Polyploidy underlies co-option and diversification of biosynthetic triterpene pathways in the apple tribe.

Whole-genome duplication (WGD) plays important roles in plant evolution and function, yet little is known about how WGD underlies metabolic diversification of natural products that bear significant medicinal properties, especially in nonmodel trees. Here, we reveal how WGD laid the foundation for co-option and differentiation of medicinally important ursane triterpene pathway duplicates, generating distinct chemotypes between species and between developmental stages in the apple tribe. After generating chromosome-level assemblies of a widely cultivated loquat variety and Gillenia trifoliata, we define differentially evolved, duplicated gene pathways and date the WGD in the apple tribe at 13.5 to 27.1 Mya, much more recent than previously thought. We then functionally characterize contrasting metabolic pathways responsible for major triterpene biosynthesis in G. trifoliata and loquat, which pre- and postdate the Maleae WGD, respectively. Our work mechanistically details the metabolic diversity that arose post-WGD and provides insights into the genomic basis of medicinal properties of loquat, which has been used in both traditional and modern medicines.

Tahibacter harae sp. nov., isolated from pig farm soil in Guangdong, PR China.

In the process of exploring the microbial diversity of pig farms, a Gram-stain-negative, aerobic, rod-shaped, non-spore-forming, non-motile bacterial strain, designated P2KT, was isolated from soil sample collected at a pig farm, Guangdong Province, PR China. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain P2KT belonged to the genus Tahibacter, with the highest sequence similarity to Tahibacter aquaticus PYM5-11T (98.6%) and Tahibacter caeni BUT-6T (98.3 %). The genome size of strain P2KT was 6.0 Mb with a DNA G+C content of 68.3 mol%. Average nucleotide identity values between strain P2KT and the type strains of the genus Tahibacter were 81.1-81.6 %. The digital DNA-DNA hybridization values between P2KT and these relative species were 24.5-25.6%. The polar lipids were phosphatidylethanolamine, phosphatidylglycerol, an unknown aminolipids, two unknown lipids and three unknown phospholipids. The major respiratory quinone of strain P2KT was ubiquinone Q-8, and the main fatty acids (>10.0 % of total fatty acids) of strain P2KT were iso-C15:0, iso-C16:0 and summed feature 9 (C16:0 10-methyl and/or iso-C17:1 ω9c). Based on phenotypic and genotypic data, strain P2KT represents a novel species within the genus Tahibacter, for which the name Tahibacter harae sp. nov. is proposed, with the type strain P2KT (=GDMCC 1.3107T=JCM 35231T).

Marine Dehalogenator and Its Chaperones: Microbial Duties and Responses in 2,4,6-Trichlorophenol Dechlorination.

Marine environments contain diverse halogenated organic compounds (HOCs), both anthropogenic and natural, nourishing a group of versatile organohalide-respiring bacteria (OHRB). Here, we identified a novel OHRB (Peptococcaceae DCH) with conserved motifs but phylogenetically diverse reductive dehalogenase catalytic subunit (RdhAs) from marine enrichment culture. Further analyses clearly demonstrate the horizontal gene transfer of rdhAs among marine OHRB. Moreover, 2,4,6-trichlorophenol (TCP) was dechlorinated to 2,4-dichlorophenol and terminated at 4-chlorophenol in culture. Dendrosporobacter and Methanosarcina were the two dominant genera, and the constructed and verified metabolic pathways clearly demonstrated that the former provided various substrates for other microbes, while the latter drew nutrients, but might provide little benefit to microbial dehalogenation. Furthermore, Dendrosporobacter could readily adapt to TCP, and sporulation-related proteins of Dendrosporobacter were significantly upregulated in TCP-free controls, whereas other microbes (e.g., Methanosarcina and Aminivibrio) became more active, providing insights into how HOCs shape microbial communities. Additionally, sulfate could affect the dechlorination of Peptococcaceae DCH, but not debromination. Considering their electron accessibility and energy generation, the results clearly demonstrate that bromophenols are more suitable than chlorophenols for the enrichment of OHRB in marine environments. This study will greatly enhance our understanding of marine OHRB (rdhAs), auxiliary microbes, and microbial HOC adaptive mechanisms.

Recent progress of direct thiocyanation reactions.

Thiocyanates are common in natural products, synthetic drugs and bioactive molecules. Many thiocyanate derivatives show excellent antibacterial, antiparasitic and anticancer activities. Thiocyanation can introduce SCN groups into parent molecules for constructing SCN-containing small organic molecules. Among them, the direct introduction method mainly includes nucleophilic reaction, electrophilic reaction and free radical reaction, which can simply and quickly introduce SCN groups at the target sites to construct thiocyanates, and has broad application prospects. In this review, we summarize the research progress of direct thiocyanation in recent years.

Garcinia Biflavonoid 1 Improves Lipid Metabolism in HepG2 Cells via Regulating PPARα.

Garcinia biflavonoid 1 (GB1) is one of the active chemical components of Garcinia kola and is reported to be capable of reducing the intracellular lipid deposition, which is the most significant characteristic of non-alcoholic fatty liver disease. However, its bioactive mechanism remains elusive. In the current study, the lipid deposition was induced in HepG2 cells by exposure to oleic acid and palmitic acid (OA&PA), then the effect of GB1 on lipid metabolism and oxidative stress and the role of regulating PPARα in these cells was investigated. We found that GB1 could ameliorate the lipid deposition by reducing triglycerides (TGs) and upregulate the expression of PPARα and SIRT6, suppressing the cell apoptosis by reducing the oxidative stress and the inflammatory factors of ROS, IL10, and TNFα. The mechanism study showed that GB1 had bioactivity in a PPARα-dependent manner based on its failing to improve the lipid deposition and oxidative stress in PPARα-deficient cells. The result revealed that GB1 had significant bioactivity on improving the lipid metabolism, and its potential primary action mechanism suggested that GB1 could be a potential candidate for management of non-alcoholic fatty liver disease.

In Situ Growth of 2D Ultrathin NiCo2 O4 Nanosheet Arrays on Ni Foam for High Performance and Flexible Solid-State Supercapacitors.

In order to further overcome the shortage of electrodes with additive/binder and modulate the structure of NiCo2 O4 for supercapacitors, ultrathin NiCo2 O4 nanosheet arrays have been in situ grown on Ni foam by optimizing hydrothermal reactions based on crystal growth dynamics. The structure of ultrathin NiCo2 O4 nanosheet arrays can expose more active sites, provide abundant diffusion channels and buffer the stress caused by phase transition during charge-discharge process of supercapacitors. The optimized hydrothermal reactions can provide more ordered crystal orientations by keeping nanosheets on Ni foam completely coming from in situ growth, which will decrease the inner resistance of ultrathin NiCo2 O4 nanosheets and improve the efficiency and kinetics of electrons transfer. By the virtue of such remarkable features, the electrochemical results confirm the rationality of structural modulation and crystal orientations optimization with a drastically enhanced specific capacitance of 2017.8 F g-1 , admirable rate performance of 93.2% and outstanding stability retention of 90.9% after cycling 5000 times. More impressively, the assembled flexible solid-state asymmetric supercapacitor (ASC) shows superior energy density, power density, and high stability. The modification strategy in this paper may throw light on the rational design of new generation advanced electrode materials for high-performance flexible supercapacitors.

Real-time artificial intelligence for detection of upper gastrointestinal cancer by endoscopy: a multicentre, case-control, diagnostic study.

BACKGROUND: Upper gastrointestinal cancers (including oesophageal cancer and gastric cancer) are the most common cancers worldwide. Artificial intelligence platforms using deep learning algorithms have made remarkable progress in medical imaging but their application in upper gastrointestinal cancers has been limited. We aimed to develop and validate the Gastrointestinal Artificial Intelligence Diagnostic System (GRAIDS) for the diagnosis of upper gastrointestinal cancers through analysis of imaging data from clinical endoscopies. METHODS: This multicentre, case-control, diagnostic study was done in six hospitals of different tiers (ie, municipal, provincial, and national) in China. The images of consecutive participants, aged 18 years or older, who had not had a previous endoscopy were retrieved from all participating hospitals. All patients with upper gastrointestinal cancer lesions (including oesophageal cancer and gastric cancer) that were histologically proven malignancies were eligible for this study. Only images with standard white light were deemed eligible. The images from Sun Yat-sen University Cancer Center were randomly assigned (8:1:1) to the training and intrinsic verification datasets for developing GRAIDS, and the internal validation dataset for evaluating the performance of GRAIDS. Its diagnostic performance was evaluated using an internal and prospective validation set from Sun Yat-sen University Cancer Center (a national hospital) and additional external validation sets from five primary care hospitals. The performance of GRAIDS was also compared with endoscopists with three degrees of expertise: expert, competent, and trainee. The diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of GRAIDS and endoscopists for the identification of cancerous lesions were evaluated by calculating the 95% CIs using the Clopper-Pearson method. FINDINGS: 1 036 496 endoscopy images from 84 424 individuals were used to develop and test GRAIDS. The diagnostic accuracy in identifying upper gastrointestinal cancers was 0·955 (95% CI 0·952-0·957) in the internal validation set, 0·927 (0·925-0·929) in the prospective set, and ranged from 0·915 (0·913-0·917) to 0·977 (0·977-0·978) in the five external validation sets. GRAIDS achieved diagnostic sensitivity similar to that of the expert endoscopist (0·942 [95% CI 0·924-0·957] vs 0·945 [0·927-0·959]; p=0·692) and superior sensitivity compared with competent (0·858 [0·832-0·880], p<0·0001) and trainee (0·722 [0·691-0·752], p<0·0001) endoscopists. The positive predictive value was 0·814 (95% CI 0·788-0·838) for GRAIDS, 0·932 (0·913-0·948) for the expert endoscopist, 0·974 (0·960-0·984) for the competent endoscopist, and 0·824 (0·795-0·850) for the trainee endoscopist. The negative predictive value was 0·978 (95% CI 0·971-0·984) for GRAIDS, 0·980 (0·974-0·985) for the expert endoscopist, 0·951 (0·942-0·959) for the competent endoscopist, and 0·904 (0·893-0·916) for the trainee endoscopist. INTERPRETATION: GRAIDS achieved high diagnostic accuracy in detecting upper gastrointestinal cancers, with sensitivity similar to that of expert endoscopists and was superior to that of non-expert endoscopists. This system could assist community-based hospitals in improving their effectiveness in upper gastrointestinal cancer diagnoses. FUNDING: The National Key R&D Program of China, the Natural Science Foundation of Guangdong Province, the Science and Technology Program of Guangdong, the Science and Technology Program of Guangzhou, and the Fundamental Research Funds for the Central Universities.

A Zinc Coordination Complex Mimicking Carbonic Anhydrase for CO2 Hydrolysis and Sequestration.

Carbonic anhydrase (CA) mimicking is an effective and environmentally friendly strategy for carbon dioxide sequestration. Herein, we developed a nonanuclear CA-mimetic zinc coordination complex (1) which possesses a coordination environment similar to that of CA's catalytically active zinc sites. Complex 1 exhibited excellent reusability, solvent and thermal stability, and gram-scale synthesis, which are essential for practical applications. It was found that complex 1 exhibited outstanding catalytic performance that is much better in comparison to that of the popular CA-mimetic compound Zn-cyclen and comparable to that of the reported metal-organic frameworks (e.g., CFA-1). Moreover, we found that its catalytic activity can be significantly improved via OAc-/OH- exchange and particle size reduction treatment. This study provides important guidance for the design of highly efficient CA-mimetic materials.

UiO-66: An Advanced Platform for Investigating the Influence of Functionalization in the Adsorption Removal of Pharmaceutical Waste.

Highly efficient and selective removal of pharmaceuticals and personal care products (PPCPs) from wastewater is a great challenge and is significant. In this study, we chose UiO-66-R, which contains eight isostructural metal-organic frameworks (MOFs) with variable functional groups (-R), as a platform for systemically investigating the influence of functionalization on its adsorption behavior with respect to three classic PPCPs. We conducted kinetic, modeling, and structure-function relationship studies on PPCP removal using MOFs. The adsorption kinetics, including the adsorption rate, affinity, and separation factor ( RL), were comprehensively analyzed and simulated. The design and function of MOFs can greatly promote their adsorption capacity and the efficiency of PPCPs. The structure-function relationship study revealed that hydrogen bonding, electrostatic, and π-π interactions between MOFs and PPCP molecules played important roles in the adsorption process and significantly influenced the adsorption efficiency. This study paves a new way for the application of MOFs with respect to the removal of PPCP pollution and provides guidance for the design of new porous materials for environmental treatment and separation applications.

Practice effects of personalized interventions with interdisciplinary teamwork in type 2 diabetes remission: a retrospective study.

Objectives: A retrospective analysis of the clinical outcomes of personalized interventions for type 2 diabetes mellitus (T2DM) in an interdisciplinary team. Methods: Under the guidance of an interdisciplinary team, 40 patients with T2DM underwent a systematic examination at the beginning of the intervention, 3 months after the intervention, and 3 months of follow-up at the end of the intervention (i.e., at 6 months). Key indicators such as fasting plasma glucose (FPG), 2-hour postprandial glucose (2hPG), fasting insulin level (FINS), glycated hemoglobin (HbA1c), blood lipids, and body mass index (BMI) were measured. Results: After the 3-month intervention, participants' BMI, FPG, 2hPG, FINS, and HbA1c improved significantly, with statistically significant differences (P<0.05).These metrics remained essentially stable at the 3-month follow-up. Of all the participants, 92.5% (37 cases in total) successfully discontinued their medication after 3 months of intervention, of which 80% (32 cases) remained stable during the 3-month follow-up after discontinuation, fulfilling the criteria for remission of T2DM; 2 cases successfully reduced the dose of their medication, and only 1 case was maintained on the original treatment. Conclusions: Through an interdisciplinary team intervention strategy, we significantly optimized the glucose metabolism, lipid metabolism, and BMI status of patients with T2DM, making diabetes remission an achievable goal, which provides valuable experience for further optimization of diabetes prevention and control protocols.

Plant polysaccharide-derived edible film packaging for instant food: Rapid dissolution in hot water coupled with exceptional mechanical and barrier characteristics.

A comprehensive multiscale analysis was conducted to explore the effects of different ratios of these materials on its properties. The results show that KC played a crucial role in controlling solution viscosity and gel and sol temperatures. The dissolution time at high water temperatures primarily decreased with an increase in SA content. Higher KC and CS content increased tensile strength (TS) and elongation at break (ε), while also exhibiting better thermal stability. Water vapor transmission (WVT) and permeability (PV) initially decreased, then increased with the increase of SA and CS contents. Finally, an SA:KC:CS ratio of 1:3:2 showed optimal comprehensive properties, with a dissolution time of about 60.0 ± 3.8 s, TS of 23.80 ± 0.29 MPa, ε of 18.61 ± 0.34 %, WVT of 21.74 ± 0.62 g/m2·24h, and PV of 5.39 ± 0.17 meq/kg. Meanwhile, the SA:KC:CS edible food packaging only introduced minimal effects on food after dissolution, and the total bacterial count met regulatory standards.

Cuproptosis-related gene FDX1 as a prognostic biomarker for kidney renal clear cell carcinoma correlates with immune checkpoints and immune cell infiltration.

Background: Kidney renal clear cell carcinoma (KIRC) is not sensitive to radiotherapy and chemotherapy, and only some KIRC patients can benefit from immunotherapy and targeted therapy. Cuproptosis is a new mechanism of cell death, which is closely related to tumor progression, prognosis and immunity. The identification of prognostic markers related to cuproptosis in KIRC may provide targets for treatment and improve the prognosis of KIRC patients. Methods: Ten cuproptosis-related genes were analyzed for differential expression in KIRC-TCGA and a prognostic model was constructed. Nomogram diagnostic model was used to screen independent prognostic molecules. The screened molecules were verified in multiple datasets (GSE36895 and GSE53757), and in KIRC tumor tissues by RT-PCR and immunohistochemistry (IHC). Clinical correlation of cuproptosis-related independent prognostic molecules was analyzed. According to the molecular expression, the two groups were divided into high and low expression groups, and the differences of immune checkpoint and tumor infiltrating lymphocytes (TILs) between the two groups were compared by EPIC algorithm. The potential Immune checkpoint blocking (ICB) response of high and low expression groups was predicted by the "TIDE" algorithm. Results: FDX1 and DLAT were protective factors, while CDKN2A was a risk factor. FDX1 was an independent prognostic molecule by Nomogram, and low expressed in tumor tissues compared with adjacent tissues (p < 0.05). FDX1 was positively correlated with CD274, HAVCR2, PDCD1LG2, and negatively correlated with CTLA4, LAG3, and PDCD1. The TIDE score of low-FDX1 group was higher than that of high-FDX1 group. The abundance of CD4+ T cells, CD8+ T cells and Endothelial cells in FDX1-low group was lower than that in FDX1-high group (p < 0.05). Conclusion: FDX1, as a key cuproptosis-related gene, was also an independent prognostic molecule of KIRC. FDX1 might become an interesting biomarker and potential therapeutic target for KIRC.

High expression of IL6 and decrease in immune cells in COVID-19 patients combined with myocardial injury.

Purpose: Myocardial injury, as a serious complication of coronavirus disease-2019 (COVID-19), increases the occurrence of adverse outcomes. Identification of key regulatory molecules of myocardial injury may help formulate corresponding treatment strategies and improve the prognosis of COVID-19 patients. Methods: Gene Set Enrichment Analysis (GSEA) was conducted to identify co-regulatory pathways. Differentially expressed genes (DEGs) in GSE150392 and GSE169241 were screened and an intersection analysis with key genes of the co-regulatory pathway was conducted. A protein-protein interaction (PPI) network was constructed to screen for key regulatory genes. Preliminarily screened genes were verified using other datasets to identify genes with consistent expression. Based on the hierarchical cluster, we divided the patients from GSE177477 into high- and low-risk groups and compared the proportion of immune cells. A total of 267 COVID-19 patients from the Zhejiang Provincial Hospital of Chinese Medicine from December 26, 2022, to January 11, 2023, were enrolled to verify the bioinformatics results. Univariate and multivariate analyses were performed to analyze the risk factors for myocardial injury. According to high-sensitivity troponin (hsTnI) levels, patients with COVID-19 were divided into high- and low-sensitivity groups, and interleukin 6 (IL6) expression and lymphocyte subsets were compared. Patients were also divided into high and low groups according to the IL6 expression, and hsTnI levels were compared. Results: Interleukin signaling pathway and GPCR ligand binding were shown to be co-regulatory pathways in myocardial injury associated with COVID-19. According to the hierarchical cluster analysis of seven genes (IL6, NFKBIA, CSF1, CXCL1, IL1R1, SOCS3, and CASP1), patients with myocardial injury could be distinguished from those without myocardial injury. Age, IL6 levels, and hospital stay may be factors influencing myocardial injury caused by COVID-19. Compared with COVID-19 patients without myocardial injury, the levels of IL6 in patients with myocardial injury increased, while the number of CD4+ T cells, CD8+ T cells, B cells, and NK cells decreased (P<0.05). The hsTnI levels in COVID-19 patients with high IL6 levels were higher than those in patients with low IL6 (P<0.05). Conclusions: The COVID-19 patients with myocardial injury had elevated IL6 expression and decreased lymphocyte counts. IL6 may participate in myocardial injury through the interleukin signaling pathway.

Retroperitoneal laparoscopic renal biopsy: an 8 year experience at a single centre.

PURPOSE: To present our experience and outcome of consecutive laparoscopic renal biopsy (LRB) in a series of Chinese patients over an 8 year period. METHODS: Between January 1, 2013, and December 31, 2020, 104 patients (M/F 71/33, age 43.6 ± 16.0 years) were enrolled. All patients underwent LRB for various indications, e.g., dialysis dependence (33.7%), serum levels of creatinine ≥ 442 µmol/L (20.2%), morbid obesity (18.3%), uncontrolled severe hypertension (14.4%), aberrant renal anatomy (5.8%), solitary kidney (2.9%), deaf-mutes (2.9%), failed percutaneous biopsy (1.0%) and patient choice (1.0%). The kidney was approached via the laparoscopic retroperitoneal route using a three-port technique. Then, 16-gauge true-cut needle biopsy was performed and haemostasis was achieved by compression. Topical collagen mesh was used if necessary. RESULTS: Renal tissue was obtained in all cases. The operative time and amount of blood loss were significantly (P < 0.05) lower in 2017-2020 than 2013-2016 [42.6 ± 1.5 min and 9.6 ± 0.7 mL, respectively (n = 61) vs. 51.2 ± 1.3 min and 14.4 ± 0.9 mL, respectively (n = 43)], while the hospital stay was not significantly different between the two periods. The rate of tissue adequacy and median number of glomeruli were significantly higher in 2017-2020 than 2013-2016 [100% and 52 (IQR 24-94), respectively vs. 93% and 35 (IQR 6-98), respectively). Two postoperative complications occurred in the first 4 years: disseminated intravascular coagulation (DIC) during the operation and injury at the hilum of the kidney (n = 1 each). The renal pathological diagnoses were also complex: 70.2% of the cases were independent pathological types, including IgA nephropathy (IgAN) (13.5%), Henoch-Schönlein purpura nephritis (HSPN) (2.9%), focal segmental glomerulosclerosis (FSGS) (9.6%), membranous glomerulonephritis (MN) (1.9%), lupus nephritis (LN) (3.8%), crescentic glomerulonephritis (CreGN) (7.7%), diabetic nephropathy (DN) (10.6%), tubulointerstitial nephritis (TIN) (11.5%) and malignant hypertensive nephropathy (MHTN) (8.7%). However, the rates of combinations of two and three pathological types were 25.0% and 4.8%, respectively. CONCLUSION: Retroperitoneal LRB is a safe, reliable, minimally invasive alternative for patients in whom PRB in not feasible. As a helpful supplement to PRB, it may be necessary to use this technique more often in the future.

Characteristics of a lipase ArEstA with lytic activity against drug-resistant pathogen from a novel myxobacterium, Archangium lipolyticum sp. nov.

Bacteriolytic myxobacteria are versatile micropredators and are proposed as potential biocontrol agents against diverse bacterial and fungal pathogens. Isolation of new myxobacteria species and exploration of effective predatory products are necessary for successful biocontrol of pathogens. In this study, a myxobacterium strain CY-1 was isolated from a soil sample of a pig farm using the Escherichia coli baiting method. Based on the morphological observation, physiological test, 16S rRNA gene sequence, and genomic data, strain CY-1 was identified as a novel species of the myxobacterial genus Archangium, for which the name Archangium lipolyticum sp. nov. was proposed. Subsequent predation tests indicated that the strain efficiently lysed drug-resistant pathogens, with a higher predatory activity against E. coli 64 than Staphylococcus aureus GDMCC 1.771 (MRSA). The lysis of extracellular proteins against ester-bond-containing substrates (tributyrin, tween 80, egg-yolk, and autoclaved drug-resistant pathogens) inspired the mining of secreted predatory products with lipolytic activity. Furthermore, a lipase ArEstA was identified from the genome of CY-1, and the heterologously expressed and purified enzyme showed bacteriolytic activity against Gram-negative bacteria E. coli 64 but not against Gram-positive MRSA, possibly due to different accessibility of enzyme to lipid substrates in different preys. Our research not only provided a novel myxobacterium species and a candidate enzyme for the development of new biocontrol agents but also reported an experimental basis for further study on different mechanisms of secreted predatory products in myxobacterial killing and degrading of Gram-negative and Gram-positive preys.

Raspberry polyphenols alleviate neurodegenerative diseases: through gut microbiota and ROS signals.

Neurodegenerative diseases are neurological disorders that become more prevalent with age, usually caused by damage or loss of neurons or their myelin sheaths, such as Alzheimer's disease and epilepsy. Reactive oxygen species (ROS) are important triggers for neurodegenerative disease development, and mitigation of oxidative stress caused by ROS imbalance in the human body is important for the treatment of these diseases. As a widespread delicious fruit, the raspberry is widely used in the field of food and medicine because of its abundant polyphenols and other bioactive substances. Polyphenols from a wide variety of raspberry sources could alleviate neurodegenerative diseases. This review aims to summarize the current roles of these polyphenols in maintaining neurological stability by regulating the composition and metabolism of the intestinal flora and the gut-brain axis signal transmission. Especially, we discuss the therapeutic effects on neurodegenerative diseases of raspberry polyphenols through intestinal microorganisms and ROS signals, by means of summary and analysis. Finally, methods of improving the digestibility and utilization of raspberry polyphenols are proposed, which will provide a potential way for raspberry polyphenols to guarantee the health of the human nervous system.

F18:A-:B1 Plasmids Carrying blaCTX-M-55 Are Prevalent among Escherichia coli Isolated from Duck-Fish Polyculture Farms.

We determined the prevalence and molecular characteristics of blaCTX-M-55-positive Escherichia coli (E. coli) isolated from duck-fish polyculture farms in Guangzhou, China. A total of 914 E. coli strains were isolated from 2008 duck and environmental samples (water, soil and plants) collected from four duck fish polyculture farms between 2017 and 2019. Among them, 196 strains were CTX-M-1G-positive strains by PCR, and 177 (90%) blaCTX-M-1G-producing strains were blaCTX-M-55-positive. MIC results showed that the 177 blaCTX-M-55-positive strains were highly resistant to ciprofloxacin, ceftiofur and florfenicol, with antibiotic resistance rates above 95%. Among the 177 strains, 37 strains carrying the F18:A-:B1 plasmid and 10 strains carrying the F33:A-:B- plasmid were selected for further study. Pulse field gel electrophoresis (PFGE) combined with S1-PFGE, Southern hybridization and whole-genome sequencing (WGS) analysis showed that both horizontal transfer and clonal spread contributed to dissemination of the blaCTX-M-55 gene among the E. coli. blaCTX-M-55 was located on different F18:A-:B1 plasmids with sizes between ~76 and ~173 kb. In addition, the presence of blaCTX-M-55 with other resistance genes (e.g., tetA, floR, fosA3, blaTEM, aadA5 CmlA and InuF) on the same F18:A-:B1 plasmid may result in co-selection of resistance determinants and accelerate the dissemination of blaCTX-M-55 in E. coli. In summary, the F18:A-:B1 plasmid may play an important role in the transmission of blaCTX-M-55 in E. coli, and the continuous monitoring of the prevalence and transmission mechanism of blaCTX-M-55 in duck-fish polyculture farms remains important.

Antimicrobial resistome during the transition from an integrated to a monoculture aquaculture farm in southern China.

Integrated and monoculture freshwater aquaculture systems are often regarded as important reservoirs for antimicrobial resistance genes (ARGs) and antimicrobial resistance bacteria (ARBs), yet only a few studies have assessed differences in the antimicrobial resistome and antibiotic residues between aquaculture modes. In this study, a metagenomic approach was used to comprehensively explore the dynamic patterns and potential transmission mechanisms of ARGs in ducks, human workers, fish, water and sediments during the transition from an integrated to a monoculture freshwater aquaculture mode and to investigate the associations of ARGs with potential hosts in microbial communities using network analysis and a binning approach. The results showed that the abundance and diversity of ARGs were higher under integrated fish-duck farming than in single fish ponds. During the transition from an integrated to a monoculture aquaculture farm, ARGs in workers and sediments were not easily removed. However, ARGs in the aquatic environment underwent regular changes. In addition, duck manure was probably the most dominant source of ARGs in the duck farm environment. Network analysis indicated that Escherichia spp. were the most dominant hosts of ARGs. Variation partitioning analysis (VPA) showed that in water samples, the bacterial community played an important role in the ARG profile. In addition, we identified a potential risk of the presence of highly virulent and antimicrobial-resistant Klebsiella pneumoniae in workers. These results help assess the risk of ARG transmission in integrated and monoculture aquaculture farms and suggest that we should strengthen the monitoring of long-term resistance in integrated aquaculture environments.

Ginsenosides Rc, as a novel SIRT6 activator, protects mice against high fat diet induced NAFLD.

Background: Hepatic lipid disorder impaired mitochondrial homeostasis and intracellular redox balance, triggering development of non-alcohol fatty liver disease (NAFLD), while effective therapeutic approach remains inadequate. Ginsenosides Rc has been reported to maintain glucose balance in adipose tissue, while its role in regulating lipid metabolism remain vacant. Thus, we investigated the function and mechanism of ginsenosides Rc in defending high fat diet (HFD)-induced NAFLD. Methods: Mice primary hepatocytes (MPHs) challenged with oleic acid & palmitic acid were used to test the effects of ginsenosides Rc on intracellular lipid metabolism. RNAseq and molecular docking study were performed to explore potential targets of ginsenosides Rc in defending lipid deposition. Wild type and liver specific sirtuin 6 (SIRT6, 50721) deficient mice on HFD for 12 weeks were subjected to different dose of ginsenosides Rc to determine the function and detailed mechanism in vivo. Results: We identified ginsenosides Rc as a novel SIRT6 activator via increasing its expression and deacetylase activity. Ginsenosides Rc defends OA&PA-induced lipid deposition in MPHs and protects mice against HFD-induced metabolic disorder in dosage dependent manner. Ginsenosides Rc (20mg/kg) injection improved glucose intolerance, insulin resistance, oxidative stress and inflammation response in HFD mice. Ginsenosides Rc treatment accelerates peroxisome proliferator activated receptor alpha (PPAR-α, 19013)-mediated fatty acid oxidation in vivo and in vitro. Hepatic specific SIRT6 deletion abolished ginsenoside Rc-derived protective effects against HFD-induced NAFLD. Conclusion: Ginsenosides Rc protects mice against HFD-induced hepatosteatosis by improving PPAR-α-mediated fatty acid oxidation and antioxidant capacity in a SIRT6 dependent manner, and providing a promising strategy for NAFLD.

Crosstalk between PML and p53 in response to TGF-ß1: A new mechanism of cardiac fibroblast activation.

Cardiac fibrosis is a common pathological cardiac remodeling in a variety of heart diseases, characterized by the activation of cardiac fibroblasts. Our previous study uncovered that promyelocytic leukemia protein (PML)-associated SUMO processes is a new regulator of cardiac hypertrophy and heart failure. The present study aimed to explore the role of PML in cardiac fibroblasts activation. Here we found that PML is significantly upregulated in cardiac fibrotic tissue and activated cardiac fibroblasts treated with transforming growth factor-ß1 (TGF-ß1). Gain- and loss-of-function experiments showed that PML impacted cardiac fibroblasts activation after TGF-ß1 treatment. Further study demonstrated that p53 acts as the transcriptional regulator of PML, and participated in TGF-ß1 induced the increase of PML expression and PML nuclear bodies (PML-NBs) formation. Knockdown or pharmacological inhibition of p53 produced inhibitory effects on the activation of cardiac fibroblasts. We further found that PML also may stabilize p53 through inhibiting its ubiquitin-mediated proteasomal degradation in cardiac fibroblasts. Collectively, this study suggests that PML crosstalk with p53 regulates cardiac fibroblasts activation, which provides a novel therapeutic strategy for cardiac fibrosis.