Identification of HSP90B1 in pan-cancer hallmarks to aid development of a potential therapeutic target.

Heat shock proteins play crucial roles in various biochemical processes, encompassing protein folding and translocation. HSP90B1, a conserved member of the heat shock protein family, growing evidences have demonstrated that it might be closely associated with cancer development. In the present study, we employed multi-omics analyses and cohort validations to explore the dynamic expression of HSP90B1 in pan-cancer and comprehensively evaluate HSP90B1 as a novel biomarker that hold promise for precision cancer diagnostics and therapeutics. The results suggest HSP90B1 was highly expressed in various kinds of tumors, often correlating with a poor prognosis. Notably, methylation of HSP90B1 emerged as a protective factor in several cancer types. In immune infiltration analysis, the expression of HSP90B1 in most tumors showed a negative association with CD8 + T cells. HSP90B1 expression was positively correlated with microsatellite instability and tumor mutational burden. HSP90B1 expression was also discovered to be positively correlated with tumor metabolism, cell cycle-related pathways and the expression of immune checkpoint genes. The expression of HSP90B1 was mainly negatively correlated with immunostimulatory genes and positively correlated with immunosuppressive genes, as well as strongly correlated with chemokines and their receptor genes. In addition, the HSP90B1 inhibitor PU-WS13 demonstrated significant efficacy in suppressing cancer cell proliferation in both leukemic and solid tumor cells, and remarkably reduced the expression of the cancer cell surface immune checkpoint PD-L1. The single-cell RNA sequencing analysis further highlighted that HSP90B1 was significantly higher in tumor cells compared to surrounding cells, revealing a potential target therapeutic window. Taken together, HSP90B1 emerges as a promising avenue for breakthroughs in cancer diagnosis, prognosis and therapy. This study provides a rationale for HSP90B1 targeted cancer diagnosis and therapy in future.

Rosuvastatin suppresses TNF-α-induced matrix catabolism, pyroptosis and senescence via the HMGB1/NF-κB signaling pathway in nucleus pulposus cells.

Intervertebral disc degeneration is mainly caused by irregular matrix metabolism in nucleus pulposus cells and involves inflammatory factors such as TNF-α. Rosuvastatin, which is widely used in the clinic to reduce cholesterol levels, exerts anti-inflammatory effects, but whether rosuvastatin participates in IDD remains unclear. The current study aims to investigate the regulatory effect of rosuvastatin on IDD and the potential mechanism. In vitro experiments demonstrate that rosuvastatin promotes matrix anabolism and suppresses catabolism in response to TNF-α stimulation. In addition, rosuvastatin inhibits cell pyroptosis and senescence induced by TNF-α. These results demonstrate the therapeutic effect of rosuvastatin on IDD. We further find that HMGB1, a gene closely related to cholesterol metabolism and the inflammatory response, is upregulated in response to TNF-α stimulation. HMGB1 inhibition or knockdown successfully alleviates TNF-α-induced ECM degradation, senescence and pyroptosis. Subsequently, we find that HMGB1 is regulated by rosuvastatin and that its overexpression abrogates the protective effect of rosuvastatin. We then verify that the NF-κB pathway is the underlying pathway regulated by rosuvastatin and HMGB1. In vivo experiments also reveal that rosuvastatin inhibits IDD progression by alleviating pyroptosis and senescence and downregulating HMGB1 and p65. This study might provide new insight into therapeutic strategies for IDD.

Association between averaged meteorological factors and tuberculosis risk: A systematic review and meta-analysis.

Inconsistencies were discovered in the findings regarding the effects of meteorological factors on tuberculosis (TB). This study conducted a systematic review of published studies on the relationship between TB and meteorological factors and used a meta-analysis to investigate the pooled effects in order to provide evidence for future research and policymakers. The literature search was completed by August 3rd, 2021, using three databases: PubMed, Web of Science and Embase. Relative risks (RRs) in included studies were extracted and all effect estimates were combined together using meta-analysis. Subgroup analyses were carried out based on the resolution of exposure time, regional climate, and national income level. A total of eight studies were included after screening for inclusion and exclusion criteria. Our results show that TB risk was positively correlated with precipitation (RR = 1.32, 95% CI: 1.14, 1.51), while temperature (RR = 1.15, 95% CI: 1.00, 1.32), humidity (RR = 1.05, 95% CI: 0.99, 1.10), air pressure (RR = 0.89, 95% CI: 0.69, 1.14) and sunshine duration (RR = 0.95, 95% CI: 0.80, 1.13) all had no statistically significant correlation. Subgroup analysis shows that quarterly measure resolution, low and middle Human Development Index (HDI) level and subtropical climate increase TB risk not only in precipitation, but also in temperature and humidity. Moreover, less heterogeneity was observed in "high and extremely high" HDI areas and subtropical areas than that in other subgroups (I2 = 0%). Precipitation, a subtropical climate, and a low HDI level are all positive influence factors to tuberculosis. Therefore, residents and public health managers should take precautionary measures ahead of time, especially in extreme weather conditions.

Chromobox homolog 4 overexpression inhibits TNF-α-induced matrix catabolism and senescence by suppressing activation of the NF-κB signaling pathway in nucleus pulposus cells.

Intervertebral disc degeneration (IDD) is featured as enhanced catabolism of extracellular matrix (ECM) in the nucleus pulposus (NP), in which tumor necrosis factor-alpha (TNF-α)-related cell senescence is involved. Chromobox homolog protein 4 (CBX4) exhibits anti-inflammatory effects and shows promising therapeutic potential. Thus, in the present study, we explore the role of CBX4 in IDD. Immunohistochemistry staining reveals that CBX4 expression is decreased in severe degenerative NP tissues compared to mild degenerative tissues, and real-time PCR and western blot analysis results show that CBX4 expression is downregulated under TNF-α stimulation in NP cells. siRNA and adenoviruses are used to knockdown or overexpress CBX4, respectively. The results demonstrate that CBX4 knockdown augments the catabolism of ECM in human NP cells, while CBX4 overexpression in rat NP cells restores the ECM degradation induced by TNF-α, as illustrated by immunofluorescence and western blot analysis. In addition, transcriptome sequencing results reveal the regulatory effect of CBX4 on the cell cycle, and further western blot analysis and senescence-associated ß-galactosidase staining assay indicate that CBX4 overexpression alleviates cell senescence in the presence of TNF-α. Moreover, the phosphorylation of p65, which indicates the activation of NF-κB signaling, is measured by western blot analysis and immunofluorescence assay, and the results reveal that CBX4 overexpression reduces the TNF-α-induced increase in the p-p65/p65 ratio. In addition, the effect of CBX4 overexpression in NP cells is suppressed by NF-κB agonist. In summary, our results indicate that CBX4 overexpression can suppress TNF-α-induced matrix catabolism and cell senescence in the NP by inhibiting NF-κB activation. This study may provide new approaches for preventing and treating IDD.

Dynamics and Correlation Among Viral Positivity, Seroconversion, and Disease Severity in COVID-19 : A Retrospective Study.

BACKGROUND: The understanding of viral positivity and seroconversion during the course of coronavirus disease 2019 (COVID-19) is limited. OBJECTIVE: To describe patterns of viral polymerase chain reaction (PCR) positivity and evaluate their correlations with seroconversion and disease severity. DESIGN: Retrospective cohort study. SETTING: 3 designated specialty care centers for COVID-19 in Wuhan, China. PARTICIPANTS: 3192 adult patients with COVID-19. MEASUREMENTS: Demographic, clinical, and laboratory data. RESULTS: Among 12 780 reverse transcriptase PCR tests for severe acute respiratory syndrome coronavirus 2 that were done, 24.0% had positive results. In 2142 patients with laboratory-confirmed COVID-19, the viral positivity rate peaked within the first 3 days. The median duration of viral positivity was 24.0 days (95% CI, 18.9 to 29.1 days) in critically ill patients and 18.0 days (CI, 16.8 to 19.1 days) in noncritically ill patients. Being critically ill was an independent risk factor for longer viral positivity (hazard ratio, 0.700 [CI, 0.595 to 0.824]; P < 0.001). In patients with laboratory-confirmed COVID-19, the IgM-positive rate was 19.3% in the first week, peaked in the fifth week (81.5%), and then decreased steadily to around 55% within 9 to 10 weeks. The IgG-positive rate was 44.6% in the first week, reached 93.3% in the fourth week, and then remained high. Similar antibody responses were seen in clinically diagnosed cases. Serum inflammatory markers remained higher in critically ill patients. Among noncritically ill patients, a higher proportion of those with persistent viral positivity had low IgM titers (<100 AU/mL) during the entire course compared with those with short viral positivity. LIMITATION: Retrospective study and irregular viral and serology testing. CONCLUSION: The rate of viral PCR positivity peaked within the initial few days. Seroconversion rates peaked within 4 to 5 weeks. Dynamic laboratory index changes corresponded well to clinical signs, the recovery process, and disease severity. Low IgM titers (<100 AU/mL) are an independent risk factor for persistent viral positivity. PRIMARY FUNDING SOURCE: None.

Assessing the effects of elevated ozone on physiology, growth, yield and quality of soybean in the past 40 years: A meta-analysis.

Soybean (Glycine max) production is seriously threatened by ground-level ozone (O3) pollution. The goal of our study is to summarize the impacts of O3 on physiology, growth, yield, and quality of soybean, as well as root parameters. We performed meta-analysis on the collated 48 peer-reviewed papers published between 1980 and 2019 to quantitatively summarize the response of soybean to elevated O3 concentrations ([O3]). Relative to charcoal-filtered air (CF), elevated [O3] significantly accelerated chlorophyll degradation, enhanced foliar injury, and inhibited growth of soybean, evidenced by great reductions in leaf area (-20.8%), biomass of leaves (-13.8%), shoot (-22.8%), and root (-16.9%). Shoot of soybean was more sensitive to O3 than root in case of biomass. Chronic ozone exposure of about 75.5 ppb posed pronounced decrease in seed yield of soybean (-28.3%). In addition, root environment in pot contributes to higher reduction in shoot biomass and yield of soybean. Negative linear relationships were observed between yield loss and intensity of O3 treatment, AOT40. The larger loss in seed yield was significantly associated with higher reduction in shoot biomass and other yield component. This meta-analysis demonstrates the effects of elevated O3 on soybean were pronounced, suggesting that O3 pollution is still a soaring threat to the productivity of soybean in regions with high ozone levels.

Identification of miR-125b targets involved in acute promyelocytic leukemia cell proliferation.

Acute promyelocytic leukemia (APL) is characterized by the presence of the PML-RARα fusion protein. We have previously found that PML-RARα-regulated miR-125b is highly expressed in APL; however, the characteristics of the regulatory effects and mechanisms of miR-125b involved in APL proliferation have yet to be clarified. In this study, we demonstrate that miR-125b promotes the proliferation of APL cells with the involvement of the PI3K/Akt and MAPK signaling pathways. Furthermore, we identified BTG2, MAP3K11, RPS6KA1 and PRDM1 as putative targets of miR-125b, which we verified using luciferase reporter constructs. Moreover, we demonstrate that the expression of miR-125b targets is downregulated in leukemic cells in patients with APL. Thus, our results provide evidence that miR-125b can modulate multiple oncogenic cell proliferation pathways and may be a novel therapeutic target for APL.

Metabolic engineering of Corynebacterium glutamicum strain ATCC13032 to produce L-methionine.

L-Methionine-producing strain QW102/pJYW-4-hom(m) -lysC(m) -brnFE was developed from Corynebacterium glutamicum strain ATCC13032, using metabolic engineering strategies. These strategies involved (i) deletion of the gene thrB encoding homoserine kinase to increase the precursor supply, (ii) deletion of the gene mcbR encoding the regulator McbR to release the transcriptional repression to various genes in the l-methionine biosynthetic pathway, (iii) overexpression of the gene lysC(m) encoding feedback-resistant aspartate kinase and the gene hom(m) encoding feedback-resistant homoserine dehydrogenase to further increase the precursor supply, and (iv) overexpression of the gene cluster brnF and brnE encoding the export protein complex BrnFE to increase extracellular l-methionine concentration. QW102/pJYW-4-hom(m) -lysC(m) -brnFE produced 42.2 mM (6.3 g/L) l-methionine after 64-H fed-batch fermentation. These results suggest that l-methionine-producing strains can be developed from wild-type C. glutamicum strains by rationally metabolic engineering.

Bone mineral density in patients with primary ovarian insufficiency: A systematic review and Meta-Analysis.

INTRODUCTION: Premature menopause is a major complication of primary ovarian insufficiency (POI), and this loss is closely relates to bone mineral density (BMD). Previous research has indicated potential associations between BMD and POI. This study set out to provide the first systematic literature review and meta-analysison account of BMD content among women with POI. METHODS: Studies including women with POI and controls were eligible from PubMed, Embase, Cochrane Library and Web of Science databases (from their inception to April 2022). Two reviewers independently evaluated study eligibility. The meta-analysis was performed using the DerSimonian and Laird random effects model. RESULTS: Ten studies featuring 578 women with POI and 480 controls were selected. BMD content of femur neck (SMD:-0.76; 95 % CI: -1.20 to -0.31; P = 0.0008), the BMD content of nondominating forearm (SMD:-0.67; 95 % CI: -1.15 to -0.18; P = 0.007) were significantly decreased in women with POI. However, no differences were seen in other regions (lumbar spine, total hip, hipneck). DISCUSSION: The results of this study indicate that BMD content altered in patients with primary ovarian insufficiency. An implication of this is the possibility that hormone replacement therapy to minimize the prevalence of fracture morbidity and mortality associated with osteopenia in patients with POI.

Application of a Magnetic Resonance Imaging-Based Lumbar Vertebral Bone Quality Scoring System in Patients with Degenerative Lumbar Scoliosis.

BACKGROUND: Although dual-energy X-ray absorptiometry is still the gold standard for diagnosing osteoporosis, it can lead to inaccurate bone mineral density measurements due to lumbar degeneration and scoliosis. Many researchers have investigated diagnostic methods for osteoporosis in patients with degenerative lumbar scoliosis (DLS). This study aimed to investigate the differences between conventional vertebral bone quality (VBQ) scores and modified VBQ scores in patients with DLS and the influence of lumbar scoliosis on VBQ scores. METHODS: We retrospectively collected the clinical and radiological data of 68 patients with DLS admitted to Sun Yat-sen Memorial Hospital from July 2018 to April 2023. The patients were classified into one of 2 groups based on the T score of the left femoral neck. VBQ scores relative to cerebrospinal fluid at different levels, VBQ scores on different planes and single-level VBQ scores were compared. Receiver operating characteristic analysis was also performed. Different modified VBQ scores were compared between the moderate scoliosis group (10°

Glutamine Mitigates Oxidative Stress-Induced Matrix Degradation, Ferroptosis, and Pyroptosis in Nucleus Pulposus Cells via Deubiquitinating and Stabilizing Nrf2.

Aims: Intervertebral disc degeneration (IDD) is closely related to low back pain, which is a prevalent age-related problem worldwide; however, the mechanism underlying IDD is unknown. Glutamine, a free amino acid prevalent in plasma, is recognized for its anti-inflammatory and antioxidant properties in various diseases, and the current study aims to clarify the effect and mechanism of glutamine in IDD. Results: A synergistic interplay was observed between pyroptosis and ferroptosis within degenerated human disc specimens. Glutamine significantly mitigated IDD in both ex vivo and in vivo experimental models. Moreover, glutamine protected nucleus pulposus (NP) cells after tert-butyl hydroperoxide (TBHP)-induced pyroptosis, ferroptosis, and extracellular matrix (ECM) degradation in vitro. Glutamine protected NP cells from TBHP-induced ferroptosis by promoting the nuclear factor erythroid 2-related factor 2 (Nrf2) accumulation by inhibiting its ubiquitin-proteasome degradation and inhibiting lipid oxidation. Innovation and Conclusions: A direct correlation is evident in the progression of IDD between the processes of pyroptosis and ferroptosis. Glutamine suppressed oxidative stress-induced cellular processes, including pyroptosis, ferroptosis, and ECM degradation through deubiquitinating Nrf2 and inhibiting lipid oxidation in NP cells. Glutamine is a promising novel therapeutic target for the management of IDD.

Comprehensive multi-omics analysis reveals WEE1 as a synergistic lethal target with hyperthermia through CDK1 super-activation.

Hyperthermic intraperitoneal chemotherapy's role in ovarian cancer remains controversial, hindered by limited understanding of hyperthermia-induced tumor cellular changes. This limits developing potent combinatory strategies anchored in hyperthermic intraperitoneal therapy (HIPET). Here, we perform a comprehensive multi-omics study on ovarian cancer cells under hyperthermia, unveiling a distinct molecular panorama, primarily characterized by rapid protein phosphorylation changes. Based on the phospho-signature, we pinpoint CDK1 kinase is hyperactivated during hyperthermia, influencing the global signaling landscape. We observe dynamic, reversible CDK1 activity, causing replication arrest and early mitotic entry post-hyperthermia. Subsequent drug screening shows WEE1 inhibition synergistically destroys cancer cells with hyperthermia. An in-house developed miniaturized device confirms hyperthermia and WEE1 inhibitor combination significantly reduces tumors in vivo. These findings offer additional insights into HIPET, detailing molecular mechanisms of hyperthermia and identifying precise drug combinations for targeted treatment. This research propels the concept of precise hyperthermic intraperitoneal therapy, highlighting its potential against ovarian cancer.

Glutamine suppresses senescence and promotes autophagy through glycolysis inhibition-mediated AMPKα lactylation in intervertebral disc degeneration.

Regulating metabolic disorders has become a promising focus in treating intervertebral disc degeneration (IDD). A few drugs regulating metabolism, such as atorvastatin, metformin, and melatonin, show positive effects in treating IDD. Glutamine participates in multiple metabolic processes, including glutaminolysis and glycolysis; however, its impact on IDD is unclear. The current study reveals that glutamine levels are decreased in severely degenerated human nucleus pulposus (NP) tissues and aging Sprague-Dawley (SD) rat nucleus pulposus tissues, while lactate accumulation and lactylation are increased. Supplementary glutamine suppresses glycolysis and reduces lactate production, which downregulates adenosine-5'-monophosphate-activated protein kinase α (AMPKα) lactylation and upregulates AMPKα phosphorylation. Moreover, glutamine treatment reduces NP cell senescence and enhances autophagy and matrix synthesis via inhibition of glycolysis and AMPK lactylation, and glycolysis inhibition suppresses lactylation. Our results indicate that glutamine could prevent IDD by glycolysis inhibition-decreased AMPKα lactylation, which promotes autophagy and suppresses NP cell senescence.

Genomic profiling of a multi-lineage and multi-passage patient-derived xenograft biobank reflects heterogeneity of ovarian cancer.

Ovarian cancer (OC) manifests as a complex disease characterized by inter- and intra-patient heterogeneity. Despite enhanced biological and genetic insights, OC remains a recalcitrant malignancy with minimal survival improvement. Based on multi-site sampling and a multi-lineage patient-derived xenograft (PDX) establishment strategy, we present herein the establishment of a comprehensive PDX biobank from histologically and molecularly heterogeneous OC patients. Comprehensive profiling of matched PDX and patient samples demonstrates that PDXs closely recapitulate parental tumors. By leveraging multi-lineage models, we reveal that the previously reported genomic disparities of PDX could be mainly attributed to intra-patient spatial heterogeneity instead of substantial model-independent genomic evolution. Moreover, DNA damage response pathway inhibitor (DDRi) screening uncovers heterogeneous responses across models. Prolonged iterative drug exposure recapitulates acquired drug resistance in initially sensitive models. Meanwhile, interrogation of induced drug-resistant (IDR) models reveals that suppressed interferon (IFN) response and activated Wnt/ß-catenin signaling contribute to acquired DDRi drug resistance.

Proteogenomic insights into early-onset endometrioid endometrial carcinoma: predictors for fertility-sparing therapy response.

Endometrial carcinoma remains a public health concern with a growing incidence, particularly in younger women. Preserving fertility is a crucial consideration in the management of early-onset endometrioid endometrial carcinoma (EEEC), particularly in patients under 40 who maintain both reproductive desire and capacity. To illuminate the molecular characteristics of EEEC, we undertook a large-scale multi-omics study of 215 patients with endometrial carcinoma, including 81 with EEEC. We reveal an unexpected association between exposome-related mutational signature and EEEC, characterized by specific CTNNB1 and SIGLEC10 hotspot mutations and disruption of downstream pathways. Interestingly, SIGLEC10Q144K mutation in EEECs resulted in aberrant SIGLEC-10 protein expression and promoted progestin resistance by interacting with estrogen receptor alpha. We also identified potential protein biomarkers for progestin response in fertility-sparing treatment for EEEC. Collectively, our study establishes a proteogenomic resource of EEECs, uncovering the interactions between exposome and genomic susceptibilities that contribute to the development of primary prevention and early detection strategies for EEECs.

Effect of Alleviating Fibrosis with EGCG-Modified Bone Graft in Murine Model Depended on Less Accumulation of Inflammatory Macrophage.

In response to current trends in the modification of guided bone regeneration (GBR) materials, we aimed to build upon our previous studies on epigallocatechin-3-gallate (EGCG) by immersing a commonly used bone graft primarily composed of hydroxyapatite (HA) in EGCG solution, expecting to obtain superior bone material integration after implantation. Bone grafts are commonly used for bone repair, in which the bone extracellular matrix is stimulated to promote osteogenesis. However, due to its profibrosis effect, this osteoconductive material commonly exhibits implant failure. In addition to providing a basic release profile of EGCG-modified bone graft (E-HA) to clarify the relationship between this material and the environment, we have examined the integration effect via subcutaneous implantation experiments. In this manner, we have assessed the aggregation of proinflammatory macrophages, the formation of fibrous capsules, and an enhanced cell viability observed in cultured RAW 264.7 cells. Among these results, we focus on proinflammatory macrophages due to their close relationship with fibrosis, which is the most important process in the immune response. Immunofluorescent staining results showed that E-HA substantially compromised the formation of fibrous capsules in hematoxylin-eosin-stained sections, which exhibited less proinflammatory macrophage recruitment; meanwhile, the cell viability was improved. This work lays the foundation for future studies on GBR.

Pan-cancer analysis of IFN-γ with possible immunotherapeutic significance: a verification of single-cell sequencing and bulk omics research.

Background: Interferon-gamma (IFN-γ), commonly referred to as type II interferon, is a crucial cytokine that coordinates the tumor immune process and has received considerable attention in tumor immunotherapy research. Previous studies have discussed the role and mechanisms associated with IFN-γ in specific tumors or diseases, but the relevant role of IFN-γ in pan-cancer remains uncertain. Methods: TCGA and GTEx RNA expression data and clinical data were downloaded. Additionally, we analyzed the role of IFN-γ on tumors by using a bioinformatic approach, which included the analysis of the correlation between IFN-γ in different tumors and expression, prognosis, functional status, TMB, MSI, immune cell infiltration, and TIDE. We also developed a PPI network for topological analysis of the network, identifying hub genes as those having a degree greater than IFN-γ levels. Result: IFN-γ was differentially expressed and predicted different survival statuses in a majority of tumor types in TCGA. Additionally, IFN-γ expression was strongly linked to factors like infiltration of T cells, immune checkpoints, immune-activating genes, immunosuppressive genes, chemokines, and chemokine receptors, as well as tumor purity, functional statuses, and prognostic value. Also, prognosis, CNV, and treatment response were all substantially correlated with IFN-γ-related gene expression. Particularly, the IFN-γ-related gene STAT1 exhibited the greatest percentage of SNVs and the largest percentage of SNPs in UCEC. Elevated expression levels of IFN-γ-related genes were found in a wide variety of tumor types, and this was shown to be positively linked to drug sensitivity for 20 different types of drugs. Conclusion: IFN-γ is a good indicator of response to tumor immunotherapy and is likely to limit tumor progression, offering a novel approach for immunotherapy's future development.

Comprehensive landscape of the IPAF inflammasomes in pan-cancer: A bulk omics research and single-cell sequencing validation.

BACKGROUND: IPAF (ICE-protease Activating Factor) is a nucleotide-binding/leucine-rich repeat (NLR) protein known as the cysteine-associated recruitment domain 12 (CARD12). Previous studies only discuss the role of IPAF inflammasomes in specific tumors. The role of IPAF inflammasomes in pan-cancer is still unclear. Therefore, we performed a comprehensive analysis of IPAF inflammasome in 33 tumors. METHODS: We used databases like The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) from the UCSC XENA (http://xena.ucsc.edu/) to retrieve and analyze gene expression. The influence of IPAF inflammasome on the prognosis of tumor patients was analyzed using univariate Cox regression analysis and Kaplan-Meier survival analysis. Furthermore, we conducted the following analysis: Single-sample gene set enrichment analysis, single-cell level functional state analysis, single-cell sequencing, immune cell infiltration analysis, and tumor immune dysfunction and exclusion (TIDE) score. RESULTS: First, the differential expression of IPAF inflammasome-related genes (IPAF-RGs) in 33 tumors were analyzed. The results revealed that IPAF-RGs were significantly and differentially expressed in eight tumors. The prognostic significance of IPAF inflammasome scores was different in different tumors. A positive correlation was observed between IPAF inflammasomes scores and CD8+ T cells in most tumors. Further analysis revealed that IPAF inflammasome might affect tumor immunity mainly by mediating effector T cell recruitment via the expression of chemokines such as CXCL9, CXCL10, and CCL5. The analysis of TIDE and IPAF inflammasome scores revealed a significant negative correlation between IPAF inflammasome and TIDE scores in 11 tumors. CONCLUSION: A pan-cancer analysis of IPAF inflammasome in various tumors was performed. The results highlight the potential value of IPAF inflammasome in response to immunotherapy in patients and provide a new direction for future immunotherapy.

BRD9 Inhibition Attenuates Matrix Degradation and Pyroptosis in Nucleus Pulposus by Modulating the NOX1/ROS/NF-κB axis.

Intervertebral disc degeneration (IDD) is considered to be the leading cause of low back pain (LBP). The progression of IDD is closely related to the inflammatory microenvironment, which results in extracellular matrix degradation and cell death. One of the proteins, which have been shown to participate in the inflammatory response, is the bromodomain-containing protein 9 (BRD9). This study aimed to investigate the role and mechanism of BRD9 in regulating IDD. The tumor necrosis factor-α (TNF-α) was used to mimic the inflammatory microenvironment in vitro. Western blot, RT-PCR, immunohistochemistry, immunofluorescence, and flow cytometry were used to demonstrate the effect of BRD9 inhibition or knockdown on matrix metabolism and pyroptosis. We found that the expression of BRD9 was upregulated as IDD progressed. BRD9 inhibition or knockdown alleviated TNF-α-induced matrix degradation, reactive oxygen species (ROS) production, and pyroptosis in rat nucleus pulposus cells. Mechanistically, RNA-seq was used to investigate the mechanism of BRD9 in promoting IDD. Further investigation revealed that BRD9 regulated NOX1 expression. Inhibition of NOX1 could abrogate matrix degradation, ROS production, and pyroptosis caused by BRD9 overexpression. In vivo, the radiological and histological evaluation showed that the pharmacological inhibition of BRD9 alleviated IDD development in rat IDD model. Our results indicated that BRD9 could promote IDD via the NOX1/ROS/ NF-κB axis by inducing matrix degradation and pyroptosis. Targeting BRD9 may be a potential therapeutic strategy in treating IDD.

Is there an association between the lunar phases and hospital admission for different episode types in bipolar disorder? A retrospective study in northern China.

The effects of the moon on mental activities remain contentious. Few studies have investigated associations between lunar phases and different types of bipolar disorder (BD) episodes. In the current study, 7,452 patients with BD from three hospitals were enrolled. Patients were divided into two groups on the basis of episode types, and the effects of lunar phase were examined for each type. The cosinor analysis revealed moon-related rhythmicity in admissions for BD in a period of 14.75 days. There were fewer admissions around the new moon and the full moon. There was no significant difference between different groups in acrophase. There was possibly a temporal lag between the onset of BD and hospitalization. Thus, it is too early to draw firm conclusions about the impact of lunar phases on BD. Sleep might be a middle way from moon effect to admissions of BD. These results have implications for future disease prevention strategies and research.