Increased thrombospondin-1 levels contribute to epileptic susceptibility in neonatal hyperthermia without seizures via altered synaptogenesis.

Childhood febrile seizures (FS) represent one of the most common types of seizures and may lead to severe neurological damage and an increased risk of epilepsy. However, most children with fevers do not show clinical manifestations of convulsions, and the consequences of hyperthermia without seizures remain elusive. This study focused on hyperthermia not reaching the individual's seizure threshold (sub-FS stimulus). Changes in thrombospondin-1 (TSP-1) levels, synapses, seizure susceptibility, and seizure severity in subsequent FS were investigated in rats exposed to sub-FS stimuli. Pharmacological and genetic interventions were used to explore the role of TSP-1 in sub-FS-induced effects. We found that after sub-FS stimuli, the levels of TSP-1 and synapses, especially excitatory synapses, were concomitantly increased, with increased epilepsy and FS susceptibility. Moreover, more severe neuronal damage was found in subsequent FS. These changes were temperature dependent. Reducing TSP-1 levels by genetic intervention or inhibiting the activation of transforming growth factor-ß1 (TGF-ß1) by Leu-Ser-Lys-Leu (LSKL) led to lower synapse/excitatory synapse levels, decreased epileptic susceptibility, and attenuated neuronal injury after FS stimuli. Our study confirmed that even without seizures, hyperthermia may promote synaptogenesis, increase epileptic and FS susceptibility, and lead to more severe neuronal damage by subsequent FS. Inhibition of the TSP-1/TGF-ß1 pathway may be a new therapeutic target to prevent detrimental sub-FS sequelae.

Visible-light Excited and Highly Photostable Organic Fluorophore with dual-state Emission.

Organic fluorophores with dual-state emission (DSE) are rare or difficult to observe because most of them display either aggregation-induced emission (AIE) or aggregation-caused quenching (ACQ). Amazing works have been accomplished, yet most of the DSE compounds were excited by UV light which limits their wide application in bioimaging. In this work, we achieved a visible-light excited DSE fluorophore and realized its imaging in SKOV-3 cells and zebrafish. The naphtho[2',3':4,5]imidazo[1,2-a]pyridine (NIP) core ensures its emission in dilute solution. Meanwhile, the twisted phenyl ring blocks fluorescence quenching induced by the π-π stacking and leads to the emission of the solid. The fluorescence intensity is steady even after 6 h of continuous intense sunlight. More importantly, photostability of NIP in cells is much better than commercial dye (mitochondrial green).

Multiomics analyses of Jining Grey goat and Boer goat reveal genomic regions associated with fatty acid and amino acid metabolism and muscle development.

Objective: Jining Grey Goat is a local Chinese goat breed that is well known for its high fertility and excellent meat quality but shows low meat production performance. Numerous studies have focused on revealing the genetic mechanism of its high fertility, but its highlighting meat quality and muscle growth mechanism still need to be studied. Methods: In this research, an integrative analysis of the genomics and transcriptomics of Jining Grey goats compared with Boer goats was performed to identify candidate genes and pathways related to the mechanisms of meat quality and muscle development. Results: Our results overlap among five genes (ABHD2, FN1, PGM2L1, PRKAG3, RAVER2) and detected a set of candidate genes associated with fatty acid metabolism (PRKAG3, HADHB, FASN, ACADM), amino acid metabolism (KMT2C, PLOD3, NSD2, SETDB1, STT3B, MAN1A2, BCKDHB, NAT8L, P4HA3) and muscle development (MSTN, PPARGC1A, ANKRD2). Several pathways have also been detected, such as the FoxO signaling pathway and Apelin signaling pathway that play roles in lipid metabolism, lysine degradation, N-glycan biosynthesis, valine, leucine and isoleucine degradation that involving with amino acid metabolism. Conclusion: The comparative genomic and transcriptomic analysis of Jining Grey Goat and Boer Goat revealed the mechanisms underlying the meat quality and meat productive performance of goats. These results provide valuable information for future breeding in goats.

Mental health survey among front-line medical workers after 2 years of supporting COVID-19 efforts in Hubei Province.

During the outbreak of COVID-19 in China, many health care workers have been involved in the front-line fight against the epidemic and have experienced major psychological challenges. This study was aimed at assessing the mental health of front-line health workers after 2 years of COVID-19 efforts. We recruited front-line health workers from Liaoning province who supported Hubei, the epicenter of the COVID-19 outbreak. The Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder scale (GAD-7), and Insomnia Severity Index (ISI) were used to assess psychological status. A total of 1101 of 1354 contacted individuals completed the survey (participation rate of 81.31%): 963 (87.5%) were 20-45 years of age, 919 (83.47%) were women, 845 (76.7%) were nurses, and 245 (22.3%) were physicians. After 2 years, the mental health symptoms among survey respondents were as follows: 46.6% had depression, 35.5% had anxiety, and 38.1% had insomnia. Thus, 2 years after the COVID-19 pandemic, the front-line health workers who had assisted Hubei province during the COVID­19 pandemic in China still had high levels of depression, anxiety, and insomnia. Our findings suggest that the pandemic has had significant long-term effects on the mental health of front-line health workers. Therefore, mental health policies should offer long-term rather than short-term services.

Magnetic resonance imaging for evaluation of bowel inflammation and disease activity in Crohn's disease: A systematic review and meta-analysis / Imágenes por resonancia magnética para la evaluación de la inflamación intestinal y la actividad de la enfermedad en la enfermedad de Crohn: una revisión sistemática y un metaanálisis

Background: The aim of this systematic review and meta-analysis was to determine the performance of magnetic resonance imaging (MRI) in the diagnosis of bowel inflammation and disease activity in Crohn's disease (CD). Methods: MEDLINE, Embase and Web of Science databases of biomedical literature were systematically searched to identify studies that investigated the diagnostic accuracy of MRI in diagnosing bowel inflammation and disease activity in CD by comparing it with reference standards. Quality Assessment of Diagnostic Accuracy Studies-2 tool was used to assess study quality. The summary sensitivity and specificity were estimated using the bivariate model, and hierarchical summary receiver operating characteristic (HSROC) parameters were calculated and plotted. Results: Of 5492 citations of interest, 34 articles contained the diagnostic accuracy data. Of these, results for the small bowel and the colorectum were reported separately in 19 studies and jointly by 21 studies. The meta-analytic summary sensitivity and specificity under the bivariate model were 90.9% (95% CI, 85.8%–94.2%) and 90.2% (95% CI, 81.9%–95.0%), respectively. The sensitivities and specificities of individual studies ranged from 55% to 100% and 51% to 100%, respectively. Substantial heterogeneity was observed in both sensitivity (I2=84.9%) and specificity (I2=78.8%). The HSROC curve also showed considerable heterogeneity between studies. Conclusion: Although the meta-analytic summary accuracy of MRI was high for the diagnosis of bowel inflammation in CD, the summary estimates might be unreliable due to the presence of high heterogeneity.(AU)

Antecedentes: El objetivo de esta revisión sistemática y metaanálisis fue determinar el rendimiento de la resonancia magnética nuclear (RM) en el diagnóstico de la inflamación intestinal y la actividad de la enfermedad en la enfermedad de Crohn (EC). Métodos: Se realizaron búsquedas sistemáticas en las bases de datos de literatura biomédica de MEDLINE, Embase y Web of Science para identificar estudios que investigaran la precisión diagnóstica de la RM en el diagnóstico de la inflamación intestinal y la actividad de la enfermedad en la EC comparándola con estándares de referencia. Evaluación de la calidad de los estudios de precisión diagnóstica: se utilizó la herramienta 2 para evaluar la calidad del estudio. La sensibilidad y la especificidad resumidas se estimaron mediante el modelo bivariado, y se calcularon y trazaron los parámetros de características operativas del receptor resumidas jerárquicas (HSROC). Resultados: De 5.492 citas de interés, 34 artículos contenían datos de precisión diagnóstica. De estos, los resultados para el intestino delgado y el colorrectal se informaron por separado en 19 estudios y en forma conjunta en 21 estudios. La sensibilidad y la especificidad del resumen metanalítico bajo el modelo bivariado fueron del 90,9% (IC del 95%, 85,8%-94,2%) y el 90,2% (IC del 95%, 81,9%-95,0%), respectivamente. Las sensibilidades y especificidades de los estudios individuales variaron del 55 al 100% y del 51 al 100%, respectivamente. Se observó heterogeneidad sustancial tanto en la sensibilidad (I2=84,9%) como en la especificidad (I2=78,8%). La curva HSROC también mostró una considerable heterogeneidad entre los estudios. Conclusión: Aunque la precisión del resumen metaanalítico de la RM fue alta para el diagnóstico de inflamación intestinal en la EC, las estimaciones del resumen pueden no ser confiables debido a la presencia de una gran heterogeneidad.(AU)

Mortality and excess life-years lost in patients with schizophrenia under community care: a 5-year follow-up cohort study.

OBJECTIVE: Mortality rate is a general indicator which can be used to measure care and management of schizophrenia. This cohort study evaluated the standardized mortality ratios (SMRs) of all-cause mortality and life-years lost (LYLs) in patients with schizophrenia under a community care program in China. METHODS: Data were obtained from the National Community Care Program System for Severe Mental Disorders. A total of 99,214 patients diagnosed with schizophrenia were enrolled before December 2014 and followed between 2015 and 2019. A total of 9,483 patients died. Crude mortality rates (CMRs) and SMRs were then stratified by natural vs. unnatural causes, and major groups of death were standardized according to the 2010 National Population SMRs. The corresponding LYLs at birth were also calculated by gender and age. RESULTS: The SMRs of patients with schizophrenia were significantly elevated during the study period, with an overall SMR of 4.98 (95%CI 2.67-7.32). Neoplasms, cardiovascular diseases, cerebrovascular diseases, external injuries, and poisonings were the most significant causes of death among patients with schizophrenia compared to the general population. The mean LYLs of patients with schizophrenia were 15.28 (95%CI 13.26-17.30). Males with schizophrenia lost 15.82 life-years (95%CI 13.48-18.16), and females lost 14.59 life-years (95%CI 13.12-16.06). CONCLUSIONS: Patients with schizophrenia under community care had a high mortality rate in our study, even though mental health services have been integrated into the general healthcare system in China to narrow treatment gaps in mental health for > 10 years. In terms of mortality outcome indicators, effective and quality mental health services still have a long way to go. The current study demonstrates the potential for improved prevention and treatment of individuals with schizophrenia under community care.

Magnetic resonance imaging for evaluation of bowel inflammation and disease activity in Crohn's disease: A systematic review and meta-analysis.

BACKGROUND: The aim of this systematic review and meta-analysis was to determine the performance of magnetic resonance imaging (MRI) in the diagnosis of bowel inflammation and disease activity in Crohn's disease (CD). METHODS: MEDLINE, Embase and Web of Science databases of biomedical literature were systematically searched to identify studies that investigated the diagnostic accuracy of MRI in diagnosing bowel inflammation and disease activity in CD by comparing it with reference standards. Quality Assessment of Diagnostic Accuracy Studies-2 tool was used to assess study quality. The summary sensitivity and specificity were estimated using the bivariate model, and hierarchical summary receiver operating characteristic (HSROC) parameters were calculated and plotted. RESULTS: Of 5492 citations of interest, 34 articles contained the diagnostic accuracy data. Of these, results for the small bowel and the colorectum were reported separately in 19 studies and jointly by 21 studies. The meta-analytic summary sensitivity and specificity under the bivariate model were 90.9% (95% CI, 85.8%-94.2%) and 90.2% (95% CI, 81.9%-95.0%), respectively. The sensitivities and specificities of individual studies ranged from 55% to 100% and 51% to 100%, respectively. Substantial heterogeneity was observed in both sensitivity (I2=84.9%) and specificity (I2=78.8%). The HSROC curve also showed considerable heterogeneity between studies. CONCLUSION: Although the meta-analytic summary accuracy of MRI was high for the diagnosis of bowel inflammation in CD, the summary estimates might be unreliable due to the presence of high heterogeneity.

Mortality and excess life-years lost in patients with schizophrenia under community care: a 5-year follow-up cohort study

Objective: Mortality rate is a general indicator which can be used to measure care and management of schizophrenia. This cohort study evaluated the standardized mortality ratios (SMRs) of all-cause mortality and life-years lost (LYLs) in patients with schizophrenia under a community care program in China. Methods: Data were obtained from the National Community Care Program System for Severe Mental Disorders. A total of 99,214 patients diagnosed with schizophrenia were enrolled before December 2014 and followed between 2015 and 2019. A total of 9,483 patients died. Crude mortality rates (CMRs) and SMRs were then stratified by natural vs. unnatural causes, and major groups of death were standardized according to the 2010 National Population SMRs. The corresponding LYLs at birth were also calculated by gender and age. Results: The SMRs of patients with schizophrenia were significantly elevated during the study period, with an overall SMR of 4.98 (95%CI 2.67-7.32). Neoplasms, cardiovascular diseases, cerebrovascular diseases, external injuries, and poisonings were the most significant causes of death among patients with schizophrenia compared to the general population. The mean LYLs of patients with schizophrenia were 15.28 (95%CI 13.26-17.30). Males with schizophrenia lost 15.82 life-years (95%CI 13.48-18.16), and females lost 14.59 life-years (95%CI 13.12-16.06). Conclusions: Patients with schizophrenia under community care had a high mortality rate in our study, even though mental health services have been integrated into the general healthcare system in China to narrow treatment gaps in mental health for > 10 years. In terms of mortality outcome indicators, effective and quality mental health services still have a long way to go. The current study demonstrates the potential for improved prevention and treatment of individuals with schizophrenia under community care.

Attenuated iron stress and oxidative stress may participate in anti-seizure and neuroprotective roles of xenon in pentylenetetrazole-induced epileptogenesis.

The previous studies have demonstrated the excellent neuroprotective effects of xenon. In this study, we verified the anti-seizure and neuroprotective roles of xenon in epileptogenesis and evaluated the involvement of oxidative stress and iron accumulation in the protective roles of xenon. Epileptogenesis was induced by pentylenetetrazole (PTZ) treatment in Sprague-Dawley rats. During epileptogenesis, we found increased levels of iron and oxidative stress accompanied by elevated levels of divalent metal transporter protein 1 and iron regulatory protein 1, which are closely associated with iron accumulation. Meanwhile, the levels of autophagy and mitophagy increased, alongside significant neuronal damage and cognitive deficits. Xenon treatment reversed these effects: oxidative stress and iron stress were reduced, neuronal injury and seizure severity were attenuated, and learning and memory deficits were improved. Thus, our results confirmed the neuroprotective and anti-seizure effects of xenon treatment in PTZ-induced epileptogenesis. The reduction in oxidative and iron stress may be the main mechanisms underlying xenon treatment. Thus, this study provides a potential intervention strategy for epileptogenesis.

Whole genome sequencing of Luxi Black Head sheep for screening selection signatures associated with important traits.

OBJECTIVE: Luxi Black Head sheep (LBH) is the first crossbreed specialized for meat production and was developed by crossbreeding Black Head Dorper sheep (DP) and Small Tailed Han sheep (STH) in the farming areas of northern China. Research on the genomic variations and selection signatures of LBH caused by continuous artificial selection is of great significance for identifying the genetic mechanisms of important traits of sheep and for the continuous breeding of LBH. METHODS: We explored the genetic relationships of LBH, DP, and several Mongolian sheep breeds by constructing phylogenetic tree, principal component analysis and linkage disequilibrium analysis. In addition, we analysed 29 whole genomes of sheep. The genomewide selection signatures have been scanned with four methods heterozygosity (HP), fixation index (FST), cross-population extended haplotype homozygosity (XP-EHH) and the nucleotide diversity (θπ) ratio. RESULTS: The genetic relationships analysis showed that LBH appeared to be an independent cluster closer to DP. The candidate signatures of positive selection in sheep genome revealed candidate genes for developmental process (HoxA gene cluster, BCL2L11, TSHR), immunity (CXCL6, CXCL1, SKAP2, PTK6, MST1R), growth (PDGFD, FGF18, SRF, SOCS2), and reproduction (BCAS3, TRIM24, ASTL, FNDC3A). Moreover, two signalling pathways closely related to reproduction, the thyroid hormone signalling pathway and the oxytocin signalling pathway, were detected. CONCLUSION: The selective sweep analysis of LBH genome revealed candidate genes and signalling pathways associated with developmental process, immunity, growth, and reproduction. Our findings provide a valuable resource for sheep breeding and insight into the mechanisms of artificial selection.

Detecting novel Indel variants within the GHR gene and their associations with growth traits in Luxi Blackhead sheep.

The growth hormone is important in the regulation of metabolism and energy homeostasis and acts through a growth hormone receptor (GHR). In this work, genetic variations within the ovine GHR gene were identified and tested for associations with body morphometric traits in Chinese Luxi Blackhead (LXBH) sheep. Novel deletion loci in the LXBH GHR gene included P2-del-23 bp and P8-del-23 bp indel variants. The polymorphic information content (PIC) was 0.329 in P2-del-23 bp and 0.257 in P8-del-23 bp. Moreover, both indel polymorphisms were not at Hardy-Weinberg equilibrium (p < 0.05) in the LXBH population. Statistical analyses revealed that the P2-del-23 bp and P8-del-23 bp indels were significantly associated (p < 0.05) with several growth traits in rams and ewes, including body weight, body height, chest depth, chest width, chest circumference, cannon circumference, paunch girth and hip width. Among the tested sheep, the body traits of those with genotype DD were superior to those with II and ID genotypes, suggesting that the 'D' allele was responsible for the positive effects on growth traits. Thus, these results indicate that the P2-del-23 bp and P8-del-23 bp indel sites and the DD genotype can be useful in marker-assisted selection in sheep.

circATP2A2 promotes osteosarcoma progression by upregulating MYH9.

Osteosarcoma (OS) is a highly metastatic primary malignant tumor. CircRNA hsa_circ_0028173 (circATP2A2) has been uncovered to be related to the advancement of OS. However, the biological role of circATP2A2 in OS has not been validated. circATP2A2 and MYH9 were upregulated while miR-335-5p was downregulated in OS. OS patients with high circATP2A2 expression displayed a shorter overall survival and the area under curve of circATP2A2 was 0.77, manifesting that circATP2A2 might be a diagnostic and prognostic biomarker. circATP2A2 silencing repressed OS cell proliferation and glycolysis in vivo and constrained OS cell proliferation, glycolysis, migration, and invasion in vitro. circATP2A2 regulated MYH9 expression through sponging miR-335-5p. MiR-335-5p inhibitor reversed the repressive effect of circATP2A2 knockdown on OS cell malignancy and glycolysis. MYH9 overexpression overturned miR-335-5p upregulation-mediated OS cell malignancy and glycolysis. circATP2A2 accelerated OS cell malignancy and glycolysis through upregulating MYH9 via sponging miR-335-5p, offering a promising target for OS treatment.

Efficacies and complications of internal fixations with PHILOS plate and intramedullary Multiloc® nails in the surgical treatment of proximal humerus fractures.

OBJECTIVE: To compare the efficacies of internal fixations with proximal humeral internal locking system (PHILOS) plate and intramedullary MultiLoc® nails in the surgical treatment of proximal humerus fractures (PHF). METHODS: A total of 115 patients with PHF admitted to our hospital were selected as the research subjects, and were randomly divided into PHILOS group (n=57) and MultiLoc group (n=58). PHILOS group was treated with internal fixation with PHILOS plate, while MultiLoc group was treated with internal fixation with intramedullary MultiLoc® nails. RESULTS: MultiLoc group was superior to PHILOS group in the surgical duration and amount of intraoperative hemorrhage (P < 0.05). At 1 week after surgery, the visual analogue scale (VAS) scores in MultiLoc group were lower than those in PHILOS group (P < 0.05). After surgery, MultiLoc group had a shorter time of occurrence of bony callus and disappearance of fracture line (P < 0.05) and a lower incidence of complications (0.00% vs. 3.51%) (P > 0.05) compared with PHILOS group. At 6 months after surgery, MultiLoc group had higher abduction and external rotation angles and higher scores of Constant-Murley and American Shoulder and Elbow Surgeons (ASES) than PHILOS group (P < 0.05). CONCLUSION: The internal fixations with PHILOS plate and intramedullary MultiLoc® nails are effective in the treatment of PHF. However, the internal fixation with intramedullary MultiLoc® nails is superior to the internal fixation with PHILOS plate in alleviating pain and expediting the postoperative restoration of joint function.

Hyperpolarized 3 helium MRI measured apparent diffusion coefficient and its correlations with pulmonary functions tests in patients with chronic obstructive pulmonary disease: A meta-analysis.

BACKGROUND: This study evaluates role of hyperpolarized 3 helium (3 He) MRI measured apparent diffusion coefficient (ADC) in examining pulmonary function of chronic obstructive pulmonary disease (COPD) patients. METHODS: After literature search in electronic databases, studies were selected by following precise eligibility criteria. Meta-analyses were performed to estimate mean difference in ADC between COPD patients and healthy individuals and to seek correlations between lung ADC and pulmonary function. Metaregression analyses were performed to seek relationships between ADC and age, gender, BMI, cigarette pack-years, and pulmonary function tests. RESULTS: Twenty-five studies (622 COPD patients and 469 healthy controls) were included. Lung ADC was 0.402 (95% confidence interval [CI]: 0.374, 0.429) in COPD patients and 0.228 (95% CI: 0.205, 0.252) in healthy individuals (mean difference 0.160 [95% CI: 0.127, 0.193]; p < 0.001). In metaregression, age (coefficient: 0.006; p = 0.004), pack-years (coefficient: 0.005; p = 0.018), forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratio (coefficient: -1.815; p = 0.007), percent predicted diffusion capacity of carbon monoxide (DLCO) (coefficient: -0.004; p = 0.008), and percent predicted inspiratory capacity (coefficient: -0.004; p = 0.012) were significantly associated with ADC in COPD patients. In meta-analysis of correlation coefficients, ADC was significantly correlated with FEV1 (r = -0.62; p < 0.00001), FEV1/FVC (r = -0.80; p < 0.00001), DLCO (r = -0.85; p < 0.00001), functional residual capacity (r = 0.71; p < 0.00001), reserve volume (r = 0.53; p = 0.0001), and emphysema index (r = 0.89; p < 0.00001). CONCLUSION: Hyperpolarized 3 He MRI measured ADC was higher in COPD patients than in healthy individuals and was inversely associated with FEV1, FEV1/FVC, DLCO, and inspiratory capacity.

A novel 23 bp indel mutation in PRL gene is associated with growth traits in Luxi Blackhead sheep.

Prolactin is a highly versatile pituitary hormone with multiple biological functions. PRL expression is regulated by POU1F1 and the prophet of POU1F1 (PROP1). The aim of this study was to investigate the indel variations in ovine PRL and the directly related (PROP1 and POU1F1) genes, and their associations with growth traits in Luxi Blackhead (LXBH) sheep. A monomorphism in PROP1 and POU1F1 genes, and one novel 23-bp insertion mutation in the PRL gene, were identified in LXBH sheep. The 23 bp insertion mutation within PRL gene was significantly associated with several body measurements (e.g., body weight, body height) in sheep of different ages (p < 0.05). Ram lambs (p = 0.036) of genotype insertion/insertion (II) had significantly higher body weights. Weaners (p = 0.018) of genotypes insertion/insertion (II) and insertion/deletion (ID) also had significantly higher body weights compared with male sheep of deletion/deletion (DD) genotype. Moreover, among ewe lambs, individuals of genotype insertion/insertion (II) had a higher paunch girth compared to those with other genotypes (p = 0.044). These findings indicate that a 23 bp indel variant of the ovine PRL gene is correlated with body measurements in LXBH sheep. The findings have potential utility for sheep breeding programs based on marker-assisted selection.

The effects of temperature on human mortality in a Chinese city: burden of disease calculation, attributable risk exploration, and vulnerability identification.

Few studies have examined the attributable fraction (AF) of temperature to mortality and Years of Life Lost (YLL), especially in developing countries. This study aims to explore the short-term effect of the cold and hot temperatures on the cause-specific YLL and mortality, discover the attributable contributions from the temperature variations, and identify the vulnerable populations in Weifang, China. Daily registered death information and meteorological data over the period 2010-2016 were obtained in Weifang, a northern Chinese city. Generalized additive Poisson and Gaussian regression models were used to assess the impacts of temperatures on both mortality and YLL, explore the AF of the temperature variations on mortality, after adjusting for other covariates. Both hot and cold temperatures have had significant negative impacts on cause-specific mortality counts and YLL, with heat presented an acute and short effect and the cold temperatures had delayed effects and lasted for several days. In terms of the attributable fraction calculations, the contributions from cold effects was higher than that of hot effects on non-accidental, cardiovascular, and respiratory deaths (YLL 10.88 vs. 1.23%, 19.58 vs. 1.71%, and 14.47 vs. 3.05%; mortality 13.97 vs. 1.65%, 19.20 vs. 1.59%, and 14.89 vs. 3.09%), respectively. The elderly and women and people with low education level were the most vulnerable. The findings will provide important scientific evidences and policy implications for developing adaptation strategies to reduce the adverse effect of cold and hot exposure in Weifang, in terms of resource allocation, healthcare workforce capacity building, and community health education, especially for the vulnerable groups.

Facile Preparation and Photocatalytic Properties of TiO2 Fiber Membrane with Wrinkle Structure.

Herein, TiO2 fiber membrane with wrinkle structure was fabricated by an electrospinning technique in combination with a sol-gel process. The as-prepared TiO2 membranes were interwoven with interconnected nanofibers. The surfacial and morphological features of the obtained TiO2 fiber membrane could be tuned by varying the content of the precursor, titanium (IV) n-butoxide. The nature of wrinkle structure and high surface area demonstrates an impact on the electron-hole separation and charge transfer during photocatalytic tests, thereby leading to an obvious enhancement in the photocatalytic performance. The results revealed the resultant TPNs-20 sample displayed the best photocatalytic performance toward the removal of methyl orange (MO), and its degradation degree was up to 97% within 70 min. Furthermore, a photocatalytic mechanism is proposed on the basis of results and analysis, which indicates that ˙OH and ˙O-2 radicals are the main reactive species responsbile for the enhanced photocatalytic activity. We anticipate that controllable synthesis of promising TiO2 fiber membranes in this study provides new insight into the development of efficient photocatalysts for high-performance environmental remediation.

MicroRNA­212 inhibits the proliferation and invasion of human renal cell carcinoma by targeting FOXA1.

MicroRNA­212 (miR­212) has been observed to be significantly deregulated in various types of human cancer. However, the clinical significance of miR­212 and the associated molecular signaling pathways involved in the progression of renal cell carcinoma (RCC) remain unclear. In the present study, miR­212 expression was significantly downregulated in RCC tissues compared with adjacent non­tumor tissues. Clinical association analysis indicated that low expression of miR­212 was prominently associated with large tumor size, advanced tumor, nodes, metastasis stage and lymph node metastasis. In vitro studies revealed that upregulation of miR­212 inhibited cell proliferation, migration and invasion, and induced apoptosis in Caki­1 cells. Forkhead box protein A1 (FOXA1) was identified as a direct target of miR­212 in RCC cells via luciferase reporter assays and western blotting. In addition, FOXA1 expression was upregulated in RCC tissues compared with adjacent noncancerous tissues. An inverse correlation between FOXA1 and miR­212 expression was observed in RCC tissues. Notably, FOXA1 overexpression partially rescued miR­212­mediated inhibition of cell proliferation, migration and invasion in RCC cells. These results suggested that miR­212 suppresses RCC proliferation and invasion by modulating FOXA1, suggesting that miR­212 may have potential as a therapeutic target in RCC.

MicroRNA-338-3p targets SOX4 and inhibits cell proliferation and invasion of renal cell carcinoma.

MicroRNA (miR)-338-3p has been reported to be involved in tumor progression and development in various types of cancer. However, the biological function of miR-338-3p and its related molecular pathways involved in the progression of renal cell carcinoma (RCC) are unknown. The present study aimed to investigate the biological role and underlying mechanism of miR-338-3p in RCC cells. It was demonstrated that miR-338-3p expression level was significantly downregulated (P<0.05) in RCC tissues and cell lines. Clinical association analysis indicated that low expression of miR-338-3p was significantly associated with advanced TNM stage and lymph node metastasis (P<0.05). Function assays revealed that restoration of miR-338-3p in RCC cells significantly inhibited cell proliferation, colony formation, migration and invasion (P<0.05). Notably, sex-determining region Y-box 4 (SOX4) was identified as a direct target of miR-338-3p in RCC cells through a luciferase reporter assay, reverse transcription-quantitative polymerase chain reaction and western blot analysis. Furthermore, SOX4 overexpression partially rescued miR-338-3p-mediated inhibition of cell proliferation, colony formation, migration and invasion in RCC cells. These results suggested that miR-338-3p functioned as a tumor suppressor in RCC cells by modulating SOX4, suggesting that miR-338-3p may have a potential use in the treatment of RCC.

Knockdown of PARP-1 Inhibits Proliferation and ERK Signals, Increasing Drug Sensitivity in Osteosarcoma U2OS Cells.

Poly(ADP-ribose) polymerase 1 (PARP-1) is reported to be involved in DNA repair and is now recognized as a key regulator in carcinogenesis. However, the potential role and the molecular mechanism underlying the effect of PARP-1 on osteosarcoma (OS) cells have not been elucidated. In this study, the results showed that knockdown of PARP-1 resulted in decreased cell proliferation, increased cell apoptosis, and G0/G1 phase arrest in U2OS cells. In addition, increased expression of active caspase 3 and Bax, but reduced Bcl-2, cyclin D1, and phosphorylated extracellular signal regulated kinase 1/2 (pERK1/2) were observed in PARP-1 knockdown in U2OS cells. Moreover, knockdown of PARP-1 correlated with elevated chemosensitivity of U2OS cells to cisplatin through inactivation of the ERK1/2 signaling pathway. In conclusion, our findings demonstrated that PARP-1 plays an important role in regulating OS growth, combining PARP-1 gene therapy with traditional chemotherapy, and may serve as a promising approach to OS therapy.