Radiolytic Effects on Biological and Abiotic Amino Acids in Shallow Subsurface Ices on Europa and Enceladus.

Europa and Enceladus are key targets to search for evidence of life in our solar system. However, the surface and shallow subsurface of both airless icy moons are constantly bombarded by ionizing radiation that could degrade chemical biosignatures. Therefore, sampling of icy surfaces in future life detection missions to Europa and Enceladus requires a clear understanding of the necessary ice depth where unaltered organic biomolecules might be present. We conducted radiolysis experiments by exposing individual amino acids in ices and amino acids from dead microorganisms in ices to gamma radiation to simulate conditions on these icy worlds. In the pure amino acid samples, glycine did not show a detectable decrease in abundance, whereas the abundance of isovaline decreased by 40% after 4 MGy of exposure. Amino acids in dead Escherichia coli (E. coli) organic matter exhibited a gradual decline in abundances with the increase of exposure dosage, although at much slower rates than individual amino acids. The majority of amino acids in dead A. woodii samples demonstrated a step function decline as opposed to a gradual decline. After the initial drop in abundance with 1 MGy of exposure, those amino acids did not display further decreases in abundance after exposure up to 4 MGy. New radiolysis constants for isolated amino acids and amino acids in dead E. coli material for Europa/Enceladus-like conditions have been derived. Slow rates of amino acid destruction in biological samples under Europa and Enceladus-like surface conditions bolster the case for future life detection measurements by Europa and Enceladus lander missions. Based on our measurements, the "safe" sampling depth on Europa is ∼20 cm at high latitudes of the trailing hemisphere in the area of little impact gardening. Subsurface sampling is not required for the detection of amino acids on Enceladus-these molecules will survive radiolysis at any location on the Enceladus surface. If the stability of amino acids observed in A. woodii organic materials is confirmed in other microorganisms, then the survival of amino acids from a potential biosphere in Europa ice would be significantly increased.

High-Throughput Screening for Oligonucleotide Detection by ADE-OPI-MS.

Oligonucleotides represent a class of shorter DNA or RNA nucleic acid polymers extensively applied in the biomedical field. Despite progress in detecting and analyzing oligonucleotides, high-throughput analysis of the samples remains challenging. In this work, a high-throughput analysis method for oligonucleotide analysis was developed based on acoustic droplet ejection-open port interface-mass spectrometry (ADE-OPI-MS) technology. This approach was applied to determine the enzymatic activity of terminal deoxynucleotide transferase (TdT) for DNA synthesis, with a rate of 3 s/sample, which enhanced single-sample analysis efficiency approximately 60-fold over the previous gel analysis. After testing approximately 10,000 TdT mutants, we obtained three new variants with higher catalytic activities. Finally, by integrating these mutants, the catalytic activity of TdT was improved about 4 times compared to the starting mutant. Our results successfully established a high-throughput screening method for oligonucleotide analysis, which not only provides a foundation to engineer highly efficient TdT for ab initio synthesis of DNA but also paves the way for the potential application of oligonucleotide analysis in biomedical fields.

Development and validation of a scoring system to predict the mortality of hospitalized patients with SARS-CoV-2 Omicron: a nationwide, multicentre study.

BACKGROUND: The Omicron variant broke out in China at the end of 2022, causing a considerable number of severe cases and even deaths. The study aimed to identify risk factors for death in patients hospitalized with SARS-CoV-2 Omicron infection and to establish a scoring system for predicting mortality. METHODS: 1817 patients were enrolled at eight hospitals in China from December 2022 to May 2023, including 815 patients in the training group and 1002 patients in the validation group. Forty-six clinical and laboratory features were screened using LASSO regression and multivariable logistic regression. RESULTS: In the training set, 730 patients were discharged and 85 patients died. In the validation set, 918 patients were discharged and 84 patients died. LASSO regression identified age, levels of interleukin (IL) -6, blood urea nitrogen (BUN), lactate dehydrogenase (LDH), and D-dimer; neutrophil count, neutrophil-to-lymphocyte ratio (NLR) as associated with mortality. Multivariable logistic regression analysis showed that older age, IL-6, BUN, LDH and D-dimer were significant independent risk factors. Based on these variables, a scoring system was developed with a sensitivity of 83.6% and a specificity of 83.5% in the training group, and a sensitivity of 79.8% and a sensitivity of 83.0% in the validation group. CONCLUSIONS: A scoring system based on age, IL-6, BUN, LDH and D-dime can help clinicians identify patients with poor prognosis early.

Discovery and characterization of BRBV-sheep virus in nasal swabs from domestic sheep in China.

Introduction: The escalating occurrence of infectious disease outbreaks in humans and animals necessitates innovative, effective, and integrated research to better comprehend their transmission and dynamics. Viral infection in livestock has led to profound economic losses globally. Pneumonia is the prevalent cause of death in sheep. However, very few studies exist regarding virus-related pathogens in sheep. Metagenomics sequencing technologies in livestock research hold significant potential to elucidate these contingencies and enhance our understanding. Methods: Therefore, this study aims to characterize respiratory viromes in paired nasal swabs from Inner Mongolian feedlot sheep in China using metaviromic sequencing. Through deep sequencing, de novo assembly, and similarity searches using translated protein sequences, several previously uncharacterized and known viruses were identified in this study. Results: Among these discoveries, a novel Bovine Rhinitis B Virus (BRBV) (BRBV-sheep) strain was serendipitously detected in the nasal swabs of domestic sheep (Ovis aries). To facilitate further molecular epidemiological studies, the entire genome of BRBV-sheep was also determined. Owing to the unique sequence characteristics and phylogenetic position of BRBV-sheep, genetically distinct lineages of BRBV in sheep may exist. A TaqMan-based qRT-PCR assay targeting the 3D polymerase gene was developed and used to screen 592 clinical sheep specimens. The results showed that 44.59% of the samples (264/592) were positive. These findings suggest that BRBV sheep are widespread among Inner Mongolian herds. Conclusion: This discovery marks the initial identification of BRBV in sheep within Inner Mongolia, China. These findings contribute to our understanding of the epidemiology and genetic evolution of BRBV. Recognizing the presence of BRBV in sheep informs strategies for disease management and surveillance and the potential development of targeted interventions to control its spread.

Unlocking the formate utilization of wild-type Yarrowia lipolytica through adaptive laboratory evolution.

Synthetic biology is contributing to the advancement of the global net-negative carbon economy, with emphasis on formate as a member of the one-carbon substrate garnering substantial attention. In this study, we employed base editing tools to facilitate adaptive evolution, achieving a formate tolerance of Yarrowia lipolytica to 1 M within 2 months. This effort resulted in two mutant strains, designated as M25-70 and M25-14, both exhibiting significantly enhanced formate utilization capabilities. Transcriptomic analysis revealed the upregulation of nine endogenous genes encoding formate dehydrogenases when cultivated utilizing formate as the sole carbon source. Furthermore, we uncovered the pivotal role of the glyoxylate and threonine-based serine pathway in enhancing glycine supply to promote formate assimilation. The full potential of Y. lipolytica to tolerate and utilize formate establishing the foundation for pyruvate carboxylase-based carbon sequestration pathways. Importantly, this study highlights the existence of a natural formate metabolic pathway in Y. lipolytica.

Assessment of drug-drug interaction of dapagliflozin with LCZ696 based on an LC-MS/MS method.

The co-administration of dapagliflozin (DPF) and sacubitril/valsartan (LCZ696) has emerged as a promising therapeutic approach for managing heart failure. Given that DPF and LCZ696 are substrates for P-glycoprotein, there is a plausible potential for drug-drug interactions when administered concomitantly. To investigate the pharmacokinetic changes when these drugs are co-administered, we have established and validated a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method capable of simultaneously detecting DPF, LBQ657 (the active metabolite of sacubitril) and valsartan in rat plasma. This method has demonstrated selectivity, sensitivity, and accuracy. Drug-drug interactions were examined by the LC-MS/MS method. The mechanisms were investigated using everted intestinal sac models and Caco-2 cells. The results showed that DPF significantly increased the area under the curve (AUC(0-t)) (3,563.3 ± 651.7 vs. 7,146.5 ± 1,714.9 h µg/L) of LBQ657 (the active metabolite of sacubitril) and the AUC(0-t) (24,022.4 ± 6,774.3 vs. 55,728.3 ± 32,446.3 h µg/L) of valsartan after oral co-administration. Dapagliflozin significantly increased the amount of LBQ657 and valsartan in intestinal sacs by 1- and 1.25-fold at 2.25 h. Caco-2 cell uptake studies confirmed that P-glycoprotein is the transporter involved in this interaction. This finding enhances the understanding of drug-drug interactions in the treatment of heart failure and provides a guidence for clinical therapy.

Inactivation of adenosine receptor 2A suppresses endothelial-to-mesenchymal transition and inhibits subretinal fibrosis in mice.

Anti-vascular endothelial growth factor therapy has had a substantial impact on the treatment of choroidal neovascularization (CNV) in patients with neovascular age-related macular degeneration (nAMD), the leading cause of vision loss in older adults. Despite treatment, many patients with nAMD still develop severe and irreversible visual impairment because of the development of subretinal fibrosis. We recently reported the anti-inflammatory and antiangiogenic effects of inhibiting the gene encoding adenosine receptor 2A (Adora2a), which has been implicated in cardiovascular disease. Here, using two mouse models of subretinal fibrosis (mice with laser injury-induced CNV or mice with a deficiency in the very low-density lipoprotein receptor), we found that deletion of Adora2a either globally or specifically in endothelial cells reduced subretinal fibrosis independently of angiogenesis. We showed that Adora2a-dependent endothelial-to-mesenchymal transition contributed to the development of subretinal fibrosis in mice with laser injury-induced CNV. Deficiency of Adora2a in cultured mouse and human choroidal endothelial cells suppressed induction of the endothelial-to-mesenchymal transition. A metabolomics analysis of cultured human choroidal endothelial cells showed that ADORA2A knockdown with an siRNA reversed the increase in succinate because of decreased succinate dehydrogenase B expression under fibrotic conditions. Pharmacological inhibition of ADORA2A with a small-molecule KW6002 in both mouse models recapitulated the reduction in subretinal fibrosis observed in mice with genetic deletion of Adora2a. ADORA2A inhibition may be a therapeutic approach to treat subretinal fibrosis associated with nAMD.

Moscatilin inhibits vascular calcification by activating IL13RA2-dependent inhibition of STAT3 and attenuating the WNT3/ß-catenin signalling pathway.

INTRODUCTION: Vascular calcification, a devastating vascular complication accompanying atherosclerotic cardiovascular disease and chronic kidney disease, increases the incidence of adverse cardiovascular events and compromises the efficacy of vascular interventions. However, effective therapeutic drugs and treatments to delay or prevent vascular calcification are lacking. OBJECTIVES: This study was designed to test the therapeutic effects and mechanism of Moscatilin (also known as dendrophenol) from Dendrobium huoshanense (an eminent traditional Chinese medicine) in suppressing vascular calcification in vitro, ex vivo and in vivo. METHODS: Male C57BL/6J mice (25-week-old) were subjected to nicotine and vitamin D3 (VD3) treatment to induce vascular calcification. In vitro, we established the cellular model of osteogenesis of human aortic smooth muscle cells (HASMCs) under phosphate conditions. RESULTS: By utilizing an in-house drug screening strategy, we identified Moscatilin as a new naturally-occurring chemical entity to reduce HASMC calcium accumulation. The protective effects of Moscatilin against vascular calcification were verified in cultured HASMCs. Unbiased transcriptional profiling analysis and cellular thermal shift assay suggested that Moscatilin suppresses vascular calcification via binding to interleukin 13 receptor subunit A2 (IL13RA2) and augmenting its expression. Furthermore, IL13RA2 was reduced during HASMC osteogenesis, thus promoting the secretion of inflammatory factors via STAT3. We further validated the participation of Moscatilin-inhibited vascular calcification by the classical WNT/ß-catenin pathway, among which WNT3 played a key role in this process. Moscatilin mitigated the crosstalk between WNT3/ß-catenin and IL13RA2/STAT3 to reduce osteogenic differentiation of HASMCs. CONCLUSION: This study supports the potential of Moscatilin as a new naturally-occurring candidate drug for treating vascular calcification via regulating the IL13RA2/STAT3 and WNT3/ß-catenin signalling pathways.

[Clinical metabolomics of Zicuiyin in treatment of diabetic kidney disease].

This study aimed to analyze the therapeutic effect of Zicuiyin on diabetic kidney disease(DKD) and explore the possible targets of this formula. Eighteen DKD patients treated in the endocrine department or nephrology department of Second Affilia-ted Hospital of Tianjin University of Traditional Chinese Medicine from January to December in 2019 were enrolled and assigned into a test group(n=10) and a control group(n=8). Both groups received routine chemical medicine treatment. In addition, the test group was treated with Zicuiyin and the control group with Huangkui Capsules for 8 weeks. The clinical trial was approved by the Ethics Committee of Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine, with the ethical approval No. 2017-023-01, and all the patients signed the informed consent form. The results showed that the 8-week treatment with Zicuiyin lowered the level of glycosylated hemoglobin(HbA1c) and recovered the 24 h urinary protein(24hUP), 24 h urinary microalbumin(24hmAlb), urine albumin-to-creatinine ratio(UACR), and estimated glomerular filtration rate(eGFR) of the patients with 24hUP<3.5 g. According to the different levels in 24hUP, all the patients were divided into two subgroups(subgroup A with 24hUP<3.5 g and subgroup B with 24hUP≥3.5 g). The ultra-high performance liquid chromatography-quadrupole-time-of-flight tandem mass spectrometry(UPLC-Q-TOF-MS/MS)-based non-targeted metabolomics analysis was conducted on the baseline serum samples from diffe-rent subgroups of patients. Nineteen biomarker candidates were identified to distinguish the metabolic differences between the two subgroups, and their correlations with clinical indicators were analyzed. Zicuiyin lowered the levels of phenylalanine, pseudouridine, and adenosine [fold change(FC)<0.5, P<0.05] in subgroup A. The results indicated that Zicuiyin was more effective on the DKD patients with low urinary protein levels, and its targets were involved in phenylalanine metabolism and nucleoside metabolism.

Effects of heated-treating temperature on the stability and electrochemical performance of alginate-based multi-crosslinked biomembranes.

In this study, the organosilane nanoparticles as additive and crosslinker were prepared and incorporated into sodium alginate to fabricate a series of alginate-based multi-crosslinked biomembranes at different thermal treatment temperature without the usage of another crosslinking agent. The effects of treatment temperature on the stability of biomembranes including dimensional, oxidative, hydrolytic and mechanical stability were investigated in detail. As a whole, the stability of biomembranes exhibited increasing tendency with the increment of treatment temperature due to the formation of more compact internal network structure. The electrochemical performance of biomembranes in respect to their potential as proton exchange membranes for direct methanol fuel cell application were also investigated based on the treatment temperature. The results revealed that the biomembranes possessed excellent methanol resistance and the methanol diffusion coefficient decreased with the increment of treatment temperature. The biomembrane with 120 °C heat-treatment showed the optimal selectivity (14.30 × 105 Ss cm-3), which was about 1.77 and 68.10 times of that and of M-80 (8.09 × 105 Ss cm-3) and Nafion@117 (0.21 × 105 Ss cm-3), respectively. Fuel cell performance measurements showed that M-120 possessed higher maximum power density and cell stability compared with M-80 and Nafion@117, indicating its best adaptability for use in direct methanol fuel cell.

A proteome-wide screen identifies the calcium binding proteins, S100A8/S100A9, as clinically relevant therapeutic targets in aortic dissection.

Aortic dissection (AD) is a fatal cardiovascular disease with limited pharmacotherapies. To discover novel therapeutic targets for AD, the present study was conducted on ascending aorta samples from AD patients versus those from control subjects using proteomic analysis. Integrated proteomic data analysis identified S100 calcium-binding proteins A8 and A9 (S100A8/A9) as new therapeutic targets for AD. As assessed by ELISA, the circulating levels of S100A8/A9 were elevated in AD patients. In addition, we validated the upregulation of S100A8/A9 in a mouse model of AD. In vitro and in vivo studies substantiated that S100A8/A9, as danger-associated molecular pattern molecules, promotes the smooth muscle cells phenotypic switch by inhibiting serum response factor (SRF) activity but elevating NF-κB dependent inflammatory response. Depletion of S100A8/A9 attenuates the occurrence and development of AD. As a proof of concept, we tested the safety and efficacy of pharmacological inhibition of S100A8/A9 by ABR-25757 (paquinimod) in a mouse model of AD. We observed that ABR-25757 ameliorated the incidence of rupture and improved elastin morphology associated with AD. Further single-cell RNA sequencing disclosed that the phenotypic switch of vascular smooth muscle cells (VSMCs) and inflammatory response pathways were responsible for ABR-25757-mediated protection against AD. Thus, this study reveals the regulatory mechanism of S100A8/A9 in AD and offers a potential therapeutic avenue to treat AD by targeting S100A8/A9.

Sheathless CESI-MS versus LC-MS: Results of qualitative and quantitative analyses of the primary and secondary metabolites of Pleioblastus amarus bamboo shoots.

The bamboo shoot of Pleioblastus amarus (Keng) Keng f. is a medicinal and edible resource in China. In this study, three separation techniques were applied to identify the primary and secondary metabolites component of P. amarus bamboo shoots, including sheathless capillary electrophoresis electrospray ionization-mass spectrometry (CESI-MS), reverse-phase liquid chromatography-MS (RPLC-MS), and hydrophilic interaction liquid chromatography-MS (HILIC-MS). A total of 201 metabolites were identified by the three methods. Among those metabolites, 146 were identified by RPLC-MS, 85 were identified by HILIC-MS, and 46 were identified by sheathless CESI-MS. These methods were complementary and had a linear coefficient. CESI-MS presented advantages in the identification of isomers, high sensitivity, very low sample usage, and good detection of polar and nonpolar metabolites, showing its unique applications in food analysis and prospects in metabolic research.

Myeloid PFKFB3-mediated glycolysis promotes kidney fibrosis.

Excessive renal fibrosis is a common pathology in progressive chronic kidney diseases. Inflammatory injury and aberrant repair processes contribute to the development of kidney fibrosis. Myeloid cells, particularly monocytes/macrophages, play a crucial role in kidney fibrosis by releasing their proinflammatory cytokines and extracellular matrix components such as collagen and fibronectin into the microenvironment of the injured kidney. Numerous signaling pathways have been identified in relation to these activities. However, the involvement of metabolic pathways in myeloid cell functions during the development of renal fibrosis remains understudied. In our study, we initially reanalyzed single-cell RNA sequencing data of renal myeloid cells from Dr. Denby's group and observed an increased gene expression in glycolytic pathway in myeloid cells that are critical for renal inflammation and fibrosis. To investigate the role of myeloid glycolysis in renal fibrosis, we utilized a model of unilateral ureteral obstruction in mice deficient of Pfkfb3, an activator of glycolysis, in myeloid cells (Pfkfb3 ΔMϕ ) and their wild type littermates (Pfkfb3 WT). We observed a significant reduction in fibrosis in the obstructive kidneys of Pfkfb3 ΔMϕ mice compared to Pfkfb3 WT mice. This was accompanied by a substantial decrease in macrophage infiltration, as well as a decrease of M1 and M2 macrophages and a suppression of macrophage to obtain myofibroblast phenotype in the obstructive kidneys of Pfkfb3 ΔMϕ mice. Mechanistic studies indicate that glycolytic metabolites stabilize HIF1α, leading to alterations in macrophage phenotype that contribute to renal fibrosis. In conclusion, our study implicates that targeting myeloid glycolysis represents a novel approach to inhibit renal fibrosis.

Natural Magnolol ameliorates coccidiosis infected with Eimeria tenella by affecting antioxidant, anti-inflammatory, and gut microbiota of chicks.

Magnolol, a natural extract from magnolia officinalis, has received growing interest in its bioactive properties such as antioxidant, anti-inflammatory, and antibacterial activities. Nevertheless, there is little research on Magnolol in the treatment of parasitic infections currently. Eimeria tenella (E. tenella) infection causes damage to epithelial cells and cecal mucosa, resulting in increased intestinal permeability, which is pretty detrimental to the balance of the intestinal microenvironment. However, at present, in the treatment of chicken coccidiosis, the abuse of antibiotics is quite serious, which has brought losses and harms to the chicken farming industry that cannot be ignored. In this study, based on the excellent antioxidant and anti-inflammatory properties of Magnolol, we proved that it does have a desirable therapeutic potential on chicks infected with E. tenella. Actually, the results showed that the clinical symptoms of the chicks infected with E. tenella were relieved and their growth performance was restored by Magnolol treatment. Furthermore, Magnolol improved the antioxidant and anti-inflammatory properties of chicks. Meanwhile, the Magnolol reversed the imbalance of the intestinal microbiota of sick chicks, which recovered the diversity, promoted the potential beneficial bacteria, and inhabited the potential pathogenic bacteria. Overall, Magnolol may be an alternative to chemical drugs that are effective in treating E. tenella infections.

Neuromuscular Magnetic Field Measurement Based on Superconducting Bio-Sensors.

These years, disease-causing and disabling diseases have caused great concern. Neurological musculoskeletal disorders are diverse and affect people of a wide range of ages. And the lack of comprehensive diagnostic methods places a huge burden on healthcare systems and social economies. In this paper, the current status of clinical research on neuromuscular diseases is introduced, and the advantages of magnetic field measurement compared with clinical diagnostic methods are illustrated. A comprehensive description of the related technology of superconducting quantum interference devices (SQUIDs), magnetic field detection noise suppression scheme, the development trend of the sensor detection system, and the application and model establishment of the neuromuscular magnetic field is also given in this paper. The current research and development trends worldwide are compared simultaneously, and finally the conclusions and outlook are put forward. Based on the description of the existing literature and the ideas of other researchers, the next development trends and my own research ideas are presented in this paper, that is, starting from the establishment of a neuromuscular model, combining medical and industrial work, designing a sensor system that meets clinical needs, and laying the foundation for the clinical application of a bio-magnetic system. This review promotes a combination between medicine and industry, and guides researchers on considering the challenges of sensor development in terms of clinical needs. In addition, in this paper, the development trends are described, including the establishment of the model, the clinical demand for sensors, and the challenges of system development so as to give certain guidance to researchers.

PFKFB3-Mediated Glycolysis Boosts Fibroblast Activation and Subsequent Kidney Fibrosis.

Renal fibrosis, a hallmark of chronic kidney diseases, is driven by the activation of renal fibroblasts. Recent studies have highlighted the role of glycolysis in this process. Nevertheless, one critical glycolytic activator, 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3), remains unexplored in renal fibrosis. Upon reanalyzing the single-cell sequencing data from Dr. Humphreys' lab, we noticed an upregulation of glycolysis, gluconeogenesis, and the TGFß signaling pathway in myofibroblasts from fibrotic kidneys after unilateral ureter obstruction (UUO) or kidney ischemia/reperfusion. Furthermore, our experiments showed significant induction of PFKFB3 in mouse kidneys following UUO or kidney ischemia/reperfusion. To delve deeper into the role of PFKFB3, we generated mice with Pfkfb3 deficiency, specifically in myofibroblasts (Pfkfb3f/f/PostnMCM). Following UUO or kidney ischemia/reperfusion, a substantial decrease in fibrosis in the injured kidneys of Pfkfb3f/f/PostnMCM mice was identified compared to their wild-type littermates. Additionally, in cultured renal fibroblast NRK-49F cells, PFKFB3 was elevated upon exposure to TGFß1, accompanied by an increase in α-SMA and fibronectin. Notably, this upregulation was significantly diminished with PFKFB3 knockdown, correlated with glycolysis suppression. Mechanistically, the glycolytic metabolite lactate promoted the fibrotic activation of NRK-49F cells. In conclusion, our study demonstrates the critical role of PFKFB3 in driving fibroblast activation and subsequent renal fibrosis.

Emergence of novel tigecycline resistance gene tet(X5) variant in multidrug-resistant Acinetobacter indicus of swine farming environments.

Antibiotic-resistant bacteria are emerging all the time, but the continued emergence of novel resistance genes and genetic structures is even more alarming. Tigecycline is currently the important last barrier in the treatment of multidrug-resistant (MDR) infections. tet(X), a resistance gene to tigecycline, is the most prevalent and constantly emerging novel variants. In this research, we characterized two MDR Acinetobacter indicus strains to tigecycline that were identified and analyzed by antimicrobial susceptibility testing, conjugation transfer, whole genome sequencing (WGS) and bioinformatics analysis, and gene function analysis. The results showed that three tet(X) variants were carried in BDT201, including tet(X6) on the chromosome, tet(X3) on the plasmid pBDT201-2, and a novel tet(X5) variant adjacent to the ISAba1 elements on the plasmid pBDT201-3. The novel Tet(X5) variant showed 98.7% amino acid identity with Tet(X5) and was named Tet(X5.4). By expressing tet(X5.4) gene, the tigecycline minimum inhibitory concentration (MIC) values for Escherichia coli JM109 increased 32- fold (from 0.13 to 4 mg/L). BDT2076 contained tigecycline and carbapenems resistance genes, such as tet(X3), blaOXA-58, blaNDM-3, and blaCARB-2. The continuous emergence of MDR bacteria and resistance genes is a global environmental health issue that can not be ignored and therefore needs to pay more urgent attention to it.

Research progress of circular RNA molecules in aging and age-related diseases.

Circular RNAs (circRNAs) are a class of single-chain endogenous closed circular RNAs that do not have a poly(A) tail at the 3' end and a cap structure at the 5' end and are connected end-to-end by covalent bonds. CircRNAs, which are pervasive, diverse, stable, and conversed, have functions in transcriptional control and protein translation and play vital roles in modulating cell senescence, individual aging, as well as the occurrence and development of age-related diseases. Studies in recent years were reviewed from aspects including the biosynthesis mechanisms, classification, expression, biomedical functions, associations with aging and age-related diseases, and potential clinical applications of circRNAs. It will provide the theoretic basis for exploring the molecular biological mechanisms of aging, using circRNA as the therapeutic target to delay aging, and finding therapeutic strategies to prevent and treat age-related diseases.

Comparison of the Effects between Tannins Extracted from Different Natural Plants on Growth Performance, Antioxidant Capacity, Immunity, and Intestinal Flora of Broiler Chickens.

In this study, four plant tannins, including AT (Acacia mearnsii tannin, 68%), CT (Castanea sativa tannin, 60%), QT (Schinopsis lorenzii tannin, 73%) and TT (Caesalpinia spinosa tannin, 50%) were added to broiler diets for 42 days to evaluate and compare their effects on growth performance, antioxidant capacity, immune performance and gut microbiota in broilers. The results showed that the supplementation of five tannins could increase the production of T-AOC, GSH-Px, SOD and CAT and reduce the production of MDA in the serum of broilers (p < 0.01), but the antioxidant effect of the AT group was lower than that of the other three groups (p < 0.01). All four tannins decreased the level of the pro-inflammatory factor IL-1ß and increased the level of the anti-inflammatory factor IL-10 (p < 0.01). CT, QT and TT decreased the levels of pro-inflammatory factors IL-6 and TNF-α (p < 0.01), while AT and CT increased the level of IL-2 in serum (p < 0.01). Supplementation with four tannins also increased the levels of IgG, IgM, IgA and sIgA in serum (p < 0.01) and the levels of ZO-1, claudin-1 and occludin in the jejunum (p < 0.01). The detection results of ALT and AST showed that CT, QT and TT decreased the concentrations of ALT and AST in serum (p < 0.01). The results of the gut microbiota showed that the abundance of Clostridia and Subdoligranulum increased, and the abundance of Oscillospiraceae decreased, compared to the control group after adding the four tannins to the diets (p > 0.05). In addition, CT, QT and TT decreased the abundance of Lactobacillus and increased the abundance of Bacteroides compared to the control group, while AT showed the opposite result (p > 0.05). Overall, our study shows that tannins derived from different plants have their own unique effects on broilers. AT and CT can promote broilers' growth better than other tannins, CT has the best ability to improve immune and antioxidant properties, and QT and TT have the best effect on broilers' liver protection.

Growth differentiation factor 15 is dispensable for acetaminophen-induced liver injury in mice.

Acetaminophen (APAP)-induced liver injury (AILI) has been recognized as a pivotal contributor to drug-induced liver failure in Western countries, but its molecular mechanism remains poorly understood. Growth differentiation factor 15 (GDF15) is a pleiotropic factor that alleviates non-alcoholic liver steatohepatitis, liver fibrosis and liver injury. The aim of the present study was to examine the possibility whether GDF15 confers protection against AILI. We found that the gene expression of Gdf15 was increased significantly after APAP overdose in mice. Next, the role of Gdf15 in AILI was evaluated by hepatic Gdf15 overexpression (using adeno-associated virus serotype 8), injection with recombinant human GDF15 (rhGDF15) and Gdf15 knockout mice after challenge with APAP. A marked elevation of Gdf15 was observed after AILI. However, there were no significant differences in AILI-related liver injury and JNK phosphorylation after Gdf15 overexpression, rhGDF15 injection or Gdf15 deficiency. Together, we conclude that, despite a noticeable elevation of Gdf15 level after AILI, Gdf15 is dispensable for APAP-induced AILI. Our study further suggests that genomic analysis of mRNA expression after APAP overdose is of limited relevance unless followed up by a functional analysis of candidate genes in vivo.