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Abstract Straw pollution and the increasing scarcity of phosphorus resources in many regions of China have had severe impacts on the growing conditions for crop plants. Using microbial methods to enhance straw decomposition rate and phosphorus utilization offers effective solutions to address these problems. In this study, a microbial consortium 6 + 1 (consisting of a straw-degrading bacterium and a phosphate-solubilizing bacterium) was formulated based on their performance in straw degradation and phosphorus solubilization. The degradation rate of straw by 6 + 1 microbial consortium reached 48.3% within 7 days (The degradation ability was 7% higher than that of single bacteria), and the phosphorus dissolution rate of insoluble phosphorus reached 117.54 mg·L− 1 (The phosphorus solubilization ability was 29.81% higher than that of single bacteria). In addition, the activity of lignocellulosic degrading enzyme system was significantly increased, the activities of endoglucanase, β-glucosidase and xylanase in the microbial consortium were significantly higher than those in the single strain (23.16%, 28.02% and 28.86%, respectively). Then the microbial consortium was processed into microbial agents and tested in rice pots. The results showed that the microbial agent significantly increased the content of organic matter, available phosphorus and available nitrogen in the soil. Ongoing research focuses on the determination of the effects and mechanisms of a functional hybrid system of straw degradation and phosphorus removal. The characteristics of the two strains are as follows: Straw-degrading bacteria can efficiently degrade straw to produce glucose-based carbon sources when only straw is used as a carbon source. Phosphate-solubilizing bacteria can efficiently use glucose as a carbon source, produce organic acids to dissolve insoluble phosphorus and consume glucose at an extremely fast rate. The analysis suggests that the microbial consortium 6 + 1 outperformed individual strains in terms of both performance and application effects. The two strains within the microbial consortium promote each other during their growth processes, resulting in a significantly higher rate of carbon source consumption compared to the individual strains in isolation. This increased demand for carbon sources within the growth system facilitates the degradation of straw by the strains. At the same time, the substantial carbon consumption during the metabolic process generated a large number of organic acids, leading to the solubilization of insoluble phosphorus. It also provides a basis for the construction of this type of microbial consortium.

Abstract Background Metastasis is the leading cause of death among prostate cancer (PCa) patients. Obesity is associated with both PCa-specific and all-cause mortality. High-fat diet (HFD) is a risk factor contributing to obesity. However, the association of HFD with PCa metastasis and its underlying mechanisms are unclear. Methods Tumor xenografts were conducted by intrasplenic injections. The ability of migration or invasion was detected by transwell assay. The expression levels of RPS27 were detected by QRT-PCR and western blot. Results The present study verified the increase in PCa metastasis caused by HFD in mice. Bioinformatics analysis demonstrated increased RPS27 in the experimentally induced PCa in HFD mice, indicating that it is an unfavorable prognostic factor. Intrasplenic injections were used to demonstrate that RPS27 overexpression promotes, while RPS27 knockdown significantly reduces, PCa liver metastasis. Moreover, RPS27 inhibition suppresses the effects of HFD on PCa metastasis. Further mRNA sequencing analysis revealed that RPS27 promotes PCa metastasis by selectively enhancing the expression of various genes. Conclusion Our findings indicate that HFD increases the risk of PCa metastasis by elevating RPS27 expression and, subsequently, the expression of genes involved in PRAD progression. Therefore, RPS27 may serve as a novel target for the diagnosis and treatment of metastatic PCa.

Abstract Background: Optimal adjuvant chemotherapy after laparoscopic surgery in gastric cancer (GC) patients is still undefined. We aimed to evaluate the efficacy of S‐1 plus oxaliplatin (SOX) and capecitabine plus oxaliplatin (CAPOX) in patients with GC after laparoscopic gastrectomy. Methods: A non‐inferiority randomized controlled clinical trial was performed in China. Patients with advanced GC who underwent laparoscopic D2 gastrectomy were randomly assigned to receive SOX and CAPOX regimens. Results: In total, 191 patients were screened between May 2018 and June 2019, and 140 (73.3%) were included in the modified intent‐to‐treat analysis (mITT), of whom 69 and 71 were assigned to the SOX and CAPOX groups, respectively. The SOX group had similar 3‐year overall survival (OS) and disease‐free survival to the CAPOX group. Subgroup analysis revealed significantly better OS in the SOX group for male patients ([HR] = 0.395; 95% [CI], 0.153–1.019; p = 0.045), age >60 (HR = 0.219; 95% [CI], 0.064–0.753; p = 0.016), tumors in the gastric antrum (HR = 0.273; 95% [CI], 0.076–0.981; p = 0.047), and moderately differentiated tumors (HR = 0.338; 95% [CI], 0.110–1.041; p = 0.041). There were no significant differences observed in terms of adverse events and recurrence patterns between the two groups. Conclusion: Adjuvant SOX was non‐inferior to CAPOX treatments for patients with GC who underwent curative laparoscopic D2 gastrectomy. For male patients, aged >60 years, tumors in the gastric antrum, and moderately differentiated tumors, adjuvant SOX may achieve an improvement compared with CAPOX.

The aim of this qualitative systematic review is to analyze the barriers and facilitators to the uptake of antihypertensive medication in hypertensive patients. The databases of PubMed, Embase, Web of Science, CINAHL, Cochrane Library, MEDLINE, China National Knowledge Infrastructure, Wanfang, VIP, and Chinese Biomedical were searched from inception to June 2023. The studies were screened, extracted, and assessed independently by two researchers. Previously, the researchers used the Joanna Briggs Institute Critical Appraisal Checklist for Qualitative Research to assess the quality of the included studies. A total of 27 studies were considered, resulting in two combined findings: a good level of knowledge, belief, and behavior and adequate social support were facilitators of medication adherence in hypertensive patients. In contrast, lack of medication literacy, difficulty adapting to roles, reduced sense of benefit from treatment, limited access to healthcare resources, and unintentional nonadherence were barriers. Medication adherence in hypertensive patients remains a challenge to be addressed. Future research should explore how complex interventions using a combination of evidence-based strategies and targeting multiple adherence behaviors (eg, long-term adherence to medication) are effective in improving medication adherence.

Abstract Background Metastatic castration‐resistant prostate cancer (mCRPC) remains fatal and incurable, despite a variety of treatments that can delay disease progression and prolong life. Immune checkpoint therapy is a promising treatment. However, emerging evidence suggests that exosomal programmed necrosis ligand 1 (PD‐L1) directly binds to PD‐1 on the surface of T cells in the drain lineage lymph nodes or neutralizes administered PD‐L1 antibodies, resulting in poor response to anti‐PD‐L1 therapy in mCRPC. Materials and Methods Western blotting and immunofluorescence were performed to compare PD‐L1 levels in exosomes derived from different prostate cancer cells. PC3 cells were subcutaneously injected into nude mice, and then ELISA assay was used to detect human specific PD‐L1 in exosomes purified from mouse serum. The function of CD8+ T cells was detected by T cell mediated tumor cell killing assay and FACS analysis. A subcutaneous xenograft model was established using mouse prostate cancer cell RM1, exosomes with or without PD‐L1 were injected every 3 days, and then tumor size and weight were analyzed to evaluate the effect of exosomal PD‐L1. Results Herein, we found that exosomal‐PD‐L1 was taken up by tumor cells expressing low levels of PD‐L1, thereby protecting them from T‐cell killing. Higher levels of PD‐L1 were detected in exosomes derived from the highly malignant prostate cancer PC3 and DU145 cell lines. Moreover, exosomal PD‐L1 was taken up by the PD‐L1‐low‐expressing LNCaP cell line and inhibited the killing function of CD8‐T cells on tumor cells. The growth rate of RM1‐derived subcutaneous tumors was decreased after knockdown of PD‐L1 in tumor cells, whereas the growth rate recovered following exosomal PD‐L1 tail vein injection. Furthermore, in the serum of mice with PCa subcutaneous tumors, PD‐L1 was mainly present on exosomes. Conclusion In summary, tumor cells share PD‐L1 synergistically against T cells through exosomes. Inhibition of exosome secretion or prevention of PD‐L1 sorting into exosomes may improve the therapeutic response of prostate tumors to anti‐PD‐L1 therapy.

Abstract Background Human papillomavirus (HPV) has been proposed as a potential pathogenetic organism involved in prostate cancer (PCa), but the association between HPV infection and relevant genomic changes in PCa is poorly understood. Methods To evaluate the relationship between HPV genotypes and genomic alterations in PCa, HPV capture sequencing of DNA isolated from 59 Han Chinese PCa patients was performed using an Illumina HiSeq2500. Additionally, whole-exome sequencing of DNA from these 59 PCa tissue samples and matched normal tissues was carried out using the BGI DNBSEQ platform. HPV infection status and genotyping were determined, and the genetic disparities between HPV-positive and HPV-negative PCa were evaluated. Results The presence of the high-risk HPV genome was identified in 16.9% of our cohort, and HPV16 was the most frequent genotype detected. The overall mutational burden in HPV-positive and HPV-negative PCa was similar, with an average of 2.68/Mb versus 2.58/Mb, respectively, in the targeted whole-exome region. HPV-negative tumors showed a mutational spectrum concordant with published PCa analyses with enrichment for mutations in SPOP, FOXA1, and MED12. HPV-positive tumors showed more mutations in KMT2C, KMT2D and ERCC2. Copy number alterations per sample were comparable between the two groups. However, the significantly amplified or deleted regions of the two groups only partially overlapped. We identified amplifications in oncogenes, including FCGR2B and CCND1, and deletions of tumor suppressors, such as CCNC and RB1, only in HPV-negative tumors. HPV-positive tumors showed unique deletions of tumor suppressors such as NTRK1 and JAK1. Conclusions The genomic mutational landscape of PCa differs based on HPV infection status. This work adds evidence for the direct involvement of HPV in PCa etiology. Different genomic features render HPV-positive PCa a unique subpopulation that might benefit from virus-targeted therapy.

Background The prevalence of synthetic drug abuse is high. In China, synthetic drugs have become the most commonly abused drugs characterized by strong addiction and great difficulty in quitting. The addicts are easily prone to serious psychological dependence and other psychological problems, which leading to relapse after withdrawal treatment. Therefore, exploring the influencing factors of mental health status in individuals addicted to new synthetic drugs has clinical and social significance for the prevention and management of synthetic drug addicts. Objective To explore the associated factors of mental health status and their intercorrelations in individuals addicted to new synthetic drugs. Methods One hundred and ninety-six people getting addicted to new synthetic drugs with inpatient withdrawal treatment were selected from Ankang Hospital of Tianjin Municipal Public Security Bureau from January 2018 to April 2019. Sociodemographic data and drug abuse-related clinical data were collected. The Symptom Checklist-90 (SCL-90) , Eysenck Personality Questionaire-Revised, Short Scale For Chinese (EPQ-RSC) , and Simplified Coping Style Questionnaire (SCSQ) were used to investigate the mental health. Spearman rank correlation analysis was used to analyze the inercorrelations of the influencing factors of mental health. SPSS 22.0 software was used for statistical analysis, and AMOS 22.0 was used to build a model for path analysis of data. Results The average total score of SCL-90 rated by the participants was (206.62±26.66) , which was higher than that rated by Chinese norm (P

Objective To provide references for clinical prediction of blood preparation and blood consumption, as well as the influencing factors of mass-transfusion by analyzing the perioperative blood transfusion in patients underwent heart transplantation. Methods The blood transfusions of 44 patients with heart transplantation completed in the Department of Cardiac Surgery of our hospital from March 2014 to January 2022 were retrospectively collected. Patient information included age, gender, preoperative diagnosis, relevant medical history, history of cardiac surgery, and history of antithrombotic medication. The risk factors of perioperative red blood cell transfusion in patients with heart transplantation were analyzed by univariate analysis method and multivariate logistic regression method. Results All 44(100%) heart transplant patients received blood components: the average transfusion units of red blood cells was 3.75(0, 7.5) U (72.73%), plasma 1 140 (597.5, 1782.5) mL (97.73%), cryoprecipitate 10(9.5±10) U(88.64%), platelets 1(1, 1.25) therapeutic amount (86.36%). The rate of massive transfusion of red blood cells was 45.45% (20/44). The univariate analysis found that there were significant differences in preoperative use of antithrombotic drugs, blood loss, and cardiopulmonary bypass time between the red blood cell transfusion group≤4 U (n=24) and the red blood cell transfusion group >4 U (n=20) (P

Abstract Background The gonadotropin-releasing hormone (GnRH) stimulation test is time-consuming, invasive, and costly. However, it is the diagnostic gold standard for central precocious puberty (CPP), which in girls is defined as the onset of secondary sexual characteristics before the age of 8 years accompanied by breast buds, accelerated growth, and advanced bone age. This meta-analysis was performed to compare the diagnostic value of urinary gonadotropins and the GnRH stimulation test for CPP. Methods We searched six databases for relevant literature. In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we estimated the sensitivity, specificity, area under the summary receiver operating characteristic curve (AUC), and publication bias. Results Six eligible trials fulfilled the inclusion criteria. In the meta-analysis of urinary luteinizing hormone (ULH), after excluding the data of one study, we obtained an AUC of 0.90 (sensitivity = 0.81, specificity = 0.85). The meta-analysis of the ULH to urinary follicle-stimulating hormone (UFSH) ratio revealed an AUC of 0.8116 (sensitivity = 0.79, specificity = 0.84). Conclusion Both the ULH level and ULH:UFSH ratio are effective and available approaches for CPP diagnosis. Trial Registration INPLASY 2021120076 .

Abstract Blockade of the binding between neonatal Fc receptor and IgG‐Fc reduces circulating IgG, and thus emerges as a potential therapy for IgG‐mediated autoimmune conditions. This was a double blind, randomized, single ascending dose study to evaluate the safety, pharmacokinetics, and pharmacodynamics of HBM9161 (a fully humanized Fc receptor monoclonal antibody) in healthy Chinese volunteers. Subjects were randomized to receive a single s.c. dose of HBM9161 or placebo in a 3:1 ratio in 3 dosing cohorts (340 mg, 510 mg, or 680 mg, respectively), and then followed up for 85 days. Study end points included incidence of adverse event (AE), serum drug concentration, IgG and its subclasses, and anti‐drug antibodies (ADAs). Twenty‐four subjects were randomized. Dose‐dependent reduction of total IgG occurred rapidly from baseline to reach nadir at day 11, then recovered steadily from day 11 to day 85. The mean maximum percentage reductions from baseline total IgG were 21.0 ± 9.3%, 39.8 ± 5.13%, and 41.2 ± 10.4% for subjects receiving HBM9161 340 mg, 510 mg, and 680 mg, respectively. The exposure of HBM9161 (areas under the curve [AUCs] and peak plasma concentration [Cmax]) increased in a more than dose‐proportional manner at the dose examined. All reported AEs were mild in severity. The most reported AEs in the HBM9161 groups were influenza‐like illness and rash. Two subjects developed ADA during the study period. A single s.c. dose of HBM9161 results in sustained and dose‐dependent IgG reduction, and was well‐tolerated at a dose up to 680 mg in Chinese subjects. The data warrant further investigation of its effects in IgG‐mediated autoimmune disorders.

Macrolide antibiotics are important drugs to combat infections. The pharmacokinetics (PK) of these drugs are essential for the determination of their optimal dose regimens, which affect antimicrobial pharmacodynamics and treatment success. For most drugs, the measurement of their concentrations in plasma/serum is the surrogate for drug concentrations in target tissues for therapy. However, for macrolides, simple reliance on total or free drug concentrations in serum/plasma might be misleading. The macrolide antibiotic concentrations of serum/plasma, interstitial fluid (ISF), and target tissue itself usually yield very different PK results. In fact, the PK of a macrolide antibiotic based on serum/plasma concentrations alone is not an ideal predictor for the in vivo efficacy against respiratory pathogens. Instead, the PK based on drug concentrations at the site of infection or ISF provide much more clinically relevant information than serum/plasma concentrations. This review aims to summarize and compare/discuss the use of drug concentrations of serum/plasma, airway ISF, and tissues for computing the PK of macrolides. A better understanding of the PK of macrolide antibiotics based on airway ISF concentrations will help optimize the antibacterial dose regimen as well as minimizing toxicity and the emergence of drug resistance in clinical practice.

Rapid epicentral distance estimation is of great significance for earthquake early warning (EEW). To rapidly and reliably predict epicentral distance, we developed machine learning models with multiple feature inputs for epicentral distance estimation using a single station and explored the feasibility of three machine learning methods, namely, Random Forest, eXtreme Gradient Boosting, and Support Vector Machine, for epicentral distance estimation. We used strong-motion data recorded by the Japanese Kyoshin network within a range of 1° (~112 km) from the epicenter to train machine learning models. We used 30 features extracted from the P-wave signal as inputs to the machine learning models and the epicentral distance as the prediction target of the models. For the same test data set, within 0.1-5 s after the P-wave arrival, the epicentral distance estimation results of these three machine learning models were similar. Furthermore, these three machine learning methods can obtain smaller mean absolute errors and root mean square errors, as well as larger coefficients of determination (R²), for epicentral distance estimation than traditional EEW epicentral distance estimation methods, indicating that these three machine learning models can effectively improve the accuracy of epicentral distance estimation to a certain extent. In addition, we analyzed the importance of different features as inputs to machine learning models using SHapley additive exPlanations. We found that using the top 15 important features as inputs, these three machine learning models can also achieve good results for epicentral distance estimation. Based on our results, we inferred that the machine learning models for estimating epicentral distance proposed in this study are meaningful in EEW. [ABSTRACT FROM AUTHOR]

Based on the precipitation data from the meteorological and hydrological stations and the Quantitative Precipitation Estimation (QPE) from radars over Jiangxi between May and June in 2019, we have made a fusion test of hourly precipitation from the meteorological and hydrological stations and by radars with 1 km×1 km resolution by using the space-time multiscale analysis system (STMAS), and made an analysis and assessment of fusion test results. The results show that the precipitation detected by meteorological stations, hydrological stations and radars has a similar spatial distribution. It is found that the severe precipitation zones and the patterns of precipitation distribution are very consistent. Comparing with the precipitation observed, the different fusion test results have a consistent variation tendency, but all are the underestimating to a certain extent. Those fused precipitation from the hydrological stations have a significant improvement in underestimation. The independent verification results indicate that the test results fused precipitation from hydrological stations have an obvious improvement in the accuracy of different level of precipitation, whose correlation coefficient increases by 9.2%, and root mean square error and mean absolute error decreases by 14.3% and 12.1%, respectively. After further fusing precipitation from hydrological stations, precipitation fusion results of different height areas are significantly improved, especially in the areas of elevation greater than 800 m whose correlation coefficient increases by 8.8% and root mean square error decreases by 14.1%.

Objective: We aimed to characterize the epidemiological and clinical characteristics of sporadic Creutzfeldt–Jakob disease (sCJD) in eastern China in this retrospective study.Methods: This study enrolled 67 patients with sCJD hospitalized in a grade-A tertiary hospital in eastern China from January 2010 to January 2020. Demographic data, clinical symptoms, brain magnetic resonance imaging (MRI), electroencephalogram (EEG), cerebrospinal fluid (CSF) 14-3-3 protein test, polymerase chain reaction (PCR), and DNA sequence determination of genes were collected and analyzed.Results: There were 62 patients with probable sCJD and 5 patients with possible sCJD. Male (28 cases) to female (39 cases) ratio was 1:1.39. Mean age at disease onset was 64.42 ± 9.00 years (range: 29–88 years), and mean survival time was 9.39 ± 12.58 months (range: 1–60 months for patients who received the follow-ups). The most common onset symptoms were dementia (49.25%), movement disorder (44.78%), and visual disturbance (22.39%), while the most frequent clinical manifestations were language disorders (74.63%), ataxia (70.15%), and myoclonus (70.15%). The positive rates of brain MRI abnormalities, 14-3-3 protein in CSF, and periodic sharp wave complexes (PSWCs) on EEG were 84.90, 68.00, and 46.03%, respectively. The 14-3-3 protein positive (p = 0.033) and PSWCs on EEG (p = 0.020) acted as the favorable and unfavorable factor for over 1 year of survival time, respectively.Conclusions: There were some differences in epidemiological and clinical characteristics among patients in China and those of other countries. The prognosis and its influencing factors were relatively unexplored in China. The mean survival time of Chinese patients was longer than that of Caucasian patients but shorter than that of Japanese patients. The 14-3-3 protein in CSF and PSWCs on EEG were both closely related to the survival time. It is necessary to promote autopsy or biopsy to better understand sCJD in China.

Recently, exosomes have been emerged as promising drug delivery carriers, while certain tissues are intrinsically resistant to exosomes. Therapeutically improving the drug delivery efficiency in these tissues/organs would certainly broaden the potential application of exosomes in future. Ultrasound-targeted microbubble destruction (UTMD) is a promising technique for non-invasive, targeted drug delivery. In this study, we explore the possibility that UTMD assists exosome delivery in these intrinsically resistant tissues. Mice were subjected to tail vein injection of DiR-labeled exosomes together with/without UTMD of SonoVueTM, followed by in vivo and ex vivo tracking of the exosomes. As expected, heart, adipose tissue, and skeletal muscle were found reluctant to exosomes from different origins. Targeted destruction of the ultrasound microbubbles (SonoVueTM) in the heart and adipose tissue region significantly increased the exosome infiltration and endocytosis there, as revealed by fluorescence imaging and confocal laser scanning microscope (CLSM). UTMD treatment 1 h prior to exosome injection failed to facilitate the exosome endocytosis in the targeted region, indicating that the transient promoting effects of UTMD. Moreover, increases of UTMD (numerous pulses) did not linearly enhance the exosome delivery. Together, our study here has established a novel strategy for targeted delivery of exosomes in the reluctant tissues, by combining the advantages of ultrasound microbubbles and exosomes in drug delivery.

Background: Veterinary management of mitral valve regurgitation due to mxyomatous valve disease in dogs is limited to medical treatments, which only postpones the onset of congestive heart failure or alleviates clinical symptoms. Most surgical procedures to manage this condition in humans require cardiopulmonary bypass and have a high risk of complications.Animals: Eight dogs with naturally occurring mitral valve regurgitation.Methods: Prospective observational study. All dogs were treated with a novel edge-to-edge transcatheter device named ValveClamp. The total surgical procedural time and total catheterization time were recorded. Echocardiographic variables measured pre- and post-procedure were compared using Wilcoxin-signed rank test with a P < 0.05 considered significant. Data were expressed as median and interquartile range and absolute numbers and percentages.Results: The procedural success rate was 100% and all the dogs survived without complications. The median (interquartile range) total surgical procedural time was 86.5 (76–96.2) minutes and catheterization time was 23.5 (22–33.8) minutes. Echocardiography revealed a significant reduction in mitral regurgitation severity in all dogs following the procedure based on both a reduced mitral regurgitant maximum jet area (P = 0.012) and a reduced mitral regurgitant maximum jet area to left atrial area (P = 0.018).Conclusion: The ValveClamp device is effective at reducing the severity of mitral regurgitation in dogs with naturally occurring myxomatous valve disease.

Therapeutically intervening the function of RNA in vivo remains a big challenge. We here developed an exosome-based strategy to deliver engineered RNA-binding protein for the purpose of recruiting specific RNA to the lysosomes for degradation. As a proof-of-principle study, RNA-binding protein HuR was fused to the C-terminus of Lamp2b, a membrane protein localized in both exosome and lysosome. The fusion protein was able to be incorporated into the exosomes. Moreover, exosomes engineered with Lamp2b-HuR successfully decreased the abundance of RNA targets possibly via lysosome-mediated degradation, especially when the exosomes were acidified. The system was specifically effective in macrophages, which are lysosome enriched and resistant to routine transfection mediated RNAi strategy. In the CCl4-induced liver injury mouse model, we found that delivery of acidified exosomes engineered with Lamp2b-HuR significantly reduced liver fibrosis, together with decreased miR-155 and other inflammatory genes. In summary, the established exosome-based RNA-binding protein delivery strategy, namely “exosome-mediated lysosomal clearance”, takes the advantage of exosome in targeted delivery and holds great promise in regulating a set of genes in vivo.

Abstract Demand response has the potential to bring significant benefits to the optimal sizing of distributed generation (DG) resources for microgrids planning. This paper presents an integrated resources planning model considering the impact of interruptible loads (IL) and shiftable loads (SL) in microgrids, which simultaneously deals with supply side and demand side resources and minimizes the overall planning cost of the microgrid. The proposed model can be applied to offer a quantitative assessment how IL and SL can contribute to microgrid planning. The pure peak clipping model with IL and SL is also provided for comparisons. Moreover, sensitivity analysis of parameters in the model is performed. Numerical results confirm that the proposed model is an effective method for reducing the planning cost of microgrids. It was also found that the major contributing factors of IL and SL have great impact on the economic benefits of the proposed model in low-carbon economy environments.

Astrogliosis has long been recognized in Parkinson's disease (PD), the most common neurodegenerative movement disorder. However, the mechanisms of how astroglia become activated remain unclear. Reciprocal interactions between microglia and astroglia play a pivotal role in regulating the activities of astroglia. The purpose of this study is to investigate the mechanism by which microglia regulate astrogliosis by using lipopolysaccharide (LPS) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse PD models. We found that the activation of microglia preceded astroglia in the substantia nigra of mice treated with either LPS or MPTP. Furthermore, suppression of microglial activation by pharmacological inhibition or genetic deletion of NADPH oxidase (NOX2) in mice attenuated astrogliosis. The important role of NOX2 in microglial regulation of astrogliosis was further mirrored in a mixed-glia culture system. Mechanistically, H2O2, a product of microglial NOX2 activation, serves as a direct signal to regulate astrogliosis. Astrogliosis was induced by H2O2 through a process in which extracellularly generated H2O2 diffused into the cytoplasm and subsequently stimulated activation of transcription factors, STAT1 and STAT3. STAT1/3 activation regulated the immunological functions of H2O2-induced astrogliosis since AG490, an inhibitor of STAT1/3, attenuated the gene expressions of both proinflammatory and neurotrophic factors in H2O2-treated astrocyte. Our findings indicate that microglial NOX2-generated H2O2 is able to regulate the immunological functions of astroglia via a STAT1/3-dependent manner, providing additional evidence for the immune pathogenesis and therapeutic studies of PD. Keywords: Parkinson's disease, NADPH oxidase, Microglia, Astrocyte, STATs, H2O2

The effective treatment of patients suffering from neuropathic pain remains challenging. Dexmedetomidine (DEX) possesses anti-inflammatory activity. However, the role of DEX in neuropathic pain is still unclear. The aim of the present study was to examine DEX an α2-adrenoceptor agonist could improve pain hypersensitivity and reduce inflammatory in a chronic constriction injury (CCI) model of the sciatic nerve in Sprague-Dawley rats. Dex was intrathecally administrated 1-h after operation. The paw mechanical withdrawal threshold (MWT) and paw withdrawal thermal latency (PWTL) were measured on day 1 before operation and on days 1, 7, 14 and 21 after operation, respectively. On day 21, all the rats were decapitated to collect the L4-6 segments of the spinal cord to examine IL-1, TNF-α, IL-6, NR2B, NF-κB, and iNOS mRNA levels using RT-PCR. The postoperative MWT and PWTL were significantly decreased in CCI, and DEX groups as compared to those before surgery and Sham group (P

A two and a half-year old Simmental bull was presented to Iowa State University’s Food Animal and Camelid Hospital for anorexia and lethargy of several days. Clostridium perfringens type A was identified via fecal culture and toxin genotyping. Hemorrhagic bowel syndrome (HBS) was diagnosed based on microbiological results along with abdominal ultrasonography, complete blood count, and serum biochemistry. Aggressive multi-modal therapy was employed including intravenously administered fluid therapy, potassium penicillin, lidocaine, flunixin, and pantoprazole among other supportive care. The bull was discharged after 15 days of hospitalization and recovered uneventfully to full function by the next breeding season. Currently all case reports with regard to HBS in beef cattle describe mortality. While the dairy cattle literature demonstrates that HBS has a high mortality rate, and suggests that surgical intervention has a higher prognosis when compared to medical therapy in dairy cattle. Our case would provide support to aggressive medical treatment for HBS in beef cattle.