Interlamellar-Spacing Engineering of Stable and Toxicity-Reduced 2D Perovskite Single Crystal for High-Resolution X-ray Imaging.

Two-dimensional (2D) lead halide perovskites are excellent candidates for X-ray detection due to their high resistivity, high ion migration barrier, and large X-ray absorption coefficients. However, the high toxicity and long interlamellar distance of the 2D perovskites limit their wide application in high sensitivity X-ray detection. Herein, we demonstrate stable and toxicity-reduced 2D perovskite single crystals (SCs) realized by interlamellar-spacing engineering via a distortion self-balancing strategy. The engineered low-toxicity 2D SC detectors achieve high stability, large mobility-lifetime product, and therefore high-performance X-ray detection. Specifically, the detectors exhibit a record high sensitivity of 13488 µC Gy1- cm-2, a low detection limit of 8.23 nGy s-1, as well as a high spatial resolution of 8.56 lp mm-1 in X-ray imaging, all of which are far better than those of the high-toxicity 2D lead-based perovskite detectors. These advances provide a new technical solution for the low-cost fabrication of low-toxicity, scalable X-ray detectors.

SEH1L siliencing induces ferroptosis and suppresses hepatocellular carcinoma progression via ATF3/HMOX1/GPX4 axis.

SEH1 like nucleoporin (SEH1L) is an important component of nuclear pore complex (NPC), which is crucial in the regulation of cell division. However, the interrelation between SEH1L expression and tumor progression is less studied. In this research, we performed a systematic bioinformatic analysis about SEH1L using TCGA, Timer 2.0, Cbioportal, UCLAN and CellMiner™ databases in pan-cancer. Besides, we further validated the bioinformatic results through in vitro and in vivo experiments in HCC, including transcriptome sequencing, real-time quantitative PCR (RT-qPCR), western blotting (WB), immunohistochemistry (IHC), cell proliferation assays, clone formation, EdU, transwell, flow cytometry and subcutaneous tumor model. Our results suggested that SEH1L was significantly up-regulated and related to poor prognosis in most cancers, and may serve as a potential biomarker. SEH1L could promote HCC progression in vitro and in vivo. Besides, the next generation sequencing suggested that 684 genes was significantly up-regulated and 678 genes was down-regulated after the knock down of SEH1L. SEH1L siliencing could activate ATF3/HMOX1/GPX4 axis, decrease mitochondrial membrane potential and GSH, but increase ROS and MDA, and these effects could be reversed by the knock down of ATF3. This study indicated that SEH1L siliencing could induce ferroptosis and suppresses hepatocellular carcinoma (HCC) progression via ATF3/HMOX1/GPX4 axis.

Analysis of differentially expressed genes in torn rotator cuff tendon tissues in diabetic patients through RNA-sequencing.

BACKGROUND: Rotator cuff tears (RCT) is a common musculoskeletal disorder in the shoulder which cause pain and functional disability. Diabetes mellitus (DM) is characterized by impaired ability of producing or responding to insulin and has been reported to act as a risk factor of the progression of rotator cuff tendinopathy and tear. Long non-coding RNAs (lncRNAs) are involved in the development of various diseases, but little is known about their potential roles involved in RCT of diabetic patients. METHODS: RNA-Sequencing (RNA-Seq) was used in this study to profile differentially expressed lncRNAs and mRNAs in RCT samples between 3 diabetic and 3 nondiabetic patients. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis were performed to annotate the function of the differentially expressed genes (DEGs). LncRNA-mRNA co-expression network and competing endogenous RNA (ceRNA) network were constructed to elucidate the potential molecular mechanisms of DM affecting RCT. RESULTS: In total, 505 lncRNAs and 388 mRNAs were detected to be differentially expressed in RCT samples between diabetic and nondiabetic patients. GO functional analysis indicated that related lncRNAs and mRNAs were involved in metabolic process, immune system process and others. KEGG pathway analysis indicated that related mRNAs were involved in ferroptosis, PI3K-Akt signaling pathway, Wnt signaling pathway, JAK-STAT signaling pathway and IL-17 signaling pathway and others. LncRNA-mRNA co-expression network was constructed, and ceRNA network showed the interaction of differentially expressed RNAs, comprising 5 lncRNAs, 2 mRNAs, and 142 miRNAs. TF regulation analysis revealed that STAT affected the progression of RCT by regulating the apoptosis pathway in diabetic patients. CONCLUSIONS: We preliminarily dissected the differential expression profile of lncRNAs and mRNAs in torn rotator cuff tendon between diabetic and nondiabetic patients. And the bioinformatic analysis suggested some important RNAs and signaling pathways regarding inflammation and apoptosis were involved in diabetic RCT. Our findings offer a new perspective on the association between DM and progression of RCT.

A multi-omics analysis reveals CLSPN is associated with prognosis, immune microenvironment and drug resistance in cancers.

BACKGROUND: Immunotherapy is effective only in limited patients. It is urgent to discover a novel biomarker to predict immune cells infiltration status and immunotherapy response of different cancers. CLSPN has been reported to play a pivotal role in various biological processes. However, a comprehensive analysis of CLSPN in cancers has not been conducted. METHODS: To show the whole picture of CLSPN in cancers, a pan-cancer analysis was conducted in 9125 tumor samples across 33 cancer types by integrating transcriptomic, epigenomic and pharmacogenomics data. Moreover, the role of CLSPN in cancer was validated by CCK-8, EDU, colony formation and flow cytometry in vitro and tumor cell derived xenograft model in vivo. RESULTS: CLSPN expression was generally upregulated in most cancer types and was significantly associated with prognosis in different tumor samples. Moreover, elevated CLSPN expression was closely correlated with immune cells infiltration, TMB (tumor mutational burden), MSI (microsatellite instability), MMR (mismatch repair), DNA methylation and stemness score across 33 cancer types. Enrichment analysis of functional genes revealed that CLSPN participated in the regulation of numerous signaling pathways involved in cell cycle and inflammatory response. The expression of CLSPN in LUAD patients were further analyzed at the single-cell level. Knockdown CLSPN significantly inhibited cancer cell proliferation and cell cycle related cyclin-dependent kinase (CDK) family and Cyclin family expression in LUAD (lung adenocarcinoma) both in vitro and in vivo experiments. Finally, we conducted structure-based virtual screening by modelling the structure of CHK1 kinase domain and Claspin phosphopeptide complex. The top five hit compounds were screened and validated by molecular docking and Connectivity Map (CMap) analysis. CONCLUSION: Our multi-omics analysis offers a systematic understanding of the roles of CLSPN in pan-cancer and provides a potential target for future cancer treatment.

Circular RNA Sequencing Reveals Serum Exosome Circular RNA Panel for High-Grade Astrocytoma Diagnosis.

BACKGROUND: Although major advances have been made in the histopathological diagnosis of high-grade astrocytoma (HGA), methods for effective and noninvasive diagnosis remain largely unknown. Exosomes can cross the blood-brain barrier and are readily accessible in human biofluids, making them promising biomarkers for HGA. Circular RNAs (circRNAs) have potential as tumor biomarkers owing to their stability, conservation, and tissue specificity. However, the landscape and characteristics of exosome circRNAs in HGA remain to be studied. METHODS: CircRNA deep sequencing and bioinformatics approaches were used to generate a circRNA profiling database and analyze the features of HGA cell circRNAs and HGA cell-derived exosome circRNAs. Exosome circRNA expression in the serum and tissues of healthy individuals and patients with HGA was detected using reverse transcription-quantitative PCR. Additionally, the receiver operating characteristic curve and overall survival curves were analyzed. RESULTS: By investigating the characteristics of HGA cell-derived exosome circRNAs and HGA cell circRNAs, we observed that exosomes were more likely to enrich short-exon and suppressor circRNAs than HGA cells. Moreover, a serum exosome circRNA panel including hsa_circ_0075828, hsa_circ_0003828, and hsa_circ_0002976 could be used to screen for HGA, whereas a good prognosis panel comprised high concentrations of hsa_circ_0005019, hsa_circ_0000880, hsa_circ_0051680, and hsa_circ_0006365. CONCLUSIONS: This study revealed a comprehensive circRNA landscape in HGA exosomes and cells. The serum exosome circexosome circRNA panel and tissue circRNAs are potentially useful for HGA liquid biopsy and prognosis monitoring. Exosome circRNAs as novel targets should facilitate further biomarker discovery and aid in HGA diagnosis and therapy monitoring.

AMICA1 is a diagnostic and prognostic biomarker and induces immune cells infiltration by activating cGAS-STING signaling in lung adenocarcinoma.

BACKGROUND: Adhesion molecule interacting with CXADR antigen 1 (AMICA1), also known as Junction Adhesion Molecule Like (JAML), a recently identified member of the JAMs family, plays a critical role in mediating cancer development and immune cells transmigration. However, AMICA1 has never been reported to be related to the genesis, development and immunotherapy effect of lung adenocarcinoma (LUAD). In this research, we investigated the role of AMICA1 in LUAD through bioinformatic analysis and in vitro experiments. METHODS: Bioinformatic analysis from TCGA and GEO databases were used to investigate the expression level of AMICA1 and the correlation between AMICA1 and clinical parameters in LUAD patients. The LinkedOmics database was analyzed to investigate the co-expression network of AMICA1. TIMER and TISIDB databases were used to analyze the correlation between AMICA1 expression and immune infiltration level. Except for bioinformatic analysis, the AMICA1 mRNA (26 patients) and protein level (6 patients) were also detected by real-time PCR and western blot. The infiltration level of CD8+ T cells (15 patients) and PD1+ T cells (13 patients) were detected by immunohistochemistry. The diagnostic value of AMICA1 was revealed by receiver operating characteristic (ROC) curves. The Spearman correlation coefficient was used to analyze the correlation between AMICA1 expression and CD8+ T cells and PD1+ T cells infiltration level. RESULTS: Bioinformatic data from public database and our data showed that AMICA1 was significantly downregulated in LUAD. Decreased AMICA1 expression in LUAD was associated with higher T stage, M stage and pathological stage. Kaplan-Meier survival analysis indicated that patients with low AMICA1 expression had a worse prognosis. ROC curves showed that AMICA1 had high diagnostic accuracy for LUAD patients. Multivariate Cox analysis further displayed that AMICA1 expression level was an independent prognostic factor for LUAD patients. Moreover, the expression of AMICA1 was significantly different in the immune cells subtype and was obviously linked to immune cells infiltration. In vitro experiments suggested that AMICA1 significantly suppressed the proliferation of LUAD cells and played an important role in activating cGAS-STING signaling. CONCLUSIONS: Our study suggested that AMICA1 might function as a diagnostic and prognostic biomarker and significantly suppressed the proliferation of LUAD cells. Besides, AMICA1 is positively correlated with immune cells infiltration in LUAD, and cGAS-STING signaling might play an important role in the process.

A comprehensive analysis of the efficacy and safety of COVID-19 vaccines.

The numbers of cases and deaths from coronavirus disease 2019 (COVID-19) are continuously increasing. Many people are concerned about the efficacy and safety of the COVID-19 vaccines. We performed a comprehensive analysis of the published trials of COVID-19 vaccines and the real-world data from the Vaccine Adverse Event Reporting System. Globally, our research found that the efficacy of all vaccines exceeded 70%, and RNA-based vaccines had the highest efficacy of 94.29%; moreover, Black or African American people, young people, and males may experience greater vaccine efficacy. The spectrum of vaccine-related adverse drug reactions (ADRs) is extremely broad, and the most frequent ADRs are pain, fatigue, and headache. Most ADRs are tolerable and are mainly grade 1 or 2 in severity. Some severe ADRs have been identified (thromboembolic events, 21-75 cases per million doses; myocarditis/pericarditis, 2-3 cases per million doses). In summary, vaccines are a powerful tool that can be used to control the COVID-19 pandemic, with high efficacy and tolerable ADRs. In addition, the spectrum of ADRs associated with the vaccines is broad, and most of the reactions appear within a week, although some may be delayed. Therefore, ADRs after vaccination need to be identified and addressed in a timely manner.

CircRNA: functions and properties of a novel potential biomarker for cancer.

Circular RNAs, a novel class of endogenous noncoding RNAs, are characterized by their covalently closed loop structures without a 5' cap or a 3' Poly A tail. Although the mechanisms of circular RNAs' generation and function are not fully clear, recent research has shown that circular RNAs may function as potential molecular markers for disease diagnosis and treatment and play an important role in the initiation and progression of human diseases, especially in tumours. This review summarizes some information about categories, biogenesis, functions at the molecular level, properties of circular RNAs and the possibility of circular RNAs as biomarkers in cancers.

Converting "cold" to "hot": epigenetics strategies to improve immune therapy effect by regulating tumor-associated immune suppressive cells.

Significant developments in cancer treatment have been made since the advent of immune therapies. However, there are still some patients with malignant tumors who do not benefit from immunotherapy. Tumors without immunogenicity are called "cold" tumors which are unresponsive to immunotherapy, and the opposite are "hot" tumors. Immune suppressive cells (ISCs) refer to cells which can inhibit the immune response such as tumor-associated macrophages (TAMs), myeloid-derived suppressor cells (MDSCs), regulatory T (Treg) cells and so on. The more ISCs infiltrated, the weaker the immunogenicity of the tumor, showing the characteristics of "cold" tumor. The dysfunction of ISCs in the tumor microenvironment (TME) may play essential roles in insensitive therapeutic reaction. Previous studies have found that epigenetic mechanisms play an important role in the regulation of ISCs. Regulating ISCs may be a new approach to transforming "cold" tumors into "hot" tumors. Here, we focused on the function of ISCs in the TME and discussed how epigenetics is involved in regulating ISCs. In addition, we summarized the mechanisms by which the epigenetic drugs convert immunotherapy-insensitive tumors into immunotherapy-sensitive tumors which would be an innovative tendency for future immunotherapy in "cold" tumor.

A Hybrid Scaffold Induces Chondrogenic Differentiation and Enhances In Vivo Cartilage Regeneration.

Extensively researched tissue engineering strategies involve incorporating cells into suitable biomaterials, offering promising alternatives to boost tissue repair. In this study, a hybrid scaffold, Gel-DCM, which integrates a photoreactive gelatin-hyaluronic acid hydrogel (Gel) with an oriented porous decellularized cartilage matrix (DCM), was designed to facilitate chondrogenic differentiation and cartilage repair. The Gel-DCM exhibited excellent biocompatibility in vitro, promoting favorable survival and growth of human adipose-derived stem cells (hADSCs) and articular chondrocytes (hACs). Gene expression analysis indicated that the hACs expanded within the Gel-DCM exhibited enhanced chondrogenic phenotype. In addition, Gel-DCM promoted chondrogenesis of hADSCs without the supplementation of exogenous growth factors. Following this, in vivo experiments were conducted where empty Gel-DCM or Gel-DCM loaded with hACs/hADSCs were used and implanted to repair osteochondral defects in a rat model. In the control group, no implants were delivered to the injury site. Interestingly, macroscopic, histological, and microcomputed tomography scanning results revealed superior cartilage restoration and subchondral bone reconstruction in the empty Gel-DCM group compared with the control group. Moreover, both hACs-loaded and hADSCs-loaded Gel-DCM implants exhibited superior repair of hyaline cartilage and successful reconstruction of subchondral bone, whereas defects in the control groups were predominantly filled with fibrous tissue. These observations suggest that the Gel-DCM can provide an appropriate three-dimensional chondrogenic microenvironment, and its combination with reparative cell sources, ACs or ADSCs, holds great potential for facilitating cartilage regeneration.

Immune infiltration related CENPI associates with the malignant features and drug resistance of lung adenocarcinoma.

Centromere protein I (CENPI) is an important member of centromeric proteins family, which is crucial to chromosome alignment and segregation. Nevertheless, the interrelation between CENPI expression and tumor progression is in the shadows. In this reserch, we carried out a panoramic bioinformatic analysis about CENPI with TCGA, Timer 2.0, Oncomine, GEPIA, Cbioportal, LinkedOmics and CancerSEA databases. Besides, our bioinformatic results have been further confirmed through in vitro experiments, including Real-Time quantitative PCR (RT-qPCR), immunofluorescence (IF), immunohistochemistry (IHC), western blotting (WB), cell proliferation assays, EdU, cell cycle and apoptosis test. Our results suggested that CENPI was increased in most of the cancers, and may serve as a potential biomarker. What's more, the knock down of CENPI inhibited the expression of CDK2 in lung adenocarcinoma (LUAD), and resulted in the arrest of G0/G1 phase and apoptosis. Besides, CENPI was related to immune cells infiltration and drug sensitivity in pan-cancer, and can act as a potential treatment target to cure cancer patients.

The causal relationship between 41 inflammatory cytokines and hypothyroidism: bidirectional two-sample Mendelian randomization study.

Objective: Investigating the association between inflammatory cytokines and hypothyroidism remains challenging due to limitations in traditional observational studies. In this study, we employed Mendelian randomization (MR) to assess the causal relationship between 41 inflammatory cytokines and hypothyroidism. Method: Inflammatory cytokines in 30,155 individuals of European ancestry with hypothyroidism and in a GWAS summary containing 8,293 healthy participants were included in the study for bidirectional two-sample MR analysis. We utilized inverse variance weighting (IVW), weighted median (WM), and Mendelian randomization-Egger (MR-Egger) methods. Multiple sensitivity analyses, including MR-Egger intercept test, leave-one-out analysis, funnel plot, scatterplot, and MR-PRESSO, were applied to evaluate assumptions. Results: We found evidence of a causal effect of IL-7 and macrophage inflammatory protein-1ß (MIP-1ß) on the risk of hypothyroidism, and a causal effect of hypothyroidism on several cytokines, including granulocyte colony-stimulating factor (G-CSF), IL-13, IL-16, IL-2rα, IL-6, IL-7, IL-9, interferon-γ-inducible protein 10 (IP10), monokine induced by interferon (IFN)-γ (MIG), macrophage inflammatory protein-1ß (MIP-1ß), stem cell growth factors-ß (SCGF-ß), stromal cell derived factor-1α (SDF-1α), and tumor necrosis factor-α (TNF-α). Conclusion: Our study suggests that IL-7 and MIP-1ß may play a role in the pathogenesis of hypothyroidism, and that hypothyroidism may induce a systemic inflammatory response involving multiple cytokines. These findings may have implications for the prevention and treatment of hypothyroidism and its complications. However, further experimental studies are needed to validate the causal relationships and the potential of these cytokines as drug targets.

RASGRP2 is a potential immune-related biomarker and regulates mitochondrial-dependent apoptosis in lung adenocarcinoma.

Background: Ras guanine nucleotide-releasing protein 2 (RASGRP2), one of the guanine nucleotide exchange factors (GEFs), has attracted much attention in recent years. However, the correlation between RASGRP2 and immune infiltration and malignant features in lung adenocarcinoma (LUAD) has rarely been mentioned. Methods: The Limma package and the LASSO regression model were performed to screen for differentially expressed genes. Data from the TCGA and 5 GEO databases were used to explore the expression level of RASGRP2 in LUAD patients. A weighted co-expression network and LinkFinder module were established to find the related genes of RASGRP2. The ESTIMATE algorithm was used to analyze the correlation between RASGRP2 and immune infiltration in LUAD. Tumor-infiltrating immune cells were sorted and sequenced at the single-cell level to analyze differences in RASGRP2. Real-time PCR and immunohistochemistry were performed in the real-world cohort to verify the expression of RASGRP2 and its correlation with immune-related genes. Clone formation and EdU assays were used to verify the proliferation ability. The proportion of apoptotic cells was analyzed by flow cytometry. Observation of mitochondrial membrane potential (MMP) changes by fluorescence microscopy. Results: Our results suggested that decreased RASGRP2 was associated with worse clinical parameters and prognosis in LUAD patients. And we constructed a FLI1-HSA-miR-1976-RASGRP2 transcriptional network to support the role of RASGRP2. Enrichment analysis revealed that RASGRP2 was involved in lymphocyte activation and leukocyte adhesion. RASGRP2 was found to be positively correlated with the infiltration of most immune cells, immunoregulators, and chemokines in a subsequent study. Meanwhile, the real-world cohort confirmed that the expression levels of PDCD1, CTLA4, CD40LG, CCL14, CXCR5, and CCR7 were higher in the high-RASGRP2 expression group. Cytological experiments proved that RASGRP2 inhibited cell proliferation in LUAD by regulating mitochondrial-dependent apoptosis. Conclusion: RASGRP2 was a potential immune-related biomarker of LUAD. In addition, RASGRP2 was involved in the malignant progression of LUAD through the regulation of mitochondrial-dependent apoptosis.

A Multi-Omics Analysis of NASH-Related Prognostic Biomarkers Associated with Drug Sensitivity and Immune Infiltration in Hepatocellular Carcinoma.

Background: Nonalcoholic steatohepatitis (NASH)-driven hepatocellular carcinoma (HCC) is becoming a major health-related problem. The exploration of NASH-related prognostic biomarkers and therapeutic targets is necessary. Methods: Data were downloaded from the GEO database. The "glmnet" package was used to identify differentially expressed genes (DEGs). The prognostic model was constructed by the univariate Cox and LASSO regression analyses. Validation of the expression and prognosis by immunohistochemistry (IHC) in vitro. Drug sensitivity and immune cell infiltration were analyzed by CTR-DB and ImmuCellAI. Results: We constructed a prognostic model that identified the NASH-related gene set (DLAT, IDH3B, and MAP3K4), which was validated in a real-world cohort. Next, seven prognostic transcription factors (TFs) were identified. The prognostic ceRNA network included three mRNAs, four miRNAs, and seven lncRNAs. Finally, we found that the gene set was associated with drug response which was validated in six clinical trial cohorts. Moreover, the expression level of the gene set was inversely correlated with CD8 T cell infiltration in HCC. Conclusions: We established a NASH-related prognostic model. Upstream transcriptome analysis and the ceRNA network provided clues for mechanism exploration. The mutant profile, drug sensitivity, and immune infiltration analysis further guided precise diagnosis and treatment strategies.

Incorporating marine particulate carbon into machine learning for accurate estimation of coastal chlorophyll-a.

Accurate predictions of coastal ocean chlorophyll-a (Chl-a) concentrations are necessary for dynamic water quality monitoring, with eutrophication as a critical factor. Prior studies that used the driven-data method have typically overlooked the relationship between Chl-a and marine particulate carbon. To address this gap, marine particulate carbon was incorporated into machine learning (ML) and deep learning (DL) models to estimate Chl-a concentrations in the Yang Jiang coastal ocean of China. Incorporating particulate organic carbon (POC) and particulate inorganic carbon (PIC) as predictors can lead to successful Chl-a estimation. The Gaussian process regression (GPR) model significantly outperforming the DL model in terms of stability and robustness. A lower POC/Chl-a ratio was observed in coastal areas, in contrast to the higher ratios detected in the southern regions of the study area. This study highlights the efficacy of the GPR model for estimating Chl-a and the importance of considering POC in modeling Chl-a concentrations.

Lipophagy-related gene RAB7A is involved in immune regulation and malignant progression in hepatocellular carcinoma.

BACKGROUND: RAB7A (RAS-related in Brain 7A) is an important member of the RAS oncogene family. However, the correlation between RAB7A and the development and immune infiltration of hepatocellular carcinoma (HCC) has rarely been studied. Here, we studied the role of RAB7A in HCC through bioinformatics analysis, real-world cohort validation, and in vitro experimental exploration. MATERIALS AND METHODS: The RAB7A expression level was analyzed through TCGA, HPA and TISIDB databases. TIMER and TISCH were used to analyze the correlation between RAB7A and tumor immune microenvironment. The expression of RAB7A was detected through real-time PCR and western blotting. The cell proliferation was detected by EdU and CCK8. Wound-healing and transwell assays were used to test the invasion and migration ability. Cell cycle distribution and reactive oxygen species (ROS) content were analyzed by flow cytometry. Identification of epithelial-mesenchymal transition (EMT) was performed by immunofluorescence double staining. Immunohistochemistry (IHC) was used to evaluate the correlation between RAB7A and immune checkpoints. RESULTS: RAB7A is upregulated in most of the tumor types, and the upregulation of RAB7A is associated with a poorer prognosis in many cancers. The results showed that RAB7A was significantly positively correlated with the infiltration of macrophages and cancer-associated fibroblasts (CAFs), but negatively correlated with M2-type macrophages in most tumors. The single-cell atlas also revealed the distribution and proportion of RAB7A in immune cells of HCC. The in vitro experiments suggested that RAB7A was increased in HCC tissue and cell lines. The knockdown of RAB7A inhibited the activation of the PIK3CA-AKT pathway and suppressed the expression of CDK4, CDK6 and CCNA2. Knockdown of RAB7A induced G0/G1 arrest and ROS accumulation in HCC. In addition, overexpression of RAB7A enhanced migration and invasion by inducing EMT. The real-world cohort showed that the expression level of RAB7A was positively correlated with the expression levels of TGFBR1 and PD-L1. CONCLUSIONS: RAB7A may serve as a potential tumor prognostic and immune infiltration-related biomarker, predicting immunotherapy efficacy in certain cancer types, especially in HCC. Besides, RAB7A was a multi-pathway target involved in the malignant progression of HCC.

Have one's view of the important overshadowed by the trivial: chronic progressive external ophthalmoplegia combined with unilateral facial nerve injury: a case report and literature review.

Chronic progressive external ophthalmoplegia (CPEO) is a mitochondrial encephalomyopathy that is characterized by progressive ptosis and impaired ocular motility. Owing to its nonspecific clinical manifestations, CPEO is often misdiagnosed as other conditions. Herein, we present the case of a 34-year-old woman who primarily presented with incomplete left eyelid closure and limited bilateral eye movements. During the 6-year disease course, she was diagnosed with myasthenia gravis and cranial polyneuritis. Finally, skeletal muscle tissue biopsy confirmed the diagnosis. Biopsy revealed pathological changes in mitochondrial myopathy. Furthermore, mitochondrial gene testing of the skeletal muscle revealed a single chrmM:8469-13447 deletion. In addition, we summarized the findings of 26 patients with CPEO/Kearns-Sayre syndrome who were misdiagnosed with other diseases owing to ocular symptoms. In conclusion, we reported a rare clinical case and emphasized the symptomatic diversity of CPEO. Furthermore, we provided a brief review of the diagnosis and differential diagnosis of the disease.

MTFR2 shapes a barrier of immune microenvironment in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death in the world. Mitochondrial fission regulator 2 (MTFR2) is involved in the development of various cancers. However, the roles of MTFR2 in HCC remain unknown. In this study, we conducted a comprehensive analysis of MTFR2 in HCC, which was generated from integrative MTFR2 analyses of eight HCC cell lines, and three datasets (public dataset, real-world dataset, and immunotherapy dataset) derived from bulk HCC tissues, survival, and immunotherapy data. We demonstrated that the expression level of MTFR2 is upregulated in HCC, leading to poor prognosis. MTFR2 is positively correlated with the level of immune cell infiltration, multiple immune checkpoints and immunotherapy response prediction pathways, and acts as an important role in cancer-immunity cycle. In conclusion, our work indicates that MTFR2 can shape a barrier of immune microenvironment and result in poor prognosis in hepatocellular carcinoma, but the immune barrier may be broken by immunotherapy.

A cancer-associated fibroblast subtypes-based signature enables the evaluation of immunotherapy response and prognosis in bladder cancer.

Bladder cancer (BLCA) is one of the most prevalent and heterogeneous urinary malignant tumors. Previous researches have reported a significant association between cancer-associated fibroblasts (CAFs) and poor prognosis of tumor patients. However, uncertainty surrounds the role of CAFs in the BLCA tumor microenvironment, necessitating further investigation into the CAFs-related gene signatures in BLCA. In this study, we identified three CAF subtypes in BLCA according to single-cell RNA-seq data and constructed CAFs-related risk score (CRRS) by screening 102,714 signatures. The survival analysis, ROC curves, and nomogram suggested that CRRS was a valuable predictor in 2,042 patients from 9 available public datasets and Xiangya real-world cohort. We further revealed the significant correlation between CRRS and clinicopathological characteristics, genome alterations, and epithelial-mesenchymal transition (EMT). A high CRRS indicated a non-inflamed phenotype and a lower remission rate of immunotherapy in BLCA. In conclusion, the CRRS had the potential to predict the prognosis and immunotherapy response of BLCA patients.

Pan-Cancer and Single-Cell Analysis Reveals CENPL as a Cancer Prognosis and Immune Infiltration-Related Biomarker.

Background: Centromere protein L (CENPL) is an important member of the centromere protein (CENP) family. However, the correlation between CENPL expression and cancer development and immune infiltration has rarely been studied. Here, we studied the role of CENPL in pan-cancer and further verified the results in lung adenocarcinoma (LUAD) through in vitro experiments. Methods: The CENPL expression level was studied with TIMER 2.0 and Oncomine databases. The potential value of CENPL as a diagnostic and prognostic biomarker in pan-cancer was evaluated with the TCGA database and GEPIA. The CENPL mutation character was analyzed using the cBioPortal database. The LinkedOmics and CancerSEA databases were used to carry out the function analysis of CENPL. The role of CENPL in immune infiltration was studied using the TIMER and TISIDB websites. Moreover, the expression of CENPL was detected through RT-qPCR and Western blotting. Immunohistochemistry was used to evaluate the infiltration level of CD8+ T cells. Cell proliferation was detected by EdU and CCK8. A flow cytometer was used to analyze the influence of CENPL in cell cycle and apoptosis. Results: CENPL was increased in most of the cancers. The upregulation and mutation of CENPL were associated with a poorer prognosis in many cancers. The results showed a significant positive correlation between CENPL and myeloid-derived suppressor cell (MDSC) infiltration and a negative correlation between CENPL and T-cell NK infiltration in most of the cancers. CENPL regulated cell proliferation and cell cycle, and was negatively correlated with the inflammation level of LUAD. The in vitro experiments suggested that CENPL was increased in LUAD tissue and cell lines. There was a negative correlation between CENPL expression and CD8+ T-cell infiltration. The knockdown of CENPL significantly suppressed the expression of CDK2 and CCNE2, and induced G0/G1 arrest and apoptosis of LUAD. Conclusions: CENPL may function as a potential biomarker and oncogene in pan-cancer, especially LUAD. Furthermore, CENPL was associated with immune cell infiltration in pan-cancer, providing a potential immune therapy target for tumor treatment.