The effectiveness of gliding arc discharge plasma in sterilizing artificial seawater contaminated with Vibrio parahaemolyticus.

The rapid proliferation of the halophilic pathogen Vibrio parahaemolyticus poses a severe health hazard to halobios and significantly impedes intensive mariculture. This study aimed to evaluate the potential application of gliding arc discharge plasma (GADP) to control the infection of Vibrio parahaemolyticus in mariculture. This study investigated the inactivation ability of GADP against Vibrio parahaemolyticus in artificial seawater (ASW), changes in the water quality of GADP-treated ASW, and possible inactivation mechanisms of GADP against Vibrio parahaemolyticus in ASW. The results indicate that GADP effectively inactivated Vibrio parahaemolyticus in ASW. As the volume of ASW increased, the time required for GADP sterilization also increased. However, the complete sterilization of 5000 mL of ASW containing Vibrio parahaemolyticus of approximately 1.0 × 104 CFU/mL was achieved within 20 min. Water quality tests of the GADP-treated ASW demonstrated that there were no significant changes in salinity or temperature when Vibrio parahaemolyticus (1.0 ×104 CFU/mL) was completely inactivated. In contrast to the acidification observed in plasma-activated water (PAW) in most studies, the pH of ASW did not decrease after treatment with GADP. The H2O2 concentration in the GADP-treated ASW decreased after post-treatment. The NO2-concentration in the GADP-treated ASW remained unchanged after post-treatment. Further analysis revealed that GADP induced oxidative stress in Vibrio parahaemolyticus, which increased cell membrane permeability and intracellular ROS levels of Vibrio parahaemolyticus. This study provides a viable solution for infection with the halophilic pathogen Vibrio parahaemolyticus and demonstrates the potential of GADP in mariculture.

Guanylate-binding protein 1 inhibits Hantaan virus infection by restricting virus entry.

Hantaan virus (HTNV) infection can cause hemorrhagic fever with renal syndrome (HFRS) in humans, and currently, there are no long-standing protective vaccines or specific antivirals available. Guanylate-binding protein 1 (GBP1) is an interferon-stimulated gene that defends against various pathogen infections. However, the function of GBP1 in HTNV infection remains unknown. Here, we describe how GBP1 prevents HTNV infection by obstructing virus entry. We found that HTNV infection induced GBP1 expression and that overexpression of GBP1 inhibited HTNV infection, while knockout of GBP1 had the opposite effect. Interestingly, GBP1 did not affect interferon (IFN) signaling during HTNV infection. Instead, GBP1 prevented HTNV from entering cells through clathrin-mediated endocytosis (CME). We also discovered that GBP1 specifically interacted with actin but not dynamin 2 (DNM2) and made it difficult for DNM2 to be recruited by actin, which may account for the suppression of CME during HTNV infection. These findings establish an antiviral role for GBP1 in inhibiting HTNV infection and help us better understand how GBP1 regulates HTNV entry and could potentially aid in developing treatments for this virus.

Prognostic value of miR-223 for pregnancy outcomes in patients with in vitro fertilisation and intracytoplasmic sperm injection.

BACKGROUND: This study aimed to analyse the expression of microRNA-223 (miR-223) in embryo culture medium and its correlation with pregnancy outcomes. METHODS: Two hundred and two patients undergoing in vitro fertilisation/intracytoplasmic sperm injection (IVF/ICSI) were divided into clinical pregnancy group (n = 101) and non-pregnant group (n = 101). The baseline data, clinical indicators, and the expression level of miR-223 in the embryo medium were compared between the two groups. Logistic regression analysis was used to analyse the relationship between each index and the pregnancy outcome. Receiver operator characteristic curve was carried out to evaluate the differential ability of miR-223 in pregnancy status. Bioinformatics methods were used to identify the target genes of miR-223 and elucidate their functions. RESULTS: Compared with pregnancy group, the non-pregnancy group exhibited a reduction in miR-223 expression (p < 0.001). Multivariate analysis revealed that miR-223 reduction was an independent factor for pregnancy failure (p < 0.05). The ROC curve demonstrated the discriminative capability of miR-223 in distinguishing pregnancy and non-pregnancy. In addition, bioinformatics analysis indicated that the target genes of miR-223 were predominantly located in the endocytic vesicle membrane and were primarily enriched in adenosine monophosphate-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) signalling pathways. CONCLUSION: In this study, levels of miR-223 in the embryo culture medium predicted pregnancy outcomes in subjects undergoing IVF/ICSI. Low expression of miR-223 was a risk factor for adverse pregnancy outcomes in subjects.

In this study, 202 patients who underwent IVF/ICSI were retrospectively analysed and categorised into pregnant and non-pregnant groups based on their pregnancy status. The examination of embryo culture medium samples from both groups revealed that the non-pregnant group exhibited lower miR-223 expression compared to the pregnant group. Subsequent ROC analysis demonstrated the clinical relevance of miR-223 in effectively distinguishing between pregnant and non-pregnant states. Multi-factor analysis further established that the diminished expression of miR-223 independently influenced the likelihood of successful pregnancy.

T-cell immunoglobulin and mucin 1 (TIM-1) mediates infection of Hantaan virus in Jurkat T cells.

Hantaan virus (HTNV) is a major public health concern due to its ability to cause hemorrhagic fever with renal syndrome (HFRS) in Eurasia. Symptoms of HFRS include fever, hemorrhage, immune dysfunction and renal impairment, and severe cases can be fatal. T cell-mediated adaptive immune responses play a pivotal role in countering HTNV infection. However, our understanding of HTNV and T cell interactions in the disease progression is limited. In this study, we found that human CD4+ T cells can be directly infected with HTNV, thereby facilitating viral replication and production. Additionally, T-cell immunoglobulin and mucin 1 (TIM-1) participated in the process of HTNV infection of Jurkat T cells, and further observed that HTNV enters Jurkat T cells via the clathrin-dependent endocytosis pathway. These findings not only affirm the susceptibility of human CD4+ T lymphocytes to HTNV but also shed light on the viral tropism. Our research elucidates a mode of the interaction between the virus infection process and the immune system. Critically, this study provides new insights into the pathogenesis of HTNV and the implications for antiviral research.

Veliparib exerts protective effects in intracerebral hemorrhage mice by inhibiting the inflammatory response and accelerating hematoma resolution.

Poly (ADP-ribose) polymerase (PARP) inhibitors have potent anti-inflammatory effects, including the suppression of brain microglial activation. Veliparib, a well-known PARP1/2 inhibitor, exhibits particularly high brain penetration, but its effects on stroke outcome is unknown. Here, the effects of veliparib on the short-term outcome of intracerebral hemorrhage (ICH), the most lethal type of stroke, were investigated. Collagenase-induced mice ICH model was applied, and the T2-weighted magnetic resonance imaging was performed to evaluate lesion volume. Motor function and hematoma volume were also measured. We further performed immunofluorescence, enzyme linked immunosorbent assay, flow cytometry, and blood-brain barrier assessment to explore the potential mechanisms. Our results demonstrated veliparib reduced the ICH lesion volume dose-dependently and at a dosage of 5 mg/kg, veliparib significantly improved mouse motor function and promoted hematoma resolution at days 3 and 7 post-ICH. Veliparib inhibited glial activation and downregulated the production of pro-inflammatory cytokines. Veliparib significantly decreased microglia counts and inhibited peripheral immune cell infiltration into the brain on day 3 after ICH. Veliparib improved blood-brain barrier integrity at day 3 after ICH. These findings demonstrate that veliparib improves ICH outcome by inhibiting inflammatory responses and may represent a promising novel therapy for ICH.

[Infection of human normal lung epithelial cells by Hantaan virus (HTNV) and its impact on innate immunity and metabolism].

Objective To confirm that Hantaan virus (HTNV) can infect BEAS-2B human normal lung epithelial cells and examine the host immune response and metabolic changes induced by HTNV infection by transcriptomic analysis. Methods Western blotting, quantitative real-time PCR and immunofluorescence assay were used to assess the viral load in BEAS-2B cells, and RNA sequencing was employed for transcriptomic analysis. Results Following the infection of BEAS-2B cells with HTNV, there was an increase in the expression of HTNV nucleocapsid protein (NP) and small segment (S) over time. A transcriptomic analysis of these infected cells at 48-hour mark identified 328 genes that were differentially expressed. GO and KEGG enrichment analysis revealed that these differences were primarily associated with interferon response and innate immune pattern recognition receptor pathways. Protein-protein interaction network analysis identified several genes related to innate immune responses, including four genes encoding disintegrin and metalloproteinase with thrombospondin motifs. Metabolic pathway analysis showed three genes related to terpenoid backbone biosynthesis, two genes related to glycolysis/gluconeogenesis and two genes related to steroid hormone biosynthesis. Subcellular localization analysis indicated that many of the differentially expressed genes were located in mitochondria. Conclusion HTNV is capable of effectively infecting BEAS-2B cells, making them a suitable in vitro model for studying HTNV infection in human lung epithelial. By utilizing bioinformatics methods to screen for differentially expressed genes and metabolic pathways associated with HTNV infection, researchers can establish a theoretical foundation for investigating the molecular mechanisms underling HTNV infection.

One-Pot Synthesis of Ce-SSZ-39 Zeolite with Performance in the NH3-SCR Reaction.

Cu-SSZ-39 zeolite with 8-membered rings is regarded as a very promising catalyst in the NH3-SCR reaction, but its hydrothermal stability still remains to be improved. One of the solutions to promote hydrothermal stability is the insertion of rare earth elements in the product. Nevertheless, normal ion exchange of rare earth elements limits their contents in the zeolite product due to their large hydrated ionic radius and alkaline environment under hydrothermal conditions. Herein, we for the first time present a new method for the one-pot synthesis of Ce-SSZ-39 zeolite under solvent-free conditions. The key to success is the use of Ce-FAU zeolite as a precursor. The obtained product shows good crystallinity, sheet-like morphology, large BET surface area, and 4-coordinated Al species. Detailed investigations illustrate that Ce species in the Cu/Ce-SSZ-39 zeolite micropore can prevent the dealumination and thus formation of CuAlOx species during hydrothermal aging at 850 °C for 16 h, giving the excellent hydrothermal stability and thus showing the excellent catalytic performance in the NH3-SCR reaction. One-pot synthesis of Ce-SSZ-39 zeolite with excellent catalytic performance might open a new door for developing very efficient selective catalytic reduction (SCR) catalysts in near future.

RING finger protein 122-like (RNF122L) negatively regulates antiviral immune response by targeting STING in common carp (Cyprinus carpio L.).

Stimulator of interferon genes (STING), as an imperative adaptor protein in innate immune, responds to nucleic acid from invading pathogens to build antiviral responses in host cells. Aberrant activation of STING may trigger tissue damage and autoimmune diseases. Given the decisive role in initiating innate immune response, the activity of STING is intricately governed by several posttranslational modifications, including phosphorylation and ubiquitination. Here, we cloned and characterized a novel RNF122 homolog from common carp (named CcRNF122L). Expression analysis disclosed that the expression of CcRNF122L is up-regulated under spring viremia of carp virus (SVCV) stimulation in vivo and in vitro. Overexpression of CcRNF122L hampers SVCV- or poly(I:C)-mediated the expression of IFN-1 and ISGs in a dose-dependent way. Mechanistically, CcRNF122L interacts with STING and promotes the polyubiquitylation of STING. This polyubiquitylation event inhibits the aggregation of STING and the subsequent recruitment of TBK1 and IRF3 to the signaling complex. Additionally, the deletion of the TM domain abolishes the negative regulatory function of CcRNF122L. Collectively, our discoveries unveil a mechanism that governs the STING function and the precise adjustment of the innate immune response in teleost.

Gut microbiota induced epigenetic modifications in the non-alcoholic fatty liver disease pathogenesis.

Non-alcoholic fatty liver disease (NAFLD) represents a growing global health concern that can lead to liver disease and cancer. It is characterized by an excessive accumulation of fat in the liver, unrelated to excessive alcohol consumption. Studies indicate that the gut microbiota-host crosstalk may play a causal role in NAFLD pathogenesis, with epigenetic modification serving as a key mechanism for regulating this interaction. In this review, we explore how the interplay between gut microbiota and the host epigenome impacts the development of NAFLD. Specifically, we discuss how gut microbiota-derived factors, such as lipopolysaccharides (LPS) and short-chain fatty acids (SCFAs), can modulate the DNA methylation and histone acetylation of genes associated with NAFLD, subsequently affecting lipid metabolism and immune homeostasis. Although the current literature suggests a link between gut microbiota and NAFLD development, our understanding of the molecular mechanisms and signaling pathways underlying this crosstalk remains limited. Therefore, more comprehensive epigenomic and multi-omic studies, including broader clinical and animal experiments, are needed to further explore the mechanisms linking the gut microbiota to NAFLD-associated genes. These studies are anticipated to improve microbial markers based on epigenetic strategies and provide novel insights into the pathogenesis of NAFLD, ultimately addressing a significant unmet clinical need.

Penifuranone A: A Novel Alkaloid from the Mangrove Endophytic Fungus Penicillium crustosum SCNU-F0006.

One previously undescribed alkaloid, named penifuranone A (1), and three known compounds (2-4) were isolated from the mangrove endophytic fungus Penicillium crustosum SCNU-F0006. The structure of the new alkaloid (1) was elucidated based on extensive spectroscopic data analysis and single-crystal X-ray diffraction analysis. Four natural isolates and one new synthetic derivative of penifuranone A, compound 1a, were screened for their antimicrobial, antioxidant, and anti-inflammatory activities. Bioassays revealed that penifuranone A (1) exhibited strong anti-inflammatory activity in vitro by inhibiting nitric oxide (NO) production in lipopolysaccharide-activated RAW264.7 cells with an IC50 value of 42.2 µM. The docking study revealed that compound 1 exhibited an ideal fit within the active site of the murine inducible nitric oxide synthase (iNOS), establishing characteristic hydrogen bonds.

Unraveling resistance mechanisms in anti-CD19 chimeric antigen receptor-T therapy for B-ALL: a novel in vitro model and insights into target antigen dynamics.

BACKGROUND: Cellular immunotherapy, represented by the chimeric antigen receptor T cell (CAR-T), has exhibited high response rates, durable remission, and safety in vitro and in clinical trials. Unfortunately, anti-CD19 CAR-T (CART-19) treatment alone is prone to relapse and has a particularly poor prognosis in relapsed/refractory (r/r) B-ALL patients. To date, addressing or reducing relapse remains one of the research priorities to achieve broad clinical application. METHODS: We manufactured second generation CART-19 cells and validated their efficacy and safety in vitro and in vivo. Through co-culture of Nalm-6 cells with short-term cultured CART-19 cells, CD19-negative Nalm-6 cells were detected by flow cytometry, and further investigation of the relapsed cells and their resistance mechanisms was evaluated in vitro. RESULTS: In this study, we demonstrated that CART-19 cells had enhanced and specific antileukemic activities, and the survival of B-ALL mouse models after CART-19 treatment was significantly prolonged. We then shortened the culture time and applied the serum-free culture to expand CAR-T cells, followed by co-culturing CART-19 cells with Nalm-6 cells. Surprisingly, we observed the proliferation of CD19-negative Nalm-6 cells around 28 days. Identification of potential resistance mechanisms showed that the relapsed cells express truncated CD19 proteins with decreased levels and, more importantly, CAR expression was detected on the relapsed cell surface, which may ultimately keep them antigen-negative. Furthermore, it was validated that CART-22 and tandem CART-22/19 cells could effectively kill the relapsed cells, but neither could completely eradicate them. CONCLUSIONS: We successfully generated CART-19 cells and obtained a CD19-negative refractory relapsed B-ALL cell line, providing new insights into the underlying mechanisms of resistance and a new in vitro model for the treatment of r/r B-ALL patients with low antigen density.

Development of a nomogram to predict the risk of secondary failure of platelet recovery in patients with ß-thalassemia major after hematopoietic stem cell transplantation: a retrospective study.

Background: Secondary failure of platelet recovery (SFPR) is a common complication that influences survival and quality of life of patients with ß-thalassemia major (ß-TM) after hematopoietic stem cell transplantation (HSCT). Objectives: A model to predict the risk of SFPR in ß-TM patients after HSCT was developed. Design: A retrospective study was used to develop the prediction model. Methods: The clinical data for 218 ß-TM patients who received HSCT comprised the training set, and those for another 89 patients represented the validation set. The least absolute shrinkage and selection operator regression algorithm was used to identify the critical clinical factors with nonzero coefficients for constructing the nomogram. Calibration curve, C-index, and receiver operating characteristic curve assessments and decision curve analysis (DCA) were used to evaluate the calibration, discrimination, accuracy, and clinical usefulness of the nomogram. Internal and external validation were used to test and verify the predictive model. Results: The nomogram based on pretransplant serum ferritin, hepatomegaly, mycophenolate mofetil use, and posttransplant serum albumin could be conveniently used to predict the SFPR risk of thalassemia patients after HSCT. The calibration curve of the nomogram revealed good concordance between the training and validation sets. The nomogram showed good discrimination with a C-index of 0.780 (95% CI: 70.3-85.7) and 0.868 (95% CI: 78.5-95.1) and AUCs of 0.780 and 0.868 in the training and validation sets, respectively. A high C-index value of 0.766 was reached in the interval validation assessment. DCA confirmed that the nomogram was clinically useful when intervention was decided at the possibility threshold ranging from 3% to 83%. Conclusion: We constructed a nomogram model to predict the risk of SFPR in patients with ß-TM after HSCT. The nomogram has a good predictive ability and may be used by clinicians to identify SFPR patients early and recommend effective preventive measures.

Acacetin Attenuates Sepsis-induced Acute Lung Injury via NLRC3-NF-κB Pathway.

Acacetin, a flavonoid derived compound has been recognized for its diverse biological activities, such as anti-oxidative and anti-inflammatory effects. Acute lung injury (ALI) is a severe condition characterized by respiratory insufficiency and tissue damage, commonly triggered by pneumonia and severe sepsis. These conditions induce an inflammatory response via Toll-like receptor 4 (TLR4) signaling activation. This study explored acacetin's therapeutic potential against lipopolysaccharide (LPS) induced ALI in mice, focusing on its ability to modulate the NF-κB pathway via regulation of the Nod-like receptor family CARD domain containing 3 (NLRC3), a signal sensor that plays an important role in the regulation of inflammation and the maintenance of homeostasis. Our findings revealed that high-dose acacetin reduced the mortality rate of ALI mice, significantly ameliorated LPS-induced lung pathological changes, reduced lung edema, and decreased the expression of inflammatory mediators in lung tissues. This protective impact of acacetin appears to stem form its capacity to enhance NLRC3 expression, which, intern, can inhibit the activation of NF-κB and subsequently inhibit the production of inflammatory mediators. NLRC3 deficiency inhibits the protective effect of acacetin on ALI mice. Molecular docking also verified that acacetin tightly bound acacetin to NLRC3. Additionally, acacetin was found to influence macrophage recruitment dynamics via NLRC3, inhibiting the overactivation of NLRC3-NF-κB related pathways. Taken together, our results indicate that acacetin inhibited LPS-induced acute lung injury and macrophage overrecruitment to the lungs in mice by upregulating NLRC3.

A novel tryptanthrin-based "on-off-on" probe for sequential sensing Cu2+/S2- in water samples.

Copper ions (Cu2+) and sulfide (S2-) play essential roles in many physiologies and pathologic processes. Herein, a new "on-off-on" tryptanthrin-based probe TR-1 (TR-1) has been designed and synthesized in a facile and economical way. TR-1 exhibited highly selective and sensitive response to Cu2+ without any interference over 14 competitive metal ions and the detection limit downs to 24 nM, which is far below the Chinese standard of fishery water quality (157 nM). The 'in situ' prepared complex TR-1 + Cu2+ could also be applied to detect S2- with the detection limit of 62 nM. Further, TR-1 was potentially applied for the analysis of copper ions in water samples.

NLRX1: a key regulator in mitochondrial respiration and colorectal cancer progression.

Colorectal cancer (CRC) is a prevalent and aggressive malignancy with high mortality rates and significant risks to human well-being. Population-wide screening for tumor suppressor genes and oncogenes shows promise for reducing the incidence and fatality of CRC. Recent studies have suggested that NLRX1, an innate immunity suppressor, may play a role in regulating chronic inflammation and tumorigenesis. However, further investigation is needed to understand the specific role of NLRX1 in CRC. To evaluate the impact of NLRX1 on migration, invasion, and metastasis, two human colon cancer cell lines were studied in vitro. Additionally, a knockout mouse tumor-bearing model was used to validate the inhibitory effect of NLRX1 on tumor emergence and progression. The Seahorse XF96 technology was employed to assess mitochondrial function and glycolysis in colorectal cancer cells overexpressing NLRX1. Moreover, public databases were consulted to analyze gene and protein expression levels of NLRX1. Finally, the results were validated using a series of CRC patient samples. Our findings demonstrate that downregulation of NLRX1 enhances proliferation, colony formation, and tumor-forming capacity in HCT116 and LoVo cells. Conversely, overexpression of NLRX1 negatively impacts basal respiration and mitochondrial ATP-linked respiration in both cell lines, resulting in a notable decrease in maximal respiration during the standard mitochondrial stress test. Furthermore, analysis of data from the TCGA database reveals a significant reduction in NLRX1 expression in colon and rectal cancer tissues compared to normal tissues. This result was validated using clinical samples, where immunohistochemistry staining and western blotting demonstrated a notable reduction in NLRX1 protein levels in CRC compared to adjacent normal tissues. The decreased expression of NLRX1 may serve as a significant prognostic indicator and diagnostic biomarker for CRC patients.

Transcriptome Analysis Reveals Novel Genes Potentially Involved in Tuberization in Potato.

The formation and development of tubers, the primary edible and economic organ of potatoes, directly affect their yield and quality. The regulatory network and mechanism of tuberization have been preliminarily revealed in recent years, but plenty of relevant genes remain to be discovered. A few candidate genes were provided due to the simplicity of sampling and result analysis of previous transcriptomes related to tuberization. We sequenced and thoroughly analyzed the transcriptomes of thirteen tissues from potato plants at the tuber proliferation phase to provide more reference information and gene resources. Among them, eight tissues were stolons and tubers at different developmental stages, which we focused on. Five critical periods of tuberization were selected to perform an analysis of differentially expressed genes (DEGs), according to the results of the tissue correlation. Compared with the unswollen stolons (Sto), 2751, 4897, 6635, and 9700 DEGs were detected in the slightly swollen stolons (Sto1), swollen stolons (Sto2), tubers of proliferation stage 1 (Tu1), and tubers of proliferation stage 4 (Tu4). A total of 854 transcription factors and 164 hormone pathway genes were identified in the DEGs. Furthermore, three co-expression networks associated with Sto-Sto1, Sto2-Tu1, and tubers of proliferation stages two to five (Tu2-Tu5) were built using the weighted gene co-expression network analysis (WGCNA). Thirty hub genes (HGs) and 30 hub transcription factors (HTFs) were screened and focalized in these networks. We found that five HGs were reported to regulate tuberization, and most of the remaining HGs and HTFs co-expressed with them. The orthologs of these HGs and HTFs were reported to regulate processes (e.g., flowering, cell division, hormone synthesis, metabolism and signal transduction, sucrose transport, and starch synthesis) that were also required for tuberization. Such results further support their potential to control tuberization. Our study provides insights and countless candidate genes of the regulatory network of tuberization, laying the foundation for further elucidating the genetic basis of tuber development.

Comprehensive characterization of immunogenic cell death in acute myeloid leukemia revealing the association with prognosis and tumor immune microenvironment.

BACKGROUND: This study aimed to explore the clinical significance of immunogenic cell death (ICD) in acute myeloid leukemia (AML) and its relationship with the tumor immune microenvironment characteristics. It also aimed to provide a potential perspective for bridging the pathogenesis of AML and immunological research, and to provide a theoretical basis for precise individualized treatment of AML patients. METHODS: Firstly, we identified two subtypes associated with ICD by consensus clustering and explored the biological enrichment pathways, somatic mutations, and tumor microenvironment landscape between the ICD subtypes. Additionally, we developed and validated a prognostic model associated with ICD-related genes. Finally, we conducted a preliminary exploration of the construction of disease regulatory networks and prediction of small molecule drugs based on five signature genes. RESULTS: Differentially expressed ICD-related genes can distinguish AML into subgroups with significant differences in clinical characteristics and survival prognosis. The relationship between the ICD- high subgroup and the immune microenvironment was tight, showing significant enrichment in immune-related pathways such as antibody production in the intestinal immune environment, allograft rejection, and Leishmaniasis infection. Additionally, the ICD- high subtype showed significant upregulation in a variety of immune cells such as B_cells, Macrophages_M2, Monocytes, and T_cells_CD4. We constructed a prognostic risk feature based on five signature genes (TNF, CXCR3, CD4, PIK3CA and CALR), and the time-dependent ROC curve confirmed the high accuracy in predicting the clinical outcomes. CONCLUSION: There is a strong close relationship between the ICD- high subgroup and the immune microenvironment. Immunogenicity-related genes have the potential to be a prognostic biomarker for AML.

P2X7 receptor antagonists modulate experimental autoimmune neuritis via regulation of NLRP3 inflammasome activation and Th17 and Th1 cell differentiation.

BACKGROUND: Guillain-Barré syndrome (GBS), a post-infectious, immune-mediated, acute demyelinating disease of the peripheral nerves and nerve roots, represents the most prevalent and severe acute paralyzing neuropathy. Purinergic P2X7 receptors (P2X7R) play a crucial role in central nervous system inflammation. However, little is known about their role in the immune-inflammatory response within the peripheral nervous system. METHODS: Initially, we assessed the expression of purinergic P2X7R in the peripheral blood of patients with GBS using flow cytometry and qRT-PCR. Next, we explored the expression of P2 X7R in CD4+ T cells, CD8+ T cells, and macrophages within the sciatic nerves and spleens of rats using immunofluorescence labeling and flow cytometry. The P2X7R antagonist brilliant blue G (BBG) was employed to examine its therapeutic impact on rats with experimental autoimmune neuritis (EAN) induced by immunization with the P0180 - 199 peptide. We analyzed CD4+ T cell differentiation in splenic mononuclear cells using flow cytometry, assessed Th17 cell differentiation in the sciatic nerve through immunofluorescence staining, and examined the expression of pro-inflammatory cytokine mRNA using RT-PCR. Additionally, we performed protein blotting to assess the expression of P2X7R and NLRP3-related inflammatory proteins within the sciatic nerve. Lastly, we utilized flow cytometry and immunofluorescence labeling to examine the expression of NLRP3 on CD4+ T cells in rats with EAN. RESULTS: P2X7R expression was elevated not only in the peripheral blood of patients with GBS but also in rats with EAN. In rats with EAN, inhibiting P2X7R with BBG alleviated neurological symptoms, reduced demyelination, decreased inflammatory cell infiltration of the peripheral nerves, and improved nerve conduction. BBG also limited the production of pro-inflammatory molecules, down-regulated the expression of P2X7R and NLRP3, and suppressed the differentiation of Th1 and Th17 cells, thus protecting against EAN. These effects collectively contribute to modifying the inflammatory environment and enhancing outcomes in EAN rats. CONCLUSIONS: Suppression of P2X7R relieved EAN manifestation by regulating CD4+ T cell differentiation and NLRP3 inflammasome activation. This finding underscores the potential significance of P2X7R as a target for anti-inflammatory treatments, advancing research and management of GBS.

Clinical features and genetic spectrum of a multicenter Chinese cohort with myotonic dystrophy type 1.

BACKGROUND: As the most common subtype of adult muscular dystrophy worldwide, large cohort reports on myotonic dystrophy type I (DM1) in China are still lacking. This study aims to analyze the genetic and clinical characteristics of Chinese Han DM1 patients. METHODS: Based on the multicenter collaborating effort of the Pan-Yangtze River Delta Alliance for Neuromuscular Disorders, patients with suspected clinical diagnoses of DM1 were genetically confirmed from January 2020 to April 2023. Peak CTG repeats in the DMPK gene were analyzed using triplet repeat-primed PCR (TP-PCR) and flanking PCR. Time-to-event analysis of onset age in females and males was performed. Additionally, detailed clinical features and longitudinal changes from the disease onset in 64 DM1 patients were retrospectively collected and analyzed. The Epworth Sleepiness Scale and Fatigue Severity Scale were used to quantify the severity of daytime sleepiness and fatigue. RESULTS: Among the 211 genetically confirmed DM1 patients, the mean age at diagnosis was 40.9 ± 12.2 (range: 12-74) with a male-to-female ratio of 124:87. The average size of CTG repeats was 511.3 (range: 92-1945). Among the DM1 patients with comprehensive clinical data (n = 64, mean age 41.0 ± 12.0), the age at onset was significantly earlier in males than in females (4.8 years earlier, p = 0.026). Muscle weakness (92.2%), myotonia (85.9%), and fatigue (73.4%) were the most prevalent clinical features. The predominant involved muscles at onset are hands (weakness or myotonia) (52.6%) and legs (walking disability) (42.1%). Of them, 70.3% of patients had daytime sleepiness, 14.1% had cataract surgery, 7.8% used wheelchairs, 4.7% required ventilatory support, and 1.6% required gastric tubes. Regarding the comorbidities, 4.7% of patients had tumors, 17.2% had diabetes, 23.4% had dyspnea, 28.1% had intermittent insomnia, 43.8% experienced dysphagia, and 25% exhibited cognitive impairment. Chinese patients exhibited smaller size of CTG repeats (468 ± 139) than those reported in Italy (613 ± 623), the US (629 ± 386), and Japan (625 [302, 1047]), and milder phenotypes with less multisystem involvement. CONCLUSION: The Chinese Han DM1 patients presented milder phenotypes compared to their Caucasian and Japanese counterparts. A male predominance and an early age of onset were identified in male Chinese Han DM1 patients.

The Pd (II) Reduction Mechanisms in Bacillus megaterium Y-4 Revealed by Proteomic Analysis.

Many studies have been conducted on the microbial reduction of Pd (II) to palladium nanoparticles (Pd-NPs) due to the environmental friendliness, low cost, and the decreased toxicity of Pd (II) ions. In this study, we investigate the reduction mechanism of Pd (II) by Bacillus megaterium Y-4 through proteomics. The data are available via ProteomeXchange with identifier PXD049711. Our results revealed that B. megaterium Y-4 may use the endogenous electron donor (NAD(P)H) generated by nirB, tdh, and fabG and reductase to reduce Pd (II) to Pd-NPs. The expression levels of fabG, tdh, gudB, and rocG that generate NAD(P)H were further increased, and the number of reduced Pd-NPs was further increased with the exogenous electron donor sodium formate. Endogenous electron mediators such as quinones and flavins in B. megaterium Y-4 can further enhance Pd (II) reduction. The findings provided invaluable information regarding the reduction mechanism of Pd (II) by B. megaterium Y-4 at the proteome level.