Isotopes illustrate vertical transport of anthropogenic Pb by reversible scavenging within Pacific Ocean particle veils.

Reversible scavenging, the oceanographic process by which dissolved metals exchange onto and off sinking particles and are thereby transported to deeper depths, has been well established for the metal thorium for decades. Reversible scavenging both deepens the elemental distribution of adsorptive elements and shortens their oceanic residence times in the ocean compared to nonadsorptive metals, and scavenging ultimately removes elements from the ocean via sedimentation. Thus, it is important to understand which metals undergo reversible scavenging and under what conditions. Recently, reversible scavenging has been invoked in global biogeochemical models of a range of metals including lead, iron, copper, and zinc to fit modeled data to observations of oceanic dissolved metal distributions. Nonetheless, the effects of reversible scavenging remain difficult to visualize in ocean sections of dissolved metals and to distinguish from other processes such as biological regeneration. Here, we show that particle-rich "veils" descending from high-productivity zones in the equatorial and North Pacific provide idealized illustrations of reversible scavenging of dissolved lead (Pb). A meridional section of dissolved Pb isotope ratios across the central Pacific shows that where particle concentrations are sufficiently high, such as within particle veils, vertical transport of anthropogenic surface-dissolved Pb isotope ratios toward the deep ocean is manifested as columnar isotope anomalies. Modeling of this effect shows that reversible scavenging within particle-rich waters allows anthropogenic Pb isotope ratios from the surface to penetrate ancient deep waters on timescales sufficiently rapid to overcome horizontal mixing of deep water Pb isotope ratios along abyssal isopycnals.

Enhanced detection limit in an exceptional surface-based fiber resonator by manipulating Fano interference.

An exceptional surface (ES) has advantages in improving sensing robustness and enhancing frequency splitting. Typically, the eigenvalue splitting must exceed the mode linewidth in order to be clearly visible in the spectrum, which limits the precision of the ES-based sensing structure. In this paper, a strategy for manipulating spectral line shape in an ES-based structure is experimentally realized. In addition, the limit of the minimum detectable displacement can be further reduced by monitoring the peak intensity of the Fano interference line shape. The demonstration of Fano interference in an ES-based system opens the way for a new class of ultrasensitive optical sensors.

New isolate of sweet potato virus 2 from Ipomoea nil: molecular characterization, codon usage bias, and phylogenetic analysis based on complete genome.

BACKGROUND: Viral diseases of sweet potatoes are causing severe crop losses worldwide. More than 30 viruses have been identified to infect sweet potatoes among which the sweet potato latent virus (SPLV), sweet potato mild speckling virus (SPMSV), sweet potato virus G (SPVG) and sweet potato virus 2 (SPV2) have been recognized as distinct species of the genus Potyvirus in the family Potyviridae. The sweet potato virus 2 (SPV2) is a primary pathogen affecting sweet potato crops. METHODS: In this study, we detected an SPV2 isolate (named SPV2-LN) in Ipomoea nil in China. The complete genomic sequence of SPV2-LN was obtained using sequencing of small RNAs, RT-PCR, and RACE amplification. The codon usage, phylogeny, recombination analysis and selective pressure analysis were assessed on the SPV2-LN genome. RESULTS: The complete genome of SPV2-LN consisted of 10,606 nt (GenBank No. OR842902), encoding 3425 amino acids. There were 28 codons in the SPV2-LN genome with a relative synonymous codon usage (RSCU) value greater than 1, of which 21 end in A/U. Among the 12 proteins of SPV2, P3 and P3N-PIPO exhibited the highest variability in their amino acid sequences, while P1 was the most conserved, with an amino acid sequence identity of 87-95.3%. The phylogenetic analysis showed that 21 SPV2 isolates were clustered into four groups, and SPV2-LN was clustered together with isolate yu-17-47 (MK778808) in group IV. Recombination analysis indicated no major recombination sites in SPV2-LN. Selective pressure analysis showed dN/dS of the 12 proteins of SPV2 were less than 1, indicating that all were undergoing negative selection, except for P1N-PISPO. CONCLUSION: This study identified a sweet potato virus, SPV2-LN, in Ipomoea nil. Sequence identities and genome analysis showed high similarity between our isolate and a Chinese isolate, yu-17-47, isolated from sweet potato. These results will provide a theoretical basis for understanding the genetic evolution and viral spread of SPV2.

First-principles prediction of ferroelectric Janus Si2XY (X/Y = S/Se/Te, X ≠ Y) monolayers with negative Poisson's ratios.

Nowadays, two-dimensional (2D) materials with Janus structures evoke much attention due to their unique mechanical and electronic properties. In this work, Janus Pma2-Si2XY (X/Y = S/Se/Te, X ≠ Y) ferroelectric monolayers are firstly proposed and systematically investigated by first-principles calculations. These monolayers exhibit remarkable mechanical properties, including small Young's modulus values, negative Poisson's ratios (NPRs) and large critical strains, reflecting their exceptional flexibility and stretchability. More strikingly, the novel structures of Si2STe and Si2SeTe also endow them with in-plane spontaneous polarization (Ps) and low energy barrier for phase transition, with Ps and energy barrier values being 1.632 × 10-10 C m-1 and 159 meV for Si2STe and 1.149 × 10-10 C m-1 and 196.6 meV for Si2SeTe. The ab initio molecular dynamics (AIMD) simulations reveal high Curie temperatures (Tc) for Si2STe and Si2SeTe, ranging between 1300 K and 1400 K. Additionally, Si2XY monolayers exhibit high anisotropic carrier mobility (∼103 cm2 V-1 s-1) and an extraordinary light absorption coefficient (∼105 cm-1). Our research not only broadens the family of 2D Janus ferroelectric materials, but also demonstrates their potential applications in nanomechanical, nanoelectronic and optoelectronic devices.

Janus monolayer PXC (X = As/Sb) for photocatalytic water splitting with a negative Poisson's ratio.

Two-dimensional (2D) Janus materials have attracted considerable attention in photocatalysis owing to their robust redox capability and efficient segregation. In this study, we propose a novel Janus monolayer structure, denoted as PXC (X = As/Sb), exhibiting favorable stability in terms of dynamics, thermal properties, and mechanical characteristics. The PXC monolayers demonstrate a relatively smaller Young's modulus (132.5/119.5 N m-1 for PAsC/PSbC) and large negative Poisson's ratios (-0.15/-0.101 for PAsC/PSbC). Moreover, the HSE06 + SOC functional results show that PAsC/PSbC are indirect semiconductors with a 2.33/1.43 eV band gap, exhibiting a suitable band alignment for photocatalytic water splitting. The calculated high carrier mobility (104 cm2 V-1 s-1), along with a significant discrepancy, determined by the deformation potential theory and the built-up field induced by the large intrinsic dipole, effectively suppresses the recombination of photogenerated carriers. Furthermore, PXC monolayers possess a strong absorption capacity in the visible and ultraviolet light region (105 cm-1). Therefore, our results indicate that PXC monolayers hold great potential for application in the field of photocatalytic water splitting.

Circadian rhythms of melatonin and its relationship with anhedonia in patients with mood disorders: a cross-sectional study.

BACKGROUND: Mood disorders are strongly associated with melatonin disturbances. However, it is unclear whether there is a difference in melatonin concentrations and melatonin circadian rhythm profiles between depression and bipolar disorder. In addition, the relationship between anhedonia, a common symptom of affective disorders, and its melatonin circadian rhythm remains under-investigated. METHODS: Thirty-four patients with depression disorder, 20 patients diagnosed with bipolar disorder and 21 healthy controls participated in this study. The Revised Physical Anhedonia Scale (RPAS) was performed to assess anhedonia. Saliva samples were collected from all subjects at fixed time points (a total of 14 points) in two consecutive days for measuring the melatonin concentrations to fit circadian rhythms of subjects. Melatonin circadian rhythms were compared between the three groups using ANOVA. Partial correlation analysis and linear regression analysis were used to explore the correlation between melatonin rhythm variables and anhedonia. RESULTS: We found that the peak phase of melatonin in the depression group was significantly advanced compared to the control group (P < 0.001) and the bipolar disorder group (P = 0.004). The peak phase of melatonin and RPAS showed a negative correlation (P = 0.003) in depression patients, which was also demonstrated in the multiple linear regression model (B=-2.47, P = 0.006). CONCLUSIONS: These results suggest that circadian rhythms of melatonin are differentiated in depression and bipolar disorder and correlate with anhedonia in depression. Future research needs to explore the neurobiological mechanisms linking anhedonia and melatonin circadian rhythms in depressed patients.

Post-stroke hand gesture recognition via one-shot transfer learning using prototypical networks.

BACKGROUND: In-home rehabilitation systems are a promising, potential alternative to conventional therapy for stroke survivors. Unfortunately, physiological differences between participants and sensor displacement in wearable sensors pose a significant challenge to classifier performance, particularly for people with stroke who may encounter difficulties repeatedly performing trials. This makes it challenging to create reliable in-home rehabilitation systems that can accurately classify gestures. METHODS: Twenty individuals who suffered a stroke performed seven different gestures (mass flexion, mass extension, wrist volar flexion, wrist dorsiflexion, forearm pronation, forearm supination, and rest) related to activities of daily living. They performed these gestures while wearing EMG sensors on the forearm, as well as FMG sensors and an IMU on the wrist. We developed a model based on prototypical networks for one-shot transfer learning, K-Best feature selection, and increased window size to improve model accuracy. Our model was evaluated against conventional transfer learning with neural networks, as well as subject-dependent and subject-independent classifiers: neural networks, LGBM, LDA, and SVM. RESULTS: Our proposed model achieved 82.2% hand-gesture classification accuracy, which was better (P<0.05) than one-shot transfer learning with neural networks (63.17%), neural networks (59.72%), LGBM (65.09%), LDA (63.35%), and SVM (54.5%). In addition, our model performed similarly to subject-dependent classifiers, slightly lower than SVM (83.84%) but higher than neural networks (81.62%), LGBM (80.79%), and LDA (74.89%). Using K-Best features improved the accuracy in 3 of the 6 classifiers used for evaluation, while not affecting the accuracy in the other classifiers. Increasing the window size improved the accuracy of all the classifiers by an average of 4.28%. CONCLUSION: Our proposed model showed significant improvements in hand-gesture recognition accuracy in individuals who have had a stroke as compared with conventional transfer learning, neural networks and traditional machine learning approaches. In addition, K-Best feature selection and increased window size can further improve the accuracy. This approach could help to alleviate the impact of physiological differences and create a subject-independent model for stroke survivors that improves the classification accuracy of wearable sensors. TRIAL REGISTRATION NUMBER: The study was registered in Chinese Clinical Trial Registry with registration number CHiCTR1800017568 in 2018/08/04.

Dissolved trace elements in the Ganges-Brahmaputra-Meghna River Basin: A new approach for estimating trace element flux inputs from rivers into the world's oceans.

Understanding the changes in the chemical compositions of dissolved trace elements from source to sink is important for determining their spatiotemporal variations and the contributions from each sub-catchment in the Ganges, Brahmaputra, and Meghna Rivers. To estimate weathering and matter transfer in these Rivers and the Ganges-Brahmaputra-Meghna (G-B-M) Estuary, we measured 15 dissolved trace element concentrations from surface and bottom water samples and exchangeable trace metals from suspended particulate matter (SPM). From December 2019 to January 2020, post-monsoon samples were collected from the upstream of the three rivers and the G-B-M Estuary. Dissolved trace elements in the Ganges and Meghna Rivers exhibited remarkable spatial variations, whereas those in the Brahmaputra River and the G-B-M Estuary were uniform. The dissolved trace elements, basic information (river length and drainage area), and physicochemical parameters (pH, dissolved oxygen, and conductivity) of the three rivers were inconsistent. The sample sites near urban areas and industrial centers had high concentrations of dissolved trace elements. In the G-B-M Estuary, iron and lead concentrations decreased along the salinity gradient, whereas selenium levels gradually increased, which may have been released by the SPM owing to its highly exchangeable trace metals. Compared with historical concentrations, trace elements that entered the G-B Estuary from the Ganges and Brahmaputra Rivers exhibited either decreased or increased metal fluxes due to additional terrigenous sources, suggesting that the inputs of trace element flux from the Ganges and Brahmaputra Rivers into the oceans may need to be re-evaluated. Furthermore, Fe and Pb concentrations and river fluxes in the Ganges and Changjiang have decreased in recent years. Hence, the fluxes of certain trace elements that enter the oceans from large rivers may require re-evaluation.

Breviscapine alleviates NASH by inhibiting TGF-ß-activated kinase 1-dependent signaling.

BACKGROUND AND AIMS: NAFLD is a key component of metabolic syndrome, ranging from nonalcoholic fatty liver to NASH, and is now becoming the leading cause of cirrhosis and HCC worldwide. However, due to the complex and unclear pathophysiological mechanism, there are no specific approved agents for treating NASH. Breviscapine, a natural flavonoid prescription drug isolated from the traditional Chinese herb Erigeron breviscapus, exhibits a wide range of pharmacological properties, including effects on metabolism. However, the anti-NASH efficacy and mechanisms of breviscapine have not yet been characterized. APPROACH AND RESULTS: We evaluated the effects of breviscapine on the development of hepatic steatosis, inflammation, and fibrosis in vivo and in vitro under metabolic stress. Breviscapine treatment significantly reduced lipid accumulation, inflammatory cell infiltration, liver injury, and fibrosis in mice fed a high-fat diet, a high-fat/high-cholesterol diet, or a methionine- and choline-deficient diet. In addition, breviscapine attenuated lipid accumulation, inflammation, and lipotoxicity in hepatocytes undergoing metabolic stress. RNA-sequencing and multiomics analyses further indicated that the key mechanism linking the anti-NASH effects of breviscapine was inhibition of TGF-ß-activated kinase 1 (TAK1) phosphorylation and the subsequent mitogen-activated protein kinase signaling cascade. Treatment with the TAK1 inhibitor 5Z-7-oxozeaenol abrogated breviscapine-mediated hepatoprotection under metabolic stress. Molecular docking illustrated that breviscapine directly bound to TAK1. CONCLUSION: Breviscapine prevents metabolic stress-induced NASH progression through direct inhibition of TAK1 signaling. Breviscapine might be a therapeutic candidate for the treatment of NASH.

Differential regulation of single microtubules and bundles by a three-protein module.

A remarkable feature of the microtubule cytoskeleton is the coexistence of subpopulations having different dynamic properties. A prominent example is the anaphase spindle, where stable antiparallel bundles exist alongside dynamic microtubules and provide spatial cues for cytokinesis. How are the dynamics of spatially proximal arrays differentially regulated? We reconstitute a minimal system of three midzone proteins: microtubule-crosslinker PRC1 and its interactors CLASP1 and Kif4A, proteins that promote and suppress microtubule elongation, respectively. We find that their collective activity promotes elongation of single microtubules while simultaneously stalling polymerization of crosslinked bundles. This differentiation arises from (1) strong rescue activity of CLASP1, which overcomes the weaker effects of Kif4A on single microtubules, and (2) lower microtubule- and PRC1-binding affinity of CLASP1, which permits the dominance of Kif4A at overlaps. In addition to canonical mechanisms where antagonistic regulators set microtubule length, our findings illuminate design principles by which collective regulator activity creates microenvironments of arrays with distinct dynamic properties.

First description study on molecular characterization of Hemiclepsis khankiana (Hirudinea: Glossiphoniidae) in China.

BACKGROUND: Leeches are an integral component of aquatic biocenosis and can be found in a wide range of ecosystems such as freshwater, saltwater, flowing, and still-water ecosystems. It especially plays an important role in the freshwater benthic community and is an important part of the food web. In this study, a leech species was found in the mantle cavity of wild freshwater mussels in Zigong City, Sichuan Province, China, and its identity was determined through morphological analysis and molecular biological analysis. RESULTS: The leech is Hemiclepsis khankiana, a new species of Hemiclepsis that has been discovered in Russia in recent years. Through morphological analysis, the current survey observed that the morphological characteristics of Hemiclepsis khankiana eyespots were significantly different from the first reported description. The first pair of eyespots on the leech were separated and clear, while it had been reduced to unclear shadows in the previous report. The phylogenetic tree based on the COI gene showed that the COI gene sequence obtained in this study was in the same evolutionary branch as Hemiclepsis khankiana (MN295420, MN295421). Genetically, it was most closely related to Hemiclepsis kasmiana (mean COI p-distance = 3.98%). CONCLUSIONS: The current study reported on the new distribution range of Hemiclepsis khankiana, which was initially discovered in China. This study indicates that the distribution range of the leech species has expanded, laying a foundation for further studies in China.

Preparation of Gold Nanoparticles via Anodic Stripping of Copper Underpotential Deposition in Bulk Gold Electrodeposition for High-Performance Electrochemical Sensing of Bisphenol A.

Bisphenol A is one of the most widely used industrial compounds. Over the years, it has raised severe concern as a potential hazard to the human endocrine system and the environment. Developing robust and easy-to-use sensors for bisphenol A is important in various areas, such as controlling and monitoring water purification and sewage water systems, food safety monitoring, etc. Here, we report an electrochemical method to fabricate a bisphenol A (BPA) sensor based on a modified Au nanoparticles/multiwalled carbon nanotubes composite electrocatalyst electrode (AuCu-UPD/MWCNTs/GCE). Firstly, the Au-Cu alloy was prepared via a convenient and controllable Cu underpotential/bulk Au co-electrodeposition on a multiwalled modified carbon nanotubes glassy carbon electrode (GCE). Then, the AuCu-UPD/MWCNTs/GCE was obtained via the electrochemical anodic stripping of Cu underpotential deposition (UPD). Our novel prepared sensor enables the high-electrocatalytic and high-performance sensing of BPA. Under optimal conditions, the modified electrode showed a two-segment linear response from 0.01 to 1 µM and 1 to 20 µM with a limit of detection (LOD) of 2.43 nM based on differential pulse voltammetry (DPV). Determination of BPA in real water samples using AuCu-UPD/MWCNTs/GCE yielded satisfactory results. The proposed electrochemical sensor is promising for the development of a simple, low-cost water quality monitoring system for the detection of BPA in ambient water samples.

[Analysis on Key Points of Safety and Effectiveness Evaluation of Wearable Rehabilitation Walking Aid Robot].

OBJECTIVE: To analyze the key points of evaluation on the safety and effectiveness of wearable rehabilitation walking aid robot, then improve its quality control ability. METHODS: Combined with the functional and structural characteristics of the wearable rehabilitation walking aid robot, the key points of quality evaluation were analyzed from the aspects of electrical safety and main performance. Some reasonable suggestions were put forward for the design and development of the robot. RESULTS: The key points of safety and effectiveness evaluation of wearable rehabilitation aid walking robot focused on battery, protection device, operation parameters, static load strength, network security, environmental adaptability and other aspects. CONCLUSIONS: By analyzing the key points of safety and effectiveness evaluation of wearable rehabilitation walking aid robot, certain ideas are provided for the design and development of such products, and reference is provided for the improvement of product quality evaluation system.

[Simulator of Heart Rate and Respiratory Rate for Monitoring Accuracy of Intelligent Sleep Monitoring Devices].

OBJECTIVE: Invent a simulator which provides a simulation of heart rate and respiratory rate to the intelligent sleep monitoring devices based on precision pressure sensors. METHODS: The simulator was composed of control part and simulated silicone doll. The simulated silicone doll contains heartbeat simulator and breathing simulation airbag. Heartbeat and breathing combination pressure signal can be produced according to frequency set values. Frequencies of pressure signal of the simulator were compared with the monitoring results of intelligent sleep monitoring devices with known accuracy to verify the frequency accuracy of pressure signal of the simulator. Verified the repeatability and stability of the simulator with a stopwatch. RESULTS: The heart rate of the simulator was with in ±2 beats per minute of the monitoring results of intelligent sleep monitoring devices and the respiratory rate of the simulator was with in ±2 times per minute of the monitoring results. The repeatability and stability of the simulator was better than ±5% according to results with a stopwatch. CONCLUSIONS: It's practicable to use the simulator which provides a simulation of heart rate and respiratory rate to the accuracy test of the intelligent sleep monitoring devices based on precision pressure sensor.

Hepatocyte glutathione S-transferase mu 2 prevents non-alcoholic steatohepatitis by suppressing ASK1 signaling.

BACKGROUND & AIMS: Non-alcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease worldwide. The advanced stage of NAFLD, non-alcoholic steatohepatitis (NASH), has been recognized as a leading cause of end-stage liver injury for which there are no FDA-approved therapeutic options. Glutathione S-transferase Mu 2 (GSTM2) is a phase II detoxification enzyme. However, the roles of GSTM2 in NASH have not been elucidated. METHODS: Multiple RNA-seq analyses were used to identify hepatic GSTM2 expression in NASH. In vitro and in vivo gain- or loss-of-function approaches were used to investigate the role and molecular mechanism of GSTM2 in NASH. RESULTS: We identified GSTM2 as a sensitive responder and effective suppressor of NASH progression. GSTM2 was significantly downregulated during NASH progression. Hepatocyte GSTM2 deficiency markedly aggravated insulin resistance, hepatic steatosis, inflammation and fibrosis induced by a high-fat diet and a high-fat/high-cholesterol diet. Mechanistically, GSTM2 sustained MAPK pathway signaling by directly interacting with apoptosis signal-regulating kinase 1 (ASK1). GSTM2 directly bound to the N-terminal region of ASK1 and inhibited ASK1 N-terminal dimerization to subsequently repress ASK1 phosphorylation and the activation of its downstream JNK/p38 signaling pathway under conditions of metabolic dysfunction. CONCLUSIONS: These data demonstrated that hepatocyte GSTM2 is an endogenous suppressor that protects against NASH progression by blocking ASK1 N-terminal dimerization and phosphorylation. Activating GSTM2 holds promise as a therapeutic strategy for NASH. CLINICAL TRIAL NUMBER: IIT-2021-277. LAY SUMMARY: New therapeutic strategies for non-alcoholic steatohepatitis are urgently needed. We identified that the protein GSTM2 exerts a protective effect in response to metabolic stress. Therapies that aim to increase the activity of GSTM2 could hold promise for the treatment of non-alcoholic steatohepatitis.

Involvement of kynurenine pathway between inflammation and glutamate in the underlying etiopathology of CUMS-induced depression mouse model.

Inflammation and glutamate (GLU) are widely thought to participate in the pathogenesis of depression, and current evidence suggests that the development of depression is associated with the activation of the kynurenine pathway (KP). However, the exact mechanism of KP among the inflammation, GLU and depression remain poorly understood. In this study, we examined the involvement of KP, inflammation and GLU in depressive phenotype induced by chronic unpredictable mild stress (CUMS) in C57B/6 J mice. Our results showed that CUMS caused depressive like-behavior in the sucrose preference test, tail suspension test and forced swimming test. From a molecular perspective, CUMS upregulated the peripheral and central inflammatory response and activated indoleamine 2,3-dioxygenase (IDO), the rate-limiting enzyme of KP, which converts tryptophan (TRP) into kynurenine (KYN). KYN is a precursor for QA in microglia, which could activate the N-methyl-D-aspartate receptor (NMDAR), increasing the GLU release, mirrored by increased IDO activity, quinolinic acid and GLU levels in the hippocampus, prefrontal cortex and serum. However, intervention with IDO inhibitor 1-methyl-DL-tryptophan (50 mg/kg/s.c.) and 1-methyl-L-tryptophan (15 mg/kg/i.p.) reversed the depressive-like behaviors and adjusted central and peripheral KP's metabolisms levels as well as GLU content, but the inflammation levels were not completely affected. These results provide certain evidence that KP may be a vital pathway mediated by IDO linking inflammation and glutamate, contributing to depression.

Comprehensive investigation of antibiotic resistance gene content in cfiA-harboring Bacteroides fragilis isolates of human and animal origins by whole genome sequencing.

INTRODUCTION: The emergence of multidrug resistance in Bacteroides fragilis, especially the phylogenetic lineage carrying the carbapenemase gene cfiA, represents an increasing threat to human health. However, knowledge on the diversity of the multidrug-resistant strains and the genetic elements carrying the antibiotic resistance genes (ARGs) remains limited. AIM: The objective of the study was to describe the resistome in cfiA-positive B. fragilis. METHODS: A collection of cfiA-positive B. fragilis from diverse human (8 bacteremias, 15 wound infections) and animal (2 chickens, 2 pigs, 6 dogs, 3 cats) sources in Hong Kong, 2015-2017 was analysed by whole genome sequencing. RESULTS: In the 36 isolates, 13 distinct ARGs (total number 83, median 2, range 0-7 per isolate) other than cfiA were detected. ARGs encoding resistance to aminoglycosides, ß-lactams, macrolides, sulphonamides and tetracyclines were carried by CTn341-like, CTnHyb-like, Tn5220-like, Tn4555-like and Tn613-like transposons and were detected in phylogenetically diverse isolates of different host sources. Only few ARGs encoding resistance to metronidazole and tetracyclines were localized on plasmids. In two chicken isolates, a novel transposon (designated as Tn6994) was found to be involved in the dissemination of multiple ARGs mediating resistance to multiple antibiotics, including metronidazole and linezolid that are critically important for treatment of anaerobic infections. In mating experiments, Tn6994 and the associated phenotypic resistance could be transferred to Bacteroides nordii recipient. CONCLUSION: This study illustrates the importance of transposons in the dissemination of ARGs in the cfiA-positive division of B. fragilis. One Health approach is necessary to track the dissemination of ARGs.

Cordycepin Ameliorates Nonalcoholic Steatohepatitis by Activation of the AMP-Activated Protein Kinase Signaling Pathway.

BACKGROUND AND AIMS: Nonalcoholic fatty liver disease, especially nonalcoholic steatohepatitis (NASH), has become a major cause of liver transplantation and liver-associated death. NASH is the hepatic manifestation of metabolic syndrome and is characterized by hepatic steatosis, inflammation, hepatocellular injury, and different degrees of fibrosis. However, there is no US Food and Drug Administration-approved medication to treat this devastating disease. Therapeutic activators of the AMP-activated protein kinase (AMPK) have been proposed as a potential treatment for metabolic diseases such as NASH. Cordycepin, a natural product isolated from the traditional Chinese medicine Cordyceps militaris, has recently emerged as a promising drug candidate for metabolic diseases. APPROACH AND RESULTS: We evaluated the effects of cordycepin on lipid storage in hepatocytes, inflammation, and fibrosis development in mice with NASH. Cordycepin attenuated lipid accumulation, inflammation, and lipotoxicity in hepatocytes subjected to metabolic stress. In addition, cordycepin treatment significantly and dose-dependently decreased the elevated levels of serum aminotransferases in mice with diet-induced NASH. Furthermore, cordycepin treatment significantly reduced hepatic triglyceride accumulation, inflammatory cell infiltration, and hepatic fibrosis in mice. In vitro and in vivo mechanistic studies revealed that a key mechanism linking the protective effects of cordycepin were AMPK phosphorylation-dependent, as indicated by the finding that treatment with the AMPK inhibitor Compound C abrogated cordycepin-induced hepatoprotection in hepatocytes and mice with NASH. CONCLUSION: Cordycepin exerts significant protective effects against hepatic steatosis, inflammation, liver injury, and fibrosis in mice under metabolic stress through activation of the AMPK signaling pathway. Cordycepin might be an AMPK activator that can be used for the treatment of NASH.

TRIM25 activates AKT/mTOR by inhibiting PTEN via K63-linked polyubiquitination in non-small cell lung cancer.

The PTEN/AKT/mTOR signaling pathway is frequently dysregulated in non-small cell lung cancer (NSCLC), but the mechanisms are not well-understood. The present study found that the ubiquitin ligase TRIM25 is highly expressed in NSCLC tissues and promotes NSCLC cell survival and tumor growth. Mechanistic studies revealed that TRIM25 binds to PTEN and mediates its K63-linked ubiquitination at K266. This modification prevents the plasma membrane translocation of PTEN and reduces its phosphatase activity therefore accumulating PI(3,4,5)P3. TRIM25 thus activates the AKT/mTOR signaling. Moreover, we found that the antibacterial nitroxoline can activate PTEN by reducing its K63-linked polyubiquitination and sensitizes NSCLC to cisplatin-induced apoptosis. This study thus identified a novel modulation on the PTEN signaling pathway by TRIM25 and provides a potential target for NSCLC treatment.

Diversity of genomic clusters and CfiA/cfiA alleles in Bacteroides fragilis isolates from human and animals.

OBJECTIVES: To compare the phylogeny of cfiA-positive Bacteroides fragilis isolates from diverse human and animal sources. METHOD: Complete genome sequences were obtained from 42 cfiA-positive B. fragilis isolates (Hong Kong, 2015-2017) and additional 24 genomes deposited in the GenBank (multiple countries, 1985-2019) were included. The genomic clusters were constructed using PopPUNK. The CfiA alleles and polymorphism in the cfiA locus were analyzed in silico. RESULTS: The 66 isolates were grouped into 12 genomic clusters (BFSC-1 to 12). Human infection isolates were distributed in diverse clusters, being many of them common to fecal isolates from both human and animals. Thirteen CfiA alleles including 2 novel ones were identified. CfiA-1 (n = 28) is the predominating allele, following by CfiA-13 (n = 8), CfiA-4 (n = 7) and CfiA-14 (n = 6). The other CfiA alleles were identified in 1-3 isolates. Six patterns of gene context were identified in the regions flanking cfiA locus. No consistent association between genomic clusters and CfiA alleles could be detected. Similarly, markedly elevated imipenem MIC was linked to the integration, immediately upstram of cfiA of an IS element but not the CfiA allele or gene context. CONCLUSION: The phylogeny of cfiA-positive B. fragilis isolates causing human diseases was diverse and overlaped with those from human and animal carriage.