the interaction between grade and Internet addiction was also significant (p