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ABSTRACT Non-typhoidal Salmonella (NTS) is a common zoonotic foodborne pathogen, whose rising antimicrobial resistance has been an urgent threat to global public health. Here, we reported two carbapenem-resistant Salmonella enterica (CRSE) strains (NBFE-049 and NBFE-164) carrying the blaNDM genes, which were recovered from two Chinese children, belonged to Salmonella enterica serovar Typhimurium (S. Typhimurium) monophasic variant (S. 1,4,[5],12:i:-) ST34 (a sequence type) and S. Typhimurium ST19, respectively. Genes blaNDM-5 and blaNDM-13 were detected in NBFE-049 and NBFE-164, respectively. The blaNDM-5 in NBFE-049 was located in an IncHI2-type plasmid, named pNBFE-049. In NBFE-164, the blaNDM-13 was located in an IncI1-type plasmid, named pNBFE-164. The plasmid pNBFE-164 successfully transferred its resistance phenotype into the recipient strain Escherichia coli J53 with a high efficiency of 1.1 × 10−2, while no transconjugants were obtained in pNBFE-049 conjugation assays. We further elucidated the genetic relationships of globally occurring New Delhi Metallo-β-lactamase (NDM)-positive strains and locally distributed clinical strains within the same serovar. The closest relative of NBFE-049 was clinical Salmonella strain 1722, which was recovered in 2020 and differed by only three Single Nucleotide Polymorphisms (SNPs). No NDM-positive ST19 could be found in the National Center for Biotechnology Information (NCBI) database, and NBFE-164 showed a close genetic relationship with the other ST19 in this area. To sum up, we suggested the potential contributions of clonal spread and plasmid-mediated blaNDM transfer in CRSE dissemination. This study reported the complete genome of two blaNDM-carrying S. Typhimurium isolates, shedding new insights into the antimicrobial resistance mechanisms and dissemination patterns of the emerging CRSE.IMPORTANCENTS is one of the most common zoonotic pathogens that causes foodborne illnesses, while S. Typhimurium is one of the most common serovars. With the rising prevalence of multi-resistant Salmonella worldwide, carbapenems have emerged as the last-line antibiotics for treating severe bacterial infections. In this study, we reported the genomic characteristics of two carbapenem-resistant S. Typhimurium strains, which were recovered from two pediatric patients, carrying blaNDM-5 and blaNDM-13, providing new insights into the antimicrobial resistance deteriminants and transmission risk of blaNDM-positive NTS in China. We suggested the potential contributions of clonal spread and plasmid-mediated blaNDM transfer in CRSE dissemination. Future enhanced surveillance policy should mitigate CRSE spreading, and more importantly, clinical antimicrobial therapeutic regimens should be adjusted accordingly.

Abstract Background Duck hepatitis A virus (DHAV) is a single-stranded, positive-strand small RNA virus that causes a very high mortality rate in ducklings. The DHAV-3 subtype incidence rate has recently increased in China, causing great economic losses to the waterfowl breeding industry. We analyzed the protection rate of DHAV vaccines used in mainland China from 2009 to 2021 and evaluated the effectiveness of vaccine prevention and control to reduce the economic losses caused by DHAV to the waterfowl breeding industry. We screened five electronic research databases and obtained 14 studies and patents on the protection efficiency of DHAV-1 and DHAV-3 vaccines. Results Meta-analysis demonstrated that immunized ducklings produced higher antibody levels and had a significantly higher survival rate than non-immunized ducklings [relative risk (RR) = 12, 95% confidence interval (CI) 6–26, P

Angluin's L$^*$ algorithm learns the minimal deterministic finite automaton (DFA) of a regular language using membership and equivalence queries. Its probabilistic approximatively correct (PAC) version substitutes an equivalence query by numerous random membership queries to get a high level confidence to the answer. Thus it can be applied to any kind of device and may be viewed as an algorithm for synthesizing an automaton abstracting the behavior of the device based on observations. Here we are interested on how Angluin's PAC learning algorithm behaves for devices which are obtained from a DFA by introducing some noise. More precisely we study whether Angluin's algorithm reduces the noise and produces a DFA closer to the original one than the noisy device. We propose several ways to introduce the noise: (1) the noisy device inverts the classification of words w.r.t. the DFA with a small probability, (2) the noisy device modifies with a small probability the letters of the word before asking its classification w.r.t. the DFA, (3) the noisy device combines the classification of a word w.r.t. the DFA and its classification w.r.t. a counter automaton, and (4) the noisy DFA is obtained by a random process from two DFA such that the language of the first one is included in the second one. Then when a word is accepted (resp. rejected) by the first (resp. second) one, it is also accepted (resp. rejected) and in the remaining cases, it is accepted with probability 0.5. Our main experimental contributions consist in showing that: (1) Angluin's algorithm behaves well whenever the noisy device is produced by a random process, (2) but poorly with a structured noise, and, that (3) is able to eliminate pathological behaviours specified in a regular way. Theoretically, we show that randomness almost surely yields systems with non-recursively enumerable languages.

Hepatic ischemia-reperfusion injury (HIRI) is a complex pathological phenomenon dominated by the innate immune system and involves a variety of immune cells. This condition frequently occurs during hepatectomy, liver transplantation or hemorrhagic shock. HIRI represents an important factor in the poor prognosis of patients after liver surgery. However, there is still a lack of effective intervention to reduce the incidence of HIRI. In this study, we aimed to describe the overall structure of scientific research on HIRI over the past 20 years and provide valuable information and guidelines for future researchers. Bibliometric analysis was used to comprehensively review developments in HIRI and changes in our understanding of HIRI over the past two decades. We identified a total of 4267 articles on HIRI that were published over the past 20 years of which basic research was predominant. Collaboration network analysis revealed that China, the University of California Los Angeles, and Ronald W Busuttil were the most influential country, institute, and scholar, respectively. Co-occurrence cluster analysis revealed that ischemic preconditioning, liver cirrhosis, hepatic I/R injury, autophagy, acute liver failure, oxygen, donation after circulatory death, Nlrp3, remote organ, and microdialysis were the top 10 clusters. Keyword burst detection indicated that autophagy, inflammation, and early allograft dysfunction represent the current research hotspots. In summary, this is the first bibliometric analysis of HIRI research. Our timely analysis of these hotpots and research trends may provide a framework for future researchers and further promote research on the key mechanisms and therapeutic measures in this field.

Abstract Background There is unmet need for effective therapies of intrauterine adhesions (IUAs) that are common cause of menstrual disturbance and infertility, since current clinical procedures do not improve prognosis for patients with moderate to severe IUA, with a recurrence rate of 23–50%. Stem cell-based therapy has emerged as a therapeutic option with unsolved issues for IUA patients in the past few years. Primary endometrial epithelial cells for cell therapy are largely hampered with the extremely limited proliferation capacity of uterine epithelial cells. This study was to evaluate whether IUA is curable with conditionally reprogrammed (CR) endometrial epithelial cells. Methods Mouse endometrial epithelial cells (MEECs) were isolated from C57BL female mice, and long-term cultures of MEECs were established and maintained with conditional reprogramming (CR) method. DNA damage response analysis, soft agar assay, and matrigel 3D culture were carried out to determine the normal biological characteristics of CR-MEECs. The tissue-specific differentiation potential of MEECs was analyzed with air–liquid interface (ALI) 3D culture, hematoxylin and eosin (H&E) staining, Masson’s trichrome and DAB staining, immunofluorescence assay. IUA mice were constructed and transplanted with CR-MEECs. Repair and mechanisms of MEECs transplantation in IUA mice were measured with qRT-PCR, Masson’s trichrome, and DAB staining. Results We first successfully established long-term cultures of MEECs using CR approach. CR-MEECs maintained a rapid and stable proliferation in this co-culture system. Our data confirmed that CR-MEECs retained normal biological characteristics and endometrium tissue-specific differentiation potential. CR-MEECs also expressed estrogen and progesterone receptors and maintained the exquisite sensitivity to sex hormones in vitro. Most importantly, allogeneic transplantation of CR-MEECs successfully repaired the injured endometrium and significantly improved the pregnancy rate of IUA mice. Conclusions Conditionally reprogrammed physiological endometrial epithelial cells provide a novel strategy in IUA clinics in a personalized or generalized manner and also serve as a physiological model to explore biology of endometrial epithelial cells and mechanisms of IUA.

Abstract Background Pregnancy-associated listeriosis is a severe infectious disease and potentially leads to fetal/neonatal fatal, while limited information on pregnancy-associated listeriosis is available in China. This study aimed to reveal the clinical characteristics and outcomes of pregnancy-associated listeriosis cases and provide references for treating and managing this disease. Methods We performed a retrospective study on maternal and neonatal patients with pregnancy-associated listeriosis. The clinical characteristics of pregnancy-associated listeriosis were studied, and the outcome determinants of neonatal listeriosis were explored. Results 14 cases of pregnancy-associated listeriosis were identified. The incidence of pregnancy-associated listeriosis in our hospital was 16.69/100,000 births. All of the 14 maternal patients eventually recovered after delivery shortly with no sequelae. None of the 12 mothers who delivered in this hospital received antepartum first-line empirical treatment. Among the 14 neonatal cases, 1 was late-onset listeriosis and 13 were early-onset cases; 11 survived and 3 died. Fatality rates were significantly higher in outborn neonates (P = 0.005). Besides, higher mortality rates were observed in neonates with lower birth weight (P = 0.038), gestational age

With the improvement of people's material living standards, more and more people start to pay attention to health issues. This paper takes the health field as the main research object, and discusses the current development and status quo of the health field. Through literature review, it is found that the current health field mainly focuses on the single monitoring of a certain organ or body function, and there are limitations in systematic health monitoring research, and most of the research stays at the stage of human body monitoring. Therefore, this paper intends to design a sports health monitoring and management system based on artificial intelligence. The system is mainly divided into a body temperature monitoring module, a blood pressure monitoring module and an exercise monitoring module, through which the user's health data is monitored. In order to ensure the practicability of the system, this paper selects three common life states in daily life for experimental testing, namely exercise state, rest state and sick state. The experimental test results show that each monitoring module can operate correctly and normally under three different states. The lowest temperature was 36.5° and the highest temperature was 37.1° under the exercise state. The lowest blood pressure is 70 in the resting state, and the highest blood pressure is 80. In the sick state, the maximum value of motor threshold is 0.2, the minimum value is 0.1, and the threshold difference is 0.1. Each module reads and backs up relevant data, and sends it to the platform for intelligent analysis. The platform will analyze and compare the data of different modules at the same time, judge the health status of the user at that time, choose whether to issue a health alert for the user, and finally complete the entire system process of the health monitoring management system. This proves that the sports health monitoring management system based on artificial intelligence algorithm designed in this paper is effective and feasible.

Burn is one of the leading causes of death and disability in children worldwide, and wound infection is an excellent challenge in burn treatment. We performed a retrospective review of pediatric burn patients with wound infections to reveal their clinical data and investigate pathogens’ distribution and drug resistance patterns to provide references for treatment. As a result, 330 pediatric burn patients with wound infections were identified; 65.8% (217/330) were

Abstract Background This study aims to determine the real incidence of pericolic lymph nodes metastasis beyond 10 cm proximal to the tumor (pPCN) and its prognostic significance in rectal cancer patients. Methods Consecutive patients with rectal cancer underwent curative resection between 2015 and 2017 were included. Margin distance was marked and measured in vivo and lymph nodes were harvested on fresh specimens. Clinicopathological characteristics and oncological outcomes (3-year overall survival (OS) and disease-free survival (DFS)) were analyzed between patients with pPCN and patients without pPCN (nPCN). Results There were 298 patients in the nPCN group and 14 patients (4.5%) in pPCN group. Baseline characteristics were balanced except more patients received preoperative or postoperative chemoradiotherapy in pPCN group. Preoperative more advanced cTNM stage (log-rank p = 0.005) and intraoperative more pericolic lymph nodes beyond 10 cm proximal to the tumor (PCNs) (log-rank p = 0.002) were independent risk factors for pPCN. The maximum short-axis diameter of mesenteric lymph nodes ≥8 mm was also contributed to predicting the pPCN. pPCN was an independent prognostic indicator and associated with worse 3-year OS (66% vs 91%, Cox p = 0.033) and DFS (58% vs 92%, Cox p = 0.012). Conclusion The incidence of pPCN was higher than expected. Patients with high-risk factors (cTNM stage III or more PCNs) might get benefits from an extended proximal bowel resection to avoid residual positive PCNs.

Objective Patients with non-small-cell lung cancer (NSCLC) and primary or acquired resistance do not respond to targeted drugs. We explored whether cancer cells can be cultured from liquid biopsies from patients with primary resistance to tyrosine kinase inhibitors (TKIs). We aimed to predict patients’ responses to drugs according to in vitro drug testing results. Methods Cancer cell cultures were established from the pleural effusion of a patient with TKI-resistant NSCLC using a conditional reprogramming technique. Phenotypic drug sensitivity tests were performed using the Cell Counting Kit-8 assay. We tested individual drugs and compared the synergistic and inhibitory effects of drug combinations. Results The results of our in vitro sensitivity test using the combination of cisplatin and pemetrexed were correlated with the patient’s response. Conclusion This represents the first successful report of predictive testing for combination therapy in patients with epidermal growth factor receptor-mutant NSCLC and primary TKI resistance. This strategy should be applicable to both chemotherapies and targeted therapies, and it will significantly improve the clinical treatment and management of patients with NSCLC and primary or acquired resistance to targeted therapies, as well as patients lacking targetable mutations.

Staphylococcus epidermidis is frequently associated with biofilm-related infections. Biofilms drastically reduce the efficacy of conventional antibiotics and the host immune system. In S. epidermidis biofilm formation, a major role is played by the YycG/YycF two-component system, and previous findings have indicated that inhibitors targeting the cytoplasmic HATPase_c domain of YycG kinase in S. epidermidis exhibit bactericidal and biofilm-killing activities. Therefore, we hypothesized that monoclonal antibodies (mAbs) against YycG extracellular (YycGex) domain would block the signal transduction and influence the biofilm formation of S. epidermidis. In this study, we screened out two YycGex-specific mAbs showing the highest affinity for the target, mAbs 2F3 and 1H1. These mAbs inhibited S. epidermidis biofilm formation in a dose-dependent manner, and at a concentration of 160 μg/mL, mAbs 2F3 and 1H1 caused 78.3 and 93.1% biofilm reduction, respectively, relative to normal mouse IgG control. When co-cultivated with YycGex mAbs, S. epidermidis cells showed diminished initial-adherence capacity, and the antibody treatment further led to a marked decrease in the synthesis of polysaccharide intercellular adhesin and in the transcriptional level of genes encoding proteins involved in biofilm formation. Lastly, we determined that the epitopes recognized by the two YycGex mAbs are located within aa 59–70 of the YycGex domain. It indicates that the YycGex domain may be a potential candidate as a vaccine for the prevention of S. epidermidis biofilm infections.

Infections of emerging and reemerging viruses (SARS-CoVs, influenza H1N1, etc.) largely and globally affect human health. Animal models often fail to reflect a physiological status because of species tropism of virus infection. Conventional cell lines are usually genetically and phenotypically different from primary cells. Developing an in vitro physiological model to study the infection of emerging viruses will facilitate our understanding of virus-host cell interactions, thereby benefiting antiviral drug discovery. In the current work, we first established normal airway epithelial cells (upper and lower airway track) in 2D and 3D culture systems using conditional reprogramming (CR) and air-liquid interface (ALI) techniques. These long-term cultures maintained differentiation potential. More importantly, these cells express two types of influenza virus receptors, α2-6-Gal- and α2-3-Gal-linked sialic acids, and angiotensin-converting enzyme 2 (ACE2), a receptor for SARS-CoVs as well. These cells were permissive to the infection of pandemic influenza H1N1 (H1N1pdm). In contrast, the lung cancer cell line A549 and immortalized airway epithelial cells (16HBE) were not susceptible to H1N1 infection. A virus-induced cytopathic effect (CPE) on 2D CRC cultures developed in a time-dependent manner. The pathological effects were also readily observed spreading from the apical layer to the basal layer of the 3D ALI culture. This integrated 2D CRC and 3D ALI cultures provide a physiological and personalized in vitro model to study the infection of emerging viruses. This novel model can be used for studying virus biology and host response to viral infection and for antiviral drug discovery.

The two-component signal transduction system PhoP/PhoQ is an important regulator for stress responses and virulence in most Gram-negative bacteria, but characterization of PhoP/PhoQ in Shigella has not been thoroughly investigated. In the present study, we found that deletion of phoPQ (ΔphoPQ) from Shigella flexneri 2a 301 (Sf301) resulted in a significant decline (reduced by more than 15-fold) in invasion of HeLa cells and Caco-2 cells, and less inflammation (− or +) compared to Sf301 (+++) in the guinea pig Sereny test. In low Mg2+ (10 μM) medium or pH 5 medium, the ΔphoPQ strain exhibited a growth deficiency compared to Sf301. The ΔphoPQ strain was more sensitive than Sf301 to polymyxin B, an important antimicrobial agent for treating multi-resistant Gram-negative infections. By comparing the transcriptional profiles of ΔphoPQ and Sf301 using DNA microarrays, 117 differentially expressed genes (DEGs) were identified, which were involved in Mg2+ transport, lipopolysaccharide modification, acid resistance, bacterial virulence, respiratory, and energy metabolism. Based on the reported PhoP box motif [(T/G) GTTTA-5nt-(T/G) GTTTA], we screened 38 suspected PhoP target operons in S. flexneri, and 11 of them (phoPQ, mgtA, slyB, yoaE, yrbL, icsA, yhiWX, rstA, hdeAB, pagP, and shf–rfbU-virK-msbB2) were demonstrated to be PhoP-regulated genes based on electrophoretic mobility shift assays and β-galactosidase assays. One of these PhoP-regulated genes, icsA, is a well-known virulence factor in S. flexneri. In conclusion, our data suggest that the PhoP/PhoQ system modulates S. flexneri virulence (in an icsA-dependent manner) and stress responses of Mg2+, pH and antibacterial peptides.