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Aim. It has been reported that more than half of breast cancer (BC) could be identified as HER2-low-positive, which might be a distinct subtype. But the results are controversial. We aim to compare the survival outcomes between HER2-low-positive and HER2-0 BC with Asian women based on HR status or Ki-67 index. Methods. Between January 2009 and December 2017, HER2-nonamplified BC in our single institute was identified. Patients were classified as HER2-low and HER2-0 cohort. Clinical characteristics were compared between these two groups and survival outcomes were calculated by the Kaplan–Meier method. We also performed subgroup analysis according to Ki-67 index and hormone-receptor (HR) status. Results. Of the 2,230 included patients, 536 presented with HER2-0, and 1,694 with HER2-low positive. After a median follow-up of 85 months (range: 1–152 months), the 8-year OS, BCSS, and RFS of the overall cohort were 91%, 95%, and 89%, respectively. In comparison with the HER2-0 cohort, majority of HER2-low-expression BC concurrently presented with HR positive (82.3% vs. 69%, P < 0.001 ). There was no significant survival difference between the two groups in terms of OS, BCSS, and RFS (all p > 0.05 ). We then performed subgroup analysis according to HR status and Ki-67 index ( p > 0.05 ), while OS ( p = 0.026 ) and BCSS ( p = 0.052 ) of HER2-0 BC with high Ki-67 index were significantly poorer than that of HER2-low positive with high Ki-67, but not for RFS ( p = 0.17 ). Conclusion. Among early stage HER2-nonamplified BC, no significant survival difference could be found between HER2-low positive and HER2-0 cohort regardless of HR status. Survival outcomes of HER2-low positive with high Ki-67 seem to be poorer than that of HER2-0 tumors with high Ki-67 index.

Background Previous studies have presented inconsistent results on the relationship between serum uric acid and skeletal muscle mass (SMM). We aimed to explore whether a higher serum uric acid level was associated with low SMM in the Chinese population. Methods We performed a cross-sectional analysis of 6595 subjects aged 45 years or older. They were tested for fasting blood glucose, total cholesterol, triglycerides, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol, uric acid, blood urea nitrogen, creatinine, and estimated glomerular filtration rate. SMM was accessed by dual-energy x-ray absorptiometry using two approaches: weight-adjusted appendicular skeletal muscle mass (ASM)% and ASM/BMI (body mass index (kg/m2)). Low SMM was defined as a cut-off point of ASM/BMI Results Compared with their normal group, patients with hyperuricemia had lower ASM% (29.33±2.33 vs 30.03±2.34 for males and 24.71±1.99 vs 25.19±2.07 for females, P Conclusions In a middle-aged and elderly Chinese population, hyperuricemia is independently and positively associated with low SMM and can vary by age and gender.

The island-type greenway should emphasize the role of maintaining and promoting the island cultural landscape as it serves the function of a general greenway green infrastructure while also having a unique landscape appearance. The northern greenway of Pingtan is used as an example in the paper to illustrate how regional culture is perceived. The first part of the analysis looks at how demographic factors affect the quality of cultural perception. The study reveals that: from a gender perspective, women are more likely than men to perceive regional culture; from an age perspective, people between the ages of 18 and 40 are more likely to perceive regional culture; older people and children are less likely to perceive regional culture; and from a level of education perspective, the higher the education, the stronger the perception. The relationship between tourists’ perceived quality, cognitive image, perceived value, satisfaction, and loyalty to the cultural expression of the greenway landscape is then analyzed by building a structural equation model. According to the findings, visitors’ perceptions of the island’s cultural quality have a positive impact on their cognitive images and perceptions of value, while their satisfaction with the cultural expressions along the coastal greenway has a positive impact on their loyalty.

Type I collagen carboxyl-terminal peptide β (β-CTX) increases in osteoporosis. The study aimed to explore the relationship between serum β-CTX and the risk of osteoporosis as well as sarcopenia in Chinese elderly inpatients. Around 228 patients whose age >65 years were recruited in this cross-sectional study. Dual-energy X-ray scanning was used to access skeletal muscle and bone mass. Serum concentration of β-CTX as well as the prevalence of osteoporosis were significantly higher in low skeletal muscle index (SMI) group than that in the normal SMI group (P < 0.05). Serum β-CTX levels negatively correlated with SMI and bone mass (P < 0.05). Total muscle mass, appendicular skeletal muscle mass, SMI, total bone mass, and bone mass at various sites including the limbs, spine, and pelvis decreased significantly, and the prevalence of low SMI increased with the increase of the quartiles of β-CTX. Higher serum β-CTX had an increased risk of low SMI and osteoporosis (P < 0.05). Summarily, with increasing serum β-CTX levels, both muscle and bone mass decreased in Chinese elderly inpatients. Serum β-CTX was positively associated with the risk of not only osteoporosis but also skeletal muscle loss.

The relationship between the pathological classification and recurrence of duodenal papillary adenomas (DPAs) has not been elucidated. We studied the clinicopathological characteristics of DPAs with different pathological types and conducted long-term follow-up to explore its prognosis and identify methods for appropriate clinical management of DPAs.In total, 95 DPA cases confirmed by postoperative pathology were enrolled, of which 58 underwent endoscopic papillectomy (EP) and 37 underwent pancreatoduodenectomy (PD). The cases were classified into three anatomical and two histomorphological types according to the histopathology and location of endoscopic features. We analyzed the clinicopathological characteristics of DPAs with different pathological types and investigated the factors associated with recurrence in the EP subgroup.Although EP was associated with fewer adverse events, the complete resection rate was significantly lower (72.4% vs. 100.0%, p 0.001) and the recurrence rate significantly higher than with PD (16.3% vs. 0.0%, p 0.001). Among eight EP cases with recurrence, six had intra-DPA (75%). A positive resection margin (HR 23.67, 95% CI 6.42-87.27; p 0.001) and MUC2-negative status (HR 3.47, 95% CI 1.16-10.40; p = 0.026) were independent risk factors for recurrence after EP.We identified different pathological types within DPAs, which presented varying clinicopathological features. The majority of peri-DPAs and mixed-DPAs were of the intestinal type histologically and EP is the primary recommendation. However, intra-DPA was mainly of the pancreaticobiliary type, which tends to get positive resection margins; thus, surgical resection is more suitable.

The PNPLA3 and TM6SF2 gene variants have been found to cause NAFLD with a favourable cardiovascular risk profile.To investigate the effects of the NAFLD risk alleles on the all-cause and cause-specific mortality in 5581 Chinese adults.The genome-wide genotypes were detected using a genotyping array and serum lipoprotein profiles were examined using 1H NMR platform. Liver fat content (LFC) was measured using a quantitative ultrasound method. The vital status was determined using official registration data.Genome-wide association analysis showed that a series of variants in PNPLA3 were associated with LFC, including rs738409 CG variant (P = 8.6 × 10The PNPLA3 rs738409 CG variant and its combination with TM6SF2 rs58542926 CT and MBOAT7 rs641738 CT variants increase liver-specific mortality but reduce cardiovascular mortality in overweight/obese Chinese.

Tanshinone IIa (TanIIa), an ingredient of Radix Salviae Miltiorrhizae, has an anticancer effect on various solid tumors with high efficiency and low toxicity. Nonetheless, the underlying role of TanIIa in acute promyelocytic leukemia (APL) remains unclear. Here, we revealed that TanIIa drastically inhibited NB4 cell viability with an IC50 value of 31.25 μmol/L. Using flow cytometry apoptosis assay, we identified that TanIIa dose-dependently exacerbated NB4 cell apoptosis. Mechanistically, TanIIa upregulated apoptotic factor levels, namely, cleaved-caspase 9, cleaved-caspase 3, and cleaved-PARP-1. Moreover, we noticed that TanIIa dose-dependently suppressed the PI3K/Akt/mTOR axis. This axis not only functions as an essential antiapoptotic modulator but also serves as a suppressant regulator of autophagy. Correspondingly, we detected the levels of autophagic marker, namely, LC3B, which were increased after the TanIIa treatment. Furthermore, the autophagy inhibitor Baf-A1 could effectively reverse the TanIIa-induced apoptosis, manifesting that TanIIa eliminated NB4 cells in an autophagy-dependent manner. In conclusion, tanshinone IIa exerts anti-APL effects through triggering autophagy and apoptosis in NB4 cells.

White matter hyperintensity (WMH) is associated with vascular hemodynamic alterations and reflects white matter injury. To date, the sex difference of tract-specific WMH and the relationship between high blood pressure (BP) and tract-specific WMH remain unclear. We recruited 515 subjects from the Shanghai Changfeng study (range 53-89 years, mean age 67.33 years). Systolic and diastolic blood pressure (SBP and DBP) were collected and used to calculate pulse pressure (PP). Magnetic resonance T1 and T2 FLAIR images were acquired to measure WMH and calculate WMH index. The ANCOVA test was performed to test the difference between sexes, and the linear regression model was used to examine the associations between BP and WMH index. Men showed higher WMH index than women in all white matter tracts (p .001, respectively) except for the bilateral superior longitudinal fasciculus (SLF) and its left temporal part (tSLF). High SBP and PP was associated with a lower WMH index on the left corticospinal tract (CST), SLF, tSLF and right cingulum in hippocampus (p ≤ .001, respectively) in women, while high DBP was associated with a higher WMH index on the bilateral CST (left p .001; right p = .001), left inferior longitudinal fasciculus (p .001) and inferior fronto-occipital fasciculus (p = .002) in men. Men tend to have more WMH compared to women. A high SBP/PP relates to a lower WMH burden in women. This suggests that women could benefit from higher blood pressure in older age.

Background: End-stage renal disease is associated with a high risk of cardiovascular events. It is unknown, however, whether mild-to-moderate kidney dysfunction is causally related to coronary heart disease (CHD) and stroke. Methods: Observational analyses were conducted using individual-level data from 4 population data sources (Emerging Risk Factors Collaboration, EPIC-CVD [European Prospective Investigation into Cancer and Nutrition–Cardiovascular Disease Study], Million Veteran Program, and UK Biobank), comprising 648 135 participants with no history of cardiovascular disease or diabetes at baseline, yielding 42 858 and 15 693 incident CHD and stroke events, respectively, during 6.8 million person-years of follow-up. Using a genetic risk score of 218 variants for estimated glomerular filtration rate (eGFR), we conducted Mendelian randomization analyses involving 413 718 participants (25 917 CHD and 8622 strokes) in EPIC-CVD, Million Veteran Program, and UK Biobank. Results: There were U-shaped observational associations of creatinine-based eGFR with CHD and stroke, with higher risk in participants with eGFR values 105 mL·min –1 ·1.73 m –2 , compared with those with eGFR between 60 and 105 mL·min –1 ·1.73 m –2 . Mendelian randomization analyses for CHD showed an association among participants with eGFR –1 ·1.73 m –2 , with a 14% (95% CI, 3%–27%) higher CHD risk per 5 mL·min –1 ·1.73 m –2 lower genetically predicted eGFR, but not for those with eGFR >105 mL·min –1 ·1.73 m –2 . Results were not materially different after adjustment for factors associated with the eGFR genetic risk score, such as lipoprotein(a), triglycerides, hemoglobin A1c, and blood pressure. Mendelian randomization results for stroke were nonsignificant but broadly similar to those for CHD. Conclusions: In people without manifest cardiovascular disease or diabetes, mild-to-moderate kidney dysfunction is causally related to risk of CHD, highlighting the potential value of preventive approaches that preserve and modulate kidney function.

Context Previous genome-wide association studies (GWASs) of bone mineral density (BMD) were mainly conducted in Europeans. Objective To explore genetic variants that affect BMD and sex differences in a Chinese population. Methods A total of 5428 middle-aged and elderly Chinese were included. Dual-energy X-ray absorptiometry was used to measure BMD at the lumbar spine, and total and specific sites of the hip. A mixed linear model was used to analyze the associations between BMD and autosomal genetic variants, adjusting for age, age squared, sex, and menopausal women (model 1); model 2 was further adjusted for height and weight. A GWAS of osteoporosis in the Biobank Japan (BBJ) project was used for replication. GWAMA software was used to detect the statistical significance of sex differences of estimated effects. Gene annotation and pathway enrichment analysis were performed. Results Women lost BMD at earlier ages and faster than men. The 2 models identified a total of 12 loci that were associated with BMD at any site. Single nucleotide polymorphisms rs72354346, rs2024219, rs1463093, rs10037512, and rs5880932 were successfully replicated in the BBJ. Variations of rs79262027 G>A (VKORC1L1) and rs4795209 A>G (DDX52) were associated with BMD only in men, and rs1239055408 G>GA (KCNJ2) was associated with BMD only in women. Gene enrichment analysis showed that BMD in a Chinese elderly population was mainly related to ossification, bone resorption, sex hormones, and kidney physiology. Conclusion The present GWAS identified 12 loci that were significantly associated with BMD at any site in a Chinese population, and 3 of them showed sex differences in their effects.

Background Previous studies have presented osteoporosis and sarcopenia frequently occur concomitantly in elderly. Type I collagen carboxyl-terminal peptide β (β-CTX) usually increases in osteoporosis. However, the relationship between β-CTX and muscle mass remains unclear. This study aimed to explore the association between serum β-CTX and the risk of sarcopenia in elderly inpatients. Methods 228 patients > 65 years were recruited in this cross-sectional study. Dual-energy X-ray scanning (DXA) was used to access skeletal muscle and bone mass. Skeletal muscle mass index (SMI) was defined as appendicular skeletal muscle mass (ASM) divided by height2. Serum markers of bone remodeling were detected by electrochemical immunofluorescence assay. Results Serum concentration of β-CTX as well as the prevalence of osteoporosis were higher in low SMI group than in the normal SMI group. Correlation analysis showed that serum β-CTX levels negatively correlated with SMI and bone mass. Across the quartiles of serum β-CTX, total skeletal muscle mass (TSM), ASM, SMI, total bone mass (TBM) and bone mass at various sites including the limbs, spine and pelvis decreased significantly, wherea the prevalence of low SMI and osteoporosis increased. Logistic regression analysis showed the higher quartiles of serum β-CTX had an increased risk of low SMI and osteoporosis, compared to the lowest quartile (the third and fourth quartiles for low SMI and the fourth quartile for osteoporosis). Conclusions With increasing serum β-CTX levels, muscle and bone mass decreased in Chinese elderly inpatients. Serum β-CTX was positively associated with the risk of osteoporosis and muscle loss.

Sarcopenia, the age-related loss of muscle mass and function, is closely associated and frequently concomitant with non-alcoholic fatty liver disease (NAFLD). We aimed to investigate the clinical features of the sarcopenic NAFLD patients from middle-aged and older people.A total of 1305 patients with NAFLD from the Shanghai Changfeng Study were included for analysis. Sarcopenia was diagnosed based on the height-adjusted appendicular skeletal muscle mass (ASM/heightAmong the middle-aged and older population, 68.1% of patients with sarcopenia and NAFLD were lean. Sarcopenia was independently associated with increased risk of carotid plaque (OR, 2.22; 95%CI 1.23-4.02) and liver fibrosis (OR, 2.07; 95%CI 1.24-3.44), and the sarcopenic lean NAFLD patients were characterized by a higher risk of carotid plaque (p = 0.008) and liver fibrosis (p = 0.001) than the non-sarcopenic lean NAFLD patients, despite their lower BMI and similar prevalence of metabolic syndrome and diabetes. Further serum metabolomic examination indicated that the sarcopenic lean NAFLD patients presented a distinct metabolomic profile prone to carotid plaque and liver fibrosis, with upregulated serum valine, N-acetylneuraminyl-glycoproteins, lactic acid, small LDL triglycerides and VLDL5 components, and reduced components of HDL4. A sarcopenic characterization score based on above metabolites was established and could also predict increased risk of carotid plaque and liver fibrosis.The presence of sarcopenia identifies a special subgroup of lean NAFLD with increased risk of cardiovascular disease and liver fibrosis clinically.

Recent advances indicate that bone and energy metabolism are closely related. However, little direct evidence on causality has been provided in humans. We aimed to assess the association of three bone-related biomarkers-25 hydroxyvitamin D (25OHD), parathyroid hormone (PTH), and osteocalcin (OCN)-with several metabolic phenotypes and investigate any causal relevance to the associations using a Mendelian randomization (MR) study. Serum 25OHD, PTH, and total OCN were measured at baseline in 5169 eligible Chinese participants in Changfeng study. Partial correlation and bivariate GREML analysis were used to estimate phenotypic and genetic correlations, respectively. Multiple linear regression and logistic regression were used to assess linear associations. Genomewide association analysis (GWAS) was performed. Bidirectional two-sample MR analyses were conducted to examine causal relationships between OCN and body mass index (BMI), diastolic blood pressure (DBP), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), glycated hemoglobin A1c (HbA1c), and type 2 diabetes (T2DM), using our GWAS result of OCN and GWAS statistics from Biobank Japan project (BBJ) and the largest meta-analysis of T2DM GWAS in East Asian population. Circulating OCN was significantly associated with higher DBP and HDL-C and decreased TG, blood glucose level, insulin resistance, liver fat content, bone mineral density, BMI, and a favorable body fat distribution pattern. GWAS identified one novel serum PTH locus and two novel serum OCN loci, explaining 0.81% and 1.98% of variances of PTH and OCN levels, respectively. MR analysis suggested a causal effect of T2DM on lower circulating OCN concentration (causal effect: -0.03; -0.05 to -0.01; p = 0.006 for T2DM_BBJ and -0.03; -0.05 to -0.01; p = 0.001 for T2DM_EAS). These findings indicate that T2DM might impact bone remodeling and provide a resource for understanding complex relationships between osteocalcin and metabolic (and related) traits in humans. © 2021 American Society for Bone and Mineral Research (ASBMR).

Introduction: It has been well recognized that sarcopenia is closely related with osteoporosis, while the relationship between bone mass at different sites and muscle mass remains largely unexplored. This study aims to explore the relationship between bone mass at different sites and skeletal muscle mass in older adults. Methods: A total of 228 patients over 65 years old were enrolled in this study, and then 180 valid participants with accessible dual-energy X-ray absorptiometry (DXA) scanning data and absence of malignant tumors, mobility disorders, serious liver and kidney disease, and cardiac insufficiency were selected (138 male and 42 female). These individuals were further divided into control group and low skeletal muscle mass index (SMI) group. DXA scanning was used to access skeletal muscle mass and bone mass. SMI or body mass index was defined as appendicular muscle mass or weight divided by squared height, respectively. Low SMI 2 in male or 2 in female was defined as low SMI; while the bone density score at or below 2.5 standard deviations (T-score) below normal peak bone values, was regarded as osteoporosis. Results: The average age of enrolled patients was 82.72 years; the ratios of osteoporosis, low SMI, and low SMI with osteoporosis were 48.8%, 23.3%, and 15.0%, respectively. Compared with the control group, the prevalence of osteoporosis was higher, and the total bone mass and bone mass at various sites including limbs, spine, and pelvis, were all lower in low SMI group. Correlation analysis showed that SMI was positively related with total bone mass and bone mass at various sites. Covariance analysis showed that only total bone mass and appendicular bone mass decreased with decreasing SMI. After multiple adjustment, osteoporosis was positively related with the prevalence of low SMI, as evidenced by logistic regression analysis (odds ratio = 1.33, 95% confidential interval: 1.04–3.24, p = 0.045). Furthermore, compared with the highest quartile of appendicular bone mass, the lowest quartile was related with the increasing prevalence of low SMI (odds ratio = 7.29, 95% confidential interval: 1.21–67.45, p = 0.042). Conclusion: Compared with the other sites, the bone mass reduction at limbs of older adults was positively associated with skeletal muscle loss. It may be more beneficial to increase bone mass at the limbs for improved sarcopenia prevention and therapy. Further investigations are needed to explore the effects of other confounders (e.g., energy, calcium and vitamin D intake, and physical activity) on the osteoporosis and sarcopenia in older adults.

Sarcopenia is an age-dependent skeletal muscle disorder that is common in patients with heart failure. The current study aimed to investigate the associations of sarcopenia with carotid atherosclerosis, cardiovascular disease and cardiac arrhythmia in a middle-aged and elderly population without clinical heart failure.A total of 2432 participants (992 men and 1440 women) from Shanghai Changfeng Study were included for analysis. The degree of sarcopenia was measured using height-adjusted appendicular skeletal muscle mass (ASM/heightSarcopenia was associated with higher prevalence of carotid atherosclerosis (26.4% vs 20.4%, P = 0.027), myocardial infarction (4.0% vs 1.1%, P = 0.001), and premature ventricular contraction (4.0% vs 2.0%, P = 0.034) in the participants with normal body weight, and higher prevalence of carotid atherosclerosis (45.0% vs 31.2%, P = 0.016), myocardial infarction (10.0% vs 4.3%, P = 0.020) and atrial fibrillation (7.5% vs 1.3%, P 0.001) in those with overweight/obese status. After adjustment for age, gender, cigarette smoking, alcohol drinking, menopausal status in women and other metabolic and inflammatory confounding factors, sarcopenia was independently associated with the risk of myocardial infarction in the whole population, and the risk of atrial fibrillation in the overweight/obese participants (all P 0.05). Compared with nonsarcopenic lean participants, the risk of myocardial infarction was gradually increased in sarcopenic lean (OR 3.08 [1.28-7.45], P = 0.012) and sarcopenic overweight/obese participants (OR 4.07 [1.31-12.62], P = 0.015). For the atrial fibrillation, the participants with either sarcopenia or overweight/obesity alone showed no higher risk. However, concomitant sarcopenia and overweight/obesity was associated with approximately 5-fold risk of atrial fibrillation (OR 5.68 [1.34-24.12], P = 0.019) after multiple adjustment.Sarcopenia is associated with myocardial infarction and atrial fibrillation in middle-aged and elderly adults without clinical heart failure.

Osteocalcin regulates energy metabolism in an active undercarboxylated/uncarboxylated form. However, its role on the development of non-alcoholic fatty liver disease (NAFLD) is still controversial. In the current study, we investigated the causal relationship of circulating osteocalcin with NAFLD in two human cohorts and studied the effect of uncarboxylated osteocalcin on liver lipid metabolism through animal models. We analyzed the correlations of serum total/uncarboxylated osteocalcin with liver steatosis/fibrosis in a liver biopsy cohort of 196 participants, and the causal relationship between serum osteocalcin and the incidence/remission of NAFLD in a prospective community cohort of 2055 subjects from Shanghai Changfeng Study. Serum total osteocalcin was positively correlated with uncarboxylated osteocalcin (r = 0.528, p < .001). Total and uncarboxylated osteocalcin quartiles were inversely associated with liver steatosis, inflammation, ballooning, and fibrosis grades in both male and female participants (all p for trend

Objective To explore the effect of berberine (BBR) on skeletal muscle mass and metabolism and the possible mechanism. Methods Eight-week-old male C57BL/6 mice were fed with a high-fat diet (HFD) for 8 weeks to establish the insulin resistance obesity model. Then, mice were randomly divided into two groups (normal chow diet (NCD) and HFD), while NCD and HFD were further classified into two groups respectively, which were NCD+CS (Carmellose Sodium), NCD+BBR, HFD+CS and HFD+BBR. After the BBR intervention, insulin tolerance test (ITT) and glucose tolerance test (GTT) were carried out. Metabolic parameters and inflammatory biomarkers were detected. Various parts of adipose tissue and gastrocnemius were separated and measured. The gastrocnemius muscle was selected for tissue staining. The mRNA expression of myostatin (Mstn) was tested by quantitative real-time PCR (RT-PCR). Western blotting was performed to detect the expression of Mstn, phosphatidylinositol 3-kinase (PI3K), protein kinase B (Akt), small ribonucleoprotein particle protein 2 (Smd2), small ribonucleoprotein particle protein 3 (Smd3), and small ribonucleoprotein particle protein 4 (Smd4). Results Both body weights (P

Crystal structures and superconducting properties of C2 LiSeH4 and Pmm2 LiSeH6 were studied under pressure using first-principles calculations.

IQ motif containing GTPase activating protein 1 (IQGAP1) is a scaffold protein to transduce multiple signals from the extracellular microenvironment. However, whether IQGAP1 mediates EGF-induced cancer progression has been not observed. In this research, we explored the immunological correlations of IQGAP1. IQGAP1 was up-regulated in most cancer and related to poor prognosis in ovarian cancer. In addition, IQGAP1 was correlated with immune-related genes and tumor-infiltrating lymphocytes. IQGAP1 was a novel EGF-response gene, which was up-regulated by EGF. As the downstream of EGFR, IQGAP1 mediated EGF-induced proliferation, migration and invasion of tumor cells and was essential for EGF-induced PD-L1 expression as well. Mechanically, IQGAP1 interacted with STATs and mediated their phosphorylation. Furthermore, Curcumin inhibited EGFR/IQGAP1 axis to down-regulate PD-L1 and suppress cancer progression. To sum up, IQGAP1 responds to EGF stimulation and mediates EGF-induced phosphorylation of STATs, which is a novel promising target for blocking the EGF-induced cancer progression.

Articular cartilage defects cannot adequately self-repair because of avascular and complex tissues. Although various scaffold materials have been reported to promote cartilage repair, challenges remain in this field. In the present study, an orientated microtubules scaffold that consisted of collagen, chitosan, silk fibroin, and polylysine-heparin sodium nanoparticles containing transforming growth factor β1 (TGF-β1), was constructed using a unidirectional freeze-drying method. The collagen/chitosan/0.5silk fibroin scaffolds showed optimal properties via the evaluation of physicochemical characterization, mechanical properties and biocompatibility. The collagen/chitosan/0.5silk fibroin scaffolds containing polylysine-heparin sodium nanoparticles loaded with TGF-β1 (COL/CS/0.5SF-TPHNs) could control the slow release of TGF-β1. Simultaneously, the in vitro COL/CS/0.5SF-TPHNs scaffolds exhibited not only an excellent biocompatibility to support mouse mesenchymal stem cells (mBMSCs) adhesion and proliferation, but also exhibited excellent repair effect in cartilage defects of rabbit models in vivo. Our results showed that the COL/CS/0.5SF-TPHNs scaffolds have the potential to induce articular cartilage formation, mainly because TGF-β1 could induce the mBMSCs to differentiate into chondrocytes and osteoblasts. Consequently, the current study can achieve cartilage repair, and COL/CS/0.5SF-TPHNs scaffolds are expected to be potential composites for cartilage tissue engineering.

Background Motoric cognitive risk syndrome (MCR) is a newly proposed predementia syndrome incorporating subjective cognitive complaints and slow gait. Previous studies have reported that subjective cognitive complaints and slow gait are associated with frailty in cognitively unimpaired older adults, but little is known about the link between MCR and frailty in older adults. Therefore, the aim of the study was to explore the associations of MCR and its components with frailty in older Chinese adults. Methods In an observational cross-sectional study, a total of 429 older adults aged 60 years and older were admitted to the geriatric department. According to MCR criteria, all participants were classified into 4 groups: 1) the MCR group; 2) the subjective cognitive complaints only group; 3) the slow gait only group; and 4) the healthy control group. Physical frailty was assessed by the Clinical Frailty Scale (CFS). Multivariate logistic regression analysis was used to examine the association between MCR and frailty in older adults. Results The prevalence rates of subjective cognitive complaints, slow gait and MCR were 15.9, 10.0 and 4.0%, respectively. After adjusting for confounding variables, the logistic regression analysis showed that slow gait (odds ratio [OR]: 3.40, 95% confidence interval [CI]: 1.40–8.23, P = 0.007) and MCR (OR: 5.53, 95% CI: 1.46–20.89, P = 0.012) were independently associated with frailty, but subjective cognitive complaints were not. Conclusions MCR and slow gait were significantly associated with frailty in older Chinese adults. Further studies should prospectively determine the causal relationship between MCR and frailty.

Purpose The study aimed to investigate the association between body composition and frailty in elder inpatients. Patients and Methods This is a cross-sectional study including 656 elder inpatients (275 females and 381 males) aged ≥65 years, from department of geriatrics of Zhejiang Hospital between January 2018 and March 2019. Sociodemographic, health-related data and anthropometric measurements were evaluated. Body composition was assessed by bioimpedance analysis (BIA), mainly including skeletal muscle mass, body fat mass, total body water, fat-free mass,percent body fat, basal metabolic rate. Frailty was assessed by Clinical Frailty Scale (CFS). Univariate logistic regression was used to analyze the association between body composition and frailty. Results Frailty was present in 43.9% of the participants. Frail inpatients showed higher waist circumference, body fat mass and percent body fat, non-frail inpatients showed greater upper arm circumference, calf circumference, skeletal muscle mass, total body water, fat-free mass and basal metabolic rate. Subjects with underweight (body mass index (BMI)

Increasing the forest's productivity is a global concern and there is a need to develop innovative technologies. The use of biochar (BC) in the restoration of degraded sites is mounting. Therefore,...

Context: The relationship between resveratrol and histone acetylation in renal cell carcinoma (RCC) has not yet been reported. Objective: To explore the functional role of resveratrol in RCC. Materials and methods: Functional experiments were performed to determine proliferatio n of ACHN cells with treatment of resveratrol (0, 7.8125, 15.625, 31.25 and 62.5 μg/mL, for 12, 24 and 48 h of culture) or 0.1 μM SAHA. The enzyme activities of MMP-2/-9 were measured by gelatine zymography and histone acetylation by Western blot. Results: When the cells were treated with 15.625, 31.25 and 62.5 μg/mL resveratrol, ACHN cells viability was 73.2 ± 3.5%, 61.4 ± 3.1%, 50.2 ± 4.7% for 12 h, 62.7 ± 4.5%, 52.4 ± 5.5%, 40.2 ± 3.8% for 24 h, and 60.8 ± 3.7%, 39.4 ± 5.1%, 37.6 ± 2.7% for 48 h, and the wound closure (%) of migration was increased from 0.6 to 0.7, 0.85, 0.9 for 12 h and from 0.23 to 0.3, 0.48, 0.59 for 24 h. The invasion rate was 8.5 ± 0.9%, 7.4 ± 0.3% and 5.8 ± 0.6%, and cell cycle was arrested at G1 from 42.5 ± 2.9% to 55.3 ± 5.7%, 59.8 ± 3.4%, 68.7 ± 4.6%. MMP-2/-9 expression (p

Dendrocalamus latiflorus Munro is a woody clumping bamboo with rapid shoot growth. Both genetic transformation and clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) gene editing techniques are available for D. latiflorus, enabling reverse genetic approaches. Thus, D. latiflorus has the potential to be a model bamboo species. However, the genome sequence of D. latiflorus has remained unreported due to its polyploidy and large genome size. Here, we sequenced the D. latiflorus genome and assembled it into three allele-aware subgenomes (AABBCC), representing the largest genome of a major bamboo species. We assembled 70 allelic chromosomes (2, 737 Mb) for hexaploid D. latiflorus using both single-molecule sequencing from the Pacific Biosciences (PacBio) Sequel platform and chromosome conformation capture sequencing (Hi-C). Repetitive sequences comprised 52.65% of the D. latiflorus genome. We annotated 135 231 protein-coding genes in the genome based on transcriptomes from eight different tissues. Transcriptome sequencing using RNA-Seq and PacBio single-molecule real-time long-read isoform sequencing revealed highly differential alternative splicing (AS) between non-abortive and abortive shoots, suggesting that AS regulates the abortion rate of bamboo shoots. This high-quality hexaploid genome and comprehensive strand-specific transcriptome datasets for this Poaceae family member will pave the way for bamboo research using D. latiflorus as a model species.

Proteins are the effector molecules of biology and are the target of most drugs. To identify proteins and related pathways that may play a causal role in stroke pathogenesis, we used Mendelian randomisation (MR). We tested potential causal effects of 308 plasma proteins (measured in 4,994 blood donors from the INTERVAL study) on stroke outcomes (derived from the MEGASTROKE GWAS) in a two-sample MR framework and assessed whether these associations could be mediated by cardiovascular risk factors. We extended the analysis to identify whether pharmacological targeting of these proteins might have potential adverse side-effects or beneficial effects for other conditions through Phenome-wide MR (Phe-MR) in UK Biobank. MR showed an association between stroke and genetically predicted plasma levels of TFPI, IL6RA, MMP12, CD40, TMPRSS5 and CD6 (P≤1.62⋅10−4). We identified six risk factors (atrial fibrillation, body mass index, smoking, blood pressure, white matter hyperintensities and type 2 diabetes) that were associated with stroke (P≤0.0071) using MR. The association of TFPI, IL6RA and TMPRSS5 with stroke could be mediated by these risk factors, such as body mass index, white matter hyperintensity and atrial fibrillation. Thirty-six additional proteins were potentially causal for one or more of these risk factors. The Phe-MR suggested that targeting TFPI could have potential beneficial effects on other disorders of arteries and hyperlipidaemia in addition to stroke. Our results highlight novel causal pathways and potential therapeutic targets for stroke.

Proteins are the effector molecules of biology and are the target of most drugs. To identify proteins and related pathways that may play a causal role in stroke pathogenesis, we used Mendelian randomisation (MR). We tested potential causal effects of 308 plasma proteins (measured in 4,994 blood donors from the INTERVAL study) on stroke outcomes (derived from the MEGASTROKE GWAS) in a two-sample MR framework and assessed whether these associations could be mediated by cardiovascular risk factors. We extended the analysis to identify whether pharmacological targeting of these proteins might have potential adverse side-effects or beneficial effects for other conditions through Phenome-wide MR (Phe-MR) in UK Biobank.MR showed an association between stroke and genetically predicted plasma levels of TFPI, IL6RA, MMP12, CD40, TMPRSS5 and CD6 (P≤1.62×10−4). We identified six risk factors (atrial fibrillation, body mass index, smoking, blood pressure, white matter hyperintensities and type 2 diabetes) that were associated with stroke (P≤0.0071) using MR. The association of TFPI, IL6RA and TMPRSS5 with stroke could be mediated by these risk factors, such as body mass index, white matter hyperintensity and atrial fibrillation. Thirty-six additional proteins were potentially causal for one or more of these risk factors. The Phe-MR suggested that targeting TFPI could have potential beneficial effects on other disorders of arteries and hyperlipidaemia in addition to stroke. Our results highlight novel causal pathways and potential therapeutic targets for stroke.

Gastric cancer is a heterogeneous group of diseases with only a fraction of patients responds to immunotherapy. The relationships between tumor DNA damage response, the immune system and immunotherapy have recently attracted attention. Accumulating evidence indicate that DNA repair landscape is a significant factor in driving response to immune checkpoint blockade (ICB) therapy. In this study, to explore new prognostic and predictive biomarkers for gastric cancer patients who are sensitive and responsible to immunotherapy, we developed a novel 15-DNA repair gene signature (DRGS) and its related scoring system and evaluated the efficiency of DRGS in discriminating different molecular and immune characteristics and therapeutic outcomes of gastric adenocarcinoma. The results showed that DRGS high score patients showed significantly better therapeutic outcomes compared to DRGS low score patients (P < 0.001). Integrated analysis of multi-omics data demonstrated that the patients with high DRGS score were characteristic of high levels of anti-tumor lymphocytes infiltration, tumor mutation burden (TMB) and PD-L1 expression, and these patients exhibited a longer overall survival and may benefit more from ICB therapy, as compared to the low-score patients. Therefore, the DRGS and its scoring system may have implications in tailoring immunotherapy in gastric cancers.

Aberrant signaling of EGFR (ErbB) family members, in particular epidermal growth factor receptor (EGFR) and human epidermal growth factor 2 (HER2), is associated with the occurrence and development of many types of human malignancies (e.g., breast, lung, and gastric cancers), and dual targeting of EGFR/HER2 by small-molecular inhibitors has proven to be an effective therapeutic approach for treating these cancers. Herein we extracted and isolated from the medicinal plant Sophora alopecuroides L. a new natural product, dubbed Cytisine N-methylene-(4',7-dihydroxy-3'-methoxy)-isoflavone (CNI1) that features a unique molecular framework. Our biochemical kinase assay suggested that one of its derivative CNI3 exhibited the best, micromolar (μM) inhibition activities against the EGFR (IC

This study evaluated the effects of different light spectra (white light, WL, blue light, BL and red light, RL) on the root morphological traits and metabolites accumulation and biosynthesis in Sarcandra glabra. We performed transcriptomic and metabolomic profiling by RNA-seq and ultra-performance liquid chromatography−electrospray ionization−tandem mass spectrometry (UPLC-ESI-MS/MS), respectively. When morphological features were compared to WL, BL substantially increased under-ground fresh weight, root length, root surface area, and root volume, while RL inhibited these indices. A total of 433 metabolites were identified, of which 40, 18, and 68 compounds differentially accumulated in roots under WL (WG) vs. roots under BL (BG), WG vs. roots under RL (RG), and RG vs. BG, respectively. In addition, the contents of sinapyl alcohol, sinapic acid, fraxetin, and 6-methylcoumarin decreased significantly in BG and RG. In contrast, chlorogenic acid, rosmarinyl glucoside, quercitrin and quercetin were increased considerably in BG. Furthermore, the contents of eight terpenoids compounds significantly reduced in BG. Following transcriptomic profiling, several key genes related to biosynthesis of phenylpropanoid-derived and terpenoids metabolites were differentially expressed, such as caffeic acid 3-O-methyltransferase) (COMT), hydroxycinnamoyl-CoA shikimate hydroxycinnamoyl transferase (HCT), O-methyltransferase (OMT), and 1-deoxy-D-xylulose-5-phosphate synthetase (DXS). In summary, our findings showed that BL was suitable for growth and accumulation of bioactive metabolites in root tissue of S. glabra. Exposure to a higher ratio of BL might have the potential to improve the production and quality of S. glabra seedlings, but this needs to be confirmed further.

Angiotensin-converting enzyme 2 (ACE2) is known as a host cell receptor for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which is identified to be dysregulated in multiple tumors. Although the characterization of abnormal ACE2 expression in malignancies has been preliminarily explored, in-depth analysis of ACE2 in breast cancer (BRCA) has not been elucidated. A systematic pan-cancer analysis was conducted to assess the expression pattern and immunological role of ACE2 based on RNA-sequencing (RNA-seq) data downloaded from The Cancer Genome Atlas (TCGA). Next, correlations between ACE2 expression immunological characteristics in the BRCA tumor microenvironment (TME) were evaluated. Also, the role of ACE2 in predicting the clinical features and the response to therapeutic options in BRCA was estimated. These findings were subsequently validated in another public transcriptomic cohort as well as a recruited cohort. ACE2 was lowly expressed in most cancers compared with adjacent tissues. ACE2 was positively correlated with immunomodulators, tumor-infiltrating immune cells (TIICs), cancer immunity cycles, immune checkpoints, and tumor mutation burden (TMB). Besides, high ACE2 levels indicated the triple-negative breast cancer (TNBC) subtype of BRCA, lower response to endocrine therapy and higher response to chemotherapy, anti-ERBB therapy, antiangiogenic therapy and immunotherapy. To sum up, ACE2 correlates with an inflamed TME and identifies immuno-hot tumors, which may be used as an auxiliary biomarker for the identification of immunological characteristics in BRCA.

Introduction: Intestinal microbiota affects human health and aging. The composition of intestinal microbiota and inflammation indices in elderly Chinese, especially centenarians, is unclear. Objective: This study aimed to explore the relationships between intestinal microbiota and inflammation in healthy housebound elders in Shanghai, China. Methods: We enrolled 156 differently aged adults and assigned them into 4 groups: those aged 35–64 years were assigned into Group AD; 65–79 years into Group YO; 80–94 years into Group MO; and 95–102 years into Group VO. Results: The diversity of intestinal microbiota in Group VO was significantly reduced compared with that of the other 3 groups. Bacteroidetes abundance in Group VO was significantly lower than that in Groups AD, YO, or MO; Proteobacteria abundance showed the opposite trend. Akkermansia, Bifidobacterium, and Lactobacillus abundance in Group VO was significantly higher than that in the other 3 groups; Anaerostipes, Butyricicoccus, and Faecalibacterium abundance showed the opposite trend. Solobacterium abundance in Group VO was significantly lower than that in the other 3 groups; Campylobacter, Porphyromonas, Escherichia, and Pseudomonas abundance showed the opposite trend. Plasma levels of tumor necrosis factor-α (TNF-α), IL-6, and IL-8 in Group VO were significantly higher than those in Groups AD, YO, and MO, while those in Group MO were significantly higher than those in Groups AD and YO. IL-1β and IL-10 plasma levels were not significantly different among the 4 groups. Proteobacteria abundance was positively correlated with TNF-α and IL-8 levels, while Campylobacter abundance was positively correlated with those of TNF-α and IL-6. Anaerostipes and Faecalibacterium abundance was negatively correlated with TNF-α and IL-6 levels. Conclusions: The diversity of intestinal microbiota in the oldest participants (centenarians) decreased significantly, with several beneficial bacterial strains showing increased or decreased abundance; harmful bacterial species showed a similar trend. Our oldest participants (centenarians) demonstrated significantly increased levels of pro-inflammatory cytokines, which may be related to inflammaging.

Branch patterns play a key role in assessing plant architecture and are adapted to forest ecosystems. The study aimed to reveal the pattern of branch traits at various distances and orientations from the seashore. For that reason, four sites with various distances from the seashore (SP1: 50–60 m, SP2: 60–100 m, SP3: 100–200 m, and SP4: 200–800 m) were selected and branch traits of Dendrocalamus minor var. amoenus were determined in Dongshan Island, China. The results showed that there were differences in the branch traits between both the 1st-order and 2nd-order branches, and distance from seashore had a significant impact on branch angle, length, diameter, and the number of leaves of 1st-order branches, whereas branch diameter, length, and the number of leaves of 2nd-order branches. In different orientations, the branch angle, length, number, and diameters of the 1st-order and 2nd-order branches showed no significant differences. Nonetheless, the number of leaves of the 1st-order branches were significantly influenced by different orientations. D. minor var. amoenus exhibited strong phenotypic plasticity with longer branches and formed a sparse crown shape. It adjusted the fractal dimension of the crown and branches by modulating the allometric growth relationships among branching traits to adapt to harsh coastal pressure. This study would provide valuable recommendations for D. minor var. amoenus as windbreaks in the coastal climate.

Xiufang Hong,1,2 Jing Yan,1 Liyu Xu,1 Shanshan Shen,1 Xingkun Zeng,1 Lingyan Chen1 1Department of Geriatrics, Zhejiang Hospital, Hangzhou 310013, People’s Republic of China; 2The Second School of Medicine, Zhejiang Chinese Medical University, Hangzhou 310053, People’s Republic of China Objective: The definition of frailty still lacks quantitative biomarkers. This study aimed to investigate the relationship between nutrition-related biomarkers and frailty in hospitalized older patients.Materials and methods: This is a cross-sectional study including 380 hospitalized older patients. The patients were categorized as nonfrail (n=140), prefrail (n=81), and frail (n=159) by the criteria of frailty phenotype. The nutritional status was assessed using the mini nutritional assessment-short form (MNA-SF), levels of serum transferrin (TNF), prealbumin (PA), total protein (TP), albumin (ALB), retinol-binding protein (RBP), and hemoglobin (Hb).Results: The grip strength, levels of serum TFN, TP, ALB, Hb, and MNA-SF scores all decreased significantly in the order of nonfrail, prefrail, and frail groups (P

The calcium hydrides and lanthanum hydrides under high pressures have been reported to have good superconducting properties with high-T C. In this work, the structures and superconductivities of Ca–La–H ternary hydrides have been studied by genetic algorithm and density functional theory calculations. Our results show that at the pressure range of 100–300 GPa, the most stable structure of CaLaH12 has a Cmmm symmetry, in which there is a H24 hydrogen cage. It can be expected to have high possibility to be synthesized due to its large stability. Furthermore, the predicted T C of the Cmmm-CaLaH12 structure is about 140 K at 150 GPa, and when the pressure decreases to 30 GPa, the CaLaH12 structure with a C2/m symmetry has a predicted T C of about 49 K. The CaLaH12 is suggested to be a stable good superconductor with large stability and performs well at relatively low pressures.

Stigma is a key determinant of mental health among patients with epilepsy (PWE). In prior work, many PWE have been found to exhibit impaired executive function (EF) and to lack sufficient social support. This study was developed to explore factors that may influence stigma in PWE with a focus on the associations among EF, social support, and stigma in this patient population.A questionnaire was administered to 121 patients with primary epilepsy as a means of collecting clinical and demographic details. The severity of EF impairment, social support levels, and stigma were analyzed using the Behavior Rating Inventory of Executive Function-Adult (BRIEF-A), the Social Support Rating Scale, and the Kilifi Stigma Scale for Epilepsy-Chinese (KSSE-C). Descriptive analyses were used to evaluate demographic details, and parameters associated with stigma were identified through multiple linear stepwise analyses. Spearman's correlation analyses and moderated mediation analyses were utilized to examine relationships between impaired EF, social support, and stigma. Significant mediation effects were identified using the SPSS PROCESS macro via a bootstrap approach.Up to 95.9% of the 121 PWE in this study were affected by stigma, with differneces in stigma being associated with long-term residence (urban or rural), family monthly income, disease control status (controlled or uncontrolled), and medication types. Multiple stepwise linear regression analyses revealed that the number of years of education (t = - 4.58, P 0.001), family monthly income per capita (t = -3.43, P = 0.001), and age of first episode (t = -2.71, P = 0.008) for PWE were negatively correlated with stigma scores, while long-term residence (t = 2.79, P = 0.006), course of disease (t = 3.65, P 0.001), disease control (t = 2.79, P = 0.006), and types of medication (t = 2.73, P = 0.007) were positively correlated with stigma scores. Impaired EF was found to be significantly associated with stigma (β = 0.64, P 0.001), and social support was able to mediate the association between stigma and impaired EF (β = 0.64, P 0.001). Non-parametric bootstrap analysis results revealed the indirect impact of EF through social support (95% bootstrap CI = 0.11, 0.22), with the indirect influence of social support accounting for 44.3% of the overall effect of stigma.These results offer new insight into the interactive mechanisms that underlie stigma and EF, in addition to clarifying the ability of social support to mediate this relationship. These data thus highlight valuable theoretical and methodological approaches to preventing stigma in PWE, suggesting that stigma in PWE can be effectively reduced by bolstering EF, and social support plays a mediating effect in this context.

Background Previous studies have presented skeletal muscle loss was associated with diabetes mellitus (DM) and non-alcoholic fatty liver disease (NAFLD). However, whether the presence of NAFLD could influence the association between skeletal muscle mass and DM was still unknown. The aim of the present study was to investigate the relationship of skeletal muscle mass with diabetes in Chinese middle-aged and older community population, and whether the association could be effected by NAFLD. Methods A cross-sectional study of 5,626 residents aged 45 and above in Changfeng community in Shanghai were conducted. Skeletal muscle mass (SMM) was detected by dual-energy X ray absorption (DXA) and calculated as ASM% [appendicular skeletal muscle mass (ASM) (kg) /body weight*100%]. Liver fat content (LFC) was measured using a quantitative ultrasound method. Multivariate logistic regression analyses were conducted to investigate the association between ASM% quartiles with DM. Results With ASM% decreasing, fasting blood glucose (FBG), 2-hour postprandial blood glucose (2hBG) and Homeostasis model assessment for insulin resistance (HOMA-IR) as well as LFC increased in both genders, and the prevalence of diabetes and NAFLD also increased. Spearman analysis showed ASM% was negatively correlated with FBG, 2hBG and LFC. Stepwise logistic regression analysis showed after multiple adjustments, ASM% quartile was negatively associated with the risk of diabetes only in male, but not in female. Subgroup analysis found the ASM% quartiles remained negatively correlated with the risk of diabetes in male non-NAFLD population, but not in NAFLD population. When stratified by LFC quartiles, the results was similar. After multivariate adjustments, low ASM% was negatively correlated with the risk of diabetes only in the first and second LFC quartile in male, and the association remained insignificant in each LFC quartile in female. Conclusions Skeletal muscle mass was negatively associated with the risk of diabetes in male population but not in female. The presence of NAFLD weakened this association. The results suggested stratified management of diabetes should be considered according to skeletal muscle mass and the presence of NAFLD.