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IntroductionEnterocytozoon bieneusi is one of the most important zoonotic pathogens, responsible for nearly 90% of human infections. Its host spectrum is broad in China, encompassing humans, non-human primates, domestic animals, wildlife, and wastewater. Wild rodents have the potential to act as carriers of E. bieneusi, facilitating the parasite’s transmission to humans and domestic animals.MethodsThe present study involved the collection of 344 wild rodents, representing nine species, from three provinces in China. The prevalence and genotypes of E. bieneusi were determined through amplification of the ITS gene. Evolutionary analysis was conducted using Mega 5.0 with the neighbor-joining method (Kimura 2-parameter model, 1,000 replicates).ResultsAmong the sampled wild rodents, 41 (11.92%) were tested positive for E. bieneusi. Rattus flavipectus exhibited the highest prevalence (11/39), while Bandicota indica and Rattus rattus sladeni showed no infections (0/39 and 0/5, respectively), highlighting significant differences. Environmental factors strongly influenced E. bieneusi infection; rodents residing in lake beaches (10.27%, 15/146) and fields (19.95%, 18/95) were more susceptible compared to those in mountainous areas (7.77%, 8/103). The study identified four known genotypes (D, Type IV, SDD5, PigEBITS7) and five novel genotypes (HNRV-1 to HNRV-3, GXRL-1, GXRL-2) in the investigated wild rodents, with Genotype D exhibiting the highest prevalence.DiscussionRemarkably, this study reports the presence of E. bieneusi, R. flavipectus, M. fortis, A. agrarius, R. losea, and N. lotipes for the first time. These findings underscore the common occurrence of E. bieneusi infection in wild rodents in China, highlighting its diverse nature and significant potential for zoonotic transmission. Hence, it is imperative to conduct a comprehensive epidemiological investigation of rodent infection with E. bieneusi, particularly focusing on wild rodents that are closely associated with humans. Additionally, developing appropriate measures and monitoring strategies to minimize the risk of infection is essential.

IntroductionBlastocystis is one of the most critical intestinal protozoans in various hosts, including humans and mice. To determine the status of Blastocystis infection in wild rodents in China.MethodsA total of 344 faecal samples were collected from seven wild rodent species from three provinces, and the small subunit ribosomal RNA (SSU rRNA) genes of Blastocystis were amplified to determine their prevalence and subtypes.ResultsOf the 344 samples, 54 (15.70%) were detected as Blastocystis-positive. The prevalence of Blastocystis was 26.14% (40/153), 7.95% (7/88), and 6.80% (7/103) in wild rodents from Hunan Province, Yunnan Province, and Guangxi Province, respectively. The prevalence of Blastocystis in different wild rodent species varied from 0.00% (0/13) in Mus musculus to 40.00% (2/5) in Rattus rattus sladeni. The prevalence of Blastocystis in samples from the lake beach area (27.40%, 40/146) was significantly higher than in those from the mountain (6.80%, 7/103) and field regions (7.37%, 7/95). The prevalence in different seasons was 26.14% in summer (40/153), 7.95% in autumn (7/88), and 6.80% in winter (7/103). Moreover, a total of two Blastocystis subtypes were identified in the investigated wild rodents, including ST4 and ST5.DiscussionThe present study discovered the existence of Blastocystis infection in Rattus favipectus, Microtus fortis, Apodemus agrarius, Bandicota indica, Rattus rattus sladeni, and Rattus losea, expanding the host range of this parasite. The findings also demonstrate that wild rodents may be an important potential infection source for Blastocystis infection in humans and other animals.

ObjectiveThe safety results of different recommended doses of sodium-glucose cotransporter 2 inhibitors (SGLT-2i) for patients with type 2 diabetes mellitus (T2DM) remain uncertain. This study aims to comprehensively estimate and rank the relative safety outcomes with different doses of SGLT-2i for T2DM.MethodsPubMed, Embase, the Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, Chinese National Knowledge Infrastructure, WanFang database, and SinoMed database were searched from the inception to 31 May 2023. We included double-blind randomized controlled trials (RCTs) comparing SGLT-2i with placebo or another antihyperglycemic as oral monotherapy in the adults with a diagnosis of T2DM.ResultsTwenty-five RCTs with 12,990 patients randomly assigned to 10 pharmacological interventions and placebo were included. Regarding genital infections (GI), all SGLT-2i, except for ertugliflozin and ipragliflozin, were associated with a higher risk of GI compared to placebo. Empagliflozin 10mg/d (88.2%, odds ratio [OR] 7.90, 95% credible interval [CrI] 3.39 to 22.08) may be the riskiest, followed by empagliflozin 25mg/d (83.4%, OR 7.22, 95%CrI 3.11 to 20.04)) and canagliflozin 300mg/d (70.8%, OR 5.33, 95%CrI 2.25 to 13.83) based on probability rankings. Additionally, dapagliflozin 10mg/d ranked highest for urinary tract infections (UTI, OR 2.11, 95%CrI 1.20 to 3.79, 87.2%), renal impairment (80.7%), and nasopharyngitis (81.6%) when compared to placebo and other treatments. No increased risk of harm was observed with different doses of SGLT-2i regarding hypoglycemia, acute kidney injury, diabetic ketoacidosis, or fracture. Further subgroup analysis by gender revealed no significantly increased risk of UTI. Dapagliflozin 10mg/d (91.9%) and canagliflozin 300mg/d (88.8%) ranked first in the female and male subgroups, respectively, according to the probability rankings for GI.ConclusionCurrent evidence indicated that SGLT-2i did not significantly increase the risk of harm when comparing different doses, except for dapagliflozin 10mg/d, which showed an increased risk of UTI and may be associated with a higher risk of renal impairment and nasopharyngitis. Additionally, compared with placebo and metformin, the risk of GI was notably elevated for empagliflozin 10mg/d, canagliflozin 300mg/d, and dapagliflozin 10mg/d. However, it is important to note that further well-designed RCTs with larger sample sizes are necessary to verify and optimize the current body of evidence.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023396023.

BackgroundSince abnormal aerobic glycolysis was first identified in cancer cells, many studies have focused on its mechanisms. The purpose of this study was to analyze the global research status of the Warburg effect in cancer using bibliometrics.MethodsArticles published from 01 January 2013 to 31 December 2022 (n=2,067) were retrieved from the Web of Science core collection database and analyzed using VOSviewer and CiteSpace software.ResultsOver the past decade, there was an overall increase in the number of annual publications. China was the most productive country with 790 articles, while the United States received the most citations, with 25,657 citations in total. Oncotarget was the most productive and most cited journal, with 99 articles and 4,191 citations, respectively. International cooperation was common, with the USA cooperating most with other countries. Lactate metabolism, citrate production, and non-coding RNAs related to the Warburg effect have received increasing attention in cancer research. These areas may become future research trends.ConclusionThe study findings help summarize the research status and hotspots of the Warburg effect cancer, and will inform subsequent research.

Cancer cachexia is a multifactorial syndrome defined by progressive loss of body weight with specific depletion of skeletal muscle and adipose tissue. Since there are no FDA-approved drugs that are available, nutritional intervention is recommended as a supporting therapy. Creatine supplementation has an ergogenic effect in various types of sports training, but the regulatory effects of creatine supplementation in cancer cachexia remain unknown. In this study, we investigated the impact of creatine supplementation on cachectic weight loss and muscle loss protection in a tumor-bearing cachectic mouse model, and the underlying molecular mechanism of body weight protection was further assessed. We observed decreased serum creatine levels in patients with cancer cachexia, and the creatine content in skeletal muscle was also significantly decreased in cachectic skeletal muscle in the C26 tumor-bearing mouse model. Creatine supplementation protected against cancer cachexia-associated body weight loss and muscle wasting and induced greater improvements in grip strength. Mechanistically, creatine treatment altered the dysfunction and morphological abnormalities of mitochondria, thus protecting against cachectic muscle wasting by inhibiting the abnormal overactivation of the ubiquitin proteasome system (UPS) and autophagic lysosomal system (ALS). In addition, electron microscopy revealed that creatine supplementation alleviated the observed increase in the percentage of damaged mitochondria in C26 mice, indicating that nutritional intervention with creatine supplementation effectively counteracts mitochondrial dysfunction to mitigate muscle loss in cancer cachexia. These results uncover a previously uncharacterized role for creatine in cachectic muscle wasting by modulating cellular energy metabolism to reduce the level of muscle cell atrophy.

Fertilizer management can influence soil microbes, soil properties, enzymatic activities, abundance and community structure. However, information on the effects of biochar in combination with organic-inorganic fertilizer after 3 years under pomelo orchard on soil bacterial abundance, soil properties and enzyme activities are not clear. Therefore, we conducted a field experiment with seven treatments, i.e., (1) Ck (control), (2) T1 (2 kg biochar plant–1), (3) T2 (4 kg biochar plant–1), (4) T3 (2 kg organic-inorganic mixed fertilizer plant–1), (5) T4 (4 kg biochar + 1.7 kg organic-inorganic mixed fertilizer plant–1), (6) T5 (4 kg biochar + 1.4 kg organic-inorganic mixed fertilizer plant–1), and (7) T6 (4 kg biochar + 1.1 kg organic-inorganic mixed fertilizer plant–1). The soil microbial communities were characterized using high-throughput sequencing of 16S and internal transcribed spacer (ITS) ribosomal RNA gene amplicons. The results showed that biochar combined with organic-organic fertilizer significantly improved soil properties (pH, alkali hydrolysable nitrogen, available phosphorus, available potassium, and available magnesium) and soil enzymatic activities [urease, dehydrogenase (DHO), invertase and nitrate reductase (NR) activities]. Furthermore, soil bacterial relative abundance was higher in biochar and organic-inorganic treatments as compared to control plots and the most abundant phyla were Acidobacteria (40%), Proteobacteria (21%), Chloroflexi (17%), Planctomycetes (8%), Bacteroidetes (4%), Verrucomicrobia (2%), and Gemmatimonadetes (1%) among others. Among the treatments, Acidothermus, Acidibacter, Candidatus Solibacter and F473 bacterial genera were highest in combined biochar and organic-inorganic treatments. The lowest bacterial abundance and bacterial compositions were recorded in control plots. The correlation analysis showed that soil attributes, including soil enzymes, were positively correlated with Chloroflexi, Planctomycetes, verrucomicrobia, GAL15 and WPS-2 bacterial abundance. This study demonstrated that biochar with organic-inorganic fertilizer improves soil nutrients, enzymatic activities and bacterial abundance.

Purpose: To assess the quality of clinical practice guidelines (CPGs) related to drug therapy for prevention and control of ventilator-associated pneumonia (VAP) and compare the differences and similarities between recommendations.Methods: Electronic databases (including PubMed, Cochrane library, Embase, Web of Science), guideline development organizations, and professional societies were searched to identify CPGs for VAP from 20 January 2012 to 20 January 2022. The Appraisal of Guidelines Research & Evaluation (AGREE) II instrument was used to evaluate the quality of the guidelines. The recommendations on drug therapy for prevention and treatment for each guideline were extracted, and then a descriptive synthesis was performed to analyze the scope/topic, and consistency of the recommendations.Results: Thirteen CPGs were included. The median score and interquartile range (IQR) in each domain are shown below: scope and purpose 72.22% (63.89%,83.33%); stakeholder involvement 44.44% (38.89%,52.78%); rigor of development 43.75% (31.25%,57.29%); clarity and presentation 94.44% (77.78%,94.44%); applicability 20.83 (8.34%,33.34%) and editorial independence 50% (33.33%,66.67%). We extracted 21 recommendations on drug therapy for prevention of VAP and 51 recommendations on drugs used for treatment. Some controversies remained among the included guidelines.Conclusion: There is considerable variability in the development processes and reporting of VAP guidelines. Despite many similarities, the recommendations still had some inconsistencies in the details. For the prevention and treatment of VAP, local microbial epidemiology and antibiotic sensitivity must be considered, and recommendations should be regularly revised as new evidence emerges.

Canine distemper (CD) caused by canine distemper virus (CDV) is one of the major infectious diseases in minks, bringing serious economic losses to the mink breeding industry. By an integrated analysis of microRNA (miRNA)-messenger RNA (mRNA), the present study analyzed the changes in the mink transcriptome upon CDV infection in mink lung epithelial cells (Mv. l. Lu cells) for the first time. A total of 4,734 differentially expressed mRNAs (2,691 upregulated and 2,043 downregulated) with |log2(FoldChange) |>1 and P-adj2 and P-adj

Biochar amendment can influence the abundance, activity, and community structure of soil microbes. However, scare information is present about the effect of the combined application of biochar with synthetic nitrogen (N) fertilizer under paddy field condition. We aimed to resolve this research gap in rice field conditions through different biochar in combination with N fertilizers on soil nutrients, soil microbial communities, and rice grain yield. The present study involves eight treatments in the form of biochar (0, 10, 20, and 30 t ha–1) and N (135 and 180 kg ha–1) fertilizer amendments. The soil microbial communities were characterized using high-throughput sequencing of 16S and Internal transcribed spacer (ITS) ribosomal RNA gene amplicons. Experiential findings showed that the treatments had biochar amendments along with N fertilizer significantly advanced soil pH, soil organic carbon (SOC), total nitrogen (TN), soil microbial carbon (SMBC), soil microbial nitrogen (SMBN), and rice grain yield in comparison to sole N application. Furthermore, in comparison with control in the first year (2019), biochar amendment mixed with N fertilizer had more desirable relative abundance of microorganism, phyla Acidobacteria, Actinobacteria, Proteobacteria, and Verrucomicrobia with better relative abundance ranging from 8.49, 4.60, 46.30, and 1.51% in T7, respectively. Similarly, during 2020, bacteria phyla Acidobacteria, Actinobacteria, Bacteroidetes, Gemmatimonadetes, Planctomycetes, and Verrucomicrobia were resulted in higher and ranging from 8.69, 5.18, 3.5, 1.9, 4.0, and 1.6%, in biochar applied treatments, respectively, as compared to control (T1). Among the treatments, Sphingopyxis and Thiobacillus bacterial genus were in higher proportion in T7 and T3, respectively, as compared to other treatments and Bacillus was higher in T6. Interestingly, biochar addition significantly decreased the soil fungi phyla Ascomycota, Basidiomycota, Chytridiomycota, and Rozellomycota, in 2020 as compared to 2019. Whereas biochar addition to soil decreased Echria, Kohlmeyeriopsis, and Westerdykella fungal genus as compared to non-biochar treatments. The redundancy analysis showed that soil biochemical traits were positively correlated with soil bacteria. In addition, correlation analysis showed that soil bacteria including Acidobacteria, Actinobacteria, Bacteroidetes, Planctomycetes, and Proteobacteria strongly correlated with rice grain yield. This study demonstrated that soil nutrients and bacteria contribute to an increase in rice yield in combined biochar amendment with lower N treatments.

Enterocytozoon (E.) bieneusi and Cryptosporidium spp. are the most important zoonotic enteric pathogens associated with diarrheal diseases in animals and humans. However, it is still not known whether E. bieneusi and Cryptosporidium spp. are carried by wild rodents in Shanxi, Guangxi, Zhejiang, Shandong, and Inner Mongolia, China. In the present study, a total of 536 feces samples were collected from Rattus (R.) norvegicus, Mus musculus, Spermophilus (S.) dauricus, and Lasiopodomys brandti in six provinces of China, and were detected by PCR amplification of the SSU rRNA gene of Cryptosporidium spp. and ITS gene of E. bieneusi from June 2017 to November 2020. Among 536 wild rodents, 62 (11.6%) and 18 (3.4%) samples were detected as E. bieneusi- and Cryptosporidium spp.-positive, respectively. Differential prevalence rates of E. bieneusi and Cryptosporidium spp. were found in different regions. E. bieneusi was more prevalent in R. norvegicus, whereas Cryptosporidium spp. was more frequently identified in S. dauricus. Sequence analysis indicated that three known Cryptosporidium species/genotypes (Cryptosporidium viatorum, Cryptosporidium felis, and Cryptosporidium sp. rat genotype II/III) and two uncertain Cryptosporidium species (Cryptosporidium sp. novel1 and Cryptosporidium sp. novel2) were present in the investigated wild rodents. Meanwhile, 5 known E. bieneusi genotypes (XJP-II, EbpC, EbpA, D, and NCF7) and 11 novel E. bieneusi genotypes (ZJR1 to ZJR7, GXM1, HLJC1, HLJC2, and SDR1) were also observed. This is the first report for existence of E. bieneusi and Cryptosporidium spp. in wild rodents in Shanxi, Guangxi, Zhejiang, and Shandong, China. The present study also demonstrated the existence of E. bieneusi and Cryptosporidium spp. in S. dauricus worldwide for the first time. This study not only provided the basic data for the distribution of E. bieneusi and Cryptosporidium genotypes/species, but also expanded the host range of the two parasites. Moreover, the zoonotic E. bieneusi and Cryptosporidium species/genotypes were identified in the present study, suggesting wild rodents are a potential source of human infections.

Cryptosporidium is an enteric apicomplexan parasite, which can infect multiple mammals including livestock and wildlife. Tibetan Antelope (Pantholops hodgsonii) is one of the most famous wildlife species, that belongs to the first class protected wild animals in China. However, it has not been known whether Tibetan Antelope is infected with Cryptosporidium so far. The objective of the present study was to determine the prevalence and characterization of Cryptosporidium species infection in Tibetan Antelope and the corresponding species by using molecular biological method. In the current study, a total of 627 fecal samples were randomly collected from Tibetan Antelope in the Tibet Autonomous Region (2019–2020), and were examined by PCR amplification of the small subunit ribosomal RNA (SSU rRNA) gene. Among 627 samples, 19 (3.03%, 19/627) were examined as Cryptosporidium-positive, with 7 (2.33%, 7/300) in females and 12 (3.67%, 12/327) in males. The analysis of SSU rRNA gene sequence suggested that only two Cryptosporidium species, namely, C. xiaoi and C. ubiquitum, were identified in this study. This is the first evidence for an existence of Cryptosporidium in Tibetan Antelope. These findings extend the host range for Cryptosporidium spp. and also provide important data support for prevention and control of Cryptosporidium infection in Tibetan Antelope.

Echinococcosis is a zoonosis caused by the larval stage of cestode species that belong to the genus Echinococcus. The infection of hydatid in sheep is very common in China, especially in the northwestern China. Here, we conducted the first systematic review and meta-analysis of echinococcosis in sheep in China. Six databases (PubMed, ScienceDirect, Baidu Library, CNKI, Wanfang, and VIP Chinese Journal Database) were used to retrieve the literatures on echinococcosis in sheep in China from 1983 to 2020, and 74 studies. The random effects model was used in the “meta” package of the R software and the PFT was chosen for rate conversion. The research data were analyzed through subgroup analysis and univariate meta-regression analysis to reveal the factors that lead to research heterogeneity. The combined prevalence of Echinococcus in the selected period was estimated to be 30.9% (192,094/826,406). In the analysis of sampling year, the lowest positive rate was 13.9% (10,296/177,318) after 2011. The highest prevalence of Echinococcus was 51.1% (278/531) in the southwestern China. The highest infection rate in sheep was 20.1% (58,344/597,815) in the liver. The analysis based on age showed that the infection rate of elderly sheep was significantly higher than that in younger animals (P < 0.05). We also evaluated the effects of different geographic and climatic factors on the prevalence of Echinococcus in sheep. The results showed that the prevalence of Echinococcus was higher in high altitude, cold, humid, and high rainfall areas. It is necessary to carry out long-term monitoring and control of echinococcosis, cut off the infection route, and reduce the risk of infection in the high risk areas.

Enterocytozoon bieneusi is the most important causative agent of microsporidiosis and can infect almost all vertebrate and invertebrate hosts, including minks (Neovison vison). In the present study, a total of 298 feces samples (including 79 from Heilongjiang province, 31 from Hebei province, 67 from Jilin province, 90 from Liaoning province, and 31 from Shandong province, Northern China) were examined by nested PCR amplification of the internal transcribed spacer (ITS) region of the rRNA gene. The overall prevalence of E. bieneusi in minks was 10.1%, with 10.5% in Jilin province, 32.3% in Hebei province, 8.9% in Liaoning province, 0% in Shandong province, and 6.3% in Heilongjiang province. Furthermore, multiple logistic regression analysis revealed that region was only risk factors associated with E. bieneusi infection in the investigated minks. Five E. bieneusi ITS genotypes (three known genotypes, namely D, Peru11, and EbpC; two novel genotypes, namely, NCM-1 and NCM-2) were found in the current study. Importantly, genotypes D, Peru11 and EbpC, previously identified in humans, were also found in minks, which suggested that minks are the potential sources of human microsporidiosis. To the best of our knowledge, this is the first report of E. bieneusi infection in minks worldwide. The results of the present survey have implications for the controlling E. bieneusi infection in minks, other animals and humans.

Enterocytozoon bieneusi is an important zoonotic parasite. It can infect virtually all animal species and has a global distribution. However, the prevalence of E. bieneusi in donkeys (Equus asinus) has only been reported in Algeria and Spain, and no information is available concerning genotypes of E. bieneusi in donkeys worldwide. In the present study, a total of 301 donkey fecal samples (48 from Jilin Province, 224 from Shandong Province and 29 from Liaoning Province) were collected and examined by PCR amplification of the internal transcribed spacer (ITS) region. The overall E. bieneusi prevalence was 5.3% (16/301), with 6.3% (3/48) in Jilin Province, 4.9% (11/224) in Shandong Province, and 6.9% (2/29) in Liaoning Province. Prevalence in different age groups ranged from 4.2 to 5.5%. E. bieneusi prevalence in donkeys sampled in different seasons varied from 4.2 to 6.5%. Altogether, four E. bieneusi genotypes were identified in this study, with two known genotypes (J and D) and two novel genotypes (NCD-1and NCD-2). Phylogenetic analysis revealed that genotypes D, NCD-1 and NCD-2 belonged to group 1, while the remaining genotype J was clustered into group 2. These findings revealed the occurrence of E. bieneusi in donkeys in China for the first time. Moreover, the present study also firstly genotyped the E. bieneusi in donkeys worldwide. These findings extend the distribution of E. bieneusi genotypes and provide baseline data for controlling E. bieneusi infection in donkeys, other animals and humans. [ABSTRACT FROM AUTHOR]

Chronic liver disease or repeated damage to hepatocytes can give rise to hepatic fibrosis. Hepatic fibrosis (HF) is a pathological process of excessive sedimentation of extracellular matrix (ECM) proteins such as collagens, glycoproteins, and proteoglycans (PGs) in the hepatic parenchyma. Changes in the composition of the ECM lead to the stiffness of the matrix that destroys its inherent mechanical homeostasis, and a mechanical homeostasis imbalance activates hepatic stellate cells (HSCs) into myofibroblasts, which can overproliferate and secrete large amounts of ECM proteins. Excessive ECM proteins are gradually deposited in the Disse gap, and matrix regeneration fails, which further leads to changes in ECM components and an increase in stiffness, forming a vicious cycle. These processes promote the occurrence and development of hepatic fibrosis. In this review, the dynamic process of ECM remodeling of HF and the activation of HSCs into mechanotransduction signaling pathways for myofibroblasts to participate in HF are discussed. These mechanotransduction signaling pathways may have potential therapeutic targets for repairing or reversing fibrosis.

Periodontitis is a type of systemic immune inflammation that is caused by the complex infection of a variety of microorganisms in the subgingival plaque and the imbalance of the microbial ecological environment in the mouth. Periodontitis and chronic kidney disease (CKD) share many risk factors, such as obesity, smoking, and age. A growing body of data supports a strong correlation between periodontitis and kidney disease. Evidence supports the role of periodontal inflammation and elevated serum inflammatory mediators in renal atherosclerosis, renal deterioration, and end-stage renal disease (ESRD) development. Periodontitis is a risk factor for kidney disease. However, to our knowledge, there are few studies detailing the possible link between periodontitis and CKD. This review summarizes the possible mechanisms underlying periodontitis and CKD. More importantly, it highlights novel and potential pathogenic factors for CKD, including bacteria, pro-inflammatory mediators and oxidative stress. However, most research on the relationship between periodontitis and systemic disease has not determined causality, and these diseases are largely linked by bidirectional associations. Future research will focus on exploring these links to contribute to new treatments for CKD.