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A silver(i) isocyanide complex was used as a catalyst to activate alkynes rapidly and carry out intramolecular electrophilic addition of alkynes to synthesize various different-sized rings in excellent yields under mild conditions.

We report a "green chemistry"-based Ugi cascade reaction to furnish a series of 2,5-diketopiperazines (through nucleophilic attack of amides upon ketones in Ugi adducts) at moderate-to-good yields. Investigation with the MTT assay revealed compound (±) 5c to exhibit potent anticancer activities against acute myeloid leukaemia (MV411; IC

Objectives This study aims to explore the prevalence of sexual satisfaction among Chinese cancer survivors, and explore the association of sexual satisfaction with comorbidity and lifestyle factors. Methods A cross‐sectional study was performed among 3996 Chinese cancer survivors recruited at Shanghai Cancer Rehabilitation Club from March to April 2017. Data were collected through self‐reported questionnaires. The questionnaire includes information about demographic, cancer characteristics, comorbidities, lifestyle factors, and sexual satisfaction. Sexual satisfaction was measured by a single‐item scale. The distribution of sexual satisfaction among different demographic and cancer characteristics was compared using the chi‐squared test. Logistic regression models were conducted to assess the effects of lifestyle factors, comorbidities on sexual satisfaction after adjustment for demographic and cancer characteristics. Results More than 40% of male and female cancer survivors reported no sexual satisfaction. Sexual satisfaction of cancer survivors is significantly associated with both the number and the type of comorbidities. Heart disease, musculoskeletal system disease, diabetes, and hyperlipidemia are the comorbidities significantly associated with sexual satisfaction of cancer survivors. Lifestyle factors other than smoking, including exercise or fitness, drinking alcohol, and eating fruits and vegetables are significantly correlated with sexual satisfaction. Besides, all of the above associations show gender differences. In addition, demographic characteristics include sex, age, marital status, living status, and average monthly income are also significantly associated with sexual satisfaction of cancer survivors. Conclusion Comorbidity and lifestyle factors are associated with sexual satisfaction of cancer survivors, and the associations show gender differences. Improving the lifestyles of cancer survivors, and controlling and reducing their comorbidities are important for improving their sexual satisfaction., This study aims to investigate the prevalence of sexual satisfaction among Chinese cancer survivors, and explore the association of sexual satisfaction with comorbidity and lifestyle factors. Comorbidity and lifestyle factors are associated with sexual satisfaction of cancer survivors, and the associations show gender differences. Improving the lifestyles of cancer survivors, and controlling and reducing their comorbidities are important for improving their sexual satisfaction.

Coronavirus disease 2019 (COVID-19) and tuberculosis (TB) are major public health and social issues worldwide. The long-term follow-up of COVID-19 with pulmonary TB (PTB) survivors after discharge is unclear. This study aimed to comprehensively describe clinical outcomes, including sequela and recurrence at 3, 12, and 24 months after discharge, among COVID-19 with PTB survivors.From January 22, 2020 to May 6, 2022, with a follow-up by August 26, 2022, a prospective, multicenter follow-up study was conducted on COVID-19 with PTB survivors after discharge in 13 hospitals from four provinces in China. Clinical outcomes, including sequela, recurrence of COVID-19, and PTB survivors, were collectedThirty-two COVID-19 with PTB survivors were included. The median age was 52 (45, 59) years, and 23 (71.9%) were men. Among them, nearly two-thirds (62.5%) of the survivors were moderate, three (9.4%) were severe, and more than half (59.4%) had at least one comorbidity (PTB excluded). The proportion of COVID-19 survivors with at least one sequela symptom decreased from 40.6% at 3 months to 15.8% at 24 months, with anxiety having a higher proportion over a follow-up. Cough and amnesia recovered at the 12-month follow-up, while anxiety, fatigue, and trouble sleeping remained after 24 months. Additionally, one (3.1%) case presented two recurrences of PTB and no re-positive COVID-19 during the follow-up period.The proportion of long symptoms in COVID-19 with PTB survivors decreased over time, while nearly one in six still experience persistent symptoms with a higher proportion of anxiety. The recurrence of PTB and the psychological support of COVID-19 with PTB after discharge require more attention.

Background To investigate the influence of diabetes duration and glycemic control, assessed by glycated hemoglobin (HbA1c) levels, on risk of incident dementia. Methods The present study is a prospective study of 461 563 participants from the UK Biobank. The age at diabetes diagnosis was determined by self-report. Diabetes duration was calculated as baseline age minus age at diagnosis. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) with 95% confidential intervals (CIs). Results During a median follow-up of 8.1 years, 2 233 dementia cases were recorded. As compared with normoglycemic individuals, individuals with diabetes had higher risk of all-cause dementia, and the risk increased with increasing duration of diabetes; compared with participants with diabetes duration of Conclusions Diabetes duration appeared to be associated with the risk of incident dementia due to factors beyond glycemic control. Clinicians should consider not only glycemic control but also diabetes duration in dementia risk assessments for patients with diabetes.

The A-type Aurora kinase is upregulated in many human cancers, and it stabilizes MYC-family oncoproteins, which have long been considered an undruggable target. Here, we describe the design and synthesis of a series of pyrimidine-based derivatives able to inhibit Aurora A kinase activity and reduce levels of cMYC and MYCN. Through structure-based drug design of a small molecule that induces the DFG-out conformation of Aurora A kinase, lead compound 13 was identified, which potently (IC50 < 200 nM) inhibited the proliferation of high-MYC expressing small-cell lung cancer (SCLC) cell lines. Pharmacokinetic optimization of 13 by prodrug strategies resulted in orally bioavailable 25, which demonstrated an 8-fold higher oral AUC (F = 62.3%). Pharmacodynamic studies of 25 showed it to effectively reduce cMYC protein levels, leading to >80% tumor regression of NCI-H446 SCLC xenograft tumors in mice. These results support the potential of 25 for the treatment of MYC-amplified cancers including SCLC.

Upregulation of Aurora kinases has been associated with increased tumor progression, and thus they are appealing targets for the development of anti-cancer therapies. In addition to have a critical role in cell cycle regulation, Aurora kinases have been shown to stabilize MYC-family oncoproteins for the maintenance of malignancy. Aurora kinase inhibitors such as Alisertib has demonstrated compelling anti-tumor efficacies; however, the reported side effects including serious haematological disturbances have limited its risk-benefit ratio in clinical use. In this study we discovered a novel pyrimidine-based Aurora kinase inhibitor compound A that degraded MYC- and MYCN- oncoproteins with better potency than Alisertib. The acyl-based prodrug design leads to the discovery of compound B which was able to regress MYC- or MYCN- overexpressing tumor xenografts including small cell lung cancer, neuroblastoma, hepatocellular carcinoma and medulloblastoma using a once-a-week (QW) oral dosing regimen. Pharmacokinetic studies revealed that the tumor/plasma ratio of compound B was about 20 at 24 h post drug administration, and the active compound remained detectable in the tumors after 7 days. No significant haematological or liver/kidney biochemical aberration was observed in mice treated with up to 500 mg/kg of DBPR728 on a QW dosing regimen in a 21-day cycle. The unique pharmacokinetic and molecular properties of compound B hold potential clinical promise for treating MYC- and MYCN- amplified tumors with manageable on-target haematological adverse effects caused by Aurora kinase inhibition. Citation Format: Ya-Hui Chi, Chun-Ping Chang, Teng-Kuang Yeh, Wan-Ping Wang, Yen-Ting Chen, Chia-Hua Tsai, Yan-Fu Chen, Yi-Yu Ke, Jing-Ya Wang, Ching-Ping Chen, Tsung-Chih Hsieh, Mine-Hsine Wu, Chiung-Tong Chen. Targeting myc-amplified cancers with a novel prodrug inhibiting aurora A kinase [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 523.

OBJECTIVE The 2017 American College of Cardiology/American Heart Association blood pressure (BP) guidelines lowered the hypertension threshold from a SBP/DBP level of at least 140/90 mmHg to at least 130/80 mmHg. The cardiovascular impact of isolated systolic hypertension (ISH) and isolated diastolic hypertension (IDH) under the new definition remains unclear. METHODS We used data from the UK Biobank study, which is a prospective population-based cohort study. Participants were categorized into five groups: normal BP, normal high BP, ISH, IDH and systolic and diastolic hypertension. The primary endpoint for this study was the composite of nonfatal myocardial infarction (MI), nonfatal ischaemic stroke, nonfatal haemorrhagic stroke and cardiovascular disease (CVD) death. We also explored the results for the above-mentioned CVD outcomes separately. Baseline BP measurements were obtained twice after the participant had been at rest for at least 5 min in a seated position. RESULTS We included 385 955 participants who were not taking antihypertensive medications, were free of CVD at baseline and had available data on BP measurements. During a median follow-up of 8.1 years, 8959 CVD events were recorded, including 4729 nonfatal MIs, 2287 nonfatal ischaemic strokes, 813 nonfatal haemorrhagic strokes, and 1826 CVD deaths. According to the hypertension threshold of at least 130/80 mmHg by the American College of Cardiology/American Heart Association guidelines, both ISH (hazard ratio 1.39; 95% confidence interval 1.27, 1.15) and IDH (hazard ratio 1.28; 95% confidence interval 1.15, 1.43) were significantly associated with a higher overall CVD risk than normal BP. ISH was associated with most CVD risk, except for ischaemic stroke, while the excess CVD risk associated with IDH appeared to be driven mainly by MI and CVD death. We found heterogeneity by sex and age regarding the effects of IDH on overall CVD risk, with significant associations in younger adults (age

Translocator protein 18 kDa (TSPO) is mainly distributed in the outer mitochondrial membrane of steroid-synthesizing cells in the central and peripheral nervous systems. It mediates cholesterol transportation across the phospholipid membrane, which is a prerequisite for neurosteroid synthesis. Though the ligand of TSPO has clinical value in the diagnosis and treatment of neuropsychiatric disorders, the pharmacological study of TSPO for anti-postpartum depression has not been reported. In this study, the classical method of reproductive hormone withdrawal was used to construct a rat model of postpartum depression (PPD). The effect of YL-IPA08, a new ligand compound of TSPO, on PPD was evaluated using multiple behavioral tests at progressive time points. Additionally, real-time quantitative PCR, Western-blotting and an enzyme linked immunosorbent assay were conducted to elucidate the potential molecular mechanism of such effect. We report that the levels of TSPO and neurosteroids in the hippocampus and prefrontal cortex were significantly decreased in PPD rats compared to healthy controls. After 3 weeks of drug treatment, the levels of TSPO and neurosteroids in the hippocampus of PPD rats were increased, and anxiety and depressive like behaviors were alleviated. Meanwhile, compared with sertraline treatment, a positive control in this study, YL-IPA08 treatment had a shorter onset time. Our results suggest that the anxiolytic and anti-depressive activity of YL-IPA08 has significant value in the treatment of PPD and that TSPO may be a potential new target for the treatment of PPD.

Correction for ‘An intramolecular hydrogen bond-promoted “green” Ugi cascade reaction for the synthesis of 2,5-diketopiperazines with anticancer activity’ by Jie Li et al., RSC Adv., 2022, 12, 33175–33179, https://doi.org/10.1039/D2RA04958A.

Background Physical activity and good nutrition are important behavioral factors in promoting health and preventing disease. It is important to understand the factors affecting physical activity and nutrition. The purpose of this study was to explore whether social capital has an effect on physical activity and nutrition, and whether health literacy plays a mediating role between social capital and physical activity as well as nutrition. Methods This cross-sectional study was performed in a certain district of Shanghai in March and April 2017. Data was collected using a self-reported questionnaire, which included questions on sociodemographic characteristics, social capital, health literacy and health-promoting lifestyle profile-II. Health-promoting lifestyle profile-II measures the behaviours or habits of physical activity and healthy nutrition. An explore factor analysis of the principal components with varimax rotation was carried out on the social capital scale. Descriptive statistics was used to summarize the sociodemographic of participants. Mediation analysis was performed using the bootstrapping tests to examine whether health literacy mediate the relationship between social capital and physical activity as well as nutrition. Results The explore factor analysis results showed that social capital has five dimensions, namely social participation, social support, social network, control over life and feelings about the community. There is a positive correlation between social capital, health literacy, physical activity and nutrition. The correlation coefficient varied from 0.135 to 0.594. Mediation analysis demonstrated health literacy played a partial mediating effect between social capital and physical activity as well as nutrition. In the relationship between physical activity and social capital, the indirect effect of health literacy accounted for 8.20 to 12.65% of the total effect. In the relationship between nutrition and social capital, the mediation effect of health literacy accounted for 4.93 to 12.71% of the total effect. Conclusion Social capital can promote physical activity and nutrition by disseminating health information. Enhancing the social capital of residents will help increase physical activity and develop healthy eating habits. Attention should also be paid to the improvement of residents’ health literacy.

The cause of nuclear shape abnormalities which are often seen in pre-neoplastic and malignant tissues is not clear. In this study we report that deformation of the nucleus can be induced by TGFb1 stimulation in several cell lines including Huh7. In our results, the upregulated histone H3.3 expression downstream of SMAD signaling contributed to TGFb1-induced nuclear deformation, a process of which requires incorporation of the nuclear envelope (NE) proteins lamin B1 and SUN1. During this process, the NE constitutively ruptured and reformed with no observable indications of DNA damage response. Contrast to lamin B1 which was relatively stationary around the nucleus, the upregulated lamin A was highly mobile, shuttling between the nucleus and cytoplasm, and clustering at the nuclear periphery. The chromatin regions that lost NE coverage formed a supra-nucleosomal structure characterized by elevated histone H3K27me3 and histone H1, the formation of which depended on the presence of lamin A. These results provide evidence that shape of the nucleus can be modulated through TGFb1-induced compositional changes in the chromatin and nuclear lamina.

Interkinetic nuclear migration (INM) is a process by which nuclei oscillate between the basal and apical surfaces of epithelial cells in coordination with the cell cycle. The cytoskeletal machinery including microtubules and actin has been reported to drive apical INM; however, the role of nuclear proteins in this process has yet to be fully elucidated. Here, we investigated the function of a SUN-domain protein, Sun1, in zebrafish. We found that zebrafish sun1 is highly expressed in the ventricular zone of the brain. Knocking down sun1 with antisense morpholino oligonucleotides reduced the abundance of nestin- and gfap-expressing neural stem cells and progenitor cells. The live-cell imaging results showed that sun1 morphant cells migrated toward the basal side during the S phase but failed to migrate apically during the G2 phase. On the contrary, the passive stochastic movement during the G2 phase was unaffected. Furthermore, down regulation of sun1 was shown to reduce the expression of genes associated with the Notch pathway, whereas the expression of genes in the Wnt pathway was less perturbed. Findings from this research suggest that the Sun1-mediated nucleo-cytoskeletal interaction contributes to apical nuclear migration, and may thus affect exposure to Notch signal, thereby altering the composition of the progenitor pool in the embryonic neurogenesis of zebrafish.

γδ T cells are a unique population of lymphocytes that have regulatory roles in patients with chronic hepatitis B (CHB); however, their role in acute hepatitis B (AHB) infection remains unclear. Phenotype and function of γδ T cells were analyzed in 29 AHB patients, 28 CHB patients, and 30 healthy controls (HCs) using immunofunctional assays. Compared with HCs and CHB patients, decreased peripheral and increased hepatic γδ T cells were found in AHB patients. Increased hepatic γδ T cells in AHB patients were attributed to elevated hepatic chemokine levels. Peripheral γδ T cells exhibited highly activated and terminally differentiated memory phenotype in AHB patients. Consistently, peripheral γδ T cells in AHB patients showed increased cytotoxic capacity and enhanced antiviral activity which was further proved in longitudinal study. Activated γδ T cells in AHB patients exhibited increased cytotoxicity and capacity for viral clearance associated with liver injury and the control of infection.

Over the decades, there have been continuous efforts to enhance the quality of human life. Postmenopausal syndrome is a serious concern for the wellbeing of a woman's health. Hormonal therapy is currently the mainstay of treatment for this condition. However, this therapy could lead to estrogen abuse, leading to adverse reactions and side effects. As a result, hormonal therapy has been unsuccessful in ameliorating postmenopausal syndrome. Cistanche deserticola is a classical tonic herb in traditional Chinese medicine. It exhibits significant estrogenic activity. The main active compounds of this herb are glycosides. In a previous experiment, three important factors contributing to the total glycoside yield, acteoside yield, and estrogenic activity were identified, namely, eluent concentration, pH, and eluent volume. In this experiment, an optimal purification process was determined using a central composite design-response surface methodology to obtain glycosides from this herb. An eluent (ethanol) concentration of 85% and volume of 25 BV at a pH of 11 was found to be optimal. Twenty-one active compounds were identified by a high-performance liquid chromatography/ quadrupole time-of-flight mass spectrometry assay. This study provides valuable insights for further in-depth research evaluating the estrogenic activities of total glycosides of Cistanche deserticola.

Background Breast cancer is a common tumor in China and has become a public health problem in modern society. Stress plays an important role in the occurrence and progression of cancer. At present, the current situation of stress on breast cancer survivors (BCSs) in China has not been fully understood. This study aims to explore the stress and coping strategies of Chinese BCSs, which provide suggestions to help BCSs reduce stress. Methods Sixty-three BCSs from the Shanghai Cancer Rehabilitation Club in China were included in this study and were divided into eight focus groups. These were transcribed verbatim, coded using thematic analysis and analyzed using NVivo 11. Results Three themes were extracted from the data to address our research objectives: stress, coping strategies and expectations. The stress of BCSs included psychological stress, stress caused by physical pain, economic stress, stress caused by the change of life status, and stress caused by information overload; the coping strategies included self-strategies and help from others; from the perspective of the survivors, they put forward their expectations for both the society and themselves. Conclusions This study shows that BCSs face a variety of stress. In the face of stress, BCSs need comprehensive support, including social and family support to cope with stressors. The findings from this study provide evidence for improving the quality of life among BCSs.

Background Echinococcosis is considered a neglected zoonotic disease and has been a major worldwide public health problem. Although it is known that health literacy is closely related to health behaviours and health outcomes, few studies have paid attention to echinococcosis related health literacy. This study aims to examine the association between echinococcosis-specific health literacy (ES-HL) and behavioural intention to prevent echinococcosis (BIPE) among herdsmen on the Tibet Plateauin in China. Methods A cross-sectional study of 401 Tibetan herdsmen was conducted in Gande county of Qinghai Province, China. Participants were recruited from August to September 2018 and from February to March 2019. A self-developed questionnaire was used to measure demographic information, ES-HL and BIPE. Hierarchical regression analysis was done to identify the factors associated with BIPE. Results In the hierarchical regression analysis, we entered age, sex, education level, marital state and family monthly income per capita into model 1 which explained a significant amount of variance in BIPE (Adjusted R2 change = 0.029, P = 0.006). Sex (β = − 0.125, P = 0.013) and family monthly income per capita (β = − 0.133, P = 0.009) were found to be associated with BIPE. Subsequently, the three factors of ES-HL were added to Model 1 to create Model 2. In Model 2, the two factors of ES-HL, perceived echinococcosis information support (β = 0.229, P P = 0.089) was not found to be associated with BIPE. The model improved significantly when ES-HL was included (Model 2) explaining the 25.8% of variance of BIPE (Adjust R2 change =0.229, P Conclusions ES-HL is an important predictor of whether individuals take preventive actions against echinococcosis. An ES-HL promotion action project should be developed targeting specific populations to enhance the prevention of echinococcosis.

This study aims to investigate the serial multiple mediation of physical activity and perceived stress in the relationship between individual social capital and quality of life (QOL) in breast cancer survivors (BCSs). This study was conducted among 520 BCSs between March and April 2017 in Shanghai, China. Data were collected using the Individual Social Capital Scale, the Health-Promoting Lifestyle Profile-II, the Perceived Stress Scale-14 and the EORTC QLQ-C30. Ordinary least-squares regression and the bootstrap method was used to test the significance of the serial multiple mediation model. The serial-multiple mediations of physical activity and perceived stress were found significant in the relationship of QOL with all five dimensions of individual social capital. The separate mediations of two single mediating variables were found significant in the relationship of QOL with control over life and feeling about the community. In the relationship of QOL with social participation, social network and social support, the separate mediation of physical activity was significant, while the separate mediation of perceived stress was not significant. A multidisciplinary team approach and a variety of delivery systems are needed to address the social, physical and psychological issues for improving QOL among BCSs.

Background: Since the coronavirus disease 2019 (COVID-19) outbreak in Wuhan in late 2019, China has been implementing an unprecedented quarantine strategy cover

Introduction The differentiation of benign and malignant sub-centimetre (≤10 mm) lung nodules (SCLNs) is challenging. Computed tomography (CT)-guided biopsy has been widely used for the diagnosis of lung nodules or masses. However, studies regarding CT-guided biopsies for SCLNs are still lacking. Objectives To evaluate the feasibility and diagnostic accuracy of CT-guided biopsies for SCLNs. Methods From December 2011 to October 2017, 102 patients with SCLNs underwent CT-guided lung biopsies. Data on technical success, diagnostic performance and procedure-related complications were collected and analysed. Results The technical success rate of CT-guided biopsy for SCLNs was 99% (101/102). One patient failed to undergo the procedure. A total of 101 SCLNs in 101 patients were examined. The biopsy diagnostic results included 38 malignant cases, 1 suspected malignant case, 5 specific benign cases and 57 non-specific benign cases. The final diagnoses included 49 malignant cases, 49 benign cases and 3 cases of undiagnosed lesions. The sensitivity, specificity and overall diagnostic accuracy were 80% (39/49), 100% (49/49) and 90% (88/98), respectively. Based on the univariate and multivariate logistic regression analyses, the independent risk factors for diagnostic failure were small tissue sample numbers (P = 0.048) and procedure-related hemoptysis (P = 0.004). Pneumothorax was found in 13 patients (13%). Based on the univariate and multivariate logistic regression analyses, the independent risk factor for pneumothorax was the decubitus position (P = 0.011). Hemoptysis was found in seven patients (7%). Conclusions CT-guided biopsy is a safe and highly accurate diagnostic method for SCLNs.

Mutations in lamin A (LMNA) are responsible for a variety of human dystrophic and metabolic diseases. Here, we created a mouse model in which progerin, the lamin A mutant protein that causes Hutchinson–Gilford progeria syndrome (HGPS), can be inducibly overexpressed. Muscle‐specific overexpression of progerin was sufficient to induce muscular dystrophy and alter whole‐body energy expenditure, leading to premature death. Intriguingly, sarcolipin (Sln), an endoplasmic reticulum (ER)‐associated protein involved in heat production, is upregulated in progerin‐expressing and Lmna knockout (Lmna −/−) skeletal muscle. The depletion of Sln accelerated the early death of Lmna −/− mice. An examination at the molecular level revealed that progerin recruits Sln and Calnexin to the nuclear periphery. Furthermore, progerin‐expressing myoblasts presented enhanced store‐operated Ca2+ entry, as well as increased co‐localization of STIM1 and ORAI1. These findings suggest that progerin dysregulates calcium homeostasis through an interaction with a subset of ER‐associated proteins, resulting in thermogenic and metabolic abnormalities., A model for progerin in calcium homeostasis and thermogenesis. In the molecular level, progerin can recruits a subset of endoplasmic reticulum (ER) proteins including Sln and Calnexin, but not SERCA2 or Calreticulin to the nuclear periphery, and may thus induce ER stress and enhance store‐operated calcium entry. The disturbed calcium homeostasis in progeric muscle may trigger transcriptional activation of Sln and ER‐stress associated genes and alter muscle‐based thermogenesis, leading to premature death of the animals. Cyt., cytosolic.

Traumatic brain injury (TBI) is a leading cause of mortality and morbidity worldwide. Neuroinflammation is prominent in the short and long-term consequences of neuronal injuries that occur after TBI. Neuroinflammation involves the activation of glia, including microglia and astrocytes, to release inflammatory mediators within the brain, and the subsequent recruitment of peripheral immune cells. Various animal models of TBI have been developed that have proved valuable to elucidate the pathophysiology of the disorder and to assess the safety and efficacy of novel therapies prior to clinical trials. These models provide an excellent platform to delineate key injury mechanisms that associate with types of injury (concussion, contusion, and penetration injuries) that occur clinically for the investigation of mild, moderate, and severe forms of TBI. Additionally, TBI modeling in genetically engineered mice, in particular, has aided the identification of key molecules and pathways for putative injury mechanisms, as targets for development of novel therapies for human TBI. This Review details the evidence showing that neuroinflammation, characterized by the activation of microglia and astrocytes and elevated production of inflammatory mediators, is a critical process occurring in various TBI animal models, provides a broad overview of commonly used animal models of TBI, and overviews representative techniques to quantify markers of the brain inflammatory process. A better understanding of neuroinflammation could open therapeutic avenues for abrogation of secondary cell death and behavioral symptoms that may mediate the progression of TBI.

Methamphetamine (METH)-induced cell death contributes to the pathogenesis of neurotoxicity; however, the relative roles of oxidative stress, apoptosis, and autophagy remain unclear. L-Ascorbate, also called vitamin (Vit.) C, confers partial protection against METH neurotoxicity via induction of heme oxygenase-1. We further investigated the role of Vit. C in METH-induced oxidative stress, apoptosis, and autophagy in cortical cells. Exposure to lower concentrations (0.1, 0.5, 1 mM) of METH had insignificant effects on ROS production, whereas cells exposed to 5 mM METH exhibited ROS production in a time-dependent manner. We confirmed METH-induced apoptosis (by nuclear morphology revealed by Hoechst 33258 staining and Western blot showing the protein levels of pro-caspase 3 and cleaved caspase 3) and autophagy (by Western blot showing the protein levels of Belin-1 and conversion of microtubule-associated light chain (LC)3-I to LC3-II and autophagosome staining by monodansylcadaverine). The apoptosis as revealed by cleaved caspase-3 expression marked an increase at 18 h after METH exposure while both autophagic markers, Beclin 1 and LC3-II, marked an increase in cells exposed to METH for 6 and 24 h, respectively. Treating cells with Vit. C 30 min before METH exposure time-dependently attenuated the production of ROS. Vitamin C also attenuated METH-induced Beclin 1 and LC3-II expression and METH toxicity. Treatment of cells with Vit. C before METH exposure attenuated the expression of cleaved caspase-3 and reduced the number of METH-induced apoptotic cells. We suggest that the protective effect of Vit. C against METH toxicity might be through attenuation of ROS production, autophagy, and apoptosis.

Aging is an evolutionally conserved process that limits life activity. Cellular aging is the result of accumulated genetic damage, epigenetic damage and molecular exhaustion, as well as altered inter-cellular communication; these lead to impaired organ function and increased vulnerability to death. Skeletal muscle constitutes ~40% of the human body’s mass. In addition to maintaining skeletal structure and allowing locomotion, which enables essential daily activities to be completed, skeletal muscle also plays major roles in thermogenesis, metabolism and the functioning of the endocrine system. Unlike many other organs that have a defined size once adulthood is reached, skeletal muscle is able to alter its structural and functional properties in response to changes in environmental conditions. Muscle mass usually remains stable during early life; however, it begins to decline at a rate of ~1% year in men and ~0.5% in women after the age of 50 years. On the other hand, different exercise training regimens are able to restore muscle homeostasis at the molecular, cellular and organismal levels, thereby improving systemic health. Here we give an overview of the molecular factors that contribute to lifespan and healthspan, and discuss the effects of the longevity gene Cisd2 and middle-to-old age exercise on muscle metabolism and changes in the muscle transcriptome in mice during very old age.

Objective To investigate the correlation of HIF-2α, ABCG2 and OCT-4 with chemotherapy resistant gastric cancer in humans. Methods Fifty-two patients who were confirmed to have advanced gastric cancer with the aid of electronic endoscopy and pathology in the Department of Gastroenterology, Affiliated Hospital of Weifang Medical College, were enrolled in the study. According to the effect of FOL-FOX4 chemotherapy that these patients had experienced, they were divided into three groups: CR+PR (complete remission+partial remission) group, SD (stable disease) group and PD (progressive disease) group. The expression levels of HIF-2α, ABCG2, and OCT-4 mRNA and protein were assessed in different groups by using RT-PCR and immunocytochemistry. Results Two patients achieved CR , 19 achieved PR , 25 showed SD, and 6 showed PD. In other words, CR+PR were seen in 21 patients (40.4%), SD in 25(48.1%), PD in 6(11.5%). In CR+PR group, the expression levels of HIF-2α, ABCG2 and OCT4 mRNA and protein were low, but the above mentioned expressions were significantly increased in SD group and PD group. The expression levels of HIF-2α, ABCG2 and Oct-4 mRNA and protein were highest in the PD group, lower in the SD group, and lowest in the CR + PR groups (all P

Migration and organization of the nucleus are essential for the proliferation and differentiation of cells, including neurons. However, the relationship between the positioning of the nucleus and cellular morphogenesis remains poorly understood. Inherited recessive cerebellar ataxia has been attributed to mutations in SYNE1, a component of the linker of nucleoskeleton and cytoskeleton (LINC) complex. Regardless, Syne1-mutant mice present with normal cerebellar development. The Sad1-Unc-84 homology (SUN)-domain proteins are located at the inner nuclear membrane and recruit Syne proteins through the KASH domain to the outer nuclear membrane. Here, we report an unrecognized contribution of Sun1 and Sun2 to the postnatal development of murine cerebellum. Mice depleted of Sun1 showed a marked reduction in the cerebellar volume, and this phenotype is exacerbated with additional loss of a Sun2 allele. Consistent with these histological changes, Sun1−/− and Sun1−/−Sun2+/− mice exhibited defective motor coordination. Results of immunohistochemical analyses suggested that Sun1 is highly expressed in Purkinje cells and recruits Syne2 to the periphery of the nucleus. Approximately 33% of Purkinje cells in Sun1−/− mice and 66% of Purkinje cells in Sun1−/−Sun2+/− mice were absent from the surface of the internal granule layer (IGL), whereas the proliferation and migration of granule neurons were unaffected. Furthermore, the Sun1−/−Sun2+/− Purkinje cells exhibited retarded primary dendrite specification, reduced dendritic complexity and aberrant patterning of synapses. Our findings reveal a cell-type-specific role for Sun1 and Sun2 in nucleokinesis during cerebellar development, and we propose the use of Sun-deficient mice as a model for studying cerebellar ataxia that is associated with mutation of human SYNE genes or loss of Purkinje cells., Summary: Mice lacking Sun proteins serve as a working model to study SYNE1-associated cerebellar ataxia; they will also be useful in identifying therapeutic targets for neurodegenerative diseases involving Purkinje cell loss.

The paper studies the basic characteristics and the definition of the wireless sensor networks, the time synchronization of wireless sensor network and the algorithm of time synchronization in wireless sensor networks. This paper studies the RBS algorithm and its improved algorithm. The research results have practical significance to the rapid development of network and the future network.

This paper studied the technology of PTN networking structure and networking planning technology. We studied the key technology of PTN, the relevant algorithm to optimize PTN networking. Using matlab simulation software we realize kruskal algorithm to construct minimum spanning tree. The results of this study can improve the efficiency of the network, and reduce network construction, reduce the operation cost. It has good social and economic significance.