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Abstract Background Dogs—whether pets, rural, or stray—exhibit distinct living styles that influence their fecal microbiota and resistomes, yet these dynamics remain underexplored. This study aimed to analyze and compare the fecal microbiota and resistomes of three groups of dogs (37 pets, 20 rural, and 25 stray dogs) in Shanghai, China. Results Metagenomic analysis revealed substantial differences in fecal microbial composition and metabolic activities among the dog groups. Pet dogs displayed the lowest microbial diversity. Using Shapley Additive Explanations (SHAP), an interpretable machine learning approach, Ligilactobacillus emerged as the most diverse genus, with significantly higher SHAP values in stray dogs, suggesting enhanced adaptability to more variable and less controlled environments. Across all samples, 587 antibiotic resistance genes (ARGs) were identified, conferring resistance to 14 antibiotic classes. A striking observation was the detection of mcr-1 in one pet dog, indicating a potential public health risk. The floR gene was identified as a key differentiator in resistance profiles, particularly in pet and rural dogs, likely due to antibiotic exposure in their environments. Conclusion This study provides the first comprehensive assessment of fecal microbiota and resistome variations among dogs with different lifestyles, revealing a less resilient microbiome and heightened antimicrobial resistance in pet dogs, which could have public health implications. Graphical Abstract

Abstract Background The zoonotic infectious diseases of poverty (zIDPs) are a group of diseases contributing to global poverty, with significant impacts on a substantial population. This study aims to describe the global, regional, and national burden of zIDPs—schistosomiasis, cystic echinococcosis, cysticercosis, and food-borne trematodiases (FBTs)—to support policy making and resource allocation for their control and elimination. Methods Data of zIDPs from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 were retrieved from 1990 to 2021. The age-standardized prevalence rate (ASPR), age-standardized mortality rate (ASMR), and age-standardized disability-adjusted life-year (DALY) rate were described and the estimated annual percentage changes (EAPCs) were calculated to quantify their burden and temporal trends. Spearman correlation analysis was conducted to examine the relationship between age-standardized rates and Socio-demographic Index (SDI). Results In 2021, these zIDPs exhibited a certain level of ASPRs and age-standardized DALY rates, while maintaining relatively low ASMRs. Noticeably, schistosomiasis presented the highest ASPR of 1914.299 (95% UI: 1378.920, 2510.853 per 100,000 population) and an age-standardized DALY rate of 21.895 (95% UI: 12.937, 37.278 per 100,000 population) among the zIDPs. The tapestry of burden—woven predominantly through low and lower-middle SDI regions—stretched across Africa, Latin America, and parts of Asia. From 1990 to 2021, a kaleidoscopic shift was observed globally as ASPRs, ASMRs, and age-standardized DALY rates declined significantly, as reflected by the EAPC values. Negative correlations were observed between the ASPRs, ASMRs, age-standardized DALY rates of schistosomiasis (r value = − 0.610, − 0.622 and − 0.610), cystic echinococcosis (− 0.676 of ASMR, − 0.550 of age-standardized DALYs), cysticercosis (− 0.420, − 0.797 and − 0.591) and the SDI. In contrast, a slight positive correlation was noted between the ASPR, age-standardized DALY rates of FBTs and SDI with r value of 0.221 and 0.213, respectively. Conclusion The burden of zIDPs declined across almost all endemic regions from 1990 to 2021, yet still predominated in low and low-middle SDI regions. Substantial challenges exist to achieve the goal of control and elimination of zIDPs, and integrated approaches based on One Health need to be strengthened to improve health outcomes. Graphical Abstract

Abstract Background Certain infectious diseases are caused by specific bacterial pathogens, including syphilis, gonorrhea, typhoid and paratyphoid fever, diphtheria, pertussis, tetanus, leprosy, and tuberculosis. These diseases significantly impact global health, contributing heavily to the disease burden. The study aims to thoroughly evaluate the global burden of syphilis, gonorrhea, typhoid and paratyphoid fever, diphtheria, pertussis, tetanus, and leprosy. Methods Leveraging the Global Burden of Disease (GBD) study 2021, age-specific and Socio-demographic Index (SDI)-specific incidence, disability-adjusted life-years (DALYs), and death for eight specific bacterial infections across 204 countries and territories from 1990 to 2021 were analyzed. Percentage changes in age-standardized incidence rate (ASIR), DALY rate, and mortality rate (ASMR) were also examined, with a focus on disease distribution across different regions, age groups, genders, and SDI. Results By 2021, among the eight diseases, gonococcal infection had the highest global ASIR [1096.58 per 100,000 population, 95% uncertainty interval (UI): 838.70, 1385.47 per 100,000 population], and syphilis had the highest global age-standardized DALY rate (107.13 per 100,000 population, 95% UI: 41.77, 212.12 per 100,000 population). Except for syphilis and gonococcal infection, the age-standardized DALY rate of the remaining diseases decreased by at least 55% compared to 1990, with tetanus showing the largest decrease by at least 90%. Globally, significant declines in the ASIR, age-standardized DALY rate, and ASMR for these eight bacterial infections have been observed in association with increases in the SDI. Regions with lower SDI, such as sub-Saharan Africa, experienced a relatively higher burden of these eight bacterial infections. Conclusions Although there has been an overall decline in these eight diseases, they continue to pose significant public health challenges, particularly in low SDI regions. To further reduce this burden in these areas, targeted intervention strategies are essential, including multi-sectoral collaboration, policy support, improved WASH management, and enhanced research efforts. Graphical Abstract

Abstract Ventilator-associated pneumonia (VAP) and pyogenic liver abscess (PLA) due to Klebsiella pneumoniae infection can trigger life-threatening malignant consequences, however, there are few studies on the strain-associated clinical pathogenic mechanisms between VAP and PLA. A total of 266 patients consist of 129 VAP and 137 PLA were included for analysis in this study. We conducted a comprehensive survey for the two groups of K. pneumoniae isolates, including phenotypic experiments, clinical epidemiology, genomic analysis, and instrumental analysis, i.e., to obtain the genomic differential profile of K. pneumoniae strains responsible for two distinct infection outcomes. We found that PLA group had a propensity for specific underlying diseases, especially diabetes and cholelithiasis. The resistance level of VAP was significantly higher than that of PLA (78.57% vs. 36%, P

Abstract Background Antimicrobial resistance (AMR) is one of the greatest threats to animal and public health. Here, we conducted a dynamic surveillance of Escherichia coli on Chongming Island in Shanghai during 2009–2021 to identify the characteristics and trends of Chongming’s AMR pandemic. Methods Rectal (cloaca) swabs from four poultry and nine swine farms (Chongming Island, 2009–2021) were collected for E. coli strains acquisition. The micro-broth dilution method was used to test antimicrobial susceptibility of E. coli isolates against 10 antimicrobial classes including 15 antimicrobials. Utilizing generalized linear mixed models (GLMMs) and co-occurrence analyses, we further explored the multiple-drug-resistance (MDR) combinations and dynamic patterns of E. coli over 10 years in two food animals. Results Total of 863 MDR isolates were found among 945 collected E. coli isolates, 337 from poultry and 608 from swine. Both isolates exhibited high resistant rates (> 70%) to tetracyclines, phenicols, sulfonamides, penicillins, and aminoglycosides (only in swine). The resistant rates of swine isolates to penicillins, aminoglycosides, tetracyclines, phenicols, and polymyxins were significantly higher than those of poultry isolates, whereas resistance to fluoroquinolones was reversed. Resistance to polymyxins decreased similarly in swine (42.4% in 2009 to 0.0% in 2021) and poultry isolates (from 16.5% to 0.0%). However, resistance to other seven antimicrobial classes (excluding carbapenems and penicillins) declined dramatically in swine isolates, particularly fluoroquinolones (from 80.5% to 14.4%), and tendencies of resistance to the seven classes showed markedly divergent patterns in poultry isolates. Using Poisson GLMMs, the AMR carriage since 2016 was significantly lower than that of 2009 (odds ratio

Abstract Background Antimicrobial resistance (AMR) is one of the top ten global public health challenges. However, given the lack of a comprehensive assessment of worldwide AMR status, our objective is to develop a One Health-based system-wide evaluation tool on global AMR. Methods We have further developed the three-hierarchical Global One Health Index (GOHI)-AMR indicator scheme, which consists of five key indicators, 17 indicators, and 49 sub-indicators, by incorporating 146 countries’ data from diverse authoritative databases, including WHO's Global Antimicrobial Resistance and Use Surveillance System (GLASS) and the European CDC. We investigated the overall- or sub-rankings of GOHI-AMR at the international/regional/national levels for data preprocessing and score calculation utilizing the existing GOHI methodology. Additionally, a correlation analysis was conducted between the GOHI-AMR and other socioeconomic factors. Results The average GOHI-AMR score for 146 countries is 38.45. As expected, high-income countries (HICs) outperform the other three income groups on overall rankings and all five key indicators of GOHI-AMR, whereas low-income countries unexpectedly outperform upper-middle-income countries and lower-middle-income countries on the antibiotics-resistant key indicator (ARR) and ARR-subordinate indicators, including carbapenem-, β-lactam-, and quinolone resistance, and even HICs on aminoglycoside resistance. There were no significant differences among the four groups on the environmental-monitoring indicator (P > 0.05). GOHI-AMR was positively correlated with gross domestic product, life expectancy, and AMR-related publications, but negatively with natural growth rate and chronic respiratory disease. In contrast to Cyprus, the remarkably lower prevalence of "ESKAPE pathogens" in high-scoring Sweden and Denmark highlights Europe's huge gaps. China and Russia outperformed the other three BRICS countries on all key indicators, particularly India's ARR and Brazil's AMR laboratory network and coordination capacity. Furthermore, significant internal disparities in carbapenem-resistant Klebsiella pneumoniae (CRKP) and methicillin-resistant Staphylococcus aureus (MRSA) prevalence were observed between China and the USA, with MRSA prevalence both gradually declining, whereas CRKP prevalence has been declining in the USA but increasing in China, consistent with higher carbapenems-related indicator’ performance in USA. Conclusions GOHI-AMR is the most comprehensive tool currently available for the assessment of AMR status worldwide. We discovered unique features impacting AMR in each country and offered precise recommendations to improve the capacity to tackle AMR in low-ranking countries. Graphical Abstract

Abstract Background Brucellosis poses a serious threat to human and animal health, particularly in developing countries such as China. The Inner Mongolia Autonomous Region is one of the most severely brucellosis-endemic provinces in China. Currently, the host immune responses functioning to control Brucella infection and development remain poorly understood. The aim of this study is to further clarify the key immunity characteristics of diverse stages of brucellosis in Inner Mongolia. Methods We collected a total of 733 blood samples from acute (n = 137), chronic (n = 316), inapparent (n = 35), recovery (n = 99), and healthy (n = 146) groups from the rural community of Inner Mongolia between 2014 and 2015. The proportions of CD4+, CD8+, Th1, Th2, and Th17 T cells in peripheral blood and the expression of TLR2 and TLR4 in lymphocytes, monocytes and granulocytes were examined using flow cytometry analysis. The differences among the five groups were compared using one-way ANOVA and the Kruskal–Wallis method, respectively. Results Our results revealed that the proportions of CD4+ and CD8+ T cells were significantly different among the acute, chronic, recovery, and healthy control groups (P 0.05). The proportion of Th2 lymphocytes was significantly higher in the acute and healthy groups than in the inapparent group (P 0.5), except for the inapparent group between lymphocytes and granulocytes (r = 0.34). Conclusions Two key factors (CD8+ T cells and TLR4) in human immune profiles may closely correlate with the progression of brucellosis. The detailed function of TLR4 in the context of a greater number of cell types or tissues in human or animal brucellosis and in larger samples should be further explored in the future. Graphical Abstract

Abstract High levels of ROS cause oxidative stress, which plays a critical role in cell death. As a ROS effector protein, PRL2 senses ROS and controls phagocyte bactericidal activity during infection. Here we report PRL2 regulates oxidative stress induced cell death. PRL2 senses oxidative stress via highly reactive cysteine residues at 46 and 101. The oxidation of PRL2 causes protein degradation and supports pro-survival PDK1/AKT signal which in turn to protect cells against oxidative stress. As a result, PRL2 levels have a high correlation with oxidative stress induced cell death. In vivo experiments showed PRL2 deficient cells survive better in inflammatory oxidative environment and resist to ionizing radiation. Our finding suggests PRL2 serves as a negative regulator in cell adaptation to oxidative stress. Therefore, PRL2 could be targeted to modulate cell viability in inflammation or irradiation associated therapy.

Abstract We have entered the post-antibiotic era. Phage therapy has recently been given renewed attention because bacteriophages are easily available and can kill bacteria. Many reports have demonstrated successful phage treatment of bacterial infection, whereas some studies have shown that phage therapy is not as effective as expected. In general, establishment of a standard operating procedure will ensure the success of phage therapy. In this paper, the whole operating procedure for phage therapy in clinical practice is explored and analyzed to comprehensively understand the success of using phage for the treatment of bacterial infectious disease in the future. The procedure includes the following: enrollment of patients for phage therapy; establishment of phage libraries; pathogenic bacterial isolation and identification; screening for effective phages against pathogenic bacteria; phage formulation preparation; phage preparation administration strategy and route; monitoring the efficacy of phage therapy; and detection of the emergence of phage-resistant strains. Finally, we outline the whole standard operating procedure for phage therapy in clinical practice. It is believed that phage therapy will be used successfully, especially in personalized medicine for the treatment of bacterial infectious diseases. Hopefully, this procedure will provide support for the entry of phage therapy into the clinic as soon as possible.