In situ reprogramming of cardiac fibroblasts into cardiomyocytes in mouse heart with chemicals.

Cardiomyocytes are terminal differentiated cells and have limited ability to proliferate or regenerate. Condition like myocardial infarction causes massive death of cardiomyocytes and is the leading cause of death. Previous studies have demonstrated that cardiac fibroblasts can be induced to transdifferentiate into cardiomyocytes in vitro and in vivo by forced expression of cardiac transcription factors and microRNAs. Our previous study have demonstrated that full chemical cocktails could also induce fibroblast to cardiomyocyte transdifferentiation both in vitro and in vivo. With the development of tissue clearing techniques, it is possible to visualize the reprogramming at the whole-organ level. In this study, we investigated the effect of the chemical cocktail CRFVPTM in inducing in situ fibroblast to cardiomyocyte transdifferentiation with two strains of genetic tracing mice, and the reprogramming was observed at whole-heart level with CUBIC tissue clearing technique and 3D imaging. In addition, single-cell RNA sequencing (scRNA-seq) confirmed the generation of cardiomyocytes from cardiac fibroblasts which carries the tracing marker. Our study confirms the use of small molecule cocktails in inducing in situ fibroblast to cardiomyocyte reprogramming at the whole-heart level and proof-of-conceptly providing a new source of naturally incorporated cardiomyocytes to help heart regeneration.

Comprehensive assessment of osteoporosis in lumbar spine using compositional MR imaging of trabecular bone.

OBJECTIVES: To comprehensively assess osteoporosis in the lumbar spine, a compositional MR imaging technique is proposed to quantify proton fractions for all the water components as well as fat in lumbar vertebrae measured by a combination of a 3D short repetition time adiabatic inversion recovery prepared ultrashort echo time (STAIR-UTE) MRI and IDEAL-IQ. METHODS: A total of 182 participants underwent MRI, quantitative CT, and DXA. Lumbar collagen-bound water proton fraction (CBWPF), free water proton fraction (FWPF), total water proton fraction (TWPF), bone mineral density (BMD), and T-score were calculated in three vertebrae (L2-L4) for each subject. The correlations of the CBWPF, FWPF, and TWPF with BMD and T-score were investigated respectively. A comprehensive diagnostic model combining all the water components and clinical characteristics was established. The performances of all the water components and the comprehensive diagnostic model to discriminate between normal, osteopenia, and osteoporosis cohorts were also evaluated using receiver operator characteristic (ROC). RESULTS: The CBWPF showed strong correlations with BMD (r = 0.85, p < 0.001) and T-score (r = 0.72, p < 0.001), while the FWPF and TWPF showed moderate correlations with BMD (r = 0.65 and 0.68, p < 0.001) and T-score (r = 0.47 and 0.49, p < 0.001). The high area under the curve values obtained from ROC analysis demonstrated that CBWPF, FWPF, and TWPF have the potential to differentiate the normal, osteopenia, and osteoporosis cohorts. At the same time, the comprehensive diagnostic model shows the best performance. CONCLUSIONS: The compositional MRI technique, which quantifies CBWPF, FWPF, and TWPF in trabecular bone, is promising in the assessment of bone quality. KEY POINTS: • Compositional MR imaging technique is able to quantify proton fractions for all the water components (i.e., collagen-bound water proton fraction (CBWPF), free water proton fraction (FWPF), and total water proton fraction (TWPF)) in the human lumbar spine. • The biomarkers derived from the compositional MR imaging technique showed moderate to high correlations with bone mineral density (BMD) and T-score and showed good performance in distinguishing people with different bone mass. • The comprehensive diagnostic model incorporating CBWPF, FWPF, TWPF, and clinical characteristics showed the highest clinical diagnostic capability for the assessment of osteoporosis.

Genomic prediction of pig growth traits based on machine learning.

This study aimed to assess and compare the performance of different machine learning models in predicting selected pig growth traits and genomic estimated breeding values (GEBV) using automated machine learning, with the goal of optimizing whole-genome evaluation methods in pig breeding. The research employed genomic information, pedigree matrices, fixed effects, and phenotype data from 9968 pigs across multiple companies to derive four optimal machine learning models: deep learning (DL), random forest (RF), gradient boosting machine (GBM), and extreme gradient boosting (XGB). Through 10-fold cross-validation, predictions were made for GEBV and phenotypes of pigs reaching weight milestones (100 kg and 115 kg) with adjustments for backfat and days to weight. The findings indicated that machine learning models exhibited higher accuracy in predicting GEBV compared to phenotypic traits. Notably, GBM demonstrated superior GEBV prediction accuracy, with values of 0.683, 0.710, 0.866, and 0.871 for B100, B115, D100, and D115, respectively, slightly outperforming other methods. In phenotype prediction, GBM emerged as the best-performing model for pigs with B100, B115, D100, and D115 traits, achieving prediction accuracies of 0.547, followed by DL at 0.547, and then XGB with accuracies of 0.672 and 0.670. In terms of model training time, RF required the most time, while GBM and DL fell in between, and XGB demonstrated the shortest training time. In summary, machine learning models obtained through automated techniques exhibited higher GEBV prediction accuracy compared to phenotypic traits. GBM emerged as the overall top performer in terms of prediction accuracy and training time efficiency, while XGB demonstrated the ability to train accurate prediction models within a short timeframe. RF, on the other hand, had longer training times and insufficient accuracy, rendering it unsuitable for predicting pig growth traits and GEBV.

Enantioselective Nickel-Catalyzed Hydrosilylation of 1,1-Disubstituted Allenes.

Here, we report the first example of Ni-catalyzed asymmetric hydrosilylation of 1,1-disubstituted allenes with high level of regioselectivities and enantioselectivities. The key to achieve this stereoselective hydrosilylation reaction was the development of the SPSiOL-derived bisphosphite ligands (SPSiPO). This protocol features broad substrate scope, excellent functional group, and heterocycle tolerance, thus provides a versatile method for the construction of enantioenriched tertiary allylsilanes in a straightforward and atom-economic manner. DFT calculations were performed to reveal the reaction mechanism and the origins of the enantioselectivity.

Prevalence and risk factors of bluetongue virus infection in sheep and goats in China: A systematic review and meta-analysis.

Bluetongue is a viral disease transmitted by the bite of bloodsucking insects, which mainly occurs in sheep, goats, and cattle. Bluetongue is characterized by fever, leukopenia, and severe catarrhal inflammation of the oral and gastrointestinal mucosa. The present study aimed to evaluate and analyze the prevalence of bluetongue and its associated risk factors in sheep and goats in China. We collected 59 publications from 1988 to 2019 through searches at ScienceDirect, PubMed, the Chongqing VIP Chinese journal database, Wanfang database, and Chinese Web of knowledge. In these studies, a total of 123,982 sheep and goats across 7 regions of China were investigated, and the pooled prevalence of bluetongue in sheep and goats was 18.6%, as assessed using serological methods. The prevalence of bluetongue in Southern China was 30.3%, which was significantly higher than that in Northeastern China (4.7%). The prevalence of bluetongue between sheep (12.9%) and goats (28.1%) was significantly different (P < 0.05). Detection methods subgroup analysis showed that the prevalence of bluetongue was significantly higher (P < 0.05) in the others group (43.8%) than in the agar immunodiffusion (15.9%) and enzyme-linked immunosorbent assay groups (20.5%). In addition, different geographical factors (latitude range, longitude range, altitude range, average precipitation, and average temperature) could affect the prevalence. Our results suggested that bluetongue is widespread in sheep and goats, and sheep and goats in contact with insect media, such as Culicoides, or in a warm and humid environment, could have an increased prevalence of bluetongue disease. Animal disease prevention and control departments should focus on continuous monitoring of the bluetongue epidemic in sheep and goats to prevent and control outbreaks.

Safety application of muscle relaxants and the traditional low-frequency ventilation during the flexible or rigid bronchoscopy in patients with central airway obstruction: a retrospective observational study.

BACKGROUND: Bronchoscopy treatments of central airway obstruction (CAO) under general anesthesia are high-risky procedures, and posing a giant challenge to the anesthesiologists. We summarized and analyzed our clinical experience in patients with CAO undergoing flexible or rigid bronchoscopy, to estimate the safety of skeletal muscle relaxants application and the traditional Low-frequency ventilation. METHODS: Clinical data of 375 patients with CAO who underwent urgent endoscopic treatments in general anesthesia from January 2016 to October 2019 were retrospectively reviewed. The use ratio of skeletal muscle relaxants, dose of skeletal muscle relaxants used, the incidence of perioperative adverse events, adequacy of ventilation and gas exchange, post-operative recovery between rigid bronchoscopy and flexible bronchoscopy therapy, and risk factors for postoperative ICU admission were evaluated. RESULTS: Of the 375 patients with CAO, 204 patients were treated with flexible bronchoscopy and 171 patients were treated with rigid bronchoscopy. Muscle relaxants were used in 362 of 375 patients (including 313 cisatracurium, 45 rocuronium, 4 atracurium, and 13 unrecorded). The usage rate of muscle relaxants (96.5% in total) was very high in patients with CAO who underwent either flexible bronchoscopy (96.6%) or rigid bronchoscopy (96.5%) therapy. The dosage of skeletal muscle relaxants (Cisatracium) used was higher in rigid bronchoscopy compared with flexible bronchoscopy therapy (10.8 ± 3.8 VS 11.6 ± 3.6 mg, respectively, p < 0.05). No patient suffered the failure of ventilation, bronchospasm and intraoperative cough either in flexible or rigid bronchoscopy therapy. Hypoxemia was occurred in 13 patients (8 in flexible, 5 in rigid bronchoscopy) during the procedure, and reintubation after extubation happened in 2 patients with flexible bronchoscopy. Sufficient ventilation was successfully established using the traditional Low-frequency ventilation with no significant carbon dioxide accumulation and hypoxemia occurred both in flexible and rigid bronchoscopy group (p > 0.05). Three patients (1 in flexible and 2 in rigid) died, during the post-operative recovery, and the higher grade of American Society of Anesthesiologists (ASA) and obvious dyspnea or orthopnea were the independent risk factors for postoperative ICU admission. CONCLUSION: The muscle relaxants and low-frequency traditional ventilation can be safely used both in flexible and rigid bronchoscopy treatments in patients with CAO. These results may provide strong clinical evidence for optimizing the anesthesia management of bronchoscopy for these patients.

Discovery of diverse diterpenoid scaffolds from Euphorbia antiquorum and their activity against RANKL-induced osteoclastogenesis.

Seven new diterpenoids, euphorantones A-D (1, 3, 6, and 10), 8,12,13-epi-3,7,12-O-triacetyl-8-O-(2-methylbutanoyl)-ingol (9), 8,12,13-epi-3,12-O-diacetyl-7-O-benzoyl-8-methoxyingol (11), 2,3-epi-7,12-diacetate-8-benzoate-ingol (12), together with eighteen known compounds (2, 4-5, 7-8, and 13-25), were isolated from the aerial parts of Euphorbia antiquorum L.. The structures of new compounds 1, 3, 6, and 9-12 were elucidated by extensive spectroscopic analyses. The absolute configurations of new compounds were assigned using X-ray diffraction, Rh2(OCOCF3)4-induced CD spectrum, and confirmed through comparison of the calculated and experimental 13C NMR and electronic circular dichroism (ECD) data. Compounds 1-25 were evaluated for their inhibition of RANKL-induced osteoclastogenesis. Compound 1 showed the most potent inhibition of RANKL-induced osteoclastogenesis with IC50 value of 0.3 µM. It inhibited NFAT transcript activity and osteoclast related genes TRAcP, CTSK, and NFATc1 expression.

A nanocomposite consisting of ZnO decorated graphene oxide nanoribbons for resistive sensing of NO2 gas at room temperature.

A composite prepared from zinc oxide and graphene oxide nanoribbons (ZnO/GONR) is demonstrated to enable improved room temperature (RT) detection of nitrogen dioxide (NO2). Low-cost hydrothermal synthesis is used to construct the composite. The properties of the resistive sensor, including the sensitivity, response and recovery times, repeatability and selectivity, were investigated in the NO2 concentration range from 1 to 50 ppm at RT. The sensor, typically operated at a voltage of 5 V, exhibits a low detection limit of 1 ppm, a fast response-recovery time, and excellent repeatability which outperforms that of pure ZnO sensors. The sensing mechanism is explained in terms of a redox reaction between NO2 and oxygen anions on the surface of the ZnO/GONR composite. Graphical abstract Schematic representation of the NO2 sensing mechanisms on the surface of the ZnO/GONR composite and overall improved NO2 gas-sensing performance.

Activation of corticotropin-releasing factor neurons and microglia in paraventricular nucleus precipitates visceral hypersensitivity induced by colorectal distension in rats.

Visceral hypersensitivity is a major contributor to irritable bowel syndrome and other disorders with visceral pain. Substantial evidence has established that glial activation and neuro-glial interaction play a key role in the establishment and maintenance of visceral hypersensitivity. We recently demonstrated that activation of spinal microglial toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear factor κB (NF-κB) signaling facilitated the development of visceral hypersensitivity in a rat model developed by neonatal and adult colorectal distensions (CRDs). Hypothalamic paraventricular nucleus (PVN) plays a pivotal role in the pathogenesis of chronic pain. In this study, we examined the mechanism by which microglia and neurons in PVN establish and maintain visceral hypersensitivity and the involvement of TLR4 signaling. Visceral hypersensitivity was precipitated by adult colorectal distension (CRD) only in rats that experienced neonatal CRDs. Visceral hypersensitivity was associated with an increase in the expression of c-fos, corticotropin-releasing factor (CRF) protein and mRNA in PVN, which could be prevented by intra-PVN infusion of lidocaine or small interfering RNA targeting the CRF gene. These results suggest PVN CRF neurons modulate visceral hypersensitivity. Adult CRD induced an increase in the expression of Iba-1 (a microglial marker), TLR4 protein, and its downstream effectors MyD88, NF-κB, as well as proinflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) only in rats that experienced neonatal CRDs. Intra-PVN infusion of minocycline, a nonselective microglial inhibitor, attenuated the hyperactivity of TLR4 signaling cascade, microglial activation, and visceral hypersensitivity. Taken together, these data suggest that neonatal CRDs induce a glial activation in PVN. Adult CRD potentiates the glial and CRF neuronal activity, and precipitates visceral hypersensitivity and pain. TLR4 signaling and proinflammatory cytokines TNF-α and IL-1ß may participate in neuro-glial interaction during the pathogenesis of visceral hypersensitivity.

A Meta-Analysis of Bovine Chlamydia Prevalence in Cattle in China from 1989 to 2020.

Chlamydia bovis is a widespread infection disease caused by the mixed infection of Chlamydia psittaci, Chlamydia pecorum, Chlamydia abortus, and Chlamydia suis in cattle. Although many studies have investigated Chlamydia infection in cattle, there is no nationwide study on the prevalence of Chlamydia infection in cattle of China. We constructed the first meta-analysis to assess the infection rate and infection risk factors of Chlamydia in cattle in China, and we searched PubMed, ScienceDirect, Chinese Web of Knowledge, Wanfang, and VIP Chinese journal database for studies reporting Chlamydia infection in cattle from April 29, 2020. We collected a total of 563 publications from 1989 to 2019, and finally, 78 studies were eligible, which included 152,364 cattle from 27 provinces across the country. We estimated the pooled prevalence of Chlamydia in cattle was 14.2% (95% confidence interval [CI]: 12.2 to 16.4). The prevalence of bovine Chlamydia in China collected before 2000 (14.8%, 95% CI: 5.6 to 27.3) showed the highest prevalence rate. The highest prevalence was found in Central China (22.6%, 95% CI: 12.8 to 34.2). The prevalence of Chlamydia spp. between abortion cattle (39.1%, 95% CI: 24.6 to 54.6) and healthy cattle (8.3%, 95% CI: 3.1 to 15.2) showed significant variation (p < 0.05). In detection methods subgroup, enzyme-linked immunosorbent assay (30.5%, 95% CI: 21.5 to 40.3) showed the highest prevalence. In the age subgroup, the prevalence rate of age >1 year (16.6%, 95% CI: 12.6 to 20.9) was higher compared with age ≤1 year (9.8%, 95% CI: 6.7 to 13.3). Yaks (17.8%, 95% CI: 13.3 to 22.8) showed the highest Chlamydia prevalence among the varieties of bovine. We also estimated the potential risk factors such as feeding model, sample classification, sampling seasons, bovine gender, parity, and quality level of included studies. Our findings suggested that Chlamydia was prevalent in cattle in China. So we should pay attention to bovine Chlamydia and take necessary measures to prevent it.

Prevalence of Eimeria Spp. Among Goats in China: A Systematic Review and Meta-Analysis.

Eimeria spp. infection can cause weight loss in goats, and severe cases can lead to the death of lambs, resulting in economic losses to the goat industry. To explore the pooled prevalence of Eimeria spp. in goats in China, we obtained 70 related publications from five databases and conducted a meta-analysis. In China, the combined prevalence of Eimeria spp. in goats was 78.7% (95% confidence interval (CI): 68.15-87.67). Among them, the most serious infections occurred in Northeast China (88.0%, 95% CI: 83.54-91.86). The main Eimeria species were E. alijevi (43.7%, 95% CI: 29.53-58.45), E. arloingi (49.7%, 95% CI: 34.83-64.49), E. christenseni (41.2%, 95% CI: 27.07-56.16), and E. ninakohlyakimovae (35.9%, 95% CI: 21.02-52.31). In the sampling year subgroup, 2006 or later presented a lower prevalence (75.3%, 95%CI: 58.72-88.72). In terms of age, the point estimate for young goats (≤ 1 year) was higher (89.9%, 95% CI: 80.82-96.48). The Float (NaCl) method showed the lowest prevalence of Eimeria spp. in goats (75.9%, 95%CI: 62.00-87.46). In the season subgroup, the highest prevalence was in summer (81.5%, 95%CI: 49.62-99.18). Female goats presented a higher prevalence of Eimeria spp. infection than male goats (70.7%, 95%CI: 27.90-98.96). The prevalence was lower in the intensive feeding model (77.4%, 95%CI: 66.56-86.67) and higher in free feeding goats (79.4%, 95%CI: 66.46-89.92). In addition, we also analyzed the potential relationship between geographical factors and the prevalence of Eimeria spp. infection in goats in China. Our findings suggested that Eimeria spp. infection in goats is widespread in China. Despite the overall downward trend, this infection cannot be ignored. We recommend that breeders use anticoccidial drugs to prevent and treat this disease, while improving the feeding conditions and managemental practices to reduce the economic losses caused by Eimeria infection to the goat industry.

Automatic Grading of Disc Herniation, Central Canal Stenosis and Nerve Roots Compression in Lumbar Magnetic Resonance Image Diagnosis.

Aim: Accurate severity grading of lumbar spine disease by magnetic resonance images (MRIs) plays an important role in selecting appropriate treatment for the disease. However, interpreting these complex MRIs is a repetitive and time-consuming workload for clinicians, especially radiologists. Here, we aim to develop a multi-task classification model based on artificial intelligence for automated grading of lumbar disc herniation (LDH), lumbar central canal stenosis (LCCS) and lumbar nerve roots compression (LNRC) at lumbar axial MRIs. Methods: Total 15254 lumbar axial T2W MRIs as the internal dataset obtained from the Fifth Affiliated Hospital of Sun Yat-sen University from January 2015 to May 2019 and 1273 axial T2W MRIs as the external test dataset obtained from the Third Affiliated Hospital of Southern Medical University from June 2016 to December 2017 were analyzed in this retrospective study. Two clinicians annotated and graded all MRIs using the three international classification systems. In agreement, these results served as the reference standard; In disagreement, outcomes were adjudicated by an expert surgeon to establish the reference standard. The internal dataset was randomly split into an internal training set (70%), validation set (15%) and test set (15%). The multi-task classification model based on ResNet-50 consists of a backbone network for feature extraction and three fully-connected (FC) networks for classification and performs the classification tasks of LDH, LCCS, and LNRC at lumbar MRIs. Precision, accuracy, sensitivity, specificity, F1 scores, confusion matrices, receiver-operating characteristics and interrater agreement (Gwet k) were utilized to assess the model's performance on the internal test dataset and external test datasets. Results: A total of 1115 patients, including 1015 patients from the internal dataset and 100 patients from the external test dataset [mean age, 49 years ± 15 (standard deviation); 543 women], were evaluated in this study. The overall accuracies of grading for LDH, LCCS and LNRC were 84.17% (74.16%), 86.99% (79.65%) and 81.21% (74.16%) respectively on the internal (external) test dataset. Internal and external testing of three spinal diseases showed substantial to the almost perfect agreement (k, 0.67 - 0.85) for the multi-task classification model. Conclusion: The multi-task classification model has achieved promising performance in the automated grading of LDH, LCCS and LNRC at lumbar axial T2W MRIs.

Prevalence of Bovine Viral Diarrhea Virus in Ovine and Caprine Flocks: A Global Systematic Review and Meta-Analysis.

Background: Bovine viral diarrhea virus (BVDV) is the causative agent of bovine viral diarrhea. It can infect cattle, sheep, pigs, and other animals, causing diarrhea, miscarriage, and stillbirth, among other symptoms, and it can result in huge economic losses to animal husbandry. There are reports on BVDV infection rates in sheep and goat herds from all over the world and this meta-analysis aimed to evaluate the prevalence of and risk factors for BVDV in sheep and goats. Results: Using the data of 41,297 sheep and goats in 24 countries/regions to calculate a comprehensive prevalence rate for BVDV. The overall prevalence of BVDV infection in sheep and goats was estimated to be 8.6% (95% CI: 5.2-12.7) by immunological methods and 7.3% (95% CI: 2.7-13.7) by molecular methods. Analysis by national income level revealed that prevalence is higher in middle-income countries than in high-income countries (P < 0.05). The study also compared prevalence rates by species of BVDV, sampling year, and test species, but did not find significant differences. Conclusion: This systematic review and meta-analysis is the first to determine the global prevalence of BVDV in ovine and caprine flocks. The prevalence of BVDV in sheep and goat populations varies from region to region, and the situation is not optimistic in some countries.

Prevalence and infection risk factors of bovine Eimeria in China: a systematic review and meta-analysis.

Eimeria spp. cause the disease coccidiosis, which results in chronic wasting of livestock and can lead to the death of the animal. The disease, common worldwide, has caused huge economic losses to the cattle industry in particular. This is the first systematic review and meta-analysis of the prevalence of bovine Eimeria in China. Our search of five databases including PubMed, ScienceDirect, China National Knowledge Infrastructure (CNKI), Chongqing VIP, and Wan Fang for articles published up to February 29, 2020 on the prevalence of Eimeria in cattle in mainland China yielded 46 articles, in which the prevalence of cattle ranged from 4.6% to 87.5%. The rate of bovine Eimeria infection has been decreasing year by year, from 57.9% before 2000 to 25.0% after 2015, but it is still high. We also analyzed the region, sampling years, detection methods, feeding model, seasons, and species of bovine Eimeria. We recommend that prevention strategies should focus on strengthening detection of Eimeria in calves in the intensive farming model.

TITLE: Prévalence et facteurs de risque des infections des bovins par Eimeria en Chine : revue systématique et méta-analyse. ABSTRACT: Les espèces d'Eimeria provoquent la coccidiose, une maladie qui entraîne l'émaciation chronique du bétail et peut entraîner la mort de l'animal. La maladie, répandue dans le monde entier, a causé d'énormes pertes économiques à l'industrie bovine en particulier. Ceci est la première revue systématique et méta-analyse de la prévalence des Eimeria des bovins en Chine. Notre recherche dans cinq bases de données, dont PubMed, ScienceDirect, China National Knowledge Infrastructure (CNKI), Chongqing VIP et Wan Fang, pour des articles publiés jusqu'au 29 février 2020, sur la prévalence des Eimeria chez les bovins en Chine continentale, a donné 46 articles, dans lesquels la prévalence chez les bovins variait de 4,6 % à 87,5 %. Le taux d'infection des bovins par Eimeria a diminué d'année en année, passant de 57,9 % avant 2000 à 25,0 % après 2015, mais il est toujours élevé. Nous avons également analysé la région, les années d'échantillonnage, les méthodes de détection, le modèle d'alimentation, les saisons et les espèces d'Eimeria de bovins. Nous recommandons que les stratégies de prévention se concentrent sur le renforcement de la détection des Eimeria chez les veaux dans les élevages intensifs.

Seroprevalence of Brucellosis in Buffalo Worldwide and Associated Risk Factors: A Systematic Review and Meta-Analysis.

Background: Brucellosis is an important zoonotic disease caused by Brucella spp. Brucellosis is widely distributed in more than 160 or 170 countries around the world, where it poses a huge threat to animal husbandry and human health. About 150 million head of water buffalo, distributed across more than 40 countries worldwide, are kept for the purposes of service, milk, and meat. High incidence of Brucella spp. in buffalo has negatively affected dairy products and meat products. Results: We searched all research related to seroprevalence of brucellosis in water buffalo anywhere in the world in PubMed, Science Direct, SpringerLink, China National Knowledge Infrastructure, Wanfang Database, and VIP Chinese Journal Databases. A total of 26 articles published from 1985 to 2020 met the final selection criteria. The overall seroprevalence of buffalo brucellosis worldwide was 9.7%. The seroprevalence before 2010 (20.8%) (95% CI: 5.6-42.2) was much higher than the seroprevalence rate from 2010 to 2020 (4.2%) (95% CI: 1.8-7.5). Subgroup analysis by feeding mode found that the point estimate of seroprevalence in stock buffalo (11.5%) (95% CI: 3.6-23.0) was higher than that in captive buffalo (10.6%) (95% CI: 4.9-18.1). Subgroup analysis by farming mode found that the seroprevalence was higher in captive-bred buffalo (10.7%) (95% CI: 6.6-15.7) than in intensively farmed buffalo (8.5) (95% CI: 0.9-22.2). The seroprevalence in buffalo living in dry lands (6.4%) (95% CI: 2.0-12.9) is greater than that in buffalo living in wetlands (5.1%) (95% CI: 1.8-10.4) (P < 0.05). The seroprevalence in female buffalo (10.1%) (95% CI: 3.4-19.7) was higher than that in male buffalo (4.4%) (95% CI: 2.0-7.4). The seroprevalence in lactating buffalo was higher than that in buffalo of other ages (26.9%) (95% CI: 1.8-66.5). Subgroup analysis by detection method found that the seroprevalence detected by the complement fixation test (27.3%) (95% CI: 0.7-70.8) was much higher than that detected by other methods. Conclusion: The results of this meta-analysis showed that buffalo brucellosis infection is very common in buffalo herds around the world. Although the seroprevalence of brucellosis in buffalo and humans is relatively low, serious effects upon animal husbandry and public health make it necessary to take effective control and preventive measures to control the spread of this disease.

Global Comprehensive Literature Review and Meta-Analysis of Brucella spp. in Swine Based on Publications From 2000 to 2020.

Background: Brucellosis, a zoonotic disease, infects various hosts, including swine and humans. It has reemerged in recent years as a public health concern, and current studies on brucellosis infection in swine have been conducted worldwide. However, no meta-analyses of global brucellosis infection in swine have been published. The aim of this study was to provide an overview of Brucella species (spp.) in swine worldwide and the factors associated with its persistence. Results: We searched seven databases for published epidemiological studies on brucellosis in pigs, including the Chinese National Knowledge Infrastructure, Wanfang Data, SpringerLink, ScienceDirect, Web of Science, the VIP Chinese Journal Database and PubMed. We selected 119 articles published from January 1, 2000 to January 3, 2020 for inclusion in the meta-analysis and analyzed the data using a random-effects model. Funnel plots and Egger's test showed significant publication bias in the included studies. The results of the sensitivity analysis showed that our study was relatively stable and reliable. The prevalence of brucellosis in swine was 2.1% (95% CI: 1.6-2.6), of which the highest infection rate, which was found in Europe, was 17.4% (95% CI: 11.1-24.9). The prevalence in feral pigs (15.0%, 95% CI: 8.4-23.2) was higher than that in domestic pigs (1.1%, 95% CI 0.2-2.5). The prevalence in high-income countries (15.7%, 95% CI 8.0-25.3) was significantly higher than that in middle- (0.8%, 95% CI 0.5-1.1), and low-income countries (0.1%, 95% CI 0.0-0.2). The prevalence was highest in finishing pigs at 4.9% (95% CI 0.9-11.0), and lowest among suckling pigs at 0% (95% CI 0.0-0.5). Conclusion: The Brucella prevalence in pig herds currently is distributed widely throughout the world. In some countries, swine brucellosis may be a neglected zoonotic disease. We recommend long-term monitoring of the prevalence of brucellosis in domestic and wild pig herds. Attention should also be paid to animal welfare on intensive pig farms; controlling the breeding density may play an important role in reducing the spread of brucellosis among pigs.

Small-Conductance Ca2+-Activated K+ Channels 2 in the Hypothalamic Paraventricular Nucleus Precipitates Visceral Hypersensitivity Induced by Neonatal Colorectal Distension in Rats.

Visceral hypersensitivity is one of the pivotal pathophysiological features of visceral pain in irritable bowel syndrome (IBS). Small-conductance Ca2+-activated K+ channel (SK) is critical for a variety of functions in the central nervous system (CNS), nonetheless, whether it is involved in the pathogenesis of visceral hypersensitivity remain elusive. In this study, we examined mechanism of SK2 in hypothalamic paraventricular nucleus (PVN) in the pathogenesis of visceral hypersensitivity induced by neonatal colorectal distension (CRD). Rats undergoing neonatal CRD presented with visceral hypersensitivity as well as downregulated membrane SK2 channel and p-PKA. Intra-PVN administration of either the membrane protein transport inhibitor dynasore or the SK2 activator 1-EBIO upregulated the expression of membrane SK2 in PVN and mitigated visceral hypersensitivity. In addition, 1-EBIO administration reversed the increase in neuronal firing rates in PVN in rats undergoing neonatal CRD. On the contrary, intra-PVN administration of either the SK2 inhibitor apamin or PKA activator 8-Br-cAMP exacerbated the visceral hypersensitivity. Taken together, these findings demonstrated that visceral hypersensitivity is related to the downregulation of membrane SK2 in PVN, which may be attributed to the activation of PKA; pharmacologic activation of SK2 alleviated visceral hypersensitivity, which brings prospect of SK2 activators as a new intervention for visceral pain.

Lung Cancer Cells-Controlled Dkk-1 Production in Brain Metastatic Cascade Drive Microglia to Acquire a Pro-tumorigenic Phenotype.

OBJECTIVES: Organotropism is primarily determined by tumor-derived exosomes. To date, the role of lung cancer cells-derived exosomes underlying the pre-metastatic niche formation is unclear. MATERIALS AND METHODS: The animal models of retro-orbital and intra-ventricular injection were constructed to administrate lung cancer cells-derived exosomes. Cytokine array was used to screen the cytokines released from brain endothelium after internalization of lung cancer cells-derived exosomes. The cellular co-culture system was established to mimic microglia-vascular niche contained lung cancer cells-derived exosomes. The levels of Dkk-1 and the activities of microglia were analyzed by qRT-PCR, western blot and immunofluorescence. In vivo selections of highly brain metastatic cells were performed to analyze the direct interaction of lung cancer cells with microglia. RESULTS: Animal studies demonstrated that there was a suppressive signal transferred from brain endothelium to microglia after internalization of lung cancer cells-derived exosomes into brain endothelium, which caused an absolutely less M1 phenotypic microglia and a relatively more M2 phenotypic microglia. Further results indicated that lung cancer cells-derived exosomes induced a release of endogenous Dkk-1 from brain endothelium, which rendered microglia to acquire a pro-tumorigenic feature in pre-metastatic niche. Subsequently, the declines of Dkk-1 in metastatic lung cancer cells removed the suppression on microglia and enhanced microglial activation in metastatic niche. CONCLUSION: Our findings shed a new light on the synergistic reaction of the different cells in "neurovascular units" toward the metastatic messages from lung cancer cells and provided a potential therapeutic pathway for lung cancer metastasis to brain.

Identification of Key Candidate Proteins and Pathways Associated with Temozolomide Resistance in Glioblastoma Based on Subcellular Proteomics and Bioinformatical Analysis.

TMZ resistance remains one of the main reasons why treatment of glioblastoma (GBM) fails. In order to investigate the underlying proteins and pathways associated with TMZ resistance, we conducted a cytoplasmic proteome research of U87 cells treated with TMZ for 1 week, followed by differentially expressed proteins (DEPs) screening, KEGG pathway analysis, protein-protein interaction (PPI) network construction, and validation of key candidate proteins in TCGA dataset. A total of 161 DEPs including 65 upregulated proteins and 96 downregulated proteins were identified. Upregulated DEPs were mainly related to regulation in actin cytoskeleton, focal adhesion, and phagosome and PI3K-AKT signaling pathways which were consistent with our previous studies. Further, the most significant module consisted of 28 downregulated proteins that were filtered from the PPI network, and 9 proteins (DHX9, HNRNPR, RPL3, HNRNPA3, SF1, DDX5, EIF5B, BTF3, and RPL8) among them were identified as the key candidate proteins, which were significantly associated with prognosis of GBM patients and mainly involved in ribosome and spliceosome pathway. Taking the above into consideration, we firstly identified candidate proteins and pathways associated with TMZ resistance in GBM using proteomics and bioinformatic analysis, and these proteins could be potential biomarkers for prevention or prediction of TMZ resistance in the future.