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Abstract N1-methyladenosine (m1A) is a post-transcriptionally modified RNA molecule that plays a pivotal role in the regulation of various biological functions and activities. Especially in cancer cell invasion, proliferation and cell cycle regulation. Over recent years, there has been a burgeoning interest in investigating the m1A modification of RNA. Most studies have focused on the regulation of m1A in cancer enrichment areas and different regions. This review provides a comprehensive overview of the methodologies employed for the detection of m1A modification. Furthermore, this review delves into the key players in m1A modification, known as the “writers,” “erasers,” and “readers.” m1A modification is modified by the m1A methyltransferases, or writers, such as TRMT6, TRMT61A, TRMT61B, TRMT10C, NML, and, removed by the demethylases, or erasers, including FTO and ALKBH1, ALKBH3. It is recognized by m1A-binding proteins YTHDF1, TYHDF2, TYHDF3, and TYHDC1, also known as “readers”. Additionally, we explore the intricate relationship between m1A modification and its regulators and their implications for the development and progression of specific types of cancer, we discuss how m1A modification can potentially facilitate the discovery of novel approaches for cancer diagnosis, treatment, and prognosis. Our summary of m1A methylated adenosine modification detection methods and regulatory mechanisms in various cancers provides useful insights for cancer diagnosis, treatment, and prognosis. Video Abstract

Abstract N4-acetylcytidine (ac4C) is a highly conserved chemical modification widely found in eukaryotic and prokaryotic RNA, such as tRNA, rRNA, and mRNA. This modification is significantly associated with various human diseases, especially cancer, and its formation depends on the catalytic activity of N-acetyltransferase 10 (NAT10), the only known protein that produces ac4C. This review discusses the detection techniques and regulatory mechanisms of ac4C and summarizes ac4C correlation with tumor occurrence, development, prognosis, and drug therapy. It also comments on a new biomarker for early tumor diagnosis and prognosis prediction and a new target for tumor therapy. Video Abstract

ABSTRACTEmerging mobile colistin resistance (mcr) genes pose a significant threat to public health for colistin was used as the last resort to treat multidrug-resistant (MDR) pathogenic bacterial infections. Hypervirulent Klebsiella pneumoniae (hvKP) is a clinically significant pathogen resulting in highly invasive infections, often complicated by devastating dissemination. Worryingly, the untreatable and severe infections caused by mcr-harbouring hvKP leave the selection of antibiotics for clinical anti-infective treatment in a dilemma. Herein, we screened 3,461 isolates from a tertiary teaching hospital from November 2018 to March 2021, and an mcr-8.2-harbouring hvKP FAHZZU2591 with a conjugative plasmid was identified from paediatric sepsis. This is the first report of MCR-8-producing hvKP from paediatric sepsis to our best knowledge. The susceptibility, genetic features, and plasmid profiles of the isolate were investigated. Further, we assessed the virulence potential of FAHZZU2591 and verified its pathogenicity and invasive capacity using a mouse model. The phylogenetic analysis of mcr-8-bearing K. pneumoniae revealed that China is the predominant reservoir of the mcr-8 gene, and the clinic is the primary source. Our work highlights the risk for the spread of mcr-positive hvKP in clinical, especially in paediatric sepsis, and the persistent surveillance of colistin-resistance hvKP is urgent.

Abstract Objective To study the risk factors and prediction models of multidrug resistance in patients with tuberculosis and diabetes and those with a history of tuberculosis treatment. Methods A total of 256 tuberculosis patients with diabetes who were registered in Luoyang city, Henan Province, from January 2018 to December 2021. Logistic regression analysis was performed to analyse the risk factors for multidrug resistance. ROC curves were used to analyse the predictive model for multidrug resistance. Results Age

The emergence of carbapenemase significantly threatens public health. It is prevalent worldwide but rare in Aeromonas caviae. Unlike most bacterial species, A. caviae has two distinct flagella systems, which are closely related to biofilm formation. The ability to form biofilms on host tissues or inert surfaces constitutes an important cause of many persistent infections, which causes difficulties in clinical treatment. Here, we report on a multidrug-resistant (MDR) A. caviae carrying blaNDM–1 with a novel sequence type 1,416. The strong ability of biofilm formation of FAHZZU2447 was verified by a crystal violet assay. The resistome profile and location of the blaNDM–1 gene were determined by antimicrobial susceptibility testing, S1 nuclease pulsed-field gel electrophoresis (S1-PFGE), and Southern blot analysis. Moreover, the strain underwent whole-genome sequencing to identify its genomic characteristics. In addition, the blaNDM–1 gene was located on a ∼243 kb plasmid with genetic context IS1R-blaNDM–1-ble-trpF-dsbD-hp-sul1-qacE. Phylogenetic analysis indicated the transmission of A. caviae in China, Japan, and Thailand. Our study aimed to elucidate the genomic features of blaNDM–1-producing A. caviae, thereby clarifying the distribution of A. caviae worldwide and emphasizing the harmfulness of biofilm formation to the clinic. Further comprehensive surveillance of this species is needed to control further dissemination.

The worldwide spread of carbapenem-resistant Enterobacteriaceae (CRE) has led to a major challenge to human health. In this case, colistin is often used to treat the infection caused by CRE. However, the coexistence of genes conferring resistance to carbapenem and colistin is of great concern. In this work, we reported the coexistence of blaOXA-181, blaCTX-M-55, and mcr-8 in an ST273 Klebsiella pneumoniae isolate for the first time. The species identification was performed using MALDI-TOF MS, and the presence of various antimicrobial resistance genes (ARGs) and virulence genes were detected by PCR and whole-genome sequencing. Antimicrobial susceptibility testing showed that K. pneumoniae 5589 was resistant to aztreonam, imipenem, meropenem, ceftriaxone, cefotaxime, ceftazidime, levofloxacin, ciprofloxacin, gentamicin, piperacillin-tazobactam, cefepime, and polymyxin B, but sensitive to amikacin. S1-pulsed-field gel electrophoresis (PFGE) and Southern blotting revealed the mcr-8 gene was carried on a ~ 138 kb plasmid with a conserved structure (IS903B-ymoA-inhA-mcr-8-copR-baeS-dgkA-ampC). In addition, blaOXA-181 was found on another ~51 kb plasmid with a composite transposon flanked by insertion sequence IS26. The in vitro conjugation experiments and plasmid sequence probe indicated that the plasmid p5589-OXA-181 and the p5589-mcr-8 were conjugative, which may contribute to the propagation of ARGs. Relevant detection and investigation measures should be taken to control the prevalence of pathogens coharboring blaOXA-181, blaCTX-M-55 and mcr-8.

Mobile colistin resistance (mcr) genes represent an emerging threat to public health. Reports on the prevalence, antimicrobial profiles, and clonality of MCR-9-producing Enterobacter cloacae complex (ECC) isolates on a national scale in China are limited. We screened 3,373 samples from humans, animals, and the environment and identified eleven MCR-9-positive ECC isolates. We further investigated their susceptibility, epidemiology, plasmid profiles, genetic features, and virulence potential. Ten strains were isolated from severe bloodstream infection cases, especially three of them were recovered from neonatal sepsis. Enterobacter hormaechei was the most predominant species among the MCR-9-producing ECC population. Moreover, the co-existence of MCR-9, CTX-M, and SHV-12 encoding genes in MCR-9-positive isolates was globally observed. Notably, mcr-9 was mainly carried by IncHI2 plasmids, and we found a novel ~187 kb IncFII plasmid harboring mcr-9, with low similarity with known plasmids. In summary, our study presented genomic insights into genetic characteristics of MCR-9-producing ECC isolates retrieved from human, animal, and environment samples with one health perspective. This study is the first to reveal NDM-1- and MCR-9-co-producing ECC from neonatal sepsis in China. Our data highlights the risk for the hidden spread of the mcr-9 colistin resistance gene.

Plant height is an important indicator in the ideal plant model and contributes to optimizing yield and lodging resistance. The emergence of a dwarfing phenotype provides an opportunity for plant height improvement. In a previous study, we identified a dwarf mutant Si1 in pumpkin (Cucurbita moschata D.) obtained by ethyl methane sulfonate (EMS) mutagenesis of the inbred line N87. Phenotype identification for Si1 revealed a decrease in cell size and shorter internodes than those of wild type. Genetic analysis revealed that the dwarf mutant trait was controlled by a single recessive gene, CmaSI1. By bulked segregant analysis (BSA) and subsequent fine mapping, we mapped the CmaSI1 locus to a 463 kb region on chromosome 8 that contained 28 annotated genes in the F2 population. Only one nonsynonymous single nucleotide polymorphism (SNP) in CmoCh08G006170 was obtained according to whole-genome resequencing of the two parents. CmoCh08G006170, a homolog of Arabidopsis gibberellin 3-beta hydroxylase (GA3ox), is a key enzyme in the regulation of bioactive gibberellins (GAs). RNA-seq analysis and qRT-PCR showed that the expression level of CmoCh08G006170 in stems of Si1 was changed compared with that of wild type. The dwarf phenotype could be restored by exogenous GA3 treatment, suggesting that Si1 is a GA-deficient mutant. The above results demonstrated that CmoCh08G006170 may be the candidate gene controlling the dwarf phenotype. This study provides an important theoretical basis for the genetic regulation of vine length and crop breeding in pumpkin.

Abstract Reduced graphene oxide/SiO2 (RGO/SiO2) serving as a novel spherical support for Ziegler-Natta (Z-N) catalyst is reported. The surface and interior of the support has a porous architecture formed by RGO/SiO2 sandwich structure. The sandwich structure is like a brick wall coated with a graphene layer of concreted as skeleton which could withstand external pressures and endow the structure with higher support stabilities. After loading the Z-N catalyst, the active components anchor on the surface and internal pores of the supports. When the ethylene molecules meet the active centers, the molecular chains grow from the surface and internal catalytic sites in a regular and well-organized way. And the process of the nascent molecular chains filled in the sandwich structure polymerization could ensure the graphene disperse uniformly in the polymer matrix. Compared with traditional methods, the porous spherical graphene support of this strategy has far more advantages and could maintain an intrinsic graphene performance in the nanocomposites.

Abstract The gut microbiota is altered in liver diseases, and several probiotics have been shown to reduce the degree of liver damage. We hypothesized that oral administration of specific Bifidobacterium strains isolated from healthy guts could attenuate liver injury. Five strains were tested in this study. Acute liver injury was induced by D-galactosamine after pretreating Sprague-Dawley rats with the Bifidobacterium strains, and liver function, liver and ileum histology, plasma cytokines, bacterial translocation and the gut microbiome were assessed. Two strains, Bifidobacterium pseudocatenulatum LI09 and Bifidobacterium catenulatum LI10, conferred liver protection, as well as alleviated the increase in plasma M-CSF, MIP-1α and MCP-1 and bacterial translocation. They also ameliorated ileal mucosal injury and gut flora dysbiosis, especially the enrichment of the opportunistic pathogen Parasutterella and the depletion of the SCFA-producing bacteria Anaerostipes, Coprococcus and Clostridium XI. Negative correlations were found between MIP-1α / MCP-1 and Odoribacter (LI09 group) and MIP-1α / M-CSF and Flavonifractor (LI10 group). Our results indicate that the liver protection effects might be mediated through gut microbiota modification, which thus affect the host immune profile. The desirable characteristics of these two strains may enable them to serve as potential probiotics for the prevention or adjuvant treatment of liver injury.

Abstract Alterations in the gut microbiome have been reported in liver cirrhosis, and probiotic interventions are considered a potential treatment strategy. This study aimed to evaluate the effects and mechanisms of Lactobacillus salivarius LI01, Pediococcus pentosaceus LI05, Lactobacillus rhamnosus GG, Clostridium butyricum MIYAIRI and Bacillus licheniformis Zhengchangsheng on CCl4-induced cirrhotic rats. Only administration of LI01 or LI05 prevented liver fibrosis and down-regulated the hepatic expression of profibrogenic genes. Serum endotoxins, bacterial translocations (BTs), and destruction of intestinal mucosal ultrastructure were reduced in rats treated with LI01 or LI05, indicating maintenance of the gut barrier as a mechanism; this was further confirmed by the reduction of not only hepatic inflammatory cytokines, such as TNF-α, IL-6, and IL-17A, but also hepatic TLR2, TLR4, TLR5 and TLR9. Metagenomic sequencing of 16S rRNA gene showed an increase in potential beneficial bacteria, such as Elusimicrobium and Prevotella, and a decrease in pathogenic bacteria, such as Escherichia. These alterations in gut microbiome were correlated with profibrogenic genes, gut barrier markers and inflammatory cytokines. In conclusion, L. salivarius LI01 and P. pentosaceus LI05 attenuated liver fibrosis by protecting the intestinal barrier and promoting microbiome health. These results suggest novel strategies for the prevention of liver cirrhosis.

The dissemination of Klebsiella pneumoniae carbapenemases (KPCs) among Gram-negative bacteria is an important threat to global health. However, KPC-producing bacteria from environmental samples are rarely reported. This study aimed to elucidate the underlying resistance mechanisms of three carbapenem-resistant Aeromonas taiwanensis isolates recovered from river sediment samples. Pulsed-field gel electrophoresis (PFGE) and whole genome sequencing (WGS) analysis indicated a close evolutionary relationship among A. taiwanensis isolates. S1-PFGE, Southern blot and conjugation assays confirmed the presence of blaKPC–2 and qnrS2 genes on a non-conjugative plasmid in these isolates. Plasmid analysis further showed that pKPC-1713 is an IncP-6 plasmid with a length of 53,205 bp, which can be transformed into DH5α strain and mediated carbapenems and quinolones resistance. The plasmid backbone of p1713-KPC demonstrated 99% sequence identity to that of IncP-6-type plasmid pKPC-cd17 from Aeromonas spp. and IncP-6-type plasmid: 1 from Citrobacter freundii at 74% coverage. A 14,808 bp insertion sequence was observed between merT gene and hypothetical protein in p1713-KPC, which include the quinolone resistance qnrS2 gene. Emergence of plasmid-borned blaKPC and qnrS2 genes from A. taiwanensis isolates highlights their possible dissemination into the environment. Therefore, potential detection of such plasmids from clinical isolates should be closely monitored.

A novel avian-origin influenza A (H7N9) virus emerged and spread among humans in Eastern China in 2013. Prophylactic treatment with antibiotics and probiotics for secondary infection is as important as antiviral treatment. This study aims to assess the ability of probiotic treatment to restore internal homeostasis under antibiotic pressure and to reduce/ameliorate the risk of secondary infections resulting from infection with the H7N9 virus.This is a retrospective study in archival samples. Between April 1 and May 10, 2013, 113 stool, sputum, and blood specimens were collected and analyzed by denaturing gradient gel electrophoresis (DGGE) to determine the composition of the patient microbiomes. Microbial diversity was calculated using Gel-Pro analyzer and Past software. Cluster analysis of DGGE pattern profiles was employed to create a phylogenetic tree for each patient, and multidimensional scaling (MDS) and principal component analysis (PCA) were performed to visualize relationships between individual lanes.Five patients had secondary infections, including Klebsiella pneumonia, Acinetobacter baumanii and Candida albicans infection. The DGGE profiles of fecal samples obtained at different time points from the same individual were clearly different, particularly for patients with secondary infections. Shannon's diversity index and evenness index were lower in all infected groups compared to the control group. After B. subtilis and E. faecium or C. butyricum administration, the fecal bacterial profiles of patients who had not been treated with antibiotics displayed a trend of increasing diversity and evenness. C. butyricum failed to reduce/ameliorate secondary infection in H7N9-infected patients, but administration of B. subtilis and E. faecium appeared to reduce/ameliorate secondary infection in one patient.H7N9 infection might decrease intestinal microbial diversity and species richness in humans. C. butyricum failed to reduce/ameliorate secondary infection in H7N9-infected patients. B. subtilis and E. faecium may also play a role in reducing/ameliorating secondary infection in these patients.

Chrysomya megacephala (Fabricius), a prevalent necrophagous blowfly that is easily mass reared, is noted for being a mechanical vector of pathogenic microorganisms, a pollinator of numerous crops, and a resource insect in forensic investigation in the postmortem interval. In the present study, in order to comprehensively understand the physiological and biochemical functions of C. megacephala, we performed RNA-sequencing and digital gene expression (DGE) profiling using Solexa/Illumina sequencing technology.A total of 39,098,662 clean reads were assembled into 27,588 unigenes with a mean length of 768 nt. All unigenes were searched against the Nt database, Nr database, Swiss-Prot, Cluster of Orthologous Groups (COG) and Kyoto Encyclopedia of Genes and Genome (KEGG) with the BLASTn or BLASTx algorithm (E-value

Abstract To describe the fetal death rate of birth defects (including a broad range of specific defects) and to explore the relationship between fetal deaths from birth defects and a broad range of demographic characteristics. Data was derived from the birth defects surveillance system in Hunan Province, China, 2016–2020. Fetal death refers to the intrauterine death of a fetus at any time during the pregnancy, including medical termination of pregnancy. Fetal death rate is the number of fetal deaths per 100 births (including live births and fetal deaths) in a specified group (unit: %). The fetal death rate of birth defects with 95% confidence intervals (CI) was calculated by the log-binomial method. Crude odds ratios (ORs) were calculated to examine the relationship between each demographic characteristic and fetal deaths from birth defects. This study included 847,755 births, and 23,420 birth defects were identified. A total of 11,955 fetal deaths from birth defects were identified, with a fetal death rate of 51.05% (95% CI 50.13–51.96). 15.78% (1887 cases) of fetal deaths from birth defects were at a gestational age of

ObjectiveBirth defect of any type is undesirable and often pose a negative impact on the health and development of the newborn. Birth defects surveillance with datasets from surveillance health-related programs are useful to predict the pattern of birth defects and take preventive measures. In this study, the total prevalence, perinatal prevalence, and livebirth prevalence of birth defects were compared.MethodsData were obtained from the Birth Defects Surveillance System in Hunan Province, China, 2016–2020. The total prevalence is the number of birth defects (including livebirths, stillbirths, and selective terminations of pregnancy) per 1,000 births (including livebirths and stillbirths). The perinatal prevalence is the number of birth defects (between 28 weeks gestation and 7 days postpartum) per 1,000 births. The livebirth prevalence is the number of liveborn birth defects per 1,000 births (unit: ‰). Underestimated proportion (unit: %) is the reduction level of perinatal prevalence or livebirth prevalence compared to the total prevalence. Prevalence with 95% confidence intervals (CI) was calculated using the log-binomial method. Chi-square tests (χ2) were used to examine if significant differences existed in prevalence or underestimated proportion between different groups.ResultsA total of 847,755 births were included in this study, and 23,420 birth defects were identified, including 14,459 (61.74%) birth defects with gestational age > =28 weeks, and 11,465 (48.95%) birth defects in livebirths. The total prevalence, perinatal prevalence, and livebirth prevalence of birth defects were 27.63‰ (95%CI, 27.27–27.98), 17.06‰ (95%CI, 16.78–17.33), and 13.52‰ (95%CI, 13.28–13.77), respectively, and significant differences existed between them (χ2 = 4798.55, p 0.05).ConclusionThe total prevalence and livebirth prevalence of birth defects in Hunan Province, China, was not well studied. A systematic study was conducted to compare the total prevalence, perinatal prevalence, and livebirth prevalence of birth defects. The study reveals that significant differences existed between the total prevalence, perinatal prevalence, and livebirth prevalence of birth defects (including many specific defects), and year, sex, residence, and maternal age had significant impacts on it. The outcomes of the study will help to take preventive measures for birth defects as well as benefit the people involving public health and policymakers to improve the current scenario.

Abstract Objective To explore risk factors for birth defects (including a broad range of specific defects). Methods Data were derived from the Population-based Birth Defects Surveillance System in Hunan Province, China, 2014–2020. The surveillance population included all live births, stillbirths, infant deaths, and legal termination of pregnancy between 28 weeks gestation and 42 days postpartum. The prevalence of birth defects (number of birth defects per 1000 infants) and its 95% confidence interval (CI) were calculated. Multivariate logistic regression analysis (method: Forward, Wald, α = 0.05) and adjusted odds ratios (ORs) were used to identify risk factors for birth defects. We used the presence or absence of birth defects (or specific defects) as the dependent variable, and eight variables (sex, residence, number of births, paternal age, maternal age, number of pregnancies, parity, and maternal household registration) were entered as independent variables in multivariate logistic regression analysis. Results Our study included 143,118 infants, and 2984 birth defects were identified, with a prevalence of 20.85% (95%CI: 20.10–21.60). Multivariate logistic regression analyses showed that seven variables (except for parity) were associated with birth defects (or specific defects). There were five factors associated with the overall birth defects. The risk factors included males (OR = 1.49, 95%CI: 1.39–1.61), multiple births (OR = 1.44, 95%CI: 1.18–1.76), paternal age = 35 (OR = 1.56, 95%CI: 1.33–1.81), and maternal non-local household registration (OR = 2.96, 95%CI: 2.39–3.67). Some factors were associated with the specific defects. Males were risk factors for congenital metabolic disorders (OR = 3.86, 95%CI: 3.15–4.72), congenital limb defects (OR = 1.34, 95%CI: 1.14–1.58), and congenital kidney and urinary defects (OR = 2.35, 95%CI: 1.65–3.34). Rural areas were risk factors for congenital metabolic disorders (OR = 1.21, 95%CI: 1.01–1.44). Multiple births were risk factors for congenital heart defects (OR = 2.09, 95%CI: 1.55–2.82), congenital kidney and urinary defects (OR = 2.14, 95%CI: 1.05–4.37), and cleft lip and/or palate (OR = 2.85, 95%CI: 1.32–6.15). Paternal age =35 was the risk factor for congenital heart defects (OR = 1.51, 95%CI: 1.14–1.99), congenital limb defects (OR = 1.98, 95%CI: 1.41–2.78), and congenital ear defects (OR = 1.82, 95%CI: 1.06–3.10). Number of pregnancies = 2 was the risk factor for congenital nervous system defects (OR = 2.27, 95%CI: 1.19–4.32), >=4 was the risk factor for chromosomal abnormalities (OR = 2.03, 95%CI: 1.06–3.88) and congenital nervous system defects (OR = 3.03, 95%CI: 1.23–7.47). Maternal non-local household registration was the risk factor for congenital heart defects (OR = 3.57, 95%CI: 2.54–5.03), congenital metabolic disorders (OR = 1.89, 95%CI: 1.06–3.37), congenital limb defects (OR = 2.94, 95%CI: 1.86–4.66), and congenital ear defects (OR = 3.26, 95%CI: 1.60–6.65). Conclusion In summary, several risk factors were associated with birth defects (including a broad range of specific defects). One risk factor may be associated with several defects, and one defect may be associated with several risk factors. Future studies should examine the mechanisms. Our findings have significant public health implications as some factors are modifiable or avoidable, such as promoting childbirths at the appropriate age, improving the medical and socio-economic conditions of non-local household registration residents, and devoting more resources to some specific defects in high-risk groups, which may help reducing birth defects in China.