Methyltransferase Dnmt3a upregulates HDAC9 to deacetylate the kinase TBK1 for activation of antiviral innate immunity.

The DNA methyltransferase Dnmt3a has high expression in terminally differentiated macrophages; however, its role in innate immunity remains unknown. Here we report that deficiency in Dnmt3a selectively impaired the production of type I interferons triggered by pattern-recognition receptors (PRRs), but not that of the proinflammatory cytokines TNF and IL-6. Dnmt3a-deficient mice exhibited enhanced susceptibility to viral challenge. Dnmt3a did not directly regulate the transcription of genes encoding type I interferons; instead, it increased the production of type I interferons through an epigenetic mechanism by maintaining high expression of the histone deacetylase HDAC9. In turn, HDAC9 directly maintained the deacetylation status of the key PRR signaling molecule TBK1 and enhanced its kinase activity. Our data add mechanistic insight into the crosstalk between epigenetic modifications and post-translational modifications in the regulation of PRR signaling and activation of antiviral innate immune responses.

Beyond Conventional Enhancements: Self-Organization of a Buffer Material on Tin Oxide as a Game-Changer for Improving the Performance of Inverted Organic Solar Cells.

Inverted organic solar cells (OSCs) have garnered significant interest due to their remarkable stability. In this study, the efficiency and stability of inverted OSCs are enhanced via the in situ self-organization (SO) of an interfacial modification material Phen-NaDPO onto tin oxide (SnO2). During the device fabrication, Phen-NaDPO is spin-coated with the active materials all together on SnO2. Driven by the interactions with SnO2 and the thermodynamic forces due to its high surface energy and the convection flow, Phen-NaDPO spontaneously migrates to the SnO2 interface, resulting in the formation of an in situ modification layer on SnO2. This self-organization of Phen-NaDPO not only effectively reduces the work function of SnO2, but also enhances the ordered molecular stacking and manipulates the vertical morphology of the active layer, which suppress the surface trap-assisted recombination and minimize the charge extraction. As a result, the SO devices based on PM6:Y6 exhibit significantly improved photovoltaic performance with an enhanced power conversion efficiency of 17.62%. Moreover, the stability of the SO device is also improved. Furthermore, the SO ternary devices based on PM6:D18:L8-BO achieved an impressive PCE of 18.87%, standing as one of the highest values for single-junction inverted organic solar cells to date.

Constitutive MHC class I molecules negatively regulate TLR-triggered inflammatory responses via the Fps-SHP-2 pathway.

The molecular mechanisms that fine-tune Toll-like receptor (TLR)-triggered innate inflammatory responses remain to be fully elucidated. Major histocompatibility complex (MHC) molecules can mediate reverse signaling and have nonclassical functions. Here we found that constitutively expressed membrane MHC class I molecules attenuated TLR-triggered innate inflammatory responses via reverse signaling, which protected mice from sepsis. The intracellular domain of MHC class I molecules was phosphorylated by the kinase Src after TLR activation, then the tyrosine kinase Fps was recruited via its Src homology 2 domain to phosphorylated MHC class I molecules. This led to enhanced Fps activity and recruitment of the phosphatase SHP-2, which interfered with TLR signaling mediated by the signaling molecule TRAF6. Thus, constitutive MHC class I molecules engage in crosstalk with TLR signaling via the Fps-SHP-2 pathway and control TLR-triggered innate inflammatory responses.

Nanoparticles transfected with plasmid-encoded lncRNA-OIP5-AS1 inhibit renal ischemia-reperfusion injury in mice via the miR-410-3p/Nrf2 axis.

Nanostructures composed of liposomes and polydopamine (PDA) have demonstrated efficacy as carriers for delivering plasmids, effectively alleviating renal cell carcinoma. However, their role in acute kidney injury (AKI) remains unclear. This study aimed to investigate the effects of the plasmid-encoded lncRNA-OIP5-AS1@PDA nanoparticles (POP-NPs) on renal ischemia/reperfusion (RI/R) injury and explore the underlying mechanisms. RI/R or OGD/R models were established in mice and HK-2 cells, respectively. In vivo, vector or POP-NPs were administered (10 nmol, IV) 48 h after RI/R treatment. In the RI/R mouse model, the OIP5-AS1 and Nrf2/HO-1 expressions were down-regulated, while miR-410-3p expression was upregulated. POP-NPs treatment effectively reversed RI/R-induced renal tissue injury, restoring altered levels of blood urea nitrogen, creatinine, malondialdehyde, inflammatory factors (IL-8, IL-6, TNF-α), ROS, apoptosis, miR-410-3p, as well as the suppressed expression of SOD and Nrf2/HO-1 in the model mice. Similar results were obtained in cell models treated with POP-NPs. Additionally, miR-410-3p mimics could reverse the effects of POP-NPs on cellular models, partially counteracted by Nrf2 agonists. The binding relationship between OIP5-AS1 and miR-410-3p, alongside miR-410-3p and Nrf2, has been substantiated by dual-luciferase reporter and RNA pull-down assays. The study revealed that POP-NPs can attenuate RI/R-induced injury through miR-410-3p/Nrf2 axis. These findings lay the groundwork for future targeted therapeutic approaches utilizing nanoparticles for RI/R-induced AKI.

DM-MOGA: a multi-objective optimization genetic algorithm for identifying disease modules of non-small cell lung cancer.

BACKGROUND: Constructing molecular interaction networks from microarray data and then identifying disease module biomarkers can provide insight into the underlying pathogenic mechanisms of non-small cell lung cancer. A promising approach for identifying disease modules in the network is community detection. RESULTS: In order to identify disease modules from gene co-expression networks, a community detection method is proposed based on multi-objective optimization genetic algorithm with decomposition. The method is named DM-MOGA and possesses two highlights. First, the boundary correction strategy is designed for the modules obtained in the process of local module detection and pre-simplification. Second, during the evolution, we introduce Davies-Bouldin index and clustering coefficient as fitness functions which are improved and migrated to weighted networks. In order to identify modules that are more relevant to diseases, the above strategies are designed to consider the network topology of genes and the strength of connections with other genes at the same time. Experimental results of different gene expression datasets of non-small cell lung cancer demonstrate that the core modules obtained by DM-MOGA are more effective than those obtained by several other advanced module identification methods. CONCLUSIONS: The proposed method identifies disease-relevant modules by optimizing two novel fitness functions to simultaneously consider the local topology of each gene and its connection strength with other genes. The association of the identified core modules with lung cancer has been confirmed by pathway and gene ontology enrichment analysis.

Effect of Paclobutrazol Application on Enhancing the Efficacy of Nitenpyram against the Brown Planthopper, Nilaparvata lugens.

The brown planthopper (BPH), Nilaparvata lugens, is one of the most destructive rice pests in Asia. It has already developed a high level of resistance to many commonly used insecticides including nitenpyram (NIT), which is a main synthetic insecticide that is used to control BPH with a much shorter persistence compared to other neonicotinoid insecticides. Recently, we found that an exogenous supplement of paclobutrazol (PZ) could significantly enhance the efficacy of NIT against BPH, and the molecular mechanism underlying this synergistic effect was explored. The results showed that the addition of a range of 150-300 mg/L PZ increased the toxicity of NIT against BPH with the highest mortalities of 78.0-87.0% on the 16th day after treatments, and PZ could also significantly prolong the persistence of the NIT efficacies. Further investigation suggested that PZ directly increased the content of flavonoids and H2O2 in rice and increased the activity of polyphenol oxidase, which might be involved in the constitutive defense of rice in advance. Additionally, there was an interaction between PZ and BPH infestation, indicating that PZ might activate the host defense responses. Therefore, PZ increased the efficacy of NIT against the brown planthoppers by enhancing the constitutive and inducible defense responses of rice. Our study showed for the first time that PZ could contribute to improving the control effects of insecticides via inducing the defense responses in rice plants against BPH, which provided an important theoretical basis for developing novel pest management strategies in the field.

Recycling Valuable Metals from Spent Lithium-Ion Batteries Using Carbothermal Shock Method.

Pyrometallurgy technique is usually applied as a pretreatment to enhance the leaching efficiencies in the hydrometallurgy process for recovering valuable metals from spent lithium-ion batteries. However, traditional pyrometallurgy processes are energy and time consuming. Here, we report a carbothermal shock (CTS) method for reducing LiNi0.3 Co0.2 Mn0.5 O2 (NCM325) cathode materials with uniform temperature distribution, high heating and cooling rates, high temperatures, and ultrafast reaction times. Li can be selectively leached through water leaching after CTS process with an efficiency of >90 %. Ni, Co, and Mn are recovered by dilute acid leaching with efficiencies >98 %. The CTS reduction strategy is feasible for various spent cathode materials, including NCM111, NCM523, NCM622, NCM811, LiCoO2 , and LiMn2 O4 . The CTS process, with its low energy consumption and potential scale application, provides an efficient and environmentally friendly way for recovering spent lithium-ion batteries.

A smart enzyme reactor based on a photo-responsive hydrogel for purifying water from phenol contaminated sources.

In this paper, a smart enzyme reactor (SER) was synthesized using immobilized tyrosinase (Tyr) in a photo-responsive hydrogel via a polydopamine-assisted self-assembly strategy for purifying water from phenol contaminated water. PDA was not only utilized as a binder between Tyr and the hydrogel to prevent the leakage of Tyr with relatively high enzymatic activity from the SER, but also acted as a light absorber to trigger the hydrophilic/hydrophobic switching of PNIPAm hydrogels to realize the efficient reclamation of clean water. Experimental results showed that the SER maintained a well-defined porous structure with excellent elasticity, which was beneficial for water transport and enzyme accessibility. And the stability and reusability of Tyr in the degradation of phenol were all improved. Furthermore, clean water could be reclaimed completely and facilely by light irradiation after enzymatic remediation in the SER.

Knockdown of the chromatin remodeling ATPase gene Brahma impairs the reproductive potential of the brown planthopper, Nilaparvata lugens.

The brown planthopper (BPH), Nilaparvata lugens (Stål), is one of the most destructive pests in rice-growing regions of Asia. Extensive studies have suggested that SWI/SNF chromatin remodeling ATPase Brahma (BRM) plays multiple roles in the insect model Drosophila. Yet much less is known about the physiological properties for NlBRM. In the present study, the cloned full-length cDNA of NlBRM was 5637 bp and contained an ORF of 5292 bp encoding a 194.53 kD protein. The spatiotemporal dynamics of NlBRM was investigated by qPCR, which showed that it was abundantly expressed in the egg and ovary. Then significant downregulation of NlBRM by dsRNA injection had a relatively greater impact on female survival than male. Moreover, the number of oviposition marks of the NlBRM-RNAi females were declined by 61.11% - 73.33% compared with the controls during the subsequent 5 days after dsRNA injection. Meanwhile, the number of newly hatched BPH nymphs also decreased correspondingly by 93.56% - 100%. Phenotypic analysis revealed that none of normally banana-shaped eggs were discernable in the ovaries of NlBRM-deficient females, where mRNA expression of N. lugens vitellogenin gene was also reduced. Our results demonstrated that NlBRM played a crucial role in ovarian development and fecundity of BPH, likely by regulating the vitellogenin gene in vivo, which could be as a promising target for parental RNAi-based control of this serious rice pest.

The effect of maternal gestational diabetes on maternal and neonatal outcomes in twin pregnancies: a systematic review and meta-analysis.

Diabetes and twin pregnancies are known risk factors for poor perinatal and neonatal outcomes. However, the effects of these two entities occurring together are still unclear. PubMed, Scopus and Google Scholar databases were searched in a systematic manner to identify observational studies among twin pregnancies, which documented the association of gestational diabetes with maternal and neonatal outcomes. All the analysis was done using STATA software. The meta-analysis included 21 studies, of which majority were retrospective data based. Mothers with gestational diabetes had higher risks of hypertensive disorder in pregnancy, caesarean section, large for gestational age baby, NICU admission and neonatal hypoglycaemia compared to mothers without gestational diabetes. Diabetic mothers were at reduced risk of small for gestational age baby and low APGAR score. No statistically significant differences in the risk of low birth weight, mean birth weight, prematurity and neonatal death were noted. This meta-analysis observed increased risks of detrimental maternal, neonatal and perinatal outcomes in twin pregnancies complicated by gestational diabetes, underscoring the need for the early detection and management of gestational diabetes.

A comparative study of mini- versus standard laparoscopy in the treatment of renal cysts.

INTRODUCTION: This study aimed to investigate the safety and efficacy of mini-laparoscopy for renal cyst unroofing. MATERIAL AND METHODS: Eighty-six patients for treatment of renal cysts that met the selection criteria were included in this study. They were divided into two groups. Forty-five patients underwent cyst unroofing via mini-laparoscopy (Group M), and 43 patients underwent cyst unroofing via standard laparoscopy (Group S). There were no differences between the two groups in terms of sex, age, body mass index or clinical data. Data from the groups were recorded and analyzed. RESULTS: The average hospital stays were shorter (p = .039) and postoperative painkiller demand was lower (p = .031) in Group M than in Group S. Forty-one out of 45 procedures in Group M were successful, and all 43 cases in Group S were successfully. With a follow-up period of 0.5 to 5.5 years, there was no significant difference in recovery rate (p = .213). Questionnaires showed that patients in Group M were significantly more satisfied with their cosmetic results than were patients in Group S (p = .041). CONCLUSION: Our findings suggest that renal cyst decortications with mini-laparoscopic instruments are as safe and effective as procedures using standard laparoscopic instruments. Cosmetically, the results are better with mini-laparoscopy than with standard laparoscopic unroofing.

Management of large renal stones with super-mini percutaneous nephrolithotomy: an international multicentre comparative study.

OBJECTIVES: To comparatively evaluate the clinical outcomes of super-mini percutaneous nephrolithotomy (SMP) and mini-percutaneous nephrolithotomy (Miniperc) for treating urinary tract calculi of >2 cm. PATIENTS AND METHODS: An international multicentre, retrospective cohort study was conducted at 20 tertiary care hospitals across five countries (China, the Philippines, Qatar, UK, and Kuwait) between April 2016 and May 2019. SMP and Miniperc were performed in 3525 patients with renal calculi with diameters of >2 cm. The primary endpoint was the stone-free rate (SFR). The secondary outcomes included: blood loss, operating time, postoperative pain scores, auxiliary procedures, complications, tubeless rate, and hospital stay. Propensity score matching analysis was used to balance the selection bias between the two groups. RESULTS: In all, 2012 and 1513 patients underwent SMP and Miniperc, respectively. After matching, 1380 patients from each group were included for further analysis. Overall, there was no significant difference in the mean operating time or SFR between the two groups. However, the hospital stay and postoperative pain score were significantly in favour of SMP (both P < 0.001). The tubeless rate was significantly higher in the SMP group (72.6% vs 57.8%, P < 0.001). Postoperative fever was much more common in the Miniperc group (12.0% vs 8.4%, P = 0.002). When the patients were further classified into three subgroups based on stones diameters (2-3, 3-4, and >4 cm). The advantages of SMP were most obvious in the 2-3 cm stone group and diminished as the size of the stone increased, with longer operating time in the latter two subgroups. Compared with Miniperc, the SFR of SMP was comparable for 3-4 cm stones, but lower for >4 cm stones. There was no statistical difference in blood transfusions and renal embolisations between the two groups. CONCLUSIONS: Our data showed that SMP is an ideal treatment option for stones of <4 cm and is more efficacious for stones of 2-3 cm, with lesser postoperative fever, blood loss, and pain compared to Miniperc. SMP was less effective for stones of >4 cm, with a prolonged operating time.

PSO-CFDP: A Particle Swarm Optimization-Based Automatic Density Peaks Clustering Method for Cancer Subtyping.

Cancer subtyping is of great importance for the prediction, diagnosis, and precise treatment of cancer patients. Many clustering methods have been proposed for cancer subtyping. In 2014, a clustering algorithm named Clustering by Fast Search and Find of Density Peaks (CFDP) was proposed and published in Science, which has been applied to cancer subtyping and achieved attractive results. However, CFDP requires to set two key parameters (cluster centers and cutoff distance) manually, while their optimal values are difficult to be determined. To overcome this limitation, an automatic clustering method named PSO-CFDP is proposed in this paper, in which cluster centers and cutoff distance are automatically determined by running an improved particle swarm optimization (PSO) algorithm multiple times. Experiments using PSO-CFDP, as well as LR-CFDP, STClu, CH-CCFDAC, and CFDP, were performed on four benchmark data-sets and two real cancer gene expression datasets. The results show that PSO-CFDP can determine cluster centers and cutoff distance automatically within controllable time/cost and, therefore, improve the accuracy of cancer subtyping.

FAM83H-AS1 is associated with clinical progression and modulates cell proliferation, migration, and invasion in bladder cancer.

FAM83H-AS1, also known as oncogenic long noncoding RNA (lncRNA)-3, is a novel lncRNA that has been suggested to be dysregulated in a variety of human cancers. However, the expression status and function of FAM83H-AS1 in bladder cancer are still unknown. The object of our study is to explore the clinical value of FAM83H-AS1 in patients with bladder cancer and the biological function of FAM83H-AS1 in bladder cancer cells. In our results, the expression of FAM83H-AS1 was obviously elevated in bladder cancer tissue samples and bladder cancer cell lines compared with adjacent normal tissue samples and normal bladder epithelial cell lines, respectively. In addition, high expression of FAM83H-AS1 was associated with advanced clinical stage and the presence of muscularis invasion and served as an independent poor prognostic factor for overall survival in patients with bladder cancer. The loss-of-function study showed that silencing FAM83H-AS1 expression suppressed cell proliferation, migration, and invasion and induced cycle arrest at G0/G1 phase. In conclusion, FAM83H-AS1 is involved in the progression of bladder cancer and serves as a prognostic biomarker and potential therapeutic target for patients with bladder cancer.

Epidemiology of Clostridium difficile infection in hospitalized adults and the first isolation of C. difficile PCR ribotype 027 in central China.

BACKGROUND: Clostridium difficile infection (CDI) is an emerging healthcare problem in the world. The purpose of this study was to perform a systematic epidemiological research of CDI in Tongji hospital, the central of China. METHODS: Stool samples from hospitalized adults suspected of CDI were enrolled. The diagnosis of CDI were based on the combination of clinical symptoms and laboratory results. Clinical features of CDI and non-CDI patients were compared by appropriate statistical tests to determine the risk factors of CDI. Multilocus sequence typing (MLST) was employed for molecular epidemiological analysis. Susceptibility testing and relevant antimicrobial agent resistance genes were performed as well. RESULTS: From June 2016 to September 2017, 839 hospitalized adults were enrolled. Among them, 107 (12.8%, 107/839) patients were C. difficile culture positive, and 73 (8.7%, 73/839) were infected with toxigenic C. difficile (TCD), with tcdA + tcdB+ strains accounting for 90.4% (66/73) and tcdA-tcdB+ for 9.6% (7/73). Meanwhile, two TCD strains were binary toxin positive and one of them was finally identified as CD027. Severe symptoms were observed in these two cases. Multivariate analysis indicated antibiotic exposure (p = 0.001, OR = 5.035) and kidney disease (p = 0.015, OR = 8.329) significantly increased the risk of CDI. Phylogenetic tree analysis demonstrated 21 different STs, including one new ST (ST467); and the most dominant type was ST54 (35.6%, 26/73). Multidrug-resistant (MDR) TCD were 53.4% (39/73); resistance to ciprofloxacin, erythromycin, and clindamycin were > 50%. Other antibiotics showed relative efficiency and all strains were susceptible to metronidazole and vancomycin. All moxifloxacin-resistant isolates carried a mutation in GyrA (Thr82 → Ile), with one both having mutation in GyrB (Ser366 → Ala). CONCLUSIONS: Knowledge of epidemiological information for CDI is limited in China. Our finding indicated tcdA + tcdB+ C. difficile strains were the dominant for CDI in our hospital. Significant risk factors for CDI in our setting appeared to be antibiotic exposure and kidney disease. Metronidazole and vancomycin were still effective for CDI. Although no outbreak was observed, the first isolation of CD027 in center China implied the potential spread of this hypervirulent clone. Further studies are needed to enhance our understanding of the epidemiology of CDI in China.

[Dietary microelements intakes status of elderly people from different areas in Zhejiang Province in 2010-2012].

OBJECTIVE: To assess the situations of dietary microelements intakes among elderly people in different areas of Zhejiang Province, and analyze the food sources of microelements. METHODS: Data were obtained from the 2010-2012 Chinese National Nutrition and Health Survey in Zhejiang Province. 832 elderly people( 434 male, 398 female, age was( 68. 02±6. 68) years) were from large cities, small-medium cities and rural counties. The 24-hour dietary recall method for 3 consecutive days was used to collect food intake information to analyze dietary intakes among elderly people of Fe, Mn, Cu, Zn, Se and their sources in different areas. RESULTS: The elderly people'intakes of Mn was 4. 86( 3. 44, 6. 45) mg/d, Cu was 1. 69( 1. 13, 2. 27) mg/d, and Se was36. 85( 21. 32, 54. 21) µg/d, those were generally low. The intake of Zn was 10. 15( 7. 94, 12. 62) mg/d in males, was low as well. Intakes of Mn, Cu, Se were significantly different in different areas, small-medium cities had highest intakes of Mn( 5. 87 mg/d)and Cu( 1. 88 mg/d), large cities had a highest intake of Se( 45. 47 µg/d). The food sources of microelements were slightly variant. Rural counties had less fungi and algae sources of Fe and Mn than large cities and small-medium cities. The Cu from vegetables were higher than dried legumes and the Se from poultry and poultry products were higher than eggs in rural counties. The Zn from fish, shellfish and mollusk were higher than dried legumes in large cities. CONCLUSION: The insufficient status of microelements intakes among elderly people in Zhejiang Province was serious, and there were differences among elderly people from different areas in intakes and food sources of microelements.

Unravelling the Self-Assembly of Diketopyrrolopyrrole-Based Photovoltaic Molecules.

The nanostructure of bulk heterojunction in an organic solar cell dominating the electron transport process plays an important role in improving the device efficiency. However, there is still a great need for further understanding the local nanostructures from the viewpoint of molecular design because of the complex alignment in the solid film. In this work, four kinds of photovoltaic materials containing a diketopyrrolopyrrole (DPP) unit combined with other different building blocks were selected and their self-assembled structures on a solid surface were studied by scanning tunneling microscopy technique in combination with theory calculations. The results reveal these DPP-based photovoltaic molecules self-assembled into different nanostructures, which strongly depend on the chemical structure, in particular the backbones and alkyl side chains. The planarities of backbones are affected both by molecule-substrate interaction and steric hindrance induced by the substituted thiophene or benzo[ b]thiophene units on DPP and porphyrin building blocks. The substituted branched alkyl side chains are out of the plane, which are influenced by the alignments of molecular backbones. In addition, the solution concentration also shows a large effect on the self-assembled nanostructures. This systematic research on the self-assembled structures of DPP-based semiconductors on a surface would provide guidance for designing materials and controlling the morphology of a donor/acceptor heterojunction system.

Characteristics of diarrheagenic Escherichia coli among children under 5 years of age with acute diarrhea: a hospital based study.

BACKGROUND: Diarrhea is the leading infectious cause of childhood morbidity and mortality. Among bacterial agents, diarrheagenic Escherichia coli (DEC) is the major causal agent of childhood diarrhea in developing countries, particularly in children under the age of 5 years. Here, we performed a hospital-based prospective study to explore the pathotype distribution, epidemiological characteristics and antibiotic resistance patterns of DEC from < 5-year-old diarrheal children. METHODS: Between August 2015 and September 2016, 684 stool samples were collected from children (< 5 years old) with acute diarrhea. All samples were cultured and identified by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) and biochemical tests. PCR was used for subtyping, and enteropathogenic E. coli (EPEC) isolates were identified simultaneously with serology. Furthermore, antimicrobial sensitivity tests and sequencing of antibiotic resistance-related genes were conducted. RESULTS: DEC strains were identified in 7.9% of the 684 stool samples. Among them, the most commonly detected pathotype was EPEC (50.0% of DEC), of which 77.8% were classified as atypical EPEC (aEPEC). Age and seasonal distribution revealed that DEC tended to infect younger children and to occur in summer/autumn periods. Multidrug-resistant DEC isolates were 66.7%; resistance rates to ampicillin, co-trimoxazole, cefazolin, cefuroxime, cefotaxime, and ciprofloxacin were ≥ 50%. Among 5 carbapenem-resistant DEC, 60.0% were positive for carbapenemase genes (2 blaNDM-1 and 1 blaKPC-2). Among 30 cephalosporin-resistant DEC, 93.3% were positive for extended-spectrum ß-lactamase (ESBL) genes, with blaTEM-1 and blaCTX-M-55 being the most common types. However, no gyrA or gyrB genes were detected in 16 quinolone-resistant isolates. Notably, aEPEC, which has not received much attention before, also exhibited high rates of drug resistance (81.0%, 66.7%, and 14.3% for ampicillin, co-trimoxazole , and carbapenem resistance, respectively). CONCLUSIONS: EPEC was the most frequent DEC pathotype in acute diarrheal children, with aEPEC emerging as a dominant diarrheal agent in central China. Most DEC strains were multidrug-resistant, making even ciprofloxacin unsuitable for empiric treatment against DEC infection. Among carbapenem-resistant DEC strains, those harboring blaNDM-1 and blaKPC-2 were the main causal agents. blaTEM-1 and blaCTX-M-55 were the major genetic determinants associated with high levels of cephalosporin resistance.