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Hai-Tao Niu, Yang Liu, Yan-Zhou Wang, Yong Tian, Ming Yang, Hong-Sheng Jiang Department of Neurosurgery, Cangzhou Central Hospital, Cangzhou, Hebei 061000, People’s Republic of ChinaCorrespondence: Hai-Tao NiuDepartment of Neurosurgery, Cangzhou Central Hospital, No. 16, Xinhua West Road, Cangzhou, Hebei 061000, People’s Republic of ChinaEmail niujyrlps02495@163.comPurpose: At present, comprehensive therapy has been widely used in the treatment of glioma, but the curative effect is not good, and the survival rate of patients is low. Therefore, it is crucial to explore further the regulatory mechanism of the occurrence and development of glioma and find potential therapeutic targets. We aimed to investigate the columbamine (a tetrahydroisoquinoline alkaloid derived from the rhizome of Chinese herbal medicine Rhizoma Coptidis) on glioma progression.Methods: MTT, clone formation assay, wound healing assay, and transwell assay were performed to detect the cell viability, proliferation, migration, and invasion ability. Flow cytometry, TUNEL, and Western blot were used to identify the apoptosis level in glioma cells. PTEN inhibitor (SF1670) and AKT activator (SC79) were used to explore the mechanism of columbamine on glioma cell progression.Results: Columbamine inhibits proliferation, migration, invasion, and induces apoptosis in glioma cell lines (SHG44 and U251). Columbamine prevents phosphorylation of AKT and promotes the expression of PTEN. Blocking PTEN level or inducing phosphorylation of AKT attenuates columbamine function on SHG44 cells proliferation, metastasis, and apoptosis.Conclusion: In this research, we find that columbamine could inhibit proliferation and metastasis of glioma cell lines, and promote apoptosis of glioma cell lines via regulating PTEN/AKT signal pathway. It provides a new theoretical basis for the development of anti-glioma drugs.Keywords: columbamine, glioma, proliferation, PTEN, AKT

Dopamine depletion and microstructural degradation underlie the neurodegenerative processes in Parkinson’s disease (PD). To explore early alterations and underlying associations of dopamine and microstructure in PD patients utilizing the hybrid positron emission tomography (PET)-magnetic resonance imaging (MRI). Twenty-five PD patients in early stages and twenty-four matched healthy controls underwent hybrid 18F-fluorodopa (DOPA) PET-diffusion tensor imaging (DTI) scanning. The striatal standardized uptake value ratio (SUVR), DTI maps (fractional anisotropy, FA; mean diffusivity, MD) in subcortical grey matter, and deterministic tractography of the nigrostriatal pathway were processed. Values in more affected (MA) side, less affected (LA) side and mean were analysed. Correlations and mediations among PET, DTI and clinical characteristics were further analysed. PD groups exhibited asymmetric pattern of dopaminergic dysfunction in putamen, impaired integrity in the microstructures (nigral FA, putaminal MD, and FA of nigrostriatal projection). On MA side, significant associations between DTI metrics (nigral FA, putaminal MD, and FA of nigrostriatal projection) and motor performance were significantly mediated by putaminal SUVR, respectively. Early asymmetric disruptions in putaminal dopamine concentrations and nigrostriatal pathway microstructure were detected using hybrid PET-MRI. The findings further implied that molecular degeneration mediates the modulation of microstructural disorganization on motor dysfunction in the early stages of PD., To explore early alterations and underlying associations of dopamine levels and microstructure in Parkinson’s Disease (PD), Shang et al use a hybrid positron emission tomography (PET)-magnetic resonance imaging (MRI) approach in early stage patients and age-matched controls. Their data implies that molecular degeneration mediates the effects of microstructural disorganization on motor dysfunction in the early stages of PD.

Abnormal accumulation of α-synuclein contributes to the formation of Lewy bodies in the substantia nigra, which is considered the typical pathological hallmark of Parkinson’s disease. Recent research indicates that angiotensin-(1–7) plays a crucial role in several neurodegenerative disorders, including Parkinson’s disease, but the underlying mechanisms remain elusive. In this study, we used intraperitoneal administration of rotenone to male Sprague-Dawley rats for 4 weeks to establish a Parkinson’s disease model. We investigated whether angiotensin-(1–7) is neuroprotective in this model by continuous administration of angiotensin-(1–7) into the right substantia nigra for 4 weeks. We found that angiotensin-(1–7) infusion relieved characteristic parkinsonian behaviors and reduced α-synuclein aggregation in the substantia nigra. Primary dopaminergic neurons were extracted from newborn Sprague-Dawley rat substantia nigras and treated with rotenone, angiotensin-(1–7), and/or the Mas receptor blocker A-779 for 24 hours. After binding to the Mas receptor, angiotensin-(1–7) attenuated apoptosis and α-synuclein aggregation in rotenone-treated cells. Primary dopaminergic neurons were also treated with angiotensin-(1–7) and/or the autophagy inhibitor 3-methyladenine for 24 hours. Angiotensin-(1–7) increased α-synuclein removal and increased the autophagy of rotenone-treated cells. We conclude that angiotensin-(1–7) reduces α-synuclein aggregation by alleviating autophagy dysfunction in Parkinson’s disease. Therefore, the angiotensin-(1–7)/Mas receptor axis plays an important role in the pathogenesis of Parkinson’s disease and angiotensin-(1–7) has potential therapeutic value for Parkinson’s disease. All experiments were approved by the Biological Research Ethics Committee of Nanjing First Hospital (approval No. DWSY-2000932) in January 2020.

Objective: Previous studies revealed that 18F-FDOPA uptake was significantly decreased in the subregions of striatum contralateral to the side with predominant symptoms and was helpful for improving the early diagnostic accuracy of PD. However, in these studies, more than half of the PD patients already have bilateral motor symptoms (mH&Y stage≥2). This study was aimed to extend previous findings to a milder disease stage. Methods: Sixteen PD patients with only mild and unilateral motor symptoms (mH&Y stage=1 and disease duration≤2 years) and 22 healthy controls were involved. Striatal 18F-FDOPA uptake was analyzed using a ratio approach. Results: The SORs in the subregions of the contralateral striatum, including caudate, anterior putamen and posterior putamen were significantly decreased in the mild stage PD patients. The SOR for the contralateral posterior putamen had the largest area under the receiver operating characteristic curve (0.963) and separated mild stage PD patients from healthy controls with a sensitivity of 93.75% and a specificity of 95.45% when the cut-off value of Conclusion: These data indicate that contralateral posterior putaminal 18F-FDOPA uptake may represent a potential marker for early diagnosis of PD, especially in patients with only mild and unilateral motor symptoms.

Purpose The aim of this study was to examine the association between eHealth literacy and health-related quality of life (HRQoL) and explore whether health-promoting behaviors mediate the association between eHealth literacy and HRQoL among Chinese older adults. Methods An anonymous cross-sectional survey was conducted among 2300 adults aged 60 or older from Jinan, China. The eHealth Literacy Scale, Short-Form Health-Promoting Lifestyle Profile, and Short-Form Health Survey (SF-12) were used to measure eHealth literacy, health-promoting behaviors, and HRQoL. Multivariate linear regression analyses were conducted to test the association between eHealth literacy, health-promoting behaviors, and HRQoL. The mediation analyses, composed of PROCESS analysis and bootstrapping method, were preformed to test both total (c), direct (c'), and indirect effects (a*b) of eHealth literacy on HRQOL through health-promoting behaviors. Results Regression analyses indicated that eHealth literacy (B = 0.487, p B = 0.257, p c' = 0.183, p a*b = 0.125, bootstrapped 95% confidence interval (CI) = 0.094–0.157). The indirect effect accounted for 40.6% of the total effect (c = 0.308, bootstrapped 95% CI 0.241–0.376) of eHealth literacy on HRQoL. Conclusions Health-promoting behaviors mediated the association between eHealth literacy and HRQoL in Chinese older adults. The establishment of interventions focused on health-promoting behavior may be an effective way to help older adults with low eHealth literacy improve their HRQoL.

Based on the perturbation method, axisymmetric contact vibration of a rigid spherical punch on a piezoelectric half-space is studied in this paper. It is assumed that the rigid punch is a perfect insulating body with zero electric charge distribution. A compressive force composed of a static force and a time-harmonic force is applied to the spherical punch normally on the top of the surface. The variable contact radius and contact pressure are caused at the contact region for this dynamic contact problem. With the aid of Hankel integral transform technique, the dynamic contact model is established and the dynamic contact stiffness is derived from different contact displacement conditions, including two-point and one-point displacement conditions. Numerical examples are provided to show the effects of the oscillating frequency, contact displacement condition, internal friction, piezoelectric effect and material constants on the dynamic contact stiffness.

Parkinson's disease (PD) seriously threatens human's health. Researches have shown a close correlation between long non-coding RNAs (lncRNAs) and PD. However, the biological function of lncRNA homeobox transcript antisense RNA (HOTAIR) in PD remains largely unknown. In this study, we established PD models in vivo and in vitro by using 1-methyl-4-phenyl-2, 3, 6-tetrahydropyridine (MPTP) and 1-methyl-4-phenylpyridinium (MPP+) to assess the role of HOTAIR in pyroptotic cell death and neuronal damage. RNA immunoprecipitation (RIP) and dual luciferase reporter assay were used to verify the interaction between miR-326 and HOTAIR or ELAV like RNA binding protein 1 (ELAVL1). LncRNA HOTAIR was upregulated in PD mice and MPP+ induced SH-SY5Y cells. Additionally, knockdown of HOTAIR notably attenuated the symptom of PD in vivo. Downregulation of HOTAIR could obviously promoted cell viability and suppressed NLR family pyrin domain containing 3 (NLRP3) mediated pyroptotic cell death of SH-SY5Y cells in the presence of MPP+. Further, lncRNA HOTAIR positively regulated ELAVL1 expression by targeting miR-326, and downregulation of HOTAIR or ELAVL1 notably suppressed promotive effects of miR-326 inhibitor on MPP+ induced pyroptosis via activation of NLRP3 inflammasome. Collectively, HOTAIR silencing significantly inhibits neuronal damage through repressing NLRP3 mediated pyroptosis activation via regulation of miR-326/ELAVL1 axis in PD, which may contribute to a better understanding of PD pathogenesis and provide new treatment strategies for this disease.

Group 3 innate lymphoid cells (ILC3) are an important regulator for immunity, inflammation and tissue homeostasis in the intestine, but how ILC3 activation is regulated remains elusive. Here we identify a new circular RNA (circRNA) circKcnt2 that is induced in ILC3s during intestinal inflammation. Deletion of circKcnt2 causes gut ILC3 activation and severe colitis in mice. Mechanistically, circKcnt2, as a nuclear circRNA, recruits the nucleosome remodeling deacetylase (NuRD) complex onto Batf promoter to inhibit Batf expression; this in turn suppresses Il17 expression and thereby ILC3 inactivation to promote innate colitis resolution. Furthermore, Mbd3−/−Rag1−/− and circKcnt2−/−Rag1−/− mice develop severe innate colitis following dextran sodium sulfate (DSS) treatments, while simultaneous deletion of Batf promotes colitis resolution. In summary, our data support a function of the circRNA circKcnt2 in regulating ILC3 inactivation and resolution of innate colitis., Type 3 innate lymphoid cells (ILC3) are involved in maintaining gut immune homeostasis. Here the authors identify a circular RNA, circKcnt2, to be induced in ILC3s from inflamed gut, yet circKcnt2 deletion aggravates mouse experimental colitis, thereby implicating circKcnt2 as a potential feedback regulator of ILC3 activation and gut immunity.

Homeobox transcript antisense RNA (HOTAIR), has been associated with neuroprotective effects in Parkinson’s disease (PD). However, the underlying mechanisms still remain unclear. Hence, this present study attempted to clarify the functional relevance of HOTAIR in PD. We established an in vivo mouse model of PD using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and an in vitro cell model of PD by treating dopaminergic neuron MN9D cells with 1-methyl-4-phenylpyridinium species (MPP+). The expressions of somatostatin receptor 1 (SSTR1) and HOTAIR were altered to examine their effects on MN9D cell viability and apoptosis, as well as on movement impairments in MPTP-induced PD mouse model. The results indicated that HOTAIR expression was upregulated and SSTR1 was downregulated in in vivo and in vitro PD models. HOTAIR could bind to the promoter region of SSTR1, resulting in an increase of SSTR1 methylation through the recruitment of DNA methyltransferases in PD cell models. Notably, overexpression of HOTAIR and silencing of SSTR1 enhanced dopaminergic neuron apoptosis in MN9D cells and exacerbated dyskinesia in MPTP-induced PD mouse model. Collectively, overexpressed HOTAIR stimulates DNA methylation of SSTR1 to reduce SSTR1 expression, thereby accelerating dyskinesia and facilitating dopaminergic neuron apoptosis in a MPTP-lesioned PD mouse model via activation of the ERK1/2 axis., Graphical Abstract, HOTAIR-induced SSTR1 gene methylation results in a decline of SSTR1 expression, which accelerates the progression of dyskinesia in a MPTP-lesioned mouse model of Parkinson’s disease.

The gut microbiome is a complex ecosystem that contributes to host nutrition and health. However, our current knowledge of the relationship between ambient temperature and gut microbiota of poultry is still limited. The objective of the present study was to characterize the intestinal microbiota of ducks exposed to high ambient temperature. Sixty 60-day-old Shaoxing ducks were allocated to control and heat-treated groups. The ducks in the control group were kept at 25°C, and the ducks in the heat treatment group were raised at 30-40°C, which simulated the temperature change of day and night in summer. After 15 D, the intestinal contents of the duodenum, jejunum, and ileum were obtained from 6 ducks of each group. Genomic DNA was extracted and amplified based on the V4-V5 hypervariable region of 16S rRNA. The results showed that Firmicutes was the dominant bacterial phylum with the highest abundance in the contents of the small intestine of ducks, and the relative abundance of the phylum Firmicutes in all 3 intestinal segments was increased by high temperature. At the genus level, Lactobacillus was found to be the most dominant bacterial genus across 3 gut segments, and its abundance was increased in ducks under heat treatment. Compared with the corresponding intestine segment of control ducks, a total of 36 genera in the duodenum, 19 genera in the jejunum, and 6 genera in the ileum of heat-treated ducks were found to be significantly different in the abundance (linear discriminant analysis score >3.0, P < 0.05). Functional prediction of gut microbiota revealed that high temperature caused changes in the abundance of metabolism and transcription-related pathways. It is noteworthy that most of the altered pathways are related to metabolism. In conclusion, high temperature induced remarkable taxonomic changes in the gut microbiome of ducks, which might be related to the negative effects of high temperature in ducks. Our present study provided an important theoretical ground for high-temperature intervention.

Background This study is conducted to investigate the protective role of elevated microRNA-375 (miR-375) in dopaminergic neurons in Parkinson's disease through down-regulating transcription factor specificity protein 1 (SP1). Results The successfully modeled rats with Parkinson's disease showed aggregated neurobehavioral change, increased neuroinflammatory response and oxidative stress, and lowered dopamine content. Parkinson's disease rats treated with overexpressed miR-375 displayed improved neurobehavioral change, ameliorated neuroinflammatory response and oxidative stress, heightened dopamine content and abated neuronal apoptosis by down-regulating SP1. Up-regulation of SP1 reversed the protective effect of upregulated miR-375 on Parkinson's disease. Conclusion Up-regulation of miR-375 ameliorated the damage of dopaminergic neurons, reduced oxidative stress and inflammation in Parkinson's disease by inhibiting SP1. Methods Parkinson's disease rat model was established by targeted injection of 6-hydroxydopamine to damage the substantia nigra striatum. The successfully modeled Parkinson's disease rats were intracerebroventricularly injected with miR-375 mimics or pcDNA3.1-SP1. The functions of miR-375 and SP1 in neurobehavioral change, neuroinflammatory response, oxidative stress, dopamine content and expression of apoptosis-related proteins in the substantia nigra of Parkinson's disease rats were evaluated. The target relation of miR-375 and SP1 was confirmed by bioinformatics analysis and dual luciferase reporter gene assay.

Rumors in social media not only affect the health of online social networks, but also reduce the quality of information accessed by social media users. When emergencies occur, the rapid spread of rumors can even trigger mass anxiety and panic. However, the existing studies did not make a clear distinction between rumor and non-rumor information in public emergencies, so that they cannot effectively predict the rumor retweeting behavior. To this end, a model for predicting rumor retweeting behavior is presented based on the convolutional neural networks (CNN) called R-CNN model in the paper. In this model, the rumor retweeting behavior is considered as an important driving force of increasing the depth and breadth of rumor cascades, and four feature vectors are constructed with the historical textual content published by users, consisting of attention to public emergencies, attention to rumors, reaction time and tweeting frequency. To input the quantitative feature vectors for R-CNN, a K-means based core tweets extraction method is proposed to select the right tweets, and the quantitative feature representations are proposed. The predictive capability of the model has been proved by experiments base on two rumor datasets of emergencies crawled from Sina weibo. Experimental results indicate that the prediction accuracy of the model reaches 88%, and it can be improved by 7% on average compared with other models.

Objective This research was aimed to investigate the effects of baicalin on 6-hydroxydopamine (6-OHDA)-induced rat model of Parkinson's disease (PD) and the main mechanism of baicalin based on metabolomics. Methods The rat model of PD was induced by 6-OHDA. The protective effects of baicalin on rat model of PD were evaluated by open field test and rotarod test. The anti-PD efficacy of baicalin was evaluated by examining the morphologic changes of neurons and the level of monoamine neurotransmitters in the striatum, the number and morphology of tyrosine hydroxylase (TH)-positive neurons, and oxidative stress. Combined with metabolomics methods, the pharmacodynamic mechanism of baicalin on PD pathogenesis was also explored. Results Baicalin treatment improved the rod time and voluntary movement in rat model of PD (P

Hepatocellular carcinoma (HCC) accounts for the majority of primary liver cancers and is characterized by high recurrence and heterogeneity, yet its mechanism is not well understood. Here we show that N1-methyladenosine methylation (m1A) in tRNA is remarkably elevated in hepatocellular carcinoma (HCC) patient tumour tissues. Moreover, m1A methylation signals are increased in liver cancer stem cells (CSCs) and are negatively correlated with HCC patient survival. TRMT6 and TRMT61A, forming m1A methyltransferase complex, are highly expressed in advanced HCC tumours and are negatively correlated with HCC survival. TRMT6/TRMT61A-mediated m1A methylation is required for liver tumourigenesis. Mechanistically, TRMT6/TRMT61A elevates the m1A methylation in a subset of tRNA to increase PPARδ translation, which in turn triggers cholesterol synthesis to activate Hedgehog signaling, eventually driving self-renewal of liver CSCs and tumourigenesis. Finally, we identify a potent inhibitor against TRMT6/TRMT61A complex that exerts effective therapeutic effect on liver cancer., Metabolic adaptation has been reported to promote cancer, yet the underlying mechanisms are not clear. Here, the authors show that m1A methylation in tRNA regulates cholesterol metabolism in liver cancer stem cells and m1A inhibition decreases tumourigenesis in preclinical models of hepatocellular carcinoma.

Background Hepatocellular carcinoma (HCC) is one of the most intractable tumors in the world due to its high rate of recurrence and heterogeneity. Liver cancer initiating cells also called cancer stem cells (CSCs) play a critical role in resistance against typical therapy and high tumor-initiating potential. However, the role of the novel circular RNA (circRNA) circIPO11 in the maintenance of liver cancer initiating cells remains elusive. Methods CircRNAs highly conserved in humans and mice were identified from 3 primary HCC samples by circRNA array. The expression and function of circIPO11 were further evaluated by Northern blot, limiting dilution xenograft analysis, chromatin isolation by RNA purification-PCR assay (ChIRP) and HCC patient-derived tumor cells (PDC) models. CircIpo11 knockout (KO) mice were generated by a CRISPR/Cas9 technology. Results CircIPO11 is highly expressed in HCC tumor tissues and liver CSCs. CircIPO11 is required for the self-renewal maintenance of liver CSCs to initiate HCC development. Mechanistically, circIPO11 recruits TOP1 to GLI1 promoter to trigger its transcription, leading to the activation of Hedgehog signaling. Moreover, GLI1 is also highly expressed in HCC tumor tissues and liver CSCs, and TOP1 expression levels positively correlate with the metastasis, recurrence and survival of HCC patients. Additionally, circIPO11 knockout in mice suppresses the progression of chemically induced liver cancer development. Conclusion Our findings reveal that circIPO11 drives the self-renewal of liver CSCs and promotes the propagation of HCC via activating Hedgehog signaling pathway. Antisense oligonucleotides (ASOs) against circIPO11 combined with TOP1 inhibitor camptothecin (CPT) exert synergistic antitumor effect. Therefore, circIPO11 and the Hedgehog signaling pathway may provide new potential targets for the treatment of HCC patients.

OBJECTIVE To compare the long-term survival outcomes of patients with apparent early-stage uterine serous carcinoma (USC) who underwent laparoscopic staging surgery with those who underwent open surgical staging. METHODS A total of 295 patients from four Chinese teaching hospitals were included. Overall survival (OS) and disease-free survival (DFS) were estimated and compared using the Kaplan-Meier method and the log-rank test among patients after laparoscopic surgery or open surgery. The Cox proportional hazards regression model was applied to adjust for potential confounding factors. RESULTS For patients with apparent early-stage USC, laparoscopic surgery was associated with deteriorated DFS (hazard ratio [HR] 1.83, 95% confidence interval [CI] 1.15-2.93, P = 0.012), and there was no significant difference in OS between the two groups (HR 1.74, 95% CI 0.99-3.08, P = 0.056). However, after adjusting for confounding factors, the surgical approach was not an independent prognostic factor for DFS (adjusted HR 1.16, 95% CI 0.63-2.12, P = 0.636) and OS (adjusted HR 1.11, 95% CI 0.52-2.38, P = 0.794) in apparent early-stage USC. CONCLUSION For apparent early-stage USC, laparoscopic surgery is safe. This needs to be confirmed by future prospective clinical trials.

Background As a country with one-fifth of the global population, China has experienced explosive growth in ischaemic stroke (IS) burden with significant ethnic and geographic disparities. The aim of this study was to examine the differences in potentially modifiable risk factors for ischaemic stroke among the Han population and two ethnic minorities (Tujia and Miao). Methods A case-control study was conducted with 324 cases of first-ever ischaemic stroke from the hospitals of the Xiangxi Tujia and Miao Autonomous Prefecture and 394 controls from communities covering the same area between May 1, 2018, and April 30, 2019. Structured questionnaires were administered, and physical examinations were performed in the same manner for cases and controls. Univariate and multivariate logistic regression analyses with adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were used to examine the association between risk factors and ischaemic stroke. An additive model was used to study the interaction between the modifiable risk factors and ethnicity with R software. Results Higher high-sensitivity C-reactive protein levels (OR 50.54, 95%CI 29.76–85.85), higher monthly family income (4.18, 2.40–7.28), increased frequency of hot pot consumption (2.90, 1.21–6.93), diabetes mellitus (2.62, 1.48–4.62), a higher apolipoprotein (Apo)B/ApoA1 ratio (2.60, 1.39–4.85), hypertension (2.52, 1.45–4.40) and moderate-intensity physical activity (0.50, 0.28–0.89) were associated with ischaemic stroke. There was an additive interaction between the ApoB/ApoA1 ratio and ethnicity in the Tujia and Miao populations with first-ever ischaemic stroke (the relative excess risk due to the interaction was 5.75, 95% CI 0.58 ~ 10.92; the attributable proportion due to the interaction was 0.65, 95% CI 0.38 ~ 0.91; the synergy index was 3.66, 95% CI 1.35 ~ 9.93). Conclusions This is the first case-control study examining modifiable risk factors for ischaemic stroke among the Han population and two ethnic minorities (Tujia and Miao) in China. Some differences were observed in the impact of risk factors among these ethnic groups. Our results may help interpret health-related data, including surveillance and research, when developing strategies for stroke prevention.

Lijun Fan,1,2 Shiyuan Wang,1,3 Hui Xue,1,3 Yue Ding,1,2 Jingwen Wang,1,2 Yong Tian,1,2 Wei Du1,3 1Key Laboratory of Environmental Medicine Engineering of Ministry of Education, School of Public Health, Southeast University, Nanjing, People’s Republic of China; 2Department of Medical Insurance, School of Public Health, Southeast University, Nanjing, People’s Republic of China; 3Department of Epidemiology and Biostatistics, School of Public Health, Southeast University, Nanjing, People’s Republic of ChinaCorrespondence: Wei DuDepartment of Epidemiology and Biostatistics, School of Public Health, Southeast University, No. 87 Dingjiaqiao, Nanjing, 210009, People’s Republic of ChinaEmail duwei@seu.edu.cnPurpose: Population ageing is posing an unprecedented challenge globally, necessitating a better understanding of modifiable factors and underlying pathways that could contribute to health and longevity in older age. We thus aim to investigate how the modifiable social support (and its various sources) is related to mortality among older adults, as well as whether and to what extent geriatric frailty plays a role in mediating the relationship.Methods: We included 11,934 community-dwelling adults (≥ 65) from four waves of the Chinese Longitudinal Healthy Longevity Survey (2008– 2018). Frailty was constructed by 44 health deficits, following a validated frailty index scale. Social support was measured using a sum score of three dimensions (family support, social service and social security) with 22 items. The outcome was all-cause mortality. Multivariate logistic or linear regression models were employed when appropriate to assess the associations among social support, frailty and mortality. Mediation analysis was applied to examine the role of frailty underlying the pathway between social support and mortality risk.Results: A higher sum score of social support at baseline reduced mortality risk during the 10-year follow-up period (AOR=0.947, 95% CI=0.917∼ 0.977). Amongst three sources of social support, family support and social security availability showed significantly protective effect against mortality, while social service revealed only non-significant effect. A higher level in the overall social support (β=− 0.066, 95% CI=− 0.113∼-0.020) or family support (β=− 0.121, 95% CI=− 0.202∼-0.039) was also significantly associated with decreased frailty. Meanwhile, frailty partially mediated the relationship of mortality with the overall social support and family support, where the proportion of mediation equaled to 17.1% and 20.5%, respectively.Conclusion: Social support could be associated with reduced risks for frailty and mortality, and such protective influences are especially manifested in its family support component among Chinese older adults. Frailty functions as potential mediator underlying the association of mortality with social support and family support. Our findings indicate the importance of social support as an integral part of geriatric care and underline the potential benefits of frailty assessment and intervention.Keywords: social support, frailty, mortality, older adults, mediation, China

Intestinal stem cells (ISCs) are maintained by stemness signaling for precise modulation of self-renewal and differentiation under homeostasis. However, the way in which intestinal immune cells regulate the self-renewal of ISCs remains elusive. Here we found that mouse and human Lgr5+ ISCs showed high expression of the immune cell-associated circular RNA circPan3 (originating from the Pan3 gene transcript). Deletion of circPan3 in Lgr5+ ISCs impaired their self-renewal capacity and the regeneration of gut epithelium in a manner dependent on immune cells. circPan3 bound mRNA encoding the cytokine IL-13 receptor subunit IL-13Rα1 (Il13ra1) in ISCs to increase its stability, which led to the expression of IL-13Rα1 in ISCs. IL-13 produced by group 2 innate lymphoid cells in the crypt niche engaged IL-13Rα1 on crypt ISCs and activated signaling mediated by IL-13‒IL-13R, which in turn initiated expression of the transcription factor Foxp1. Foxp1 is associated with β-catenin in rendering its nuclear translocation, which caused activation of the β-catenin pathway and the maintenance of Lgr5+ ISCs.

Coreopsis tinctoria flowers, a well-known medicinal and edible plant, have been reported to possess antioxidant and anti-inflammatory activities. However, its protective effects and underlying mechanisms on liver injury remain unclear. The aim of this study was to investigate the underlying mechanisms by which Coreopsis tinctoria flowers phenolic extract (CTP) alleviated D-galactosamine and lipopolysaccharide (D-GalN/LPS) induced acute liver injury in mice. Our results showed that pretreatment with CTP improved liver histology while decreased levels of serum aminotransferase and malondialdehyde. CTP also increased levels of glutathione in D-GalN/LPS -induced acute liver injury mice by up-regulation of nuclear factor erythroid 2-related factor 2 (Nrf2), peroxisome proliferator-activated receptor alpha (PPARα), and peroxisome proliferator-activated receptor gamma (PPARγ). In conclusion, results suggested that CTP protected against D-GalN/LPS -induced acute liver injury by up-regulation of Nrf2, PPARα, and PPARγ.

Background To determine the clinical value of multigene polymorphisms, LDL-C and sdLDL-C on T2DM therapy. Methods In total, 352 T2DM patients before and after treatment and 48 healthy individuals were enrolled in this study. LDL-C and sdLDL-C were detected in 352 T2DM patients and 48 healthy individuals by Quantimetrix Lipoprint System. The 11 gene polymorphisms—HTR3B (rs2276307, A > G), APOE (rs7412, c.526C > T), APOE (rs429358, c.388 T > C), CYP2C9*3 (rs1057910, c.1075A > C), KIF6 (rs20455, c.2155 T > C), HMGCR (rs17238540, T > G), HMGCR (rs17244841, A > T), ABCB1 (rs2032582, A > C/T), HTR7 (rs1935349, C > T), SLCO1B1 (rs4149056, c.521 T > C), and CETP (rs708272, G > A)—were screened in these 352 T2DM patients by the Agena Bioscience MassARRAY system before therapy. Results Genetic polymorphisms associated with T2DM and statin effects in pretreatment patients were detected, then results showed that all 11 genes had heterozygous mutation, and 7 genes had homozygous mutation in 352 T2DM patients, more specifically reflected that these gene polymorphisms were common in Chinese T2DM patients. LDL-C and sdLDL-C were detected before and after treatment, sdLDL mainly existed in T2DM patients, and T2DM patients had higher mean levels of sdLDL-C than healthy people. After pharmacotherapy, the coincidence rates of decreases in LDL-C and sdLDL-C levels were 88.35% (311/352) and 84.09% (296/352), consistent with patients in remission. Conclusions Gene polymorphisms related to pharmacotherapy were common in Chinese T2DM patients. And the expression of LDL-C and sdLDL-C was consistent with the T2DM disease course. Combined multigene screening before therapy and LDL-C and sdLDL-C detection before and after therapy could better assist T2DM treatment.

Background: As a country with one-fifth of the global population, China has had explosive growth in ischemic stroke burden with significant ethnic and geographic disparities. The aim of this study was to examine the relative risk of potentially modifiable risk factors for ischemic stroke among the Han population and two ethnic minorities (Tujia and Miao).Methods: A case-control study was conducted: 324 cases of first-ever IS from the hospitals of the Xiangxi Tujia and Miao Autonomous Prefecture and 394 controls were surveyed using structured questionnaires from communities covering the same area. Univariate and multivariate logistic regression analyses with adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were used to examine the association between risk factors and ischemic stroke. The additive model was used to study the interaction between the modifiable risk factor and ethnicity in the R software.Results: Higher high-sensitivity C-reactive protein level(OR 50.54, 95%CI 29.76-85.85), higher monthly family income(4.18, 2.40-7.28), increased frequency of hot pot consumption (2.90, 1.21-6.93), diabetes mellitus (2.62, 1.48-4.62), higher apolipoprotein(Apo)B/ApoA1 ratio(2.60, 1.39-4.85), hypertension(2.52, 1.45-4.40) and moderate-intensity physical activity(0.50, 0.28-0.89) were associated with ischemic stroke. There is an additive interaction between ApoB/ApoA1 ratio and ethnicity in Tujia and Miao populations with first-ever ischemic stroke (the relative excess risk due to interaction was 5.75, 95%CI 0.58~10.92; the attributable proportion due to interaction was 0.65, 95%CI 0.38~0.91; the synergy was 3.66, 95%CI 1.35~9.93). Conclusions: It is the first case-control study examining modifiable risk factors for ischemic stroke among the Han population and two ethnic minorities (Tujia and Miao) in China, some differences were observed in the impact of risk factors among these ethnic groups. Our results may help interpret health-related data, including surveillance and research, when developing strategies for stroke prevention.

Survival rates are usually used to evaluate the effect of cancer treatment and prevention. No study has focused on the characteristic of population-based cancer survival in Fujian, which is regarded as one of the high-risk areas of cancer in China. This study aims to analyze the 5-year relative survival of patients in Fujian Province using population-based cancer registry data. A total of 8 population-based registries in Fujian Province reported cancer cases diagnosed in 2012-2014. Relative survival was calculated as the ratio between observed survival and expected survival. The 5-year relative survival for all cancers combined was 36.19% and the age-standardized 5-year relative survival for all patients was 31.80%. Females had higher relative survival than males (38.90% and 27.00%). The patients in urban areas had higher relative survival than those in rural areas (32.34% and 31.29%). Lung, gastric, liver, colorectal, and esophageal cancers were the five most common cancers, with 5-year relative survival below 50%. This is the first study that evaluated the population-based cancer relative survival in Fujian, China. Our study suggests that the overall survival of cancer patients in Fujian Province is poor. Furthermore, the results of this study can be used as a baseline for further research in Fujian, and provide important evidence for cancer etiology research.

Tuft cells as a type of intestinal epithelial cells exist in epithelial barriers that play a critical role in immunity against parasite infection. It remains elusive about whether Tuft cells participate in bacterial eradication. Here we identify Sh2d6 as a signature marker for CD45+ Tuft-2 cells. Tuft-2 cells are derived from Lgr5+ intestinal stem cells but not bone marrow cells. Depletion of Tuft-2 cells is susceptible to bacterial infection. Tuft-2 cells quickly expand over bacterial infection and sense bacterial metabolite N-undecanoylglycine through vomeronasal receptor Vmn2r26. Mechanistically, Vmn2r26 engagement with N-undecanoylglycine activates GPCR-PLCγ2-Ca2+ signal axis, which initiates prostaglandin D2 (PGD2) production. PGD2 enhances mucus secretion of Goblet cells and induces antibacterial immunity. Moreover, Vmn2r26 signaling also promotes SpiB expression, which is responsible for Tuft-2 cell development and expansion over bacterial challenge. Our findings reveal a novel function of Tuft-2 cells in immunity against bacterial infection through Vmn2r26-mediated recognition of bacterial metabolites.

To investigate the molecular mechanism of long noncoding RNA cancer susceptibility candidate 9 involved in gefitinib resistance in non-small cell lung cancer cells by regulating microRNA-382-5p/ phosphoinositidedependent protein kinase-1/mammalian target of rapamycin complex 2 signal axis. 10 cases of serum before treatment and 10 cases of drug resistant serum after gefitinib treatment were collected from December 2019 to December 2020. The expression levels in non-small cell lung cancer tissues or cell lines were detected by real-time quantitative reverse transcription polymerase chain reaction. Cell counting kit 8, transwell and cell flow cytometry were used to detect the sensitivity of non-small cell lung cancer cells to gifetinib. Double luciferase reporter assay was used to verify the targeting relationship and the regulatory relationship was detected by western blotting and real-time quantitative reverse transcription polymerase chain reaction. Cancer susceptibility candidate 9 was highly expressed in non-small cell lung cancer tissues and drug-resistant HCC827/G cells. Overexpression of cancer susceptibility candidate 9 can significantly promote the proliferation, invasion and inhibit apoptosis of HCC827/G cells. At the same time, dual luciferase reporter assay confirmed that cancer susceptibility candidate 9 could negatively regulate the expression of microRNA-382-5p and microRNA-185-5p could bind to the 3'UTR of phosphoinositidedependent protein kinase-1 and mammalian target of rapamycin complex 2 and negatively regulate the expression of phosphoinositide-dependent protein kinase-1 and mammalian target of rapamycin complex 2. Further experiments showed that cancer susceptibility candidate 9 could up regulate the drug resistance of HCC827/G cells to gefitinib by down regulating the inhibition of microRNA-382-5p on phosphoinositide-dependent protein kinase-1 and mammalian target of rapamycin complex 2, thereby promoting the proliferation, invasion and inhibiting apoptosis of HCC827/G cells. Cancer susceptibility candidate 9 induces gefitinib resistance in non-small cell lung cancer cells by regulating microRNA-382- 5p/phosphoinositide-dependent protein kinase-1/mammalian target of rapamycin complex 2 signal axis.

Altres ajuts: Cancer Center (CORE) Support grant CA 21765, i l'American Lebanese Syrian Associated Charities Altres ajuts: NIH/GM45737 Choline cytidylyltransferase (CCT) is the rate-limiting enzyme in the phosphatidylcholine biosynthetic pathway. Here, we demonstrate that CCTα-mediated phosphatidylcholine synthesis is required to maintain normal Golgi structure and function as well as cytokine secretion from the Golgi complex. CCTα is localized to the trans-Golgi region and its expression is increased in lipopolysaccharide (LPS)-stimulated wild-type macrophages. Although LPS triggers transient reorganization of Golgi morphology in wild-type macrophages, similar structural alterations persist in CCTα-deficient cells. Pro-tumor necrosis factor α and interleukin-6 remain lodged in the secretory compartment of CCTα-deficient macrophages after LPS stimulation. However, the lysosomal-mediated secretion pathways for interleukin-1β secretion and constitutive apolipoprotein E secretion are unaltered. Exogenous lysophosphatidylcholine restores LPS-stimulated secretion from CCTα-deficient cells, and elevated diacylglycerol levels alone do not impede secretion of pro-tumor necrosis factor α or interleukin-6. These results identify CCTα as a key component in membrane biogenesis during LPS-stimulated cytokine secretion from the Golgi complex.

At present, comprehensive therapy has been widely used in the treatment of glioma, but the curative effect is not good, and the survival rate of patients is low. Therefore, it is crucial to explore further the regulatory mechanism of the occurrence and development of glioma and find potential therapeutic targets. We aimed to investigate the columbamine (a tetrahydroisoquinoline alkaloid derived from the rhizome of Chinese herbal medicine Rhizoma Coptidis) on glioma progression.MTT, clone formation assay, wound healing assay, and transwell assay were performed to detect the cell viability, proliferation, migration, and invasion ability. Flow cytometry, TUNEL, and Western blot were used to identify the apoptosis level in glioma cells. PTEN inhibitor (SF1670) and AKT activator (SC79) were used to explore the mechanism of columbamine on glioma cell progression.Columbamine inhibits proliferation, migration, invasion, and induces apoptosis in glioma cell lines (SHG44 and U251). Columbamine prevents phosphorylation of AKT and promotes the expression of PTEN. Blocking PTEN level or inducing phosphorylation of AKT attenuates columbamine function on SHG44 cells proliferation, metastasis, and apoptosis.In this research, we find that columbamine could inhibit proliferation and metastasis of glioma cell lines, and promote apoptosis of glioma cell lines via regulating PTEN/AKT signal pathway. It provides a new theoretical basis for the development of anti-glioma drugs.

Frailty, a multidimensional syndrome characterized by vulnerability to stressors, is an emerging public health priority with high prevalence in older adults. Frailty has been identified to predictive negative health outcomes, yet quantified evidence regarding its effect on health care systems is scarce. This study examines how frailty affects health care utilization, and explores whether these associations varied by gender.Cohort study with a 2-year follow-up.and Participants: Data were derived from 2 waves (2011 and 2013) of the China Health and Retirement Longitudinal Study, and 3119 community-dwelling participants aged ≥60 years were analyzed.Frailty was assessed by a validated frailty phenotype scale, and measures for health care utilization were self-reported. Panel data approach of mixed-effects regression models was used to examine the associations.Longitudinal results demonstrated that compared with robustness, prefrailty and frailty were both significantly associated with increased likelihood of outpatient visit, inpatient visit, and inpatient length of stay, even after adjusting for multimorbidity in multivariate analyses (all P .05). Every 1-component increase in frailty was also found to significantly increase the risk for health care utilization [any outpatient visit: adjusted odds ratio (OR) 1.30, 95% confidence interval (CI) 1.14-1.48; number of outpatient visits: adjusted incident rate ratio (IRR) 1.34, 95% CI 1.18-1.53; any inpatient visit: adjusted OR 1.44, 95% CI 1.22-1.71; number of inpatient visits: adjusted IRR 1.40, 95% CI 1.20-1.62; inpatient length of stay: adjusted IRR 1.50, 95% CI 1.18-1.92]. The preceding associations were similarly observed irrespective of gender.Frailty is a significant predictor for increased health care utilization among community-dwelling older adults. These findings have important implications for routine clinical practice and public health investment. Early screening and intervention for potentially modifiable frailty could translate into considerable savings for households and health care systems.

Avian eggshell color is an interesting genetic trait. Here, we report that the blue eggshell color of the domestic duck is caused by two cis-regulatory G to A transitions upstream of ABCG2, which encodes an efflux transporter. The juxtaposed blue eggshell allele A-A exhibited higher promoter activity and stronger nuclear protein binding capacity than the white eggshell allele G-G. Transcription factor analysis suggested differential binding capability of CTCF between blue eggshell and white eggshell alleles. Knockdown of CTCF expression significantly decreased the promoter activity of the blue eggshell but not the white eggshell allele. DNA methylation analysis revealed similar high methylation of the region upstream of the CTCF binding sites in both blue-eggshelled and white-eggshelled ducks. However, DNA methylation levels downstream of the binding sites were decreased and 35% lower in blue-eggshelled ducks than in white-eggshelled ducks. Consistent with the in vitro regulatory pattern of causative sites, ABCG2 exhibited higher expression in uteruses of blue-eggshelled ducks and also showed polarized distribution in their endometrial epithelial cells, distributing at the apical surface of endometrial epithelial cells and with orientation toward the uterine cavity, where the eggshell is pigmented. In conclusion, our results suggest that two cis-regulatory SNPs upstream of ABCG2 are the causative mutations for blue eggshells in ducks. The blue eggshell variant up-regulated ABCG2 expression through recruiting CTCF binding, which may function as a barrier element to shield the downstream region from high methylation levels present upstream. ABCG2 was identified as the only candidate causative gene for blue eggshells; it may function as an efflux transporter of biliverdin to the uterine cavity., Author summary Avian eggshell color is an interesting genetic trait that has been related to numerous interesting biological functions, such as crypsis, mimicry, and protection from ultraviolet radiation. In ducks, blue eggshells are a dominant Mendelian trait. The color is preferred by customers and has become one of the main breeding targets in laying ducks in China. In this study, we identified that duck blue eggshells are likely caused by two cis-regulatory variations that synergistically up-regulate ABCG2 expression in the uterus. ABCG2 was identified as the only candidate causative gene for blue eggshell; it may function as an efflux transporter of biliverdin to the uterine cavity, where the eggshell is pigmented. Our study provides useful molecular markers for breeding of blue-eggshelled ducks.

Background The aim of the present study was to evaluate the prognosis among patients with a single large hepatocellular carcinoma (HCC) >5 cm compared with other patients in Barcelona Clinic Liver Cancer (BCLC) stage A or stage B. Material/Methods Data on patients with BCLC stage A/B HCC were collected between 2008 and 2012. BCLC stage A was subclassified as A1 (single tumor, 2–5 cm, or 2–3 nodules ≤3 cm), or A2 (single tumor >5 cm). Overall survival (OS) was evaluated and compared. Results Among 1005 patients with HCC, 455 were stage A1, 188 were stage A2, and 362 were stage B. The OS of stage A2 patients was significantly worse than that of stage A1 patients (median survival, 30.6 vs. 43.2 months, p5 cm had a comparable survival with BCLC stage B. HCC >5 cm should therefore be classified as an intermediate stage.

Around 15% of patients with Parkinson's disease (PD) have a family history, and 5–10% have confirmed genetic causes. PRKN is the most common gene responsible for early-onset Parkinson's disease (EOPD), while rare variants of PLA2G6 likely raise PD susceptibility in the Chinese population. We investigated the genetic information of 13 members of a Han Chinese family with known EOPD by whole-exome sequencing and Sanger sequencing, and analyzed the clinical history, physical examination, blood laboratory test, and brain imaging data of the patients. Two members, including the proband, were suspected of having EOPD. A novel homozygous frameshift mutation, c.856delT, and a compound heterozygous mutation, c.1321T>C/c.856delT of PRKN, were identified, as well as two single nucleotide variants of PLA2G6 and TENM4. The proband exhibited a rare symmetrical resting tremor limited to her lower limbs and never exhibited signs of rigidity. 18F-DOPA PET/CT scan indicated a symmetrical reduced signaling in the striatum. The novel frameshift mutation and compound heterozygous mutation of PRKN are likely to be the genetic causes of EOPD in this family.

The abuse of antibiotics for agricultural purposes has been under scrutiny. Therefore, there is an urgent need to find antibiotic substitutes in animal production. The effects of chlorogenic acid, β-D-Glucan, astragalus flavone, CpG-DNA, and chicken IgG on spleen antioxidant capacity, apoptosis, and the immune response in Shaoxing ducklings were investigated in this study. The ducklings treated with β-D-Glucan, astragalus flavone, CpG-DNA, and chicken IgG showed significant reduction in catalase and superoxide dismutase activities. The five immunopotentiators facilitated caspase three expression and reduced Bcl2 expression in the spleen. Compared to the control group, the protein level of COX2 was significantly up-regulated in the chlorogenic acid, CpG-DNA, and chicken IgG groups. The protein level of iNOS expression was significantly improved in all immunopotentiator groups, except for the astragalus flavone group. The five immunopotentiators induced IL-1β, IFN-α, IFN-β, TNF-α, RIG-I, TLR3, and TLR7 gene expression. In summary, chlorogenic acid, β-D-Glucan, astragalus flavone, CpG-DNA, and chicken IgG, as immunopotentiators, improved the innate immune response in the ducklings, which not only provides a new avenue for the development of efficient approaches to prevent pathogen infections, but also offers an alternative to antibiotics in animal production.

// Qing Gao 1,* , Zhou Ou 1,* , Teng Jiang 1,* , You-Yong Tian 1 , Jun-Shan Zhou 1 , Liang Wu 1 , Jian-Quan Shi 1 and Ying-Dong Zhang 1 1 Department of Neurology, Nanjing First Hospital, Nanjing Medical University, Nanjing, PR China * These authors as co-first authors Correspondence to: Ying-Dong Zhang, email: // Keywords : renin-angiotensin system; angiotensin II; Parkinson’s disease; apoptosis; azilsartan; Gerotarget Received : January 02, 2017 Accepted : February 08, 2017 Published : February 25, 2017 Abstract Loss of dopaminergic neurons within the substantia nigra (SN) is a pathological hallmark of Parkinson’s disease (PD), which leads to the onset of motor symptoms. Previously, our in vitro studies revealed that Angiotensin II (Ang II) induced apoptosis of dopaminergic neurons through its type 1 receptor (AT1R), but these findings needed to be confirmed via animal experiments. Here, using a rotenone-induced rat model of PD, we observed an overactivation of Ang II/AT1R axis in the SN, since Ang II level and AT1R expression were markedly increased. Furthermore, we provided in vivo evidence that Ang II directly elicited apoptosis of dopaminergic neurons via activation of AT1R in the SN of rats. More importantly, we showed for the first time that oral administration of azilsartan, a newly developed AT1R blocker approved by the U.S. Food and Drug Administration for hypertension treatment, rescued the apoptosis of dopaminergic neurons and relieved the characteristic parkinsonian symptoms in PD rats. These results support the application of AT1R blockers in PD therapy, and strengthen the notion that many therapeutic agents may possess pleiotropic action in addition to their main applications.

The goal of the present study was to elucidate the mechanism by which long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (lncRNA MALAT1) promotes inflammation in Parkinson’s disease (PD). 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was used to induce PD development in C57BL/6 mice, and tyrosine hydroxylase (TH) expression was analysed by immunohistochemical analysis. Western blot and qPCR analyses were conducted to assess the expression of protein and mRNA levels, respectively. Lipopolysaccharide/adenosine triphosphate (LPS/ATP) was used to activate microglia in vitro. Chromatin immunoprecipitation (ChIP), RNA pull-down and RNA immunoprecipitation chip (RIP) assays were performed to investigate the interaction among specific molecules. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to evaluate cell viability and proliferation. Flow cytometry was performed to analyse cell apoptosis after staining. The dichlorofluorescein diacetate (DCFH-DA) assay was used to measure the generation of reactive oxygen species (ROS) in cells. The results showed that MALAT1 was highly expressed in the brains of MPTP-induced PD model mice and in LPS/ATP-induced microglia cells. Knockdown of MALAT1 inhibited elevated nuclear factor (erythroid-derived 2)-like-2 factor (NRF2) expression, thereby inhibiting inflammasome activation and ROS production. MALAT1 was shown to promote neuroinflammation by recruiting enhancer of zeste homologue 2 (EZH2) to the promoter of NRF2, suppressing Nrf2 expression. In summary, MALAT1 epigenetically inhibits NRF2, thereby inducing inflammasome activation and reactive oxygen species (ROS) production in PD mouse and microglial cell models.

Background Social capital has been linked to health behaviours, but the underlying mechanism is unclear. Previous studies have found that health literacy played the role of a mediator in the relationships among social capital, individual physical activity and nutrition. But it is not clear whether eHealth literacy mediates the impact of social capital on health behaviours. Therefore, our research aimed to explore the relationships among social capital (structural and cognitive social capital), eHealth literacy, and the health behaviours of elderly people, and to analyse the mediating effect of eHealth literacy, while providing a theoretical basis for a health behaviour intervention for elderly people. Methods From January to February 2019, we conducted a cross-sectional survey of 1201 Chinese people aged over 60 years using the Chinese Shortened Social Capital Scale (contains two subscales of structural social capital and cognitive social capital), eHealth Literacy Scale, and Health-Promoting Lifestyle Profile. We used structural equation modelling to test a hypothetical mediation model. Results The mean scores of social capital was 72.07 (SD = 13.03), 17.24 (SD = 9.34) for eHealth literacy, and 112.23 (SD = 23.25) for health behaviours. Social capital and eHealth literacy were significantly correlated with health behaviours, and social capital and structural social capital were significantly correlated with eHealth literacy. Lastly, eHealth literacy mediated the relationship between structural social capital and health behaviours. Conclusions eHealth literacy was an important mediating factor for elderly people’s structural social capital and health behaviours. Therefore, social capital and eHealth literacy must be considered when designing and implementing health behaviour intervention programmes for elderly people.

Innate lymphoid cells (ILCs) reside in mucosal surfaces to potentiate immune responses, sustain mucosal integrity and maintain tissue homeostasis. However, how tumor infiltrating ILCs modulate tumor development and progression is unclear. Here we profiled tumor infiltrating ILCs during colorectal cancer (CRC) progression by single-cell RNA sequencing. We identified six clusters of tumor infiltrating ILCs with unique features. ILC1s expressed inhibitory receptors and underwent inhibitory functional conversion at the late stage of CRC. ILC2s were classified into three subsets (called ILC2-A, -B, -C), of which ILC2-C subset could facilitate tumor progression. HS3ST1 and PD1 were highly expressed in ILC2s of late stage CRC tumors and deficiency of HS3ST1 or PD1 in ILC2s suppressed tumor growth. Moreover, ILC3s transdifferentiated into ILCregs during CRC progression and ILCregs promoted tumor growth. Of note, TGF-β signaling initiated the conversion of ILC3s to ILCregs and blockade of TGF-β signaling could disrupt the ILCreg transdifferentiation and inhibited tumor growth. Thus, intervention of ILC conversions might be a potential strategy for CRC immunotherapy.

BackgroundTo clarify the characteristic and the duration of positive nucleic acid in children infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), including asymptomatic children.MethodsA total of 32 children confirmed with SARS-CoV-2 infection between January 24 and February 12, 2020 from four provinces in Western China were enrolled in this study and followed up until discharge and quarantine 14 days later.ResultsEleven children (34%) were asymptomatic, among whom six children had normal computed tomographic (CT) scan images. Age and gender were not associated with clinical symptoms or the results of CT scan in children infected with SARS-CoV-2. The concentrations of white blood cells and neutrophils were higher in children with asymptomatic infection than in children with clinical symptoms or CT abnormalities. Patients who presented with CT abnormalities had lower D-dimer or lower total bilirubin than those who had normal CT scan but clinical symptoms. All children recovered and no one died or was admitted to the pediatric intensive care unit (PICU). The mean duration of positive SARS-CoV-2 nucleic acid was 15.4 (SD=7.2) days and similar for both asymptomatic children and children with symptoms or CT abnormalities. We found a significant negative correlation between the lymphocyte count and the duration of positive nucleic acid test.ConclusionsChildren with asymptomatic infection should be quarantined for the same duration as symptomatic patients infected with SARS-CoV-2. The clinical significance and mechanism behind the negative correlation between the number of lymphocytes and the duration of positive SARS-CoV-2 needs further study.

Through rational design, in vivo supramolecular construction of nanodrugs could precisely proceed in the lesion areas, which may apparently improve the theranostic performance of nanomaterials. Herein, a tumor microenvironment-responsive theranostic nanoplatform (Ce6-GA@MnO2-HA-PEG) has been constructed to achieve in vivo supramolecular construction and enhance the therapeutic efficacy of combined phototherapy through intracellular reassembly. Under the tumor microenvironment, such nanoplatform could undergo the process of decomposition-reassembly and form in situ photothermal assemblies. The generation of assemblies would endow this nanoplatform with the capacity of photothermal therapy. Meanwhile, this nanoplatform could alleviate hypoxia and improve the therapeutic efficacy of photodynamic therapy. The results of in vitro and in vivo experiments reveal that tumors can be ablated efficiently by the designed nanoplatform under laser irradiation. In addition, fluorescence imaging and magnetic resonance imaging can be activated by the decomposition of MnO2 to realize tumor imaging in vivo. Therefore, this multifunctional nanoplatform exhibits the capacity for boosting dual-modal imaging-guided combined phototherapy through intracellular reassembly, which may propose a new thought in cancer theranostics.

Prognostic significance of serum calcium level in patients with intracerebral hemorrhage is not well studied. The aim of the study was to identify if a relationship between admission serum calcium level and prognosis exists in patients with intracerebral hemorrhage. A total of 1262 confirmed intracerebral hemorrhage patients were included. Demographic data, medical history, medicine history, laboratory data, imaging data, clinical score, and progress note were collected from their medical records. All images of head computed tomography were reanalyzed. Ninety-day prognosis was recorded, and poor outcome was defined as death or major disability caused by intracerebral hemorrhage. During the 90-day follow-up period, 504 patients died and 226 patients suffered from major disability. Death and major disability were combined as poor prognosis. The remaining 532 patients showed good prognosis. Admission serum calcium level was lower in the patients with poor prognosis than in the patients with good prognosis (2.41 ± 0.23 mmol/l, 2.55 ± 0.26 mmol/l, P < 0.001). Admission INR and hematoma volume were higher in the patients with poor prognosis than in the patients with good prognosis (INR: 1.74 ± 0.29, 1.70 ± 0.29, P = 0.029; hematoma volume: 11.6 ± 4.4 ml, 10.7 ± 4.1 ml, P < 0.001). There was no difference in admission APTT level between the two prognosis groups (28.4 ± 5.6 s, 27.8 ± 5.4 s, P = 0.056). A multivariate COX regression analysis reported that admission serum calcium level ≤ 2.41 mmol/l was associated with the increased risk of poor prognosis (death or major disability) in the patients (HR 1.45, 95% CI 1.32–1.60). In addition, there was a significant linear association of serum calcium level with coagulation function markers and hematoma volume on admission (APTT: r = − 0.091, P = 0.001; INR: r = − 0.063, P = 0.025; hematoma volume: r = −0.108, P < 0.001). Admission serum calcium level might be a prognostic marker for intracerebral hemorrhage. Potential mechanism involved calcium-induced coagulation function abnormality.

Purpose: RNA polymerase I subunit D (POLR1D) is involved in the synthesis of ribosomal RNA precursors and small RNAs, but its mechanism in the development and progression of colorectal cancer (CRC) remains ambiguous. Thus, this research aimed to investigate POLR1D’s expression and significance in human CRC patients and evaluate its association with clinicopathological characteristics. Methods: Matched fresh-frozen cancerous and non-cancerous tissues were collected from 100 patients diagnosed with CRC. Immunohistochemical, Western blot, and quantitative real-time polymerase chain reaction analyses were adopted to validate the correlation between POLR1D expression and clinicopathological parameters in CRC tissues and adjacent normal tissues (ANTs). Results: POLR1D expression in CRC tissues was significantly higher than in the ANTs. χ2 test and Spearman’s correlative analysis showed that a high POLR1D expression is significantly associated with clinical stage, Dukes stage, tumor differentiation, depth of invasion, and metastasis (p < 0.05). It is not correlated with gender, age, and tumor location and size (p > 0.05). Kaplan-Meier survival curves show that the overall survival (OS) time for the low expression group is remarkably longer than for the high expression group (p < 0.0015). Univariate and multivariate analyses indicate that a high POLR1D expression is an independent prognostic factor for poor OS (p = 0.000). Conclusion: The findings of this study strongly indicate that POLR1D plays a pivotal role in the occurrence and progression of CRC. It might be an independent adverse prognostic factor for CRC patients and could serve as a potential therapeutic target for clinical diagnosis in CRC and anticancer drug development.

The present study aims to investigate the constituents, antioxidant activities and hepatoprotective effect of polyphenols extracted from Coreopsis tinctoria buds (CTB-PE) against acute hepatic injury. HPLC analysis showed that six compounds were identified from polyphenolic extracts. The determination of antioxidant activities revealed that the CTB-PE had DPPH radical scavenging activity, ferric-reducing antioxidant power and oxygen radical absorbance capacity. The animal experiments verified that CTB-PE pretreatment ameliorated the D-galactosamine/lipopolysaccharide-induced alterations in histopathological changes, serum biochemical indicators, antioxidant capacity and lipid peroxidation. The potential mechanisms of the hepatoprotective effect might be that CTB-PE treatment significantly enhanced the protein and mRNA expression levels of NF-E2-related factor 2 (Nrf2), peroxisome proliferator-activated receptors α (PPARα) and γ (PPARγ). It suggested that the protective effect of CTB-PE against liver damage was likely attributed to eliminate free radicals, inhibit oxidative stress response and mediate inflammatory response.

The nail is a continuous skin appendage. Cells located around the nails, which display coordinated homeostatic dynamics and release a flow of stem cells in response to regeneration, have been identified in mice. However, very few studies regarding human nail stem cells exist in the literature. Using specimens isolated from humans, we detected an unreported population of cells within the basal layer of postnatal human nail proximal folds (NPFs) and the nail matrix around the nail root. These cells were multi-expressing and expressed stem cell markers, such as keratin 15 (K15), keratin 14 (K14), keratin 19 (K19), CD29, CD34, and leucine-rich repeat-containing G protein-coupled receptor 6 (Lgr6). These cells were very similar to mouse nail stem cells in terms of cell marker expression and their location within the nail. We also found that the putative nail stem cells maintained their abundance with advancing age, but cell proliferation and nail growth rate were decreased on comparison of young and aged specimens. To summarize, we found a putative population of stem cells in postnatal human nails located at NPFs and the nail matrix. These cells may have potential for cell differentiation and be capable of responding to injury, and were retained, but may be hypofunctional during aging.