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SummaryOsteosarcopenia is defined as the concomitant occurrence of sarcopenia and osteoporosis/osteopenia. This study aimed to clarify whether osteosarcopenia implies a greater risk of fractures, mortality, and falls and to draw attention to osteosarcopenia.IntroductionOsteosarcopenia, which is characterized by the co-existence of osteoporosis/osteopenia and sarcopenia, is one of the most challenging geriatric syndromes. However, the association between osteosarcopenia and the risk of falls, fractures, disability, and mortality is controversial.MethodsWe searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials, from their inception to March 18, 2021, for cohort studies on the relationship between osteosarcopenia and fractures, falls, and mortality. Two reviewers independently extracted data and assessed study quality. A pooled analysis was performed to calculate odds ratios (ORs) and 95% confidence intervals (CIs) using fixed or random-effects models.ResultsEight cohort studies including 19,836 participants showed that osteosarcopenia significantly increased the risk of fracture (OR 2.46, 95% CI 1.83–3.30, Pheterogeneity = 0.006, I2 = 63.0%), three cohort studies involving 2601 participants indicated that osteosarcopenia significantly increased the risk of mortality (OR 1.66, 95% CI 1.23–2.26, Pheterogeneity = 0.214, I2 = 35.2%), and three cohort studies involving 3144 participants indicated that osteosarcopenia significantly increased the risk of falls (OR 1.62, 95% CI 1.28–2.04, Pheterogeneity = 0.219, I2 = 34.1%). No publication bias existed among the studies regarding the association between osteosarcopenia and fractures. The findings were robust according to the subgroup and sensitivity analyses.ConclusionsThis pooled analysis demonstrated that osteosarcopenia significantly increased the risk of fractures, falls, and mortality, thus highlighting its relevance in daily life. Therefore, we suggest that elderly persons should be aware of the risks associated with osteosarcopenia.

The pentatelluridesZrTe5andHfTe5are layered compounds with one-dimensional transition-metal chains that show a not-yet-understood temperature-dependent transition in transport properties as well as recently discovered properties suggesting topological semimetallic behavior. Here, we report magnetotransport properties for two kinds ofZrTe5single crystals grown with the chemical vapor transport (CVT) and the flux method (Flux), respectively. They show distinct transport properties at zero field: The CVT crystal displays a metallic behavior with a pronounced resistance peak and a sudden sign reversal in thermopower at approximately 130 K, consistent with previous observations of the electronic transition; in striking contrast, the Flux crystal exhibits a semiconducting-like behavior at low temperatures and a positive thermopower over the whole temperature range. For both samples, strong effects on the transport properties are observed when the magnetic field is applied along the orthorhombicbandcaxes, i.e., perpendicular to the chain direction. Refinements on the single-crystal x-ray diffraction and the measurements of energy dispersive spectroscopy reveal the presence of noticeable Te vacancies in the CVT samples, while the Flux samples are close to the stoichiometry. Analyses on the magnetotransport properties confirm that the carrier densities of the CVT sample are about two orders higher than those of the Flux sample. Our results thus indicate that the widely observed anomalous transport behaviors in pentatellurides actually take place in the Te-deficient samples. For the stoichiometric pentatellurides, our electronic structure calculations show narrow-gap semiconducting behavior, with different transport anisotropies for holes and electrons. For the degenerately dopedn-type samples, our transport calculations can result in a resistivity peak and crossover in thermopower from negative to positive at temperatures close to those observed experimentally due to a combination of bipolar effects and different anisotropies of electrons and holes. Our present work resolves the long-standing puzzle regarding the anomalous transport behaviors of pentatellurides, as well as the electronic structure in favor of a semiconducting state.

Over the past few decades, understandings and evidences concerning the role of endoplasmic reticulum (ER) stress in deciding the cell fate have been constantly growing. Generally, during ER stress, the signal transductions are mainly conducted by three ER stress transducers: protein kinase R-like endoplasmic reticulum kinase (PERK), inositol-requiring kinase 1 (IRE1) and activating transcription factor 6 (ATF6). Consequently, the harmful stimuli from the ER stress transducers induce apoptosis and autophagy, which share several crosstalks and eventually decide the cell fate. The dominance of apoptosis or autophagy induced by ER stress depends on the type and degree of the stimuli. When ER stress is too severe and prolonged, apoptosis is induced to eliminate the damaged cells; however, when stimuli are mild, cell survival is promoted to maintain normal physiological functions by inducing autophagy. Although all the three pathways participate in ER stress-induced apoptosis and autophagy, PERK shows several unique characteristics by interacting with some specific downstream effectors. Notably, there are some preliminary findings on PERK-dependent mechanisms switching autophagy and apoptosis. In this review, we particularly focused on the novel, intriguing and complicated role of PERK in ER stress-decided cell fate, and also discussed more roles of PERK in restoring cellular homeostasis. However, more in-depth knowledge of PERK in the future would facilitate our understanding about many human diseases and benefit in searching for new molecular therapeutic targets.

The time-resolved magneto-optical (MO) Voigt effect can be utilized to study the Néel order dynamics in antiferromagnetic (AFM) materials, but it has been limited for collinear AFM spin configuration. Here, we have demonstrated that in Mn 3 Sn with an inverse triangular spin structure, the quench of AFM order by ultrafast laser pulses can result in a large Voigt effect modulation. The modulated Voigt angle is significantly larger than the polarization rotation due to the crystal-structure related linear dichroism effect and the modulated MO Kerr angle arising from the ferroic ordering of cluster magnetic octupole. The AFM order quench time shows negligible change with increasing temperature approaching the Néel temperature ( T N ), in markedly contrast with the pronounced slowing-down demagnetization typically observed in conventional magnetic materials. This atypical behavior can be explained by the influence of weakened Dzyaloshinskii–Moriya interaction rather than the smaller exchange splitting on the diminished AFM order near T N . The temperature-insensitive ultrafast spin manipulation can pave the way for high-speed spintronic devices either working at a wide range of temperature or demanding spin switching near T N . Mn3Sn is an anti-ferromagnetic material which displays a large magneto-optical Kerr effect, despite lacking a ferromagnetic moment. Here, the authors show that likewise, Mn3Sn, also presents a particularly large magneto-optical Voigt signal, with a negligible change in the quench time over a wide temperature range.

Vitrification from physical vapor deposition is known to be an efficient way for tuning the kinetic and thermodynamic stability of glasses and significantly improve their properties. There is a general consensus that preparing stable glasses requires the use of high substrate temperatures close to the glass transition one, T g . Here, we challenge this empirical rule by showing the formation of Zr-based ultrastable metallic glasses (MGs) at room temperature, i.e., with a substrate temperature of only 0.43 T g . By carefully controlling the deposition rate, we can improve the stability of the obtained glasses to higher values. In contrast to conventional quenched glasses, the ultrastable MGs exhibit a large increase of T g of ∼60 K, stronger resistance against crystallization, and more homogeneous structure with less order at longer distances. Our study circumvents the limitation of substrate temperature for developing ultrastable glasses, and provides deeper insight into glasses stability and their surface dynamics. Producing ultrastable metallic glasses has always been associated with substrates heated close to the glass transition temperature. Here, the authors show that reducing the deposition rate of the metallic glass on a cold substrate produces ultrastable metallic glasses with remarkably improved stability.

The association between cognitive function and cholesterol levels is poorly understood and inconsistent results exist among the elderly. The purpose of this study is to investigate the association of cholesterol level with cognitive performance among Chinese elderly. A cross-sectional study was implemented in 2012 and data were analyzed using generalized additive models, linear regression models and logistic regression models. Community-based setting in eight longevity areas in China. A total of 2000 elderly aged 65 years and over (mean 85.8±12.0 years) participated in this study. Total cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C) concentration were determined and cognitive impairment was defined as Mini-Mental State Examination (MMSE) score≤23. There was a significant positive linear association between TC, TG, LDL-C, HDL-C and MMSE score in linear regression models. Each 1 mmol/L increase in TC, TG, LDL-C and HDL-C corresponded to a decreased risk of cognitive impairment in logistic regression models. Compared with the lowest tertile, the highest tertile of TC, LDL-C and HDL-C had a lower risk of cognitive impairment. The adjusted odds ratios and 95% CI were 0.73(0.62–0.84) for TC, 0.81(0.70–0.94) for LDL-C and 0.81(0.70–0.94) for HDL-C. There was no gender difference in the protective effects of high TC and LDL-C levels on cognitive impairment. However, for high HDL-C levels the effect was only observed in women. High TC, LDL-C and HDL-C levels were associated with lower risk of cognitive impairment in the oldest old (aged 80 and older), but not in the younger elderly (aged 65 to 79 years). These findings suggest that cholesterol levels within the high normal range are associated with better cognitive performance in Chinese elderly, specifically in the oldest old. With further validation, low cholesterol may serve a clinical indicator of risk for cognitive impairment in the elderly.

Current reports refer to the role of long noncoding RNA (lncRNA) prostate androgen-regulated transcript 1 (PART1) as a tumor suppressor in some types of cancer but as an oncogene in other kinds of cancer. In gastric cancer, it had been reported to be downregulated. However, the clinical significance and underlying mechanism of PART1 function in gastric cancer remains undefined. Here, seven differential expression levels of noncoding RNAs (DE-lncRNAs) were screened from gastric cancer through a probe reannotation of a human exon array. PART1 was selected for further study because of its high fold change number. In our cohort, PART1 was identified as a significant downregulated lncRNA in gastric cancer tissues by qPCR and in situ hybridization (ISH), and its low expression was significantly correlated with postoperative metastasis and short overall survival time after surgery. Through the results of gain-of-function experiments, PART1 was confirmed as a tumor suppressor that can decrease not only cell viability, migration, and invasion in vitro but also tumorigenesis and tumor metastasis in vivo. Mechanistically, RNA pull-down and RNA-binding protein immunoprecipitation (RIP) showed that PART1 interacts with androgen receptor (AR), and then, promyelocytic leukemia zinc finger (PLZF) is upregulated in an androgen-independent manner. In a chain reaction, chromatin immunoprecipitation (ChIP) assay additionally illustrated that PLZF upregulation increased the enrichment of EZH2 and H3K27 trimethylation in the platelet-derived growth factor (PDGFB) promotor, thereby inhibition of PDGFB and the subsequent PDGFRβ/PI3K/Akt signaling pathway. Based on these findings, we showed PART1 plays a tumor suppressor role by promoting PLZF expression followed by recruitment of EZH2 to mediate epigenetic PDGFB silencing and downstream PI3K/Akt inhibition, suggesting that PART1 has a key role in restraining the aggressive ability of GC cells and providing a novel perspective on lncRNAs in GC progression.

Purpose Hiatal hernia is renowned for the symptom of reflux, and few physicians associate a hiatal hernia with pulmonary issues. It is widely acknowledged that a hiatal hernia can be treated with surgery. However, less is known about how the surgical procedure would benefit pulmonary function. Thus, the aim of this study was to determine whether surgical repair can improve pulmonary function in patients with hiatal hernias. Methods We registered the protocol on the PROSPERO (International Prospective Register of Systematic Reviews) platform (no. CRD42022369949). We searched the PubMed, Embase, Cochrane Library, and ClinicalTrials.gov databases for cohort studies that reported on the pulmonary function of patients with hiatal hernias. The quality of each cohort study was evaluated using the Newcastle–Ottawa scale (NOS). We then calculated mean differences (MDs) with 95% confidence intervals for these continuous outcomes. Each study’s consistency was appraised using the I 2 statistic. The sensitivity analysis was performed using the trim-and-fill method. Publication bias was confirmed using the funnel plot visually and Egger regression test statistically. Results A total of 262 patients from 5 cohorts were included in the meta-analysis. The quality evaluation revealed that, of these 5 papers, 3 received 8 NOS stars out of 9 stars, 1 received 9, and the other received 7, meaning all included cohort studies were of high quality. The results showed that surgical repair for a hiatal hernia significantly improved forced expiratory volume in 1 s (FEV1; weighted mean difference [WMD]:0.200; 95% CI 0.047–0.353; I 2  = 71.6%; P  = 0.010), forced vital capacity (FVC; WMD: 0.242; 95% CI 0.161–0.323; I 2  = 7.1%; P  = 0.000), and total lung capacity (TLC; WMD: 0.223; 95% CI 0.098–0.348; I 2  = 0.0%; P  = 0.000) but had little effect on residual volume (RV; WMD: –0.028; 95% CI –0.096 to 0.039; I 2  = 8.7%; P  = 0.411) and the diffusing capacity carbon monoxide (DLCO; WMD: 0.234; 95% CI –0.486 to 0.953; I 2  = 0.0%; P  = 0.524). Conclusion For individuals with hiatal hernias, surgical repair is an efficient technique to improve respiratory function as measured by FEV1, FVC, and TLC.

Abstract Summary To elucidate the association of coffee and bone health would help fracture risk reduction via dietary intervention. Although those who had higher coffee consumption were less likely to have osteoporosis, the associations between coffee consumption and fracture risk need further investigations with better study designs.IntroductionThe associations between coffee consumption and the risk of osteoporosis and fracture remain inconclusive. We aimed to better quantify these associations by conducting meta-analyses of observational studies.MethodsRelevant studies were systematically searched on PubMed, Web of Science, Cochrane library, and Embase Database up to November 25, 2021. The odds ratio (OR) or relative risk (RR) with 95% confidence intervals (CI) was pooled and a dose–response analysis was performed.ResultsFour studies with 7114 participants for osteoporosis and thirteen studies with 391,956 participants for fracture incidence were included in the meta-analyses. High versus low coffee consumption was associated with a lower risk of osteoporosis [pooled OR (95% CI): 0.79 (0.65–0.92)], while it was non-significantly associated with fracture incidence [pooled OR (95% CI): 0.86 (0.67–1.05) at hip and 0.89 (0.42–1.36) at non-hip]. A non-linear association between the level of coffee consumption and hip fracture incidence was shown (P = 0.004). The pooled RR (95% CI) of hip fracture risk in those who consumed 1, 2–3, 4, and ≥ 9 cups of coffee per day was 0.92 (0.87–0.97), 0.89 (0.83–0.95), 0.91 (0.85–0.98), and 1.10 (0.76–1.59), respectively. The significance in the association between coffee consumption and the hip fracture incidence decreased in those studies that had larger sample size, higher quality, and more adjustments.ConclusionsA dose-dependent relationship may exist between coffee consumption and hip fracture incidence. The effect of high versus low coffee consumption was influenced by study designs. Further studies with dedicated designs are needed to confirm the independent effects of coffee consumption on bone health.

Metastasis significantly reduces the survival rate of osteosarcoma (OS) patients. Therefore, identification of novel targets remains extremely important to prevent metastasis and treat OS. In this report, we show that SPARCL1 is downregulated in OS by epigenetic methylation of promoter DNA. In vitro and in vivo experiments revealed that SPARCL1 inhibits OS metastasis. We further demonstrated that SPARCL1-activated WNT/β-catenin signaling by physical interaction with various frizzled receptors and lipoprotein receptor-related protein 5/6, leading to WNT–receptor complex stabilization. Activation of WNT/β-catenin signaling contributes to the SPARCL1-mediated inhibitory effects on OS metastasis. Furthermore, we uncovered a paracrine effect of SPARCL1 on macrophage recruitment through activated WNT/β-catenin signaling-mediated secretion of chemokine ligand5 from OS cells. These findings suggest that the targeting of SPARCL1 as a new anti-metastatic strategy for OS patients.