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Abstract Background To investigate the changes in the unhealthy eye-related behaviors of junior middle school students during the COVID-19 pandemic and the double reduction policy and its relationship with myopia. Methods Data were obtained from the 2019–2022 Tianjin Children and Youth Myopia, Common Diseases and Health Influencing Factors Survey. Latent profile analysis (LPA) and a generalized linear model (GLM) were applied to analyze the effect of eye-related behavior classes on myopia. Results A total of 2508 junior middle school students were included. The types of eye-related behavior were categorized into the medium-healthy behavior group, heavy academic burden and near-eye behavior group, insufficient lighting group and high-healthy behavior group. Students with heavy academic burdens and near-eye behavior were more likely to develop myopia than were those in the high-healthy group (OR = 1.466, 95% CI = 1.203–1.787; P

Porcine reproductive and respiratory syndrome virus (PRRSV) causes a highly contagious disease that threatens the global swine industry. Recent studies have focused on the damage that PRRSV causes to the reproductive system of male pigs, although pathological research is lacking. Therefore, we examined the pathogenic mechanisms in male piglets infected with PRRSV. Gross and histopathological changes indicated that PRRSV affected the entire reproductive system, as confirmed via immunohistochemical analysis. PRRSV infected Sertoli cells and spermatogonia. To test the new hypothesis that PRRSV infection in piglets impairs blood – testis barrier (BTB) development, we investigated the pathology of PRRSV damage in the BTB. PRRSV infection significantly decreased the quantity and proliferative capacity of Sertoli cells constituting the BTB. Zonula occludens-1 and β-catenin were downregulated in cell – cell junctions. Transcriptome analysis revealed that several crucial genes and signalling pathways involved in the growth and development of Leydig cells, Sertoli cells, and tight junctions in the testes were downregulated. Apoptosis, necroptosis, inflammatory, and oxidative stress-related pathways were activated, whereas hormone secretion-related pathways were inhibited. Many Sertoli cells and spermatogonia underwent apoptosis during early differentiation. Infected piglets exhibited disrupted androgen secretion, leading to significantly reduced testosterone and anti-Müllerian hormone levels. A cytokine storm occurred, notably upregulating cytokines such as tumour necrosis factor-α and interleukin-6. Markers of oxidative-stress damage (i.e. H2O2, malondialdehyde, and glutathione) were upregulated, whereas antioxidant-enzyme activities (i.e. superoxide dismutase, total antioxidant capacity, and catalase) were downregulated. Our results demonstrated that PRRSV infected multiple organs in the male reproductive system, which impaired growth in the BTB.

IntroductionThis study characterized Vibrio alginolyticus isolated from seafood and freshwater products in China (2020).Methods and ResultsIn total, 122 (95.31%) V. alginolyticus isolates were resistant to at least 1 antibiotic category, and 2 (1.56%) isolates were resistant to at least 3 antibiotic categories and belong to multi-drug resistance (MDR) isolates. A high prevalence rate was observed to be blaCARB (98.04%) encoding beta-lactam resistance, followed by tet (97.06%) encoding tetracycline resistance and fos (4.90%) encoding resistance to fosfomycin. Among the 57 V. alginolyticus isolates, the commonest virulence genes were type III secretion system translocated gene vopD, vopB, and vcrH (54.4%, 31/57), type III secretion system regulated gene tyeA (54.39%), followed by vscI and vscF (50.88%) encoded type III secretion system inner rod protein and needle protein, respectively. Multilocus sequence typing (MLST) showed considerable genetic diversity, with 34 distinct sequence types (STs) identified among 55 isolates. ST421 (n = 5), ST166 (n = 4), ST523 (n = 3), ST516 (n = 3), and ST507 (n = 3) were dominant STs among 55 V. alginolyticus isolates.DiscussionThese findings highlight the widespread occurrence of V. alginolyticus in both freshwater and seafood products, underscoring the critical need for vigilant monitoring of these bacteria. Such measures are essential for ensuring effective food safety management and safeguarding public health.

In recent years, the epidemiological profile of Getah virus (GETV) has become increasingly serious, posing a huge threat to animal and public health in China. GETV can cause multi-species infection, including horses, pigs, rats, cattle, kangaroos, reptiles and birds. However, there were few reports on the efficiency of the virus entering the host via routes of different systems. In the present study, a GETV strain (SC201807) was obtained from a piglet's blood in 2018 in Sichuan, China. First, we established a quantitative real-time polymerase chain reaction (qRT-PCR) SYBR assay specific to GETV. Then, we evaluated the infection efficiency of different routes using mouse animal model. 108 male mice were randomly divided into four groups as follows: intramuscular, intraoral and intranasal infection routes, and negative control. All mice in the experimental group were inoculated with 4 × 102.85 TCID50 GETV virus. Tissue tropism experiments show that GETV has a wide range of tissue distribution, and intramuscular infection is the first to infect all tissues of the body, and suggest that oral infection may be a new GETV transmission route. Histopathological examination results showed that intramuscular injection of GETV mainly caused different degrees of pathological damage to the tissues, and could rapidly induce a large amount of inflammatory regulatory factors such as IL-6 and TNF-α. Our data may help us to evaluate the risk of transmission of Porcine Getah virus and provide an experimental basis for the prevention and control of Porcine Getah virus.

Epimedium sagittatum (Sieb. et Zucc.) Maxim. (ESM) which accumulates several principal flavonoid compounds including epimedin A, B, C and icariin, is extensively utilized in traditional herbs for sexual dysfunction, osteoporosis etc. In China, ESM has a wealth of wild plant resources and characterized by significant variability in medicinal compounds accumulation. Understanding the diversity of ESMs can lead to better utilization of these plant resources. In this study, we integrated the metabolomic and transcriptomic analysis of three ESMs that originated in Anhui, Hubei and Jiangxi in China. Results showed that the flavonoid biosynthesis as well as the related gene expression in these ESMs revealed substantial differences. For example, the epimedin A, B, C and icariin as well as some related gene expression in ESMs from Anhui are significantly lower than those of in others. These results suggested that the ESMs from wild population without quality checkout may not be suitable for directly use as the materials for preparation of Chinese medicine and ESMs with different accumulation of metabolites could be used for distinct applications.

Abstract Sharing of genetic elements among different pathogens and commensals inhabiting same hosts and environments has significant implications for antimicrobial resistance (AMR), especially in settings with high antimicrobial exposure. We analysed 661 Escherichia coli and Salmonella enterica isolates collected within and across hosts and environments, in 10 Chinese chicken farms over 2.5 years using data-mining methods. Most isolates within same hosts possessed the same clinically relevant AMR-carrying mobile genetic elements (plasmids: 70.6%, transposons: 78%), which also showed recent common evolution. Supervised machine learning classifiers revealed known and novel AMR-associated mutations and genes underlying resistance to 28 antimicrobials, primarily associated with resistance in E. coli and susceptibility in S. enterica. Many were essential and affected same metabolic processes in both species, albeit with varying degrees of phylogenetic penetration. Multi-modal strategies are crucial to investigate the interplay of mobilome, resistance and metabolism in cohabiting bacteria, especially in ecological settings where community-driven resistance selection occurs.

Objective Campylobacter species are the main causes of foodborne illness worldwide, posing significant threats to public health. This study aimed to investigate the antibiotic resistance and genomic characterization of C. jejuni/C.coli from retail chickens in Beijing. Methods Antimicrobial susceptibility testing was conducted on 126 C. jejuni/C. coli isolated from retail chickens in Beijing, following CLSI protocols. Whole genomes of all isolates were sequenced using the Illumina platform. Results More C. coli (83.82%) showed multi-drug resistance than C. jejuni (8.62%). Genomic analysis demonstrated 42 sequence types (STs) and 12 clonal complexes (CCs), from which CC828 and CC52 were dominant. cdtA, cdtB and cdtC encoding cytotoxic protein were present spontaneously in most C. jejuni but not found in any C. coli isolates. The abundances of antibiotic resistance genes (ARGs) and virulence genes (VGs) in C. jejuni and C. coli were significantly different, with ARGs numbered in C. coli and VGs in C. jejuni. Conclusions High prevalence of multi-drug resistance C. coli and C. jejuni isolated from Beijing chickens were challenging clinical antibiotic usages in the treatment of Campylobacter infection. The surveillance of particular C. jejuni and C. coli STs correlated with higher resistance and virulence needs to be strengthened in the future.

An inducer is a key component in a cryogenic pump to improve its cavitation performance. The thermodynamic effects of the cryogenic medium make the cryogenic cavitation flow extremely complicated. For this reason, it is crucial to investigate the cryogenic cavitation flow of the inducer which is equipped upstream of the cryogenic pump. In this paper, the isothermal cavitation model is modified based on the law of heat conduction, and the cryogenic cavitation model of the inducer is developed by considering thermodynamic effects. The turbulence model is also modified to account for the compressibility of cryogenic cavitation flow. The methods of numerical calculations are performed to investigate the influence of thermodynamic effects on cryogenic cavitation of the inducer. The law of the spatio-temporal evolution of cryogen cavitation in the inducer is clarified. The initial position, development and collapse phenomenon of cavitation are obtained. The relationship between the generation and collapse of the cavitation and the work capacity of the inducer’s blade, the relationship between thermodynamic effects and the influence of the inducer’s blade tip leakage vortex and thermodynamic on cryogenic cavitation of the inducer are revealed.

In this paper, we investigate the electro-osmotic flow (EOF) and mass transfer of a Newtonian fluid propelled by a pressure gradient and alternating current (AC) electric field in a parallel microchannel with sinusoidal roughness and modulated charged surfaces. The two-wall roughness is described by in-phase or out-of-phase sine functions with a small amplitude δ. By employing the method of perturbation expansion, the semi-analytical solutions of the Poisson–Boltzmann (P–B) equation based on the Debye–Hückel approximation and the modified Navier–Stokes (N–S) equation are obtained. The numerical solution of the concentration equation is obtained by the finite difference method. The effects of sinusoidal roughness, modulated charged surface, and the AC electric field on the potential field, velocity field, and concentration field are discussed. Under the influence of the modulated charged surface and sinusoidal roughness, vortices are generated. The velocity oscillates due to the effect of the AC electric field. The results indicate that solute diffusion becomes enhanced when the oscillation Reynolds number is below a specific critical value, and it slows down when the oscillation Reynolds number exceeds this critical value.

Objectives Network pharmacology and molecular docking were used to predict endogenous active metabolites with protective effects in diabetic kidney disease (DKD).Methods We utilized metabolomics to screen differentially expressed metabolites in kidney tissues of mice with type 2 DKD and predicted potential targets using relevant databases. The interaction network between endogenous active metabolites and target proteins was established by integrating differentially expressed metabolites and proteins associated with DKD identified through proteomics. Gene ontology (GO) and signaling pathway enrichment analysis were performed. The biological functions of the active candidate metabolites and their effects on downstream pathways were also verified.Results Metabolomics revealed 130 differentially expressed metabolites. Through co-expression network analysis coupled with the investigation of differentially expressed proteins in proteomics, 2-hydroxyphenylpropionylglycine (2-HPG) emerged as a key regulator of DKD. 2-HPG was found to modulate the progression of DKD by regulating the conformation and activity of synaptophysin 1 (SYNJ1), with a correlation coefficient of 0.974. In vivo experiments revealed that SYNJ1 expression was significantly downregulated in the Macroalbuminuria Group compared to the Control Group and negatively correlated with proteinuria (r = −0.7137), indicating its important role in DKD progression. Immunofluorescence demonstrated that treatment with 2-HPG restores the expression of the foot process marker protein Wilms tumor-1 (WT-1) in podocytes injured by high glucose levels. Western blot and polymerase chain reaction support the involvement of SYNJ1 in this process.Conclusions This study demonstrated the significance of the 2-HPG/SYNJ1 signaling axis in safeguarding the foot process of podocytes in DKD.

Salmonella, especially antimicrobial resistant strains, remains one of the leading causes of foodborne bacterial disease. Retail chicken is a major source of human salmonellosis. Here, we investigated the prevalence, antimicrobial resistance (AMR), and genomic characteristics of Salmonella in 88 out of 360 (24.4%) chilled chicken carcasses, together with 86 Salmonella from humans with diarrhea in Qingdao, China in 2020. The most common serotypes were Enteritidis and Typhimurium (including the serotype I 4,[5],12:i:-) among Salmonella from both chicken and humans. The sequence types were consistent with serotypes, with ST11, ST34 and ST19 the most dominantly identified. Resistance to nalidixic acid, ampicillin, tetracycline and chloramphenicol were the top four detected in Salmonella from both chicken and human sources. High multi-drug resistance (MDR) and resistance to third-generation cephalosporins resistance were found in Salmonella from chicken (53.4%) and humans (75.6%). In total, 149 of 174 (85.6%) Salmonella isolates could be categorized into 60 known SNP clusters, with 8 SNP clusters detected in both sources. Furthermore, high prevalence of plasmid replicons and prophages were observed among the studied isolates. A total of 79 antimicrobial resistant genes (ARGs) were found, with aac(6′)-Iaa, blaTEM-1B, tet(A), aph(6)-Id, aph(3″)-Ib, sul2, floR and qnrS1 being the dominant ARGs. Moreover, nine CTX-M-type ESBL genes and the genes blaNMD-1, mcr-1.1, and mcr-9.1 were detected. The high incidence of MDR Salmonella, especially possessing lots of mobile genetic elements (MGEs) in this study posed a severe risk to food safety and public health, highlighting the importance of improving food hygiene measures to reduce the contamination and transmission of this bacterium. Overall, it is essential to continue monitoring the Salmonella serotypes, implement the necessary prevention and strategic control plans, and conduct an epidemiological surveillance system based on whole-genome sequencing.

During the COVID-19 pandemic, a series of outbreaks and related investigations have indicated that the virus can be transmitted via cold-chain environment media. The causal relationship between the cold chain and the introduction and spread of viruses has been established. However, due to its stealthy nature, cold-chain environment media is often overlooked. Herein, we aim to provide a systematic review of the existing evidences and logical chains of virus transmission and introduction through cold-chain, from the perspectives of epidemiological investigations, laboratory researches, and molecular epidemiological evidences of cold-chain-related outbreaks. Additionally, scientific evidences also include the survival capacity of the virus in cold-chain environments, as well as modeling of virus transmission and risk assessment. These evidences and the logical framework related to cold-chain transmission put forward the initiation of cold-chain-based epidemiology (CCBE) as one of the important portions of the epidemiology of infectious diseases. Close multidisciplinary collaboration in this field will be essential for the preparation of future pandemics.

Abstract Background It has been reported Interferon‐λ (IFN‐λ) has stronger antiviral effect than other interferons. IFN‐λ can induce antiviral interferon stimulated genes (ISGs) in epithelia to protect against virus. Pseudorabies virus (PRV) infection in pigs resulting in fatal encephalitis in newborn piglets, respiratory disorders in finishing pigs, reproductive disorders in sows and other symptoms. Objectives Since the effect of IFN‐λ on inhibiting PRV proliferation is still unknown. Inthis study, we investigate the relative contribution of porcine IFN‐λ3 toward controlling the infection of PRV in vitro. Our findings may provide a new insight for the prevention and treatment of PRV. Methods Therefore, the antiviral assay, western blot, qRT‐PCR and ELISA assay were used to investigating the contribution of IFN‐λ against PRV in PK‐15 cells. Results Here, we demonstrate that the replication of PRV in PK‐15 cells was inhibited after pre‐treatment with IFN‐λ3, and such inhibition was dose dependent. Overexpression of IFN‐λ3 receptor (IFNLR) also restricted virus titre in PK‐15 cells. In addition, IFN‐λ3 also increased the mRNA and protein expression of interferon‐stimulated genes 15 (ISG15), 2′‐5′‐oligoadenylate synthase 1 (OAS1), IFN‐inducible transmembrane 3 (IFITM3) and myxoma resistance protein 1 (Mx1) in PRV‐infected PK‐15 cells. Other than modulation ISGs, IFN‐λ specifically activated IFN‐γ mRNA expression not IFN‐α or IFN‐β. Conclusions IFN‐λ3 had antiviral activity against PRV and the upregulation of ISGs and IFN‐γ mRNA expression may be the mechanism of IFN‐λ3's antiviral activities. Thus, IFN‐λ3 has a decisive function that greatly limits PRV replication in PK‐15 cells. Our study explores the antiviral activity of IFN‐λ3 on PRV for the first time.

Continuous wave (CW) green lasers have a lot of important applications in many fields, including holography, interferometry, atom cooling and trapping, and quantum optics, and they are usually achieved by frequency-doubling 1 µm lasers based on the Nd3+ gain media. In this paper, we present an all-solid-state CW green laser with an output wavelength of 522 nm, which was directly attained by employing a Pr3+:YLF crystal pumped with a high-power fiber-coupled blue laser diode (LD) module as the gain medium. Due to the negative thermal lens effect of the Pr3+:YLF crystal, the designed laser resonator had to be lengthened with the increase in the incident pump power. As a result, when a 0.5% doped Pr3+:YLF crystal was employed as the gain medium and the incident pump power was 12 W, the length of the resonator was optimized to 311.3 mm and the maximum output power of 522 nm green laser was up to 886 mW. The obtained conversion efficiency and beam quality M2 were 11.25% and 1.15, respectively. The long-term power stability within 4.5 h was better than ±1.5% at an output power of 700 mW. The obtained watt-level green laser can also be used to generate high power CW deep UV laser for laser processing of silicon and organic materials, inspection, etc.

Background:Salvia miltiorrhiza (SM) is an effective traditional Chinese medicine for treating DKD, but the exact mechanism is elusive. In this study, we aimed to investigate and confirm the method underlying the action of the active components of SM in the treatment of DKD.Methods: Renal tissue transcriptomics and network pharmacology of DKD patients was performed to identify the active components of SM and the disease targets of DKD. Next, the point of convergence among these three groups was studied. Potential candidate genes were identified and analyzed using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). The component-target networks were modelled and visualized with Cytoscape. In addition, docking studies were performed to validate our potential target predictions. Lastly, in vitro and in vivo experiments were performed to understand the role of Dehydromiltirone (DHT), the active component of SM, in the phenotypic switching of mesangial cells.Results: Transcriptomics of DKD patients’ renal tissues screened 4,864 differentially expressed genes. Eighty-nine active components of SM and 161 common targets were found. Functional enrichment analysis indicated that 161 genes were enriched in apoptosis, the PI3K-AKT signaling pathway, and the AGE-RAGE signaling pathway in diabetes complications. Molecular docking and molecular dynamic simulations show that DHT can bind to functional PIK3CA pockets, thereby becoming a possible inhibitor of PIK3CA. In vitro study demonstrated that DHT reduced the expression of phenotypic switching markers α-SMA, Col-I, and FN in HMCs by downregulating the over-activation of the PI3K-AKT signaling pathway through the inhibition of PIK3CA. Furthermore, the DKD mouse model confirmed that DHT could reduce proteinuria and improve glomerular hypertrophy in vivo.Conclusion: DHT was identified as the key active component of SM, and its therapeutic effect on DKD was achieved by inhibiting the phenotypic switching of mesangial cells via the PIK3CA signaling pathway.

Abstract Pseudorabies virus (PRV), also known as suid Alphaherpesvirus 1 (SuHV-1), which is one of the most devastating infectious pathogen of swine industry worldwide. Vaccination is the safest and most effective PRV prevention and control strategy. B cell receptor (BCR) is membrane-bound immunoglobulin located on the surface of B cells capable of specifically binding foreign antigens, which is one of the most important molecules regulating the proliferation and function of B cells. Here, to assess the molecular diversity of BCR H-CDR3 repertoire after different PRV strains infection, we detected the IGHV, IGHD, IGHJ genes usage and CDR3 sequence changes of mice spleen with PRV vaccine strain (Bartha-K61), variant strain (XJ) and mock infection by high-throughput sequencing. We found that PRV-infected groups shared partial BCR sequences, which are most likely to be PRV-specific BCR candidates. However, there were still differences in the IGHV genes usage as well as the combined usage of IGHV and IGHJ genes between the Bartha-K61 strain and XJ strain infection groups. In addition, the CDR3 sequences exhibited large differences in the types and lengths in PRV infection groups. Our study contributes to a better understanding of the host adaptive immune response to PRV infection and provides a theoretical basis for further research on novel and efficient PRV vaccines in the future.

Abstract JEV is one of the zoonotic pathogens that cause serious diseases in humans. JEV infection can cause abortion, mummified foetus and stillbirth in sows, orchitis and semen quality decline in boars, causing huge economic losses to pig industry. In order to investigate the epidemiology of JEV in pigs in Sichuan province, a rapid and efficient fluorescent Reverse transcription recombinase-aided amplification (RT-RAA) detection method was established. Aborted fetuses and testicular swollen boar samples were detected by RT-RAA in pigs in the mountain areas around Sichuan Basin, and the detection rate of JEV was 6.49%. The positive samples were identified as JEV GI strain and GIIIstrain by sequencing analysis. We analyzed the whole gene sequence of a positive sample for the GI virus. The Envelope Protein (E protein) phylogenetic tree analysis was far related to the Chinese vaccine strain SA14-14-2, and was most closely related to the JEV GI strains SH17M-07 and SD0810 isolated from China. The results showed that we established an efficient, accurate and sensitive method for clinical detection of JEV, and JEV GI strains were prevalent in Sichuan area. It provides reference for the prevention and control of JEV in Sichuan.

Acute kidney injury (AKI) is a severe and frequent complication of sepsis that occurs in intensive care units with inflammation and rapid decline in renal function as the main pathological features. Systemic inflammation, microvascular dysfunction, and tubule injury are the main causes of sepsis-induced AKI (SI-AKI). The high prevalence and death rate from SI-AKI is a great challenge for clinical treatment worldwide. However, in addition to hemodialysis, there is no effective drug to improve renal tissue damage and alleviate the decline in kidney function. We conducted a network pharmacological analysis of Salvia miltiorrhiza (SM), a traditional Chinese medicine, which is widely used for the treatment of kidney disease. Then, we combined molecular docking and a dynamics simulation to screen for the active monomer dehydromiltirone (DHT) that has therapeutic effects on SI-AKI and investigated its potential mechanism of action through experimental validation. The components and targets of SM were obtained by searching the database, and 32 overlapping genes were screened by intersection analysis with AKI targets. GO and KEGG data showed that the functions of a common gene were closely related to oxidative stress, mitochondrial function, and apoptosis. The molecular docking results combined with molecular dynamics simulations provide evidence for a binding model between DHT and cyclooxygenase-2 (COX2), both of which are mainly driven by van der Waals interactions and a hydrophobic effect. In vivo, we found that mice pretreated with an intraperitoneal injection of DHT (20 mg/kg/d) for 3 days ameliorated CLP surgery-induced renal function loss and renal tissue damage and inhibited inflammatory mediators IL-6, IL-1β, TNF-α, and MCP-1 production. In vitro, the DHT pretreatment decreased LPS-induced expression of COX2, inhibited cell death and oxidative stress, alleviated mitochondrial dysfunction, and restrained apoptosis in HK-2 cells. Our research indicates that the renal preventive effect of DHT is related to maintaining mitochondrial dynamic balance, restoring mitochondrial oxidative phosphorylation, and inhibiting cell apoptosis. The findings in this study provide a theoretical basis and a novel method for the clinical therapy of SI-AKI.

Abstract Background Hepatitis E virus (HEV) is an important zoonotic pathogen, Genotypes 3 and 4 are the main zoonotic genotype. Due to the lack of mature and effective culture cell lines, researches on genotype IV swine HEV (SHEV‐4) infection and pathogenic mechanism have been carried out in pigs, gerbils and non‐human primate models. Objectives The aim of this study was to establish a rat infection model by intra‐peritoneal infection with SHEV‐4, which provided a new research idea and scientific basis for further revealing the mechanism of HEV infection and preventing HEV infection. Methods SHEV‐4 virus was administered intra‐peritoneally to 6‐ to 8‐week‐old mice to observe the serological changes and virus release. Results According to the results of the rat serum HEV IgG, ALT and AST levels, swine HEV, minus‐strand HEV RNA can infect Sprague–Dawley rats across species, and there are no obvious clinical symptoms after infection. HEV RNA was detected in most tissues and organs after infection, but the viral load was low. The liver had pathological changes of chronic hepatitis. Conclusions We found that the rat model of porcine HEV infection is a small animal model suitable for the study of HEV infection.

Renal cell carcinoma (RCC) is the most common type of kidney cancer. Owing to the high morbidity rate of RCC, there is an urgent need for intensive research on robust materials to diagnose and treat RCC. Nanomaterials have been developed largely in the last three decades because of their numerous advantages, such as high specific surface area, simple surface functionalization, rapid onset of therapeutic action, superior biological activity, and other unique physical–chemical characteristics. Herein, first, various types of nanomaterials used in RCC treatment are introduced, including inorganic nanomaterials, lipid nanomaterials, synthetic polymer nanomaterials, and natural nanomaterials. Second, the different diagnosis and therapeutic mechanisms of nanomaterials in the kidneys are reviewed and these advantages of nanomaterials are highlighted. Furthermore, nanomaterials are investigated for the preclinical and clinical detection and treatment of RCC. Finally, the challenges and outlook of various nanomaterials for RCC diagnostic and treatment are discussed.

ABSTRACT Cronobacter is a foodborne pathogen associated with severe infections in restricted populations and particularly with high mortality in neonates and infants. The prevalence and antimicrobial resistance (AMR) phenotype of Cronobacter cultured from powdered infant formula and supplementary food were studied. The virulence factors, AMR genes, and genomic environments of the multidrug-resistant isolates were further studied. A total of 1,055 Cronobacter isolates were recovered from 12,105 samples of powdered infant formula and supplementary food collected from 29 provinces between 2018 and 2019 in China. Among these, 1,048 isolates were from infant supplementary food and 7 were from powdered infant formula. Regarding antimicrobial resistance susceptibility, 11 (1.0%) isolates were resistant and two showed resistance to four antimicrobials (ampicillin [AMP], tetracycline [TET], sulfamethoxazole-trimethoprim [SXT], and chloramphenicol [CHL]), defined as MDR. These two MDR isolates were subsequently identified as Cronobacter sakazakii sequence type 4 (ST4) (C. sakazakii Crono-589) and ST40 (C. sakazakii Crono-684). Both MDR isolates contain 11 types of virulence genes and 7 AMR genes on their genomes. Meanwhile, the IncFIB plasmids of both MDR C. sakazakii isolates also harbored 2 types of virulence genes. Results of the genomic comparative analysis indicated that food-associated C. sakazakii could acquire antimicrobial resistance determinants through horizontal gene transfer (HGT). IMPORTANCE As a foodborne pathogen, Cronobacter can cause serious infections in restricted populations and lead to death or chronic sequelae. Although a number of investigations showed that Cronobacter isolates are susceptible to most antimicrobial agents, MDR Cronobacter isolates, isolated mainly from clinical cases but occasionally from foods, have been reported in recent years. In this study, we successfully identified two MDR Cronobacter sakazakii isolates from infant foods based on nationwide surveillance and genome sequencing in China. Genomic analysis revealed that these two MDR C. sakazakii strains acquired resistance genes from other species via different evolution and transmission routes. It is important to monitor MDR C. sakazakii isolates in infant foods, and appropriate control measures should be taken to reduce the contamination with and transmission of this MDR bacterium.

Salmonella enterica serotype Indiana (S. Indiana) in Chinese poultry meat has aroused widespread concern because of its high prevalence and strong antimicrobial resistance. In consideration of the relationship in our previous study between S. Indiana and co-resistance to ciprofloxacin and cefotaxime (CIP-CTX), which were the first-line drug which were used in Salmonella infection in clinical, the antimicrobial resistance (AMR) of 224 CIP-CTX co-resistant S. Indiana isolated from retail chicken samples in China were investigated, with the aim of characterizing the AMR profiles and related resistance mechanisms to ciprofloxacin and cefotaxime among these CIP-CTX co-resistant S. Indiana isolates, all of which showed multi-drug-resistant (MDR) phenotypes. GyrA (S83F and D87N/G) with ParC (T57S and S80R) were the dominant amino acid substitution types, with oqxA, oqxB, and aac (6′)-Ib-cr identified as common plasmid-mediated quinolone resistance (PMQR)-encoding genes. Five blaCTX-M gene subtypes were identified with blaCTX-M-65 ranking at the top. Equally important, we obtained one isolate CFSA664 harboring the mcr-1 gene was ESBL producer with co-resistance to nine in ten classes of tested drugs inclduing colistin. A single circular chromosome and 3 circular plasmids were found in its genome. Among the 26 AMR genes identified, 24 were located on plasmid pCFSA664-1, including three ESBL genes, while plasmid pCFSA664-3 owning only the mcr-1 gene and sharing the same backbone structure with plasmids from Enterobacteriaceae. No insertion sequences were found near the mcr-1 gene but a relaxase-encoding gene in the flank, which could transfer into E. coli J53 at a relatively high frequency. S. Indiana in this study exhibited highly drug-resistant phenotypes, contributing to the acceleration of the dissemination and emergence of this pathogen among different sources. Surveillance and a One Health strategy are needed to limit the emergence of S. Indiana along the food chain.

Both Epimedium sutchuenense Franch. 1894 and E. fargesii Franch. 1894 are perennial herbs with excellent ornamental values due to their showy flowers. However, little molecular research has been done on these species. Here, the complete chloroplast (cp) genome of E. sutchuenense and E. fargesii was analyzed and reported. The cp genome sizes of E. sutchuenense and E. fargesii were 157, 263 and 157, 133 bp, respectively. Both the two cp genomes contained a pair of inverted repeat regions (IRs) (25,782 and 25,796 bp), separated by the small single-copy (SSC) region (17,106 and 17,071 bp) and a large single-copy (LSC) region (88,593 and 88,470 bp). A total of 113 unique genes were annotated in each of the two cp genomes, including 79 protein-coding genes, 30 tRNA genes, and four rRNA genes. Phylogenetic analysis supported a close relationship between E. sutchuenense and E. wushanense, while E. fargesii had no clear clustering branch.

Epimedium jinchengshanense Y. J. Zhang & J. Q. Li 2014 is an important ornamental and medicinal herb, but of unclear taxonomy. In this study, the complete chloroplast genome of E. jinchengshanense was sequenced. The genome was 157,169 bp in length, with a large single-copy region of 88, 520 bp, a small single-copy region of 17,075 bp and 2 inverted repeat regions of 25, 787 bp. The genome consisted of 113 unique genes, including 79 protein-coding genes, 30 tRNA genes and 4 rRNA genes. The GC contents were 38.78%. Phylogenetic analysis showed a close relationship between E. jinchengshanense and E. ilicifolium, which was explained by the morphological similarity of flowers and leaves of the two species.

Members of the genus, Klebsiella , are becoming increasingly challenging to control due to the recent convergence of multidrug resistant (MDR) and hypervirulent (hv) phenotypes in some species of concern to One Health . This short review will provide an introduction to this bacterial genus in the hospital and other settings, update Klebsiella taxonomy, and comment on recent findings describing the prevalence of Klebsiella species in the food chain, a hitherto infrequently recognised ecologic niche. The paper will also consider this bacterium in the context of the One Health paradigm and its importance to food safety and security.

The objective of the present study was to determine the prevalence, antimicrobial resistance, virulence profiles, and molecular characteristics of methicillin-resistant Staphylococcus aureus (MRSA) obtained from ready-to-eat (RTE) foods in China. Two hundred seventy-six RTE food-associated S. aureus isolates were collected from 25 provinces across China in 2018, then characterized by antimicrobial susceptibility testing, virulence factors detecting, multilocus sequence typing (MLST), spa typing, SCC mec typing and pulsed-field gel electrophoresis (PFGE). Two hundred fifty isolates (90.6%) were resistant to at least one antimicrobial agent; 73 (26.4%) isolates were multi-drug resistant (MDR). Thirty MRSA isolates were identified, among which nine toxin genes ( sea, seb, sec, sed, seh, selk, sell, selq , and tsst-1 ) were detected. Sixty percent (18/30) of the MRSA isolates harbored multiple toxin genes. Four virulence gene patterns were identified, with seb-selk-selq (30/30) being the most common pattern. Thirteen sequence types, as well as 13 spa and 4 SCC mec types were found among 30 MRSA isolates. The most prevalent MRSA lineages were CC59-t437-SCC mec IV/V (23.3% [7/30]), CC398-t011-SCC mec V (23.3% [7/30]), and CC1-t114-SCC mec IV (16.7% [5/30]). Our findings highlight the importance for the identification of prevalent clones, assessment of drug-resistance and virulence, and formulation of food safety measures for public health.

Background: Hemodialysis patients, who are often excluded from cardiovascular (CV) clinical trials, are associated with higher CV morbidity and mortality. The risk stratification scheme for these patients is lacking. Therefore, this investigation examined the independent CV prognostic value of high-sensitive cardiac troponin T (hs-cTnT) and added prognostic value over echocardiographic parameters and other clinical risk predictors in asymptomatic stable maintenance hemodialysis (MHD) patients. Methods: 181 patients with end-stage renal disease undergoing MHD were eligible from the dialysis center of Tongren Hospital, Shanghai Jiao Tong University School of Medicine between October 2017 and September 2018. These patients were followed until September 2020 or until death. The median follow-up was 31 (IQR: 21–33) months. Outcome measures were all-cause mortality, first fatal or nonfatal CV events (CVEs), and 4-point composite major adverse CVEs (MACE). We performed multivariable Cox regression analysis using demographic, clinical, laboratory, and echocardiographic data to identify predictors of CV outcomes. We also evaluated the increased discriminative value associated with the addition of echocardiographic parameters and hs-cTnT using net reclassification improvement (NRI) and integrated discrimination improvement (IDI). Results: During follow-up, 37 patients died, 84 patients suffered one or more CVEs, and 78 patients developed 4-point MACE. In univariable analyses, age, dialysis vintage, diastolic blood pressure, parathyroid hormone concentrations, hs-cTnT, B-type natriuretic peptide, left ventricular mass index (LVMI), and E/E′ predicted all end points. hs-cTnT remained a strong predictor for each end point in multivariate analysis, whereas LVMI and E/E′ did not. The addition of hs-cTnT on top of clinical and echocardiographic variables was associated with improvements in reclassification for CVEs (NRI = 44.6% [15.9–74.3%], IDI = 15.9% [5.7–31.0%], all p < 0.001), all-cause mortality (NRI = 35.5% [10.1–50.2%], p < 0.001, IDI = 4.4% [1.3–8.5%], p = 0.005), and 4-point MACE (NRI = 47.2% [16.1–64.9%], p < 0.001, IDI = 16.9% [5.5–37.3%], p = 0.005). Adding echocardiographic variables on top of clinical variables and hs-cTnT was not associated with significant improvements in NRI and IDI (all p > 0.05). Conclusions: Our data suggest that hs-cTnT is a powerful independent predictor of CV outcome and all-cause mortality in stable MHD patients. The additional use of echocardiography for improvement of risk stratification is not supported by our results.

A transient computational fluid dynamics (CFD) method based on dynamic mesh is adopted to investigate the static and dynamic performances of an annular seal with a tilted rotor. The reliability of the CFD method is verified by the experimental data, and then the variations of dynamic performance and sealing performance under different length-diameter ratios and misalignment angles are investigated by the method. The results show that the leakage flowrate of the tilted annular seal decreases with the increasing length-diameter ratio, while the whirl frequency ratio increases with the length-diameter ratio. The increase of misalignment angle has little detrimental effect on the stability of long shaft system in the three misalignment modes. In addition, the misalignment mode for the tilted position at the half-length of the annular seal can reduce the leakage flowrate.

IFN is the most potent antiviral cytokine required for the innate and adaptive immune responses, and its expression can help the host defend against viral infection. Arteriviruses have evolved strategies to antagonize the host cell’s innate immune responses, interfering with IFN expression by interfering with RIG, blocking PRR, obstructing IRF-3/7, NF-κB, and degrading STAT1 signaling pathways, thereby assisting viral immune evasion. Arteriviruses infect immune cells and may result in persistence in infected hosts. In this article, we reviewed the strategies used by Arteriviruses to antagonize IFN production and thwart IFN-activated antiviral signaling, mainly including structural and nonstructural proteins of Arteriviruses encoding IFN antagonists directly or indirectly to disrupt innate immunity. This review will certainly provide a better insight into the pathogenesis of the arthritis virus and provide a theoretical basis for developing more efficient vaccines.

ABSTRACT Sequence type 88 (ST88) methicillin-resistant Staphylococcus aureus (MRSA) has been recognized as an important pathogen that causes infections in humans, especially when it has strong biofilm production and multidrug resistance (MDR). However, knowledge of the determinants of resistance or virulence and genomic characteristics of ST88 MRSA from China is still limited. In this study, we employed the antimicrobial resistance (AMR), biofilm formation, and genomic characteristics of ST88 MRSA collected from various foods in China and estimated the worldwide divergence of ST88 MRSA with publicly available ST88 genomes. All ST88 isolates studied were identified as having resistance genes, while 50% (41/82) harbored MDR genes. All isolates carried core virulence genes related to immune modulation, adherence, secreted enzymes, and hemolysin. In addition, all 20 Chinese ST88 isolates showed biofilm production capacity, three strongly so. Bayesian phylogenetic analysis showed that Chinese ST88 clones formed an independent MRSA lineage, with two subclades associated with acquisition of type IVc staphylococcal cassette chromosome mec (SCCmec) elements. In contrast, all African ST88 strains were subtyped as SCCmecIVa, where the African clades were mixed with a few European and American isolates, suggesting potential transmission from Africa to these regions. In summary, our results revealed the evolution of ST88 MRSA in humans, animals, and foods in Africa and Asia. The food-associated ST88 genomes in this study will remedy the lack of food-associated ST88 isolates, and the study in general will extend the discussion of the potential exchanges of ST88 between humans and foods or food animals. IMPORTANCE ST88 MRSA has frequently been detected in humans, animals, and foods mainly in Africa and Asia. It can colonize and cause mild to severe infections in humans, especially children. Several studies from African countries have described its genotypic characteristics but, limited information is available on the evolution and characterization of ST88 MRSA in Asia, especially China. Meanwhile, the molecular history of its global spread remains largely unclear. In this study, we analyzed the genomic evolution of global ST88 MRSA strains in detail and identified key genetic changes associated with specific hosts or regions. Our results suggested geographical differentiation between ST88 MRSA’s evolution in Africa and its evolution in Asia, with a more recent clonal evolution in China. The introduction of ST88 MRSA in China was aligned with the acquisition of SCCmecIVc elements, specific virulent prophages, and AMR genes.

Seneca Valley virus (SVV), a non-enveloped positive single-stranded virus can cause vesicular disease in swine. However, the mechanisms by which SVV activates an innate immune response remain unknown. Mitofusin-2 (MFN2), a mitochondria-shaping protein regulating mitochondrial fusion and fission, plays a crucial role in innate immune responses. But, the roles of Mfn2 in SVV infection have not been elucidated. Here, we show that SVV inhibited Mfn2 expression and NLRP3 inflammasome, activating RIG-I/IRF7 signaling pathway to increase IFN-λ3 expression. Overexpression of Mfn2 inhibited RIG-I/IRF7 signaling pathway, thus decreasing IFN-λ3 expression and promoting SVV replication. Interestingly, overexpression of Mfn2 also activated NLRP3 inflammasome but did not inhibit SVV proliferation. That may mean the RIG-I/IRF7 signaling pathway plays a more important role in SVV proliferation in PK-15 cells. This study could provide important insights into the modulation of host metabolism during SVV infection and provide a strong theoretical basis for a better understanding of the pathogenic mechanism and immune activation mechanism of SVV.

Herpesviruses belong to large double-stranded DNA viruses. They are under a wide range of hosts and establish lifelong infection, which creates a burden on human health and animal health. Innate immunity is the host’s innate defense ability. Activating the innate immune signaling pathway and producing type I interferon is the host’s first line of defense against infectious pathogens. Emerging evidence indicates that the cGAS-STING signaling pathway plays an important role in the innate immunity in response to herpesvirus infections. In parallel, because of the constant selective pressure imposed by host immunity, herpesvirus also evolves to target the cGAS-STING signaling pathway to inhibit or escape the innate immune responses. In the current review, we insight on the classical cGAS-STING signaling pathway. We describe the activation of cGAS-STING signaling pathway during herpesvirus infections and strategies of herpesvirus targeting this pathway to evade host antiviral response. Furthermore, we outline the immunotherapy boosting cGAS-STING signaling pathway.

Non-typhoidal Salmonella (NTS) is a major cause of human salmonellosis globally. Food animals are major NTS reservoirs. An increase in antimicrobial resistance (AMR) in foodborne NTS has led to clinical treatment failures. Here, to examine the prevalence and perform characterization of foodborne NTS with AMR in China, we tested the antimicrobial susceptibility of 1,256 NTS isolates cultured from retail foods in 2020 in China. The antimicrobial susceptibility of 26 antimicrobial agents representing 12 classes was evaluated with the broth-microdilution method; the presence of ten mcr genes was screened with multi-PCR. The complete closed genomes of mcr -gene-carrying isolates were generated by hybrid assembly through whole genome sequencing on both the PacBio and Illumina platforms. Genomic features and genetic environments of the mcr-1 gene were analysed. The overall drug resistance rate was 92.28%, and the multi-drug resistance (MDR) rate was 76.53%. A total of 341 AMR profiles were determined, and resistance was highest to nalidixic acid (63.38%). Among 887 NTS isolates with MDR, 232 showed co-resistance to cefotaxime and ciprofloxacin, and 25 were resistant to ten classes of antimicrobial agents. The resistance of NTS isolated from different regions varied. Isolates from raw chicken sources most frequently showed resistance. Four NTS carried the mcr-1 gene and represented four different serotypes. Four mcr-1 gene-bearing plasmids from the four Salmonella isolates were classified into two replicon types (IncI2 and IncHI2A). Two mcr-1 genes in IncI2 type plasmids were found to be located between a PAP2 family protein-encoding gene and a relaxase-encoding gene, whereas the other two mcr-1 gene structures in IncHI2A type plasmids showed variations in the presence of insertion sequences. Our data demonstrated severe AMR among foodborne NTS isolated from food in China, thus highlighting the importance of antimicrobial susceptibility surveillance to decrease the spread of AMR, particularly to critical drugs in human medicine.

Macrophages are crucial components of the immune system and play a critical role in the initial defense against pathogens. They are highly heterogeneous and plastic and can be polarized into classically activated macrophages (M1) or selectively activated macrophages (M2) in response to local microenvironments. Macrophage polarization involves the regulation of multiple signaling pathways and transcription factors. Here, we focused on the origin of macrophages, the phenotype and polarization of macrophages, as well as the signaling pathways associated with macrophage polarization. We also highlighted the role of macrophage polarization in lung diseases. We intend to enhance the understanding of the functions and immunomodulatory features of macrophages. Based on our review, we believe that targeting macrophage phenotypes is a viable and promising strategy for treating lung diseases.

This paper analyzes the M/M/c queueing system with server working breakdown and impatient customers under the classical truncated retry strategy. The steady-state equilibrium conditions of the system are obtained using the matrixgeometric solution method. Then the steady-state probabilities and the performance indicators of the system in the steadystate case are obtained using the Markov process theory and Gauss-Seidel iterative algorithm. Numerical experiments are conducted to assess the system’s steady-state performance indicators. Finally, we developed an optimization model for the system and derived the optimal parameters from the analysis of the optimization function. [ABSTRACT FROM AUTHOR]

Annular seals can induce fluid excitation forces that severely affect the stability of the pump rotor systems. In this paper, a transient computational fluid dynamic method with a mesh deformation technique is used to study the fluid excitation forces generated on the long annular seal caused by cylindrical whirls and conical whirls. The reliability of the method is verified by comparing the simulation results with the experimental results. The whirl motion, composed of cylindrical and conical whirls, is realized by the phase difference between the whirl movements at the annular seal inlet and outlet, and the effects of the phase difference and inlet preswirl on the fluid excitation forces are studied numerically. The results show that the fluid excitation forces significantly depend on the phase difference of the rotor whirl movement, and tangential force acts as a stabilizing force only when the phase difference approaches 45°. The tangential forces of the cylindrical whirl, the conical whirl and the form of cylindrical and conical combined whirl are sensitive to inlet preswirl, while the effect of inlet preswirl on the radial forces becomes obvious only when the rotor whirls in the form of combined whirls.

Anthropogenic environments such as those created by intensive farming of livestock, have been proposed to provide ideal selection pressure for the emergence of antimicrobial-resistant Escherichia coli bacteria and antimicrobial resistance genes (ARGs) and spread to humans. Here, we performed a longitudinal study in a large-scale commercial poultry farm in China, collecting E. coli isolates from both farm and slaughterhouse; targeting animals, carcasses, workers and their households and environment. By using whole-genome phylogenetic analysis and network analysis based on single nucleotide polymorphisms (SNPs), we found highly interrelated non-pathogenic and pathogenic E. coli strains with phylogenetic intermixing, and a high prevalence of shared multidrug resistance profiles amongst livestock, human and environment. Through an original data processing pipeline which combines omics, machine learning, gene sharing network and mobile genetic elements analysis, we investigated the resistance to 26 different antimicrobials and identified 361 genes associated to antimicrobial resistance (AMR) phenotypes; 58 of these were known AMR-associated genes and 35 were associated to multidrug resistance. We uncovered an extensive network of genes, correlated to AMR phenotypes, shared among livestock, humans, farm and slaughterhouse environments. We also found several human, livestock and environmental isolates sharing closely related mobile genetic elements carrying ARGs across host species and environments. In a scenario where no consensus exists on how antibiotic use in the livestock may affect antibiotic resistance in the human population, our findings provide novel insights into the broader epidemiology of antimicrobial resistance in livestock farming. Moreover, our original data analysis method has the potential to uncover AMR transmission pathways when applied to the study of other pathogens active in other anthropogenic environments characterised by complex interconnections between host species.

The aim of this study was to perform an epidemiological analysis of the viral strains isolated from outpatients with acute gastroenteritis in Dalian, Liaoning province, China to determine the epidemiology of Norovirus (NoV). Fecal samples were collected from 789 outpatients with acute gastroenteritis in the Xigang district of Dalian, Liaoning province, China from July 2015 to December 2016. Norovirus was detected by real-time reverse transcriptase-polymerase chain reaction (RT-PCR). A selection of the positive samples identified was subsequently sequenced, and these data were analyzed by using the Norovirus Typing tool. Results showed that 38.02% (300/789) of the fecal samples were positive for NoV, of which 95.67% (287/300) were identified as genotype GII with 1.33% (4/300) identified as GI. A further 3.00% (9/300) were combined infections with both GI and GII Norovirus. When analyzing the age distribution, the infections primarily occurred in adults especially the elderly whose NoV positive rate was much higher than the average. Winter was the season when most cases were recorded during 2015 and 2016; however, another infection peak was observed in July 2016. Thirty Norovirus positive samples were successfully sequenced, and results showed that GII.4 was the most commonly identified genotype, along with GII.3 and GII.17. Norovirus is the most common pathogen for acute gastroenteritis in Dalian, Liaoning province of China. The current NoV genotype prevalence in Dalian was found to be similar to that in other regions of China. Genotype GII.4 was the most common genotype in our study, GII.3 and GII.17 were also identified.

Abstract Background Even though enterococci can cause serious infections in multiple sites, they are a rare cause of pneumonia. We reported a uremic patient with vancomycin-resistant E. faecium (VRE-fm) pneumonia, possibly related to epileptic seizures. Case presentation A 57-year old man with uremia on hemodialysis was admitted to the hospital with complaint of recurrent epileptic seizures, followed by a two-week history of recurrent fever and cough with purulent sputum. Chest CT demonstrated multiple exudation of both lungs. He was diagnosed as community acquired pneumonia. Despite antibiotic combination therapy, abnormal chest shadows aggravated. Sputum and blood cultures were initially negative, but later blood culture grew VRE-fm. We suspected aspiration of gastrointestinal content induced by epilepsy as the most likely mechanism. The patient was successfully treated with a four-week course of linezolid according to the antibiotic susceptibility testing. Conclusions Physicians should consider multi-drug resistant organisms such as VRE in uremic patients with pneumonia that fails to resolve with broad-spectrum antibiotics, especially in the cases with aspiration induced by epilepsy, immunocompromised conditions, and repeated or prolonged hospitalizations.

Abstract Diagnostic testing of biological macromolecules is of great significance for early warning of disease and cancer. Nevertheless, restricted by limited surface area and large steric hindrance, sensitive detection of macromolecules with interface‐based sensing method remains challenging. Here, a “biphasic replacement” electrochemical aptamer‐based (BRE‐AB) sensing strategy which placed capture reaction of the biomacromolecule in a homogeneous solution phase and replaced with a small diameter of single‐stranded DNA to attach to the interface is introduced. Using the BRE‐AB sensor, the ultrasensitive detection of luteinizing hormone (LH) with the detection limit of 10 × 10−12 m is demonstrated. Molecular Dynamics simulations are utilized to explore the binding mechanism of aptamer and target LH. Moreover, it is confirmed that the BRE‐AB sensor has excellent sensing performance in whole blood and undiluted plasma. Using the BRE‐AB sensor, the LH concentrations in 40 clinical samples are successfully quantified and it is found that LH is higher expressed in breast cancer patients. Furthermore, the sensor enables simple, low‐cost, and easy to regenerate and reuse, indicating potentially applicable for point‐of‐care biological macromolecules diagnostics.

Since the first report of PCV3 virus infection in 2016, it has been linked to multisystemic inflammation, reproductive failure, cardiac pathology, and clinical indications resembling porcine dermatitis and nephropathy syndrome (PDNS). However, the pathogenesis and clinical significance of PCV3 is still unclear. In this study, a PCV3 infection model was created using SPF pigs, and histopathology and fluorescence quantitative PCR were utilized to examine PCV3’s pathogenicity. Reductions in body weight gain and fever were observed during this study. However, other clinical signs such as Dermatitis and Nephropathy Syndrome were not observed through the study. Viremia was detected in the PCV3-inoculated group from 17 days post-inoculation (p.i.) until the end of the study. Nasal shedding was detected from 21 to 35 dpi and fecal shedding was detected during 25–33 days and 39 days, respectively. Gross lesions and histological evaluation were detected in various tissues and organs, including the lung, heart, kidney, lymph nodes, spleen, liver, small intestine, and testis. The heart, lung, liver, kidney, lymph nodes, and spleen showed pathological changes. The pathological features include swelling, inflammation, cell degeneration, necrosis, and hemorrhage. The lesions are consistent with multisystemic inflammation. Tissue viral load results showed only heart, lung, liver, kidney, lymph nodes, and spleen was positive by qRT-PCR. Moreover, the pro-inflammation cytokines in serum increased a lot in the PCV3-inoculated group compared to the control group, demonstrating that the induced inflammation response may be the cause of tissue damage in PCV3-infection. This study demonstrated that PCV3 can produce mild pathological damage to multiple organs, especially multisystemic inflammatory cell infiltration and prolonged viremia, viral shedding in nasal secretions. This is the first in vivo characterization of PCV3 infection in the SPF piglets model using isolated PCV3 strain, and this is also the first time to show the gross and pathological lesion with all tissue and organs in the PCV3-inoculated group. Our findings might serve as a starting point for more investigation into PCV3’s pathogenic mechanism.

In this paper, a superhydrophobic biomimetic composite coating was fabricated on brass by electrochemical etching, brushing PDMS adhesive layer, and depositing carbon soot particles. Due to the microstructure and the optimized ratio of PDMS, the contact angle of the superhydrophobic coating is up to 164° and the sliding angle is only 5°. The results of optical microscopy and morphometric laser confocal microscopy show that the prepared coating surface has a rough hierarchical structure. A high-speed digital camera recorded the droplet bouncing process on the surface of the superhydrophobic coating. The self-cleaning property of the coatings was evaluated by applying chalk dust particles as simulated solid contaminants and different kinds of liquids (including grape juice, beer, cola, and blue ink) as liquid contaminants. The coating remained superhydrophobic after physical and chemical damage tests. This work presents a strategy for fabricating superhydrophobic biomimetic composite coatings with significant self-cleaning properties, durability, and shows great potential for practical engineering applications.

ABSTRACT Antimicrobial resistance (AMR) is becoming one of the largest threats to public health worldwide, with the opportunistic pathogen Escherichia coli playing a major role in the AMR global health crisis. Unravelling the complex interplay between drug resistance and metabolic rewiring is key to understand the ability of bacteria to adapt to new treatments and to the development of new effective solutions to combat resistant infections. We developed a computational pipeline that combines machine learning with genome-scale metabolic models (GSMs) to elucidate the systemic relationships between genetic determinants of resistance and metabolism beyond annotated drug resistance genes. Our approach was used to identify genetic determinants of 12 AMR profiles for the opportunistic pathogenic bacterium E. coli. Then, to interpret the large number of identified genetic determinants, we applied a constraint-based approach using the GSM to predict the effects of genetic changes on growth, metabolite yields, and reaction fluxes. Our computational platform leads to multiple results. First, our approach corroborates 225 known AMR-conferring genes, 35 of which are known for the specific antibiotic. Second, integration with the GSM predicted 20 top-ranked genetic determinants (including accA, metK, fabD, fabG, murG, lptG, mraY, folP, and glmM) essential for growth, while a further 17 top-ranked genetic determinants linked AMR to auxotrophic behavior. Third, clusters of AMR-conferring genes affecting similar metabolic processes are revealed, which strongly suggested that metabolic adaptations in cell wall, energy, iron and nucleotide metabolism are associated with AMR. The computational solution can be used to study other human and animal pathogens. IMPORTANCE Escherichia coli is a major public health concern given its increasing level of antibiotic resistance worldwide and extraordinary capacity to acquire and spread resistance via horizontal gene transfer with surrounding species and via mutations in its existing genome. E. coli also exhibits a large amount of metabolic pathway redundancy, which promotes resistance via metabolic adaptability. In this study, we developed a computational approach that integrates machine learning with metabolic modeling to understand the correlation between AMR and metabolic adaptation mechanisms in this model bacterium. Using our approach, we identified AMR genetic determinants associated with cell wall modifications for increased permeability, virulence factor manipulation of host immunity, reduction of oxidative stress toxicity, and changes to energy metabolism. Unravelling the complex interplay between antibiotic resistance and metabolic rewiring may open new opportunities to understand the ability of E. coli, and potentially of other human and animal pathogens, to adapt to new treatments.

Cronobacter is a foodborne pathogen associated with severe infections and high mortality in neonates. The bacterium may also cause gastroenteritis, septicemia, and urinary tract and wound infectious in adults. A total of 15 Cronobacter isolates collected from 617 raw materials and environment samples from Powdered Infant Formula manufacturing factories during 2016 in Shaanxi, China, were analyzed for antimicrobial susceptibilities, species identification, biofilm formation, and whole-genome sequencing. The results showed that all 15 isolates were Cronobacter sakazakii, while the antimicrobial susceptibility test showed that all 15 C. sakazakii were pan susceptible. Most isolates were able to produce a weak biofilm, and two isolates from soil samples produced a strong biofilm formation. All isolates were classified into seven STs including ST4, ST40, ST64, ST93, ST148, ST256, and ST494, with ST64 (4/15, 26.7%) being dominant, and most were clinically related. The isolates harbored at least 11 virulence genes and two plasmids, with one isolate being positive for all virulence genes. Phylogenetic and ANI analysis showed strong clustering by sequence types and isolates from different sources or regions with a similar genomic background. The fact that isolates were obtained from raw materials and environment samples of PIF facilities shared a close phylogeny with one another suggests that cross-contamination events may have occurred between the processing room and external environments, which may give rise to a recurring risk of a continuous contamination during production.

Listeria innocua are Gram-positive rod-shaped bacteria, which are not generally infectious as opposed to Listeria monocytogenes. However, the comparatively high genomic similarity between both along with on occasion, their coexistence in similar ecological niches may present the opportunity for resistance or virulence gene transfer. In this study, three multi-drug resistant L. innocua originally cultured from food were put forward for long-read genome sequencing. Chromosome and plasmid genomes were assembled and annotated. Analysis demonstrated that the resistant phenotypes correlated well with genotypes. Three plasmids pLI42, pLI203, and pLI47-1 were identified which harbor resistance islands. Sequence alignments suggested that plasmids pLI42 and pLI203 were highly similar to a previously sequenced L. monocytogenes plasmid pLR1. Similarly, another three types of resistance gene islands were observed on chromosome, including tet(M) gene islands (transposon Tn916 orthologs), dfrG gene islands and optrA-erm(A) gene islands. All three L. innocua isolates possessed listeria pathogenicity island-4 (LIPI-4) which is linked to cases of mengitis. Further genome environment and phylogenic analysis of regions flanking LIPI-4 of L. innocua and L. monocytogenes showed that these may have common origins and with the potential to transmit from the former. Our findings raise the possible need to include both L. monocytogenes and L. innocua in food surveillance programs so as to further understand of the origins of antimicrobial resistance and virulence markers of public health importance in L. monocytogenes.

The mcr-1 gene mediating mobile colistin resistance in Escherichia coli was first reported in China in 2016 followed by reports among different species worldwide, especially in E. coli and Klebsiella. However, data on its transmission in Salmonella are still lacking. This study analyzed the antimicrobial resistance (AMR) profiles and the mcr-1 gene presence in 755 foodborne Salmonella from 26 provinces of mainland, China in 2016. Genomic features of two mcr-1-carrying isolates, genome sequencing, serotypes and further resistance profiles were studied. Among the 755 Salmonella tested, 72.6% were found to be resistant to at least one antimicrobial agent and 10% were defined as multi-drug resistant (MDR). Salmonella Derby CFSA231 and Salmonella Typhimurium CFSA629 were mcr-1-harboring isolates. Both expressed an MDR phenotype and included a single circular chromosome and one plasmid. Among the 22 AMR genes identified in S. Derby CFSA231, only the mcr-1 gene was localized on the IncX4 type plasmid pCFSA231 while 20 chromosomal AMR genes, including four plasmid-mediated quinolone resistance (PMQR) genes, were mapped within a 64 kb Salmonella genomic island (SGI) like region. S. Typhimurium CFSA629 possessed 11 resistance genes including an mcr-1.19 variant and two ESBL genes. Two IS26-flanked composite-like transposons were identified. Additionally, 153 and 152 virulence factors were separately identified in these two isolates with secretion system and fimbrial adherence determinants as the dominant virulence classes. Our study extends our concern on mcr-1-carrying Salmonella in regards to antimicrobial resistance and virulence factors, and highlight the importance of surveillance to mitigate dissemination of mcr-encoding genes among foodborne Salmonella.

ABSTRACT Staphylococcus aureus is a worldwide leading cause of numerous diseases ranging from food-poisoning to lethal infections. Methicillin-resistant S. aureus (MRSA) has been found capable of acquiring resistance to most antimicrobials. MRSA is ubiquitous and diverse even in terms of antimicrobial resistance (AMR) profiles, posing a challenge for treatment. Here, we present a comprehensive study of S. aureus in China, addressing epidemiology, phylogenetic reconstruction, genomic characterization, and identification of AMR profiles. The study analyzes 673 S. aureus isolates from food as well as from hospitalized and healthy individuals. The isolates have been collected over a 9-year period, between 2010 and 2018, from 27 provinces across China. By whole-genome sequencing, Bayesian divergence analysis, and supervised machine learning, we reconstructed the phylogeny of the isolates and compared them to references from other countries. We identified 72 sequence types (STs), of which, 29 were novel. We found 81 MRSA lineages by multilocus sequence type (MLST), spa, staphylococcal cassette chromosome mec element (SCCmec), and Panton-Valentine leukocidin (PVL) typing. In addition, novel variants of SCCmec type IV hosting extra metal and antimicrobial resistance genes, as well as a new SCCmec type, were found. New Bayesian dating of the split times of major clades showed that ST9, ST59, and ST239 in China and European countries fell in different branches, whereas this pattern was not observed for the ST398 clone. On the contrary, the clonal transmission of ST398 was more intermixed in regard to geographic origin. Finally, we identified genetic determinants of resistance to 10 antimicrobials, discriminating drug-resistant bacteria from susceptible strains in the cohort. Our results reveal the emergence of Chinese MRSA lineages enriched of AMR determinants that share similar genetic traits of antimicrobial resistance across human and food, hinting at a complex scenario of evolving transmission routes. IMPORTANCE Little information is available on the epidemiology and characterization of Staphylococcus aureus in China. The role of food is a cause of major concern: staphylococcal foodborne diseases affect thousands every year, and the presence of resistant Staphylococcus strains on raw retail meat products is well documented. We studied a large heterogeneous data set of S. aureus isolates from many provinces of China, isolated from food as well as from individuals. Our large whole-genome collection represents a unique catalogue that can be easily meta-analyzed and integrated with further studies and adds to the library of S. aureus sequences in the public domain in a currently underrepresented geographical region. The new Bayesian dating of the split times of major drug-resistant enriched clones is relevant in showing that Chinese and European methicillin-resistant S. aureus (MRSA) have evolved differently. Our machine learning approach, across a large number of antibiotics, shows novel determinants underlying resistance and reveals frequent resistant traits in specific clonal complexes, highlighting the importance of particular clonal complexes in China. Our findings substantially expand what is known of the evolution and genetic determinants of resistance in food-associated S. aureus in China and add crucial information for whole-genome sequencing (WGS)-based surveillance of S. aureus.

Kidney damage: Identifying mechanisms behind uric acid effects High serum levels of uric acid cause kidney tissue damage through cellular processes that have now been identified by researchers in China. Uric acid is a common component of urine, but causes damage if it is present in high levels in the blood (hyperuricemia). While investigating the mechanisms behind hyperuricemia, Zhibin Ye and co-workers at Fudan University in Shanghai recently showed that impairment of the Na+-K+-ATPase (NKA) signaling pathway, which regulates uric acid transportation through the kidneys, is a crucial feature of renal damage progression. The team have now shown that NKA is regulated by the AMP-activated protein kinase (AMPK) pathway, and that AMPK is enriched during the initial phases of hyperuricemia. Studies on rat models indicated that sustained AMPK activation restored NKA signaling, limiting damage from hyperuricemia.

Interferons (IFNs) play a major role in the host’s antiviral innate immunity. In response to viral infection, IFNs bind their receptors and initiate a signaling cascade, leading to the accurate transcriptional regulation of hundreds of IFN-stimulated genes (ISGs). Porcine rotavirus (PoRV) belongs to genus Rotavirus of the Reoviridae family; the infection is a global epidemic disease and a major threat to the pig industry. In this study, we found that IFN-λ3 inhibited the replication of PoRV in both MA104 cells and IPEC-J2 cells, and this inhibition was dose-dependent. Furthermore, the antiviral activity of IFN-λ3 was more potent in IPEC-J2 cells than in MA104 cells. Further research showed that IFN-λ3 and IFN-α might inhibit PoRV infection by activating ISGs, i.e., MxA, OASL and ISG15, in IPEC-J2 cells. However, the co-treatment of IFN-λ3 and IFN-α did not enhance the antiviral activity. Our data demonstrated that IFN-λ3 had antiviral activity against PoRV and may serve as a useful antiviral candidate against PoRV, as well as other viruses in swine.