Investigation of the Flipping Dynamics of 1, N6-Ethenoadenine in Alkyladenine DNA Glycosylase.

Alkyladenine DNA glycosylase (AAG) is an essential enzyme responsible for maintaining genome integrity by repairing several DNA lesions damaged by alkylation or deamination. Understanding how it can recognize and excise the lesions thus lays the foundation for therapeutic treatment against lesion-associated diseases or cancers. However, the molecular details of how the lesion can be distinguished from the matched base by AAG and how it enters the cleavage site, ready for excision, are not fully elucidated. In this study, we have revealed the molecular details of the flipping dynamics of 1, N6-ethenoadenine (εA) not only in the form of free double-stranded DNA (dsDNA) but also in the form of the AAG-dsDNA complex. Our MD simulations and PMF calculations have shown that the flipping of εA and dA is thermodynamically disfavored in the free dsDNA, even though εA has a lower flipping energy barrier than dA. By sharp contrast, the flipping of εA is thermodynamically favored in AAG with an obvious free energy drop, while dA is equally stabilized before and after the flipping. Moreover, a comparison of the PMFs in the forms of free dsDNA and the AAG-dsDNA complex has pinpointed the role of AAG in discriminating εA against dA and facilitating the flipping of εA. Besides, the flipping process is simulated along the major and minor grooves, and our results have additionally demonstrated that the flipping is not directional in the free dsDNA while flipping along the major groove is kinetically more favorable than the minor groove in the AAG-dsDNA complex. Overall, our study has offered molecular insights into the flipping dynamics of εA and revealed its discrimination mechanism by AAG, which is expected to guide further enzyme engineering for therapeutic applications.

The CREG1-FBXO27-LAMP2 axis alleviates diabetic cardiomyopathy by promoting autophagy in cardiomyocytes.

Autophagy plays an important role in the development of diabetic cardiomyopathy. Cellular repressor of E1A-stimulated genes 1 (CREG1) is an important myocardial protective factor. The aim of this study was to investigate the effects and mechanisms of CREG1 in diabetic cardiomyopathy. Male C57BL/6 J mice, Creg1 transgenic mice and cardiac-specific knockout mice were used to establish a type 2 diabetes model. Small animal ultrasound, Masson's staining and western blotting were used to evaluate cardiac function, myocardial fibrosis and autophagy. Neonatal mouse cardiomyocytes (NMCMs) were stimulated with palmitate, and the effects of CREG1 on NMCMs autophagy were examined. CREG1 deficiency exacerbated cardiac dysfunction, cardiac hypertrophy and fibrosis in mice with diabetic cardiomyopathy, which was accompanied by exacerbated autophagy dysfunction. CREG1 overexpression improved cardiac function and ameliorated cardiac hypertrophy and fibrosis in diabetic cardiomyopathy by improving autophagy. CREG1 protein expression was decreased in palmitate-induced NMCMs. CREG1 knockdown exacerbated cardiomyocyte hypertrophy and inhibited autophagy. CREG1 overexpression inhibited cardiomyocyte hypertrophy and improved autophagy. LAMP2 overexpression reversed the effect of CREG1 knockdown on palmitate-induced inhibition of cardiomyocyte autophagy. CREG1 inhibited LAMP2 protein degradation by inhibiting the protein expression of F-box protein 27 (FBXO27). Our findings indicate new roles of CREG1 in the development of diabetic cardiomyopathy.

Prevalence of transmissible gastroenteritis among swine populations in China during 1983-2022: A systematic review and meta-analysis.

BACKGROUND: Transmissible gastroenteritis virus (TGEV), which belongs to the coronaviruses (CoVs), causes diarrhea and high mortality rates in piglets and poses a huge threat and loss to the pig industry in China. METHOD: We estimated the prevalence of TGEV in Chinese pig animals from 1983 to 2022 by screening 36 papers on TGEV investigations in China from databases such as China Knowledge Network (CNKI), Wanfang Database, Science and Technology Journal Repository (VIP), PubMed, and ScienceDirect, excluding duplicate literature and other host studies according to the exclusion criteria we developed, and excluding literature with incomplete data to extract information from studies that could estimate the prevalence of TGEV infection in pigs in mainland China. RESULTS: A total of 36 studies (including data from 50,403 pigs) met our evaluation criteria. The overall estimated prevalence of TGEV infection in pigs in China is 10% (3887/50403), and the prevalence of TGEV in northeast China is 38% (2582/3078700) is significantly higher than the rest of China. The prevalence of TGEV infection was related to the sampling season and region. CONCLUSION: The results of the study show that the prevalence of TGEV is clearly seasonal and regional. Therefore, further research and monitoring of the prevalence of TGEV infection and the development of control programs based on different conditions are essential. In addition, effective and robust regulatory measures should be taken in colder regions to prevent the spread and transmission of TGEV in pigs.

Prevalence of clinical mastitis and its associated risk factors among dairy cattle in mainland China during 1982-2022: a systematic review and meta-analysis.

Background: Bovine mastitis is one of the most common and prevalent diseases affecting dairy cattle worldwide. It adversely affects the quality and quantity of milk production and leads to a significant economic loss for the farmers. Methods: This article aimed to estimate the prevalence of clinical mastitis (CM) infection in mainland China using a systematic review and meta-analysis. The research reports published during 1983-2022 in English or Chinese from databases (PubMed, Google Scholar, Cochrane Library, Science Direct, Web of Science, VIP Database for Chinese Technical Periodicals (VIP), Chinese National Knowledge Infrastructure (CNKI), and Wan Fang database) were identified after reviewing the relevant scientific literature. Based on our inclusion criteria, this study analyzed the prevalence of CM in 47 published studies prevalence extracted the total number of cattle infected with CM from the available studies, allowing us to estimate the prevalence of CM infection among these in mainland China. Results: The pooled prevalence with the 95% CI for the clinical mastitis was 10% (95% CI: 9.00, 12.00). The majority of CM was associated with lactation, parity, and age, with higher prevalence observed in late lactation 15% (95% CI: 11.00, 18.00) and mid-lactation 10% (95% CI: 6.00, 13.00) in comparison to early lactation 8% (95% CI: 5.00, 10.00). The incidence of CM increased significantly with the increase of parity and age, and the highest incidence rates were 19% (95% CI: 15.00, 23.00) and 16% (95% CI: 12.00, 19.00) at parity and age ≥7, respectively. Among the seasons, the highest prevalence of CM infection was found in autumn 9% (95% CI: 2.00, 17.00). Interestingly, no significant effects were evident regarding the influence of quarter on the prevalence of CM. Conclusion: Thus, estimating the prevalence of CM among cattle in mainland China. through meta-analysis can provide adequate measures to control CM, reduce economic losses, and prevent the spread and transmission of CM in Chinese herds.

Biodiversity and Interannual Variation of Harmful Algal Bloom Species in the Coastal Sea of Qinhuangdao, China.

For the frequent occurrence of harmful algal blooms (HABs) in the Qinhuangdao coastal sea (QCS) of the Bohai Sea in summer, we tested the hypothesis that high-biodiversity HAB species exist in the area, and a series of censuses of HAB species were conducted in the QCS in the summers of 2014-2019. Through morphological identification, we found 100 algae species representing 42 genera in 3 phytoplankton phyla in this study, among which Bacillariophyta was the most dominant phylum. We also found that the population density of Dinoflagellata increased from 2016 to 2019. In total, 59 HAB species were annotated in this study, including 39 of Bacillariophyta, 18 of Dinoflagellata and 2 of Ochrophyta, of which 13 HAB species were reported in the Bohai Sea for the first time, and most HAB species were widely distributed in the QCS in summer. Notably, four dominant HAB species displayed unique temporal and spatial distribution characteristics, while their distribution ranges and population densities increased from 2014 to 2019. The distributions of five environmental factors were different in the QCS, while the temperature, salinity, and dissolved inorganic nitrogen might be the key environmental factors influencing the distribution of dominant HAB species in the summer. In conclusion, this study provides a detailed evaluation of phytoplankton diversity and interannual variation in the QCS. The existence of a high level of biodiversity of algal bloom species suggests the need for long-term monitoring in order to further study and prevent potential HABs.

Prevalence of bovine rotavirus among cattle in mainland China: A meta-analysis.

BACKGROUND: Bovine rotavirus is the primary pathogen causing diarrhea in cattle and can be transmitted vertically through the placenta. It mainly presents with clinical signs such as depression, loss of appetite, diarrhea, vomiting, and dehydration. METHODS: A systematic review and meta-analysis were conducted to assess the prevalence of BRV infection in mainland China. We conducted a literature search on the prevalence of BRV infection in pigs between Jan 1, 1979 and Dec 31, 2021 in English and Chinese databases, including PubMed, Google Scholar, Cochrane library, Clinical Trials, VIP, CNKI, and WanFang database. Selections were made based on the title and the abstract of the paper, Search strings included if they reported the cattle samples of more than 15 cattle and provided information that allowed us to establish the prevalence of BRV. Moreover, we excluded repeated studies, reviews, other hosts. Finally, we extracted the number of cattle with BRV infection from the obtained studies and provided information that permitted us to estimate the prevalence of BRV infection in cattle in mainland China. RESULTS: The data of 29 articles (including data on 10677 cattle) are compliant with the standards. The pooled prevalence of BRV in cattle in China was 46%（6635/10677）, the pooled prevalence of BRV in cattle from Northeast China (40%) was significantly lower than those from other regions. In addition, the prevalence of BRV was associated with publication time of paper, detection methods, age of cattle, and clinical symptoms（diarrhea, etc.). CONCLUSION: Our findings suggest that BRV infection is common among cattle in China. It is, therefore, necessary to carry out further research and monitor the prevalence of BRV infection. Furthermore, powerful and effective regulatory measures should be taken to prevent the transmission and spread of BRV among cattle populations.

Exposure to BDE-47 and BDE-209 impaired antioxidative defense mechanisms in Brachionus plicatilis.

Polybrominated diphenyl ethers (PBDEs) are persistent organic pollutants (POPs) that pose serious challenges to aquatic animals and environments. Compared with BDE-47 which was one of the most toxic congeners known to date, BDE-209 is less toxic with higher abundance in biotic and abiotic samples. In this study, we have explored the effects of BDE-47 and BDE-209 at different concentrations on the radical oxygen species (ROS) levels and the antioxidant defense system of Brachionus plicatilis. Antioxidant indexes were measured, including total protein content (TSP), the activities of antioxidant enzymes, lipid peroxidation and DNA damage. The results indicated that while low concentrations of PBDEs could activate the antioxidant defense mechanisms, prolonged exposure to higher concentrations of PBDEs could impair the antioxidative capacity of B.plicatilis (P < 0.05). The overwhelming of the B.plicatilis antioxidant defense mechanism led to an accumulation of free radicals, resulting in the overactivation of lipid peroxidation and the increased frequency of DNA damage (P < 0.05). By studying the toxicity of PBDEs and the detoxification mechanism of B.plicatilis, our research has revealed useful indexes for detecting and monitoring the level of BDE-47 and BDE-209 in the future. Altogether, this study holds immense value in the field of ecotoxicology and environmental safety and will aid in the proper management of PBDEs pollution.

Prevalence of subclinical mastitis among dairy cattle and associated risks factors in China during 2012-2021: A systematic review and meta-analysis.

Bovine mastitis, especially subclinical mastitis (SCM), is one of the most prevalent and economically costly diseases in the dairy industry worldwide. Understanding the prevalence and spatial distribution of bovine SCM and its associated risk factors will facilitate the prevention and control of the disease. We reviewed published studies pertaining to epidemiological surveys of SCM among dairy cows during the past decade (2012-2021) in China from inception to March 20, 2020, with PubMed, Clinical Trial, VIP, CNKI and databases being used to identify English and Chinese articles. Therefore, we retrieved 41 studies related to epidemiological surveys of SCM among dairy cows, using our eligibility criteria. We demonstrated that the prevalence of SCM in dairy cows was 37.7% during the selected periods, indicating a slight increase in the incidence of SCM in a comparison between 2012 and 2016 and 2017-2021. The estimated prevalence of SCM was 36.4%-50.2% in the seven regions, which was no statistically significant difference. The highest prevalence of SCM was 72% in Inner Mongolia Autonomous Region, and the lowest prevalence was 19% in Hubei Province. The variation in diagnostic methods was not significant in the studies. Dairy cows' parity was a risk factor associated with the prevalence rate of SCM. Cow's age might affect the prevalence of SCM during the selected periods. This study may facilitate the control with specific strategies to reduce costs and antibiotics overuse, enhance food safety and public health.

Systemic mucormycosis caused by Rhizopus microsporus in a captive bottlenose dolphin.

A 6-year-old female bottlenose dolphin (Tursiops truncatus) kept in dolphinarium died after a 3.5-month period of lethargy and inappetence despite antibiotics and supportive care. At necropsy, gross findings included diffuse varying-sized nodules in the lungs and scattered nodules throughout the heart, spleen, mesenteric and hilar lymph node and kidney. Microscopically, the lesions were characterised by disseminated fungal pyogranulomas with numerous intralesional Mucor-like fungi. The fungi structures were demonstrated by Periodic acid-Schiff and Gomori methenamine silver stain. Molecular analyses of the fungi were Rhizopus microsporus by PCR sequencing 18S ribosomal RNA gene. Ziehl-Neelsen stain failed to show acid-fast bacterial infection. Based on pathological and molecular examination, systemic granulomatous mucormycosis was diagnosed. To our knowledge, this is the first reported case of systemic mucormycosis caused by Rhizopus microsporus in bottlenose dolphin.

Seroprevalence of influenza A (H9N2) virus infection among humans in China: A meta-analysis.

Herein, we conducted a meta-analysis aimed at comprehensively assessing avian influenza A (H9N2) virus infection seroprevalence and infection-related risk factors among humans in China. We reviewed published studies pertaining to H9N2 seroprevalence of in China from inception to March 20, 2020, with PubMed, Clinical Trial, VIP, CNKI and databases being used to identify English and Chinese articles. After excluding the incomplete literature and data, 45 studies about risk factor of human H9N2 viral infections in China were analyzed by systematic review and meta-analysis. Our results showed that 45 studies (59,590 total patients) met the inclusion criteria. Overall H9N2 infection seroprevalence in China was estimated to be 5.56% (95%CI = 3.88-7.28), while that from central China the seroprevalence was 22.72% (95%CI = 12.18-33.84), with this prevalence being greater than that observed in other regions. H9N2 infection seroprevalence was related to sampling time, testing methodology, gender, and other demographic factors. This review will provide a basis for further understanding the risk factors of H9N2 infections in China, and it is necessary to study how to formulate strict and targeted measures to prevent the spread of the virus.

Maternal transfer of antibodies specific for avian influenza viruses in captive whooper swans (Cygnus cygnus).

The transfer of maternal antibodies to offspring can effectively protect against avian influenza virus (AIV) infection during early life in chickens and can prevent AIV spread by decreasing the overall percentage of the avian population susceptible to this pathogen. Herein, we evaluated maternal antibody transfer dynamics in whooper swans (Cygnus cygnus), which represent an important AIV host species. In total, 57 eggs from 19 nests were collected to study the relationship between egg yolk AIV-specific antibody concentrations and factors including egg size, laying order, maternal serum AIV antibody titer, and maternal body condition. Overall, we found that AIV-specific antibodies were present in the serum of 63.2 % of surveyed female swans and were transferred to 50.8 % of analyzed eggs. We found maternal AIV-specific antibody concentration and body weight to be positively correlated with egg yolk AIV antibody concentration, whereas egg laying order was negatively correlated with yolk antibody titer. Overall, these findings maternal transfer of AIV-specific antibodies may function as a key mechanism governing the dynamics of AIV infection in swan populations.

The role of TGF-ß1/Smad3 signaling pathway and oxidative stress in the inhibition of osteoblast mineralization by copper chloride.

To explore the relationship of oxidative stress and TGF-ß 1/Smad3 pathway in the inhibition of osteoblast mineralization by copper chloride (CuCl2), the osteoblasts were treated with CuCl2 (0, 50 µM, 100 µM, 150 µM CuCl2 5H2O) for 24 h. We found that Cu impaired the osteoblast structure, inhibited the glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activities, alkaline phosphatase (ALP) content, mRNA expression of collagen I (COL-I), osteocalcin (OCN), insulin-like growth factor I (IGF-I), bone morphogenetic protein-2 (BMP-2), transforming growth factor ß1 (TGF-ß1) and core-binding factor α1 (Cbfα1), promoted the reactive oxygen species (ROS) production, inactivated the TGF-ß1/Smad3 pathway. It indicates that the inactivated TGF-ß1/Smad3 pathway leads to osteoblast impairment by CuCl2. It will contribute to clarify the influence of CuCl2 on the osteoblast mineralization.

Molecular detection and genotyping of bovine viral diarrhea virus in Western China.

BACKGROUND: Bovine viral diarrhea virus (BVDV) is an important global viral pathogen of cattle and other ruminants. To survey the infection rate and genetic diversity of BVDV in western China, a total of 1234 serum samples from 17 herds of dairy cattle, beef cattle and yak in 4 provinces were collected in 2019. RESULTS: All the 1234 serum samples were screened individually for BVDV by RT-PCR. Our results demonstrated that the average positive rate of BVDV was 7.2% (89/1234) in animals and 82.4% (14/17) in herds. Thirteen BVDV strains were isolated from RT-PCR positive clinical samples and they were all NCP biotype. BVDV-1a and 1c subgenotypes were identified from 22 selected virus isolates in 14 BVDV-positive herds. These results confirmed that BVDV-1a and BVDV-1c were circulating in western China, similar to the BVDV epidemics in cattle in other regions of China. CONCLUSIONS: This study provides data for monitoring and vaccination strategies of BVDV in western China.

Technical note: Development of a closed-tube isothermal multiple self-matching-initiated amplification assay for visual detection of Staphylococcus aureus in milk samples.

Staphylococcus aureus is one of the most common mastitis-causing bacteria in dairy cows. It is associated with reduced production performance in animals and with huge financial losses for the dairy industry worldwide. An accurate and sensitive method for the early diagnosis and identification of Staph. aureus in milk samples is essential. The present study aimed to establish a closed-tube isothermal multiple self-matching-initiated amplification (IMSA) technique for visual confirmation of the presence of Staph. aureus targeting the nuc conserved sequence gene. The specific primers successfully amplified the target sequence within 45 min at 63°C reaction temperature and using the optimal components of the reaction system. The positive amplicon showed bright green fluorescence under UV light when mixed with the chromogenic substrate SYBR Green I, and the negative samples remained orange in color. We observed fluorescence and a ladder-like pattern in the IMSA amplicon for all Staph. aureus strains, and we observed no significant change for the non-Staph. aureus strains. The IMSA assay had high specificity compared with loop-mediated isothermal amplification (LAMP): it confirmed the presence of all 7 Staph. aureus strains, and we found no false-positive results for the 12 non-Staph. aureus strains. The lower limit of detection for the IMSA assay was 1 × 102 cfu/mL, 10-fold more sensitive than the results obtained using LAMP. We also successfully applied the IMSA assay to confirm the presence of Staph. aureus in milk samples of cows with mastitis, and the results were consistent with those of LAMP and real-time PCR. The present study reports the use of IMSA to confirm the presence of Staph. aureus and provides a potentially useful method for rapid preliminary screening for Staph. aureus.

Surveillance of multiple subtype specific antibodies against avian influenza viruses among egg yolk in wild ducks from northeast China, 2017-2019.

Over the past decade, various avian influenza viruses have been isolated from wild ducks found in the northeast of China. To monitor the prevalence of multiple subtype specific AIVs antibodies, 1705 wild ducks' eggs from six wetlands of northeast China were analyzed for surveillance of H1, H3, H5, and H7 AIVs antibodies by c-ELISA and HI test from Jan 2017 to Dec 2019. The results show that the combined frequency of multiple subtype specific AIVs antibodies were H1 (12.32%), H3 (8.15%), H5 (2.05%), and H7 (3.46%) respectively. Therefore, a detailed analysis of the geographical distribution of AIVs in China, and the risk factors for human infection is of vital importance. This study provides basic data for other researchers to deeply study AIVs distribution characteristics, and for governments to develop detailed measures to control the spread of AIVs.

Allele combinations of maturity genes E1-E4 affect adaptation of soybean to diverse geographic regions and farming systems in China.

Appropriate flowering and maturity time are important for soybean production. Four maturity genes E1, E2, E3 and E4 have been molecularly identified and found to play major roles in the control of flowering and maturity of soybean. Here, to further investigate the effect of different allele combinations of E1-E4, we performed Kompetitive Allele Specific PCR (KASP) assays based on single nucleotide polymorphisms (SNPs) at these four E loci, and genotyped E1-E4 genes across 308 Chinese cultivars with a wide range of maturity groups. In total, twenty-one allele combinations for E1-E4 genes were identified across these Chinese cultivars. Various combinations of mutations at four E loci gave rise to the diversity of flowering and maturity time, which were associated with the adaptation of soybean cultivars to diverse geographic regions and farming systems. In particular, the cultivars with mutations at all four E loci reached flowering and maturity very early, and adapted to high-latitude cold regions. The allele combinations e1-as/e2-ns/e3-tr/E4, E1/e2-ns/E3/E4 and E1/E2/E3/E4 played important roles in the Northeast China, Huang-Huai-Hai (HHH) Rivers Valley and South China regions, respectively. Notably, E1 and E2, especially E2, affected flowering and maturity time of soybean significantly. Our study will be beneficial for germplasm evaluation, cultivar improvement and regionalization of cultivation in soybean production.

C1188D mutation abolishes specific recognition between MLL1-CXXC domain and CpG site by inducing conformational switch of flexible N-terminal.

Mixed lineage leukemia protein (MLL1 protein) recognizes the CpG site via its CXXC domain and is frequently associated with leukemia. The specific recognition is abolished by C1188D mutation, which also prevents MLL-related leukemia. In this paper, multiple molecular dynamic (MD) simulations were performed to investigate the mechanism of recognition and influences of C1188D mutation. Started from fully dissociated DNA and MLL1-CXXC domain, remarkably, the center of mass (COM) of MLL1-CXXC domain quickly concentrates on the vicinity of the CpG site in all 53 short MD simulations. Extended simulations of the wild type showed that the native complex formed in 500 ns among 4 of 53 simulations. In contrast, the C1188D mutant COM distributed broadly around the DNA and the native complex was not observed in any of the extended simulations. Simulations on the apo MLL1-CXXC domain further suggest that the wild type protein remained predominantly in an open form that closely resembles its structure in the native complex whereas C1188D mutant formed predominantly compact structures in which the N- terminal bends to D1188. This conformational switch hinders the formation of encounter complex, thus abolishes the recognition. Our study also provides clues to the study mechanism of recognition, by the CXXC domain from proteins like DNA methyltransferase and ten-eleven translocation enzymes.

Establishment and application of isothermal amplification techniques for the detection of heat-stable I enterotoxin of enterotoxigenic Escherichia coli.

The aim of this study was to establish isothermal multiple self-matching initiated amplification (IMSA) and cross-priming amplification (CPA) methods to detect heat-stable I enterotoxin (STa)-producing enterotoxigenic Escherichia coli (ETEC). To avoid cross-contamination of aerosols, a closed independent isothermal amplification tube (IAT) was used to perform the assays. Optimal amplification conditions for IMSA and CPA were selected for specificity and sensitivity, respectively, and for clinical relevance. Both IMSA and CPA assays could specifically recognize all 3-STa positive strains in which they fluoresced green under UV light, but not in the 11 non-STa strains. The results of the sensitivity analysis indicated that the detection limit of the IMSA assay was 1.5 ×102 CFU, comparable to real-time PCR, but 10-fold more sensitive than CPA and LAMP. Further evaluation of the detection methods of swine diarrhea samples demonstrated that both could successfully identify the DNA of STa-producing ETEC in clinical specimens, consistent with LAMP and qPCR methods. The results demonstrated that the IMSA and CPA methods had high specificity and sensitivity with rapid detection of ETEC, so having great potential in clinical applications.

Seroprevalence of highly pathogenic avian influenza (H5N1) virus infection among humans in mainland China: A systematic review and meta-analysis.

Although the effective transmission of the H5N1 virus from humans to humans has yet to be further observed, humans are at increased risk of a pandemic caused by H5N1. In order to fully evaluate the seroprevalence and risk factor of highly pathogenic avian influenza A (H5N1) virus infection among in mainland China, we performed a systematic review and meta-analysis. In this review, we searched literature on the seroprevalence of H5N1 infection among humans in mainland China from 1 January 1997 to 20 October 2018 in English and Chinese databases, including PubMed, Google scholar, Cochrane library, Clinical Trial, VIP, CNKI and WanFang database. We made a selection according to the title and the abstract of paper, and then, we excluded duplicated literature, and data incomplete literature according to the exclusion criteria we formulated. Finally, we extracted how many humans have H5N1 infection from the obtained studies to establish the seroprevalence of H5N1 infection among humans in mainland China. A total of 56 studies (including data of 35,159 humans) were compliant with our criteria. In China, the overall seroprevalence of H5N1 infection among humans was 2.45% (862/35,159), while the seroprevalence of H5N1 infection among humans from central China was 7.32% (213/2,911), higher than those in other regions of China. The seroprevalence of H5N1 infection was associated with test method, sampling time and demographic characteristics of humans. However, there was no significant difference in the effect of gender on the seroprevalence of H5N1 among humans in China. The purpose of this review was to better understand the real infection rate of H5N1 virus among humans and evaluate the potential risk factors for the zoonotic spread of H5N1 virus to humans. Sufficient epidemiological data are important to explore and understand the prevalent status of AIVs throughout the country and to disease control.

Low-dose nicotine promotes autophagy of cardiomyocytes by upregulating HO-1 expression.

Nicotine as a major component of addiction in cigarettes has been reported to play protective roles in some pathological processes. It is reported that activation of the nicotinic acetylcholine receptor also has a cardioprotective effect. Thus, in our study, we investigated the effect and mechanism of nicotine on the autophagy of cardiomyocytes, and whether nicotine protects cardiomyocytes against palmitic acid (PA) injury. The results indicated that low-dose nicotine promoted neonatal mouse cardiac myocytes (NMCMs) autophagy and accelerated autophagic flux while inhibiting NMCMs apoptosis, but high-dose nicotine inhibited autophagy and promoted apoptosis. Moreover, low-dose nicotine upregulated heme oxygenase-1 (HO-1) expression and knocking down HO-1 abolished the effects of nicotine on the autophagy and apoptosis of NMCMs. Methyllycaconitine citrate (α7-nAChR blocker, MLA) inhibited HO-1 expression and the effects of nicotine on autophagy and apoptosis of NMCMs. Furthermore, low-dose nicotine improved the inhibited autophagy and increased apoptosis induced by palmitic acid (PA) in NMCMs and these effects were reversed by knocking down HO-1. In conclusion, our data suggested that low-dose nicotine promoted autophagy and inhibited apoptosis of cardiomyocytes by upregulating HO-1.