Constructing a 3D Ion Transport Channel-Based CNF Composite Film with an Intercalated Structure for Superior Performance Flexible Supercapacitors.

The weak stiffness, huge thickness, and low specific capacitance of commonly utilized flexible supercapacitors hinder their great electrochemical performance. Learning from a biomimetic interface strategy, we design flexible film electrodes based on functional intercalated structures with excellent electrochemical properties and mechanical flexibility. A composite film with high strength and flexibility is created using graphene (reduced graphene oxide (rGO)) as the plane layer, layered double metal hydroxide (LDH) as the support layer, and cellulose nanofiber (CNF) as the connection agent and flexible agent. The interlayer height can be adjusted by the ion concentration. The highly interconnected network enables excellent electron and ion transport channels, facilitating rapid ion diffusion and redox reactions. Moreover, the high flexibility and mechanical properties of the film achieve multiple folding and bending. The CNF-rGO-NiCoLDH film electrode exhibits high capacitance performance (3620.5 mF cm-2 at 2 mA cm-2), excellent mechanical properties, and high flexibility. Notably, flexible all-solid assembled CNF-rGO-NiCoLDH//rGO has an extremely high area energy density of 53.5 mWh cm-2 at a power density of 1071.2 mW cm-2, along with cycling stability of 89.8% retention after 10 000 charge-discharge cycles. This work provides a perspective for designing high-performance energy storage materials for flexible electronics and wearable devices.

LKB1 regulates autophagy through AMPK/TOR signaling pathway to alleviate the damage caused by Vibrio alginolyticus infection.

LKB1 (liver kinase B1) is a key upstream kinase of AMPK and plays an important role in various cellular activities. While the function and mechanism of LKB1 have been widely reported in the study of tumor, there are few reports on its role in bacterial infectious diseases, especially in shrimp. In the present study, molecular characterization revealed that LvLKB1 has an open reading frame (ORF) of 1266 bp encoding 421 amino acids with a molecular weight of about 48 KDa, including the kinase region, N-terminal regulatory domain and C-terminal regulatory domain. LvLKB1 in hepatopancreas and hemocytes was significantly upregulated after infection with Vibrio alginolyticus (V. alginolyticus). After silencing LvLKB1 gene in Litopenaeus vannamei (L. vannamei) and artificially infecting V. alginolyticus, the survival rate of L. vannamei was significantly decreased. Subsequently, it was found that the expression of inflammatory factors in hepatopancreas and hemocytes of shrimp was up-regulated, and the expression of lipid oxidation factors was decreased after silencing LKB1, leading to the phenomenon of lipid accumulation in hepatopancreas. In order to explore the mechanism, autophagy levels of shrimp were detected after silencing LKB1, which showed that autophagy levels in hepatopancreas and hemocytes were significantly reduced. Further studies conclusively showed that silencing LvLKB1 inhibited AMPK phosphorylation induced by V. alginolyticus infection, thereby activating TOR pathway and inhibiting autophagy in shrimp. These results indicate that LvLKB1 regulates autophagy through AMPK/TOR signaling pathway to alleviate the damage caused by V. alginolyticus infection.

Hydrophobic modification of cellulose nanofibers by gallic acid and the application in pressure sensing.

Via rational molecular structure design and using gallic acid (GA) for hydrophobic modification of cellulose nanofibers (CNF), the "polymer dipole" CNF-GA with hydrophilic main chains and hydrophobic side chains was prepared, which improved the poor piezoelectric properties of CNF used for preparing pressure sensors. Due to the appearance of the side chains, the elongation at break of the CNF-GA-2, compared with CNF, was enhanced by 186 %, and the excellent tensile strength, puncture load, and tearing strength were displayed. Moreover, the significant glass transition temperature (Tg) near the human body temperature was exhibited for CNF-GA, making it possible to be applied in temperature sensing. Most importantly, the CNF-GA-2 showed the maximum hydrophobicity, with a contact angle of 76.77°. Finally, the CNF-GA-2/MXene nanocomposite film was prepared by the CNF-GA-2 with MXene through vacuum filtration. The results indicated that the film had excellent piezoelectric properties (d33 = 63.283), the generated stable induced voltage (125.6 mV), the preferable piezoresistive performance (ΔR/R0 = 2.15), the fast response/recovery time (48/61 ms), which could achieve dynamic and static responses. Moreover, this film could be used for real-time detection of limb movements (such as wrists).

Sequenced-based Rwanda population provides insights into demographic history.

Rwanda is known as the heart of Africa, reflecting the history of the world. Colonization and genocide have led to Rwanda's existing genetic structure. Herein, we used massively parallel sequencing to analyze 296 loci in 185 Rwandans and constructed a database for Rwandan forensic data for the first time. We found the following results: First, forensic parameters demonstrated that all loci were highly informative and could be used for forensic identification and paternity tests in Rwandans. Second, we found that the differences in genetic background between Rwandans and other African populations were similar but slight, as indicated by the massively parallel sequencing panel. Rwandans belonged to the African population and were inseparable from populations from neighboring countries. Also, Rwandans were closer to the European and American populations because of colonization, war, and other reasons. There was no scientific basis for racial classification established by colonization. Further research still needs to be carried out on more loci and larger Rwandan samples.

Integrative Analysis of Morphine-Induced Differential Circular RNAs and ceRNA Networks in the Medial Prefrontal Cortex.

Circular RNAs (circRNAs) are a novel type of non-coding RNAs. Despite the fact that the functional mechanisms of most circRNAs remain unknown, emerging evidence indicates that circRNAs could sponge microRNAs (miRNAs), bind to RNA binding proteins (RBP), and even be translated into protein. Recent research has demonstrated the crucial roles played by circRNAs in neuropsychiatric disorders. The medial prefrontal cortex (mPFC) is a crucial component of drug reward circuitry and exerts top-down control over cognitive functions. However, there is currently limited knowledge about the correlation between circRNAs and morphine-associated contextual memory in the mPFC. Here, we performed morphine-induced conditioned place preference (CPP) in mice and extracted mPFC tissue for RNA-sequencing. Our study represented the first attempt to identify differentially expressed circRNAs (DEcircRNAs) and mRNAs (DEmRNAs) in the mPFC after morphine-induced CPP. We identified 47 significantly up-regulated DEcircRNAs and 429 significantly up-regulated DEmRNAs, along with 74 significantly down-regulated DEcircRNAs and 391 significantly down-regulated DEmRNAs. Functional analysis revealed that both DEcircRNAs and DEmRNAs were closely associated with neuroplasticity. To further validate the DEcircRNAs, we conducted qRT-PCR, Sanger sequencing, and RNase R digestion assays. Additionally, using an integrated bioinformatics approach, we constructed ceRNA networks and identified critical circRNA/miRNA/mRNA axes that contributed to the development of morphine-associated contextual memory. In summary, our study provided novel insights into the role of circRNAs in drug-related memory, specifically from the perspective of ceRNAs.

Screening of Genes Co-Associated with Sudden Infant Death Syndrome and Infectious Sudden Death in Infancy and Bioinformatics Analysis of Their Regulatory Networks.

OBJECTIVES: The common differentially expressed mRNAs in brain, heart and liver tissues of deceased sudden infant death syndrome (SIDS) and infectious sudden death in infancy (ISDI) confirmed by autopsy was screened by bioinformatics to explore the common molecular markers and pathogenesis of SIDS and ISDI. METHODS: The datasets of GSE70422 and GSE136992 were downloaded, the limma of R software was used to screen differentially expressed mRNA in different tissue samples of SIDS and ISDI decedents for overlapping analysis. The clusterProfiler of R software was used to conduct gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. The protein-protein interaction (PPI) network was constructed by STRING database, while the hub gene was screened by cytoHubba plug-in. RESULTS: Compared with the control group, there were 19 significant differentially expressed genes in the tissue samples of SIDS and ISDI decedents, among which 16 in the heart tissue and 3 in the liver tissue, and the astrotactin 1 (ASTN1) gene expression difference in the heart tissue was most significant. The PPI network identified Ras homolog family member A (RHOA), integrin subunit alpha 1 (ITGA1), and H2B clustered histone 5 (H2BC5) were hub genes. The analysis of GO and KEGG showed that differentially expressed genes were enriched in the molecular pathways of actin cytoskeleton regulation, focal adhesion and response to mycophenolic acid. CONCLUSIONS: ASTN1, RHOA and ITGA1 may participate in the development of SIDS and ISDI. The enrichment of differentially expressed genes in immune and inflammatory pathways suggests a common molecular regulatory mechanism between SIDS and ISDI. These findings are expected to provide new biomarkers for molecular anatomy and forensic identification of SIDS and ISDI.

Comparison of two contrasting Leymus chinensis accessions reveals the roles of the cell wall and auxin in rhizome development.

Leymus chinensis, a perennial native forage grass, is widely distributed in the steppes of Inner Mongolia as the dominant species. The main reproductive strategy of this grass is clonal propagation, which occurs via the proliferation of subterranean horizontal stems known as rhizomes. To elucidate the mechanism underlying rhizome development in this grass, we collected 60 accessions of L. chinensis and evaluated their rhizome development. One accession, which we named SR-74 (Strong Rhizomes), had significantly better rhizome development capacity than the accession WR-16 (Weak Rhizomes) in terms of rhizome number, total and primary rhizome length, and number of rhizome seedlings. Rhizome elongation was positively correlated with the number of internodes in the rhizome, which affected plant biomass. Compared to WR-16, SR-74 had higher rhizome tip hardness, higher abundance of transcripts participating in the biosynthesis of cell wall components, and higher levels of the metabolites L-phenylalanine, trans-cinnamic acid, 3-coumaric acid, ferulic acid, and coniferin. These metabolites in the phenylpropanoid biosynthesis pathway are precursors of lignin. In addition, SR-74 rhizomes contained higher amounts of auxin and auxin metabolites, including L-Trp, IPA, IBA, IAA and IAA-Asp, as well as upregulated expression of the auxin biosynthesis and signaling genes YUCCA6, YUCCA8, YUCCA10, YUCCA11, PIN1, PIN2, UGT1, UGT2, UGT4, UGT10, GH3, IAA7, IAA23, and IAA30. We propose a network between auxin signaling and the cell wall underlying rhizome development in L. chinensis.

The 5-HT7 receptors in the VLO contribute to the development of morphine-induced behavioral sensitization in rats.

The 5-hydroxytryptamine 7 receptor (5-HT7R) is one of the most recently cloned serotonin receptors which have been implicated in many physiological and pathological processes including drug addiction. Behavioral sensitization is the progressive process during which re-exposure to drugs intensified the behavioral and neurochemical responses to drugs. Our previous study has demonstrated that the ventrolateral orbital cortex (VLO) is critical for morphine-induced reinforcing effect. The aim of the present study was to investigate the effect of 5-HT7Rs in the VLO on morphine-induced behavioral sensitization and their underlying molecular mechanisms. Our results showed that a single injection of morphine, followed by a low challenge dose could induce behavioral sensitization. Microinjection of the selective 5-HT7R agonist AS-19 into the VLO during the development phase significantly increased morphine-induced hyperactivity. Microinjection of the 5-HT7R antagonist SB-269970 suppressed acute morphine-induced hyperactivity and the induction of behavioral sensitization, but had no effect on the expression of behavioral sensitization. In addition, the phosphorylation of AKT (Ser 473) was increased during the expression phase of morphine-induced behavioral sensitization. Suppression of the induction phase could also block the increase of p-AKT (Ser 473). In conclusion, we demonstrated that 5-HT7Rs and p-AKT in the VLO at least partially contribute to morphine-induced behavioral sensitization.

Phosphorylation of Neurofilament Light Chain in the VLO Is Correlated with Morphine-Induced Behavioral Sensitization in Rats.

Neurofilament light chain (NF-L) plays critical roles in synapses that are relevant to neuropsychiatric diseases. Despite postmortem evidence that NF-L is decreased in opiate abusers, its role and underlying mechanisms remain largely unknown. We found that the microinjection of the histone deacetylase (HDAC) inhibitor Trichostatin A (TSA) into the ventrolateral orbital cortex (VLO) attenuated chronic morphine-induced behavioral sensitization. The microinjection of TSA blocked the chronic morphine-induced decrease of NF-L. However, our chromatin immunoprecipitation (ChIP)-qPCR results indicated that this effect was not due to the acetylation of histone H3-Lysine 9 and 14 binding to the NF-L promotor. In line with the behavioral phenotype, the microinjection of TSA also blocked the chronic morphine-induced increase of p-ERK/p-CREB/p-NF-L. Finally, we compared chronic and acute morphine-induced behavioral sensitization. We found that although both chronic and acute morphine-induced behavioral sensitization were accompanied by an increase of p-CREB/p-NF-L, TSA exhibited opposing effects on behavioral phenotype and molecular changes at different addiction contexts. Thus, our findings revealed a novel role of NF-L in morphine-induced behavioral sensitization, and therefore provided some correlational evidence of the involvement of NF-L in opiate addiction.

Moderate Intensity of Treadmill Exercise Rescues TBI-Induced Ferroptosis, Neurodegeneration, and Cognitive Impairments via Suppressing STING Pathway.

Traumatic brain injury (TBI) is a universal leading cause of long-term neurological disability and causes a huge burden to an ever-growing population. Moderate intensity of treadmill exercise has been recognized as an efficient intervention to combat TBI-induced motor and cognitive disorders, yet the underlying mechanism is still unclear. Ferroptosis is known to be highly implicated in TBI pathophysiology, and the anti-ferroptosis effects of treadmill exercise have been reported in other neurological diseases except for TBI. In addition to cytokine induction, recent evidence has demonstrated the involvement of the stimulator of interferon genes (STING) pathway in ferroptosis. Therefore, we examined the possibility that treadmill exercise might inhibit TBI-induced ferroptosis via STING pathway. In this study, we first found that a series of ferroptosis-related characteristics, including abnormal iron homeostasis, decreased glutathione peroxidase 4 (Gpx4), and increased lipid peroxidation, were detected at 44 days post TBI, substantiating the involvement of ferroptosis at the chronic stage following TBI. Furthermore, treadmill exercise potently decreased the aforementioned ferroptosis-related changes, suggesting the anti-ferroptosis role of treadmill exercise following TBI. In addition to alleviating neurodegeneration, treadmill exercise effectively reduced anxiety, enhanced spatial memory recovery, and improved social novelty post TBI. Interestingly, STING knockdown also obtained the similar anti-ferroptosis effects after TBI. More importantly, overexpression of STING largely reversed the ferroptosis inactivation caused by treadmill exercise following TBI. To conclude, moderate-intensity treadmill exercise rescues TBI-induced ferroptosis and cognitive deficits at least in part via STING pathway, broadening our understanding of neuroprotective effects induced by treadmill exercise against TBI.

Transport Layer Engineering by Hydrochloric Acid for Efficient Perovskite Solar Cells with a High Open-Circuit Voltage.

A large number of defect states that exist at the interface between a perovskite film and an electron transport layer (ETL) are detrimental to the efficiency and the stability of perovskite solar cells (PSCs). It is still a challenge to simultaneously passivate the defects on both sides by a stable and low-cost ion compound. Herein, we demonstrate a simple and effective versatile strategy by introducing hydrochloric acid into SnO2 precursor solution to passivate the defects in both SnO2 and perovskite layers and simultaneously reduce the interface energy barrier, ultimately achieving a high-performance and hysteresis-free PSCs. Hydrogen ions can neutralize -OH groups on the SnO2 surface, whereas the Cl- can not only combine with Sn4+ in ETL but also suppress the Pb-I antisite defects formed at the buried interface. The reduced nonradiative recombination and the favorable energy level alignment result in a significantly increased efficiency from 20.71 to 22.06% of PSCs due to the enhancement of open-circuit voltage. In addition, the stability of the device can also be improved. This work presents a facile and promising approach for the development of highly efficient PSCs.

Class 1 integrons and multiple mobile genetic elements in clinical isolates of the Klebsiella pneumoniae complex from a tertiary hospital in eastern China.

Background: The emergence of highly drug-resistant K. pneumoniae, has become a major public health challenge. In this work, we aim to investigate the diversity of species and sequence types (STs) of clinical Klebsiella isolates and to characterize the prevalence and structure of class 1 integrons. Methods: Based on the whole genome sequencing, species identification was performed by 16S rRNA gene homology and average nucleotide identity (ANI) analysis. STs were determined in accordance with the international MLST schemes for K. pneumoniae and K. variicola. Integron characterization and comparative genomic analysis were performed using various bioinformatic tools. Results: Species identification showed that the 167 isolates belonged to four species: K. pneumoniae, K. variicola subsp. variicola, K. quasipneumoniae and K. aerogenes. Thirty-six known and 5 novel STs were identified in K. pneumoniae, and 10 novel STs were identified in K. variicola subsp. variicola. Class 1 integrons were found in 57.49% (96/167) of the isolates, and a total of 169 resistance gene cassettes encoding 19 types of resistance genes, including carbapenem resistance gene (bla IPM-4) and class D ß-lactamases gene (bla OXA-1 and bla OXA-10), were identified. Among the 17 complete genomes, 29 class 1 integrons from 12 groups were found, only 1 group was encoded on chromosomes. Interestingly, one plasmid (pKP167-261) carrying two copies of approximately 19-kb IS26-Int1 complex resistance region that contains an integron and a multidrug resistance gene fragment. Conclusion: The results of this work demonstrated that the species and STs of the clinical Klebsiella isolates were more complex by the whole genome sequence analysis than by the traditional laboratory methods. Finding of the new structure of MGEs related to the resistance genes indicates the great importance of deeply exploring the molecular mechanisms of bacterial multidrug resistance.

Transcriptome-wide association study by different approaches reveals candidate causal genes for cannabis use disorder.

Cannabis is one of the most commonly used psychoactive substances, which could induce moderate-severe cannabis use disorders (CUD). Here, a tissue-specific transcriptome-wide association study (TWAS) of CUD was performed by FUSION and S-PrediXcan, utilizing a genome-wide association study (GWAS) dataset of CUD (including 43,380 cases and 141,385 controls of European ancestry) and gene expression reference data from 17 different brain-related and non-brain related tissues, with totally 26 TWAS-associated genes were identified, including CADM2 (P = 2.13 × 10-17), SRR (P = 8.09 × 10-9) and TUFM (P = 1.24 × 10-8). Fine-mapping of causal gene sets (FOCUS) was used to prioritize genes with strong evidence for causality, and SRR, CADM2-AS1, and SH2B1 were prioritized with a posterior probability of 0.973, 0.951, and 0.788, respectively. Furthermore, gene ontology (GO) and pathway enrichment analysis on CUD-associated genes were performed, including cytosol, protein binding, nucleoplasm, metabolic pathways, and herpes simplex virus 1 infection. These findings could provide new insights for understanding the mechanism of CUD.

Andrographis paniculata improves growth and non-specific immunity of shrimp Litopenaeus vannamei, and protects it from Vibrio alginolyticus by reducing oxidative stress and apoptosis.

Andrographis paniculata (AP) is a traditional medicinal plant with many pharmacological activities, including anti-inflammatory, antimicrobial, immunity stimulation and so on. Several studies have reported that AP plays a strong role in promoting the immune system of aquatic animals to resist several pathogens. In the present study, we investigate the effects of a diet containing AP on the immune responses, growth, and the resistance to Vibrio alginolyticus (V. alginolyticus) in Litopenaeus vannamei (L. vannamei). Four diets were formulated by adding AP at the dosage of 0% (Control), 0.25%, 0.5%, and 1% in the basal diet, respectively. Each diet was randomly fed to one group with three replicates of shrimps in a 28-day feeding trial. The results showed that dietary AP improved the growth performance and non-specific immune function of shrimps. To investigate the effect of AP on disease resistance of L. vannamei, shrimps fed with diet containing AP were challenged with V. alginolyticus. Compared with the control group, the shrimps fed diet containing AP showed significantly higher survival. Furthermore, the hepatopancreas injury in the shrimp fed with AP was less than control group at 6 h after V. alginolyticus infection. However, no difference was observed in the degree of hepatopancreas injury between AP groups and control group at 12 h and 24 h after V. alginolyticus infection. Based on this result, the samples at 6 h after V. alginolyticus infection was selected for subsequent detection. Reactive oxygen species (ROS) accumulation in hemocytes and O2- production in hepatopancreas caused by V. alginolyticus infection was significantly reduced after feeding a diet containing 0.25% and 0.5% AP (p < 0.05). In addition, we found that feeding AP significantly up-regulated the expression of pro-apoptotic genes (Bax, Caspase 3, p53) and down-regulated the expression of anti-apoptotic genes (Bcl-2) in hepatopancreas after V. alginolyticus infection. In conclusion, AP promote the growth and immunity of L. vannamei, and protects shrimps against V. alginolyticus by regulating the oxidative damage and apoptosis. These results provide useful information regarding the effects of AP extracts as a shrimp feed additive for sustainable shrimp culture.

Characterization and identification of a novel chromosomal class C ß-lactamase, LAQ-1, and comparative genomic analysis of a multidrug resistance plasmid in Lelliottia amnigena P13.

Introduction: Lelliottia amnigena, a bacterium usually isolated from natural environments, may cause human infections and has been suggested to be naturally resistant to second- and third-generation cephalosporins. Methods: In this study, we determined the whole-genome sequence of an isolate, L. Amnigena P13, isolated from animal farm sewage. On the basis of genome sequence analysis, susceptibility testing, molecular cloning, and enzyme kinetic parameter analysis, we identified a novel chromosome-encoded AmpC ß-lactamase, LAQ-1. Results and Discussion: bla LAQ-1 is resistant to penicillin G, ampicillin, and several first- to fourth-generation cephalosporins, such as cefazolin, cefoxitin and cefepime. The MIC levels of some ß-lactams, such as cefoxitin, cefepime, aztreonam and cefazolin, for the recombinant clone (pUCP24-bla LAQ-1/DH5α) increased by approximately 4- to 64-fold compared with those of the control strain (pUCP24/DH5α). The kinetic properties of LAQ-1, with the highest catalytic activity observed toward piperacillin, were basically the same as those of typical class C ß-lactamases, and avibactam had a strong inhibitory effect on its hydrolytic activity. The genetic background of bla LAQ-1 was relatively conserved, and no mobile genetic element (MGE) was found around it. The plasmid pP13-67 of L. amnigena P13 harbored 12 resistance genes [qnrS1, aph(6)-Id, aadA2, sul1, sul2, bla TEM-1, qacEΔ1, dfrA12, tetA and floR] related to different mobile genetic elements within an ~22 kb multidrug resistance region. The multidrug resistance region shared the highest nucleotide sequence similarities with those of the chromosomes or plasmids of different bacterial species, indicating the possibility of horizontal transfer of these resistance genes among different bacterial species.

Anemia - an initial manifestation of Bing-Neel syndrome: A case report.

RATIONALE: It is very likely that we will miss Bing-Neel syndrome (BNS) when its initial sign is anemia.Patient concerns: A 59-year-old woman presented with episodic loss of consciousness, anemia, and extremity muscle strength scores (5-) and extremity tendon reflexes (++). DIAGNOSES: Magnetic Resonance Imaging (MRI) showed abnormal signal in the left hippocampus, left insula, and right occipital lobe. Quantitative serum immunoglobulins showed elevated immunoglobulinm (IgM) (60.6g/L). Bone marrow biopsy showed lymphoplasmacytic lymphoma (LPL) and tested positive for the MYD88 L265P mutation suggesting Waldenström macroglobulinemia (WM). INTERVENTIONS: The patient underwent 3 plasma exchange treatments in the department of hematology followed by chemotherapy (cyclophosphamide for injection, bortezomib for injection). OUTCOMES: The patient's condition improved after treatment. LESSONS: Clinicians must remain vigilant, as BNS may be the only sign of WM progression in a patient well-controlled on treatment.

Whole-Genome Sequencing-Based Species Classification, Multilocus Sequence Typing, and Antimicrobial Resistance Mechanism Analysis of the Enterobacter cloacae Complex in Southern China.

Members of the Enterobacter cloacae complex (ECC) are important opportunistic nosocomial pathogens that are associated with a great variety of infections. Due to limited data on the genome-based classification of species and investigation of resistance mechanisms, in this work, we collected 172 clinical ECC isolates between 2019 and 2020 from three hospitals in Zhejiang, China and performed a retrospective whole-genome sequencing to analyze their population structure and drug resistance mechanisms. Of the 172 ECC isolates, 160 belonged to 9 classified species, and 12 belonged to unclassified species based on ANI analysis. Most isolates belonged to E. hormaechei (45.14%) followed by E. kobei (13.71%), which contained 126 STs, including 62 novel STs, as determined by multilocus sequence typing (MLST) analysis. Pan-genome analysis of the two ECC species showed that they have an "open" tendency, which indicated that their Pan-genome increased considerably with the addition of new genomes. A total of 80 resistance genes associated with 11 antimicrobial agent categories were identified in the genomes of all the isolates. The most prevailing resistance genes (12/29, 41.38%) were related to ß-lactams followed by aminoglycosides. A total of 247 ß-lactamase genes were identified, of which the blaACT genes were the most dominant (145/247, 58.70%), followed by the blaTEM genes (21/247, 8.50%). The inherent ACT type ß-lactamase genes differed among different species. blaACT-2 and blaACT-3 were only present in E. asburiae, while blaACT-9, blaACT-12, and blaACT-6 exclusively appeared in E. kobei, E. ludwigii, and E. mori. Among the six carbapenemase-encoding genes (blaNDM-1, blaNDM-5, blaIMP-1, blaIMP-4, blaIMP-26, and blaKPC-2) identified, two (blaNDM-1 and blaIMP-1) were identified in an ST78 E. hormaechei isolate. Comparative genomic analysis of the carbapenemase gene-related sequences was performed, and the corresponding genetic structure of these resistance genes was analyzed. Genome-wide molecular characterization of the ECC population and resistance mechanism would offer valuable insights into the effective management of ECC infection in clinical settings. IMPORTANCE The presence and emergence of multiple species/subspecies of ECC have led to diversity and complications at the taxonomic level, which impedes our further understanding of the epidemiology and clinical significance of species/subspecies of ECC. Accurate identification of ECC species is extremely important. Also, it is of great importance to study the carbapenem-resistant genes in ECC and to further understand the mechanism of horizontal transfer of the resistance genes by analyzing the surrounding environment around the genes. The occurrence of ECC carrying two MBL genes also indicates that the selection pressure of bacteria is further increased, suggesting that we need to pay special attention to the emergence of such bacteria in the clinic.

Single-cell RNA sequencing reveals a novel inhibitory effect of ApoA4 on NAFL mediated by liver-specific subsets of myeloid cells.

The liver immune microenvironment is a key element in the development of hepatic inflammation in NAFLD. ApoA4 deficiency increases the hepatic lipid burden, insulin resistance, and metabolic inflammation. However, the effect of ApoA4 on liver immune cells and the precise immune cell subsets that exacerbate fatty liver remain elusive. The aim of this study was to profile the hepatic immune cells affected by ApoA4 in NAFL. We performed scRNA-seq on liver immune cells from WT and ApoA4-deficient mice administered a high-fat diet. Immunostaining and qRT-PCR analysis were used to validate the results of scRNA-seq. We identified 10 discrete immune cell populations comprising macrophages, DCs, granulocytes, B, T and NK&NKT cells and characterized their subsets, gene expression profiles, and functional modules. ApoA4 deficiency led to significant increases in the abundance of specific subsets, including inflammatory macrophages (2-Mφ-Cxcl9 and 4-Mφ-Cxcl2) and activated granulocytes (0-Gran-Wfdc17). Moreover, ApoA4 deficiency resulted in higher Lgals3, Ctss, Fcgr2b, Spp1, Cxcl2, and Elane levels and lower Nr4a1 levels in hepatic immune cells. These genes were consistent with human NAFLD-associated marker genes linked to disease severity. The expression of NE and IL-1ß in granulocytes and macrophages as key ApoA4 targets were validate in the presence or absence of ApoA4 by immunostaining. The scRNA-seq data analyses revealed reprogramming of liver immune cells resulted from ApoA4 deficiency. We uncovered that the emergence of ApoA4-associated immune subsets (namely Cxcl9+ macrophage, Cxcl2+ macrophage and Wfdc17+ granulocyte), pathways, and NAFLD-related marker genes may promote the development of NAFL. These findings may provide novel therapeutic targets for NAFL and the foundations for further studying the effects of ApoA4 on immune cells in various diseases.

Andrographolide promote the growth and immunity of Litopenaeus vannamei, and protects shrimps against Vibrio alginolyticus by regulating inflammation and apoptosis via a ROS-JNK dependent pathway.

Vibrio alginolyticus (V. alginolyticus) is one of the major pathogens causing mass mortality of shrimps worldwide, affecting energy metabolism, immune response and development of shrimps. In the context of the prohibition of antibiotics, it is necessary to develop a drug that can protect shrimp from V. alginolyticus. Andrographolide (hereinafter called Andr), a traditional drug used in Chinese medicine, which possesses diverse biological effects including anti-bacteria, antioxidant, immune regulation. In this study, we investigated the effect of Andr on growth, immunity, and resistance to V. alginolyticus infection of Litopenaeus vannamei (L. vannamei) and elucidate the underlying molecular mechanisms. Four diets were formulated by adding Andr at the dosage of 0 g/kg (Control), 0.5 g/kg, 1 g/kg, and 2 g/kg in the basal diet, respectively. Each diet was randomly fed to one group with three replicates of shrimps in a 4-week feeding trial. The results showed that dietary Andr improved the growth performance and non-specific immune function of shrimps. L. vannamei fed with Andr diets showed lower mortality after being challenged by V. alginolyticus. After 6 h of V. alginolyticus infection, reactive oxygen species (ROS) production, tissue injury, apoptosis, expression of inflammatory factors (IL-1 ß and TNFα) and apoptosis-related genes (Bax, caspase3 and p53) were increased in hemocytes and hepatopancreas, while feeding diet with 0.5 g/kg Andr could inhibit the increase. Considering that JNK are important mediators of apoptosis, we examined the influence of Andr on JNK activity during V. alginolyticus infection. We found that Andr inhibited JNK activation induced by V. alginolyticus infection on L. vannamei. The ROS scavenger N-acetyl-l-cysteine (NAC) suppressed V. alginolyticus-induced inflammation and apoptosis, suggesting that ROS play an important role in V. alginolyticus-induced inflammation and apoptosis. Treated cells with JNK specific activator anisomycin, the inflammation and apoptosis inhibited by Andr were counteracted. Collectively, Andr promote the growth and immunity of L. vannamei, and protects shrimps against V. alginolyticus by regulating inflammation and apoptosis via a ROS-JNK dependent pathway. These results improve the understanding of the pathogenesis of V. alginolyticus infection and provide clues to the development of effective drugs against V. alginolyticus.