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Insulin resistance, a key factor in the development of type 2 diabetes mellitus (T2DM), is defined as a defect in insulin-mediated control of glucose metabolism in tissues such as liver, fat and muscle. Insulin resistance is a driving force behind various metabolic diseases, such as T2DM, hyperlipidemia, hypertension, coronary heart disease and fatty liver. Therefore, improving insulin sensitivity can be considered as an effective strategy for the prevention and treatment of these complex metabolic diseases. Cell-based models are extensively employed for the study of pathological mechanisms and drug screening, particularly in relation to insulin resistance in T2DM. Currently, numerous methods are available for the establishment of in vitro insulin resistance models, a comprehensive review of these models is required and can serve as an excellent introduction or understanding for researchers undertaking studies in this filed. This review examines and discusses the primary methods for establishing and evaluating insulin resistance cell models. Furthermore, it highlights key issues and suggestions on cell selection, establishment, evaluation and drug screening of insulin resistance, thereby providing valuable references for the future research efforts.

Abstract Aims Cardiac hypertrophy, an adaptive response of the heart to stress overload, is closely associated with heart failure and sudden cardiac death. This study aimed to investigate the therapeutic effects of chlorogenic acid (CGA) on cardiac hypertrophy and elucidate the underlying mechanisms. Methods and results To simulate cardiac hypertrophy, myocardial cells were exposed to isoproterenol (ISO, 10 μM). A rat model of ISO‐induced cardiac hypertrophy was also established. The expression levels of cardiac hypertrophy markers, endoplasmic reticulum stress (ERS) markers, and apoptosis markers were measured using quantitative reverse transcription PCR and western blotting. The apoptosis level, size of myocardial cells, and heart tissue pathological changes were determined by terminal deoxynucleotidyl transferase dUTP nick‐end labelling staining, immunofluorescence staining, haematoxylin and eosin staining, and Masson's staining. We found that CGA treatment decreased the size of ISO‐treated H9c2 cells. Moreover, CGA inhibited ISO‐induced up‐regulation of cardiac hypertrophy markers (atrial natriuretic peptide, brain natriuretic peptide, and β‐myosin heavy chain), ERS markers (C/EBP homologous protein, glucose regulatory protein 78, and protein kinase R‐like endoplasmic reticulum kinase), and apoptosis markers (bax and cleaved caspase‐12/9/3) but increased the expression of anti‐apoptosis marker bcl‐2 in a dose‐dependent way (0, 10, 50, and 100 μM). Knockdown of sphingosine‐1‐phosphate receptor 1 (S1pr1) reversed the protective effect of CGA on cardiac hypertrophy, ERS, and apoptosis in vitro (P

With the development of neonatal medicine, more and more extremely preterm infants have been treated. How to deal with hypotension is a big challenge for neonatologist in the process of diagnosis and treatment. The lack of uniformity in the definition of hypotension, challenges in measuring blood pressure accurately, and insufficient consistency between digital hypotension and hypoperfusion are the primary causes. How to check for hypotension and monitor blood pressure is thoroughly explained in the article. To give neonatologists a resource for the clinical management of hypotension in extremely preterm.

Background Echocardiographic indexes of aortic stenosis may not comprehensively reflect disease morbidity. Plasma proteomic profiling may add prognostic value in these patients. Methods and Results Proximity extension assays (Olink) of 183 circulating cardiovascular and inflammatory proteins were performed in a prospective follow‐up study of 122 asymptomatic/minimally symptomatic patients (mean±SD age, 69.1±10.9 years; 61% men) with moderate to severe aortic stenosis and preserved left ventricular ejection fraction. Protein signatures of higher‐risk echocardiographic subgroups were determined. Associations of proteins with the primary composite outcome (heart failure hospitalization, progression to New York Heart Association class III‐IV, or all‐cause mortality) were evaluated using competing risk analyses, with aortic valve replacement being the competing risk. Network analysis unveiled mutually exclusive communities of proteins and echocardiographic parameters, connected only through NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide). Members of the tumor necrosis factor receptor superfamily (TNFRSF1A, TNFRSF1B, and TNFRSF14), and trefoil factor‐3 were major hub proteins among the circulating biomarkers. Left ventricular global longitudinal strain >−15% was associated with higher levels of proteins, primarily of inflammation and immune regulation, whereas aortic valve area 15, and left atrial reservoir strain

Ti(C,N)-HfN/Ti(C,N)-WC laminated ceramics were prepared by alternately making layer method and vacuum hot pressing sintering technology, using Ti(C,N) as the matrix phase, HfN and WC as the reinforced phases for the different layers, and metal Ni and Mo as the binder phases. The effects of sintering temperature on the microstructure and mechanical properties of the laminated ceramics were investigated. The results show that with the increase of sintering temperature, the grains grow up gradually. When the sintering temperature is 1350 ℃ and 1400 ℃, the grains are small but unevenly distributed with many micro-defects. At the sintering temperature of 1450 ℃ and 1500 ℃, the grains are uniform (~1 μm) and there are fewer micro-defects. However, when the sintering temperature reaches 1550 ℃, a large number of coarse grains (~2 μm) appear. Moreover, with the increase of the sintering temperature, the flexural strength, Vickers hardness, and fracture toughness of the laminated ceramics increase first and then decrease. The laminated ceramic sintered at 1450 ℃ shows the better comprehensive mechanical properties, the flexural strength, Vickers hardness, and fracture toughness are (1263.6±17.1) MPa, (18.5±0.3) GPa, and (8.2±0.1) MPa·m1/2, respectively. In addition, the Ti(C,N)-HfN/Ti(C,N)-WC laminated ceramics exhibit the co-existence model of intergranular fracture and transgranular fracture.

In Beyond the Fifth Generation (B5G) heterogeneous edge networks, numerous users are multiplexed on a channel or served on the same frequency resource block, in which case the transmitter applies coding and the receiver uses interference cancellation. Unfortunately, uncoordinated radio resource allocation can reduce system throughput and lead to user inequity, for this reason, in this paper, channel allocation and power allocation problems are formulated to maximize the system sum rate and minimum user achievable rate. Since the construction model is non-convex and the response variables are high-dimensional, a distributed Deep Reinforcement Learning (DRL) framework called distributed Proximal Policy Optimization (PPO) is proposed to allocate or assign resources. Specifically, several simulated agents are trained in a heterogeneous environment to find robust behaviors that perform well in channel assignment and power allocation. Moreover, agents in the collection stage slow down, which hinders the learning of other agents. Therefore, a preemption strategy is further proposed in this paper to optimize the distributed PPO, form DP-PPO and successfully mitigate the straggler problem. The experimental results show that our mechanism named DP-PPO improves the performance over other DRL methods.

TiCN–WC–HfN ceramics were prepared by vacuum hot pressing sintering technology, and the effects of Re contents (molar fraction) on the microstructure and mechanical properties of the ceramics were investigated. The results show that, the TiCN–WC–HfN–Ni–Re ceramics are composed of TiC0.41N0.5, WC, HfN, TiC, Ni and Re, and TiC0.4N0.50 is the solid solution formed between TiC and TiN in the sintering process. Micro-pits and cleavage planes are discovered in the fracture surface of TiCN–WC–HfN ceramics with the different molar fraction of Re. When the molar fraction of Re is 2.5%, there are more micro-pits on the ceramic fractures. When the mole fraction of Re increases from 0 to 3.0%, the Vickers hardness, flexural strength, and fracture toughness of the TiCN–WC–HfN ceramics first increase and then decrease. When the mole fraction of Re is 2.5%, the mechanical properties of the ceramics show the best as the Vickers hardness is (19.25±0.21) GPa, bending strength is (1304±23) MPa, and fracture toughness is (7.73±0.22) MPa∙m1/2. Transgranular fracture and intergranular fracture of the TiCN–WC–HfN–Ni–Re ceramics occur during the fracture process, and the toughening mechanisms are the crack deflection and crack bridging.

The broader application of lithium-ion batteries (LIBs) is constrained by safety concerns arising from thermal runaway (TR). Accurate prediction of TR is essential to comprehend its underlying mechanisms, expedite battery design, and enhance safety protocols, thereby significantly promoting the safer use of LIBs. The complex, nonlinear nature of LIB systems presents substantial challenges in TR modeling, stemming from the need to address multiscale simulations, multiphysics coupling, and computing efficiency issues. This paper provides an extensive review and outlook on TR modeling technologies, focusing on recent advances, current challenges, and potential future directions. We begin with an overview of the evolutionary processes and underlying mechanisms of TR from multiscale perspectives, laying the foundation for TR modeling. Following a comprehensive understanding of TR phenomena and mechanisms, we introduce a multiphysics coupling model framework to encapsulate these aspects. Within this framework, we detail four fundamental physics modeling approaches: thermal, electrical, mechanical, and fluid dynamic models, highlighting the primary challenges in developing and integrating these models. To address the intrinsic trade-off between computational accuracy and efficiency, we discuss several promising modeling strategies to accelerate TR simulations and explore the role of AI in advancing next-generation TR models. Last, we discuss challenges related to data availability, model scalability, and safety standards and regulations.

Abstract Purpose With a rapid increase in older adults, progressive impairment in cognitive function has become an increasing concern owing to high social and economic burdens. The current study was designed to investigate the associations of sex hormones and bone metabolism with cognitive impairment (CI) in Chinese oldest-old females. Methods There were 396 oldest-old females from the China Hainan Oldest-old Cohort Study (CHOCS). Following standardized procedures, Mini Mental State Examination was effectively completed, and sex hormones and bone metabolism were assessed in these females. Results The median age of all females was 101 years (range: from 80 to 116). There were 340 females (86%) with CI. Participants with CI had significantly higher levels of age, progesterone, prolactin and estradiol than those without CI (P

Abstract Purpose An accurate prediction of survival prognosis is beneficial to guide clinical decision-making. This prospective study aimed to develop a model to predict one-year mortality among older patients with coronary artery disease (CAD) combined with impaired glucose tolerance (IGT) or diabetes mellitus (DM) using machine learning techniques. Methods A total of 451 patients with CAD combined with IGT and DM were finally enrolled, and those patients randomly split 70:30 into training cohort (n = 308) and validation cohort (n = 143). Results The one-year mortality was 26.83%. The least absolute shrinkage and selection operator (LASSO) method and ten-fold cross-validation identified that seven characteristics were significantly associated with one-year mortality with creatine, N-terminal pro-B-type natriuretic peptide (NT-proBNP), and chronic heart failure being risk factors and hemoglobin, high density lipoprotein cholesterol, albumin, and statins being protective factors. The gradient boosting machine model outperformed other models in terms of Brier score (0.114) and area under the curve (0.836). The gradient boosting machine model also showed favorable calibration and clinical usefulness based on calibration curve and clinical decision curve. The Shapley Additive exPlanations (SHAP) found that the top three features associated with one-year mortality were NT-proBNP, albumin, and statins. The web-based application could be available at https://starxueshu-online-application1-year-mortality-main-49cye8.streamlitapp.com/ . Conclusions This study proposes an accurate model to stratify patients with a high risk of one-year mortality. The gradient boosting machine model demonstrates promising prediction performance. Some interventions to affect NT-proBNP and albumin levels, and statins, are beneficial to improve survival outcome among patients with CAD combined with IGT or DM.

Abstract Background Spermatogenic dysfunction is an important cause of azoospermia. Numerous studies have focused on germ-cell-related genes that lead to spermatogenic impairment. However, based on the immune-privileged characteristics of the testis, the relationship of immune genes, immune cells or immune microenvironment with spermatogenic dysfunction has rarely been reported. Results Using integrated methods including single-cell RNA-seq, microarray data, clinical data analyses and histological/pathological staining, we found that testicular mast cell infiltration levels were significantly negatively related to spermatogenic function. We next identified a functional testicular immune biomarker, CCL2, and externally validated that testicular CCL2 was significantly upregulated in spermatogenic dysfunctional testes and was negatively correlated with Johnsen scores (JS) and testicular volumes. We also demonstrated that CCL2 levels showed a significant positive correlation with testicular mast cell infiltration levels. Moreover, we showed myoid cells and Leydig cells were two of the important sources of testicular CCL2 in spermatogenic dysfunction. Mechanistically, we drew a potential “myoid/Leydig cells-CCL2-ACKR1-endothelial cells-SELE-CD44-mast cells” network of somatic cell–cell communications in the testicular microenvironment, which might play roles in spermatogenic dysfunction. Conclusions The present study revealed CCL2-relevant changes in the testicular immune microenvironment in spermatogenic dysfunction, providing new evidence for the role of immunological factors in azoospermia.

Abstract Purpose This study evaluated the performance of the contrast-enhanced ultrasound (CEUS) Liver Imaging Reporting and Data System (LI-RADS) in patients without LI-RADS-defined hepatocellular carcinoma (HCC) risk factors (RF−). Methods Patients with LI-RADS-defined HCC risk factors (RF+) and RF− were enrolled in a retrospective study. Additionally, a prospective evaluation in the same centre was performed as a validation set. The diagnostic performances of the CEUS LI-RADS criteria in RF+ and RF− patients were compared. Results Overall, we included 873 patients in the analyses. In the retrospective study, the LI-RADS category (LR)-5 specificities for diagnosing HCC did not differ between the RF+ and RF− groups (77.5% [158/204] vs 91.6% [196/214], P = 0.369, respectively). However, the positive predictive value (PPV) of CEUS LR-5 was 95.9% (162/169) and 89.8% (158/176) in the RF+ and RF− groups, respectively (P = 0.029). In the prospective study, the PPV of LR-5 for HCC lesions was significantly higher in the RF+ group than in the RF− group (P = 0.030). The sensitivity and specificity did not differ between the RF+ and RF− groups (P = 0.845 and P = 0.577, respectively). Conclusions The CEUS LR-5 criteria shows clinical value for diagnosis of HCC in patients with and without risks.

Abstract Dyslipidemia and cognitive impairment are common among old adults and the occurrence of them rises exponentially with increasing age. Evidences of the relationships between serum lipids and cognitive impairment are inconsistent or equivocal among older adults. This study aimed to investigate the associations between lipid profiles and late‐life cognitive impairment among oldest‐old and centenarian adults. In this cross‐sectional study, serum lipids were biochemically measured among 606 oldest‐old adults and 653 centenarians, and cognitive function was evaluated using mini‐mental state examination (MMSE). Multivariate linear and logistic regression analyses were performed to explore the associations between serum lipids and cognitive impairment. Results showed participants with cognitive impairment had lower total cholesterol (TC) levels compared with those without cognitive impairment (p

Summary: This study was to explore epidemiological characteristics of malnutrition and factors associated with malnutrition in centenarians and oldest-old adults, so as to provide a reference for family members and government departments to take effective measures and promote healthy aging. Median age of all 1,654 participants was 100 (85, 102) years old, and prevalence of high malnutrition risk was 65.54% in all participants. Proportion of high-malnutrition risk was higher, and proportion of normal physical function was lower, in centenarians than those in oldest-old adults (p

AimThis study aims to investigate the biological effects of polyunsaturated fatty acid (PUFA)-derived metabolites in seminal plasma on male fertility and to evaluate the potential of PUFA as a biomarker for normozoospermic male infertility.MethodsFrom September 2011 to April 2012, We collected semen samples from 564 men aged 18 to 50 years old (mean=32.28 years old)ch., residing in the Sandu County, Guizhou Province, China. The donors included 376 men with normozoospermia (fertile: n=267; infertile: n=109) and 188 men with oligoasthenozoospermia (fertile: n=121; infertile: n=67). The samples thus obtained were then analyzed by liquid chromatography-mass spectrometry (LC-MS) to detect the levels of PUFA-derived metabolites in April 2013. Data were analyzed from December 1, 2020, to May 15, 2022.ResultsOur analysis of propensity score-matched cohorts revealed that the concentrations of 9/26 and 7/26 metabolites differed significantly between fertile and infertile men with normozoospermia and oligoasthenozoospermia, respectively (FDR < 0.05). In men with normozoospermia, higher levels of 7(R)-MaR1 (HR: 0.4 (95% CI [0.24, 0.64]) and 11,12-DHET (0.36 (95% CI [0.21, 0.58]) were significantly associated with a decreased risk of infertility, while higher levels of 17(S)-HDHA (HR: 2.32 (95% CI [1.44, 3.79]), LXA5 (HR: 8.38 (95% CI [4.81, 15.24]), 15d-PGJ2 (HR: 1.71 (95% CI [1.06, 2.76]), and PGJ2 (HR: 2.28 (95% CI [1.42, 3.7]) correlated with an increased risk of infertility. Our ROC model using the differentially expressed metabolites showed the value of the area under the curve to be 0.744.ConclusionThe PUFA-derived metabolites 7(R)-MaR1, 11,12-DHET, 17(S)-HDHA, LXA5, and PGJ2 might be considered as potential diagnostic biomarkers of infertility in normozoospermic men.

Abstract Background Physical independence is crucial for overall health in the elderly individuals. The life expectancy of women has been shown to be higher than that of men, which is also known as the “male–female health-survival paradox”. Sex hormones may be one of the explanations. However, the relationships between sex hormones and physical function remain unclear in the elderly females. This study was designed to explore these relationships among the Chinese oldest-old and centenarian women. Methods Data from 1226 women were obtained from the China Hainan Centenarian Cohort Study. Home interviews, physical examinations and blood analyses were conducted using standardized procedures. Variables including age, Han ethnicity, illiteracy, smoker, drinker, estradiol (E2), testosterone (T), follicle-stimulating hormone, and luteinizing hormone were used in the multivariate logistic and linear regression analyses. Results In all the participants, age [beta (95% confidence interval): − 0.84 (− 0.98, − 0.71)] and E2 levels [beta (95% confidence interval): − 0.22 (− 0.28, − 0.17)] were negatively associated with activities of daily living (ADLs) in the multivariate linear regression analyses (P

A substantial number of male infertility is caused by azoospermia. However, the underlying etiology and the molecular basis remain largely unknown. Through single-cell (sc)RNA sequencing, we had analyzed testis biopsy samples from two patients with obstructive azoospermia (OA) and nonobstructive azoospermia (NOA). We found only somatic cells in the NOA samples and explored the transcriptional changes in Sertoli cells in response to a loss of interactions with germ cells. Moreover, we observed a germ cell population discrepancy between an OA (postvasectomy) patient and a healthy individual. We confirmed this observation in a secondary study with two datasets at GSM3526588 and GSE124263 for detailed analysis wherein the regulatory mechanisms at the transcriptional level were identified. These findings thus provide valuable information on human spermatogenesis, and we also identified insightful information for further research on reproduction-related diseases.

BackgroundCardiac aging and ageing-related cardiovascular diseases remain increase medical and social burden. Discovering the molecular mechanisms associated with cardiac aging is expected to provide new perspectives for delaying aging and related disease treatment.MethodsThe samples in GEO database were divided into older group and younger group based on age. Age-associated differentially expressed genes (DEGs) were identified by limma package. Gene modules significantly associated with age were mined using weighted gene co-expression network analysis (WGCNA). Protein-protein interaction networks (PPI) networks were developed using genes within modules, and topological analysis on the networks was performed to identify hub genes in cardiac aging. Pearson correlation was used to analyze the association among hub genes and immune and immune-related pathways. Molecular docking of hub genes and the anti-aging drug Sirolimus was performed to explore the potential role of hub genes in treating cardiac aging.ResultsWe found a generally negative correlation between age and immunity, with a significant negative correlation between age and b_cell_receptor_signaling_pathway, fc_gamma_r_mediated_phagocytosis, chemokine signaling pathway, t-cell receptor signaling pathway, toll_like_receptor_signaling_pathway, and jak_stat_signaling_pathway, respectively. Finally, 10 cardiac aging-related hub genes including LCP2, PTPRC, RAC2, CD48, CD68, CCR2, CCL2, IL10, CCL5 and IGF1 were identified. 10-hub genes were closely associated with age and immune-related pathways. There was a strong binding interaction between Sirolimus-CCR2. CCR2 may be a key target for Sirolimus in the treatment of cardiac aging.ConclusionThe 10 hub genes may be potential therapeutic targets for cardiac aging, and our study provided new ideas for the treatment of cardiac aging.

Background: Depressive disorder is a common comorbidity in patients with cardiovascular diseases and is associated with increased hospitalization and death rates. The relationships between cardiac structure and function and depressive disorder remains unclear in the older adults, especially in centenarians. Therefore, this study aimed to explore the possible associations between cardiac structure and function and depressive disorder among centenarians. Methods: In the China Hainan Centenarian Cohort Study, the 15-item Geriatric Depression Scale scores and echocardiography were used to evaluate depressive disorder and cardiac structure and function, respectively. All information, including epidemiological questionnaires, physical examinations, and blood tests, was obtained following standardized procedures. Results: A total of 682 centenarians were enrolled in the study (mean age: 102.35 ± 2.72 years). The prevalence of depressive disorder in centenarians is 26.2% (179 older adults), of whom 81.2% (554 older adults) are women. Centenarians with depressive disorder have significantly higher left ventricular ejection fraction (60.02 ± 3.10) and interventricular septum thickness (9.79 ± 1.54). Stepwise multiple linear regression analysis detected positive associations of left ventricular ejection fraction (Bets: 0.093) and interventricular septum thickness (Bets: 0.440) with Geriatric Depression Scale scores. Both left ventricular ejection fraction (odds ratio: 1.081) and interventricular septum thickness (odds ratio: 1.274) were independently associated with depressive disorder in multiple logistic regression analysis (P

The extent of spermatogenic impairment on intracytoplasmic sperm injection (ICSI) outcomes and the risk of major birth defects have been little assessed. In this study, we evaluated the relationship between various spermatogenic conditions, sperm origin on ICSI outcomes, and major birth defects. A total of 934 infertile men attending the Center for Reproductive Medicine of Ren Ji Hospital (Shanghai, China) were classified into six groups: nonobstructive azoospermia (NOA; n = 84), extremely severe oligozoospermia (esOZ; n = 163), severe oligozoospermia (sOZ, n = 174), mild oligozoospermia (mOZ; n = 148), obstructive azoospermia (OAZ; n = 155), and normozoospermia (NZ; n = 210). Rates of fertilization, embryo cleavage, high-quality embryos, implantation, biochemical and clinical pregnancies, abortion, delivery, newborns, as well as major birth malformations, and other newborn outcomes were analyzed and compared among groups. The NOA group showed a statistically lower fertilization rate (68.2% vs esOZ 77.3%, sOZ 78.0%, mOZ 73.8%, OAZ 76.6%, and NZ 79.3%, all P < 0.05), but a significantly higher implantation rate (37.8%) than the groups esOZ (30.1%), sOZ (30.4%), mOZ (32.6%), and OAZ (31.0%) (all P < 0.05), which was similar to that of Group NZ (38.4%). However, there were no statistically significant differences in rates of embryo cleavage, high-quality embryos, biochemical and clinical pregnancies, abortions, deliveries, major birth malformations, and other newborn outcomes in the six groups. The results showed that NOA only negatively affects some embryological outcomes such as fertilization rate. There was no evidence of differences in other embryological and clinical outcomes with respect to sperm source or spermatogenic status. Spermatogenic failure and sperm origins do not impinge on the clinical outcomes in ICSI treatment.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the pathogen that causes coronavirus disease 2019 (COVID-19), infects humans through a strong interaction between the viral spike protein (S-protein) and angiotensin converting enzyme 2 (ACE2) receptors on the cell surface. The infection of host lung cells by SARS-CoV-2 leads to clinical symptoms in patients. However, ACE2 expression is not restricted to the lungs; altered receptors have been found in the nasal and oral mucosa, vessel, brain, pancreas, gastrointestinal tract, kidney, and heart. The future of COVID-19 is uncertain, however, new viral variants are likely to emerge. The SARS-CoV-2 Omicron variant has a total of 50 gene mutations compared with the original virus; 15 of which occur in the receptor binding domain (RBD). The RBD of the viral S-protein binds to the human ACE2 receptor for viral entry. Mutations of the ACE2–RBD interface enhance tight binding by increasing hydrogen bond interactions and expanding the accessible surface area. Extracorporeal membrane oxygenation, hyperbaric oxygen, and aggressive dialysis for the treatment of COVID-19 have shown various degrees of clinical success. The use of decoy receptors based on the ACE2 receptor as a broadly potent neutralizer of SARS-CoV-2 variants has potential as a therapeutic mechanism. Drugs such as 3E8 could block binding of the S1-subunit to ACE2 and restrict the infection of ACE2-expressing cells by a variety of coronaviruses. Here, we discuss the development of ACE2-targeted strategies for the treatment and prevention of COVID-19.

Abstract Objective The number of older people is estimated to increase from 524 million in 2010 to 1.5 billion in 2050. The factors and models of human longevity and successful aging are questions that have intrigued individuals for thousands of years. For the first time, the current study was designed to investigate the relationships between sex hormones, bone turnover, abdominal obesity, nutritional status and centenarian longevity in the oldest females. Methods The China Hainan Centenarian Cohort Study was performed in 18 cities and counties of Hainan Province using standard methodology in 500 centenarian females and 237 oldest females aged between 80 and 99 years. Results Centenarians were inversely associated with the geriatric nutritional risk index [Exp(B) (95% CI): 0.901 (0.883–0.919)] and abdominal obesity [Exp(B) (95% CI): 0.719 (0.520–0.996)] and positively associated with prolactin [Exp(B) (95% CI): 1.073 (1.044–1.103)], progesterone [Exp(B) (95% CI): 44.182 (22.036–88.584)], estradiol [Exp(B) (95% CI): 1.094 (1.071–1.119)], osteocalcin [Exp(B) (95% CI): 1.041 (1.028–1.054)], β-crossLaps [Exp(B) (95% CI): 63.141 (24.482–162.848)] and parathyroid [Exp(B) (95% CI): 1.022 (1.013–1.031)] hormone levels (P

Atherosclerosis is the primary cause of cardiovascular diseases, such as myocardial infarction and stroke, which account for the highest death toll worldwide. Macrophage is the major contributor to atherosclerosis progression, and therefore, macrophage-associated pathological process is considered an extremely important target for the diagnosis and treatment of atherosclerosis. However, the existing clinical strategies still have many bottlenecks and challenges in atherosclerosis’s early detection and management. Nanomedicine, using various nanoparticles/nanocarriers for medical purposes, can effectively load therapeutic agents, significantly improve their stability and accurately deliver them to the atherosclerotic plaques. In this review, we summarized the latest progress of the macrophage-targeted nanomedicine in the diagnosis and treatment of atherosclerosis, and their potential applications and clinical benefits are also discussed.

Objective: To analyze surveys measuring the prevalence of burnout among Chinese doctors and reveal the overall prevalence, characteristics, timeline, and factors related to burnout. Methods: A comprehensive search was conducted on China National Knowledge Infrastructure, WANFANG, PubMed, EMBASE, PsycINFO and Cochrane Library databases from their inception to 28 February 2021. Random-effects meta-analyses, meta-regression and planned subgroup analyses were performed, and the standardized mean difference was adopted for comparisons between subgroups. Egger’s and Begg’s tests were performed to evaluate publication bias. Heterogeneity across the studies was tested using the I2 statistic. The study protocol was registered on PROSPERO (CRD42018104249). Results: In total, 3,210 records were reviewed; 64 studies including 48,638 Chinese doctors were eligible for meta-analysis. The prevalence of burnout increased continuously from 2008 to 2017 and decreased significantly from 2018 to 2020, a little increase from 2020 to 2021. The overall prevalence of burnout was 75.48% (95% CI, 69.20 to 81.26; I2 = 99.23%, P < 0.001), and high burnout was 9.37% (95% CI, 4.91 to 15.05, I2 = 98.88%, P < 0.001). The prevalence of emotional exhaustion was 48.64% (95% CI, 38.73 to 58.59; I2 = 99.53%, P < 0.001), depersonalization was 54.67% (95% CI, 46.95 to 62.27; I2 = 99.20%, P < 0.001), and reduced personal accomplishment was 66.53% (95% CI, 58.13 to 74.44; I2 = 99.37%, P < 0.001). Gender, marriage, professional title and specialty all influenced burnout. Conclusions: The results showed that the total prevalence of doctor burnout in China is very high. The prevalence of burnout varies by location. Gender, marital status and professional title all affect burnout scores.

Objective: Malnutrition is prevalent in elderly with hip fracture and higher than in community-dwelling older adults. Scarce studies have examined the association between preoperative malnutrition and postoperative mortality in elderly Chinese individuals with hip fracture. This study was designed to explore the effect of preoperative malnutrition on the postoperative long-term mortality in elderly Chinese individuals undergoing hip surgery. Methods: As a single-center observational study, this study included 263 consecutive patients above 70 years old with hip fracture and elective surgery. Preoperative nutritional status was evaluated by prognostic nutritional index (PNI). Patients were divided into one group with malnutrition (26 patients with PNI ⩽ 38) and the other group without malnutrition (169 patients with PNI > 38), respectively. Results: The overall malnutrition rate was 13.3% (26 patients). The postoperative long-term mortality rates of patients with and without malnutrition had statistically significant difference [10 patients (38.5%) and 32 patients (18.9%), p

BackgroundAge-related cognitive decline (ARCD) is a common condition among older adults, affecting 100 million people worldwide. Traditional Chinese Medicine’s (TCM) constitution is closely related to the occurrence and development of diseases in the elderly population. However, little is known about the relationships between TCM constitution and ARCD in the super-aged population. The present study aimed to investigate the relationships between the TCM constitution and ARCD in Chinese centenarians and to explore the application of the constitution to prevent ARCD in the elderly population.MethodsEach participant underwent a standardized epidemiological investigation and physical examination, based on the China Hainan Centenarian Cohort Study. Data on the demographic characteristics and TCM constitution were collected using structured questionnaires.ResultsThe present study included 636 centenarians aged 100–116 years. The prevalence of ARCD was 87.7% (n = 558 centenarians). In multiple linear regression analysis, an inverse relationship between Qi depression and Mini-Mental State Examination scales was significant after controlling for a wide range of other factors (P < 0.05). In multiple logistic regression analysis, Qi depression was positively associated with ARCD after full adjustment (P < 0.05).ConclusionAs the first study in the world, the present study provides strong epidemiological evidence that Qi depression has a significant relationship with ARCD in Chinese centenarians, and regulating Qi depression may be a valuable method to prevent and treat ARCD in the elderly population.

The fork protection complex (FPC), including the proteins TIMELESS and TIPIN, stabilizes the replisome to ensure unperturbed fork progression during DNA replication. Here the authors reveal that that SDE2, a PCNA-associated protein, plays an important role in maintaining active replication and protecting stalled forks by regulating the replication fork protection complex (FPC).

Hydrogen–gasoline hybrid refueling stations can minimize construction and management costs and save land resources and are gradually becoming one of the primary modes for hydrogen refueling stations. However, catastrophic consequences may be caused as both hydrogen and gasoline are flammable and explosive. It is crucial to perform an effective risk assessment to prevent fire and explosion accidents at hybrid refueling stations. This study conducted a risk assessment of the refueling area of a hydrogen–gasoline hybrid refueling station based on the improved Accident Risk Assessment Method for Industrial Systems (ARAMIS). An improved probabilistic failure model was used to make ARAMIS more applicable to hydrogen infrastructure. Additionally, the accident consequences, i.e., jet fires and explosions, were simulated using Computational Fluid Dynamics (CFD) methods replacing the traditional empirical model. The results showed that the risk levels at the station house and the road near the refueling area were 5.80 × 10−5 and 3.37 × 10−4, respectively, and both were within the acceptable range. Furthermore, the hydrogen dispenser leaked and caused a jet fire, and the flame ignited the exposed gasoline causing a secondary accident, considered the most hazardous accident scenario. A case study was conducted to demonstrate the practicability of the methodology. This method is believed to provide trustworthy decisions for establishing safe distances from dispensers and optimizing the arrangement of the refueling area.

Abstract Background There is limited evidence in the literature to describe an analgesic protocol that takes into consideration the extent of foot and ankle surgery. The aim of this study was to develop a guide for acute postoperative pain management for podiatric surgery in Australia, and to identify opportunities to improve the current list of scheduled medicines available to podiatric surgeons. Methods A Delphi method involving 3 survey rounds was employed for this study. Twelve expert panellists in the field of podiatric surgery and anaesthesiology were invited to participate, and 10 panellists remained by the end of the study. Round 1 involved 15 open‐ended questions. These answers formed the basis of the 55 statements that were developed for the following 2 survey rounds, where panellists rated the appropriateness of each statement on a 9‐point Likert scale. The third survey round was an opportunity for panellists to revise their answers to each statement in light of the majority response. Results For mild acute postoperative pain, non‐opioid oral analgesics were recommended as an appropriate management option. For moderate and severe acute postoperative pain, both non‐opioid and opioid products were found to be appropriate by the majority. It was agreed that oral opioids be reserved for breakthrough pain at all severity levels. All other statements in the Delphi study pertaining to drug hypersensitivities or allergies, stratification of pain management, opioid prescription concerns, and access to pain medications were accepted as appropriate by the majority of panellists. Conclusion The agreed approach to acute postoperative pain management for podiatric surgeons in Australia was with a stepwise approach, utilising multimodal therapy, and reserving oral opioids for breakthrough pain. Additionally, there was consensus for podiatric surgeons in Australia to have wider access to alternative analgesics and anti‐emetics that have similar or improved efficacies with better safety profiles.

Aims: Left ventricular ejection fraction is the conventional measure used to guide heart failure management, regardless of underlying etiology. Left ventricular global longitudinal strain (LV-GLS) by speckle tracking echocardiography (STE) is a more sensitive measure of intrinsic myocardial function. We aim to establish LV-GLS as a marker of replacement myocardial fibrosis on cardiovascular magnetic resonance (CMR) and validate the prognostic value of LV-GLS thresholds associated with fibrosis.Methods and results: LV-GLS thresholds of replacement fibrosis were established in the derivation cohort: 151 patients (57 ± 10 years; 58% males) with hypertension who underwent STE to measure LV-GLS and CMR. Prognostic value of the thresholds was validated in a separate outcome cohort: 261 patients with moderate-severe aortic stenosis (AS; 71 ± 12 years; 58% males; NYHA functional class I–II) and preserved LVEF ≥50%. Primary outcome was a composite of cardiovascular mortality, heart failure hospitalization, and myocardial infarction. In the derivation cohort, LV-GLS demonstrated good discrimination (c-statistics 0.74 [0.66–0.83]; P < 0.001) and calibration (Hosmer-Lemeshow χ2 = 6.37; P = 0.605) for replacement fibrosis. In the outcome cohort, 47 events occurred over 16 [3.3, 42.2] months. Patients with LV-GLS > −15.0% (corresponding to 95% specificity to rule-in myocardial fibrosis) had the worst outcomes compared to patients with LV-GLS < −21.0% (corresponding to 95% sensitivity to rule-out myocardial fibrosis) and those between −21.0 and −15.0% (log-rank P < 0.001). LV-GLS offered independent prognostic value over clinical variables, AS severity and echocardiographic LV mass and E/e′.Conclusion: LV-GLS thresholds associated with replacement myocardial fibrosis is a novel approach to risk-stratify patients with AS and preserved LVEF.

ABSTRACT: In this study, 105 broiler chickens were fed with dietary feeds containing different contents of Dichroae Radix extract for 10 consecutive days. Then the residue depletions of its main alkaloids (febrifugine and isofebrifugine) in muscle, kidney and liver samples at different withdrawal times were determined by an ultra-performance liquid chromatography method. Results showed that the 2 alkaloids were mainly at tissue-bound formation. At withdrawal period of 0 d, their concentrations in all samples were high but decreased rapidly after 1 day of cessation (35–91%). After 5 to 7 days of cessation, their residues in muscle and kidney were not detectable, and after at least 10 days of cessation they were not detectable in liver. These results indicated that an appropriate withdrawal time for Dichroae Radix preparation was required if it is licensed as a new drug, and the best target tissue for monitoring its residue was liver.

Abstract Mechanical fastening is widely used in joining metals, particularly in automotive, aerospace, building and construction industries. However, the main concern on mechanical fastening is the issue of corrosion. An effective way to prolong the service life of steel fasteners is to apply protective coatings onto these components. This paper reviews and compares a few common coating deposition techniques, i.e., electroplating, hot-dip galvanizing, ion vapour deposition and mechanical plating, in terms of their characteristics. Compositional and microstructural properties including morphology and porosity, corrosion resistance performance and frictional performance of the coatings formed by each process are discussed in details. Hydrogen embrittlement, a premature failure often occurred on high strength steel fasteners, is also reviewed. The key results of recent studies of various metallic coatings on fasteners are presented to provide a fundamental understanding of the evolving topics, and the research gaps have been identified for further investigation.

Abstract Background This analysis was designed to investigate the relationship between drug application and mortality rate in Chinese older coronary artery disease (CAD)/chronic heart failure (CHF) patients with and without low glomerular filtration rate (GFR). Methods All 1050 Chinese hospitalized patients with diagnosed CAD were included in this analysis, and Cox Regression was used to analyze the relationship between drug application and mortality rate after multivariate adjustment. Low GFR was defined as GFR 0.05 for all). In CHF patients without low GFR, statins were significantly associated with lower mortality rate (P 0.05 for all). Conclusion Clopidogrel but not aspirin was beneficial in Chinese older CAD patients without low GFR rather than those with low GFR, and statins benefited for Chinese older CAD/CHF patients without low GFR rather than those with low GFR. These discoveries might offer some help for the therapy of Chinese older patients with cardiovascular/renal diseases.

Recently, compressive sensing (CS) and visual security (VS) have caught researchers attention in information security field. However, the measurement matrix is often reused in CS, which makes it vulnerable to chosen plaintext attack (CPA). In addition, when generating meaningful cipher images, the size of the carrier image is usually not less than the size of the plain image. In order to overcome these drawbacks, a new visually secure image encryption scheme using CS and reversible color transformation is proposed. The algorithm consists of two stages: compression and embedding. In the first stage, chaotic sequence is used to generate different structurally random matrices. When CS is performed, a random number is added during the process of sampling. By choosing different random numbers, different measurement matrices can be used to compress and encrypt the same image in different order. In the second stage, block pairing, color transformation and block replacement are employed to obtain a meaningful image. Different from the block replacement between two similar images, this paper first attempts to replace the block of the carrier image with a compressed noise-like image block. Thus, the carrier image can be smaller than the plain image, which saves the bandwidth of transmission. Both theoretical analysis and experimental results show that the proposed encryption scheme has good encryption performance, can effectively resist common attacks, and is suitable for meaningful image encryption.

Selecting optimal revegetation patterns, i.e., patterns that are more effective for soil organic carbon (SOC) and total nitrogen (TN) accumulation, is particularly important for mine land reclamation. However, there have been few evaluations of the effects of different revegetation patterns on the SOC and TN in reclaimed mine soils on the Loess Plateau, China. In this study, the SOC and TN stocks were investigated at reclaimed mine sites (RMSs), including artificially revegetated sites (ARSs) (arbors (Ar), bushes (Bu), arbor-bush mixtures (AB), and grasslands (Gr)) and a natural recovery site (NRS), as well as at undisturbed native sites (UNSs). Overall, the SOC and TN stocks in the RMSs were lower than those in the UNSs over 10–13 years after reclamation. The SOC stocks in the RMSs and UNSs only differed in the top 0–20 cm of the soil (p AB (2.88 kg m−2) ≥ Bu (2.72 kg m−2), and the TN stocks exhibited a similar trend. These results suggest that grasslands were more favorable than woodlands for SOC and TN accumulation in this arid area. Thus, in terms of the accumulation of SOC and TN, grassland planting is recommended as a revegetation pattern for areas with reclaimed mine soils.

Objective: The objective of this article is to identify factors that drive and conditions that affect foreign women entrepreneurs in China. The emphasis is on the commonalities and differences between these women and women entrepreneurs in Western developed countries as reflected in the literature. Research Design & Methods: The study was designed to include both qualitative and quantitative data to allow better understanding of the topic. Interviews with foreign women entrepreneurs were first done to gain practical field insights which were then used with the information from the literature to develop the questionnaire for the survey for quantitative data. Findings: The findings from the interviews and the survey from a very small sample show the key differences lie in internal factors like motivation and family-business orientation, but there are also similarities in terms of external characteristics, such as business nature, business size, financing source, etc. between foreign female entrepreneurs in China and those represented in studies. And the key challenges and learning reported by foreign female entrepreneurs in China are both related to culture. Implications & Recommendations: The article intends to fill the gap by offering some insights into foreign women entrepreneurs in China. Broader and in-depth empirical studies on this subject are needed to verify these initial findings, and stimulate interests in this important but neglected field. Contribution & Value Added: The originality of this work lies in contributing to some understanding that the gender plays role in entrepreneurship across cultures, particularly in China.

Spermatozoa are not mature until they transit the epididymis where they acquire motility and the ability to fertilize an egg through sequential modifications. The epididymis has three functional regions, caput, corpus, and cauda, and the luminal proteins of the epididymis play important roles in the above modifications. However, the proteins with differential enrichment between the caput and cauda are still largely unknown. To reveal the functions of the caput and cauda during sperm maturation, luminal proteins from caput and cauda of mice were analyzed by isobaric tag for relative and absolute quantitation (iTRAQ). Overall, 128 differentially enriched proteins were found, of which 46 were caput enriched and 82 were cauda enriched. Bioinformatic analysis showed that lipid metabolism was active in the caput; while anion- and cation-binding activity and phosphorus and organophosphate metabolism were active in the cauda. A new epididymal luminal protein, the caput-enriched PDZ domain containing 1 (Pdzk1), also named Na+/H+ exchange regulatory cofactor 3 (NHERF3), which plays a critical role in cholesterol metabolism and carnitine transport, was found in the lipid metabolism. Western blotting and immunofluorescence analyses showed that Pdzk1 was expressed in the epididymis but not in the testis, and localized at the middle piece of the sperm tail. Pdzk1 protein level was also reduced in the spermatozoa in case of asthenozoospermic patients compared with that in normozoospermic men, suggesting that Pdzk1 may participate in sperm maturation regulation and may be associated with male infertility. These results may provide new insights into the mechanisms of sperm maturation and male infertility.

Abstract As a family of hormones with pleiotropic effects, natriuretic peptide (NP) system includes atrial NP (ANP), B-type NP (BNP), C-type NP (CNP), dendroaspis NP and urodilatin, with NP receptor-A (guanylate cyclase-A), NP receptor-B (guanylate cyclase-B) and NP receptor-C (clearance receptor). These peptides are genetically distinct, but structurally and functionally related for regulating circulatory homeostasis in vertebrates. In humans, ANP and BNP are encoded by NP precursor A (NPPA) and NPPB genes on chromosome 1, whereas CNP is encoded by NPPC on chromosome 2. NPs are synthesized and secreted through certain mechanisms by cardiomyocytes, fibroblasts, endotheliocytes, immune cells (neutrophils, T-cells and macrophages) and immature cells (embryonic stem cells, muscle satellite cells and cardiac precursor cells). They are mainly produced by cardiovascular, brain and renal tissues in response to wall stretch and other causes. NPs provide natriuresis, diuresis, vasodilation, antiproliferation, antihypertrophy, antifibrosis and other cardiometabolic protection. NPs represent body’s own antihypertensive system, and provide compensatory protection to counterbalance vasoconstrictor-mitogenic-sodium retaining hormones, released by renin-angiotensin-aldosterone system (RAAS) and sympathetic nervous system (SNS). NPs play central roles in regulation of heart failure (HF), and are inactivated through not only NP receptor-C, but also neutral endopeptidase (NEP), dipeptidyl peptidase-4 and insulin degrading enzyme. Both BNP and N-terminal proBNP are useful biomarkers to not only make the diagnosis and assess the severity of HF, but also guide the therapy and predict the prognosis in patients with HF. Current NP-augmenting strategies include the synthesis of NPs or agonists to increase NP bioactivity and inhibition of NEP to reduce NP breakdown. Nesiritide has been established as an available therapy, and angiotensin receptor blocker NEP inhibitor (ARNI, LCZ696) has obtained extremely encouraging results with decreased morbidity and mortality. Novel pharmacological approaches based on NPs may promote a therapeutic shift from suppressing the RAAS and SNS to re-balancing neuroendocrine dysregulation in patients with HF. The current review discussed the synthesis, secretion, function and metabolism of NPs, and their diagnostic, therapeutic and prognostic values in HF.

Image encryption can be classified into pixel-level and bit-level according to the smallest processing element in the permutation and diffusion. Most pixel-level permutations only change the pixel positions, so the histograms of the permuted image and the original image are identical. The bit-level permutation can change the histogram of the image, but it is comparatively time-consuming due to bit-level computing. In this paper, we propose a new digit-level permutation. The pixel matrix of an image is decomposed into three digital matrices, and then these digital matrices are shuffled by the Henon map. This digit-level permutation combines the merits of pixel-level permutation with that of bit-level permutation. Besides, we also design a high-speed diffusion operation which exactly solves the problem that CBC-like diffusion has low efficiency. Simulations have been carried out and analyzed in detail, proving the superior security and high efficiency of our image cryptosystem.

Purpose: The number of cancer cases in China has increased rapidly from 2.1 million in 2000 to 4.3 million in 2015. As a consequence, pain management as an integral part of cancer treatment became an important health care issue. In March 2011, the Good Pain Management (GPM) program was launched to standardize the treatment of cancer pain and improve the quality of life for patients with cancer. With this work, we will describe the GPM program, its implementation experience, and highlight key lessons that can improve pain management for patients with cancer. Methods: We describe procedures for the selection, implementation, and assessment procedures for model cancer wards. We analyzed published results in areas of staff training and patient education, pain management in practice, analgesic drugs administration, and patient follow-up and satisfaction. Results: Pain management training enabled medical staff to accurately assess the level of pain and to provide effective pain relief through timely dispensation of medication. Patients with good knowledge of treatment of pain were able to overcome their aversion to opioid drugs and cooperate with nursing staff on pain assessment to achieve effective drug dose titration. Consumption of strong opioid drugs increased significantly; however, there was no change for weaker opioids. Higher pain remission rates were achieved for patients with moderate-to-severe pain levels. Proper patient follow-up after discharge enabled improved outcomes to be maintained. Conclusion: The GPM program has instituted a consistent and high standard of care for pain management at cancer wards and improved the quality of life for patients with cancer.

To assess the potential of China's industrial restructuring on energy conservation and greenhouse gas (GHG) emission reduction in 2020, this study proposes an input–output multi-choice goal programming model and method. In this model, the goals include the maximization of gross domestic product (GDP), minimization of energy consumption and GHG emission. They are subjected to the input–output balance, economy development, energy supply, and industry diversity. And four scenarios with different decision preferences are taken into accounted in the solutions of the industrial structure optimization model. The results demonstrate that industrial restructuring has potential in energy saving and emission reducing. First, after optimization, energy consumption intensity and GHG emission intensity can drop by 13.88246% and 5.33767% over 2012, and GDP can grow up at annual growth rate 6.6% from 2013–2020. Second, promoting the development of the low energy-intensive and low GHG emission intensive sectors is an effective method for energy conservation and emission reduction. Three, compared to energy intensity reduction, GHG emission intensity reduction is less effective for four scenarios. Four, there are several difficulties to achieve the amounts and intensity control targets of energy conservation and GHG emission reduction simultaneously. It is suggested that China had better strive to promote progress of technologies of energy conservation and GHG emission reduction while adjusting the industrial structure.