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This study aimed to investigate the association between daily sleep duration and incident dementia among physically and socially independent older people with/without diseases (hypertension, diabetes mellitus, cardiovascular diseases) in a Japanese age-specific cohort.We carried out a prospective cohort study including 1954 (1006 men and 948 women) Japanese individuals aged 64/65 years. Information on daily sleep duration, medical status, demographics, and lifestyle characteristics was collected by a baseline questionnaire survey and health checkup (2000-2005). Dates of incident dementia were confirmed using the nationally standardized dementia scale proposed by the Ministry of Health, Labor, and Welfare. A competing risk model was used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) for incident dementia. We treated censored cases due to death as competing events.During a median of 15.6 years of follow-up, 260 participants reported incident dementia. Compared with participants without diseases and who slept 6-7.9 h/day, those with a shorter daily sleep duration of6 h/day, presence of disease and shorter, moderate, or longer daily sleep duration ≥8 h/day had an increased risk of incident dementia (HR 1.73; 95% CI 1.04-2.88, HR 1.98; 95% CI 1.14-3.44, HR 1.44; 95% CI 1.03-2.00, and HR 2.09; 95% CI 1.41-3.09, respectively) with a significant interaction between the presence of diseases and sleep duration (p 0.001).The present findings suggest that habitual sleep duration predicts future risk of dementia.

Aging is an important medical and social problem. Excessive angiopoietin-like protein (ANGPTL)-2 signaling causes chronic tissue inflammation, promoting development and progression of aging-related diseases. Moreover, circulating ANGPTL2 levels reportedly predict the risk of some aging-related diseases and subsequent death. However, there are, as yet, no reports of whether circulating ANGPTL2 levels predict vital prognosis in younger-old, community-dwelling populations. This study investigated associations between plasma ANGPTL2 levels and all-cause and specific-cause mortality in this population. The case–cohort study was abstracted from an ongoing, age-specific prospective cohort study: the New Integrated Suburban Seniority Investigation Project. This project enrolled 3 073 participants aged 64 years at the beginning of the investigation from 1996 through 2005. A subcohort of 714 randomly sampled participants plus 387 cases representing deceased participants followed through 2015 underwent survival analysis. Plasma ANGPTL2 concentrations were positively associated with >80% and 100% higher risk of all-cause mortality and cancer mortality, respectively, after adjustment for gender, smoking, alcohol consumption, walking time, sleep duration, caloric intake, medical status, disease history, BMI, and triglyceride, creatinine, uric acid, and high sensitivity C-reactive protein levels. A more robust association between ANGPTL2 levels and all-cause and cancer mortality was seen in participants with either frailties or with lifestyles of heavier drinking or current smoking. Elevated plasma ANGPTL2 levels are associated with high all-cause and cancer mortality in a community-dwelling sample of younger-old adults. These findings expand our knowledge of human aging and associated diseases.

To explore an effective model based on radiomics features extracted from nonenhanced computed tomography (CT) images to distinguish invasive adenocarcinoma (IAC) from minimally invasive adenocarcinoma (MIA) presenting as pure ground-glass nodules (pGGNs) with bubble-like (B-pGGNs) signs.We retrospectively reviewed 511 nodules (MIA, n = 288; IAC, n = 223) between November 2012 and June 2018 from almost all pGGNs pathologically confirmed MIA or IAC. Eventually, a total of 109 B-pGGNs (MIA, n = 55; IAC, n = 54) from 109 patients fulfilling the criteria were randomly assigned to the training and test cluster at a ratio of 7:3. The gradient boosting decision tree (GBDT) method and logistic regression (LR) analysis were applied to feature selection (radiomics, semantic, and conventional CT features). LR was performed to construct three models (the conventional, radiomics and combined model). The performance of the predictive models was evaluated using the area under the curve (AUC).The radiomics model had good AUCs of 0.947 in the training cluster and of 0.945 in the test cluster. The combined model produced an AUC of 0.953 in the training cluster and of 0.945 in the test cluster. The combined model yielded no performance improvement (vs. the radiomics model). The rad_score was the only independent predictor of invasiveness.The radiomics model showed excellent predictive performance in discriminating IAC from MIA presenting as B-pGGNs and may provide a necessary reference for extending clinical practice.

Isotropic gold nanoparticles (AuNPs) can generate a plasma-plasma interaction when aggregating and can also produce ideal photothermal effects. Some studies have designed ATP-responsive nanodrug delivery systems by taking advantage of the differences between internal and external ATP in tumor cells, but few studies have focused on the photothermal effects of ATP-induced AuNP aggregation in tumors. Here, a triple-helix probe (THP) molecular switch and MUC1 aptamer-functionalized AuNPs were constructed for fluorescence imaging analysis and photothermal therapy (PTT). The MUC1 aptamer guides THP-AuNP targeting in tumor cells, followed by the high concentration of ATP inducing structural changes in triple-helix probes and causing the intracellular aggregation of AuNPs, which cannot escape from the tumor site, enabling tumor imaging while performing PTT. Therefore, the designed THP-AuNPs have promising applications in fluorescence imaging and PTT.

The protein-coding ability of circular RNAs (circRNAs) has recently been a hot topic, but the expression and roles of protein-coding circRNAs in triple-negative breast cancer (TNBC) remain uncertain. By intersecting circRNA sequencing data from clinical samples and cell lines, we identified a circRNA, termed circ-EIF6, which predicted a poorer prognosis and correlated with clinicopathological characteristics in a cohort of TNBC patients. Functionally, we showed that circ-EIF6 promoted the proliferation and metastasis of TNBC cells in vitro and in vivo. Mechanistically, we found that circ-EIF6 contains a 675-nucleotide (nt) open reading frame (ORF) and that the -150-bp sequence from ATG functioned as an internal ribosome entry site (IRES), which is required for translation initiation in 5' cap-independent coding RNAs. circ-EIF6 encodes a novel peptide, termed EIF6-224 amino acid (aa), which is responsible for the oncogenic effects of circ-EIF6. The endogenous expression of EIF6-224aa was further examined in TNBC cells and tissues by specific antibody. Moreover, EIF6-224aa directly interacted with MYH9, an oncogene in breast cancer, and decreased MYH9 degradation by inhibiting the ubiquitin-proteasome pathway and subsequently activating the Wnt/beta-catenin pathway. Our study provided novel insights into the roles of protein-coding circRNAs and supported circ-EIF6/EIF6-224aa as a novel promising prognostic and therapeutic target for tailored therapy in TNBC patients.

There is a constant drive for affordable point-of-care testing (POCT) technologies for the detection of infectious human diseases. Herein, we report a simple platform for DNA detection that takes advantage of four techniques: commercially available pregnancy test strips (PTS), amplicon generation via loop-mediated isothermal amplification (LAMP), toehold-mediated strand displacement, and noncovalent immobilization of DNA on paper surface with DNA nanoflowers. This simple, separation-free platform is highly specific, as demonstrated with the detection of rtL180M, a single-nucleotide polymorphism observed in hepatitis B virus (HBV) associated with antiviral drug resistance. It is very sensitive, capable of detecting the targeted mutation at 2 copies μL-1 . It is able to correctly identify the unmutated and rtL180M genome types of HBV in clinical samples. Given its wide adaptability, we expect this platform can be easily modified for the detection of genetic variations associated with various pathogens and human diseases.

Several studies have suggested that coatomer protein complex subunit beta 2 (COPB2) may act as an oncogene in various cancer types. However, no systematic pan-cancer analysis has been performed to date. Therefore, the present study analyzed the potential oncogenic role of COPB2 using TCGA (The Cancer Genome Atlas) and GEO (Gene Expression Omnibus) datasets. The majority of the cancer types overexpressed the COPB2 protein, and its expression significantly correlated with tumor prognosis. In certain tumors, such as those found in breast and ovarian tissues, phosphorylated S859 exhibited high expression. It was found that mutations of the COPB2 protein in kidney and endometrial cancers exhibited a significant impact on patient prognosis. It is interesting to note that COPB2 expression correlated with the number of cancer-associated fibroblasts in certain tumors, such as cervical and endocervical cancers and colon adenocarcinomas. In addition, COPB2 was involved in the transport of substances and correlated with chemotherapy sensitivity. This is considered the first pan-tumor study, which provided a relatively comprehensive understanding of the mechanism by which COPB2 promotes cancer growth.

Background Data are limited on whether several easily measured indices are independent predictors of type 2 diabetes mellitus (T2DM) in hypertensive patients. This study aimed to assess the association of hypertriglyceridemic-waist phenotype, triglyceride glucose (TyG) index, lipid accumulation product (LAP), and visceral adiposity index (VAI) with T2DM risk in hypertensive patients. Methods This cross-sectional study included 5321 hypertensive patients from the baseline survey of the Guangzhou Heart Study. Face-to-face questionnaire survey, physical examination, and fasting blood sample collection were completed for all subjects. Odds ratio (OR) with 95% confidence interval (95% CI) were calculated by using the logistic regression model. The potential nonlinear relationship was examined using restricted cubic spline regression. Results The prevalence of T2DM was 19.98% among hypertensive patients. After adjusting for confounders, participants with elevated triglyceride levels and enlarged waist circumference (HTGW) were associated with a 2.57-fold risk of T2DM (OR 2.57, 95% CI 2.05, 3.23). When comparing with subjects within the lowest quartile of the indices, those in the highest quartile of TyG, LAP, and VAI were associated with 5.35-fold (95% CI 4.33, 6.64), 2.65-fold (95% CI 2.11, 3.34), and 2.17-fold (95% CI 1.77, 2.67) risk of T2DM after adjusting for confounders. Every 1-unit increment of TyG, LAP, and VAI was associated with 81%, 38%, and 31% increased risk of T2DM, respectively. The nonlinear association was observed for TyG, LAP, and VAI (all PNon-linear Conclusions The results found that among hypertensive patients, HTGW and a higher level of TyG, LAP, and VAI were associated with an elevated risk of T2DM. The findings suggested that HTGW, TyG, LAP, and VAI may serve as simple and effective tools for T2DM risk assessment in the prevention and management of main chronic diseases.

The consensus guidelines for branch-duct intraductal papillary mucinous neoplasm (BD-IPMN) of the pancreas are mostly based on imaging features. This study aimed to determine imaging features and their diagnostic accuracy for predicting high-grade dysplasia (HGD)/malignancy in BD-IPMN, including mixed type. The PubMed, Embase, and Cochrane databases were searched, and data were extracted from relevant studies. As the main diagnostic accuracy index, diagnostic odds ratios (DORs) of imaging features for diagnosing HGD/malignancy in BD-IPMNs were pooled using the random-effects model. A bivariate random-effects approach was used to construct summary receiver operating characteristic curves for sensitivity and specificity estimation. The pooled DOR was the highest for the enhanced solid component/mural nodule (MN) (DOR, 12.21; 95 % confidence interval [CI], 6.14–24.27), followed by a main pancreatic duct (MPD) diameter of 10 mm or greater (DOR, 7.93; 95 % CI, 3.02–20.83), solid component (DOR, 4.85; 95 % CI, 2.49–9.42), lymphadenopathy (DOR, 4.84; 95 % CI, 1.11–21.06), MN (DOR, 4.48; 95 % CI, 3.15–6.39), an MPD diameter of 5 mm or greater (DOR, 3.69; 95 % CI, 2.62–5.19), abrupt change in MPD caliber with distal pancreatic atrophy (DOR, 2.65; 95 % CI, 1.66–4.24), thickened/enhancing walls (DOR, 2.38; 95 % CI, 1.57–3.60), and cyst size of 3 cm or larger (DOR, 1.98; 95 % CI, 1.48–2.64). The largest area under the curve (0.89 and 0.95, respectively) and high specificity (0.95 and 0.98, respectively) also were found for enhanced solid component/MN and an MPD diameter of 10 mm or greater, albeit with low sensitivity (0.38 and 0.14, respectively). The aforementioned imaging features could aid in predicting HGD/malignancy of BD-IPMN. Furthermore, enhanced solid component/MN and an MPD diameter of 10 mm or greater were the most important predictors of HGD/malignancy in BD-IPMN and should be considered as indications for surgery.

Cancer is one of the most common malignant diseases in the world. Hence, there is an urgent need to search for novel drugs with antitumor activity against cancer cells. AMP-17, a natural antimicrobial peptide derived from Musca domestica, has antimicrobial activity against Gram-positive bacteria, Gram-negative bacteria, and fungi. However, its antitumor activity and potential mechanism of action in cancer cells remain unclear. In this study, we focused on evaluating the in vitro antitumor activity and mechanism of AMP-17 on leukemic K562 cells. The results showed that AMP-17 exhibited anti-proliferative activity on K562 cells with an IC50 value of 58.91 ± 3.57 μg/mL. The membrane integrity of K562 was disrupted and membrane permeability was increased after AMP-17 action. Further observation using SEM and TEM images showed that the cell structure of AMP-17-treated cells was disrupted, with depressions and pore-like breaks on the cell surface, and vacuolated vesicles in the cytoplasm. Furthermore, further mechanistic studies indicated that AMP-17 induced excessive production of reactive oxygen species and calcium ions release in K562 cells, which led to disturbance of mitochondrial membrane potential and blocked ATP synthesis, followed by activation of Caspase-3 to induce apoptosis. In conclusion, these results suggest that the antitumor activity of AMP-17 may be achieved by disrupting cell structure and inducing apoptosis. Therefore, AMP-17 is expected to be a novel potential agent candidate for leukemia treatment.

Background Academic research is one of the main avenues through which humans can fight the threat of infectious diseases. However, there have been concerns regarding whether the academic system has provided sufficient efforts to fight infectious diseases we potentially face. Answering these questions could contribute to evidence-based recommendations for setting research priorities and third-mission policies. Methods With a focus on one of the most common categories of communicable diseases, infectious and parasitic diseases (IPDs), we searched Web of Science for articles and reviews relevant to IPDs published during the period 2000–2019 and retrieved WHO data on disease burden in corresponding years. The academic response patterns were explored by IPD subcategory and by human development level (an index established by the United Nations). We conduct the analysis in particular to gain insight into the dynamic relationship between disease burden and research effort on IPDs, scientific efforts contributed by countries with different development levels, and the variation trends in international joint efforts. Results The greatest burden of IPDs is clustered in the developing regions of Africa, but has received academic response from both developed and developing countries. Highly developed countries dominate the ranks of academic research in this area, yet there is also a clear increase in research efforts from the countries most affected, despite their low human development scale. In fact, the overall analysis reveals an improved capability for addressing local problems from African regions. In terms of international collaboration, highly developed countries such as the United States and United Kingdom have commonly collaborated with needy regions, whereas prolific but developing nations, like China, have not. Conclusions From a global perspective, academia has positively responded to health needs caused by IPDs. Although the relevant research output contribution is primarily from the highly developed countries, concentrated and specialized efforts from the undeveloped regions to ease their local burden can be clearly observed. Our findings also indicate a tendency to focus more on local health needs for both developed and undeveloped regions. The insights revealed in this study should benefit a more informed and systemic plan of research priorities.

Aims This cross-sectional study aimed to investigate the association between plasma homocysteine (Hcy) and chronic kidney disease (CKD) in US patients with type 2 diabetes mellitus (T2DM). Methods We used data from the 2003–2006 National Health and Nutritional Examination Surveys (NHANES). CKD was defined as an estimated glomerular filtration rate 2 and/or urinary albumin-creatine ratio ≥ 3 mg/mmol. Results This study included 1018 patients with T2DM. The mean Hcy value was 10.2 ± 4.6 μmol/L. Among the patients, 417 (40.96%) had hyperhomocysteinemia (HHcy) and 480 (47.15%) had CKD. The Hcy level was higher in patients with CKD than in those without CKD. Compared to patients with normal Hcy, those with HHcy were older and had worse renal function. After full multivariate adjustment, HHcy was positively associated with the risk of CKD in US patients with T2DM (OR, 1.17; 95% CI, 1.11–1.22; P P P Conclusions HHcy was independently associated with CKD in patients with T2DM. Further prospective studies are warranted to investigate the effect of Hcy on CKD in patients with T2DM.

We aimed to explore the association between changes in social activities and the occurrence/persistence of depressive symptoms and investigate the difference in effect sizes among the types and combinations of social activities.The study adopted a valid 15-item Geriatric Depression Scale to assess depressive symptoms in 2480 community-dwelling adults aged 64/65 years. Changes in social-related, learning, and personal activities were classified into four categories: continued low frequency (CLF), increased frequency (IF), decreased frequency (DF), and continued regular frequency (CRF)Those without depressive symptoms at baseline and who engaged in social-related (RRThe effect of personal activities was more manifest in preventing depressive symptoms than the other two kinds, regardless of depressive symptoms at baseline. Regularly engaging in a combination of all three activities at baseline and follow-up was associated with the occurrence and persistence of depressive symptoms.

Aim We aimed to clarify whether snacking habits decrease the risk of all-cause mortality in an older Japanese population. Methods The study participants were 64- or 65-year-old community-dwelling residents recruited each survey year from 1996 through 2005. Data on the frequency of snacking and other lifestyle factors were obtained during the baseline survey using self-administered questionnaires, and the participants were followed up annually until the end of 2017. In total, 2943 participants (1484 men and 1459 women) were eligible. All-cause mortality was compared among participants grouped by frequency of snacking (no snacking, one to four times/week, or every day). Results The number of deaths recorded over the study period of 43 204 person-years was 357 (24.1%) for men and 173 (11.9%) for women. The mean +/- standard deviations for the follow-up period were 14.2 +/- 4.9 years in men and 15.2 +/- 4.5 years in women. Cox proportional hazard regression analyses showed that after adjusting for potential confounding factors, the hazard ratios for women were 0.64 (95% confidence interval [CI], 0.43-0.94) in the group that had a habit of snacking one to four times/week, and 0.93 (95% CI 0.63-1.36) in the group that had a habit of snacking every day compared with those in the no snacking group. These associations were not observed among men. Conclusions A moderate frequency of snacking slightly decreases the risk of all-cause mortality among women. Our findings might be useful for improving the nutrition statuses in older female adults. Geriatr Gerontol Int center dot center dot; center dot center dot: center dot center dot-center dot center dot Geriatr Gerontol Int 2021; center dot center dot: center dot center dot-center dot center dot.

ObjectiveThis study was conducted to evaluate the association of the risk of all-cause mortality with habitual physical activity (HPA) and its different domains among Chinese adults.MethodsA total of 11,994 participants from the Guangzhou Heart Study were followed up until 1 January 2020. Information on HPA, including leisure-time physical activity (LTPA) and commute activity, was collected using a modified Global Physical Activity Questionnaire. Individual cause of death was obtained from the National Death Registry of China. Cox proportional hazards regression model was used to estimate hazard ratio (HR) and 95% confidence interval (CI) after adjustment for covariates.ResultsDuring 37,715 person-years of follow-up, 208 deaths (1.73%) were observed. When compared with the highest with the lowest exposure tertiles, HPA and LTPA were associated with 34% (HR: 0.66, 95% CI: 0.46–0.95) and 30% (HR: 0.70, 95% CI: 0.49–0.99) reduced risk of all-cause mortality after adjustment for covariates. Commute activity was not associated with mortality risk. For the specific component of LTPA, we found that every 1 MET-h/week increment of the housework was associated with a 1% (HR: 0.99, 95% CI: 0.98–0.99) decreased mortality risk, and performing brisk walking/health exercises/Yangko was associated with a 46% reduced mortality risk (HR: 0.54, 95% CI: 0.29–0.99).ConclusionThis study suggests that a higher level of HPA and LTPA was associated with a lower risk of all-cause mortality. Our findings suggest people to perform HPA, especially LTPA, as a strategy for mortality reduction and health promotion.

The vaginal microbiota dysbiosis is closely associated with the development of reproductive diseases. However, the contribution of mycobiome to intrauterine adhesion (IUA) disease remains unknown. Harnessing 16S and ITS2 rDNA sequencing analysis, we investigate both bacterial and fungal microbiota compositions across 174 samples taken from both cervical canal (CC) and middle vagina (MV) sites of IUA patients. Overall, there is no significant difference in microbial diversity between healthy subjects (HS) and IUA patients. However, we observe the IUA-specific bacterial alterations such as increased

Dietary diversity might reduce the risk of malnutrition, although it is also linked to obesity. We examined whether dietary diversity is associated with all-cause mortality in Japanese older adults based on their body mass index (BMI).The current study included 2944 people aged 64-65 years who participated in the New Integrated Suburban Seniority Investigation (NISSIN) project from 1996 to 2005. Dietary diversity was measured using the Food Variety Score (FVS), which calculates the frequency of all food items consumed daily using a self-administered food frequency questionnaire. Participants were divided into tertiles according to their FVS (first: low, second: middle, third: high). Multivariate adjusted hazard ratios with 95% confidence intervals were calculated using the Cox proportional hazard regression model. For the stratified analysis, BMI was used to divide the participants into three groups - lean (BMI20), normal (BMI 20-24.9) and overweight/obese (BMI ≥25).Overall, 454 (30.7%) men and 222 (15.2%) women died over a median follow-up period of 16.6 years. No significant association was observed between FVS and all-cause mortality. However, when grouped by BMI, for the participants in the lean group, the multivariate adjusted hazard ratios were 0.56 (95% confidence interval 0.32-0.96) for the middle FVS and 0.50 (95% confidence interval 0.25-1.02) for the high FVS, compared with the low FVS (P for trend = 0.059). In overweight/obese women, although not significant, total mortality was higher in the middle and high FVS.These findings show that dietary diversity should be promoted in lean older Japanese adults. Geriatr Gerontol Int 2022; 22: 736-744.

Background Pleural deformation is associated with the invasiveness of lung adenocarcinoma(LAC). Our study focused on the pathological components of the area adjacent pleura in pulmonary pure ground-glass nodules(pGGNs) with pleural deformations(P-pGGNs) confirmed to be invasive LAC without visceral pleural invasion (VPI) pathologically. Methods Computed tomography(CT) imaging features of nodules and pathological components of the area adjacent pleura were analyzed and recorded. Statistical analysis was performed for subgroups of P-pGGNs. Results The 81 enrolled patients with 81 P-pGGNs were finally involved in the analysis. None of solid/micropapillary group and none of VPI was observed, 54 alveoli/lepidics and 27 acinar/papillarys were observed. In P-pGGN with acinar/papillary components of the area adjacent pleura, invasive adenocarcinoma (IAC) was more common compared to minimally invasive adenocarcinoma (MIA, 74.07% vs. 25.93%; p p p p p = 0.028). Conclusions The pathological components of the area adjacent pleura in P-pGGN without VPI confirmed to be invasive LAC could included alveoli/lepidics and acinar/papillarys. Some CT indicators that can identify the pathological invasive components of the area adjacent pleura in P-pGGNs.

The association of dietary phytosterols intake with survival of esophageal squamous cell carcinoma (ESCC) remains unclear. This study was to examine the effect of dietary phytosterols intake on ESCC survival in a Chinese rural population.A total of 942 incident ESCC patients diagnosed between 2011 and 2013 in Yanting area were followed up until March 1When comparing the highest with lowest intake quartiles, intake of five specific and total phytosterols was not significantly associated with risk of death after adjustment for covariates, the adjusted HR (95% CI) for β-sitosterol, campesterol, stigmasterol, β-sitostanol, campestanol and total phytosterols was 0.90 (95% CI: 0.70-1.16), 0.92 (95% CI: 0.71-1.19), 0.86 (95% CI: 0.66-1.12), 0.93 (95% CI: 0.73-1.20), 0.94 (95% CI: 0.72-1.21), 0.89 (95% CI: 0.69-1.15), respectively.This study does not find any association between pre-diagnostic phytosterols intake and risk of all-cause mortality among ESCC patients. Further research is required to determine the effect of post-diagnostic phytosterols intake on ESCC survival.

Pancreatic ductal adenocarcinoma (PDAC) interacts closely with the tumor microenvironment (TME). The TME is remodeled by crosstalk between pancreatic cancer cells and stromal cells, and is critical for cancer progression. Extracellular vesicles (EVs), including exosomes and microvesicles, help facilitate an exchange of information both within the TME and to distant organs. EVs have also been identified as potential diagnostic biomarkers, therapeutic targets, and drug carriers for pancreatic cancer treatment. Thus, understanding the selective packaging of EVs cargo and its mechanistic impact will increase our understanding of cancer biology. In this review, we collect and analyze recent findings of the pancreatic cancer-stromal cell interactions mediated by EVs and the mechanisms involved in cancer-related immunity and chemoresistance. These studies demonstrate the vital role of EVs in pancreatic cancer reprogramming and TME remodeling. We also summarize the EVs identified as potential PDAC diagnostic biomarkers and possible therapeutic targets. This greater understanding is a promising avenue for transitioning EVs from bench to bedside.Graphical Abstract

Stimulus-responsive materials are ideal carriers for precisely controlled drug delivery due to their high selectivity. However, the complex physiological environment hinders its development in clinical medicine. Here, we aim to design a self-assembled three-dimensional (3D) DNA nanostructure drug delivery system with adenosine-5'-triphosphate (ATP)-triggered drug release for tumor fluorescence imaging analysis and targeted drug delivery. Dox@3D DNA nanostructures are self-assembled by a simple one-pot annealing reaction and embedded with drugs, which are structurally stable but can be induced using high concentrations of ATP in tumor cells to cleave and release drugs rapidly, facilitating the rapid accumulation of drugs in tumors and exerting therapeutic effects, thus effectively avoiding damage to normal tissues. This work demonstrates that 3D DNA nanostructures can be used as efficient drug nanocarriers with promising applications in tumor therapy.

DNA self-assembling nanoprobes with self-transferability and resistance to nuclease degradation have been developed and applied to live cell bio-imaging. In this work, we constructed a hairpin-functionalized DNA tetrahedron (HFDT) intramolecular catalytic self-assembly platform to detect low-abundance miRNAs by a catalyzed hairpin assembly (CHA). The designed HFDT enhances the CHA reaction efficiency and aggregates into dendrimer structures in the presence of miRNAs. This innovative "small to large" strategy can effectively change the distribution and properties of biomaterials in the organism, thus effectively retaining them inside the tumor and reducing the efflux of nanomaterials, increasing their accumulation in the tumor site and protecting them from the complex physiological environment, which has promising applications in tumor imaging.

Hepatocellular carcinoma (HCC) is one of the most important causes of cancer-related deaths and remains a major public health challenge worldwide. Considering the extensive heterogeneity of HCC, more accurate prognostic models are imperative. The circadian genes regulate the daily oscillations of key biological processes, such as nutrient metabolism in the liver. Circadian rhythm disruption has recently been recognized as an independent risk factor for cancer. In this study, The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) were compared and 248 differentially expressed genes (DEGs) of the circadian rhythm were identified. HCC was classified into two subtypes based on these DEGs. The prognostic value of each circadian rhythm-associated gene (CRG) for survival was assessed by constructing a multigene signature from TCGA cohort. A 6-gene signature was created by applying the least absolute shrinkage and selection operator (LASSO) Cox regression method, and all patients in TCGA cohort were divided into high- and low-risk groups according to their risk scores. The survival rate of patients with HCC in the low-risk group was significantly higher than that in the high-risk group ( p < 0.001 ). The patients with HCC in the Gene Expression Omnibus (GEO) cohort were also divided into two risk subgroups using the risk score of TCGA cohort, and the overall survival time (OS) was prolonged in the low-risk group ( p = 0.012 ). Based on the clinical characteristics, the risk score was an independent predictor of OS in the patients with HCC. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses showed that multiple metabolic pathways, cell cycle, etc., were enhanced in the high-risk group. Using the metabolic pathway single-sample gene set enrichment analysis (ssGSEA), it was found that the metabolic pathways in the high- and low-risk groups between TCGA and GEO cohorts were altered essentially in the same way. In conclusion, the circadian genes play an important role in HCC metabolic rearrangements and can be further used to predict the prognosis the patients with HCC.

Numerous studies have shown that circRNAs are aberrantly expressed in various cancers and play a significant role in tumor progression. However, the molecular mechanisms of circRNAs in triple-negative breast cancer (TNBC) remain ambiguous. By intersecting throughput data and qRT-PCR results from tissues and cell lines, circ-TRIO was identified as a potential oncogenic regulator of TNBC. Moreover, circ-TRIO expression was detected in TNBC tissues and was correlated with the recurrence and prognosis of TNBC patients. The circular characteristics of circ-TRIO were verified by RNase R and CHX assays. Functionally, the knockdown of circ-TRIO inhibited the proliferation, migration and invasion of TNBC cells, while the overexpression of circ-TRIO resulted in the opposite impacts. Mechanistically, a dual luciferase reporter assay and RNA immunoprecipitation were performed and indicated that circ-TRIO could combine with miR-432-5p to regulate the expression of coiled-coil domain containing 58 (CCDC58). In summary, our study illustrates that circ-TRIO plays an important role in the progression of TNBC by regulating the miR-432-5p/CCDC58 axis, which could broaden our insight into the underlying mechanisms and provide a novel prognostic marker of TNBC in the clinic.

Background We aimed to examine the association of three mineral metabolism markers, including serum calcium, inorganic phosphorus, and intact parathyroid hormone with the risk of chronic kidney disease (CKD) at all stages. Methods This retrospective cohort study involved 3563 participants, including 3274 CKD patients and 289 healthy controls. CKD is diagnosed according to clinical guidelines from the 2012 KDIGO. Effect sizes are expressed odds ratio (OR) and 95 confidence interval (CI). Results After propensity score matching, per 0.5 mg/dL increment of inorganic phosphorus was significantly associated with 1.33-, 1.61-, and 2.85-fold increased risk of CKD at stages 1–2, 4, and 5, respectively. Regarding per 8 pg/mL increment of intact parathyroid hormone, significance was only noted for stage 5. In subsidiary analyses, the risk prediction of mineral metabolism markers under study was more evident in males and hypertensive subjects. A nomogram prediction model was constructed based on age, sex, and three mineral metabolism markers for CKD, with decent accuracy. Conclusions Our findings indicate that serum calcium was associated with all-stage CKD risk, whereas the association for inorganic phosphorus and intact parathyroid hormone was significant at advanced stages.

Emerging evidence has demonstrated that circular RNAs (circRNAs) play critical roles in the development and progression of human cancer. However, the biological functions and underlying mechanisms of circRNAs in triple-negative breast cancer (TNBC) remain to be investigated. In our present study, we found that the novel circRNA circHIF1A was significantly overexpressed in breast cancer tissues and that it was associated with metastasis, poor prognosis, and the TNBC subtype. Gain- and loss-of-function experiments were conducted to investigate the biological roles of circHIF1A in TNBC. Overexpression of circHIF1A significantly promoted TNBC growth and metastasis in vitro and in vivo, while knockdown of circHIF1A exerted the opposite effects. Mechanistically, circHIF1A modulated the expression and translocation of NFIB through posttranscriptional and posttranslational modifications, resulting in the activation of the AKT/STAT3 signaling pathway and inhibition of P21. The RNA binding protein FUS could regulate the biogenesis of circHIF1A by interacting with the flanking intron, and FUS was transcriptionally regulated by NFIB, thus forming the circHIF1A/NFIB/FUS positive feedback loop. Moreover, circHIF1A could be packaged into exosomes and was upregulated in the plasma of breast cancer patients. Our findings indicated that circHIF1A played a critical role in the growth and metastasis of TNBC via a positive feedback loop and that circHIF1A could be a promising biomarker for breast cancer diagnosis and a potential therapeutic target for TNBC treatment.

Regular engagement in behavioral activities plays a crucial role against depressive symptoms in older adults. This study aims to explore the relationship between behavioral activities and the temporal evolution of depressive symptoms.We included community-dwelling Japanese adults aged 64 or 65 years with and without depressive symptoms enrolled in the New Integrated Suburban Seniority Investigation (NISSIN) project. Depressive symptoms at baseline and follow-up were assessed using the 15-item Geriatric Depression Scale. Behavioral activities were measured by self-reported questions. Risk ratios and 95% confidence intervals were calculated using modified Poisson regression, adjusting for relevant sociodemographic variables and health-related confounders.During the 6 year follow-up period, 139 (10.1%) without depressive symptoms at baseline developed such symptoms over time, while 174 (51.6%) with depressive symptoms improved to the point of these symptoms being absent. The participants without depressive symptoms at baseline and those who engaged in social activity or daily walking at a continued regular frequency (CRF) or an increased frequency (IF) and exercise habits at CRF were the least likely to have depressive symptoms onset at follow-up. There was no significant difference between the changes in behavioral activities and the improvement of depressive symptoms after controlling for confounders. Participants engaging in a greater variety of behavioral activities at CRF were less likely to experience a new onset of depressive symptoms.Consistent and regular participation in one or more behavioral activities was significantly associated with the onset of depressive symptoms in Japanese community-dwelling older adults.

Background Circular RNAs (circRNAs) represent a novel type of regulatory RNA characterized by high evolutionary conservation and stability. CircRNAs are expected to be potential diagnostic biomarkers and therapeutic targets for a variety of malignancies. However, the regulatory functions and underlying mechanisms of circRNAs in triple-negative breast cancer (TNBC) are largely unknown. Methods By using RNA high-throughput sequencing technology, qRT-PCR and in situ hybridization assays, we screened dysregulated circRNAs in breast cancer and TNBC tissues. Then in vitro assays, animal models and patient-derived organoids (PDOs) were utilized to explore the roles of the candidate circRNA in TNBC. To investigate the underlying mechanisms, RNA pull-down, RNA immunoprecipitation (RIP), co immunoprecipitation (co-IP) and Western blotting assays were carried out. Results In this study, we demonstrated that circRNA-CREIT was aberrantly downregulated in doxorubicin resistant triple-negative breast cancer (TNBC) cells and associated with a poor prognosis. The RNA binding protein DHX9 was responsible for the reduction in circRNA-CREIT by interacting with the flanking inverted repeat Alu (IRAlu) sequences and inhibiting back-splicing. By utilizing in vitro assays, animal models and patient-derived organoids, we revealed that circRNA-CREIT overexpression significantly enhanced the doxorubicin sensitivity of TNBC cells. Mechanistically, circRNA-CREIT acted as a scaffold to facilitate the interaction between PKR and the E3 ligase HACE1 and promoted proteasomal degradation of PKR protein via K48-linked polyubiquitylation. A reduced PKR/eIF2α signaling axis was identified as a critical downstream effector of circRNA-CREIT, which attenuated the assembly of stress granules (SGs) to activate the RACK1/MTK1 apoptosis signaling pathway. Further investigations revealed that a combination of the SG inhibitor ISRIB and doxorubicin synergistically inhibited TNBC tumor growth. Besides, circRNA-CREIT could be packaged into exosomes and disseminate doxorubicin sensitivity among TNBC cells. Conclusions Our study demonstrated that targeting circRNA-CREIT and SGs could serve as promising therapeutic strategies against TNBC chemoresistance.

Humane treatment requires the provision of appropriate sedation and analgesia during medical diagnosis and treatment. However, limited information is available about the status of procedural analgesic interventions in Chinese hospitals. Therefore, a nationwide survey was established to identify challenges and propose potential improvement strategies.Forty-three members of the Pain Group of Chinese Society of Anesthesiology established and reviewed the questionnaire, which included (1) general information on the hospitals, (2) the sedation/analgesia rate in gastrointestinal endoscopy, labor, flexible bronchoscopy, hysteroscopy in China, (3) staff assignments, (4) drug use for procedural analgesic interventions, and (5) difficulties in procedural analgesic interventions. The data were obtained using an online questionnaire sent to the chief anesthesiologists of Chinese hospitals above Grade II or members of the Pain Group of Chinese Society of Anesthesiology.Valid and complete questionnaires were received from 2198 (44.0%) hospitals, of which 64.5% were Grade III. The overall sedation/analgesia rates were as follows: gastroscopy (50.6%), colonoscopy (53.7%), ERCP (65.9%), induced abortion (67.5%), labor (42.3%), hysteroscopy (67.0%) and fiber bronchoscopy (52.6%). Compared with Grade II hospitals, Grade III hospitals had a higher proportion of procedural analgesic interventions services except for induced abortion. On average (median [IQR]), each anesthesiologist performed 5.7 [2.3-11.4] cases per day, with 7.3 [3.2-13.6] performed in Grade III hospitals and 3.4 [1.8-6.8] performed in Grade II hospitals (z = -7.065, p 0.001).Chinese anesthesiologists have made great efforts to achieve procedural analgesic interventions, as evidenced by the increased rate. The uneven health care provided by hospitals at different levels and in different regions and the lack of anesthesiologists are the main barriers to optimal procedural analgesic interventions.

Background The relationship of consumption of dietary fat and fatty acids with esophageal squamous cell carcinoma (ESCC) risk remains unclear. This study aimed to explore the relationship of dietary fat and fatty acids intake with ESCC risk. Methods This case-control study included 879 incident cases and 892 community-based controls recruited from Southwest China. A food frequency questionnaire was adopted to collect information about dietary information, and intake of fat, saturated fatty acid (SFA), monounsaturated fatty acid (MUFA), polyunsaturated fatty acid (PUFA), and total fatty acid (TFA) was calculated. Odds ratios (ORs) with 95% confidence intervals (95% CIs) were estimated using the logistic regression model. Results When comparing the highest with lowest intake quintiles, MUFA (OR: 0.33, 95% CI: 0.21–0.51), PUFA (OR: 0.32, 95% CI: 0.20–0.51), and TFA (OR: 0.44, 95% CI: 0.28–0.70) were related to a reduced risk of ESCC after adjusting for confounders; for non-drinkers rather than drinkers, the intake of SFA was significantly related to a 61% (OR: 0.39, 95% CI: 0.19–0.81) reduced risk of ESCC when comparing the highest with the lowest intake quintiles. Dietary fat was not related to the risk of ESCC. Conclusions This study suggested that the more intake of MUFA and PUFA, the lower risk of ESCC, whereas the protective effect of TFA was only observed among non-drinkers. Strategic nutritional programs should consider food rich in unsaturated fatty acids to mitigate the occurrence of ESCC.

Background This study aimed to assess the reproducibility and validity of a food frequency questionnaire (FFQ) developed for diet-related studies in a rural population. Methods One hundred fifty-four healthy residents were interviewed with a 76-item FFQ at baseline (FFQ1) and 1 month later (FFQ2) to assess reproducibility, and required to complete two three-day dietary recalls (DRs) between two FFQs to determine the validity by comparing DRs with FFQ1. Results Crude Spearman correlation coefficients between FFQ1 and FFQ2 ranged from 0.58 to 0.92 and energy-adjusted coefficients ranged from 0.62 to 0.92; weighted kappa statistic covered a spectrum from 0.45 to 0.81, depicting moderate to good agreements. For validity, there were moderate to strong associations (0.40–0.68) in most nutrients and food between FFQ1 and DRs; weighted kappa statistic demonstrated fair to moderate agreements for nutrients and food (0.21–0.49). Conclusions The results suggest that the FFQ has reasonably reproducibility and validity in measuring most nutrients and food intake, and it can be used to explore the dietary habits in studying the diet-disease relationship in Chinese rural populations.

Objective The relationship between physical activity (PA) and the risk of frailty has not reached a conclusive result. This systematic review with meta-analysis aimed to evaluate the effect of PA on the onset of frailty in the community-dwelling middle and older age adults by pooling data from cohort studies. Methods A systematic literature search was performed via PubMed, Embase, and Web of Science up to June 01, 2021. Pooled adjusted effect estimates (ES) with 95% confidence interval (CI) were calculated by using the random-effect model and by comparing the highest with lowest levels of PA. Heterogeneity was tested using the I2 statistic and Q-test. The quality of evidence was evaluated by using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Results A total of ten cohort studies with 14 records were selected, and the GRADE approach classified the quality of evidence as low. In comparison with the lowest level of PA, the highest level of PA was associated with 41% decreased odds of frailty (ES: 0.59, 95% CI: 0.51–0.67; I2 = 70.0%, P-heterogeneity < 0.001) after pooling results from included studies. In stratified analysis by frailty assessment approach, the highest level of PA was significantly associated with 37% (ES 0.63, 95% CI: 0.52–0.77, 49% (ES: 0.51, 95% CI: 0.41–0.63), and 30% (ES: 0.70, 95% CI: 0.65–0.75) reduced odds of frailty when pooling studies using criteria of physical frailty, multidimensional model, and accumulation of disability, respectively. Stratified analyses further by PA indicators and PA assessment tools yielded similar protective effects in any subgroups. Conclusions This study with moderate-certainty evidence shows that a higher level of PA was associated with lower odds of frailty, and the benefits of PA for frailty prevention were independent of frailty assessment tools, PA indicators, and PA assessment methods. Findings from this study may help implement active exercise strategies to prevent frailty.

Tamoxifen is the cornerstone of adjuvant therapy for hormone receptor-positive breast cancer. Despite its efficacy, limited drug sensitivity and endocrine resistance remain the important clinical challenges. The main objective of this study was to investigate fatostatin, which was found to sensitize breast cancer to the antitumour effect of tamoxifen both in vitro and in vivo.Fatostatin-induced ER degradation was detected by immunoprecipitation assay. The antitumour effect of fatostatin and tamoxifen on MCF-7 and T47D cells was assessed by MTT and colony forming assays. Cell cycle arrest was detected by flow cytometric analysis. Apoptosis was detected by annexin V/propidium iodide double staining and TUNEL assay. Autophagy was detected by MDC assay and acridine orange staining. Migration and invasion assays were performed using a Transwell system, and the efficacy of the synergistic use of fatostatin and tamoxifen in vivo was evaluated using an MCF-7 xenograft model in BALB/c nu/nu female mice.The synergistic use of fatostatin and tamoxifen significantly suppressed cell viability and invasion, induced cell cycle arrest, and regulated apoptosis and autophagy in MCF-7 and T47D cell lines via PI3K-AKT-mTOR signalling. Additionally, the expression levels of Atg7/12/13, beclin and LC3B increased while p-mTOR and P62 expression levels decreased after treatment with fatostatin and tamoxifen. Tumor growth in the xenograft model was suppressed significantly with the synergistic treatment of fatostatin and tamoxifen.Fatostatin could induce ER degradation by K48-linked polyubiquitination, which was the key mechanism contributing to tamoxifen inhibition of PI3K-AKT-mTOR signalling in breast cancer. Fatostatin may have a promising clinical use for ER-positive breast cancer patients.

Background. Coronavirus disease 2019 (COVID-19) is rapidly disseminated worldwide, and it continues to threaten global public health. Recently, the Delta variant has emerged as the most dreaded variant worldwide. COVID-19 predominantly affects the respiratory tract, and studies have reported the transient effects of COVID-19 on digestive system function. However, the relationship between the severity of the Delta variant and digestive system function remains to be investigated. Additionally, data on the ability of the inactive Chinese vaccines (Sinovac or Sinopharm) to protect against the Delta variant or COVID-19-induced gastrointestinal symptoms in the real world are insufficient. Thus, the present retrospective observational study first attempted to use the total gastrointestinal symptom rating scale scores (GSRS) to quantify the possible changes in digestive system functions following the Delta variant infection in the early stage. In addition, the study discusses the potential of inactivated vaccines in preventing severe or critical symptoms or Delta variant-induced digestive system dysfunction. Methods. To evaluate the difference between mild illness group, moderate illness group, and severe or critical illness group, analysis of variance (ANOVA) was employed to compare the three groups' total gastrointestinal symptom rating scale scores (GSRS). A chi-squared test was used to compare the differences in the ratio of the abnormal biochemical measurements among the three groups first. Then, the percentage of the vaccinated population was compared among the three groups. Additionally, the ratio of the abnormal serum markers between the vaccinated and nonvaccinated cohorts was compared. A P value P < 0.05 ). Additionally, no significant difference was observed in the abnormal serum markers ratio between day 14 and day 21 after treatment ( P > 0.05 ). A significant difference was observed in the total GSRS scores among the three groups and the ratio of the vaccinated population among the three groups ( P < 0.05 ). A significant difference was observed in the ratio of the abnormal serum ALT and AST levels between the vaccinated and nonvaccinated cohorts ( P < 0.05 ). Conclusions. In summary, serum AST, DBIL, LDH, and IL-6 levels are potential markers for distinguishing severe or critical patients in the early stage of the Delta variant infection. Additionally, changes in the levels of these serum makers are transient, and the levels can return to normal after treatment. Furthermore, severe gastrointestinal discomfort was significantly more prevalent in patients with severe or critical diseases and should thus be considered in patients diagnosed with Delta variant infection. Finally, inactivated vaccines may prevent severe or critical symptoms and Delta variant-induced liver dysfunction. Vaccination programs must be promoted to protect public health.

The study aims to examine the predictive value of arterial blood lactic acid concentration for in-hospital all-cause mortality in the intensive care unit (ICU) for patients with acute heart failure (AHF). We retrospectively analyzed the clinical data of 7558 AHF patients in the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. The exposure variable of the present study was arterial blood lactic acid concentration and the outcome variable was in-hospital all-cause death. The patients were divided into those who survived (n = 6792) and those who died (n = 766). The multivariate logistic regression model, restricted cubic spline (RCS) plot, and subgroup analysis were used to evaluate the association between lactic acid and in-hospital all-cause mortality. In addition, receiver operating curve (ROC) analysis also was performed. Finally, we further explore the association between NT-proBNP and lactic acid and in-hospital all-cause mortality. Compared with the lowest quartiles, the odds ratios with 95% confidence intervals for in-hospital all-cause mortality across the quartiles were 1.46 (1.07–2.00), 1.48 (1.09–2.00), and 2.36 (1.73–3.22) for lactic acid, and in-hospital all-cause mortality was gradually increased with lactic acid levels increasing ( P for trend P for interaction

Background We studied patients with coronavirus disease 2019 (COVID-19) infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a virus that originated in Wuhan, China, and is spreading over the country including Jiangsu Province. We studied the clinical characteristics and therapies of severe cases in Jiangsu Province. Methods A multicenter retrospective cohort study was conducted to analyze clinical, laboratory data and treatment of 60 severe cases with COVID-19 infection in Jiangsu Province between January 24, 2020 and April 20, 2020. The improvement and deterioration subgroups were compared to identify predictors of disease progression. Results A total of 653 infected cases with COVID-19 were reported in Jiangsu Province, of which 60 severe cases were included in this study. Up until April 20, 2020, the mortality of severe patients was 0%. The median age was 57 years. The average body mass index (BMI) of these patients was 25 kg/m². White blood cell counts decreased in 45.0% of patients, lymphopenia in 63.3%, thrombocytopenia in 13.3%, and procalcitonin levels in 88.3% of the patients were less than 0.5 ng/mL. There were no statistically significant differences in immunoglobulin therapy and glucocorticoids therapy between the improvement and deterioration subgroups. Logistic regression analysis identified higher levels of troponin T (odds ratio [OR]: 1.04; 95% confidence interval [CI]: 1.00-1.08; P=0.04), antiviral therapy with aerosol inhalation of interferon (OR: 6.33; 95% CI: 1.18-33.98; P=0.03), and the application of non-invasive mechanical ventilation (OR: 1.99; 95%CI: 1.17-3.41; P=0.01) as predictors of disease progression, whereas higher lymphocyte count (OR: 0.11; 95% CI: 0.02-0.57; P=0.01) and early prone ventilation were associated with improvement (OR: 0.11; 95% CI: 0.01-0.98; P=0.04). Conclusions COVID-19 infection had a low mortality rate in Jiangsu Province, China. The higher levels of troponin T and lower lymphocyte count were predictors of disease progression. Early prone ventilation may be an effective treatment for severe cases.

Background Pre-treatment PLR (platelet-lymphocyte ratio) was reported to be associated with the prognosis in gastric cancer (GC), but the results remain inconclusive. This meta-analysis aimed to investigate the prognostic potential of the pre-treatment PLR in gastric cancer. Methods We performed a systematic literature search in PubMed, Embase, and the Cochrane Library to identify eligible publications. The hazard ratio (HR)/odds ratio (OR) and its 95% confidence (CI) of survival outcomes and clinicopathological parameters were calculated. Results A total of 49 studies (51 cohorts), collecting data from 28,929 GC patients, were included in the final analysis. The pooled results demonstrated that the elevated pre-treatment PLR was significantly associated with poor overall survival (OS) (HR 1.37, 95% CI 1.26–1.49, p < 0.001; I2 = 79.90%, Ph < 0.001) and disease-free survival (DFS) (HR 1.52, 95% CI 1.22–1.90, p < 0.001, I2 = 88.6%, Ph < 0.001). Furthermore, the patients with the elevated PLR had a higher risk of lymph node metastasis (OR = 1.17, 95% CI 1.02–1.33, p = 0.023), serosal invasion (T3+T4) (OR = 1.34, 95% CI 1.10–1.64, p = 0.003), and increased advanced stage (III+IV) (OR = 1.20, 95% CI 1.06–1.37, p = 0.004). Conclusions An elevated pre-treatment PLR was a prognostic factor for poor OS and DFS and associated with poor clinicopathological parameters in GC patients.

Inflammatory bowel disease (IBD) has become a global disease with accelerating incidence worldwide in the 21st century while its accurate etiology remains unclear. In the past decade, gut microbiota dysbiosis has consistently been associated with IBD. Although many IBD-associated dysbiosis have not been proven to be a cause or an effect of IBD, it is often hypothesized that at least some of alteration in microbiome is protective or causative. In this article, we selectively reviewed the hypothesis supported by both association studies in human and pathogenesis studies in biological models. Specifically, we reviewed the potential protective bacterial pathways and species against IBD, as well as the potential causative bacterial pathways and species of IBD. We also reviewed the potential roles of some members of mycobiome and virome in IBD. Lastly, we covered the current status of therapeutic approaches targeting microbiome, which is a promising strategy to alleviate and cure this inflammatory disease.

The host–guest type molecular size matching strategy, which embodied intramolecular hydrogen bond, aromatic nucleophilic substitution and nucleophilic addition, was utilized to develop a fluorescent probe for GSH specific detection and in situ imaging in organisms.

Ischemic stroke is one of the most common diseases with high mortality and disability. This study was intended to investigate the mechanism of resveratrol (RES) regulating microglia activation through the CD147/matrix metalloproteinase-9 (MMP-9) pathway on ischemic stroke.The middle cerebral artery occlusion (MCAO) mouse model and oxygen and glucose deprivation (OGD) cell model were established. The behavioral defects, neuronal damage, cerebral infarction volume, and histopathological changes were assessed in MCAO mice. The activation of pro-inflammatory microglia CD86After RES administration, the neuronal dysfunction, infarct volume, and morphological changes of neurons were improved in MCAO mice. Meanwhile, the motivation of pro-inflammatory microglia and the release of inflammatory factors were repressed. RES suppressed the stimulation of OGD/R microglia and the release of inflammatory factors. The expression of CD147 and MMP-9 in primary microglia was up-regulated. Inhibition of CD147 can reduce pro-inflammatory microglia activation by inhibiting MMP-9 expression. RES inhibited the CD147/MMP-9 axis in OGD/R microglia, and overexpression of CD147 partially reversed the inhibitory effect of RES on the activation and release of inflammatory factors in OGD/R microglia.RES restrained the stimulation of pro-inflammatory microglia by down-regulating the CD147/MMP-9 axis, and thus protected against ischemic brain injury.

Background Gait was proved to be strongly associated with global cognitive function and multiple cognitive domains; however, previous research usually concentrated on individual gait parameters. This study used wearable sensors to measure gait parameters in different aspects and comprehensively explored the association of gait with global cognitive function and cognitive domains. Methods The data of this cross-sectional study were obtained from 236 community-dwelling Japanese older adults (125 men and 111 women) aged 70–81 years. Gait was measured by asking participants to walk a 6-m course and back using the Physilog® sensors (GaiUp®, Switzerland). Global cognitive function and cognitive domains were evaluated by face-to-face interviews using the Japanese version of the Montreal Cognitive Assessment. Twenty gait parameters were summarized as independent gait factors using factor analysis. A generalized linear model and linear regression model were used to explore the relationship of gait with global cognitive function and cognitive domains adjusted for several confounding factors. Results Factor analysis yielded four gait factors: general cycle, initial contact, propulsion, and mid-swing. Among them, general cycle factor was significantly associated with global cognitive function (β = − 0.487, [− 0.890, − 0.085]) and executive function (P = 0.049); initial contact was associated with executive function (P = 0.017). Conclusion General cycle of gait might be the better marker of global cognitive function and gait is most strongly associated with executive function. The longitudinal relationships should be examined in future cohort studies.

Prospective evidence on the association of obesity and metabolic health status and its transition over time with the risk of hyperuricemia in the Chinese population is limited. This study aims to investigate the phenotypic transition characteristics of metabolic obesity in Chinese adults and its association with hyperuricemia. Using the China Health and Retirement Longitudinal Survey (CHARLS) survey data in 2011 and 2015, 6059 adults aged ≥ 18 years were selected as the research people. The participants' general information, living habits, blood sample testing, and blood uric acid testing data during follow-up were extracted. According to body weight and metabolic health status, obesity phenotypes were divided into: metabolically normal weight group (MHNW), metabolically normal overweight/obesity group (MHOWO); metabolically abnormal normal weight group (MUNW); metabolically abnormal overweight/obese group (MUHOWO). Multiple linear regression was used to evaluate the correlation between metabolic obesity phenotype and serum uric acid level, and logistic regression model was used to analyze the association of metabolic obesity phenotype and transition with the risk of hyperuricemia. The average age of all subjects was (58.62 ± 8.93) years old, and 42.1% were male. The MHOWO phenotype was present in 19.2% of the general population and 48.6% of the baseline who were overweight or obese population. During the 4-year follow-up period, only 10.7% of participants with MHNW at baseline converted to MHOWO. Among MHOWO participants, 21.2% converted to MUHOWO. MHOWO also increased the risk of hyperuricemia (OR, 1.57; 95% CI 1.15-2.13; P = .004), both in obese and normal-weight individuals, even when metabolic status changed from unhealthy to healthy. Risk of hyperuricemia was high among those who remained metabolically unhealthy but of normal weight (OR, 3.09; 95% CI 1.51-6.30; P = .001). MHOWO also increases the risk of hyperuricemia, and MHOWO remains stable or changes to MUHOWO, which increases the risk of hyperuricemia. Therefore, close attention should be paid to the transition of metabolic health status over time, and individualized prevention strategies should be focused on metabolically unhealthy and obese individuals.

An exciting emerging topic in the noncoding RNA (ncRNA) field is the discovery of short peptides called micropeptides (≤100 amino acids), whose novel therapeutic opportunities remain under-explored. Micropeptides have been suggested to play essential regulatory roles in diverse species of physiological and pathological processes. Genomics studies have revealed that these micropeptides are encoded by small open reading frames (sORFs) concealed in misannotated ncRNAs, generally lncRNAs (long noncoding RNAs) and circRNAs (circular RNAs). These ncRNA-encoded micropeptides have been shown to contribute to tumorigenesis but little is known about their pathological mechanism because of challenges in translated sORF identification techniques. Here, we review the best-validated micropeptides involved in the progression of human tumors and discuss their therapeutic and/or prognostic potential, at the same time, we also give our own suggestions on the concept of potential-coding RNA and micropeptides.

Although there have been studies correlating DYRK2 with a number of human cancers, there has been no pan-cancer analysis. Therefore, through the TCGA database, we conducted a related study on the expression of DYRK2 in cancers.The expression of DYRK2 is obviously increased in some cancers, while the opposite is true in others, and there is a clear association between its expression and the prognosis of cancer patients.The mutation of DYRK2 is also significantly correlated with patients’ prognosis in certain human tumors. In addition, phosphorylation and methylation levels of DYRK2 are different between tumor tissues and adjacent normal tissues in various tumors. In the tumour microenvironment, the expression of DYRK2 correlates with cancer-associated fibroblast infiltration, such as BLCA or HNSC. In order to fully understand the role of DYRK2 in different tumors, we conducted a pan-cancer analysis.

Background No studies investigated the whole effect of modifiable lifestyle factors on OSA risk. This study aimed to examine the individual and combined effects of lifestyle factors on OSA risk among Chinese adults. Methods This cross-sectional study included 9733 participants aged 35 to 74 years from the baseline survey of Guangzhou Heart Study. OSA was evaluated by Berlin Questionnaire. The healthy lifestyle score (HLS), representing the overall effect of lifestyles, was derived from seven lifestyle factors: active smoking, passive smoking, alcohol, diet, waist-hip ratio, leisure-time physical activity, and mental status. Odds ratio (OR) with 95% confidence interval (CI) was calculated using the multivariate logistic regression model. Results 8107 participants were divided into the non-OSA group and 1626 participants into the OSA group. No passive smoking (OR 0.83, 95% CI 0.74–0.94), healthy waist-hip ratio (OR 0.67, 95% CI 0.58–0.77) and healthy mental status (OR 0.45, 95% CI 0. 29–0.73) were associated with a reduced risk of OSA after adjusting for confounders, while others not. Participants with higher HLS were negatively associated with OSA risk (P-trend Conclusions The results suggest that HLS reflecting the combined effect of multiple-dimensional lifestyle factors was inversely associated with OSA risk. Preventive strategies integrating multiple lifestyle factors may provide a more feasible approach for OSA prevention.

Over the last decade, mounting evidence has revealed the key roles of gut microbiota in modulating the efficacy and toxicity of anticancer drugs, via mechanisms such as immunomodulation and microbial enzymatic degradation. As such, human microbiota presents as an exciting prospect for developing biomarkers for predicting treatment outcomes and interventional approaches for improving therapeutic effects. In this review, we analyze the current knowledge of the interplays among gut microorganisms, host responses and anticancer therapies (including cytotoxic chemotherapy and targeted therapy), with an emphasis on the immunomodulation function of microbiota which facilitates the efficacy of immune checkpoint inhibitors. Moreover, we propose several microbiota-modulating strategies including fecal microbiota transplantation and probiotics, which can be pursued to optimize the use and development of anticancer treatments. We anticipate that future clinical and preclinical studies will highlight the significance of human microbiome as a promising target towards precision medicine in cancer therapies. FUNDING: National Key Research and Development Program of China (2020YFA0907800), Shenzhen Science and Technology Innovation Program (KQTD20200820145822023) and National Natural Science Foundation of China (31900056 and 32000096).

Estrogen receptor alpha (ER-α) action is critical for hormone-dependent breast cancer, and ER-α dysregulation can lead to the emergence of resistance to endocrine therapy. Here, it is found that TRIM4 is downregulated in tamoxifen (TAM)-resistant breast cancer cells, while the loss of TRIM4 is associated with an unfavorable prognosis. In vitro and in vivo experiments confirm that TRIM4 increased ER-α expression and the sensitivity of breast cancer cells to TAM. Mechanistically, TRIM4 is found to target SET, and TRIM4-SET interactions are mediated by the RING and B-box domains of TRIM4 and the carboxyl terminus of SET. Moreover, it is determined that TRIM4 catalyzed the K48-linked polyubiquitination of SET (K150 and K172), promoting its proteasomal degradation and disassociation from p53 and PP2A. Once released, p53 and PP2A are able to further promote ESR1 gene transcription and enhance mRNA stability. Moreover, univariate and multivariate Cox proportional hazards regression analyses confirm that TRIM4 expression is an independent predictor of overall survival and recurrence-free survival outcomes in patients with ER-α positive breast cancer. Taken together, the data highlights a previously undiscovered mechanism and suggest that TRIM4 is a valuable biomarker that can be analyzed to predict response to endocrine therapy in breast cancer patients.

Purpose There still exist some arguments regarding the use of postmastectomy radiotherapy (PMRT) for patients with breast cancer carrying one to three positive axillary lymph nodes considering the heterogeneity of this cohort. Here, we developed a prognostic nomogram to estimate the probability of long-term outcome in patients receiving or not receiving PMRT in order to assist in making individually locoregional treatment decisions for this particular cohort. Methods Altogether, 20,336 women, aged 18 to 80 years, diagnosed with breast cancer, and carrying one to three positive nodes were identified in the Surveillance, Epidemiology, and End Results (SEER) database. We applied multivariant Cox hazard model to determine the impact of covariates on disease-specific survival (DSS) and overall survival (OS). Then, the nomogram was built accordingly. Internal and external validations were performed to examine the accuracy of nomograms. Results Age of diagnosis, tumor grade, size, estrogen and progesterone receptor status, and number of positive nodes were independent factors of DSS and OS in the multivariate analysis. Incorporating these factors into the constructed nomogram showed high accuracy when predicting 5- and 10-year survival, with internally and externally bootstrap-corrected concordance indexes in the range of 0.6 to 0.8. Conclusion Besides the number of involved nodes, extra variables existed as predictors of survival outcomes in this cohort; therefore, the recommendation of PMRT or no PMRT requires comprehensive consideration. This clinically validated nomogram provided a useful tool that could aid decision making by estimating DSS and OS benefits from PMRT, useful in predicting 5- and 10-year DSS and OS for patients with one to three positive nodes after mastectomy. Implications for Practice This study evaluated population-based data to identify prognostic factors associated with patients with breast cancer with one to three lymph nodes and help clinicians to weigh the benefit of postmastectomy radiotherapy (PMRT). Surveillance, Epidemiology, and End Results (SEER) data were used to develop a prognostic nomogram to predict the likelihood of long-term survival with and without PMRT in order to optimize the individual locoregional control strategy for this particular cohort. This clinically validated nomogram provides a useful tool to predict 5- and 10-year disease-specific survival and overall survival for patients with one to three positive nodes and can aid tailored clinical decision making by estimating predicted benefit from PMRT.

Excess de novo likely gene-disruptive and missense variants within dozens of genes have been identified in autism spectrum disorder (ASD) and other neurodevelopmental disorders. However, many rare inherited missense variants of these high-risk genes have not been thoroughly evaluated. In this study, we analyzed the rare missense variant burden of POGZ in a large cohort of ASD patients from the Autism Clinical and Genetic Resources in China (ACGC) and further dissected the functional effect of disease-associated missense variants on neuronal development. Our results showed a significant burden of rare missense variants in ASD patients compared to the control population (P = 4.6 × 10−5, OR = 3.96), and missense variants in ASD patients showed more severe predicted functional outcomes than those in controls. Furthermore, by leveraging published large-scale sequencing data of neurodevelopmental disorders (NDDs) and sporadic case reports, we identified 8 de novo missense variants of POGZ in NDD patients. Functional analysis revealed that two inherited, but not de novo, missense variants influenced the cellular localization of POGZ and failed to rescue the defects in neurite and dendritic spine development caused by Pogz knockdown in cultured mouse primary cortical neurons. Significantly, L1CAM, an autism candidate risk gene, is differentially expressed in POGZ deficient cell lines. Reduced expression of L1cam was able to partially rescue the neurite length defects caused by Pogz knockdown. Our study showed the important roles of rare inherited missense variants of POGZ in ASD risk and neuronal development and identified the potential downstream targets of POGZ, which are important for further molecular mechanism studies.

Background:The gene metastasis-associated in colon cancer-1 (MACC1) has been reported to be overexpressed in diverse human malignancies, and an increasing amount of evidence suggests that its overexpression is associated with the development and progression of many human tumors. However, the prognostic and clinicopathological value of MACC1 in gastric cancer remains inconclusive. Therefore, we conducted this meta-analysis to investigate the effect of positive MACC1 expression on clinicopathological features and survival outcomes in gastric cancer.Methods:Medline, Web of Science, and EMBASE databases were searched for relevant articles published up to 10 April 2018. The correlation of MACC1 expression levels with overall survival and clinicopathological features was analyzed.Results:In this meta-analysis, nine studies with a total of 2103 gastric cancer patients were included. Our results showed that high expression of MACC1 was significantly related to a poor overall survival. Moreover, our meta-analysis showed that MACC1 overexpression was significantly linked to distant metastasis and vascular invasion. There were no significant correlations between positive MACC1 expression and gender, localization, tumor-node-metastasis (TNM) stage, tumor extent (T stage) and lymph node involvement (N stage)Conclusions:MACC1 expression levels can serve as a novel prognostic factor in gastric cancer patients.