Functional overlap between the mammalian Sar1a and Sar1b paralogs in vivo.

Proteins carrying a signal peptide and/or a transmembrane domain enter the intracellular secretory pathway at the endoplasmic reticulum (ER) and are transported to the Golgi apparatus via COPII vesicles or tubules. SAR1 initiates COPII coat assembly by recruiting other coat proteins to the ER membrane. Mammalian genomes encode two SAR1 paralogs, SAR1A and SAR1B. While these paralogs exhibit ~90% amino acid sequence identity, it is unknown whether they perform distinct or overlapping functions in vivo. We now report that genetic inactivation of Sar1a in mice results in lethality during midembryogenesis. We also confirm previous reports that complete deficiency of murine Sar1b results in perinatal lethality. In contrast, we demonstrate that deletion of Sar1b restricted to hepatocytes is compatible with survival, though resulting in hypocholesterolemia that can be rescued by adenovirus-mediated overexpression of either SAR1A or SAR1B. To further examine the in vivo function of these two paralogs, we genetically engineered mice with the Sar1a coding sequence replacing that of Sar1b at the endogenous Sar1b locus. Mice homozygous for this allele survive to adulthood and are phenotypically normal, demonstrating complete or near-complete overlap in function between the two SAR1 protein paralogs in mice. These data also suggest upregulation of SAR1A gene expression as a potential approach for the treatment of SAR1B deficiency (chylomicron retention disease) in humans.

Construction of ceRNA network mediated by circRNAs screening from microarray and identification of novel biomarkers for myasthenia gravis.

BACKGROUND: Recent studies have revealed that circRNA can serve as ceRNA to participate in multiple autoimmune diseases. Our study aims to explore the key circRNA as ceRNA and biomarker for MG. METHODS: We used circRNA microarray to explore differentially expressed circRNAs (DECs) from MG and compare with control. Then, we predicted the target miRNA associated with DECs and screened miRNAs by the algorithm of random walk with restart (RWR). Next, we constructed the circRNA-miRNA-mRNA ceRNA regulated network (CMMC) to identify the hub objects. Following, we detected the expression of hub-circRNAs by RT-PCR. We verify has_circ_0004183 (circFRMD4) sponging miR-145-5p regulate cells proliferation using luciferase assay and CCK-8. RESULTS: We found that the expression level of circFRMD4 and has_circ_0035381 (circPIGB) were upregulated and has_circ_0089153(circ NUP214) had the lowest expression level in MG. Finally, we proved circFRMD4 sponging miR-145-5p regulate Jurkat cells proliferation. CircFRMD4 take part in the genesis and development of MG via circFRMD4/miR145-5p axis. CONCLUSIONS: We found that circFRMD4, circPIGB and circNUP214 can be considered as valuable potential novel biomarkers for AchR + MG. CircFRMD4 participate in the development of AchR + MG via targeting binding with miR-145-5p.

Functional overlap between the mammalian Sar1a and Sar1b paralogs in vivo.

Proteins carrying a signal peptide and/or a transmembrane domain enter the intracellular secretory pathway at the endoplasmic reticulum (ER) and are transported to the Golgi apparatus via COPII vesicles or tubules. SAR1 initiates COPII coat assembly by recruiting other coat proteins to the ER membrane. Mammalian genomes encode two SAR1 paralogs, SAR1A and SAR1B. While these paralogs exhibit ~90% amino acid sequence identity, it is unknown whether they perform distinct or overlapping functions in vivo. We now report that genetic inactivation of Sar1a in mice results in lethality during mid-embryogenesis. We also confirm previous reports that complete deficiency of murine Sar1b results in perinatal lethality. In contrast, we demonstrate that deletion of Sar1b restricted to hepatocytes is compatible with survival, though resulting in hypocholesterolemia that can be rescued by adenovirus-mediated overexpression of either SAR1A or SAR1B. To further examine the in vivo function of these 2 paralogs, we genetically engineered mice with the Sar1a coding sequence replacing that of Sar1b at the endogenous Sar1b locus. Mice homozygous for this allele survive to adulthood and are phenotypically normal, demonstrating complete or near-complete overlap in function between the two SAR1 protein paralogs in mice. These data also suggest upregulation of SAR1A gene expression as a potential approach for the treatment of SAR1B deficiency (chylomicron retention disease) in humans.

Hepatic danger signaling triggers TREM2+ macrophage induction and drives steatohepatitis via MS4A7-dependent inflammasome activation.

Metabolic dysfunction-associated steatohepatitis (MASH), formerly known as nonalcoholic steatohepatitis (NASH), is an advanced stage of metabolic fatty liver disease. The pathogenic mechanisms of MASH center on hepatocyte injury and the ensuing immune response within the liver microenvironment. Recent work has implicated TREM2+ macrophages in various disease conditions, and substantial induction of TREM2+ NASH-associated macrophages (NAMs) serves as a hallmark of metabolic liver disease. Despite this, the mechanisms through which NAMs contribute to MASH pathogenesis remain poorly understood. Here, we identify membrane-spanning 4-domains a7 (MS4A7) as a NAM-specific pathogenic factor that exacerbates MASH progression in mice. Hepatic MS4A7 expression was strongly induced in mouse and human MASH and associated with the severity of liver injury. Whole-body and myeloid-specific ablation of Ms4a7 alleviated diet-induced MASH pathologies in male mice. We demonstrate that exposure to lipid droplets (LDs), released upon injury of steatotic hepatocytes, triggered NAM induction and exacerbated MASH-associated liver injury in an MS4A7-dependent manner. Mechanistically, MS4A7 drove NLRP3 inflammasome activation via direct physical interaction and shaped disease-associated cell states within the liver microenvironment. This work reveals the LD-MS4A7-NLRP3 inflammasome axis as a pathogenic driver of MASH progression and provides insights into the role of TREM2+ macrophages in disease pathogenesis.

Caspase-11/GSDMD contributes to the progression of hyperuricemic nephropathy by promoting NETs formation.

Hyperuricemia is an independent risk factor for chronic kidney disease (CKD) and promotes renal fibrosis, but the underlying mechanism remains largely unknown. Unresolved inflammation is strongly associated with renal fibrosis and is a well-known significant contributor to the progression of CKD, including hyperuricemia nephropathy. In the current study, we elucidated the impact of Caspase-11/Gasdermin D (GSDMD)-dependent neutrophil extracellular traps (NETs) on progressive hyperuricemic nephropathy. We found that the Caspase-11/GSDMD signaling were markedly activated in the kidneys of hyperuricemic nephropathy. Deletion of Gsdmd or Caspase-11 protects against the progression of hyperuricemic nephropathy by reducing kidney inflammation, proinflammatory and profibrogenic factors expression, NETs generation, α-smooth muscle actin expression, and fibrosis. Furthermore, specific deletion of Gsdmd or Caspase-11 in hematopoietic cells showed a protective effect on renal fibrosis in hyperuricemic nephropathy. Additionally, in vitro studies unveiled the capability of uric acid in inducing Caspase-11/GSDMD-dependent NETs formation, consequently enhancing α-smooth muscle actin production in macrophages. In summary, this study demonstrated the contributory role of Caspase-11/GSDMD in the progression of hyperuricemic nephropathy by promoting NETs formation, which may shed new light on the therapeutic approach to treating and reversing hyperuricemic nephropathy.

Change of epidemiological characteristics of four respiratory viral infections in children before and during COVID-19 pandemic.

OBJECTIVES: Viruses are the main infectious agents of acute respiratory infections (ARIs) in children. We aim to describe the changes in epidemic characteristics of viral ARIs in outpatient children before and during the COVID-19 pandemic. PATIENTS AND METHODS: From 2017 to 2022, the results of viral detection in oral pharyngeal swabs in 479,236 children with ARIs in the outpatient department of Children's Hospital, Zhejiang University School of Medicine, were retrospectively analyzed. Viral antigens, including adenovirus (ADV), influenza A (FLUA), influenza B (FLUB) and respiratory syncytial virus (RSV) were detected by the colloidal gold method. RESULTS: The median age was 3.4 (1.6-5.6) years. Among all the children, 159,895 cases (33.4 %) were positive for at least one virus. The total positive rate for ADV, FLUA and FLUB during the pandemic period was lower than during the pre-pandemic period in every season (pre-pandemic period vs. pandemic period11.7 % vs. 4.7 %, 13.9 % vs. 9.2 %, 7.0 % vs. 5.2 %, respectively, with overall p value < 0.001). However, the positive rate fir RSV was not significantly different between the pre-pandemic period and the pandemic period (5.6 % vs. 5.8 %, p = 0.117). Atypical timing of RSV (summer-autumn 2021) and FLUA (summer 2022) was noted. CONCLUSIONS: Public health interventions for different pathogens are maximally effective. While positive rates for ADV, FLUA and FLUB decreased during the COVID-19 pandemic period, positive rates for RSV remained similar. In RSV and FLUA, off-season outbreaks were observed. Measures need to be taken to protect children from possible infection surges due to immunity debt having accrued over the last three years.

Polypeptides from traditional Chinese medicine: Comprehensive review of perspective towards cancer management.

Cancer has always been a focus of global attention, and the difficulty of treatment and poor prognosis have always plagued humanity. Conventional chemotherapeutics and treatment with synthetic disciplines will cause adverse side effects and drug resistance. Therefore, searching for a safe, valid, and clinically effective drug is necessary. At present, some natural compounds have proved to have the potential to fight cancer. Polypeptides obtained from traditional Chinese medicine are good anti-cancer ingredients. The anticancer activity has been fully demonstrated in vivo and in vitro. However, most of the functional studies on traditional Chinese medicine polypeptides are at the stage of basic experimental research, and fewer of them have been applied to clinical trials. Hence, this review mainly discusses the chemical structure, extraction, separation and purification methods, the anti-cancer mechanism, and structure-activity relationships of traditional Chinese medicine polypeptides. It provides theoretical support for strengthening the rapid separation and purification and the overall efficacy and mechanism of action, as well as the industrialization and clinical application of traditional Chinese medicine polypeptides.

Synergistic mechanism of stir-baked curcumae radix with vinegar in dysmenorrhea rats based on UPLC-Q-TOF/MS metabolomics.

Curcumae Radix (i.e. Huangsiyujin: HSYJ), a well-known traditional Chinese medicine (TCM), has been widely used in clinical practice for many years to treat depression and primary dysmenorrhea. Modern pharmacological researches have demonstrated its anti-inflammatory, antidepressant, and dysmenorrhea relief effects. According to the processing theory of TCM, it is believed that stir-baked HSYJ with vinegar may enhance the ability to disperse stagnant hepatoqi and alleviate pain. However, whether the vinegar concoction of HSYJ can enhance the therapeutic effect on the Qi stagnation due to liver depression (LDQS) type of dysmenorrhea and what its mechanism has not been well explained. Based on the processing drugs theory of "stir-baked with vinegar into liver", a metabolomic approach was used to investigate the therapeutic effect and mechanism of stir-baked HSYJ with vinegar to enhance the treatment of dysmenorrhea in rats. By establishing a rat model of dysmenorrhea of the "LDQS" type, observation of hemorheology, uterine pathological sections, COX-2 and OTR protein expression and other indicators; analysis of urinary metabolic changes in rats by UPLC-Q-TOF-MS technique, to compare the differential biomarkers and metabolic pathways in the treatment of dysmenorrhea due to "liver stagnation and qi stagnation" before and after stir-baked HSYJ with vinegar. Stir-baked HSYJ with vinegar significantly inhibited the writhing response of rats, improved hemorheology, repaired damaged diseased uterus and inhibited high expression of COX-2 and OTR proteins in uterus; 68 differential metabolites were screened from the urine of rats, compared with the raw HSYJ, the levels of 14 metabolites were significantly changed in stir-baked HSYJ with vinegar, involving the pathways of phenylalanine, tyrosine and tryptophan metabolism, cysteine and methionine metabolism, aspartate and glutamate metabolism. The potentiating effect of stir-baked HSYJ with vinegar may be related to the regulation of multiple amino acid metabolic pathways.

Clinical Characteristics and Outcomes of AIDS-Related Burkitt Lymphoma in China: A Retrospective Single-Center Study.

Objectives: Studies on the prognosis and risk stratification of patients with acquired immune deficiency syndrome (AIDS) - related Burkitt lymphoma (AR-BL) are rare. We aim to construct a novel model to improve the risk assessment of these patients. Methods: We retrospectively analyzed the clinical data of 34 patients over the past 10 years and the factors associated with progression-free survival (PFS) and overall survival (OS) were evaluated in univariate and multivariate Cox models. Then, the novel model consisting of screened factors was compared with the existing models. Results: With a 37-month median follow-up, the overall 2-year PFS and OS rates were 40.50% and 36.18%, respectively. The OS of patients who received chemotherapy was better compared with those without chemotherapy (P = .0012). Treatment with an etoposide, prednisone, oncovin, cyclophosphamide, and hydroxydaunorubicin-based regimen was associated with longer OS and PFS compared with a cyclophosphamide, doxorubicin, vincristine, and prednisone-based regimen (OS, P = .0002; PFS, P = .0158). Chemotherapy (hazard ratio [HR] = 0.075; 95% confidence interval [CI], 0.009-0.614) and Eastern Cooperative Oncology Group Performance Status (ECOG PS) 2 to 4 (HR = 4.738; 95% CI, 1.178-19.061) were independent prognostic factors of OS in multivariate analysis and we established a novel prognostic risk stratification model named GZ8H model with chemotherapy and ECOG PS. Conclusion: GZ8H showed better stratification ability than the international prognostic index (IPI) or Burkitt lymphoma IPI (BL-IPI). Furthermore, the C-index of the nomogram used to predict OS was 0.884 in the entire cohort and the calibration curve showed excellent agreement between the predicted and actual results of OS. No human immunodeficiency virus-related factors were found to be associated with OS and PFS of AR-BL patients in our study. Overall, the clinical characteristics and outcomes in AR-BL were shown and prognostic factors for OS and PFS were identified in this study.

Uncovering impaired mitochondrial and lysosomal function in adipose-derived stem cells from obese individuals with altered biological activity.

BACKGROUND: Adipose-derived stem cells (ADSCs) have been extensively used in preclinical and clinical trials for treating various diseases. However, the differences between ADSCs from lean individuals (L-ADSCs) and those from obese individuals (O-ADSCs) have not been thoroughly investigated, particularly regarding their mitochondrial and lysosomal functions. Therefore, this study aims to evaluate the differences between L-ADSCs and O-ADSCs in terms of cell biological activity, mitochondria, and lysosomes. METHODS: We first isolated and cultured L-ADSCs and O-ADSCs. We then compared the differences between the two groups in terms of biological activity, including cell proliferation, differentiation potential, and their effect on the polarization of macrophages. Additionally, we observed the mitochondrial and lysosomal morphology of ADSCs using an electronic microscope, MitoTracker Red, and lysotracker Red dyes. We assessed mitochondrial function by examining mitochondrial membrane potential and membrane fluidity, antioxidative ability, and cell energy metabolism. Lysosomal function was evaluated by measuring autophagy and phagocytosis. Finally, we performed transcriptome analysis of the ADSCs using RNA sequencing. RESULTS: The biological activities of O-ADSCs were decreased, including cell immunophenotypic profiles, cell proliferation, and differentiation potential. Furthermore, compared to L-ADSCs, O-ADSCs promoted M1-type macrophage polarization and inhibited M2-type macrophage polarization. Additionally, the mitochondrial morphology of O-ADSCs was altered, with the size of the cells becoming smaller and mitochondrial fragments increasing. O-ADSCs also exhibited decreased mitochondrial membrane potential and membrane fluidity, antioxidative ability, and energy metabolism. With respect to lysosomes, O-ADSCs contained ungraded materials in their lysosomes, enhanced lysosomal permeability, and reduced autophagy and phagocytosis ability. RNA sequence analysis indicated that the signalling pathways related to cell senescence, cancer, and inflammation were upregulated, whereas the signalling pathways associated with stemness, cell differentiation, metabolism, and response to stress and stimuli were downregulated. CONCLUSIONS: This study indicates that ADSCs from individuals (BMI > 30 kg/m2) exhibit impaired mitochondrial and lysosomal function with decreased biological activity.

Neuregulin 4 mediates the metabolic benefits of mild cold exposure by promoting beige fat thermogenesis.

Interorgan crosstalk via secreted hormones and metabolites is a fundamental aspect of mammalian metabolic physiology. Beyond the highly specialized endocrine cells, peripheral tissues are emerging as an important source of metabolic hormones that influence energy and nutrient metabolism and contribute to disease pathogenesis. Neuregulin 4 (Nrg4) is a fat-derived hormone that protects mice from nonalcoholic steatohepatitis (NASH) and NASH-associated liver cancer by shaping hepatic lipid metabolism and the liver immune microenvironment. Despite its enriched expression in brown fat, whether NRG4 plays a role in thermogenic response and mediates the metabolic benefits of cold exposure are areas that remain unexplored. Here we show that Nrg4 expression in inguinal white adipose tissue (iWAT) is highly responsive to chronic cold exposure. Nrg4 deficiency impairs beige fat induction and renders mice more susceptible to diet-induced metabolic disorders under mild cold conditions. Using mice with adipocyte and hepatocyte-specific Nrg4 deletion, we reveal that adipose tissue-derived NRG4, but not hepatic NRG4, is essential for beige fat induction following cold acclimation. Furthermore, treatment with recombinant NRG4-Fc fusion protein promotes beige fat induction in iWAT and improves metabolic health in mice with diet-induced obesity. These findings highlight a critical role of NRG4 in mediating beige fat induction and preserving metabolic health under mild cold conditions.

PGAM5 knockout causes depressive-like behaviors in mice via ATP deficiency in the prefrontal cortex.

INTRODUCTION: Major depressive disorder (MDD) affects about 17% population in the world. Although abnormal energy metabolism plays an important role in the pathophysiology of MDD, however, how deficiency of adenosine triphosphate (ATP) products affects emotional circuit and what regulates ATP synthesis are still need to be elaborated. AIMS: Our study aimed to investigate how deficiency of PGAM5-mediated depressive behavior. RESULTS: We firstly discovered that PGAM5 knockout (PGAM5-/- ) mice generated depressive-like behaviors. The phenotype was reinforced by the observation that chronic unexpected mild stress (CUMS)-induced depressive mice exhibited lowered expression of PGAM5 in prefrontal cortex (PFC), hippocampus (HIP), and striatum. Next, we found, with the using of functional magnetic resonance imaging (fMRI), that the functional connectivity between PFC reward system and the PFC volume were reduced in PGAM5-/- mice. PGAM5 ablation resulted in the loss of dendritic spines and lowered density of PSD95 in PFC, but not in HIP. Finally, we found that PGAM5 ablation led to lowered ATP concentration in PFC, but not in HIP. Coimmunoprecipitation study showed that PGAM5 directly interacted with the ATP F1 F0 synthase without influencing the interaction between ATP F1 F0 synthase and Bcl-xl. We then conducted ATP administration to PGAM5-/- mice and found that ATP could rescue the behavioral and neuronal phenotypes of PGAM5-/- mice. CONCLUSIONS: Our findings provide convincing evidence that PGAM5 ablation generates depressive-like behaviors via restricting neuronal ATP production so as to impair the number of neuronal spines in PFC.

Dental aspiration in a pediatric patient: a case report.

Foreign body aspiration is relatively common in children, especially in children younger than 3 years, and it is associated with a high incidence and mortality rate. Because of impairments in swallowing, speech, and vision, more caution regarding foreign body aspiration is required in children with abnormal nervous system development. This report describes a clinically rare case involving a 6-year-old patient with delayed brain development and epilepsy who was found to have a tooth in the bronchus of the left lung through fiberoptic bronchoscopy. The tooth was successfully removed by an extraction procedure. A follow-up examination showed that the patient had a sequela of left lower lobe atelectasis. This case indicates that greater caution is necessary regarding foreign body aspiration, including dental aspiration, in patients with abnormal development of the nervous system.

A missed foreign body aspiration masquerading as congenital pulmonary airway malformation in a nine-year-old boy: A case report and literature review.

Although airway foreign body aspiration (FBA) is a common occurrence in any age group, unrecognized and retained foreign bodies in lungs may result in severe complications, such as lung abscess or bronchiectasis. In rare cases, FBA may present with similar clinical features as many other diseases (e.g. asthma, tumor, pulmonary eosinophilia). Here, we report a rare case of missed FBA in a nine-year-old boy, whose chest CT scan was suggestive of a cavitary lesion in the left lower lobe mimicking congenital pulmonary airway malformation (CPAM). However, surprisingly, flexible bronchoscopy revealed a peanut lodged in the lateral basal segment of left lower lobe, which was subsequently retrieved by a forceps and avoided unnecessary surgical lobectomy. Therefore, FBA can mimic other disorders (e.g. CPAM), and a high index of suspicion and additional diagnostic techniques (e.g. flexible bronchoscopy) may be required to distinguish them. Additionally, FBA should be considered in the differential diagnosis of respiratory disorders in children even lack of aspiration history.

hnRNPA2B1 promotes the occurrence and progression of hepatocellular carcinoma by downregulating PCK1 mRNA via a m6A RNA methylation manner.

BACKGROUND: N6-methyladenosine (m6A) is the most prevalent RNA modification. Although hnRNPA2B1, as a reader of m6A modification, has been reported to promote tumorigenesis in a few types of tumors, its role in hepatocellular carcinoma (HCC) and the underlying molecular mechanism remains unclear. METHODS: Multiple public databases were used to analyze the expression of hnRNPA2B1 in HCC and its correlation with survival prognosis. We employed a CRISPR-Cas9 sgRNA editing strategy to knockout hnRNPA2B1 expression in HCC cells. The biological function of hnRNPA2B1 in vitro in HCC cells was measured by CCK8, colony formation, migration, and invasion assay. The tumorigenic function of hnRNPA2B1 in vivo was determined by a subcutaneous tumor formation experiment and a HCC mouse model via tail injection of several plasmids into the mouse within 5s-7s. RNA binding protein immunoprecipitation (RIP) experiment using hnRNPA2B1 was performed to test the target genes of hnRNPA2B1 and methylated RNA immunoprecipitation (MeRIP) assay was performed to explore the m6A methylated mRNA of target genes. RESULTS: hnRNPA2B1 highly expressed in HCC tissues, correlated with high grades and poor prognosis. Its knockout reduced HCC cell proliferation, migration, and invasion in vitro, while overexpression promoted these processes. hnRNPA2B1-knockout cells inhibited tumor formation in graft experiments. In HCC mice, endogenous knockout attenuated hepatocarcinogenesis. RNA-seq showed downregulated gluconeogenesis with high hnRNPA2B1 expression. hnRNPA2B1 negatively correlated with PCK1, a key enzyme. RIP assay revealed hnRNPA2B1 binding to PCK1 mRNA. hnRNPA2B1 knockout increased m6A-methylation of PCK1 mRNA. Interestingly, PCK1 knockout partially counteracted tumor inhibition by hnRNPA2B1 knockout in mice. CONCLUSION: Our study indicated that hnRNPA2B1 is highly expressed in HCC and correlated with a poor prognosis. hnRNPA2B1 promotes the tumorigenesis and progression of HCC both in vitro and in vivo. Moreover, hnRNPA2B1 downregulates the expression of PCK1 mRNA via a m6A methylation manner. More importantly, the ability of hnRNPA2B1 to induce tumorigenesis and progression in HCC is dependent on its ability to decrease the expression of PCK1. Therefore, this study suggested that hnRNPA2B1 might be a diagnostic marker of poor prognosis of HCC and a potential therapeutic target for HCC patients.

Independent prognostic biomarker FERMT3 associated with immune infiltration and immunotherapy response in glioma.

BACKGROUND: Adult glioma progresses rapidly and has a poor clinical outcome. The focal adhesion protein Kindlin-3 (encoded by the FERMT3 gene) participates in tumor development, drug resistance, and progression. However, the relationship between Kindlin-3 and glioma prognosis or immune microenvironment is poorly understood. METHODS: We comprehensively analyzed the expression, prognostic value, mutation landscape, functional enrichment, immune infiltration, and therapeutic role of FERMT3 in glioma using multiple datasets and validated Kindlin-3 expression in clinical tissue specimens by immunohistochemistry and multiple immunofluorescence staining. RESULTS: FERMT3 is an independent predictor of glioma prognosis and is highly expressed in glioblastoma tissues. Functional enrichment analyses indicated that FERMT3 participates in multiple immune-related pathways such as immune response and cytokine production. Furthermore, FERMT3 expression was positively correlated with the infiltration of several immune cells, immune scores, and the expression of genes related to immune checkpoints. Further analyses revealed that overexpression of FERMT3 was linked to a better response to anti-PD1 therapy. Data from single-cell RNA-seq reveal that FERMT3 was largely expressed in microglial cells and tissue-resident macrophages. Multiple immunofluorescence staining confirmed the overexpression of Kindlin-3 in the glioma-associated microglia/macrophages (GAMs). CONCLUSION: The findings of this study provide a new perspective on the role of Kindlin-3 in glioma and may have a significant impact on the discovery of novel biomarkers and targeting of GAMs in the future.

[Review on the Long-term and Short-term Effects of Biochar Addition on Soil Greenhouse Gas Emissions].

Increasing concentrations of greenhouse gases in the atmosphere caused by human activities are the main cause of climate warming. Global warming is a severe challenge confronted by human society today. Reducing greenhouse gas emissions and increasing carbon sinks are the keys to addressing climate warming. Biochar addition is considered to be a promising way to reduce greenhouse gas emissions and increase carbon sinks, due to its unique physical, chemical, and biological properties. Therefore, it is of great significance to study the effects of biochar on soil greenhouse gas emissions to mitigate the greenhouse effect and achieve "carbon neutrality." The long-term and short-term effects of biochar on soil greenhouse gas emissions and their influencing mechanism were reviewed. It was found that the effects of biochar on soil greenhouse gas emissions varied with the types of biochar feedstock, pyrolysis temperature, application ratio, and soil and vegetable types. In addition, due to the different aging times and modes and cultivation methods, the mitigation effect of aged biochar on soil greenhouse gas could be enhanced or weakened or even disappeared. Further, based on the deficiencies of the previous research, the direction and focus of future research on the effects of biochar on soil greenhouse gas emissions were analyzed and prospected. It was proposed to strengthen simultaneous research on the effects of biochar on CO2, N2O, and CH4 emissions; reducing greenhouse gas emissions and carbon sequestration; different aging modes and cultivation methods of biochar; and revealing the influencing mechanism at the process level, through exploring the effects of biochar on soil carbon and nitrogen dynamics and tracing the source of greenhouse gases using 13C and 15N tracer technology.

IlNRAMP5 is required for cadmium accumulation and the growth in Iris lactea under cadmium exposures.

Iris lactea is potentially applied for remediating Cd-contaminated soils due to the strong ability of Cd uptake and accumulation. However, its molecular mechanism underlying Cd uptake pathway remains unknown. Here, we report a member of NRAMP (Natural Resistance-Associated Macrophage Protein) family, IlNRAMP5, is involved in Cd/Mn uptake and the growth in I. lactea response to Cd. IlNRAMP5 was localized onto the plasma membrane, and was induced by Cd. It was expressed in the root cortex rather than the central vasculature, and in leaf vascular bundle and mesophyll cells. Heterologous expression in yeast showed that IlNRAMP5 could transport Cd and Mn, but not Fe. Knockdown of IlNRAMP5 triggered a significant reduction in Cd uptake, further diminishing the accumulation of Cd. In addition, silencing IlNRAMP5 disrupted Mn homeostasis by lowering Mn uptake and Mn allocation, accompanied by remarkably inhibiting photosynthesis under Cd conditions. Overall, the findings suggest that IlNRAMP5 plays versatile roles in Cd accumulation by mediating Cd uptake, and contributes to maintain the growth via modulating Mn homeostasis in I. lactea under Cd exposures. This would provide a mechanistic understanding Cd phytoremediation efficiency in planta.

Analysis of endoplasmic reticulum stress-related gene signature for the prognosis and pattern in diffuse large B cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma in adults. This study aimed to determine the prognostic significance of endoplasmic reticulum (ER) stress-related genes in DLBCL. ER stress-related genes were obtained from the molecular signatures database. Gene expression data and clinical outcomes from the gene expression omnibus and TCGA datasets were collected, and differentially expressed genes (DEGs) were screened out. Gene ontology enrichment analysis, the kyoto encyclopaedia of genes and genomes pathway analysis, and geneset enrichment analysis were used to analyse the possible biological function of ER stress-related DEGs in DLBCL. Protein-protein interaction network construction using the STRING online and hub genes were identified by cytoHubba on Cytoscape software. The significant prognosis-related genes were screened, and the differential expression was validated. The immune microenvironment assessment of significant genes were evaluated. Next, the nomogram was built using univariate and multivariate Cox regression analysis. 26 ER stress-related DEGs were screened. Functional enrichment analysis showed them to be involved in the regulation of the endoplasmic reticulum mainly. NUPR1 and TRIB3 were identified as the most significant prognostic-related genes by comparison with the GSE10846, GSE11318, and TCGA datasets. NUPR1 was correlated with a good prognosis and immune infiltration in DLBCL; on the other hand, high expression of TRIB3 significantly correlated with a poor prognosis, which was an independent prognostic factor for DLBCL. In summary, we identified NUPR1 and TRIB3 as critical ER stress-related genes in DLBCL. NUPR1 might be involved in immune infiltration in DLBCL, and TRIB3 might serve as a potential therapeutic target and prognostic factor in DLBCL.

Research progress on the treatment of epilepsy with traditional Chinese medicine.

BACKGROUND: Traditional Chinese Medicine (TCM) system is a medical system that has been expanding for thousands of years that was formed by the extensive clinical practice experience of many physicians and the accumulation of personal medication habits in China. In TCM, there is a history of long-term medication for epilepsy, the main treatment for epilepsy is TCM drugs and its prescription, supplemented by TCM modalities such as acupuncture therapy, moxibustion therapy, tuina, emotion adjustment therapy, etc. PURPOSE: With the modernization of TCM, the active ingredients and molecular mechanisms of TCM for epilepsy treatment have been gradually revealed. This review aimed to comprehensively summarize the TCM treatment of epilepsy, focusing on the current TCM drugs and some TCM formulae for the treatment of epilepsy, and to discuss the research progress of TCM for the treatment of epilepsy, and to provide a reference to develop future related studies in this field. MATERIALS AND METHODS: The mechanism of action of antiepileptic drugs (AEDs) was interpreted from different perspectives by searching online databases and querying various materials identify drugs used in both modern medicine and TCM systems for the treatment of epilepsy. We collected all relevant TCM for epilepsy literature published in the last 30 years up to December 2022 from electronic databases such as PubMed, CNKI and Web of Science, and statistically analyzed the literature for the following keyword information. The search terms comprise the keywords "TCM", "phytochemistry", "pharmacological activity", "epilepsy" and "traditional application" as a combination. Scientific plant names were provided by "The Plant List" (www.theplantlist.org). RESULTS: Epilepsy is a complex and serious disease of the brain and nervous system. At present, the treatment of epilepsy in modern medicine is mainly surgery and chemotherapy, but there are many serious side effects. By summarizing the treatment of epilepsy in TCM, it is found that there are various methods to treat epilepsy in TCM, mainly TCM drugs and its formulae. Many TCM drugs have antiepileptic effects. Now found that the main effective TCM drugs for the treatment of epilepsy are Curcumae Longae Rhizoma, Scorpio, Acori Tatarinowii Rhizoma, Uncariae Ramulus Cum Uncis and Ganoderma, etc. And the main compounds that play a role in the treatment of epilepsy are curcumin, gastrodin, ligustrazine, baicalin and rhynchophylline, etc. These TCM drugs have played an important role in the treatment of epilepsy in TCM clinic. However, the chemically active components of these TCM drugs are diverse and their mechanisms of action are complex, which are not fully understood and need to be further explored. CONCLUSIONS: TCM treats epilepsy in a variety of ways, and with the discovery of a variety of potential bioactive substances for treatment of epilepsy. With the new progress in the research of other TCM treatment methods for epilepsy, TCM will have greater potential in the clinical application of epilepsy.