Cascade Dual Sites Modulate Local CO Coverage and Hydrogen-Binding Strength to Boost CO2 Electroreduction to Ethylene.

Rationally modulating the binding strength of reaction intermediates on surface sites of copper-based catalysts could facilitate C-C coupling to generate multicarbon products in an electrochemical CO2 reduction reaction. Herein, theoretical calculations reveal that cascade Ag-Cu dual sites could synergistically increase local CO coverage and lower the kinetic barrier for CO protonation, leading to enhanced asymmetric C-C coupling to generate C2H4. As a proof of concept, the Cu3N-Ag nanocubes (NCs) with Ag located in partial Cu sites and a Cu3N unit center are successfully synthesized. The Faraday efficiency and partial current density of C2H4 over Cu3N-Ag NCs are 7.8 and 9.0 times those of Cu3N NCs, respectively. In situ spectroscopies combined with theoretical calculations confirm that Ag sites produce CO and Cu sites promote asymmetric C-C coupling to *COCHO, significantly enhancing the generation of C2H4. Our work provides new insights into the cascade catalysis strategy at the atomic scale for boosting CO2 to multicarbon products.

Dual-Affinity Graphene Sheets for High-Resolution Cryo-Electron Microscopy.

With the development of cryo-electron microscopy (cryo-EM), high-resolution structures of macromolecules can be reconstructed by the single particle method efficiently. However, challenges may still persist during the specimen preparation stage. Specifically, proteins tend to adsorb at the air-water interface and exhibit a preferred orientation in vitreous ice. To overcome these challenges, we have explored dual-affinity graphene (DAG) modified with two different affinity ligands as a supporting material for cryo-EM sample preparation. The ligands can bind to distinct sites on the corresponding tagged particles, which in turn generates various orientation distributions of particles and prevents the adsorption of protein particles onto the air-water interface. As expected, the DAG exhibited high binding specificity and affinity to target macromolecules, resulting in more balanced particle Euler angular distributions compared to single functionalized graphene on two different protein cases, including the SARS -CoV-2 spike glycoprotein. We anticipate that the DAG grids will enable facile and efficient three-dimensional (3D) reconstruction for cryo-EM structural determination, providing a robust and general technique for future studies.

Disseminated talaromycosis complicated by recurrent gastrointestinal bleeding and hemorrhagic shock: a case report.

BACKGROUND: Gastrointestinal involvement is not uncommon in patients with disseminated talaromycosis, but successful management of massive gastrointestinal bleeding and hemorrhagic shock secondary to talaromycosis is rarely reported. Clinical management strategies for these patients have not been well documented. CASE PRESENTATION: Here, we reported a case of disseminated talaromycosis with recurrent gastrointestinal bleeding and hemorrhagic shock who was successfully alleviated solely with medical treatment. CONCLUSIONS: Early diagnosis and treatment for Talaromyces marneffei, intravenous fluid resuscitation, hemostatic therapy and blood transfusion are all essential for talaromycosis complicated with gastrointestinal bleeding and hemorrhagic shock. It is also necessary to warn about the possibility of bleeding induced or aggravated by endoscopic biopsy trauma.

Hydrogen-Intercalation-Induced Lattice Expansion of Pd@Pt Core-Shell Nanoparticles for Highly Efficient Electrocatalytic Alcohol Oxidation.

Lattice engineering on specific facets of metal catalysts is critically important not only for the enhancement of their catalytic performance but also for deeply understanding the effect of facet-based lattice engineering on catalytic reactions. Here, we develop a facile two-step method for the lattice expansion on specific facets, i.e., Pt(100) and Pt(111), of Pt catalysts. We first prepare the Pd@Pt core-shell nanoparticles exposed with the Pt(100) and Pt(111) facets, respectively, via the Pd-seeded epitaxial growth, and then convert the Pd core to PdH0.43 by hydrogen intercalation. The lattice expansion of the Pd core induces the lattice enlargement of the Pt shell, which can significantly promote the alcohol oxidation reaction (AOR) on both Pt(100) and Pt(111) facets. Impressively, Pt mass specific activities of 32.51 A mgPt-1 for methanol oxidation and 14.86 A mgPt-1 for ethanol oxidation, which are 41.15 and 25.19 times those of the commercial Pt/C catalyst, respectively, have been achieved on the Pt(111) facet. Density functional theory (DFT) calculations indicate that the remarkably improved catalytic performance on both the Pt(100) and the Pt(111) facets through lattice expansion arises from the enhanced OH adsorption. This work not only paves the way for lattice engineering on specific facets of nanomaterials to enhance their electrocatalytic activity but also offers a promising strategy toward the rational design and preparation of highly efficient catalysts.

Inhibiting role of rosiglitazone in the regulation of inflammatory response and protective effects for severe acute pancreatitis in mice.

OBJECTIVES: Our study aimed to probe the effects of rosiglitazone treatment on a severe acute pancreatitis (SAP) model induced by caerulein and investigate the underlying mechanism. METHODS: Differentially expressed messenger RNAs (mRNAs) in the mice of a SAP group were screened out by microarray analysis. The inflammatory response pathway was obtained from the online website DAVID Bioinformatics Resources 6.8. The interactions of caerulein and its target proteins were shown by search tool for interactions of chemicals (STITCH). Functional interactions of the genes associated with pancreatitis and the target proteins of caerulein were obtained with search tool for interactions of chemicals (STRING). SAP mice were established by hourly intraperitoneal injection of caerulein. Rosiglitazone was used as treatment drug, and pancreatic inflammation was assessed. The expression of Socs3 was studied by reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot analysis. The expression of interleukin (IL)-6, IL-1b, and Egr1 were studied by RT-PCR and Western blot analysis. RESULTS: The GSE77983 data were analyzed, and the results showed that Socs3 was overexpressed in SAP tissues. The inflammation response pathway in pancreas was selected by DAVID, STITCH, and STRING. After injection of rosiglitazone in mice, the serum levels of amylase and lipase were decreased. Furthermore, the mRNA and protein levels of Socs3 and inflammatory cytokines in pancreatic tissues were downregulated. CONCLUSIONS: Rosiglitazone could protect mice with SAP from injury by downregulating Socs3 and inhibiting the inflammatory response pathway.

Elemental Segregation in Multimetallic Core-Shell Nanoplates.

In this work, we report an element segregation phenomenon in two-dimensional (2D) core-shell nanoplates, subsequently resulting in the formation of yolk-cage nanostructures after selective electrochemical etching. By using PtCu nanoplates as templates, PtCu@Pd core-shell nanoplates are formed. Interestingly, during the growth of Ru on the PtCu@Pd core-shell nanoplates, due to the selective element diffusion, PtCuPd@PdCu@Ru nanoplates are obtained. After selectively etching of PdCu in PtCuPd@PdCu@Ru using electrochemical method, the PtCuPd@Ru yolk-cage nanostructures are obtained. As a proof-of-concept application, this unique nanostructure shows superior electrocatalytic activity and stability toward the methanol oxidation reaction as compared to the PtCu nanoplates and commercial Pt/C catalyst.

Size-Dependent Phase Transformation of Noble Metal Nanomaterials.

As an important aspect of crystal phase engineering, controlled crystal phase transformation of noble metal nanomaterials has emerged as an effective strategy to explore novel crystal phases of nanomaterials. In particular, it is of significant importance to observe the transformation pathway and reveal the transformation mechanism in situ. Here, the phase transformation behavior of face-centered cubic (fcc) Au nanoparticles (fcc-AuNPs), adhering to the surface of 4H nanodomains in 4H/fcc Au nanorods, referred to as 4H-AuNDs, during in situ transmission electron microscopy imaging is systematically studied. It is found that the phase transformation is dependent on the ratio of the size of the monocrystalline nanoparticle (NP) to the diameter of 4H-AuND. Furthermore, molecular dynamics simulation and theoretical modeling are used to explain the experimental results, giving a size-dependent phase transformation diagram which provides a general guidance to predict the phase transformation pathway between fcc and 4H Au nanomaterials. Impressively, this method is general, which is used to study the phase transformation of other metal NPs, such as Pd, Ag, and PtPdAg, adhering to 4H-AuNDs. The work opens an avenue for selective phase engineering of nanomaterials which may possess unique physicochemical properties and promising applications.

Prevalence and types of drug-resistant variants in Chinese patients with acute hepatitis B.

The presence of therapy-associated hepatitis B virus (HBV) variants is the main drawback of antiviral therapy for HBV infection. Moreover, drug-resistant variants are more insensitive to a second agent and more therapy-associated mutations will be present. To apply better nucleos(t)ide analogues (NA) and reduce the occurrence of resistance, the prevalence and types of drug-resistant mutations in acute hepatitis B patients were investigated in this study. One hundred three HBV DNA-positive patients with symptomatic acute hepatitis B that were observed from 2011 to 2013 were enrolled. Direct polymerase chain reaction sequencing was used firstly to screen HBV reverse-transcriptase domain to detect HBV mutants. Five lamivudine-resistant variants were identified. Clonal sequencing was performed for 5 resistance-positive samples and 10 other random samples. Interestingly, all detected samples harbored drug-resistant mutations, although with different percentage. Thirteen harbored lamivudine-related alone (five) or together with other NA related mutations (five with adefovir, one with entecavir, and one with telbivudine), and two of them harbored adefovir-related mutations. Also, mutations associated with four currently used NA were all detected, and the frequency is in accordance with the popularity of NA used in clinical practice. These data suggest that drug-resistant variants are present in patients with acute hepatitis B and NA should be applied more carefully for chronic hepatitis B patients developed from acute hepatitis B.

Ultrafast micro/nano-manufacturing of metastable materials for energy.

The structural engineering of metastable nanomaterials with abundant defects has attracted much attention in energy-related fields. The high-temperature shock (HTS) technique, as a rapidly developing and advanced synthesis strategy, offers significant potential for the rational design and fabrication of high-quality nanocatalysts in an ultrafast, scalable, controllable and eco-friendly way. In this review, we provide an overview of various metastable micro- and nanomaterials synthesized via HTS, including single metallic and bimetallic nanostructures, high entropy alloys, metal compounds (e.g. metal oxides) and carbon nanomaterials. Note that HTS provides a new research dimension for nanostructures, i.e. kinetic modulation. Furthermore, we summarize the application of HTS-as supporting films for transmission electron microscopy grids-in the structural engineering of 2D materials, which is vital for the direct imaging of metastable materials. Finally, we discuss the potential future applications of high-throughput and liquid-phase HTS strategies for non-equilibrium micro/nano-manufacturing beyond energy-related fields. It is believed that this emerging research field will bring new opportunities to the development of nanoscience and nanotechnology in both fundamental and practical aspects.

Rapid High-Temperature Liquid Shock Synthesis of High-Entropy Alloys for Hydrogen Evolution Reaction.

High-entropy-alloy nanoparticles (HEA-NPs) show great potential as electrocatalysts for water splitting, fuel cells, CO2 conversion, etc. However, fine-tuning the surface, morphology, structure, and crystal phase of HEA remains a great challenge. Here, the high-temperature liquid shock (HTLS) technique is applied to produce HEA-NPs, e.g., PtCoNiRuIr HEA-NPs, with tunable elemental components, ultrafine particle size, controlled crystal phases, and lattice strains. HTLS directly applied Joule heating on the liquid mixture of metal precursors, capping agents, and reducing agents, which is feasible for controlling the morphology and structure such as the atomic arrangement of the resulting products, thereby facilitating the rationally designed nanocatalysts. Impressively, the as-obtained PtCoNiRuIr HEA-NPs delivered superior activity and long-term stability for the hydrogen evolution reaction (HER), with low overpotentials at 10 mA cm-2 and 1 A cm-2 of only 18 and 408 mV, respectively, and 10000 CV stable cycles in 0.5 M H2SO4. Furthermore, in the near future, by combining the HTLS method with artificial intelligence (AI) and theoretical calculations, it is promising to provide an advanced platform for the high-throughput synthesis of HEA nanocatalysts with optimized performance for various energy applications, which is of great significance for achieving a carbon-neutral society with an effective and environmentally friendly energy system.

Chiral coordination polymer nanowires boost radiation-induced in situ tumor vaccination.

Radiation-induced in situ tumor vaccination alone is very weak and insufficient to elicit robust antitumor immune responses. In this work, we address this issue by developing chiral vidarabine monophosphate-gadolinium nanowires (aAGd-NWs) through coordination-driven self-assembly. We elucidate the mechanism of aAGd-NW assembly and characterize their distinct features, which include a negative surface charge, ultrafine topography, and right-handed chirality. Additionally, aAGd-NWs not only enhance X-ray deposition but also inhibit DNA repair, thereby enhancing radiation-induced in situ vaccination. Consequently, the in situ vaccination induced by aAGd-NWs sensitizes radiation enhances CD8+ T-cell-dependent antitumor immunity and synergistically potentiates the efficacy immune checkpoint blockade therapies against both primary and metastatic tumors. The well-established aAGd-NWs exhibit exceptional therapeutic capacity and biocompatibility, offering a promising avenue for the development of radioimmunotherapy approaches.

Astragalosides inhibit proliferation of fibroblast-like synoviocytes in experimental arthritis by modulating LncRNA S56464.1/miR-152-3p/Wnt1 signaling axis.

AIM: Astragalus membranaceus (Fisch.) Bunge., the dried root of the plant A. membranaceus, is widely used in the treatment of rheumatoid arthritis (RA) in many Chinese herbal remedies. Astragalosides (AST) is the primary medicinal ingredient of A. membranaceus and has a therapeutic effect on RA, but the specific mechanism of this effect has yet to be elucidated. METHODS: In this study, MTT and flow cytometry were used to determine the effects of AST on fibroblast-like synoviocyte (FLS) proliferation and cell cycle progression. Additionally, real-time quantitative polymerase chain reaction and Western blotting were used to determine the effects of AST on the LncRNA S56464.1/miR-152-3p/Wnt1 signaling axis and on critical genes that are essential to the Wnt pathway. RESULTS: The data showed that after the administration of AST, FLS proliferation and LncRNA S56464.1, ß-catenin, C-myc, Cyclin D1, and p-GSK-3ß(Ser9)/GSK-3ß expression were significantly reduced, and miR-152 and SFRP4 expression was notably increased. CONCLUSION: These results suggest that AST can inhibit FLS proliferation by modulating the LncRNA S56464.1/miR-152-3p/Wnt1 signaling axis and that AST may be a potential therapeutic drug for RA.

Resveratrol attenuates efavirenz-induced hepatic steatosis and hypercholesterolemia in mice by inhibiting pregnane X receptor activation and decreasing inflammation.

Efavirenz (EFV), a widely prescribed antiviral medication, has been implicated in dyslipidemia and can activate the pregnane X receptor (PXR), leading to hepatic steatosis and hypercholesterolemia in mice. Resveratrol (RES) can ameliorate hepatic steatosis and functions as a partial PXR agonist, capable of mitigating PXR expression induced by other PXR agonists. Therefore, we hypothesized that RES could attenuate EFV-induced hepatic steatosis and hypercholesterolemia by downregulating PXR expression and suppressing inflammatory cytokine production. Here, we conducted an in vivo study involving 6-week-old male mice, which were divided into 4 groups for a 7-day intervention: control (carrier solution), EFV (80 mg/kg), RES (50 mg/kg), and RES + EFV groups. Serum and hepatic tissue samples were collected to assess cholesterol and triglyceride concentrations. Hepatic lipid accumulation was evaluated through hematoxylin-eosin and oil red O staining. Polymerase chain reaction and western blot were performed to quantify hepatic inflammatory factors, lipogenic gene, and PXR expression. Our results indicated that hepatic lipid droplet accumulation was reduced in the RES + EFV group compared with the EFV group. Similarly, the expressions of hepatic inflammatory factors were attenuated in the RES + EFV group relative to the EFV group. Furthermore, RES counteracted the upregulation of hepatic lipid-metabolizing enzymes induced by EFV at both the transcriptional and protein levels. Importantly, PXR expression was downregulated in the RES + EFV group compared with the EFV group. Conclusively, our findings suggest that RES effectively mitigates EFV-induced hepatic steatosis and hypercholesterolemia by inhibiting PXR activation and decreasing inflammation.

Evaluation of Different Blood Culture Bottles for the Diagnosis of Bloodstream Infections in Patients with HIV.

INTRODUCTION: Bloodstream infection (BSI) is a significant factor contributing to hospitalization and high mortality rates among human immunodeficiency virus(HIV)-positive patients. Therefore, the timely detection of this condition is of utmost importance. Blood culture is considered the gold standard for diagnosing BSIs. Currently, BD BACTEC™ Plus Aerobic/F culture bottles and the BD BACTEC™ Myco/F Lytic culture bottles can be used for blood culture. This study aimed to evaluate the efficacy of two different types of culture bottles in diagnosing BSIs in patients with HIV. METHODS: A retrospective analysis was conducted on HIV-positive patients hospitalized in the Infection Department of Wenzhou Central Hospital between July 2019 and October 2021. A total of 246 pairs of blood samples were included, consisting of an aerobic culture vial and a Myco/F culture vial. Blood culture results and clinical diagnosis were utilized to identify the presence of BSI. RESULTS: Out of 246 cases, 84 cases had positive blood cultures. Fungal BSIs, particularly Talaromyces marneffei BSIs, were the most prevalent among patients with HIV. The positive rate of Myco/F culture bottles (89.29%) was significantly higher compared with aerobic culture bottles (69.05%; P = 0.001). In the diagnosis of fungal BSIs, the positive rate of Myco/F culture bottles was 88.57%, which was significantly higher than that of aerobic culture bottles (72.86%; P = 0.018). The Myco/F culture bottle has more advantages in diagnosing Talaromyces marneffei BSIs (P=0.028). In addition, mycobacteria were exclusively detected in Myco/F culture bottles. CONCLUSIONS: Fungal BSIs are the predominant type of infections in HIV-positive patients. Myco/F culture bottles exhibit noteworthy attributes of high positive rate in diagnosing HIV combined with BSI. These advantages are conducive to obtaining accurate culture results and minimizing missed diagnoses.

Network pharmacology approach and molecular docking to explore the potential mechanism of Wu-Wei-Wen-Tong Chubi capsules in rheumatoid arthritis.

Network pharmacology, a holistic approach based on the theory of biological network technology, integrates information from biological systems, drugs, and diseases. Here, this theory was used to predict the targets of Wu-Wei-Wen-Tong Chubi capsule (WWWT) to explore the mechanism in the treatment of rheumatoid arthritis (RA). The ingredients of each herbal medicine in WWWT were collected from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), and the active ingredients were screened through bioavailability (OB) ≥30% and drug-likeness (DL) ≥ 0.18. SwissTargetPrection and TCMSP were utilized to calculate and predict the targets of active ingredients. RA-related targets were obtained by searching the Genecards and OMIM databases. The common targets of RA and WWWT were used for gene ontology (GO), KEGG pathway enrichment, protein-protein interaction (PPI) analysis, and molecular docking. And then, four key genes were screened for subsequent verification experiments. In total, 90 active compounds and 330 potential targets of WWWT, 1310 targets of RA, and 135 intersection targets were found. Additionally, GO and pathway analysis identified 4610 significant GO terms and 147 significant KEGG pathways. Based on the PPI network, 11 key genes including IL-6, MMP-9, and TNF-α were screened out for molecular docking. Molecular docking showed that these key genes have good binding activities to active compounds of WWWT such as oroxylin a, kaempferol, and luteolin. Simultaneously, Western blot experimental validation demonstrated that the protein expressions of IL-6, MMP-9, TNF-α, and VEGFA significantly decreased after WWWT treatment. The mechanism of WWWT in treating RA involves multiple active compounds acting on multiple targets, and multiple pathways, which provides an important reference for further elucidation the mechanism and clinical applications of WWWT in the treatment of RA.

Ultrathin MOF nanosheet-based resistive sensors for highly sensitive detection of methanol.

Sensors with high-sensitivity for resistive methanol gas detection are highly desirable. Herein, we report newly designed ultrathin anionic metal-organic framework (MOF) nanosheets (NSs), with an average thickness of 10 nm and an electrical conductivity of 3.77 × 10-4 S cm-1. The ultrathin MOF NSs can be used as the active material in an electronic methanol gas sensor, which exhibits high sensitivity toward methanol gas at room temperature, i.e., high Rair/Rgas (363.2 at 100 ppm), fast gas response/recovery speed (6 s/2 s at 20 ppm), long-term stability, and superior cross-selectivity against other interfering gases.

Astragaloside regulates lncRNA LOC100912373 and the miR­17­5p/PDK1 axis to inhibit the proliferation of fibroblast­like synoviocytes in rats with rheumatoid arthritis.

Previous studies have confirmed that astragaloside (AST) exerts a positive effect on alleviating synovial and joint injury in rheumatoid arthritis (RA). However, the precise mechanisms through which AST acts in the treatment of RA remain unclear. Long non­coding RNA (lncRNA) LOC100912373 was identified as a key gene related to RA and has been proven to interact with miR­17­5p, in order to regulate the pyruvate dehydrogenase kinase 1 and protein kinase B axis (PDK1/AKT axis). The present study aimed to determine whether AST may treat RA through the interaction between lncRNA LOC100912373 and the miR­17­5p/PDK1 axis. MTT assays and flow cytometry were used to detect the proliferation and cell cycle progression of AST­treated fibroblast­like synoviocytes (FLSs). The expression of lncRNA LOC100912373 and miR­17­5p, as well as relative the mRNA expression of the PDK1 and AKT genes following AST intervention was detected by reverse transcription­quantitative PCR (RT­qPCR), immunofluorescence and western blot analysis. The results revealed that AST inhibited FLS proliferation, reduced lncRNA LOC100912373 expression levels, increased miR­17­5p expression levels, and decreased the PDK1 and p­AKT expression levels. Additionally, consecutive rescue experiments revealed that AST counteracted the effects of lncRNA LOC100912373 overexpression on FLS proliferation and cell cycle progression. On the whole, the present study demonstrates that AST inhibits FLS proliferation by regulating the expression of lncRNA LOC100912373 and the miR­17­5p/PDK1 axis.

Long non-coding RNA AK006774 inhibits cardiac ischemia-reperfusion injury via sponging miR-448.

In recent years, the incidence and mortality of myocardial infarction (MI) have been increasing throughout the world, threatening public health. Non-coding RNAs (ncRNAs), including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), play critical roles in the progression of MI. The present study aimed to investigate the role of lncRNA AK006774 in the progression of myocardial infarction and find out novel therapeutic or diagnostic target of myocardial infarction. A mouse ischemia/reperfusion (I/R) model and 2,3,5-Triphenyte-trazoliumchloride (TTC) staining were performed to evaluate the effects of AK006774 on I/R injury in vivo. Hypoxia/reoxygenation (H/R) models using primary cardiomyocytes have been established. Flow cytometry and Terminal Deoxynucleotide Transferase dUTP Nick End Labeling (TUNEL) assays were performed to evaluate the effects of AK006774 on cardiomyocyte apoptosis. Luciferase and RNA pull-down assays were performed to verify the interaction between miR-448 and its targets. Western blotting and quantitative PCR were performed to determine protein and gene expression, respectively. We first found that AK006774 overexpression reduced I/R-induced infarct area and cardiomyocyte apoptosis in vivo. Accordingly, AK006774 inhibited apoptosis and oxidative stress in cardiomyocytes subjected to H/R treatment in vitro. Mechanistically, AK006774 modulated the expression of bcl-2 by sponging miR-448. Overexpression of miR-448 antagonized the effects of AK006774 on cardiomyocyte apoptosis. The AK006774/miR-448/bcl-2 signaling axis acts as a key regulator of I/R injury and may be a potential therapeutic or diagnostic target for the treatment of MI.

Transcriptome-Wide High-Throughput m6A Sequencing of Differential m6A Methylation Patterns in the Human Rheumatoid Arthritis Fibroblast-Like Synoviocytes Cell Line MH7A.

INTRODUCTION: N6-methyladenosine (m6A) is the most frequent internal modification in eukaryotic mRNAs and is closely related to the occurrence and development of many diseases, especially tumors. However, the relationship between m6A methylation and rheumatoid arthritis (RA) is still a mystery. METHODS: Two high-throughput sequencing methods, namely, m6A modified RNA immunoprecipitation sequence (m6A-seq) and RNA sequence (RNA-seq) were performed to identify the differentially expressed m6A methylation in human rheumatoid arthritis fibroblast-like synoviocytes cell line MH7A after stimulation with TNF-α. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used to obtain enriched GO terms and significant KEGG pathways. Then, four candidate genes, Wilms tumor 1-associating protein (WTAP), receptor-interacting serine/threonine protein kinase 2 (RIPK2), Janus kinase 3 (JAK3) and tumor necrosis factor receptor SF10A (TNFRSF10A) were selected to further validate the m6A methylation, mRNA and protein expression levels in MH7A cells and synovial tissues of adjuvant arthritis (AA) rats by RT-qPCR and Western blot. RESULTS: Using m6A-seq, we identified a total of 206 genes with differentially expressed m6A methylation, of which 118 were significantly upregulated and 88 genes were significantly downregulated. Likewise, 1207 differentially mRNA expressed mRNAs were obtained by RNA-seq, of which 793 were upregulated and 414 downregulated. Further joint analysis showed that the m6A methylation and mRNA expression levels of 88 genes changed significantly, of which 30 genes displayed increased m6A methylation and decreased mRNA expression, 57 genes displayed decreased m6A methylation and increased mRNA expression increased, and 1 gene displayed increased m6A methylation and increased mRNA expression. GO and KEGG analyses indicated that these unique genes were mainly enriched in inflammation-related pathways, cell proliferation and apoptosis. In addition, the validations of WTAP, RIPK2, JAK3 and TNFRSF10A were in accordance with the m6A and RNA sequencing results. CONCLUSION: This study established the transcriptional map of m6A in MH7A cells and revealed the potential relationship between RNA methylation modification and RA related genes. The results suggested that m6A modification was associated with the occurrence and course of RA to some extent.

The abnormal distribution of NK cell subsets before HAART treatment may be related to the level of immune reconstitution in HIV patient.

BACKGROUND: HIV infection leads to the damage of NK cells, which is closely associated with the disease's progression, but whether it affects immune reconstitution after Highly Active Antiretroviral Therapy (HAART) is not clear. METHODS: From March 9 to October 31, 2017, a total of 75 confirmed cases with HIV in Wenzhou were collected and analyzed. NK cell subsets were measured and compared among three groups: the control group, the group whose CD4+ T cell counts <200/µL (named as low-CD4 group) and the group whose CD4+ T cell counts ≥200/µL (named as high-CD4 group). The lymphocytic subsets were dynamically monitored in patients with HIV after HAART. RESULTS: Patients in low-CD4 group have lower proportion of CD3-CD56dimCD16+ NK cell subset, but have higher proportion of CD3-CD56-CD16+ NK cell subsets, which were compared with patients in high-CD4 group (All P values <0.01). There is a positive correlation between the proportion of CD3-CD56-CD16+ NK cell subset and CD4+ T cell counts (r = 0.628, p < 0.001). Patients in the low-CD4 group have higher expression of PD-1 and PS on NK cells than patients in the high-CD4 group (All P values < 0.05). The odds ratio of the proportion of the CD3-CD56-CD16+ NK cell subset before treatment for HAART efficacy was 0.826 (p < 0.001). CONCLUSIONS: There are abnormalities in the proportion and function of NK cell subsets in HIV patients, which are associated with disease progression. The proportion of the CD3-CD56-CD16+ NK cell subset before treatment is related with HAART efficacy.