Hydrogel dressings for diabetic foot ulcer: A systematic review and meta-analysis.

AIM: To investigate the differences in utility between conventional dressings and hydrogel dressings for the treatment of diabetic foot ulcer (DFU). METHODS: The PubMed, Embase, Cochrane Library, CNKI, VIP and Wanfang databases were systematically searched up to 21 January 2023. Fixed/random-effect models were used to calculate the odds ratios (ORs) and mean differences (MDs) with 95% confidence intervals (CIs) for the effect size analysis, with heterogeneity determined by I2 statistics. Subgroup analyses of different classes of hydrogel were also conducted. RESULTS: A total of 15 randomized controlled trials with 872 patients were eligible for the present analysis. Compared with conventional dressings, hydrogel dressings significantly improved the healing rate (OR 4.09, 95% CI 2.83 to 5.91), shortened the healing time (MD -11.38, 95% CI -13.11 to -9.66), enhanced granulation formation (MD -3.60, 95% CI -4.21 to -3.00) and epithelial formation (MD -2.82, 95% CI -3.19 to -2.46), and reduced the incidence of bacterial infection (OR 0.10, 95% CI 0.05 to 0.18). CONCLUSION: The meta-analysis showed that hydrogel dressings are more effective in treating DFU compared with conventional dressings.

Potential added value of computed tomography radiomics to multimodal prediction models for benign and malignant breast tumors.

Background: Early diagnosis is crucial to the treatment of breast cancer, but conventional imaging detection is challenging. Radiomics has the potential to improve early diagnostic efficacy in a noninvasive manner. This study examined whether integrating computed tomography (CT) radiomics information based on ultrasound (US) models can improve the efficacy of breast cancer prediction. Methods: We retrospectively analyzed 420 patients with pathologically confirmed benign or malignant breast tumors. Clinical data and examination images were collected, and the population was divided into training (n=294) and validation (n=126) groups at a ratio of 7:3. The region of interest (ROI) was manually segmented along the tumor boundary using MaZda software, and the features of each ROI was extracted. After dimension reduction and screening, the best features were retained. Subsequently, random forest (RF), support vector machines, and K-nearest neighbor classifiers were used to establish prediction models in an US and combined-methods group. Results: Finally, 8 of the 379 features were retained in the US group. Random forest was found to be the best model, and the area under the curve (AUC) of the training and validation groups was 0.90 [95% confidence interval (CI): 0.852-0.942] and 0.85 (95% CI: 0.775-0.930), respectively. Meanwhile, 12 of the 750 features were retained in the combined group. In this regard, random forest proved to be the best model, and the AUC of the training and validation group was 0.95 (95% CI: 0.918-0.981) and 0.92 (95% CI: 0.866-0.969), respectively. The calibration curve showed a good fit of the model. The decision curve showed that the clinical net benefit of the combined group was far greater than that of any single examination, and the prediction model of the combined group exhibited a degree of practical clinical value. Conclusions: The combined model based on US and CT images has potential application value in the prognostic prediction of benign and malignant breast diseases.

Omicron BA.4/5 neutralization and cell-mediated immune responses in relation to baseline immune status and breakthrough infection among PLWH: A follow-up cohort study.

There is a paucity of data on hybrid immunity (vaccination plus breakthrough infection [BI]), especially cell-mediated responses to Omicron among immunosuppressed patients. We aim to investigate humoral and cellular responses to Omicron BA.4/5 among people living with HIV (PLWH) with/without BIs, the most prevalent variant of concern after the reopening of China. Based on our previous study, we enrolled 77 PLWH with baseline immune status of severe acute respiratory syndrome coronavirus 2 specific antibodies after inactivated vaccination. "Correlates of protection," including serological immunoassays, T cell phenotypes and memory B cells (MBC) were determined in PLWH without and with BI, together with 16 PLWH with reinfections. Higher inhibition rate of neutralizing antibodies (NAb) against BA.4/5 was elicited among PLWH with BI than those without. Omicron-reactive IL4+ CD8+ T cells were significantly elevated in PLWH experienced postvaccine infection contrasting with those did not. NAb towards wild type at baseline was associated with prolonged negative conversion time for PLWH whereas intermediate MBCs serve as protecting effectors. We uncovered that hybrid immunity intensified more protection on BA.4/5 than vaccination did. Strengthened surveillance on immunological parameters and timely clinical intervention on PLWH deficient in protection would reduce the severity and mortality in the context of coexistence with new Omicron subvariants.

Navigating Community-Based Aged Care Services From the Consumer Perspective: A Scoping Review.

BACKGROUND AND OBJECTIVES: The shift to consumer-directed aged care means that older adults need to play a more active role in navigating the complex aged care system for adequate health and social services. Challenges in the navigation process result in unmet needs and difficulty accessing available resources. This scoping review investigates how aged care navigation is conceptualized in literature and interrogates research on the experiences of older adults navigating community-based aged care services with or without support from their informal carers. RESEARCH DESIGN AND METHODS: This review follows the Joanna Briggs Institute methodological guidelines. PubMed, Scopus, and ProQuest were searched for relevant literature published from 2008 to 2021, supplemented by grey literature and manual reference list searching. Data were extracted using a predefined data-extraction table and synthesized with an inductive thematic analysis. RESULTS: The current conceptualization of aged care navigation focuses on the support provided to older adults, rather than actions taken by older adults themselves. Thematic analysis from the included studies (n = 26) revealed shared themes (lack of knowledge, social networks as information providers, complex care systems) among older adults and informal carers; unique challenges faced by older adults (difficulties with technology, waiting game), and informal carers (structural burden) in aged care navigation. DISCUSSION AND IMPLICATIONS: Findings suggest the need to comprehensively assess individual circumstances including social networks and access to informal carers as predictors of successful navigation. Changes that reduce the complexity of the aged care system and improve coordination will relieve the structural burden experienced by consumers.

Visualization of the relationship between macrophage and wound healing from the perspective of bibliometric analysis.

Macrophages play a crucial role in aiding all phases of the wound-healing process and has garnered increasing attention recently. Although a substantial body of related studies has been published, there remains a lack of comprehensive bibliometric analysis. In this study, we collected 4296 papers from the Web of Science Core Collection database. Three tools including CiteSpace, VOSviewer and one online analytical platform were employed to conduct bibliometric analysis and data visualization. Our results revealed that the annual number of publications related to macrophage and wound healing has increased exponentially with the year. The United States and China stand as the primary driving forces within this field, collectively constituting 58.2% of the total publication output. The application of biomaterials was one of the most concerned research areas in this field. According to references analysis, the current research focus has shifted to diabetic wound healing and regulating macrophage polarization. Based on the keywords analysis, we identified the following research frontiers in the future: exosomes and other extracellular vesicles; bio-derived materials and drug delivery methods such as nanoparticles, scaffolds and hydrogels; immunomodulation and macrophage polarization in the M2-state; chronic wounds, particularly those associated with diabetes; antimicrobial peptides; and antioxidant. Additionally, TNF, IL-6, IL-10, TGF-ß1 and VEGF ranked as the five genes that have garnered the most research attention in the intersection of macrophage and wound healing. All in all, our findings offered researchers a holistic view of the ongoing progress in the field of macrophages and wound healing, serving as a valuable reference for scholars and policymakers in this domain.

Discovery of indole analogues from Periplaneta americana extract and their activities on cell proliferation and recovery of ulcerative colitis in mice.

Background: As an important medicinal insect, Periplaneta americana (PA) has been applied for the treatment of wounds, burns, and ulcers with fewer side effects and a reduced recurrence rate, which provides great potential for developing new drugs based on its active constituents. Materials and methods: The main chromatographic peaks determined by high performance liquid chromatography (HPLC) in the PA concentrated ethanol-extract liquid (PACEL) were separated, purified, and identified by semi-preparative LC, mass spectrum, and 1H NMR spectroscopic analysis. The biological activities of the identified compounds were investigated by methylthiazolyldiphenyl-tetrazolium bromide (MTT) method based on in vitro human skin fibroblasts (HSF) and in vivo experiments based on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) mouse model. Furthermore, RT-qPCR of six genes related to inflammation or intestinal epithelial cell proliferation was employed to investigate the molecular mechanism of the indole analogues recovering UC in mice. Results: Five indole analogues were purified and identified from PACEL, including tryptophan (Trp), tryptamine (pa01), 1,2,3,4-tetrahydrogen-ß-carboline-3-carboxylic acid (pa02), (1S, 3S)-1-methyl-1,2,3,4-tetrahydrogen-ß-carboline-3-carboxylic acid (pa03), and (1R, 3S)-1-methyl-1,2,3,4-tetrahydrogen-ß-carboline-3-carboxylic acid (pa04), among which the pa02 and pa04 were reported in PA for the first time. In vitro and in vivo experiments showed that PACEL, Trp, and pa02 had promoting HSF proliferation activity and intragastric administration of them could alleviate symptoms of weight loss and colon length shortening in the UC mice. Although recovery activity of the compound pa01 on the colon length was not as obvious as other compounds, it showed anti-inflammatory activity in histological analysis. In addition, The RT-qPCR results indicated that the three indole analogues could alleviate DSS-induced intestinal inflammation in mice by inhibiting pro-inflammatory cytokines (MMP7, IL1α) and down-regulating BMP8B expression. Conclusion: This study reported the isolation, purification, structure identification, and biological activity of the active indole analogues in PACEL. It was found for the first time that the PA extract contained many indole analogues and Trp, which exhibited good proliferation activity on HSF fibroblasts as well as anti-UC activity in mice. These indole analogues probably are important components related to the pharmacological activity in PA.

Scientific knowledge graph and trend analysis of Tuina: A bibliometric analysis.

OBJECTIVES: Tuina is an effective complementary and alternative therapy. However, no bibliometric analysis has explored the global research status and emerging trends of tuina. Therefore, our study aimed to provide a perspective on the current state and frontier trends in the field. DESIGN: Bibliometric analysis SETTING: Tuina-related publications between January 1, 2003, and December 31, 2022, were obtained from the Web of Science Core Collection database. MAIN OUTCOME MEASURES: The knowledge graph software CiteSpace and VOSViewer were used to quantitatively analyse annual trends in annual publication volume, journals, countries, institutions, authors, cited references, and keywords. RESULTS: Overall, 1877 articles were obtained. Consequently, the number of annual publications in tuina gradually increased. China published the most articles (1402 articles, 58.01%), followed by the Chinese Academy of Sciences (110 articles, 2.57%). Original and review articles were the two main types of publications. Photonics Research ranked first (101 articles, 5.38%) as the most influential affiliate and productive journal. These articles come from 8423 authors, among whom Min Fang published the most publications, and Ernst E was co-cited most often. According to the keyword co-occurrence analysis, the new research frontiers were meta-analyses. CONCLUSION: This comprehensive bibliometric study analysed the publications on tuina and presented them visually, revealing new research trends, pivotal points, research hotspots, and frontiers. Prospective strategies and potential directions for further studies were also provided.

The AEG-1-USP10-PARP1 axis confers radioresistance in esophageal squamous cell carcinoma via facilitating homologous recombination-dependent DNA damage repair.

Radiotherapy is the standard adjuvant treatment for esophageal squamous cell carcinoma (ESCC), yet radioresistance remains a major obstacle leading to treatment failure and unfavorable prognosis. Previous reports have demonstrated the involvement of astrocyte elevated gene-1 (AEG-1) in tumorigenesis and progression of multiple malignancies. Nevertheless, the precise role of AEG-1 in the radioresistance of ESCC remains elusive. Here, we unveiled a strong correlation between aberrant AEG-1 gene overexpression and malignant progression as well as adverse prognosis in ESCC patients. Moreover, both in vitro and in vivo investigations revealed that AEG-1 significantly alleviated irradiation-induced DNA damage and enhanced radiation resistance in ESCC cells. Mechanistically, AEG-1 recruited the deubiquitinase USP10 to remove the K48-linked polyubiquitin chains at the Lys425 of PARP1, thus preventing its proteasomal degradation. This orchestrated process facilitated homologous recombination-mediated DNA double-strand breaks (DSBs) repair, culminating in mitigated DNA damage and acquired radioresistance in ESCC cells. Notably, PARP1 overexpression reversed the radiosensitizing effect caused by AEG-1 deficiency. Collectively, these findings shed new light on the mechanism of ESCC radioresistance, providing potential therapeutic targets to enhance the efficacy of radiotherapy in ESCC.

PFKFB3-driven vascular smooth muscle cell glycolysis promotes vascular calcification via the altered FoxO3 and lactate production.

A link between increased glycolysis and vascular calcification has recently been reported, but it remains unclear how increased glycolysis contributes to vascular calcification. We therefore investigated the role of PFKFB3, a critical enzyme of glycolysis, in vascular calcification. We found that PFKFB3 expression was upregulated in calcified mouse VSMCs and arteries. We showed that expression of miR-26a-5p and miR-26b-5p in calcified mouse arteries was significantly decreased, and a negative correlation between Pfkfb3 mRNA expression and miR-26a-5p or miR-26b-5p was seen in these samples. Overexpression of miR-26a/b-5p significantly inhibited PFKFB3 expression in VSMCs. Intriguingly, pharmacological inhibition of PFKFB3 using PFK15 or knockdown of PFKFB3 ameliorated vascular calcification in vD3 -overloaded mice in vivo or attenuated high phosphate (Pi)-induced VSMC calcification in vitro. Consistently, knockdown of PFKFB3 significantly reduced glycolysis and osteogenic transdifferentiation of VSMCs, whereas overexpression of PFKFB3 in VSMCs induced the opposite effects. RNA-seq analysis and subsequent experiments revealed that silencing of PFKFB3 inhibited FoxO3 expression in VSMCs. Silencing of FoxO3 phenocopied the effects of PFKFB3 depletion on Ocn and Opg expression but not Alpl in VSMCs. Pyruvate or lactate supplementation, the product of glycolysis, reversed the PFKFB3 depletion-mediated effects on ALP activity and OPG protein expression in VSMCs. Our results reveal that blockade of PFKFB3-mediated glycolysis inhibits vascular calcification in vitro and in vivo. Mechanistically, we show that FoxO3 and lactate production are involved in PFKFB3-driven osteogenic transdifferentiation of VSMCs. PFKFB3 may be a promising therapeutic target for the treatment of vascular calcification.

Advances in isothermal nucleic acid amplification methods for hepatitis B virus detection.

Hepatitis B virus (HBV) infection is a major global health problem of widespread concern. Clinically, serological assays are the most widely used diagnostic tests for HBV infection, with the presence of HBsAg in the serum being indicative of acute and chronic hepatitis B infection. However, increased identification of HBV DNA positive but HBsAg negative cases has greatly promoted the use of molecular assays for more accurate HBV diagnosis. Over the past few decades, especially since the outbreak of COVID-19, significant advancements have been made in the techniques and devices for nucleic acid testing (NAT). Nowadays, the mainstream NAT techniques can broadly be split into two categories: PCR-based methods and non-PCR-based isothermal amplification methods. As achieving point-of-care testing (POCT) or on-site testing is an important development tendency for the next-generation NAT, non-PCR-based isothermal amplification methods like nucleic acid sequence-based amplification (NASBA), rolling circle amplification (RCA), loop-mediated isothermal amplification (LAMP), helicase-dependent amplification (HDA), and recombinase polymerase amplification (RPA) have garnered significant attention in recent years. In this review, we provide a comprehensive overview of the nucleic acid isothermal amplification technologies currently used for HBV detection. The analytical performances of different methods are compared and their integration with microfluidics, lateral flow assays, and CRISPR/Cas systems is also discussed.

Alterations in the gut virome are associated with type 2 diabetes and diabetic nephropathy.

Although changes in gut microbiome have been associated with the development of T2D and its complications, the role of the gut virome remains largely unknown. Here, we characterized the gut virome alterations in T2D and its complications diabetic nephropathy (DN) by metagenomic sequencing of fecal viral-like particles. Compared with controls, T2D subjects, especially those with DN, had significantly lower viral richness and diversity. 81 viral species were identified to be significantly altered in T2D subjects, including a decrease in some phages (e.g. Flavobacterium phage and Cellulophaga phaga). DN subjects were depleted of 12 viral species, including Bacteroides phage, Anoxybacillus virus and Brevibacillus phage, and enriched in 2 phages (Shigella phage and Xylella phage). Multiple viral functions, particularly those of phage lysing host bacteria, were markedly reduced in T2D and DN. Strong viral-bacterial interactions in healthy controls were disrupted in both T2D and DN. Moreover, the combined use of gut viral and bacterial markers achieved a powerful diagnostic performance for T2D and DN, with AUC of 99.03% and 98.19%, respectively. Our results suggest that T2D and its complication DN are characterized by a significant decrease in gut viral diversity, changes in specific virus species, loss of multiple viral functions, and disruption of viral-bacterial correlations. The combined gut viral and bacterial markers have diagnostic potential for T2D and DN.

An artificial neural network-based radiomics model for predicting the radiotherapy response of advanced esophageal squamous cell carcinoma patients: a multicenter study.

Radiotherapy benefits patients with advanced esophageal squamous cell carcinoma (ESCC) in terms of symptom relief and long-term survival. In contrast, a substantial proportion of ESCC patients have not benefited from radiotherapy. This study aimed to establish and validate an artificial neural network-based radiomics model for the pretreatment prediction of the radiotherapy response of advanced ESCC by using integrated data combined with feasible baseline characteristics of computed tomography. A total of 248 patients with advanced ESCC who underwent baseline CT and received radiotherapy were enrolled in this study and were analyzed by two types of radiomics models, machine learning and deep learning. As a result, the Att. Resnet50 pretrained network model indicated superior performance, with AUCs of 0.876, 0.802 and 0.732 in the training, internal validation, and external validation cohorts, respectively. Similarly, our Att. Resnet50 pretrained network model showed excellent calibration and significant clinical benefit according to the C index and decision curve analysis. Herein, a novel pretreatment radiomics model was established based on deep learning methods and could be used for radiotherapy response prediction in advanced ESCC patients, thus providing reliable evidence for therapeutic decision-making.

Radiation induces IRAK1 expression to promote radioresistance by suppressing autophagic cell death via decreasing the ubiquitination of PRDX1 in glioma cells.

Radiotherapy is the standard adjuvant treatment for glioma patients; however, the efficacy is limited by radioresistance. The function of Interleukin-1 receptor associated kinase 1 (IRAK1) in tumorigenesis and radioresistance remains to be elucidated. IRAK1 expression and its correlation with prognosis were analyzed in glioma tissues. We found that glioma patients with overexpressed IRAK1 show a poor prognosis. Notably, ionizing radiation (IR) remarkably induces IRAK1 expression, which was decreased by STING antagonist H-151 treatment. JASPAR prediction, ChIP assays, and dual luciferase reporter assays indicated that transcription factor FOXA2, suppressed by STING inhibition, directly binds to the IRAK1 promoter region and activates its transcription. IRAK1 knockdown inhibits malignancy and enhances the radiosensitivity of glioma in vitro and in vivo. To explore the potential IRAK1 interacting targets mediating the radioresistance of glioma cells, IP/Co-IP, LC-MS/MS, GST pull-down, and ubiquitination analyses were conducted. Mechanistically, IRAK1 bound to PRDX1, a major member of antioxidant enzymes, and further prevents ubiquitination and degradation of PRDX1 mediated by E3 ubiquitin ligase HECTD3; Both the DOC and HECT domains of HECTD3 directly interacted with PRDX1 protein. Overexpression of PRDX1 reverses the radiotherapy sensitization effect of IRAK1 depletion by diminishing autophagic cell death. These results suggest the IRAK1-PRDX1 axis provides a potential therapeutic target for glioma patients.

Effects of L-carnitine supplementation on glucolipid metabolism: a systematic review and meta-analysis.

Background: L-carnitine supplementation has been utilized against glucolipid metabolism disruption. However, to the best of our knowledge, no meta-analysis process has analyzed the effects of L-carnitine supplementation on insulin resistance, fasting blood glucose, lipid metabolism, and liver enzyme levels in adults. Methods: Through the analysis and screening of 12 221 studies, 15 studies were selected from eligible trials for meta-analysis. Meta-analysis was performed in a random effect model with heterogeneity determined by I2, and subgroup analyses were used to further identify the source of heterogeneity. Result: The results showed significant effects of L-carnitine on FBG (MD = -4.94 mg dL-1, 95% CI: -7.07 to -2.82), insulin (MD = -0.99 µU mL-1, 95% CI: -1.41 to -0.56), HOMA-IR (MD = -0.58, 95% CI: -0.77 to -0.38), TG (MD = -11.22 mg dL-1, 95% CI: -19.21 to -3.22), TC (MD = -6.45 mg dL-1, 95% CI: -9.95 to -2.95, LDLc (MD = -8.28 mg dL-1, 95% CI: -11.08 to -5.47), and ALT (MD = -19.71 IU L-1, 95% CI: -36.45 to -2.96). However, no significant effect of L-carnitine supplementation was observed in HDLc (MD = -0.77 mg dL-1, 95% CI: -0.10 to -1.63) or AST (MD = -11.05 IU L-1, 95% CI: -23.08 to 0.99). The duration of carnitine supplementation was negatively associated with mean differences in FBG, as assessed by meta-regression. Conclusion: The current meta-analysis revealed that L-carnitine may have favorable effects on glucolipid profile, especially insulin, FBG, HOMA-IR, TG, TC, LDLc, and ALT levels.

SETD2 regulates chromatin accessibility and transcription to suppress lung tumorigenesis.

SETD2, a H3K36 trimethyltransferase, is the most frequently mutated epigenetic modifier in lung adenocarcinoma, with a mutation frequency of approximately 9%. However, how SETD2 loss of function promotes tumorigenesis remains unclear. Using conditional Setd2-KO mice, we demonstrated that Setd2 deficiency accelerated the initiation of KrasG12D-driven lung tumorigenesis, increased tumor burden, and significantly reduced mouse survival. An integrated chromatin accessibility and transcriptome analysis revealed a potentially novel tumor suppressor model of SETD2 in which SETD2 loss activates intronic enhancers to drive oncogenic transcriptional output, including the KRAS transcriptional signature and PRC2-repressed targets, through regulation of chromatin accessibility and histone chaperone recruitment. Importantly, SETD2 loss sensitized KRAS-mutant lung cancer to inhibition of histone chaperones, the FACT complex, or transcriptional elongation both in vitro and in vivo. Overall, our studies not only provide insight into how SETD2 loss shapes the epigenetic and transcriptional landscape to promote tumorigenesis, but they also identify potential therapeutic strategies for SETD2 mutant cancers.

Morphological specificity analysis of an image-based 3D model of airway filling in a difficult airway.

BACKGROUND: The purpose of this study was to analyze position-specific morphological changes of the upper airway and to further assess the impact of these changes in difficult airway during intubation. METHODS: This observational comparative study included two groups (n = 20 patients/group): Group A had normal airway and Group B had difficult airway. Data obtained from two-dimensional magnetic resonance imaging were imported to Mimics V20.0 software for processing. We then reconstructed three-dimensional models of upper airway filling in patients in the supine and maximum extension position based on the imaging data. Those models were projected on coronal, sagittal, and horizontal planes to investigate multiple morphological features. We measured the surface area, radial length, and corner angle of the projected areas. RESULTS: Group A had larger upper airway filling volumes compared to Group B The volumes for the supine position were 6,323.83 ± 156.06 mm3 for Group A and 5,336.22 ± 316.13 mm3 for Group B (p = 0.003). The volumes the maximum extension position were 9,186.58 ± 512.61 mm3 for Group A and 6,735.46 ± 794.63 mm3 for Group B (p = 0.003). Airway volume increased in the upper airway filling model as the body position varied from the supine to maximum extension position (Group A: volume increase 2,953.75 ± 524.6 mm3, rate of change 31%; Group B: volume increase 1,632.89 ± 662.66 mm3, rate of change 25%; p = 0.052). CONCLUSION: The three-dimensional reconstruction model developed in this study was used to digitally quantify morphological features of a difficult airway and could be used as a novel airway management assessment tool.

Molecular mechanisms of neuroendocrine differentiation in prostate cancer progression.

BACKGROUND: Rapid evolution of the therapeutic management of prostate cancer, especially in in second-generation androgen inhibitors, has increased the opportunity of transformation from prostate cancer (PCa) to neuroendocrine prostate cancer (NEPC). NEPC still lacks effective diagnostic and therapeutic interventions. Researches into the molecular characteristics of neuroendocrine differentiation is undoubtedly crucial to the discovery of new target genes for accurate diagnostic and therapeutic targets. PURPOSE: In this review, we focus on the relevant genes and molecular mechanisms that have contributed to the transformation in the progression of PCa and discuss the potential targeted molecule that might improve diagnostic accuracy and therapeutic effectiveness. METHODS: The relevant literatures from PubMed have been reviewed for this article. CONCLUSION: Several molecular characteristics influence the progression of neuroendocrine differentiation of prostate cancer which will provide a novel sight for accurate diagnosis and target therapeutic intervention for patients with NEPC.

SETD2 loss perturbs the kidney cancer epigenetic landscape to promote metastasis and engenders actionable dependencies on histone chaperone complexes.

SETD2 is a histone H3 lysine 36 (H3K36) trimethyltransferase that is mutated with high prevalence (13%) in clear cell renal cell carcinoma (ccRCC). Genomic profiling of primary ccRCC tumors reveals a positive correlation between SETD2 mutations and metastasis. However, whether and how SETD2 loss promotes metastasis remains unclear. In this study, we used a SETD2-mutant (SETD2MT) metastatic ccRCC human-derived cell line and xenograft models and showed that H3K36me3 restoration greatly reduced distant metastases of ccRCC in mice in a matrix metalloproteinase 1 (MMP1)-dependent manner. An integrated multiomics analysis using assay for transposase-accessible chromatin using sequencing (ATAC-seq), chromatin immunoprecipitation-sequencing (ChIP-seq) and RNA sequencing (RNA-seq) established a tumor suppressor model in which loss of SETD2-mediated H3K36me3 activates enhancers to drive oncogenic transcriptional output through regulation of chromatin accessibility. Furthermore, we uncovered mechanism-based therapeutic strategies for SETD2-deficient cancer through the targeting of specific histone chaperone complexes, including ASF1A/ASF1B and SPT16. Overall, SETD2 loss creates a permissive epigenetic landscape for cooperating oncogenic drivers to amplify transcriptional output, providing unique therapeutic opportunities.

RFC2: a prognosis biomarker correlated with the immune signature in diffuse lower-grade gliomas.

Diffuse lower-grade gliomas (LGG) represent the highly heterogeneous and infiltrative neoplasms in the central nervous system (CNS). Replication factor C 2 (RFC2) is a subunit of the RFC complex that modulates DNA replication and repair. However, the prognosis value of RFC2 and its association with the immune signature of tumor microenvironment (TME) in LGG remains unknown. Based on Oncomine, TCGA, GTEx, TIMER, GEPIA, and HPA databases, we evaluated RFC2 expression levels and its clinical prognostic value in LGG and other cancers. Then we analyzed the correlations between RFC2 expression and tumor mutation burden (TMB), tumor microsatellite instability (MSI), and mismatch repair (MMR) genes across cancers. And CIBERSORT and ESTIMATE algorithms were conducted to estimate the association of RFC2 with immune cell infiltration of LGG. Additionally, we performed the functional enrichment analyses of RFC2 in LGG. Then functional experiments were employed to further validate the oncogenic role of RFC2 in LGG. Our results showed that RFC2 was widely highly expressed in most types of cancer. And its expression was closely related to the clinicopathological features and prognosis in LGG and other cancer types. RFC2 levels were also correlated with TMB and MSI across various cancers. Furthermore, RFC2 was positively associated with the infiltration levels of immune cells and immune checkpoint genes in LGG. Additionally, in vitro experiments revealed that RFC2 played an oncogenic role in LGG progression. In conclusion, our findings revealed that RFC2 could serve as a reliable biomarker to predict the prognosis and immune signature for LGG.