Miracle-dz/UniFAR-FTUs huggingface dataset:
The increasing prevalence of CPV-2c in domestic dogs in China

Background Canine parvovirus type 2 (CPV-2), a serious pathogen, leads to high morbidity and mortality in dogs and several wild carnivore species. Although it is a DNA virus, it evolves particularly rapidly, with a genomic substitution rate of approximately 10−4 substitutions/site/year, close to that of some RNA viruses. Tracing the prevalence of CPV-2 in dogs is significant. Methods In this study, an aetiological survey was carried out from 2016 to 2019 in Guangdong Province, China, involving Guangzhou, Shenzhen and Dongguan. Furthermore, to systematically analyse the prevalence of CPV-2 in China, the VP2 gene sequences of all Chinese isolates were downloaded from the NCBI nucleotide database in December 2019, and changes in CPV-2 variants were examined. Results A total of 55.7% (34/61) of samples were CPV-2 positive by PCR detection and virus isolation. In addition to different variants circulating in dogs, coinfection with multiple variants was identified, as was coinfection with other canine enteric pathogens in some cases. Two previously reported amino acid sites, A5G and Q370R of CPV-2c mutants, reported in variants in China were assessed, and several CPV-2 isolates with P13S and K582N mutations were detected in this study. Finally, we speculate on the prevalence of different CPV-2 variants in China. According to the VP2 gene sequence obtained from the NCBI nucleotide database, the proportion of different variants in China has changed, and CPV-2c appears to be growing rapidly. In conclusion, this aetiology survey suggests that CPV-2 continues to be common in China and that the prevalence of CPV-2c is increasing.
miR-550-1 functions as a tumor suppressor in acute myeloid leukemia via the hippo signaling pathway

MicroRNAs (miRNAs) and N6-methyladenosine (m6A) are known to serve as key regulators of acute myeloid leukemia (AML). Our previous microarray analysis indicated miR-550-1 was significantly downregulated in AML. The specific biological roles of miR-550-1 and its indirect interactions and regulation of m6A in AML, however, remain poorly understood. At the present study, we found that miR-550-1 was significantly down-regulated in primary AML samples from human patients, likely owing to hypermethylation of the associated CpG islands. When miR-550-1 expression was induced, it impaired AML cell proliferation both in vitro and in vivo, thus suppressing tumor development. When ectopically expressed, miR-550-1 drove the G0/1 cell cycle phase arrest, differentiation, and apoptotic death of affected cells. We confirmed mechanistically that WW-domain containing transcription regulator-1 (WWTR1) gene was a downstream target of miR-550-1. Moreover, we also identified Wilms tumor 1-associated protein (WTAP), a vital component of the m6A methyltransferase complex, as a target of miR-550-1. These data indicated that miR-550-1 might mediate a decrease in m6A levels via targeting WTAP, which led to a further reduction in WWTR1 stability. Using gain- and loss-of-function approaches, we were able to determine that miR-550-1 disrupted the proliferation and tumorigenesis of AML cells at least in part via the direct targeting of WWTR1. Taken together, our results provide direct evidence that miR-550-1 acts as a tumor suppressor in the context of AML pathogenesis, suggesting that efforts to bolster miR-550-1 expression in AML patients may thus be a viable clinical strategy to improve patient outcomes.
Rigosertib ameliorates the effects of oncogenic KRAS signaling in a murine model of myeloproliferative neoplasia

Aberrant signaling triggered by oncogenic or hyperactive RAS proteins contributes to the malignant phenotypes in a significant percentage of myeloid malignancies. Of these, juvenile myelomonocytic leukemia (JMML), an aggressive childhood cancer, is largely driven by mutations in RAS genes and those that encode regulators of these proteins. The Mx1-cre kras+/G12D mouse model mirrors several key features of this disease and has been used extensively to determine the utility and mechanism of small molecule therapeutics in the context of RAS-driven myeloproliferative disorders. Treatment of disease-bearing KRASG12D mice with rigosertib (RGS), a small molecule RAS mimetic that is in phase II and III clinical trials for MDS and AML, decreased the severity of leukocytosis and splenomegaly and extended their survival. RGS also increased the frequency of HSCs and rebalanced the ratios of myeloid progenitors. Further analysis of KRASG12D HSPCs in vitro revealed that RGS suppressed hyperproliferation in response to GM-CSF and inhibited the phosphorylation of key RAS effectors. Together, these data suggest that RGS might be of clinical benefit in RAS-driven myeloid disorders.
Global RNA editome landscape discovers reduced RNA editing in glioma: loss of editing of gamma-amino butyric acid receptor alpha subunit 3 (GABRA3) favors glioma migration and invasion

Background Gliomas are the most common and lethal type of intracranial tumors. With the current treatment regime, the median survival of patients with grade IV glioma (glioblastoma/GBM) remains at 14–16 months. RNA editing modifies the function and regulation of transcripts. The development of glial tumors may be caused by altered RNA editing events. Methods In this study, we uncover the global RNA editome landscape of glioma patients from RNA-seq data of control, lower grade glioma (LGG) and GBM samples (n = 1,083). Results A-to-I editing events were found to comprise 80% of the total editing events of which 96% were located in the Alu regions. The total RNA editing events were found to be reduced in glioma compared to control samples. More specifically, we found Gamma-aminobutyric acid type A receptor alpha3 (GABRA3) to be edited (c.1026 A-to-G; pI343M) in 73% (editing ratio 0.8) of control samples compared to LGG (28.96%; 0.47) and GBM (5.2%; 0.53) samples. GABRA3 transcript level was found to be downregulated in glioma compared to control in a grade-specific manner with GBMs having the lowest level of the transcript. Further, GABRA3 transcripts were observed to be higher in edited compared to unedited glioma samples. The transcript and protein levels of exogenously expressed gene were found to be higher for edited compared to unedited GABRA3 in glioma cells. Further, exogenously expressed edited GABRA3 inhibited migration and invasion of glioma cells efficiently but not the unedited GABRA3. Conclusion Collectively, our study discovered a reduction in RNA editing during glioma development. We further demonstrate that elevated RNA editing maintains a high level of GABRA3 RNA and protein in normal glial cells which provides a less migratory environment for the normal functioning of the brain. In contrast, the reduction in GABRA3 protein levels, due to lower stability of unedited RNA, results in the loss of function which confers an aggressive phenotype to GBM tumor.
Characterization of the effects of P30-35 CAMAL on normal and leukemic myelopoiesis

P30-35 CAMAL is a component of material immunoaffinity enriched from lysates of myeloid leukemia leucocytes using the monoclonal antibody CAMAL1. Reactivity with CAMAL1 is diagnostic of myeloid leukemias. CAMAL1 enriched material inhibited myelopoiesis by normal progenitor cells in vitro. This study demonstrates that inhibition is associated with P30-35 CAMAL. Neutrophilic granulocyte colonies were preferentially inhibited by P30-35 CAMAL while higher concentrations affected all colony types. Nonadherent progenitor cell numbers were reduced in P30-35 CAMAL-treated long term cultures of normal marrow cells whereas adherent cell numbers were increased, suggesting a block in differentiation. In addition, colony formation by murine cells was inhibited by P30-35 CAMAL. As in cultures of human cells, neutrophilic granulocyte colonies were preferentially inhibited, indicating that downregulation of normal myelopoiesis by P30-35 CAMAL crosses species barriers, and might be an important regulatory mechanism. Using highly enriched P30-35 CAMAL, a stimulatory effect on CML colony formation was defined. Stimulation of colony formation occurred at low and high concentrations of P30-35 CAMAL, but was reduced at intermediate concentrations. At low concentrations of P30-35 CAMAL primitive colonies were increased, whereas high concentrations affected all colony types. Colony formation by several myeloid leukemiaderived cell lines was increased by P30-35 CAMAL.
Comparing the Efficacy and Safety of Glucagon-Like Peptide 1 Receptor Agonists with Sodium-Glucose Cotransporter 2 Inhibitors for Obese Type 2 Diabetes Patients Uncontrolled on Metformin: A Systematic Review and Meta-Analysis of Randomized Clinical Trials

Introduction To conduct the first meta-analysis of randomized controlled trials (RCTs) comparing glucagon-like peptide 1 receptor agonists (GLP-1RAs) with sodium-glucose cotransporter 2 inhibitors (SGLT-2is) for obese type 2 diabetes (T2D) patients uncontrolled on metformin. Methods We searched Pubmed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), Ovid, and Web of Science from inception to May 14, 2020, without language restrictions for eligible RCTs. The primary outcome is the mean change from baseline in glycated haemoglobin (HbA1c). Results Totally, 3 RCTs enrolled 2066 patients were identified. Compared with SGLT-2is, treatment with GLP-1RAs achieved significant reduced HbA1c by 0.40% (95% CI: −0.54, −0.25; p < 0.00001), fasting blood glucose (FBG) by 0.17 mmol/L (95% CI: −0.31, −0.04; p=0.01), and postprandial blood glucose (PBG) by 0.32 mmol/L (95% CI: −0.49, −0.14; p=0.0003) for obese T2D patients uncontrolled on metformin. The significant benefit of weight loss was seen in semaglutide (MD: −0.75; 95% CI: −1.18, −0.31; p < 0.0007). No significant difference was detected between GLP-1RAs and SGLT-2is in overall adverse events (RR: 1.03; 95% CI: 0.98, 1.09; p=0.76), but gastrointestinal events showed higher occurrence in GLP-1RAs groups compared with SGLT-2is (RR: 1.62; 95% CI: 1.37, 1.93; p < 0.00001). Subgroup analyses revealed that follow-up time did not statistically influence glycemic control. Conclusion GLP-1RAs are superior to SGLT-2is for obese T2D patients uncontrolled on metformin in glycemic control without an increase in adverse events except for a higher occurrence in gastrointestinal events. Future large longer-term follow-up clinical trials are needed to provide more evidence about the sustainable effects and safety of GLP-1RAs compared with SGLT-2is.
Yin and Yang Regulation of Liver X Receptor α Signaling Control of Cholesterol Metabolism by Poly(ADP-ribose) polymerase 1

Liver X receptor α (LXRα) controls a set of key genes involved in cholesterol metabolism. However, the molecular mechanism of this regulation remains unknown. The regulatory role of poly(ADP-ribose) polymerase 1 (PARP1) in cholesterol metabolism in the liver was examined. Activation of PARP1 in the liver suppressed LXRα sensing and prevented upregulation of genes involved in HCD-induced cholesterol disposal. Mechanistically, LXRα was poly(ADP-ribosyl)ated by activated PARP1, which decreased DNA binding capacity of LXRα, thus preventing its recruitment to the target promoter. Intriguingly, we found that unactivated PARP1 was indispensable for LXRα transactivation and target expression. Further exploration identified unactivated PARP1 as an essential component of the LXRα-promoter complex. Taken together, the results indicate that activated PARP1 suppresses LXRα activation through poly(ADP-ribosyl)ation, while unactivated PARP1 promotes LXRα activation through physical interaction. PARP1 is a pivotal regulator of LXRα signaling and cholesterol metabolism in the liver.
Susceptibility of Mature Staphylococcus Biofilms to Chinese Herbal Decoction Sanhuang Jiedu: An In Vitro Study

Background External socking and washing with the Chinese herbal Sanhuang Jiedu decoction (SHJD) can effectively control local limb infections with bone and implant exposure. However, the antibiofilm activities of this decoction in vitro have not yet been investigated. Therefore, the aim of this study was to examine the effects and characteristics of SHJD on the mature biofilms of multidrug-resistant staphylococci on a titanium surface. Methods Biofilm-forming methicillin-resistant Staphylococcus epidermidis ATCC 35984 and S. aureus ATCC 43330, and non-biofilm-forming S. epidermidis ATCC 12228 were selected as the experimental strains. The mature biofilms were prepared on titanium surfaces. The five experimental groups were based on dilution concentrations (DC) of SHJD: the control group (biofilm incubated with 0.85% NaCl solution), the SHJD (DC:1/8) group (initial SHJD solution was diluted 1/8), the SHJD (DC:1/4) group, the SHJD (DC:1/2) group, and the SHJD (DC:1/1) group (initial SHJD solution). The effects of SHJD on the mature biofilms were observed with the bacterial spread plate method, crystal violet (CV) staining, scanning electron microscopy, and confocal laser scanning microscopy. Results After culture in tryptic soy broth for 72 h, ATCC 43300 and ATCC 35984 produced mature biofilms and ATCC 12228 did not. The optical density value of ATCC 12228 was 0.11 ± 0.02, significantly lower than that of ATCC 35984 (0.42 ± 0.05) or ATCC 43300 (0.41 ± 0.03) (P < 0.05). The mature biofilms of ATCC 43300 and ATCC 35984 clearly disintegrated when incubated for 12–24 h with SHJD (DC:1/1) or SHJD (DC:1/2), showing only scattered bacterial adhesion. In the SHJD (DC:1/4) group, although many residual bacterial colonies still clustered together, presenting a biofilm structure, it was very looser than that in the SHJD (DC:1/8) group in which the biofilm was similar to that in the control group. For ATCC 12228, only colony adhesion was observed, and the number of colonies decreased as the concentration of SHJD or the culture period increased. The quantitative results for the bacterial spread plate and CV staining showed significant differences between the SHJD groups (P < 0.05). Conclusion SHJD has antibiofilm activity against multidrug-resistant Staphylococcus strains. It weakens or disrupts already-formed mature biofilms on titanium surfaces in a concentration- and incubation time-dependent manner.
NRXN1 as a novel potential target of antibody-drug conjugates for small cell lung cancer

Small cell lung cancer (SCLC) is a high-grade malignancy, and treatment strategies have not changed for decades. In this study, we searched for novel targets for antibody-drug conjugate (ADC) therapy for SCLC. We identified transmembrane proteins overexpressed specifically in SCLC with little or no expression in normal tissues and decided to focus on the cell adhesion molecule neurexin-1 (NRXN1). The cell surface overexpression of NRXN1 was confirmed using flow cytometry in SCLC cell lines (SHP77 and NCI-H526). The combination of a primary anti-NRXN1 monoclonal antibody and a secondary ADC exhibited anti-tumor activity in SCLC cell lines. Moreover, the knockout of NRXN1 in SHP77 cells resulted in a loss of the anti-tumor activity of NRXN1-mediated ADC therapy. Thus, NRXN1 could be a novel target for ADC therapy for the treatment of SCLC that is worth further research.
Clinical Effects and Safety of Electroacupuncture for the Treatment of Poststroke Dysphagia: A Comprehensive Systematic Review and Meta-Analysis

Objectives Electroacupuncture (EA), an extension of acupuncture, which is based on traditional acupuncture combined with modern electrotherapy, is commonly used for poststroke dysphagia (PSD) in clinical treatment and research. However, there is still a lack of sufficient evidence to recommend the routine use of EA for PSD. The aim of this study was to assess the efficacy and safety of EA in the treatment of PSD. Methods Randomized controlled trials (RCTs) evaluating the effects of EA on PSD were identified through a comprehensive literature search of the PubMed, Embase, Cochrane Library, Web of Science, Chinese National Knowledge Infrastructure, Chinese Biomedical Database, and VIP databases from their inception to July 2020. The quality assessment of the included trials was performed based on the guidance of the Cochrane Reviewers' Handbook, and meta-analysis (MA) was performed by using the RevMan 5.3 software. Results Sixteen trials were identified, and these included 1,216 patients with PSD. The results demonstrated that EA in combination with swallowing rehabilitation training (SRT) was significantly superior to SRT alone with regard to effective rate (OR 5.40, 95% CI [3.78, 7.72], P < 0.00001, water swallow test (WST) (MD −0.78, 95% CI [−1.07, −0.50], P < 0.00001), the video fluoroscopic swallowing study (VFSS) (MD 1.47, 95% CI [1.11, 1.84], P < 0.00001), the Ichiro Fujishima Rating Scale (IFRS) (MD 1.94, 95% CI [1.67, 2.22], P < 0.00001), and the incidence of aspiration pneumonia (IAP) (OR 0.20, 95% CI [0.06, 0.61], P=0.005). Conclusions The results showed that EA was better than the control treatment in terms of the effective rate, WST, VFSS, IFRS, and IAP of dysphagia after stroke. Strict evaluation standards and high-quality RCT designs are necessary for further exploration.
Hydrological and soil physiochemical variables determine the rhizospheric microbiota in subtropical lakeshore areas

Background Due to intensive sluice construction and other human disturbances, lakeshore vegetation has been destroyed and ecosystems greatly changed. Rhizospheric microbiota constitute a key part of a functioning rhizosphere ecosystem. Maintaining rhizosphere microbial diversity is a central, critical issue for sustaining these rhizospheric microbiota functions and associated ecosystem services. However, the community composition and abiotic factors influencing rhizospheric microbiota in lakeshore remain largely understudied. Methods The spatiotemporal composition of lakeshore rhizospheric microbiota and the factors shaping them were seasonally investigated in three subtropical floodplain lakes (Lake Chaohu, Lake Wuchang, and Lake Dahuchi) along the Yangtze River in China through 16S rRNA amplicon high-throughput sequencing. Results Our results showed that four archaeal and 21 bacterial phyla (97.04 ± 0.25% of total sequences) dominated the rhizospheric microbiota communities of three lakeshore areas. Moreover, we uncovered significant differences among rhizospheric microbiota among the lakes, seasons, and average submerged depths. The Acidobacteria, Actinobacteria, Bacteroidetes, Bathyarchaeota, Gemmatimonadetes, and Proteobacteria differed significantly among the three lakes, with more than half of these dominant phyla showing significant changes in abundance between seasons, while the DHVEG-6, Ignavibacteriae, Nitrospirae, Spirochaetes, and Zixibacteria varied considerably across the average submerged depths (n = 58 sites in total). Canonical correspondence analyses revealed that the fluctuation range of water level and pH were the most important factors influencing the microbial communities and their dominant microbiota, followed by total nitrogen, moisture, and total phosphorus in soil. These results suggest a suite of hydrological and soil physiochemical variables together governed the differential structuring of rhizospheric microbiota composition among different lakes, seasons, and sampling sites. This work thus provides valuable ecological information to better manage rhizospheric microbiota and protect the vegetation of subtropical lakeshore areas.
The Effect of Adding Neuromuscular Electrical Stimulation with Endurance and Resistance Training on Exercise Capacity and Balance in Patients with Chronic Obstructive Pulmonary Disease: A Randomized Controlled Trial

This study investigated the effectiveness of adding neuromuscular electrical stimulation (NMES) to endurance training (ET) and resistance training (RT) on exercise tolerance and balance in COPD patients. 42 patients were assigned randomly to the ET + RT + NMES group (n = 22) or ET + RT group (n = 20). Two training programs were performed including 72 sessions. The center of pressure (CoP) displacement in the mediolateral direction (CoPML), in the anteroposterior direction (CoPAP), and the center of pressure velocity (CoPV) were recorded using a stabilometric platform with eyes open (EO) and eyes closed (EC). Time up and go and Berg Balance Scale tests, 6-minute walking test (6MWT), and the maximal voluntary contraction (MVC) were measured before and after the intervention. The walking distance, the dyspnea, and the heart rate were improved after the training period (p < 0.001) for both groups (p < 0.05). The ET + RT + NMES group showed better improvement than the ET + RT group in terms of 6MWD. CoPML, CoPAP, and CoPV were significantly (p < 0.001; p < 0.05; p < 0.001, respectively) more improved in EO and EC conditions in the ET + RT + NMES group than the ET + RT group. BBS, TUG, and MVC values improved in both groups after the training (p < 0.001). The performances in TUG and MVC tests were significantly greater in the ET + RT + NMES group than those in the ET + RT group (p < 0.01; p < 0.001, respectively). Combining NMES, RT, and ET improves balance in patients with COPD.
Inhibitory effects of 2-methacryloyloxyethyl phosphorylcholine polymer on the adherence of bacteria causing upper respiratory tract infection

ABSTRACT Objective We aimed to investigate the inhibitory effect of 2-methacryloyloxyethyl phosphorylcholine (MPC) polymer on the adherence of Streptococcus pneumoniae (Spn) and nontypeable Haemophilus influenzae (NTHi) in vitro and in vivo. Materials and Methods Phosphorylcholine (PC) expression of 21 strains each of Spn and NTHi was evaluated using fluorescence-activated cell sorting; the adherence of bacteria to Detroit 562 cells and to the nasal mucosa of BALB/c mice was determined. MPC polymer-mediated inhibitory effects were compared with PC-keyhole limpet hemocyanin (PC-KLH)-mediated inhibitory effects. Results In vitro experiments showed that pretreatment with MPC polymer markedly inhibited the adherence of Spn and NTHi in a concentration dose–dependent manner independently of PC expression. No correlation was observed between PC expression and MPC polymer-mediated inhibitory effects. Contrarily, there was a significant negative correlation between PC-KLH-mediated inhibitory effects and PC expression in Spn and NTHi. The same results were obtained via in vivo experiments. The MPC polymer did not affect the histology of the nasal mucosa. Conclusions MPC polymer might be effective to reduce the occurrence of upper respiratory tract infection caused by Spn and NTHi and could be applied for the development of local treatments, such as topical gargles and nebulizer medications.