A single-cell chromatin accessibility dataset of human primed and naïve pluripotent stem cell-derived teratoma.

Teratoma, due to its remarkable ability to differentiate into multiple cell lineages, is a valuable model for studying human embryonic development. The similarity of the gene expression and chromatin accessibility patterns in these cells to those observed in vivo further underscores its potential as a research tool. Notably, teratomas derived from human naïve (pre-implantation epiblast-like) pluripotent stem cells (PSCs) have larger embryonic cell diversity and contain extraembryonic lineages, making them more suitable to study developmental processes. However, the cell type-specific epigenetic profiles of naïve PSC teratomas have not been yet characterized. Using single-cell assay for transposase-accessible chromatin sequencing (scATAC-seq), we analyzed 66,384 cell profiles from five teratomas derived from human naïve PSCs and their post-implantation epiblast-like (primed) counterparts. We observed 17 distinct cell types from both embryonic and extraembryonic lineages, resembling the corresponding cell types in human fetal tissues. Additionally, we identified key transcription factors specific to different cell types. Our dataset provides a resource for investigating gene regulatory programs in a relevant model of human embryonic development.

PGM5-AS1 Promotes Progression of Diffuse Large B-Cell Lymphoma and Immune Escape by Regulating miR-503-5p.

Purpose: Diffuse large B-cell lymphoma (DLBCL) is a prevalent malignant condition with a dismal prognosis. LncRNA PGM5 antisense RNA 1 (PGM5-AS1) appears to be intricately involved in the progression of DLBCL, yet the modulatory mechanism remains unclear. The purpose of this study was to explore the expression of lncRNA PGM5-AS1 in DLBCL and its effect on the disease progression of DLBCL, as well as to explore its mechanisms. Patients and Methods: A total of 35 patients were included in the study. The expression levels of PGM5-AS1 and miR-503-5p in DLBCL tumor tissues and cell lines were detected by RT-qPCR. Cell proliferation was assessed using CCK8. Apoptosis rate was determined by flow cytometry. Cell invasion was examined by transwell assays. The specific interaction between PGM5-AS1 and miR-503-5p was verified through dual luciferase reporter gene assays. The immune related factors were detected by ELASA kits. The CD8+ T cells cytotoxicity was evaluated by LDH cytotoxicity kit. Results: In DLBCL tumor tissues and cells, upregulated PGM5-AS1 expression, downregulated miR-503-5p expression, and elevated PD-L1 expression were observed. PGM5-AS1 functioned as a regulator in controlling DLBCL cell proliferation, apoptosis, and invasion by downregulating miR-503-5p expression. When CD8+ T cells were co-cultured with cells transfected with si-PGM5-AS1, the secretion of immunoregulatory factors increased, and the cytotoxicity of CD8+ T cells increased. These effects were mitigated by miR-503-5p inhibitors. Conclusion: PGM5-AS1 accelerated DLBCL development and facilitated tumor immune escape through the miR-503-5p. Our discoveries offered an insight into lncRNA PGM5-AS1 serving as a prospective therapeutic target for DLBCL.

Ebselen improves lipid metabolism by activating PI3K/Akt and inhibiting TLR4/JNK signaling pathway to alleviate nonalcoholic fatty liver.

Nonalcoholic fatty liver disease (NAFLD), a metabolic disease associated with obesity and type 2 diabetes. Due to its complex pathogenesis, there are still limitations in the knowledge of the disease. To date, no drug has been approved to treat NAFLD. This study aims to explore the role and mechanism of Ebselen (EbSe) in NAFLD. A high-fat diet-induced mouse model of NAFLD was employed to investigate EbSe function in NAFLD mice by EbSe gavage and to regularly monitor the mouse body weight. HE and oil red O staining were performed, respectively, to detect the pathological damage and lipid accumulation in mouse liver tissues. The biochemical and ELISA kits were employed to measure the levels of ALT, AST, TG, TC, LDL-C, HDL-C and pro-inflammatory cytokines within mouse serum or liver tissue. The expression of key proteins of PPARα, fatty acid ß oxidation-related protein, PI3K/Akt and TLR4/JNK signaling pathway was detected by western blot. EbSe significantly downregulated body weight, liver weight and liver lipid accumulation in NAFLD mice and downregulated ALT, AST, TG, TC, LDL-C and increased HDL-C serum levels. EbSe upregulated the expression levels of PPARα and fatty acid ß oxidation-associated proteins CPT1α, ACOX1, UCP2 and PGC1α. EbSe promoted Akt and PI3K phosphorylation, and inhibited TLR4 expression and JNK phosphorylation. EbSe can upregulate PPARα to promote fatty acid ß-oxidation and improve hepatic lipid metabolism. Meanwhile, EbSe also activated PI3K/Akt and inhibited TLR4/JNK signaling pathway. EbSe is predicted to be an effective therapeutic drug for treating NAFLD.

New Clerodane Diterpenoids from Tinospora capillipes with Antibacterial and Anti-Inflammatory Properties.

Four new clerodane diterpenoids, namely tinocapills A-D (1-4), and one known analogue (5) were isolated from the roots of Tinospora capillipes in the present study. The structures of these new compounds, including their absolute configurations, were determined through a combination of detailed spectroscopic analysis and theoretical statistical approaches, including electronic circular dichroism (ECD) analyses and quantum mechanical (QM)-NMR methods. Additionally, the stereostructure of 5 was confirmed via X-ray diffraction analysis. Furthermore, all these isolates were evaluated for their antibacterial and anti-inflammatory activities. Compounds 1, 2 and 5 demonstrated antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) with MICs ranging from 4 to 64 µg/mL, and compounds 3 and 4 exhibited potential anti-inflammatory effects by suppressing LPS-induced TNF-α and NO releases in RAW264.7 cells.

Comparative Analysis of mRNA, microRNA of Transcriptome, and Proteomics on CIK Cells Responses to GCRV and Aeromonas hydrophila.

Grass Carp Reovirus (GCRV) and Aeromonas hydrophila (Ah) are the causative agents of haemorrhagic disease in grass carp. This study aimed to investigate the molecular mechanisms and immune responses at the miRNA, mRNA, and protein levels in grass carp kidney cells (CIK) infected by Grass Carp Reovirus (GCRV, NV) and Aeromonas hydrophilus (Bacteria, NB) to gain insight into their pathogenesis. Within 48 h of infection with Grass Carp Reovirus (GCRV), 99 differentially expressed microRNA (DEMs), 2132 differentially expressed genes (DEGs), and 627 differentially expressed proteins (DEPs) were identified by sequencing; a total of 92 DEMs, 3162 DEGs, and 712 DEPs were identified within 48 h of infection with Aeromonas hydrophila. It is worth noting that most of the DEGs in the NV group were primarily involved in cellular processes, while most of the DEGs in the NB group were associated with metabolic pathways based on KEGG enrichment analysis. This study revealed that the mechanism of a grass carp haemorrhage caused by GCRV infection differs from that caused by the Aeromonas hydrophila infection. An important miRNA-mRNA-protein regulatory network was established based on comprehensive transcriptome and proteome analysis. Furthermore, 14 DEGs and 6 DEMs were randomly selected for the verification of RNA/small RNA-seq data by RT-qPCR. Our study not only contributes to the understanding of the pathogenesis of grass carp CIK cells infected with GCRV and Aeromonas hydrophila, but also serves as a significant reference value for other aquatic animal haemorrhagic diseases.

SMRT sequencing of a full-length transcriptome reveals cold induced alternative splicing in Vitis amurensis root.

Alternative splicing enhances diversity at the transcriptional and protein levels that widely involved in plant response to biotic and abiotic stresses. V. amurensis is an extremely cold-tolerant wild grape variety, however, studies on alternative splicing (AS) in amur grape at low temperatures are currently poorly understood. In this study, we analyzed full-length transcriptome and RNA seq data at 0, 2, and 24 h after cold stress in V. amurensis roots. Following quality control and correction, 221,170 high-quality full-length non-concatemer (FLNC) reads were identified. A total of 16,181 loci and 30,733 isoforms were identified. These included 22,868 novel isoforms from annotated genes and 2815 isoforms from 2389 novel genes. Among the distinguished novel isoforms, 673 Long non-coding RNAs (LncRNAs) and 18,164 novel isoforms open reading frame (ORF) region were found. A total of 2958 genes produced 8797 AS events, of which 189 genes were involved in the low-temperature response. Twelve transcription factors show AS during cold treatment and VaMYB108 was selected for initial exploration. Two transcripts, Chr05.63.1 (VaMYB108short) and Chr05.63.2 (VaMYB108normal) of VaMYB108, display up-regulated expression after cold treatment in amur grape roots and are both localized in the nucleus. Only VaMYB108normal exhibits transcriptional activation activity. Overexpression of either VaMYB108short or VaMYB108normal in grape roots leads to increased expression of the other transcript and both increased chilling resistance of amur grape roots. The results improve and supplement the genome annotations and provide insights for further investigation into AS mechanisms during cold stress in V. amurensis.

Task functional networks predict individual differences in the speed of emotional facial discrimination.

Every individual experiences negative emotions, such as fear and anger, significantly influencing how external information is perceived and processed. With the gradual rise in brain-behavior relationship studies, analyses investigating individual differences in negative emotion processing and a more objective measure such as the response time (RT) remain unexplored. This study aims to address this gap by establishing that the individual differences in the speed of negative facial emotion discrimination can be predicted from whole-brain functional connectivity when participants were performing a face discrimination task. Employing the connectome predictive modeling (CPM) framework, we demonstrated this in the young healthy adult group from the Human Connectome Project-Young Adults (HCP-YA) dataset and the healthy group of the Boston Adolescent Neuroimaging of Depression and Anxiety (BANDA) dataset. We identified distinct network contributions in the adult and adolescent predictive models. The highest represented brain networks involved in the adult model predictions included representations from the motor, visual association, salience, and medial frontal networks. Conversely, the adolescent predictive models showed substantial contributions from the cerebellum-frontoparietal network interactions. Finally, we observed that despite the successful within-dataset prediction in healthy adults and adolescents, the predictive models failed in the cross-dataset generalization. In conclusion, our study shows that individual differences in the speed of emotional facial discrimination can be predicted in healthy adults and adolescent samples using their functional connectivity during negative facial emotion processing. Future research is needed in the derivation of more generalizable models.

Association between Urine Specific Gravity as a Measure of Hydration Status and Risk of Type 2 Diabetes: The Kailuan Prospective Cohort Study.

Diabetes, especially type 2 diabetes (T2D), poses an unprecedented challenge to global public health. Hydration status also plays a fundamental role in human health, especially in people with T2D, which is often overlooked. This study aimed to explore the longitudinal associations between hydration status and the risk of T2D among the Chinese population. This study used data from the large community-based Kailuan cohort, which included adults who attended physical examinations from 2006 to 2007 and were followed until 2020. A total of 71,526 participants who eventually met the standards were divided into five hydration-status groups based on their levels of urine specific gravity (USG). Multivariable and time-dependent Cox proportional hazards models were employed to evaluate the associations of baseline and time-dependent hydration status with T2D incidence. Restricted cubic splines (RCS) analysis was used to examine the dose-response relationship between hydration status and the risk of T2D. Over a median 12.22-year follow-up time, 11,804 of the participants developed T2D. Compared with the optimal hydration-status group, participants with dehydration and severe dehydration had a significantly increased risk of diabetes, with adjusted hazard ratios (95% CI) of 1.30 (1.04-1.63) and 1.38 (1.10-1.74). Time-dependent analyses further confirmed the adverse effects of impending dehydration, dehydration, and severe dehydration on T2D incidence by 16%, 26%, and 33% compared with the reference group. Inadequate hydration is significantly associated with increased risks of T2D among Chinese adults. Our findings provided new epidemiological evidence and highlighted the potential role of adequate hydration status in the early prevention of T2D development.

Combining chemical analysis and toxicological methods to access the ecological risk of complex contamination in Daye Lake.

As one of the nine primary non-ferrous metal smelting bases in China, Daye Lake basin was polluted due to diverse human activities. But so far the pollution status and related ecological risks of this region have not been detailly investigated. In current study, pollutants including heavy metals, polycyclic aromatic hydrocarbons (PAHs) and organochlorine pesticides (OCPs) in eight sediment samples from Daye Lake were quantified. 18S rRNA gene sequencing was employed to profile the nematode community structure within these sediments. Model organism Caenorhabditis elegans (C. elegans) were further applied for a comprehensive ecological risk assessment of Daye Lake. Notably, Cadmium (Cd) was identified as a key driver of ecological risk, reaching an index of 1287.35. At sample point S4, OCPs particularly p,p'-DDT, displayed an extreme ecological risk with a value of 23.19. Cephalobidae and Mononchida showed strong sensitivity to pollutant levels, reinforcing their suitability as robust bioindicators. The composite pollutants in sampled sediments caused oxidative stress in C. elegans, with gene Vit-2 and Mtl-1 as sensitive biomarkers. By employing the multiple analysis methods, our data can offer valuable contributions to environmental monitoring and health risk assessment for composite polluted areas.

Non-Metal Sulfur Doping of Indium Hydroxide Nanocube for Selectively Photocatalytic Reduction of CO2 to CH4: A "One Stone Three Birds" Strategy.

Photocatalytic CO2 reduction is considered as a promising strategy for CO2 utilization and producing renewable energy, however, it remains challenge in the improvement of photocatalytic performance for wide-band-gap photocatalyst with controllable product selectivity. Herein, the sulfur-doped In(OH)3 (In(OH)xSy-z) nanocubes are developed for selective photocatalytic reduction of CO2 to CH4 under simulated light irradiation. The CH4 yield of the optimal In(OH)xSy-1.0 can be enhanced up to 39 times and the CH4 selectivity can be regulated as high as 80.75% compared to that of pristine In(OH)3. The substitution of sulfur atoms for hydroxyl groups in In(OH)3 enhances the visible light absorption capability, and further improves the hydrophilicity behavior, which promotes the H2O dissociation into protons (H*) and accelerates the dynamic proton-feeding CO2 hydrogenation. In situ DRIFTs and DFT calculation confirm that the non-metal sulfur sites significantly weaken the over-potential of the H2O oxidation and prevent the formation of ·OH radicals, enabling the stabilization of *CHO intermediates and thus facilitating CH4 production. This work highlights the promotion effect of the non-metal doping engineering on wide-band-gap photocatalysts for tailoring the product selectivity in photocatalytic CO2 reduction.

Multispecies-coadsorption-induced rapid preparation of graphene glass fiber fabric and applications in flexible pressure sensor.

Direct chemical vapor deposition (CVD) growth of graphene on dielectric/insulating materials is a promising strategy for subsequent transfer-free applications of graphene. However, graphene growth on noncatalytic substrates is faced with thorny issues, especially the limited growth rate, which severely hinders mass production and practical applications. Herein, graphene glass fiber fabric (GGFF) is developed by graphene CVD growth on glass fiber fabric. Dichloromethane is applied as a carbon precursor to accelerate graphene growth, which has a low decomposition energy barrier, and more importantly, the produced high-electronegativity Cl radical can enhance adsorption of active carbon species by Cl-CH2 coadsorption and facilitate H detachment from graphene edges. Consequently, the growth rate is increased by ~3 orders of magnitude and carbon utilization by ~960-fold, compared with conventional methane precursor. The advantageous hierarchical conductive configuration of lightweight, flexible GGFF makes it an ultrasensitive pressure sensor for human motion and physiological monitoring, such as pulse and vocal signals.

Mid1 promotes synovitis in rheumatoid arthritis via ubiquitin-dependent post-translational modification.

INTRODUCTION: Current anti-rheumatic drugs are primarily modulating immune cell activation, yet their effectiveness remained suboptimal. Therefore, novel therapeutics targeting alternative mechanisms, such as synovial activation, is urgently needed. OBJECTIVES: To explore the role of Midline-1 (Mid1) in synovial activation. METHODS: NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ (NSG) mice were used to establish a subcutaneous xenograft model. Wild-type C57BL/6, Mid1-/-, Dpp4-/-, and Mid1-/-Dpp4-/- mice were used to establish a collagen-induced arthritis model. Cell viability, cell cycle, qPCR and western blotting analysis were used to detect MH7A proliferation, dipeptidyl peptidase-4 (DPP4) and Mid1 levels. Co-immunoprecipitation and proteomic analysis identified the candidate protein of Mid1 substrates. Ubiquitination assays were used to determine DPP4 ubiquitination status. RESULTS: An increase in Mid1, an E3 ubiquitin ligase, was observed in human RA synovial tissue by GEO dataset analysis, and this elevation was confirmed in a collagen-induced mouse arthritis model. Notably, deletion of Mid1 in a collagen-induced arthritis model completely protected mice from developing arthritis. Subsequent overexpression and knockdown experiments on MH7A, a human synoviocyte cell line, unveiled a previously unrecognized role of Mid1 in synoviocyte proliferation and migration, the key aspects of synovial activation. Co-immunoprecipitation and proteomic analysis identified DPP4 as the most significant candidate of Mid1 substrates. Mechanistically, Mid1 promoted synoviocyte proliferation and migration by inducing ubiquitin-mediated proteasomal degradation of DPP4. DPP4 deficiency led to increased proliferation, migration, and inflammatory cytokine production in MH7A, while reconstitution of DPP4 significantly abolished Mid1-induced augmentation of cell proliferation and activation. Additionally, double knockout model showed that DPP4 deficiency abolished the protective effect of Mid1 defect on arthritis. CONCLUSION: Overall, our findings suggest that the ubiquitination of DPP4 by Mid1 promotes synovial cell proliferation and invasion, exacerbating synovitis in RA. These results reveal a novel mechanism that controls synovial activation, positioning Mid1 as a promising target for therapeutic intervention in RA.

Cannabidiol ameliorates PTSD-like symptoms by inhibiting neuroinflammation through its action on CB2 receptors in the brain of male mice.

Post-traumatic stress disorder (PTSD) is a debilitating mental health disease related to traumatic experience, and its treatment outcomes are unsatisfactory. Accumulating research has indicated that cannabidiol (CBD) exhibits anti-PTSD effects, however, the underlying mechanism of CBD remains inadequately investigated. Although many studies pertaining to PTSD have primarily focused on aberrations in neuronal functioning, the present study aimed to elucidate the involvement and functionality of microglia/macrophages in PTSD while also investigated the modulatory effects of CBD on neuroinflammation associated with this condition. We constructed a modified single-prolonged stress (SPS) mice PTSD model and verified the PTSD-related behaviors by various behavioral tests (contextual freezing test, elevated plus maze test, tail suspension test and novel object recognition test). We observed a significant upregulation of Iba-1 and alteration of microglial/macrophage morphology within the prefrontal cortex and hippocampus, but not the amygdala, two weeks after the PTSD-related stress, suggesting a persistent neuroinflammatory phenotype in the PTSD-modeled group. CBD (10 mg/kg, i.p.) inhibited all PTSD-related behaviors and reversed the alterations in both microglial/macrophage quantity and morphology when administered prior to behavioral assessments. We further found increased pro-inflammatory factors, decreased PSD95 expression, and impaired synaptic density in the hippocampus of the modeled group, all of which were also restored by CBD treatment. CBD dramatically increased the level of anandamide, one of the endocannabinoids, and cannabinoid type 2 receptors (CB2Rs) transcripts in the hippocampus compared with PTSD-modeled group. Importantly, we discovered the expression of CB2Rs mRNA in Arg-1-positive cells in vivo and found that the behavioral effects of CBD were diminished by CB2Rs antagonist AM630 (1 mg/kg, i.p.) and both the behavioral and molecular effects of CBD were abolished in CB2Rs knockout mice. These findings suggest that CBD would alleviate PTSD-like behaviors in mice by suppressing PTSD-related neuroinflammation and upregulation and activation of CB2Rs may serve as one of the underlying mechanisms for this therapeutic effect. The present study offers innovative experimental evidence supporting the utilization of CBD in PTSD treatment from the perspective of its regulation of neuroinflammation, and paves the way for leveraging the endocannabinoid system to regulate neuroinflammation as a potential therapeutic approach for psychiatric disorders.

Identifying symptom clusters and temporal interconnections in patients with lung tumors after CT-guided microwave ablation: A network analysis.

PURPOSE: To explore symptom clusters and interrelationships using a network analysis approach among symptoms in patients with lung tumors who underwent computed tomography (CT)-guided microwave ablation (MWA). METHODS: A longitudinal study was conducted, and 196 lung tumor patients undergoing MWA were recruited and were measured at 24 h, 48 h, and 72 h after MWA. The Chinese version of the MD Anderson Symptom Inventory and the Revised Lung Cancer Module were used to evaluate symptoms. Network analyses were performed to explore the symptom clusters and interrelationships among symptoms. RESULTS: Four stable symptom communities were identified within the networks. Distress, weight loss, and chest tightness were the central symptoms. Distress, and weight loss were also the most key bridge symptoms, followed by cough. Three symptom networks were temporally stable in terms of symptom centrality, global connectivity, and network structure. CONCLUSION: Our findings identified the central symptoms, bridge symptoms, and the stability of symptom networks of patients with lung tumors after MWA. These network results will have important implications for future targeted symptom management intervention development. Future research should focus on developing precise interventions for targeting central symptoms and bridge symptoms to promote patients' health.

Withaferin A Inhibits Liver Cancer Tumorigenesis by Suppressing Aerobic Glycolysis through the p53/IDH1/HIF-1α Signaling Axis.

BACKGROUND: The energy supply of certain cancer cells depends on aerobic glycolysis rather than oxidative phosphorylation. Our previous studies have shown that withaferin A (WA), a lactone compound derived from Withania somnifera, suppresses skin carcinogenesis at least partially by stabilizing IDH1 and promoting oxidative phosphorylation. Here, we have extended our studies to evaluate the anti-tumor effect of WA in liver cancer. METHODS: Differential expression of glycolysis-related genes between liver cancer tissues and normal tissues and prognosis were verified using an online database. Glycolysis-related protein expression was detected using western blot after overexpression and knockdown of IDH1 and mitochondrial membrane potential assay based on JC-1, and mitochondrial complex I activity was also detected. The inhibitory effect of WA on the biological functions of HepG2 cells was detected along with cell viability using MTT assay, scratch assay, clone formation assay, glucose consumption and lactate production assay. Western blot and qRT-PCR were used to detect the expression of proteins and genes related to IDH1, p53 and HIF1α signaling pathways. RESULTS: We first identified that IDH1 expression was downregulated in human liver cancer cells compared to normal liver cells. Next, we found that treatment of HepG2 cells with WA resulted in significantly increased protein levels of IDH1, accompanied by decreased levels of several glycolytic enzymes. Furthermore, we found that WA stabilized IDH1 proteins by inhibiting the degradation by the proteasome. The tumor suppressor p53 was also upregulated by WA treatment, which played a critical role in the upregulation of IDH1 and downregulation of the glycolysis-related genes. Under hypoxic conditions, glycolysis-related genes were induced, which was suppressed by WA treatment, and IDH1 expression was still maintained at higher levels under hypoxia. CONCLUSION: Taken together, our results indicated that WA suppresses liver cancer tumorigenesis by p53-mediated IDH1 upregulation, which promotes mitochondrial respiration, thereby inhibiting the HIF-1α pathway and blocking aerobic glycolysis.

Expression and potential molecular mechanism of TOP2A in metastasis of non-small cell lung cancer.

DNA topoisomerase II alpha (TOP2A) expression, gene alterations, and enzyme activity have been studied in various malignant tumors. Abnormal elevation of TOP2A expression is considered to be related to the development of non-small cell lung cancer (NSCLC). However, its association with tumor metastasis and its mode of action remains unclear. Bioinformatics, real-time quantitative PCR, immunohistochemistry and immunoblotting were used to detect TOP2A expression in NSCLC tissues and cells. Cell migration and invasion assays as well as cytoskeletal staining were performed to analyze the effects of TOP2A on the motility, migration and invasion ability of NSCLC cells. Cell cycle and apoptosis assays were used to verify the effects of TOP2A on apoptosis as well as cycle distribution in NSCLC. TOP2A expression was considerably upregulated in NSCLC and significantly correlated with tumor metastasis and the occurrence of epithelial-mesenchymal transition (EMT) in NSCLC. Additionally, by interacting with the classical ligand Wnt3a, TOP2A may trigger the canonical Wnt signaling pathway in NSCLC. These observations suggest that TOP2A promotes EMT in NSCLC by activating the Wnt/ß-catenin signaling pathway and positively regulates malignant events in NSCLC, in addition to its significant association with tumor metastasis. TOP2A promotes the metastasis of NSCLC by stimulating the canonical Wnt signaling pathway and inducing EMT. This study further elucidates the mechanism of action of TOP2A, suggesting that it might be a potential therapeutic target for anti-metastatic therapy.

A CARM1 Inhibitor Potently Suppresses Breast Cancer Both In Vitro and In Vivo.

CARM1, belonging to the protein arginine methyltransferase (PRMT) family, is intricately associated with the progression of cancer and is viewed as a promising target for both cancer diagnosis and therapy. However, the number of specific and potent CARM1 inhibitors is limited. We herein discovered a CARM1 inhibitor, iCARM1, that showed better specificity and activity toward CARM1 compared to the known CARM1 inhibitors, EZM2302 and TP-064. Similar to CARM1 knockdown, iCARM1 suppressed the expression of oncogenic estrogen/ERα-target genes, whereas activated type I interferon (IFN) and IFN-induced genes (ISGs) in breast cancer cells. Consequently, iCARM1 potently suppressed breast cancer cell growth both in vitro and in vivo. The combination of iCARM1 with either endocrine therapy drugs or etoposide demonstrated synergistic effects in inhibiting the growth of breast tumors. In summary, targeting CARM1 by iCARM1 effectively suppresses breast tumor growth, offering a promising therapeutic approach for managing breast cancers in clinical settings.

Neurofibromatosis type 1 with huge intrathoracic meningoceles misdiagnosed as pleural effusion: A case report and literature review.

BACKGROUND: Neurofibromatosis type 1 is a genetic disease that affects multiple organs and systems, leading to various clinical manifestations. In Neurofibromatosis type 1, rare intrathoracic meningoceles often occur alongside bone dysplasia. These meningoceles contain cerebrospinal fluid and can be mistakenly diagnosed as 'pleural effusion'. CASE PRESENTATION: In this case report, we mistakenly identified 'cerebrospinal fluid' as 'pleural effusion' and proceeded with drainage. This error posed significant risks to the patient and holds valuable implications for the future diagnosis and treatment of similar patients. CONCLUSIONS: In patients with Neurofibromatosis type 1 complicated by spinal deformity, there is a high incidence of intrathoracic meningoceles. Treatment strategies may differ based on the specific features of the lesions, and collaboration among multiple disciplines can significantly improve patient outcomes.

Molecular mechanism of brassinosteroids involved in root gravity response based on transcriptome analysis.

BACKGROUND: Brassinosteroids (BRs) are a class of phytohormones that regulate a wide range of developmental processes in plants. BR-associated mutants display impaired growth and response to developmental and environmental stimuli. RESULTS: Here, we found that a BR-deficient mutant det2-1 displayed abnormal root gravitropic growth in Arabidopsis, which was not present in other BR mutants. To further elucidate the role of DET2 in gravity, we performed transcriptome sequencing and analysis of det2-1 and bri1-116, bri1 null mutant allele. Expression levels of auxin, gibberellin, cytokinin, and other related genes in the two mutants of det2-1 and bri1-116 were basically the same. However, we only found that a large number of JAZ (JASMONATE ZIM-domain) genes and jasmonate synthesis-related genes were upregulated in det2-1 mutant, suggesting increased levels of endogenous JA. CONCLUSIONS: Our results also suggested that DET2 not only plays a role in BR synthesis but may also be involved in JA regulation. Our study provides a new insight into the molecular mechanism of BRs on the root gravitropism.

PD-L1 knockdown suppresses vasculogenic mimicry of non-small cell lung cancer by modulating ZEB1-triggered EMT.

BACKGROUND: PD-L1 overexpression is commonly observed in various malignancies and is strongly correlated with poor prognoses for cancer patients. Moreover, PD-L1 has been shown to play a significant role in promoting angiogenesis and epithelial-mesenchymal transition (EMT) processes across different cancer types. METHODS: The relationship between PD-L1 and vasculogenic mimicry as well as epithelial-mesenchymal transition (EMT) was explored by bioinformatics approach and immunohistochemistry. The functions of PD-L1 in regulating the expression of ZEB1 and the EMT process were assessed by Western blotting and q-PCR assays. The impact of PD-L1 on the migratory and proliferative capabilities of A549 and H1299 cells was evaluated through wound healing, cell invasion, and CCK8 assays following siRNA-mediated PD-L1 knockdown. Tube formation assay was utilized to evaluate the presence of VM structures. RESULTS: In this study, increased PD-L1 expression was observed in A549 and H1299 cells compared to normal lung epithelial cells. Immunohistochemical analysis revealed a higher prevalence of VM structures in the PD-L1-positive group compared to the PD-L1-negative group. Additionally, high PD-L1 expression was also found to be significantly associated with advanced TNM stage and increased metastasis. Following PD-L1 knockdown, NSCLC cells exhibited a notable reduction in their ability to form tube-like structures. Moreover, the levels of key EMT and VM-related markers, including N-cadherin, MMP9, VE-cadherin, and VEGFA, were significantly decreased, while E-cadherin expression was upregulated. In addition, the migration and proliferation capacities of both cell lines were significantly inhibited after PD-L1 or ZEB1 knockdown. CONCLUSIONS: Knockdown PD-L1 can inhibit ZEB1-mediated EMT, thereby hindering the formation of VM in NSCLC.