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Severe uterine injury is a major cause of endometrial scar formation and female infertility. Currently, the methods for accelerating injured uterine healing are still lacking. Genetic engineering modification of mesenchymal stem cells (MSCs) has been shown great promise in preclinical studies on regeneration. Here, we constructed a type of UC-MSCs with overexpressed bFGF (UC-MSCbFGF) and investigated the effects of the UC-MSCbFGF/scaffold on functional regeneration of the full-thickness defect uterus of the rat model. At day 7, 14, 30 after treatments, the rats were euthanized and the injured uterus were observed. The structural and functional change of uterine were assessed by hematoxylin and eosin (HE) staining, immunohistochemical staining and fertility experiment. The UC-MSCbFGF/scaffold group exhibited anti-inflammatory effect, and the number of CD45+ cell in the UC-MSCbFGF/scaffold group was significantly less than that in UC-MSCs/scaffold group and scaffold group, but higher than sham-operated group at day 7 post-mending. At day 14, the UC-MSCbFGF/scaffold group exhibited dramatically pro-angiogenesis efficacy compared with UC-MSCs/scaffold group and scaffold group. At day 30, the endometrial thickness, structure of myometrium and blood vessels in the UC-MSCbFGF/scaffold were better than those of the UC-MSCs/scaffold group and scaffold group, even close to sham-operated group. Implantation rate at injury region post-operation 30 days in the UC-MSCbFGF/scaffold group (8/16) was significantly higher than that in UC-MSCs/scaffold group (1/16) and scaffold group (0/16). Taken together, the UC-MSCbFGF/scaffold system suppressed local inflammation, promoted angiogenesis and accelerated regeneration of the defected uterine wall, and thereby greatly shortened the healing time of the injured uterus.

A total of 324 compounds were systematically characterized by feature-based molecular networking. This work provides an efficient strategy for the rapid discovery and characterization of unknown compounds in natural products.

No meta-analysis has analyzed the effect of physical activity level, period of physical activity intervention, and duration of intervention, on perinatal depression. This study was to evaluate the impact of physical activity intensity, dose, period, and duration on perinatal depression.The literature was searched via the PubMed, Embase, Cochrane Library, and Web of Science databases. Weighted mean difference (WMD) or the risk ratio (RR) was used as the effect indicator, and the effect size was represented by the 95 % confidence interval (CI). Subgroup analysis based on the perinatal stage, physical activity intensity, physical activity equivalent, and intervention duration was performed.Totally, 35 studies including 5084 women were included. Physical activity could reduce the incidence and severity of depression in perinatal women. Among depressed women with prenatal depression, low-intensity physical activity, with metabolic equivalents (METs)-min/week being450, was associated with lower levels of depression. In the general population, the risk of postpartum depression was lower in the physical activity group when the duration of intervention was ≥12 weeks, being II, III stage, and ≥450 METs-min/week. Both low and moderate-intensity physical activity were beneficial to an improved depression severity among depressed women with postpartum depression, and moderate exercise intervention could decrease the risk of postpartum depression in general pregnant women.Different types of physical activities may affect the effectiveness of interventions.Our study indicated physical activity specifically targeted at pregnant women could reduce depression risk and severity.

Background and Purpose:Reliable instruments for the measurement of perceived stress in people living with HIV (PLHIV) are crucial. However, there is no Myanmar version of such an instrument.Methods:We adapted the 35-item Perceived Stress Scale for People Living with HIV/AIDS (PSSHIV) into a Myanmar version (PSSHIV-M), and 150 PLHIV completed the survey.Results:The 31-item PSSHIV-M with a five-factor structure has a Cronbach's alpha of .85 to .95. Construct validity was demonstrated for the instrument, and the findings of Rasch analysis also suggest evidence of reliability and validity.Conclusions:The psychometric properties of the 31-item PSSHIV-M with a five-factor structure support its efficacy in ascertaining how HIV perceived stress affects Myanmar PLHIV. It could also facilitate the development of stress management interventions for that population.

Background. There has been a gradual trend towards younger ageing of acute cerebral infarction in recent years. Atherosclerotic plaque rupture followed by dislodgement of emboli and resulting arterial embolism is an important mechanism for the development of acute cerebral infarction. Traditional independent risk factors for cerebral infarction have received attention from clinicians, but the risk factors for large artery atherosclerotic cerebral infarction are still unclear. Various blood biomarkers have an important role in the early diagnosis of large artery atherosclerotic cerebral infarction. Objective. To assess the diagnostic predictive value of a group of biomarkers for large artery atherosclerotic cerebral infarction. Methods. Lipoprotein-associated phospholipase A2 (LP-PLA2), trypsin-like protein (TPS), serum amyloid A (SAA), and supersensitive C-reactive protein (hs-CRP) levels were measured in the case group (30 cases) and control group (54 cases), respectively. Results. The differences in the general data between the two groups were not statistically significant ( P > 0.05 ). Logistic regression and ROC curve analysis showed that Lp-PLA2, TPS, and SAA were positively associated with the diagnosis of large atherosclerotic cerebral infarction ( P < 0.05 ). The area under the ROC curve of the multivariate model for the biomarker group reached 0.995. Conclusion. Biomarkers are closely associated with the occurrence of large atherosclerotic cerebral infarction and can be used as clinical adjuncts for diagnosis and assessment of prognosis.

BackgroundBreast and thyroid cancer are increasingly prevalent, but it remains unclear whether the observed associations are due to heightened medical surveillance or intrinsic etiological factors. Observational studies are vulnerable to residual confounding, reverse causality, and bias, which can compromise causal inference. In this study, we employed a two-sample Mendelian randomization (MR) analysis to establish a causal link between breast cancer and heightened thyroid cancer risk.MethodsWe obtained the single nucleotide polymorphisms (SNPs) associated with breast cancer from a genome-wide association study (GWAS) conducted by the Breast Cancer Association Consortium (BCAC). The FinnGen consortium’s latest and largest accessible GWAS thyroid cancer data at the summary level. We performed four MR analyses, including the inverse-variance-weighted (IVW), weighted median, MR-Egger regression, and weighted mode, to evaluate the potential causal connection between genetically predicted breast cancer and higher risk for thyroid cancer. Sensitivity analysis, heterogeneity and pleiotropy tests were used to ensure the reliability of our findings.ResultsOur study revealed causal relationship between genetically predicted breast cancer and thyroid cancer (IVW method, odds ratio (OR) = 1.135, 95% confidence interval (CI): 1.006 to 1.279, P = 0.038). However, there was no causal association between genetically predicted triple-negative breast cancer and thyroid cancer (OR = 0.817, 95% CI: 0.610 to 1.095, P = 0.177). There was no directional pleiotropy or horizontal pleiotropy in the present study.ConclusionThis two-sample MR study supports a causal link between ER-positive breast cancer and heightened the risk of thyroid cancer. Our analysis did not reveal a direct correlation between triple-negative breast cancer and thyroid cancer.

Melamine (MEL), cyanuric acid (CYA), and phthalates have kidney toxicity, respectively. Still, no study has explored whether there is an interaction of co-exposure to MEL, CYA, and phthalates on early kidney impairment, including cystatin C (CYST), beta 2-microglobulin (β2-MG), albumin creatinine ratio (ACR), and estimated glomerular filtration rate (eGFR). Urine samples were collected from 333 adults in the National Health and Nutrition Examination Survey (NHANES) 2003-2004, and urinary MEL, CYA, and ten metabolites of phthalates were quantified. The multiple markers of early kidney impairment were also measured, including serum CYST, β2-MG, urinary ACR, and eGFR. Their associations were explored by multiple linear and multivariate logistic regression models. Meanwhile, the interactions of co-exposure to MEL, CYA, and phthalates on early kidney impairment were analyzed by Wilcoxon rank-sum test combined with the LSD test. In the multiple linear regression model, urinary concentrations of monobenzyl phthalate (MBzP), mono(3-carboxypropyl) phthalate (MCPP), mono(2-ethyl-5-carboxypentyl) phthalate (MECPP), and mono(2-ethylhexyl) phthalate (MEHP) were positively associated with urinary ACR, serum β2-MG, and CYST, respectively. Urinary concentrations of MBzP and MCPP were negatively associated with eGFR. In the multivariate logistic regression model, increased urinary CYA concentration was the risk factor of CYST abnormality with an odds ratio (OR) (95% confidence interval, 95% CI) of 2.38 (1.01, 5.60) (P = 0.047) and increased urinary MBzP concentration was the risk factor of ACR abnormality with an OR of 2.59 (1.41, 4.75) (P = 0.002). The co-exposure to MEL, CYA, and four phthalate metabolites (MEHP, MBzP, MCPP, and MECPP) presented significantly interactive effects on the markers of early kidney impairment, respectively. There were the independent and interactive effects of exposure to MEL, CYA, and specific phthalate metabolites on early kidney impairment. Due to co-exposure to multiple environmental chemicals in our daily life, more attention should be paid to the health damage raised by the synergistic effects of environmental chemicals.

Clinicopathologic characteristics of HP1y expression in CRC patients (S1); Real-time PCR primer sequences (S2); ChIP primer sequences for p21 promoter (S3).

Analysis of the effect of miR-30a on HP1γ protein and mRNA.

Description of additional methods and procedures used in the study.

Pearson's correlation scatter plot of the fold change of miR-30a and HP1g mRNA in human colorectal cancer tissues (n=38).

Colorectal cancer pathogenesis remains incompletely understood. Here, we report that the heterochromatin protein HP1γ is upregulated commonly in human colorectal cancer, where it promotes cell proliferation in vitro and in vivo. Gene-expression and promoter-binding experiments demonstrated that HP1γ directly regulated CDKN1A (p21Waf1/Cip1) in a manner associated with methylation of histone H3K9 on its promoter. We identified miR-30a as a tumor-suppressive microRNA that targets HP1γ in vitro and in vivo to specifically suppress the growth of colorectal cancer in mouse xenograft models. MiR-30a was widely downregulated in primary human colorectal cancer tissues, where its expression correlated inversely with high levels of HP1γ protein. Our results identify a new miR-30a/HP1γ/p21 regulatory axis controlling colorectal cancer development, which may offer prognostic and therapeutic opportunities. Cancer Res; 75(21); 4593–604. ©2015 AACR.

Effects of miR-30a on cell cycle and apoptosis.

BackgroundParkinsonian tremor is a common pathological tremor that affects over 6 million people worldwide. It lowers patients' quality of life and threatens their career development, especially when patients' occupation requires dexterous manipulation. In spite of current available treatments in clinics, there is a lack of low-cost, low side-effect, effective solutions for Parkinsonian tremor. Transcranial direct current stimulation (tDCS) may be an alternative treatment.ObjectiveIn this research, we explored the immediate effect of tDCS with a novel bilateral electrode setup over Parkinsonian tremor. In such a bilateral setup, the cathode was placed over the primary cortex contralateral to the more affected side of Parkinsonian tremor while the anode symmetrically over the other hemisphere. It was designed as a modification to the traditional cathodal setup. The performance of this bilateral setup was compared with three other setups including anodal setup, cathodal setup, and sham (control).MethodsA randomized, sham-controlled, double-blind, crossover experiment was carried out over 13 qualified patients diagnosed with idiopathic Parkinson's disease (PD). Before and after the stimulus of each tDCS setup, subjects were tested before and after tDCS with four measures, including the Unified Parkinson's Disease Rating Scale (UPDRS), Fahn-Tolosa-Marin Tremor Rating Scale (FTMTRS), Purdue Pegboard Test (PPT) and a self-design Continuous Tremor Signal Assessment (CTSA). Tremor intensity calculated from CTSA data were regarded as the primary outcome of the experiment.ResultsStatistical results of CTSA, FTMTRS and PPT showed both bilateral tDCS and cathodal tDCS effectively suppressed Parkinsonian tremor. A quantitative comparison of the effect in tremor suppression indicated the optimal suppressive effect was obtained with bilateral tDCS. Based on the results of UPDRS, anodal tDCS was found to benefit subjects' overall performance the most, however, it had little effect in improving Parkinsonian tremor, as revealed by the results of other evaluations.ConclusionOur study suggests a beneficial immediate effect of bilateral tDCS in Parkinsonian tremor suppression. In addition, we assume there may be an underlying interhemispheric unbalance of cortical excitability which contributes to Parkinsonian tremor genesis.Clinical trial registrationIdentifier: ChiCTR2100054804.

HSF1 plays an important protective role in endotoxemic mice. However, the protective mechanisms of HSF1 are poorly understood.

Background Respiratory and cardiovascular disease (CVD) frequently coexist; however, there is limited evidence on the relationship between chronic respiratory symptoms in young adulthood and late-onset CVD. Research Question Are chronic respiratory symptoms in young adulthood associated with CVD and all-cause mortality in later life? Study Design and Methods A total of 4,621 participants from CARDIA (Coronary Artery Risk Development in Young Adults) cohort study aged 18–30 were included. Chronic respiratory symptoms were identified through respiratory symptom questionnaires in two consecutive exams. Incident CVD and all-cause mortality were adjudicated over 30-year follow-up. Multivariable Cox proportional hazards models were used to explore association of chronic respiratory symptoms with incident CVD and all-cause mortality. Results During a median follow-up of 30.9 years, 284 CVD events (6.15%) and 378 deaths (8.18%) occurred. After multivariable adjustment for demographics, cardiovascular risk factors, smoking and lung function, the hazard ratios (95% CIs) for CVD events were 1.51 (1.18-1.93) for any respiratory symptom, 1.57 (1.18-2.09) for cough or phlegm, 1.31 (1.01-1.68) for wheeze, 1.73 (1.25-2.41) for shortness of breath, and 1.32 (1.01-1.71) for chest illnesses. Similar findings were also observed in all-cause mortality. Comparing 0 versus 3-4 respiratory symptoms, the hazard ratios (95% CIs) were 1.97 (1.34-2.91) for CVD and 1.75 (1.23-2.47) for all-cause mortality. Similar results were observed in various sensitivity analyses. Interpretation Chronic respiratory symptoms in young adulthood are associated with an increased risk of CVD and all-cause mortality in midlife independent of established cardiovascular risk factors, smoking and lung function. Identifying chronic respiratory symptoms in young adulthood may help provide prognostic information regarding future cardiovascular health.

Tight oil resources in China are mainly exploited by staged-fractured horizontal wells; horizontal wells face the problems of the rapid decline rate and low primary oil recovery. Pilot tests on the asynchronous cyclic waterflooding for the horizontal-vertical well pattern were carried out in recent years and achieved good performance. However, there are few studies on the influencing factors and parameter optimization of asynchronous cyclic waterflooding, which limits its wide application. This work took the tight oil reservoir in Yanchang formation, Fuxian area, Ordos Basin as its object, and the oil recovery mechanisms of asynchronous cyclic waterflooding for the horizontal-vertical well pattern were analyzed first. Then, the operation parameters of asynchronous cyclic waterflooding were optimized by the numerical simulation method. Among them, the injection proportion was optimized by the fuzzy synthetic evaluation method. Finally, the oilfield test was carried out based on the optimized parameters. The results showed that pressure disturbance and streamline deviation are the main oil recovery mechanisms of asynchronous cyclic waterflooding. The asynchronous mode of the diagonal well row is better than other asynchronous modes. For the injection time interval, injection-production ratio, and the injection and shut-in time, the cumulative oil production all show the trend of increasing first and then decreasing with the increase in these parameters. The optimal injection time interval and injection-production ratio are 0.5 T and 1, respectively. The optimal injection and shut-in time can be calculated by empirical formulas. Ultimately, the fuzzy synthetic evaluation model was established to optimize the injection proportion. Field practices showed that the average daily oil production of horizontal wells was increased from 1.7 to 3.0 m

The introduction of K+ into a RbNa3(Li3SiO4)4:Eu2+ phosphor to partially or completely replace Rb+ allows the emission spectrum to be modulated from blue (λ = 473 nm, FWHM = 22.5 nm) to a narrow cyan band (λ = 485 nm, FWHM = 21.1 nm).

BACKGROUND The updated metrics of “Life’s Essential 8 (LE8)” in quantifying cardiovascular health (CVH) status were released, whiles its distribution in Chinese children has not be reported. OBJECTIVE To assess the national distribution of Chinese school-aged children’s CVH status by LE8 scores and their temporal changes over time. METHODS Participants who aged between 7 and 19 years from 11 waves (1989-2018) of the China Health and Nutrition Survey were included. Scores of overall CVH and each LE8 metrics were calculated individually. Temporal changes were assessed with geographic regions, the causal relationship between health behaviors and health factors over time were built with cross-lagged panel models. RESULTS 21921 participants (52.6% boys) with data of at least four CVH components were included in the present analysis, the mean age was 13.0 (standard deviation, SD: 3.6) years. The overall CVH score remained stable in most regions with slight increased by 0.38 (95% CI: 0.29, 0.46; P CONCLUSIONS Chinese school-aged children and adolescents are generally of moderate CVH status, but mutual influences existed between CVH metrics. Interventions on diet may be the priority for promoting overall CVH in the future.

Autophagy plays an important role in endotoxemic mice, and heat shock factor 1 (HSF1) plays a crucial protective role in endotoxemic mice. However, the protective mechanisms of HSF1 are poorly understood. In this text, bioinformatics analysis, chromatin immunoprecipitation, and electrophoresis mobility shift assay were employed to investigate the underlying mechanisms. The results showed that the release of inflammatory cytokines increased and autophagy decreased significantly in

Polycyclic aromatics hydrocarbons (PAHs) are ubiquitous in foods and environment and possess carcinogenic and mutagenic potential. Foods are the main source of exposure to PAHs in the general population. In this study, we determined the concentrations of 16 European Union priority PAHs in 1,564 foodstuffs acquired from nine provinces and commonly consumed by the Chinese population. The most predominant PAH was chrysene (16.7%), followed by benz[a]anthracene (12.4%) and benzo[b]fluoranthene (11.7%). Edible vegetable oils (17.89 μg/kg) and fruits (1.97 μg/kg) had the highest and lowest concentrations of total PAHs, respectively. Suitable indicators of PAH contamination in foods were assessed based on the occurrence of other PAHs in samples negative for benzo[a]pyrene and the correlation for the PAHs and their combinations. According to our results, PAH4 was a suitable indicator, better than PAH8 and benzo[a]pyrene alone. PAH exposure in the Chinese population was estimated by combining contamination data with national individual food consumption data, based on the middle bound approach. The overall average dietary exposures for BaP and PAH4 were 3.08 and 17.61 ng/kg bw/day, respectively. The major contributors to the total dietary exposure of PAHs were cereals (39%), edible vegetable oils (28%), and vegetables (20%). We used the margin of exposure (MOE) approach to assess health risk for consumers. MOEs of the mean estimated dietary exposures were >10,000, indicating a low concern for the health of the general population and of consumers of smoked, grilled, or barbecued foods. For high consumers and children, the MOEs were

This study was aimed to investigate whether EPA and arachidonic acid (ARA), the representative n-3 or n-6 PUFA, could alleviate enterotoxigenic Escherichia coli (ETEC) K88-induced inflammation and injury of intestinal porcine epithelial cells 1 (IPEC-1) by modulating pyroptosis and necroptosis signalling pathways. IPEC-1 cells were cultured with or without EPA or ARA in the presence or absence of ETEC K88. EPA and ARA reduced ETEC K88 adhesion and endotoxin content in the supernatant. EPA and ARA increased transepithelial electrical resistance, decreased permeability of fluorescein isothiocyanate-labelled dextran, increased membrane protein expression of occludin, ZO-1 and claudin-1 and relieved disturbed distribution of these proteins. EPA and ARA also reduced cell necrosis ratio. EPA or ARA reduced mRNA and concentration of TNF-α, IL-6 and IL-8 and decreased mRNA abundances of intestinal toll-like receptors 4 and its downstream signals. Moreover, EPA and ARA downregulated mRNA expression of nod-like receptor protein 3 (NLRP3), caspase 1 and IL-18 and inhibited protein expression of NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), gasdermin D and caspase-1. Finally, EPA and ARA reduced mRNA expression of fas-associated death domain protein, caspase 8, receptor-interacting protein kinase (RIP) 1, mixed lineage kinase-like protein (MLKL), phosphoglycerate mutase 5 (PGAM5), motility-related protein 1 (Drp1) and high mobility protein 1 (HMGB1) and inhibited protein expression of phosphorylated-RIP1, p-RIP3, p-MLKL and HMGB1. These data demonstrate that EPA and ARA prevent ETEC K88-induced cell inflammation and injury, which is partly through inhibiting pyroptosis and necroptosis signalling pathways.

OBJECTIVE: We aimed to describe how the prevention and controlling strategies have been experienced by COVID-19 patients in China, especially those who had passed through the suspected, diagnosed, hospitalized, and recovery stages of the disease. DESIGN: A descriptive qualitative study followed the Standards for Reporting Qualitative Research guidelines. SAMPLES: COVID-19 patients were recruited from a COVID-19-designated facility in Shanghai, China, from April to June 2020, by the purposive sampling method. METHODS: Semi-structured, in-depth interviews by cell phone were used and transcriptions were analyzed using inductive qualitative content analysis method. RESULTS: We recruited 26 COVID-19 patients. Three theme categories emerged from the data analysis. The first was “Consciously adhere to COVID-19-related controlling strategies.” The second category was “Positive experiences of the COVID-19-related controlling strategies.” These patients experienced a quick and adequate medical response, confident in the medical system, or received help from community workers. The third category was “Negative experiences of the COVID-19-related controlling strategies.” These patients experienced psychological distress, stigma, privacy exposures, and inconveniences from the controlling strategies. CONCLUSIONS: It is urgent to develop a culturally sensitive intervention to eliminate the psychological distress and stigma of patients with COVID-19 and to protect their privacy during and after the pandemic.

Aims Few studies have examined the secular trend of the energy intake distribution, and its effect on future risk of hyperglycemia. This study aims to describe trajectories of energy intake distribution over 12 years and relate them to subsequent risk of hyperglycemia over 9 years of follow-up. Methods Our study used ten waves of data from the CHNS survey, a population-based longitudinal survey in China, ongoing since 1989. We examined a cohort of adult participants who were free from diabetes but had at least three waves of dietary data from 1997 to 2009. We assessed energy intake using three consecutive 24 h recalls. We used these data to identify trajectory groups of energy intake distribution by multi-trajectory model based on energy intake proportions of breakfast, lunch, and dinner. We followed up participants for hyperglycemia, diabetes, and impaired fasting glucose for 9 years from 2009 to 2018. Outcomes were ascertained with fasting glucose, serum HbA1c, and self-report of diabetes and/or glucose-lowering medication. We estimated relative risk (RR) for hyperglycemia, diabetes, and impaired fasting glucose by identified trajectory groups using multilevel mixed-effects modified Poisson regression with robust (sandwich) estimation of variance. Gender difference was additionally examined. Results A total of 4417 participants were included. Four trajectory groups were identified, characterized and labeled by “Energy evenly distributed with steady trend group” (Group 1), “Dinner and lunch energy dominant with relatively steady trend group” (Group 2), “Dinner energy dominant with increasing trend and breakfast energy with declining trend group” (Group 3), and “breakfast and dinner energy dominant with increasing trend group” (Group 4). During 48,091 person-years, 1053 cases of incident hyperglycemia occurred, 537 cases of incident diabetes occurred, and 516 cases of impaired fasting glucose occurred. Compared with Group 1, Group 3 was associated with higher subsequent risk of incident hyperglycemia in 9 years of follow-up (RR = 1.28, 95% CI = 1.02, 1.61). No association was found for incident diabetes and impaired fasting glucose. Among males, Group 3 was associated with higher risk of incident hyperglycemia in 9 years of follow-up (RR = 1.44, 95% CI = 1.07, 1.94). No relationship was found in females. Conclusions Energy intake distribution characterized by over 40% of energy intake from dinner with a rising trend over years was associated with higher long-term risk of hyperglycemia in Chinese adults.

As rare earth ion laser materials, any single kind type matrix can not satisfy the development requirements at the present stage, especially in the application of mid-infrared laser, which needs convenient operation, good physical and chemical properties and luminescent properties. In this study, nanocrystalline units are introduced into the glass structure to integrate their respective advantages and achieve the best balance, so as to obtain nanocrystalline-glass composites (NGC) with both crystal and amorphous properties. The results show that the emission intensity of the composited host is stronger than that of pure amorphous materials; particularly, the intensity of the 2.7 μm emission has been a significant improvement. Moreover, this method not only keeps the size of the nanocrystalline unit, but also affects the energy transfer making use of the nanostructure. Nano-glass ceramics thus might have a significant application potential; they might be used improve the performance of photonic devices and develop nano-integrated multifunctional materials.

Background The tumor inflammatory microenvironment plays a vital role in the initiation and progression of pancreatic cancer (PC). Both the lymphocyte-to-monocyte ratio (LMR) and preoperative peripheral blood monocytes are related to the prognosis of PC patients. However, the direct effect of monocytes on PC cells is not fully understood. The current study aimed to assess the effect of monocytes on PC and explore its potential mechanism. Methods The cutoff value of peripheral blood monocytes was evaluated by the receiver operating characteristic (ROC) curve. Transwell migration and invasion assays were used to detect the mobility of PC cells. The cytokines derived from monocytes were measured by quantitative real-time polymerase chain reaction (qRT-PCR). Western blotting was utilized to assess the expression of epithelial-mesenchymal transition (EMT) related markers. The expression level of Snail in PC tissue was determined by immunohistochemical (IHC) staining. Results A high monocyte count was inversely correlated with lymph node status and 5-year overall survival in PC. The PC cells underwent a cellular morphology change and increased cell motility after coculture with THP-1 monocytes. The THP-1 monocytes secreted various proinflammatory cytokines, including tumor necrosis factor-α (TNF-α) and interleukin-1α (IL-1α), which activated the nuclear factor-κB (NF-κB) signaling pathway leading to the upregulation of Snail and thereby promoting the EMT of PC cells. The expression level of Snail correlated significantly with the density of peripheral blood monocytes, and their level status was significantly associated with 5-year overall survival. Conclusions These findings indicated that elevated monocytes counts were a poor prognostic marker in PC, and monocytes could directly induce the EMT process of PC cells by upregulating Snail expression through the NF-κB signaling pathway.

To reduce the temperature difference of the heat exchanger and improve the thermal performance of organic Rankine cycle (ORC), a novel geothermal ORC-bypass flash system (ORC-f) is proposed. In this system, the latent heat proportion of working fluid and the saturated temperature of heat source are used as the basis for judgments. Further, the influence of heat source temperature and evaporation temperature on the ORC-f system is analyzed with different working fluids and compared with that of ORC system. The results show that when the heat source temperature is 403.15 K, the evaporation temperature is 313 K and 397 K, using R123 with higher latent heat proportion as working fluid, the net output power of ORC-f system is increased by 6.3 kW and 551.23 kW than that of the ORC system; using R114 with lower latent heat proportion as working fluid, the net output power of the ORC-f system is increased by 3.8 kW and 547.4 kW than that of the ORC system. When the saturated heat source temperature is not reached, the working fluid with higher latent heat proportion is used, the net output power and exergy efficiency of the ORC-f system are larger; When the saturated heat source temperature is reached, there is no need to increase the bypass flash system. Further, the thermal performance of the different working fluids of the ORC-f system is similar, and the ORC-f system can reduce the influence of the working fluid on the thermal performance.

Background Sepsis is a disease caused by multiple microbial infections resulting in excessive immune activation and multiple organ failure. Schistosoma japonicum cystatin (Sj-Cys) is a cysteine protease inhibitor and strong immunomodulator that stimulates M2 macrophages and alleviates inflammatory damage caused by sepsis. We would like to investigate whether exosomes derived from Sj-Cys treated macrophages convey the anti-inflammatory responses to mice with sepsis. Methods RAW264.7 macrophages were treated with rSj-Cys (2 µg/mL) for 48 h, the exosomes were obtained from the cell culture supernatant by ultracentrifugation and identified by transmission electron microscope, flow cytometry and Western blot assay. Sepsis was induced in BALB/c mice by cecal ligation and puncture (CLP). The mice with CLP-induced sepsis were treated with exosomes via intraperitoneal injection (10 µg/mouse). The therapeutic effect of exosomes on sepsis was assessed by observing the survival rate of mice up to 72 hours after CLP surgery and by measuring serum levels of inflammatory cytokines, liver/kidney damage biomarkers alanine aminotransferase (ALT), aspartate aminotransferase (AST)/urea nitrogen (BUN) and creatinine (Cr) in sera and observing pathological changes in tissue sections. The tissue levels of M1(iNOS), M2 (Arg-1) macrophage surface markers and TRL2/MyD88 were measured to explore possible mechanisms. Results Exosomes derived from Sj-Cys-treated macrophages exhibited significant therapeutic effect on CLP-induced sepsis in mice with prolonged survival rate and less damage of critical organs by down-regulating the pro-inflammatory factors TNF-α and IL-6 and up-regulating the anti-inflammatory factor TGF-β. The therapeutic effect of exosomes is associated with macrophage polarization from M1 (iNOS+) to M2 (Arg-1+) in infected tissues via down-regulating TRL2/MyD88 inflammatory pathway. Conclusions Exosomes derived from Sj-Cys-treated macrophages attenuated sepsis in mice through promoting macrophage polarization from M1 to M2 and reducing inflammatory responses, possibly via down-regulating TLR2/MyD88 inflammatory signaling pathway.

The purpose of this study was to investigate whether type 2 diabetes mellitus (T2DM) makes corneal endothelial cells (CECs) suffer from more severe ultraviolet A (UVA)-induced oxidative damage and explore its mechanisms via measuring the oxidant level and the antioxidant level in vitro.Corneas of spontaneous T2DM db/db mice and non-diabetes littermate control mice were irradiated with UVA, leading to oxidative damage of CECs. Anterior segment-optical coherence tomography, corneal image, and CECs immunohistochemistry staining were taken thereafter to measure central corneal thickness, corneal edema degree, and damage extent of CECs. In vitro, human corneal endothelial cells line B4G12 (HCECs) treated with high glucose (HG) and low glucose (LG) were exposed to UVA light separately. Subsequently, cellular proliferation, apoptosis, pro-oxidant factors, such as reactive oxygen species (ROS), antioxidant factors including Parkinson's disease protein 7 (DJ-1), nuclear factor-erythroid 2 related factor 2 (Nrf2), phosphorylated-Nrf2, and NAD(P)H: quinone oxidoreductase 1 (NQO1) were measured.T2DM mice presented greater oxidant damage of CECs and more distinct corneal edema compared with control mice when they were irradiated with the 150 J/cm2 UVA light. In vitro, HCECs in HG condition showed a significant decrease of proliferation, higher apoptosis extent, more ROS generation, lower expressions of DJ-1/Nrf2/NQO1, and distinct reduction of Nrf2 nuclear translocation compared to those in LG condition after exposing to 5 J/cm2 UVA light.Increase of ROS, downregulation of DJ-1/Nrf2/NQO1 expressions, and decrease of Nrf2 nuclear translocation could result in that T2DM makes CECs more vulnerable to oxidative damage.

Programmed cell death is a tightly regulated genetically controlled process that leads to cell suicide and eliminates cells that are either no longer needed or damaged/harmful. Nucleotide-binding leucine-rich repeat proteins have recently emerged as a novel class of Ca2+-permeable channels that operate in plant immune responses. This viewpoint argues that the unique structure of this channel, its permeability to other cations, and specificity of its operation make it an ideal candidate to mediate cell signaling and adaptive responses not only to pathogens but also to a broad range of abiotic stress factors.