Survival After Out-of-Hospital Cardiac Arrest Before and After Legislation for Bystander CPR.

Importance: The lack of evidence-based implementation strategies is a major contributor to increasing mortality due to out-of-hospital cardiac arrest (OHCA) in developing countries with limited resources. Objective: To evaluate whether the implementation of legislation is associated with increased bystander cardiopulmonary resuscitation (CPR) and automated external defibrillator (AED) use and improved clinical outcomes for patients experiencing OHCA and to provide policy implications for low-income and middle-income settings. Design, Setting, and Participants: This observational cohort study analyzed a prospective city registry of patients with bystander-witnessed OHCA between January 1, 2010, and December 31, 2022. The Emergency Medical Aid Act was implemented in Shenzhen, China, on October 1, 2018. An interrupted time-series analysis was used to assess changes in outcomes before and after the law. Data analysis was performed from May to October 2023. Exposure: The Emergency Medical Aid Act stipulated the use of AEDs and CPR training for the public and provided clear legal guidance for OHCA rescuing. Main Outcomes and Measures: The primary outcomes were rates of bystander-initiated CPR and use of AEDs. Secondary outcomes were rates of prehospital return of spontaneous circulation (ROSC), survival to arrival at the hospital, and survival at discharge. Results: A total of 13 751 patients with OHCA (median [IQR] age, 59 [43-76] years; 10 011 men [72.83%]) were included, with 7858 OHCAs occurring during the prelegislation period (January 1, 2010, to September 30, 2018) and 5893 OHCAs occurring during the postlegislation period (October 1, 2018, to December 31, 2022). The rates of bystander-initiated CPR (320 patients [4.10%] vs 1103 patients [18.73%]) and AED use (214 patients [4.12%] vs 182 patients [5.29%]) increased significantly after legislation implementation vs rates before the legislation. Rates of prehospital ROSC (72 patients [0.92%] vs 425 patients [7.21%]), survival to arrival at the hospital (68 patients [0.87%] vs 321 patients [5.45%]), and survival at discharge (44 patients [0.56%] vs 165 patients [2.80%]) were significantly increased during the postlegislation period. Interrupted time-series models demonstrated a significant slope change in the rates of all outcomes. Conclusions and Relevance: These findings suggest that implementation of the Emergency Medical Aid Act in China was associated with increased rates of CPR and public AED use and improved survival of patients with OHCA. The use of a systemwide approach to enact resuscitation initiatives and provide legal support may reduce the burden of OHCA in low-income and middle-income settings.

Effects of water stress on nutrients and enzyme activity in rhizosphere soils of greenhouse grape.

In grape cultivation, incorrect water regulation will lead to significant water wastage, which in turn will change soil structure and disrupt soil nutrient cycling processes. This study aimed to investigate the effects of different water regulation treatments [by setting moderate water stress (W1), mild water stress (W2), and adequate water availability (CK)] on soil physical-chemical properties and enzyme activity in greenhouse grape during the growing season. The result showed that the W2 treatment had a negative impact on the build-up of dissolved organic carbon (DOC), nitrate nitrogen (NO3-N), and available phosphorus (AP). Throughout the reproductive period, the W1 and W2 treatments decreased the soil's microbial biomass carbon (MBC) and microbial biomass nitrogen (MBN) contents, and MBC was more vulnerable to water stress. During the growth period, the trends of urease, catalase, and sucrase activities in different soil depth were ranked as 10-20 cm > 0-10 cm > 20-40 cm. The urease activity in 0-10 cm soil was suppressed by both W1 and W2 treatments, while the invertase activity in various soil layers under W1 treatment differed substantially. The W1 treatment also reduced the catalase activity in the 20-40 cm soil layer in the grape growth season. These findings suggested that W2 treatment can conserve water and enhance microbial ecology of greenhouse grape soils. Therefore, W2 treatment was the most effective water regulation measure for local greenhouse grape cultivation.

Impact of Metal Salt Oxidants and Preparation Technology on Efficacy of Bacterial Cellulose/Polypyrrole Flexible Conductive Fiber Membranes.

In this study, we investigated the preparation and characterization of flexible conductive fiber membranes (BC/PPy) using different metal salt oxidants on bacterial cellulose (BC) and pyrrole (Py) in the in situ polymerization and co-blended methods, respectively. The effects of these oxidants, namely, ferric chloride hexahydrate (FeCl3·6H2O) and silver nitrate (AgNO3), on the structural characterization, conductivity, resistance value and thermal stability of the resulting materials were assessed by scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy, Raman spectroscopy and X-ray photoelectron spectroscopy (XPS). A comparative study revealed that the BC/PPy conductive fiber membrane prepared using FeCl3·6H2O as the oxidant had a resistance value of 12 Ω, while the BC/PPy conductive fiber membrane prepared using AgNO3 as the oxidant had an electrical resistance value of 130 Ω. The conductivity of the same molar ratio of BC/PPy prepared using FeCl3·6H2O as an oxidant was 10 times higher than that of the BC/PPy prepared using AgNO3 as an oxidant. Meanwhile, the resistance values of the conductive fiber membranes prepared from BC and PPy by the co-blended method were much higher than the BC/PPy prepared by in situ polymerization. SEM and XPS analyses revealed that when FeCl3·6H2O was used as the oxidant, the Fe-doped polypyrrole conductive particles could form uniform and dense conductive layers on the BC nanofiber surfaces. These two metal salt oxidants demonstrated differences in the binding sites between PPy and BC.

PAD4 controls tumor immunity via restraining the MHC class II machinery in macrophages.

Tumor-associated macrophages (TAMs) shape tumor immunity and therapeutic efficacy. However, it is poorly understood whether and how post-translational modifications (PTMs) intrinsically affect the phenotype and function of TAMs. Here, we reveal that peptidylarginine deiminase 4 (PAD4) exhibits the highest expression among common PTM enzymes in TAMs and negatively correlates with the clinical response to immune checkpoint blockade. Genetic and pharmacological inhibition of PAD4 in macrophages prevents tumor progression in tumor-bearing mouse models, accompanied by an increase in macrophage major histocompatibility complex (MHC) class II expression and T cell effector function. Mechanistically, PAD4 citrullinates STAT1 at arginine 121, thereby promoting the interaction between STAT1 and protein inhibitor of activated STAT1 (PIAS1), and the loss of PAD4 abolishes this interaction, ablating the inhibitory role of PIAS1 in the expression of MHC class II machinery in macrophages and enhancing T cell activation. Thus, the PAD4-STAT1-PIAS1 axis is an immune restriction mechanism in macrophages and may serve as a cancer immunotherapy target.

Transcription factor PbNAC71 regulates xylem and vessel development to control plant height.

Dwarfism is an important agronomic trait in fruit breeding programs. However, the germplasm resources required to generate dwarf pear (Pyrus spp.) varieties are limited. Moreover, the mechanisms underlying dwarfism remain unclear. In this study, 'Yunnan' quince (Cydonia oblonga Mill.) had a dwarfing effect on 'Zaosu' pear. Additionally, the dwarfism-related NAC transcription factor gene PbNAC71 was isolated from pear trees comprising 'Zaosu' (scion) grafted onto 'Yunnan' quince (rootstock). Transgenic Nicotiana benthamiana and pear OHF-333 (Pyrus communis) plants overexpressing PbNAC71 exhibited dwarfism, with a substantially smaller xylem and vessel area relative to the wild-type controls. Yeast one-hybrid, dual-luciferase, chromatin immunoprecipitation-qPCR, and electrophoretic mobility shift assays indicated that PbNAC71 down-regulates PbWalls are thin 1 expression by binding to NAC-binding elements in its promoter. Yeast two-hybrid assays showed that PbNAC71 interacts with the E3 ubiquitin ligase PbRING finger protein 217 (PbRNF217). Furthermore, PbRNF217 promotes the ubiquitin-mediated degradation of PbNAC71 by the 26S proteasome, thereby regulating plant height as well as xylem and vessel development. Our findings reveal a mechanism underlying pear dwarfism and expand our understanding of the molecular basis of dwarfism in woody plants.

Synergistic Activity and Mechanism of Sanguinarine with Polymyxin B against Gram-Negative Bacterial Infections.

Compounds that potentiate the activity of clinically available antibiotics provide a complementary solution, except for developing novel antibiotics for the rapid emergence of multidrug-resistant Gram-negative bacteria (GNB). We sought to identify compounds potentiating polymyxin B (PMB), a traditional drug that has been revived as the last line for treating life-threatening GNB infections, thus reducing its nephrotoxicity and heterogeneous resistance in clinical use. In this study, we found a natural product, sanguinarine (SA), which potentiated the efficacy of PMB against GNB infections. The synergistic effect of SA with PMB was evaluated using a checkerboard assay and time-kill curves in vivo and the murine peritonitis model induced by Escherichia coli in female CD-1 mice in vivo. SA assisted PMB in accelerating the reduction in bacterial loads both in vitro and in vivo, improving the inflammatory responses and survival rate of infected animals. The subsequent detection of the intracellular ATP levels, membrane potential, and membrane integrity indicated that SA enhanced the bacterial-membrane-breaking capacity of PMB. A metabolomic analysis showed that the inhibition of energy metabolism, interference with nucleic acid biosynthesis, and the blocking of L-Ara4N-related PMB resistance may also contribute to the synergistic effect. This study is the first to reveal the synergistic activity and mechanism of SA with PMB, which highlights further insights into anti-GNB drug development.

Identification and Characterization of Chemical Constituents from Ammopiptanthus nanus Stem and Their Metabolites in Rats by UHPLC-Q-TOF-MS/MS.

Ammopiptanthus nanus as a Kirgiz medicine is widely used for the treatment of frostbite and chronic rheumatoid arthritis. However, due to a lack of systematic research on the chemical components of A. nanus and their metabolites, the bioactive components in it remain unclear. Herein, a reliable strategy based on UHPLC-Q-TOF-MS/MS was established to comprehensively analyze the chemical components and their metabolites in vivo. In total, 59 compounds were identified from A. nanus stem extract, among which 14 isoflavones, 10 isoprenylated isoflavones, 4 polyhydroxy flavonoids, 9 alkaloids and 1 polyol were characterized for the first time. After oral administration of A. nanus stem extract, 30 prototype constituents and 28 metabolites (12 phase I and 16 phase II metabolites) were speculated on and identified in rat serum, urine and feces. Furthermore, the metabolic pathways of the chemical components were systematically analyzed and proposed. In conclusion, the chemical components from A. nanus stem and their metabolites in vivo were first studied, which may provide useful chemical information for further study on the effective material basis and pharmacological mechanism of A. nanus.

Study on the Alleviating Effect and Potential Mechanism of Ethanolic Extract of Limonium aureum (L.) Hill. on Lipopolysaccharide-Induced Inflammatory Responses in Macrophages.

Inflammation is the host response of immune cells during infection and traumatic tissue injury. An uncontrolled inflammatory response leads to inflammatory cascade, which in turn triggers a variety of diseases threatening human and animal health. The use of existing inflammatory therapeutic drugs is constrained by their high cost and susceptibility to systemic side effects, and therefore new therapeutic candidates for inflammatory diseases need to be urgently developed. Natural products are characterized by wide sources and rich pharmacological activities, which are valuable resources for the development of new drugs. This study aimed to uncover the alleviating effect and potential mechanism of natural product Limonium aureum (LAH) on LPS-induced inflammatory responses in macrophages. The experimental results showed that the optimized conditions for LAH ultrasound-assisted extraction via response surface methodology were an ethanol concentration of 72%, a material-to-solvent ratio of 1:37 g/mL, an extraction temperature of 73 °C, and an extraction power of 70 W, and the average extraction rate of LAH total flavonoids was 0.3776%. Then, data of 1666 components in LAH ethanol extracts were obtained through quasi-targeted metabolomics analysis. The ELISA showed that LAH significantly inhibited the production of pro-inflammatory cytokines while promoting the secretion of anti-inflammatory cytokines. Finally, combined with the results of network pharmacology analysis and protein expression validation of hub genes, it was speculated that LAH may alleviate LPS-induced inflammatory responses of macrophages through the AKT1/RELA/PTGS2 signaling pathway and the MAPK3/JUN signaling pathway. This study preliminarily revealed the anti-inflammatory activity of LAH and the molecular mechanism of its anti-inflammatory action, and provided a theoretical basis for the development of LAH as a new natural anti-inflammatory drug.

The Combined Effects of Hourly Multi-Pollutant on the Risk of Ambulance Emergency Calls: A Seven-Year Time Series Study.

BACKGROUND: Ambulance emergency calls (AECs) are seen as a more suitable metric for syndromic surveillance due to their heightened sensitivity in reflecting the health impacts of air pollutants. Limited evidence has emphasized the combined effect of hourly air pollutants on AECs. This study aims to investigate the combined effects of multipollutants (i.e., PM2.5, PM10, Ozone, NO2, and SO2) on all-cause and cause-specific AECs by using the quantile g-computation method. METHODS: We used ambulance emergency dispatch data, air pollutant data, and meteorological data from between 1 January 2013 and 31 December 2019 in Shenzhen, China, to estimate the associations of hourly multipollutants with AECs. We followed a two-stage analytic protocol, including the distributed lag nonlinear model, to examine the predominant lag for each air pollutant, as well as the quantile g-computation model to determine the associations of air pollutant mixtures with all-cause and cause-specific AECs. RESULTS: A total of 3,022,164 patients were identified during the study period in Shenzhen. We found that each interquartile range increment in the concentrations of PM2.5, PM10, Ozone, NO2, and SO2 in 0-8 h, 0-8 h, 0-48 h, 0-28 h, and 0-24 h was associated with the highest risk of AECs. Each interquartile range increase in the mixture of air pollutants was significantly associated with a 1.67% (95% CI, 0.12-3.12%) increase in the risk of all-cause AECs, a 1.81% (95% CI, 0.25-3.39%) increase in the risk of vascular AECs, a 1.77% (95% CI, 0.44-3.11%) increase in reproductive AECs, and a 2.12% (95% CI, 0.56-3.71%) increase in AECs due to injuries. CONCLUSIONS: We found combined effects of pollutant mixtures associated with an increased risk of AECs across various causes. These findings highlight the importance of targeted policies and interventions to reduce air pollution, particularly for PM, Ozone, and NO2 emissions.

Synthesis and evaluation of novel pleuromutilin derivatives targeting the 50S ribosomal subunit for antibacterial ability.

Multidrug-resistant bacteria, particularly methicillin-resistant Staphylococcus aureus, have become a major global public health concern. Therefore, developing new antibiotics that do not possess cross-resistance for the currently available antibiotics is critical. Herein, we synthesized a novel class of pleuromutilin derivatives containing substituted triazine with improved antibacterial activity. Among these derivatives, 6d, which contains 4-dimethylamino-1,3,5-triazine in the side chain of pleuromutilin, exhibited highly promising antimicrobial activity and mitigated antibiotic resistance. The high antibacterial potency of 6d was further supported by docking model analysis and green fluorescent protein inhibition assay. Additionally, cytotoxicity and acute oral toxicity evaluation and in vivo mouse systemic infection experiments revealed that 6d possessed tolerable toxicity and promising therapeutic efficacy.

The Effect of Polymer Blends on the In Vitro Release/Degradation and Pharmacokinetics of Moxidectin-Loaded PLGA Microspheres.

To investigate the effect of polymer blends on the in vitro release/degradation and pharmacokinetics of moxidectin-loaded PLGA microspheres (MOX-MS), four formulations (F1, F2, F3 and F4) were prepared using the O/W emulsion solvent evaporation method by blending high (75/25, 75 kDa) and low (50/50, 23 kDa) molecular weight PLGA with different ratios. The addition of low-molecular-weight PLGA did not change the release mechanism of microspheres, but sped up the drug release of microspheres and drastically shortened the lag phase. The in vitro degradation results show that the release of microspheres consisted of a combination of pore diffusion and erosion, and especially autocatalysis played an important role in this process. Furthermore, an accelerated release method was also developed to reduce the period for drug release testing within one month. The pharmacokinetic results demonstrated that MOX-MS could be released for at least 60 days with only a slight blood drug concentration fluctuation. In particular, F3 displayed the highest AUC and plasma concentration (AUC0-t = 596.53 ng/mL·d, Cave (day 30-day 60) = 8.84 ng/mL), making it the optimal formulation. Overall, these results indicate that using polymer blends could easily adjust hydrophobic drug release from microspheres and notably reduce the lag phase of microspheres.

Water security assessment and driving mechanism in the ecosystem service flow condition.

Water resources are the foundation of human survival and development. Thus, it is essential to quantify the relationship between water supply and demand and assess water security to ensure sustainable use of water resources. In this study, we quantified the relationship between water supply and demand in the Yiluo River Basin (YRB) using the InVEST model, constructed a spatial flow model of water provision service at the sub-watershed scale, and analyzed the water security index (WSI) under static and dynamic conditions. Subsequently, we used geographic detectors to identify the explanatory power of the main influencing factors of the WSI. The results showed that (1) from 2005 to 2018, the water supply decreased continuously and the water demand first increased and then decreased in the YRB; (2) the spatial pattern of WSI showed that it was high in the southwest and low in the northeast, wherein the highest and lowest WSI values occurred in 2005 and 2018, respectively. From 2005 to 2018, the mean values of the static and dynamic WSI decreased from 0.77 to 0.60 and 1.56 to 1.20, respectively. (3) The precipitation factor from the supply dimension and the gross domestic product (GDP) factor from the demand dimension had the strongest explanatory power for the static WSI. For the dynamic WSI, the flow quantity of the water provision service flow had the strongest explanatory power. This study provided a reference for governments to formulate sustainable water resource management.

Anti-methicillin-resistant Staphylococcus aureus activity and safety evaluation of 14-O-[(5-ethoxycarbonyl-4,6-dimethylpyrimidine-2-yl) thioacetyl] mutilin (EDT).

Infections caused by methicillin-resistant Staphylococcus aureus (MRSA) have threated the public health worldwide, which emphasizes the urgent need for new drugs with novel mechanism of actions. 14-O-[(5-ethoxycarbonyl-4,6-dimethylpyrimidine-2-yl) thioacetyl] mutilin (EDT) is a pleuromutilin compound with high activity against several Gram-positive bacteria in vitro and in vivo. This study aimed to verifying the potential anti-MRSA activity and evaluating the safety of EDT. In in vitro antibacterial activity assays, EDT exhibited potent antibacterial activity against MRSA isolated from clinic (minimum inhibitory concentration = 0.0313-0.125 µg/mL), increased post-antibiotic effect (PAE) values and limited potential for the development of resistance. Docking model and green fluorescent protein (GFP) inhibition assay further elucidated the higher antibacterial activities of EDT via mechanism of action. In safety evaluation, EDT exhibited low cytotoxic effect and acute oral toxicity in mice and avoided to significantly increase the number of revertant colonies of six tested strains in the Ames study. Furthermore, EDT displayed a moderate inhibitory effect on CYP3A4 and moderate stability in mouse and human liver microsomes, providing a promising agent for the development of new antimicrobial candidate.

Temperature-Sensitive Fragrance Microcapsules with Double Capsule Walls: A Study on Preparation and Sustained Release Mechanism.

Microcapsules are small particles that can effectively protect a core material from degradation. Microcapsules with double capsule walls can improve stability and reduce breakage due to the fact that the physical and chemical properties of double-walled materials can complement each other, thus enhancing the quality and applicability of a microcapsule. Microcapsules can achieve controlled release of core materials by using a temperature-sensitive wall material. In this research, gelatin was used as the inner wall material for these double-walled microcapsules. The outer wall material was a composite material prepared by the reaction of a hydroxyl group in gum arabic with an amino group in N-isopropylacrylamide (NIPAM) in the presence of N, N'-methylene bisacrylamide (BIS), while lavender fragrance oil served as the core material. A complex coalescence method was used for the preparation of microcapsules with double capsule walls. The effects of different proportions of gum arabic to NIPAM on the core loading, microcapsule yield and thermal stability of microcapsules were studied in detail. Additionally, the stability of these fragrance microcapsules with double capsule walls in different solvents and pH values was evaluated. The sustained release properties and mechanism of cotton fabrics treated with prepared fragrance microcapsules were investigated. The results show that the microcapsules prepared with a 10:1 ratio of NIPAM to gum arabic have good temperature responsiveness. Therefore, clothing treated with microcapsules with temperature-sensitive wall materials can ensure that the human body has a fresh and pleasant smell in the case of perspiring in summer.

Effect of a low-cost instruction card for automated external defibrillator operation in lay rescuers: a randomized simulation study.

BACKGROUND: To evaluate whether a simplified self-instruction card can help potential rescue providers use automated external defibrillators (AEDs) more accurately and quickly. METHODS: From June 1, 2018, to November 30, 2019, a prospective longitudinal randomized controlled simulation study was conducted among 165 laypeople (18-65 years old) without prior AED training. A self-instruction card was designed to illuminate key AED operation procedures. Subjects were randomly divided into the card (n=83) and control (n=82) groups with age stratification. They were then individually evaluated in the same simulated scenario to use AED with (card group) or without the self-instruction card (control group) at baseline, post-training, and at the 3-month follow-up. RESULTS: At baseline, the card group reached a significantly higher proportion of successful defibrillation (31.1% vs. 15.9%, P=0.03), fully baring the chest (88.9% vs. 63.4%, P<0.001), correct electrode placement (32.5% vs. 17.1%, P=0.03), and resuming cardiopulmonary resuscitation (CPR) (72.3% vs. 9.8%, P<0.001). At post-training and follow-up, there were no significant differences in key behaviors, except for resuming CPR. Time to shock and time to resume CPR were shorter in the card group, while time to power-on AED was not different in each phase of tests. In the 55-65 years group, the card group achieved more skill improvements over the control group compared to the other age groups. CONCLUSION: The self-instruction card could serve as a direction for first-time AED users and as a reminder for trained subjects. This could be a practical, cost-effective way to improve the AED skills of potential rescue providers among different age groups, including seniors.

Release of glycosidically-bound volatiles in orange juice under natural conditions.

Glycosidically-bound volatiles (GBV) can be released by exogenous acid and enzymatic hydrolysis. However, the liberation of GBV in natural juice is not reported. It was found that part of the GBV in orange juice (OJ) under natural conditions can be released and the types of volatiles were considerably fewer than the ones under exogenous acid, or enzymatic hydrolysis. Seven types of aroma substances were released under endogenous enzyme, among which ethyl 3-hydroxyhexanoate and eugenol are characteristic aroma substances of OJ. Six kinds of aroma substances can be released under natural acidic conditions, none are characteristic aroma substances of OJ. Ten kinds of substances were released under endogenous enzymes in combination with the acidic condition, among which benzyl alcohol, ethyl 3-hydroxyhexanoate, citral, and eugenol are characteristic aroma substances of OJ. The results indicated that GBV may play an important role in resisting the decrease of free aroma in OJ during storage.

The emergence of multi-drug resistant and virulence gene carrying Escherichia coli strains in the dairy environment: a rising threat to the environment, animal, and public health.

Escherichia coli is a common inhabitant of the intestinal microbiota and is responsible for udder infection in dairy cattle and gastro-urinary tract infections in humans. We isolated E. coli strains from a dairy farm environment in Xinjiang, China, and investigated their epidemiological characteristics, phenotypic and genotypic resistance to antimicrobials, virulence-associated genes, and phylogenetic relationship. A total of 209 samples were collected from different sources (feces, slurry, water, milk, soil) and cultured on differential and selective agar media (MAC and EMB). The presumptive identification was done by the VITEK2 system and confirmed by 16S rRNA gene amplification by PCR. Antimicrobial susceptibility testing was done by micro-dilution assay, and genomic characterization was done by simple and multiplex polymerase chain reaction (PCR). A total of 338 E. coli strains were identified from 141/209 (67.5%) of the samples. Most of the E. coli strains were resistant to sulfamethoxazole/trimethoprim (62.43%), followed by cefotaxime (44.08%), ampicillin (33.73%), ciprofloxacin (31.36%), tetracycline (28.99%), and a lesser extent to florfenicol (7.99%), gentamicin (4.44%), amikacin (1.77%), and fosfomycin (1.18%). All of the strains were susceptible to meropenem, tigecycline, and colistin sulfate. Among the resistant strains, 44.4% were identified as multi-drug resistant (MDR) showing resistance to at least one antibiotic from ≥3 classes of antibiotics. Eighteen out of 20 antibiotic-resistance genes (ARGs) were detected with sul2 (67.3%), blaTEM (56.3%), gyrA (73.6%), tet(B) (70.4%), aph(3)-I (85.7%), floR (44.4%), and fosA3 (100%, 1/1) being the predominant genes among different classes of antibiotics. Among the virulence-associated genes (VAGs), ompA was the most prevalent (86.69%) followed by ibeB (85.0%), traT (84.91%), ompT (73.96%), fyuA (23.1%), iroN (23.1%), and irp2 gene (21.9%). Most of the E. coli strains were classified under phylogenetic group B1 (75.45%), followed by A (18.34%), C (2.96%), D (1.18%), E (1.18%), and F (0.30%). The present study identified MDR E. coli strains carrying widely distributed ARGs and VAGs from the dairy environment. The findings suggested that the dairy farm environment may serve as a source of mastitis-causing pathogens in animals and horizontal transfer of antibiotic resistance and virulence genes carrying bacterial strains to humans via contaminated milk and meat, surface water and agricultural crops.

Erratum to "Identification of anti-Mycobacterium tuberculosis agents targeting the interaction of bacterial division proteins FtsZ and SepFe" [Acta Pharmaceutica Sinica B 13 (2023) 2056-2070].

[This corrects the article DOI: 10.1016/j.apsb.2023.01.022.].

Molecular epidemiology and characterization of antimicrobial-resistant Staphylococcus haemolyticus strains isolated from dairy cattle milk in Northwest, China.

Introduction: Non-aureus Staphylococcus (NAS) species are currently the most commonly identified microbial agents causing sub-clinical infections of the udder and are also deemed as opportunistic pathogens of clinical mastitis in dairy cattle. More than 10 NAS species have been identified and studied but little is known about S. haemolyticus in accordance with dairy mastitis. The present study focused on the molecular epidemiology and genotypic characterization of S. haemolyticus isolated from dairy cattle milk in Northwest, China. Methods: In this study, a total of 356 milk samples were collected from large dairy farms in three provinces in Northwest, China. The bacterial isolation and presumptive identification were done by microbiological and biochemical methods following the molecular confirmation by 16S rRNA gene sequencing. The antimicrobial susceptibility testing (AST) was done by Kirby-Bauer disk diffusion assay and antibiotic-resistance genes (ARGs) were identified by PCR. The phylogenetic grouping and sequence typing was done by Pulsed Field Gel Electrophoresis (PFGE) and Multi-Locus Sequence Typing (MLST) respectively. Results: In total, 39/356 (11.0%) were identified as positive for S. haemolyticus. The overall prevalence of other Staphylococcus species was noted to be 39.6% (141/356), while the species distribution was as follows: S. aureus 14.9%, S. sciuri 10.4%, S. saprophyticus 7.6%, S. chromogenes 4.2%, S. simulans 1.4%, and S. epidermidis 1.1%. The antimicrobial susceptibility of 39 S. haemolyticus strains exhibited higher resistance to erythromycin (92.3%) followed by trimethoprim-sulfamethoxazole (51.3%), ciprofloxacin (43.6%), florfenicol (30.8%), cefoxitin (28.2%), and gentamicin (23.1%). All of the S. haemolyticus strains were susceptible to tetracycline, vancomycin, and linezolid. The overall percentage of multi-drug resistant (MDR) S. haemolyticus strains was noted to be 46.15% (18/39). Among ARGs, mphC was identified as predominant (82.05%), followed by ermB (33.33%), floR (30.77%), gyrA (30.77%), sul1 (28.21%), ermA (23.08%), aadD (12.82%), grlA (12.82%), aacA-aphD (10.26%), sul2 (10.26%), dfrA (7.69%), and dfrG (5.13%). The PFGE categorized 39 S. haemolyticus strains into A-H phylogenetic groups while the MLST categorized strains into eight STs with ST8 being the most predominant while other STs identified were ST3, ST11, ST22, ST32, ST19, ST16, and ST7. Conclusion: These findings provided new insights into our understanding of the epidemiology and genetic characteristics of S. haemolyticus in dairy farms to inform interventions limiting the spread of AMR in dairy production.

Development and validation of a nomogram to predict protein-energy wasting in patients with peritoneal dialysis: a multicenter cohort study.

Background: Protein-energy wasting (PEW) is a common complication in patients with peritoneal dialysis (PD). Few investigations involved risk factors identification and predictive model construction related to PEW. We aimed to develop a nomogram to predict PEW risk in patients with peritoneal dialysis. Methods: We collected data from end-stage renal disease (ESRD) patients who regularly underwent peritoneal dialysis between January 2011 and November 2022 at two hospitals retrospectively. The outcome of the nomogram was PEW. Multivariate logistic regression screened predictors and established a nomogram. We measured the predictive performance based on discrimination ability, calibration, and clinical utility. Evaluation indicators were receiver operating characteristic (ROC), calibrate curve, and decision curve analysis (DCA). The performance calculation of the internal validation cohort validated the nomogram. Results: In this study, 369 enrolled patients were divided into development (n = 210) and validation (n = 159) cohorts according to the proportion of 6:4. The incidence of PEW was 49.86%. Predictors were age, dialysis duration, glucose, C-reactive protein (CRP), creatinine clearance rate (Ccr), serum creatinine (Scr), serum calcium, and triglyceride (TG). These variables showed a good discriminate performance in development and validation cohorts (ROC = 0.769, 95% CI [0.705-0.832], ROC = 0.669, 95% CI [0.585-0.753]). This nomogram was adequately calibrated. The predicted probability was consistent with the observed outcome. Conclusion: This nomogram can predict the risk of PEW in patients with PD and provide valuable evidence for PEW prevention and decision-making.