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Frailty is a state that is closely associated with adverse health outcomes in the aging process. The frailty index (FI), which measures frailty in terms of cumulative deficits, has been widely used for frailty assessment in elderly people, and its advantage of self-reported information collection makes it applicable to a broader group of elderly people. Our study aims to simplify the Frailty Index Assessment Scale, while maintaining its reliability and accuracy, to easily and quickly assess frailty in elderly people. In this study, participants (age ≥ 65 years) from the Chinese Longitudinal Healthy Longevity Survey (CLHLS), which had 13,339, 372 and 1214 participants in 2008, 2011, and 2014, respectively, were used. The 2008 dataset was split into 80% for training and 20% for internal validation, and the data from 2011 to 2014 as external validation. In order to obtain effective predictors, we used Lasso regression, Boruta algorithm and random forest classifier score for feature selection. We used six models for predictive model construction and evaluated the models in the validation dataset. Model performance was measured by area under the curve (AUC), accuracy and F1 score. Logistic regression was found to be the best performing and most interpretable algorithm with AUC, accuracy and F1 of 0.974, 0.932 and 0.880 for the validation dataset, respectively. The AUCs for the external independent validation dataset were 0.963 and 0.977, respectively. Subgroup analysis showed that the model had good predictive power in both males and females. The predictive power was stronger among the elderly people over 80 years old, with AUC, accuracy and F1 of 0.973,0.914, and 0.893, respectively. The model also obtained good predictive power in the case of FI measured by different indicators. The model showed good robustness in the follow-up assessment of frailty status in elderly people, with the AUC remaining above 0.95 and accuracy above 0.9 over the long-term follow-up. Using machine learning techniques, we have successfully developed a simple frailty assessment prediction model based on 10 key features to shorten the frailty assessment scale with near full-scale accuracy. A user-friendly website was created to facilitate the application of this prediction model ( https://healthy-aging.shinyapps.io/Frailty_Assessment/ ).

A series of physiological and pathological changes occur after radiotherapy and accidental exposure to ionizing radiation (IR). These changes cause serious damage to human tissues and can lead to death. Radioprotective countermeasures are radioprotective agents that prevent and reduce IR injury or have therapeutic effects. Based on a good understanding of radiobiology, a number of protective agents have achieved positive results in early clinical trials. The present review grouped known radioprotective agents according to biochemical categories and potential clinical use, and reviewed radiation countermeasures, i.e., radioprotectors, radiation mitigators and radiotherapeutic agents, with an emphasis on their current status and research progress. The aim of the present review is to facilitate the selection and application of suitable radioprotectors for clinicians and researchers, to prevent or reduce IR injury.

Background Optical coherence tomography angiography (OCTA), an innovative image technique, renders visualization of ocular neovascularization through non-invasive means, which has been applied in recent years. Therefore, the present study was designed to assess the diagnostic value of OCTA in detecting the choroidal neovascularization (CNV). Methods In brief, PubMed, Web of Science and Cochrane Library databases were systematically searched from January 2014 to June 2019. Afterwards, a meta-analysis was performed to determine the pooled diagnostic accuracy in a random-effects model using STATA 15.1 and Meta-Disc 1.4 software. Quality Assessment of diagnostic Accuracy Version 2 was used to evaluate the risk of bias of each study by Revman 5.3 software. In addition, a meta-regression model was further conducted to explore potential sources of heterogeneity. Results According to pre-set inclusion and exclusion criteria, 16 eligible studies were enrolled in this study. A total of 447 CNV eyes and 414 non-CNV eyes were included to investigate the diagnostic accuracy of OCTA. As a result, the pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (PLR), diagnostic odds ratio (DOR) and the area under the summary receiver operating characteristic curve (sROC-AUC) were 0.87 (95% CI 0.81–0.92), 0.97 (95% CI 0.92–0.99), 32.7 (95% CI 10.1–105.5), 0.13 (95% CI 0.08–0.20), 252 (95% CI 63–1011) and 0.96 (95% CI 0.94–0.97), respectively. Conclusions In summary, we demonstrated that OCTA was of high diagnostic value for detecting intraocular CNV.

Background Numerous studies have indicated an obesity paradox in observational research on aging health, where being normal weight or underweight adversely affects cognitive function, while moderate obesity may offer protective benefits. This study aims to investigate the association between body mass index (BMI), waist circumference (WC), hip circumference (HC), waist-to-height ratio (WHtR), waist-to-hip ratio (WHR), abdominal volume index (AVI), and the joint effect of BMI and HC on cognitive impairment in older Chinese people. Methods A total of 10,579 participants aged 65 years and older from the 2018 Chinese Longitudinal Healthy Longevity Survey (CLHLS) were included in this cross-sectional study. BMI, WC, HC, WHtR, WHR, and AVI were calculated from height, weight, WC, and HC measurements, where weight, WC, and HC were obtained by direct measurement. Mini-Mental State Examination was used to assess cognitive impairment. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were estimated using binary logistic regression. Non-linear correlations were investigated using restricted cubic spline curves. Results In multivariate logistic regression models fully adjusted for confounding variables, our analyses showed significant negative associations of WC [OR 0.93 (95%CI 0.88–0.98), P  = .012], HC [OR 0.92 (95%CI 0.87–0.97), P  = .004], lower WHR (Q2) [OR 0.85 (95%CI 0.72-1.00), P  = .044], and AVI [OR 0.93 (95%CI 0.88–0.98), P  = .011] with cognitive impairment. Nonlinear curve analysis showed that the risk of cognitive impairment was lowest when the BMI was about 25.5 kg/m², suggesting that the optimal BMI for older Chinese people to maintain good cognitive ability may be in the overweight range. In addition, there was a non-linear “N” shaped relationship between HC and cognitive impairment, with HC having the highest risk of cognitive impairment at about 82 cm and the lowest risk at about 101 cm. The joint effects analysis indicated that the lowest risk was observed among those with normal or higher BMI but higher HC compared with participants with normal BMI levels and lower HC levels. Conclusion In older Chinese people, a low-waisted and high-hip circumference body figure is favorable for cognitive function in older people. It also found a significant association between AVI and cognitive impairment. The joint analysis of BMI and HC suggests that maintaining a normal or higher BMI with a higher HC may be more conducive to maintaining good cognitive function.

Background Frailty has become an important health problem in the middle-aged and older people population. Physical activity (PA) is a key intervention for frailty prevention and management. However, studies of the association between COVID-19 pre-pandemic PA and the worsening or improvement of frailty during the pandemic remain unclear. Methods This longitudinal cohort study used data from the English Longitudinal Study of Ageing (ELSA), including participants aged 50 and over. Three intensities of PA (vigorous, moderate, and mild) were categorized as less than once per week and at least once per week, respectively, based on participant self-report. The frailty index (FI) assessed the frailty status, defining frailty as FI ≥ 25. Logistic regression was applied to examine the association between PA and frailty, estimating odds ratios (OR) and 95% confidence intervals (95% CI). Results Of the 4379 non-frail participants at baseline (median age 67, 54.9% female), 8.1% developed frailty during a mean follow-up of 3.5 years. Among 564 frail participants at baseline (median age 71, 66.5% female), 17.9% regained health. Compared to those engaging in PA less than once per week, participants who engaged in vigorous (OR: 0.47 [95% CI: 0.35–0.62]), moderate (OR: 0.37 [95% CI: 0.29–0.48]), or mild (OR: 0.38 [95% CI: 0.26–0.56]) PA at least once a week had a lower risk of frailty worsening. Additionally, participants who engaged in moderate (OR: 2.04 [95% CI: 1.29–3.21]) or mild (OR: 2.93 [95% CI: 1.54–5.58]) PA at least once a week had a higher likelihood of frailty improvement. Sensitivity analyses based on comprehensive PA levels confirmed these findings. Participants who maintained at least one PA per week had lower frailty worsening (Vigorous, OR: 0.20 [95%CI: 0.12–0.33]; Moderate, OR: 0.13 [95%CI: 0.09–0.19]; Mild, OR: 0.20 [95%CI: 0.11–0.38]) and higher frailty improvement rates (Moderate, OR: 3.43 [95%CI: 1.93–6.11]; Mild, OR: 4.65 [95%CI: 1.90-11.42]). In addition, individuals (Vigorous, OR: 0.35 [95%CI: 0.20–0.60]; Moderate, OR: 0.36 [95%CI: 0.22–0.56]) who transitioned from inactive to active also exhibited a lower risk of frailty. Conclusions This study emphasized the critical role of PA in preventing and improving frailty in middle-aged and older people, especially during the COVID-19 pandemic. Our study also highlighted the importance of maintaining PA habits to reduce frailty risk and promote its improvement. Also, the study indicated that individuals who transitioned from inactive to active had a lower risk of frailty. These findings enriched the understanding of the association between PA and frailty and provided valuable insights for addressing the health impact of future pandemics on middle-aged and older people.

•This is the first report of the co-administration of CoronaVac with IIV4 in adults aged 18–59 years.•The occurrence of adverse reactions (AR) in all groups was no more than 20% and 98.9% of the ARs were mild or moderate.•Both concomitant or separate administration of CoronaVac and IIV4 could induce sufficient immunogenicity.•A slight interference with the immune response to CoronaVac was observed in participants in C2 subgroup.•At least two doses of CoronaVac are needed to fulfill the primary immunization of inactivated COVID-19 vaccine. Studies are needed for evidence of inactivated COVID-19 vaccine co-administered with influenza vaccine. A randomized, open-label, controlled study was conducted in Zhejiang Province, China. Eligible healthy adults aged 18–59 years underwent randomization at a ratio of 1:1:2 to receive inactivated quadrivalent influenza vaccine (IIV4) either concomitantly with the first (C1 subgroup) or the second (C2 subgroup) dose of CoronaVac, or 14 days after the first dose of CoronaVac (S group). The primary purpose of the study was to prove the non-inferiority in seroconversion rate of antibody against SARS-CoV-2. Overall, 480 participants were enrolled, with 120, 120, and 240 randomly assigned to the C1, C2, and S groups, respectively. As lower bound of the two-sided 95% confidence interval (CI) of the difference for the seroconversion rate of antibodies against SARS-CoV-2 was over −10%, the immune response for CoronaVac in the C group (93.1% [89.0, 96.0]) was non-inferior to that in the S group (95.2% [91.5, 97.6]) in the per-protocol set. A lower GMT of antibody against SARS-CoV-2 was observed in the C group as compared to the S group (27.5 vs. 38.1, P = 0.0001). Decrease of immune response to CoronaVac was mainly observed in participants received IIV4 concomitantly with their second dose of CoronaVac (C2 subgroup), with a seroconversion rate of 89.7% (95CI: 82.6%-94.5%) and a GMT of 23.3. The occurrences of vaccine related adverse reactions were no more than 20% and comparable among different groups. Most of the adverse reactions were mild and moderate. Co-administration of inactivated COVID-19 vaccine and seasonal influenza vaccine, especially the administration regimen that the seasonal influenza vaccine co-administered with the first dose of the inactivated COVID-19 vaccine, would be feasible.

Radiotherapy is one of the main treatment modalities for advanced hepatocellular carcinoma (HCC). Ferroptosis has been shown to promote the radiosensitivity of HCC cells, but it remains unclear whether epigenetic regulations function in this process. In this study, we found that the overexpression of METTL3 was associated with poor prognosis. Knockdown of METTL3 promoted radiosensitivity of HCC by inducing ferroptosis. Mechanistically, METTL3 targeted adenine (+1795) on the SLC7A11 mRNA, and the m 6 A reader IGF2BP2 promoted SLC7A11 mRNA stability by recognizing and binding to the m 6 A site. Additionally, METTL3 decreased the ubiquitination of SLC7A11 protein through the m 6 A/YTHDF2/SOCS2 axis. Furthermore, in vivo studies showed that HCC models with low METTL3/IGF2BP2 expression have higher radiosensitivity. In conclusion, our study suggests that METTL3 regulates the stability of SLC7A11 mRNA in an m 6 A/IGF2BP2-dependent manner and the ubiquitination of SLC7A11 protein through the m 6 A/YTHDF2/SOCS2 pathway, both of which require the m 6 A methyltransferase activity of METTL3. METTL3 or IGF2BP2 may be promising targets for radiotherapy of HCC. Highlights METTL3 contributed to the resistance to radiation by regulating the expression of SLC7A11 in HCC cells. METTL3 maintained the mRNA stability of SLC7A11 in an m 6 A/IGF2BP2-dependent manner, via the binding of IGF2BP2 with the m6A site (+1795) of SLC7A11 mRNA. METTL3 decreased the ubiquitination of SLC7A11 protein through the m 6 A/YTHDF2/SOCS2 axis. Knockdown of METTL3/IGF2BP2 improved the radiosensitivity of HCC.

Background: To estimate the accuracy of one-step nucleic acid amplification (OSNA) assay as an intra-operative sentinel lymph node biopsy (SLNB) for sentinel lymph node (SLN) metastasis in breast cancer. Methods: PubMed, Cochrane Library and Web of Science databases were searched by two independent reviewers to retrieve literature with per-patient analysis. The deadline was up until December 2016. A meta-analysis was performed using STATA, Meta-Disc, and Revman software. A random-effects model was used and subgroup analysis was carried out to identify possible sources of heterogeneity. Results: According to the inclusion criteria, 2833 patients from 12 studies were included in this meta-analysis. The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR) and the area under the sROC curve (AUC) for detecting SLN metastasis were 0.87 (95% CI 0.81–0.91), 0.92 (95% CI 0.86–0.95), 10.65 (95% CI 6.18–18.34), 0.14 (95% CI 0.10–0.20), 75.08 (95% CI 37.77–149.22) and 0.94 (95% CI 0.91–0.95), respectively. Conclusions: The present study adds the evidence that OSNA assay is an accurate molecular diagnostic tool for intra-operatively detecting SLN metastasis in breast cancer. One-step nucleic acid amplification assay might be introduced into clinical usage for replacing traditional intro-operative diagnostic methods of SLNB.

Background Redundancy is a common feature of genomes, presumably to ensure robust growth under different and changing conditions. Genome compaction, removing sequences nonessential for given conditions, provides a novel way to understand the core principles of life. The synthetic chromosome rearrangement and modification by loxP-mediated evolution (SCRaMbLE) system is a unique feature implanted in the synthetic yeast genome (Sc2.0), which is proposed as an effective tool for genome minimization. As the Sc2.0 project is nearing its completion, we have begun to explore the application of the SCRaMbLE system in genome compaction. Results We develop a method termed SCRaMbLE-based genome compaction (SGC) and demonstrate that a synthetic chromosome arm (synXIIL) can be efficiently reduced. The pre-introduced episomal essential gene array significantly enhances the compacting ability of SGC, not only by enabling the deletion of nonessential genes located in essential gene containing loxPsym units but also by allowing more chromosomal sequences to be removed in a single SGC process. Further compaction is achieved through iterative SGC, revealing that at least 39 out of 65 nonessential genes in synXIIL can be removed collectively without affecting cell viability at 30 °C in rich medium. Approximately 40% of the synthetic sequence, encoding 28 genes, is found to be dispensable for cell growth at 30 °C in rich medium and several genes whose functions are needed under specified conditions are identified. Conclusions We develop iterative SGC with the aid of eArray as a generic yet effective tool to compact the synthetic yeast genome.

We identified that overexpression of GCY1, YPR1, PEX5, and MBF1 enhance the vanillin tolerance of Saccharomyces cerevisiae and explored some of the related mechanisms. This provided novel targets that can be used to improve the performance of S. cerevisiae used in 2nd generation fuel ethanol production, and extended our understanding of the proteins encoded by these genes. Summary Exploring the mechanisms of tolerance in microorganisms to vanillin, which is derived from lignin, will benefit the design of robust cell factories that produce biofuels and chemicals using lignocellulosic materials. Our objective was to identify the genes related to vanillin tolerance in Saccharomyces cerevisiae. We investigated the effects on vanillin tolerance of several genes that have site mutations in the highly vanillin‐tolerant strain EMV‐8 compared to its parental line NAN‐27. The results showed that overexpression of GCY1, a gene that encodes an aldo‐keto reductase that also has mRNA‐binding activity, YPR1, a paralog of GCY1 that encodes an aldo‐keto reductase, PEX5, a gene that encodes a peroxisomal membrane signal receptor and MBF1, a gene that encodes a multiprotein bridging factor increase the specific growth rates (μ) by 49%, 41%, 44% and 48 %, respectively, in medium containing 6 mmol l−1 vanillin. Among these gene products, Gcy1p and Ypr1p showed NADPH‐dependent and NAD(P)H‐dependent vanillin reductase activity, respectively. The reductase‐inactive mutant Gcy1pY56F also increased vanillin tolerance in S. cerevisiae, suggesting that other mechanisms exist. Although TRS85 and PEX5, genes for which the mRNAs are binding targets of Gcy1p, were shown to be related to vanillin tolerance, both the mRNA and protein levels of these genes were not changed by overexpression of GCY1. The relationship between the mRNA‐binding activity of Gcy1p and its positive effect on vanillin tolerance is still not clear. Finally, we found that the point mutation D112A in Mbf1p, which disrupts the binding of Mbf1p and the TATA element‐binding protein (TBP), did not decrease the positive effect of Mbf1p on vanillin tolerance. This indicates that the binding of Mbf1p and TBP is not necessary for the positive effect on vanillin tolerance mediated by Mbf1p. We have successfully identified new genes related to vanillin tolerance and provided novel targets that can be used to improve the vanillin tolerance of S. cerevisiae. Moreover, we have extended our understanding of the proteins encoded by these genes.