A novel heterozygous variant of the SALL1 gene with atypical Townes-Brocks syndrome phenotypes in Chinese family.

Townes-Brocks syndrome (TBS) is an autosomal dominant disorder characterised by the triad of anorectal, thumb, and ear malformations. It may also be accompanied by defects in kidney, heart, eyes, hearing, and feet. TBS has been demonstrated to result from heterozygous variants in the SALL1 gene, which encodes zinc finger protein believed to function as a transcriptional repressor. The clinical characteristics of an atypical TBS phenotype patient from a Chinese family are described, with predominant manifestations including external ear dysplasia, unilateral renal hypoplasia with mild renal dysfunction, and hearing impairment. A novel heterozygous variant c.3060T>A (p.Tyr1020*) in exon 2 of the SALL1 gene was identified in this proband. Pyrosequencing of the complementary DNA of the proband revealed that the variant transcript accounted for 48% of the total transcripts in peripheral leukocytes, indicating that this variant transcript has not undergone nonsense-mediated mRNA decay. This variant c.3060T > A is located at the terminal end of exon 2, proximal to the 3' end of the SALL1 gene, and exerts a relatively minor impact on protein function. We suggest that the atypical TBS phenotype observed in the proband may be attributed to the truncated protein retaining partial SALL1 function.

Functional analysis of the CTNS gene exonic variants predicted to affect splicing.

Cystinosis is a severe, monogenic systemic disease caused by variants in CTNS gene. Currently, there is growing evidence that exonic variants in many diseases can affect pre-mRNA splicing. The impact of CTNS gene exonic variants on splicing regulation may be underestimated due to the lack of routine studies at the RNA level. Here, we analyzed 59 exonic variants in the CTNS gene using bioinformatics tools and identified candidate variants that may induce splicing alterations by minigene assays. We identified six exonic variants that induce splicing alterations by disrupting the ratio of exonic splicing enhancers/exonic splicing silencers (ESEs/ESSs) or by interfering with the recognition of classical splice sites, or both. Our results help in the correct molecular characterization of variants in cystinosis and inform emerging therapies. Furthermore, our work suggests that the combination of in silico and in vitro assays facilitates to assess the effects of DNA variants driving rare genetic diseases on splicing regulation and will enhance the clinical utility of variant functional annotation.

Differentiation of Sinonasal NKT From Diffuse Large B-Cell Lymphoma Using Machine Learning and MRI-Based Radiomics.

PURPOSE: The aim of this study was to construct and validate a noninvasive radiomics method based on magnetic resonance imaging to differentiate sinonasal extranodal natural killer/T-cell lymphoma from diffuse large B-cell lymphoma. METHODS: We collected magnetic resonance imaging scans, including contrast-enhanced T1-weighted imaging and T2-weighted imaging, from 133 patients with non-Hodgkin lymphoma (103 sinonasal extranodal natural killer/T-cell lymphoma and 30 diffuse large B-cell lymphoma) and randomly split them into training and testing cohorts at a ratio of 7:3. Clinical characteristics and image performance were analyzed to build a logistic regression clinical-image model. The radiomics features were extracted on contrast-enhanced T1-weighted imaging and T2-weighted imaging images. Maximum relevance minimum redundancy, selectKbest, and the least absolute shrinkage and selection operator algorithms (LASSO) were applied for feature selection after balancing the training set. Five machine learning classifiers were used to construct the single and combined sequences radiomics models. Sensitivity, specificity, accuracy, precision, F1score, the area under receiver operating characteristic curve, and the area under precision-recall curve were compared between the 15 models and the clinical-image model. The diagnostic results of the best model were compared with those of 2 radiologists. RESULTS: The combined sequence model using support vector machine proves to be the best, incorporating 7 features and providing the highest values of specificity (0.903), accuracy (0.900), precision (0.727), F1score (0.800), and area under precision-recall curve (0.919) with relatively high sensitivity (0.889) in the testing set, along with a minimum Brier score. The diagnostic results differed significantly ( P < 0.05) from those of radiology residents, but not significantly ( P > 0.05) from those of experienced radiologists. CONCLUSIONS: Magnetic resonance imaging based on machine learning and radiomics to identify the type of sinonasal non-Hodgkin lymphoma is effective and has the potential to help radiology residents for diagnosis and be a supplement for biopsy.

Identification of exosomal miR-484 role in reprogramming mitochondrial metabolism in pancreatic cancer through Wnt/MAPK axis control.

The microRNAs (miRNAs) are potent regulators of tumorigenesis in various cancers, especially pancreatic cancer. The abnormal expression of miRNAs can be observed in tumor cells. Noteworthy, miRNAs could be transferred by exosomes as small extracellular vesicles in regulation of carcinogenesis. This research focused on exploring the roles and mechanisms of exosomal miR-484, derived from human bone marrow mesenchymal stem cells (hBMSCs), in the context of molecular interactions and regulation of mitochondrial metabolism. Exosomes were isolated for the examination of miR-484 expression. The impacts of hBMSCs-derived exosomal miR-484 on pancreatic cancer cells were studied using various assays. Evaluation of mitochondrial function and metabolism was performed. Wnt/MAPK pathway-related protein expression was assessed, and an in vivo tumor xenograft model was utilized to examine the functions. Our findings demonstrated a decreased miR-484 expression in pancreatic cancer cells. However, hBMSCs-derived exosomal miR-484 inhibited the proliferation and migration of these cells, while inducing apoptosis. Moreover, miR-484 led to an upsurge in reactive oxygen species production, a decrease in ATP levels, and a disruption in mitochondrial metabolism. In vivo analyses showed that hBMSCs-derived exosomal miR-484 lessened tumor size and weight, while also suppressing the expression of mitochondrial biomarkers. Further, there was a decline in ß-catenin and p-p38 protein levels both in vitro and in vivo. The addition of LiCl restored the disrupted mitochondrial metabolism. Conclusively, our results suggest that hBMSCs-derived exosomal miR-484 mitigates the malignant transformation and mitochondrial metabolism of pancreatic cancer by deactivating the Wnt/MAPK pathway.

Targeting neoadjuvant chemotherapy-induced metabolic reprogramming in pancreatic cancer promotes anti-tumor immunity and chemo-response.

The molecular dynamics of pancreatic ductal adenocarcinoma (PDAC) under chemotherapy remain incompletely understood. The widespread use of neoadjuvant chemotherapy (NAC) provides a unique opportunity to investigate PDAC samples post-chemotherapy. Leveraging a cohort from Fudan University Shanghai Cancer Center, encompassing PDAC samples with and without exposure to neoadjuvant albumin-bound paclitaxel and gemcitabine (AG), we have compiled data from single-cell and spatial transcriptomes, proteomes, bulk transcriptomes, and metabolomes, deepening our comprehension of the molecular changes in PDACs in response to chemotherapy. Metabolic flux analysis reveals that NAC induces a reprogramming of PDAC metabolic patterns and enhances immunogenicity. Notably, NAC leads to the downregulation of glycolysis and the upregulation of CD36. Tissue microarray analysis demonstrates that high CD36 expression is linked to poorer survival in patients receiving postoperative AG. Targeting CD36 synergistically improves the PDAC response to AG both in vitro and in vivo, including patient-derived preclinical models.

A Strong Adhesive Biological Hydrogel for Colon Leakage Repair and Abdominal Adhesion Prevention.

Colon leakage is one of the most severe complications in abdominal trauma or surgery cases. It can lead to severe abdominal infection and abdominal adhesions, resulting in prolonged hospital stays and increased mortality. In this study, a photosensitive hydrogel is proposed, which can swiftly form a strong adhesion coating on the damaged colon after UV irradiation, to realize quick cure and suture-free repair of colon leakage. The newly developed biological gel consists of hyaluronic acid methacryloyl (HAMA) and hyaluronic acid o-nitroso benzaldehyde (HANB) in the optimal ratio of 3: 1, which exerts both the rapid photocuring properties of HAMA and the strong tissue adhesion properties of HANB. HAMA/HANB shows excellent adhesion stability on wet surfaces, presenting controllable mechanical properties, ductility, adhesion stability, and chemical stability; it also evades foreign body response, which relieves the degree of abdominal adhesion. The underlying mechanism for HAMA/HANB promoting wound healing in colon leakage involves the reconstruction of the colon barrier, as well as the regulation of the immune reaction and neovascularization. In all, HAMA/HANB is a promising alternative suture-free approach for repairing colon leakage; it has a reliable healing effect and is expected to be extended to clinical application for other organ injuries.

A Novel Neutrophil Extracellular Traps Signature for Overall Survival Prediction and Tumor Microenvironment Identification in Gastric Cancer.

Background: Neutrophil extracellular traps (NETs) released by neutrophils are crucial for cancer development, metastasis, and can indicate gastric cancer (GC) patients' prognosis. This study reveals the relevance of NETs-related genes to GC through transcriptome analysis. Methods: We obtained transcriptome sequencing data of GC from UCSC Xena and screened prognostic NETs-related genes by GEPIA2 database. The signature for NETs was subsequently created using the LASSO-Cox regression. The clinical value of model was further explored using the nomogram and was externally validated by the GEO database. After that, we employed GO, KEGG, and GSEA enrichment analyses to evaluate the bio-functional enrichment and related pathways. Additionally, ESTIMATE, MCP counter, and ssGSEA scores were used to investigate the immunological microenvironment of GC patients. Finally, in the external cohort, neutrophil elastase (NE)-DNA complexes were measured by ELISA, and the prognostic value of NE-DNA in GC was investigated using Cox analysis. Results: Seven NETs-associated genes (PDE4B, CD93, CTSG, IL6, ELANE, KCNJ15, and CRISPLD2) were filtered to establish the signature and participated in building the nomogram. In comparison to the high-risk group, the overall survival (OS) was much longer in the low-risk group (P=0.005). The validation cohort demonstrated the acceptable predictive ability of the nomogram. The signature was enriched in biological features such as extracellular matrix organization, epithelial-mesenchymal transition and inflammatory response. Moreover, there were substantial differences in immune cell infiltration across the different risk groups (p<0.001), especially the high-risk group having more immune cells that are engaged in the antigen presentation process and associated functions. Finally, in the external cohort, NE-DNA levels were shown to be an independent factor affecting OS prognosis (p=0.006). Conclusion: Overall, this research identified a novel signature based on seven NETs-associated genes to predict prognosis and identify tumor microenvironment of GC. And high NE-DNA level may be a critical factor in the poor OS associated with NETs.

CRIP1 fosters MDSC trafficking and resets tumour microenvironment via facilitating NF-κB/p65 nuclear translocation in pancreatic ductal adenocarcinoma.

OBJECTIVE: Pancreatic ductal adenocarcinoma (PDAC) is among the most immunosuppressive tumour types. The tumour immune microenvironment (TIME) is largely driven by interactions between immune cells and heterogeneous tumour cells. Here, we aimed to investigate the mechanism of tumour cells in TIME formation and provide potential combination treatment strategies for PDAC patients based on genotypic heterogeneity. DESIGN: Highly multiplexed imaging mass cytometry, RNA sequencing, mass cytometry by time of flight and multiplex immunofluorescence staining were performed to identify the pro-oncogenic proteins associated with low immune activation in PDAC. An in vitro coculture system, an orthotopic PDAC allograft tumour model, flow cytometry and immunohistochemistry were used to explore the biological functions of cysteine-rich intestinal protein 1 (CRIP1) in tumour progression and TIME formation. RNA sequencing, mass spectrometry and chromatin immunoprecipitation were subsequently conducted to investigate the underlying mechanisms of CRIP1. RESULTS: Our results showed that CRIP1 was frequently upregulated in PDAC tissues with low immune activation. Elevated CRIP1 expression induced high levels of myeloid-derived suppressor cell (MDSC) infiltration and fostered an immunosuppressive tumour microenvironment. Mechanistically, we primarily showed that CRIP1 bound to nuclear factor kappa-B (NF-κB)/p65 and facilitated its nuclear translocation in an importin-dependent manner, leading to the transcriptional activation of CXCL1/5. PDAC-derived CXCL1/5 facilitated the chemotactic migration of MDSCs to drive immunosuppression. SX-682, an inhibitor of CXCR1/2, blocked tumour MDSC recruitment and enhanced T-cell activation. The combination of anti-PD-L1 therapy with SX-682 elicited increased CD8+T cell infiltration and potent antitumor activity in tumour-bearing mice with high CRIP1 expression. CONCLUSIONS: The CRIP1/NF-κB/CXCL axis is critical for triggering immune evasion and TIME formation in PDAC. Blockade of this signalling pathway prevents MDSC trafficking and thereby sensitises PDAC to immunotherapy.

The Treatment Outcomes of Radiotherapy and Surgical Treatment for Patients with Cavernous Sinus Hemangioma: A Meta-Analysis.

OBJECTIVE: Cavernous sinus hemangiomas (CSHs) are infrequent benign neoplasms. This meta-analysis was conducted with the objective of examining the prognostic outcomes of surgical interventions and radiotherapy (RT) in patients diagnosed with CSHs. METHODS: A comprehensive literature search was performed across PubMed, Embase, and Web of Science databases, with traceability up to June 22, 2021. The evaluation of continuous variables was conducted by applying the weighted mean difference (WMD) and 95% confidence interval. A one-arm meta-analysis was used to scrutinize the tumor control rate, clinical improvement rate, recovery rates of abducens nerve palsy and visual disturbance, total resection rate, and the incidence rate of permanent nerve palsy post-treatment. RESULTS: In total, 29 articles were incorporated into the meta-analysis. Post-RT for CSHs, a significant reduction in tumor volume was observed (WMD [95% confidence interval] = -17.16 [-21.52, -12.80] cm3). The tumor control rate, clinical improvement rate, recovery rate of abducens nerve palsy, and the recovery rate of visual disturbance were 97.1% (92.9, 99.7), 91.9% (82.3, 98.5), 95.6% (83.2, 100.0), and 86.3% (65.0, 99.5), respectively. Following surgical treatment, the total resection rate, mean intraoperative blood loss, recovery rate of visual disturbance, incidence rate of permanent nerve palsy, and recovery rate of abducens nerve palsy were 73.2% (57.1, 86.9), 971.17 mL (584.07, 1358.27), 66.4% (32.4, 0.942), 16.0% (4.6, 31.1), and 70.6% (51.0, 87.7), respectively. Notably, the recovery rate of abducens nerve palsy post-RT was markedly higher than postsurgical treatment. CONCLUSIONS: The results of this meta-analysis underscore that RT is an effective and safe treatment modality for CSHs. Furthermore, the prognostic outcomes of RT demonstrated superiority over surgical intervention.

Microbiota Regulates Pancreatic Cancer Carcinogenesis through Altered Immune Response.

The microbiota is present in many parts of the human body and plays essential roles. The most typical case is the occurrence and development of cancer. Pancreatic cancer (PC), one of the most aggressive and lethal types of cancer, has recently attracted the attention of researchers. Recent research has revealed that the microbiota regulates PC carcinogenesis via an altered immune response. Specifically, the microbiota, in several sites, including the oral cavity, gastrointestinal tract, and pancreatic tissue, along with the numerous small molecules and metabolites it produces, influences cancer progression and treatment by activating oncogenic signaling, enhancing oncogenic metabolic pathways, altering cancer cell proliferation, and triggering chronic inflammation that suppresses tumor immunity. Diagnostics and treatments based on or in combination with the microbiota offer novel insights to improve efficiency compared with existing therapies.

Prognostic value of inflammatory markers and clinical features for survival in advanced or metastatic esophageal squamous cell carcinoma patients receiving anti-programmed death 1 treatment.

Purpose: This study aims to assess the prognostic value of inflammatory markers and clinical features in advanced or metastatic esophageal squamous cell carcinoma (ESCC) patients receiving anti-programmed death 1 (PD-1) treatment. Methods: Based on receiver operating characteristic curve (ROC) analysis, Youden's indexes were applied to determine the cut-off values for inflammatory markers, including neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocye ratio (dNLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII). Wilcoxon test was conducted to evaluate the changes in above inflammatory markers. Kaplan-Meier method was utilized to estimate progression-free survival (PFS) and overall survival (OS), and the Log-rank test was used to compare the different survival between groups. Univariate and multivariate Cox regression analyses were performed to assess the prognostic value of inflammatory markers and clinical features. Results: 162 advanced or metastatic ESCC patients receiving anti-PD-1 treatment were enrolled in this retrospective study. The cut-off values of NLR, dNLR, MLR, PLR, and SII were 4.748, 2.214, 0.309, 250.505, and 887.895, respectively. NLR, dNLR, PLR, and SII declined significantly among the partial response (PR) (P<0.001, P<0.001, P=0.036, P<0.001), objective response rate (ORR) (P<0.001, P<0.001, P=0.036, P<0.001), and disease control rate (DCR) (P<0.001, P<0.001, P=0.038, P<0.001) groups, respectively. Significant increases were found in NLR (P<0.001), dNLR (P<0.001), MLR (P=0.001), and SII (P=0.024) when anti-PD-1 treatment failed. Multivariate Cox regression analysis indicated that NLR (P<0.001, P=0.002), lymph node metastasis (P=0.013, P=0.001), Eastern Cooperative Oncology Group Performance Status (ECOG PS) (P=0.008, P=0.002), and treatment lines (P=0.037, P=0.048) were significant prognostic indicators of PFS and OS. Additionally, SII (P=0.016) was also significantly related to OS in ESCC patients. The risk score model showed that low risk patients prolonged PFS and OS than those with middle or high risk (P<0.001, P<0.001). Conclusion: Inflammatory markers can reflect short-term outcomes of anti-PD-1 treatment for ESCC patients. NLR, lymph node metastases, ECOG PS, and treatment lines are significant prognostic indicators for PFS and OS. And the risk score model constructed based on the above factors has favourable prognostic predictive value.

A Machine-Learning-Based Bibliometric Analysis of Cell Membrane-Coated Nanoparticles in Biomedical Applications over the Past Eleven Years.

Cell membrane encapsulation is a growing concept in nanomedicine, for it achieves the purpose of camouflage nanoparticles, realizing the convenience for drug delivery, bio-imaging, and detoxification. Cell membranes are constructed by bilayer lipid phospholipid layers, which have unique properties in cellular uptake mechanism, targeting ability, immunomodulation, and regeneration. Current medical applications of cell membranes include cancers, inflammations, regenerations, and so on. In this article, a general bibliometric overview is conducted of cell membrane-coated nanoparticles covering 11 years of evolution in order to provide researchers in the field with a comprehensive view of the relevant achievements and trends. The authors analyze the data from Web of Science Core Collection database, and extract the annual publications and citations, most productive countries/regions, most influential scholars, the collaborations of journals and institutions. The authors also divided cell membranes into several subgroups to further understand the application of different cell membranes in medical scenarios. This study summarizes the current research overview in cell membrane-coated nanoparticles and intuitively provides a direction for future research.

Taurodeoxycholic acid-YAP1 upregulates OTX1 in promoting gallbladder cancer malignancy through IFITM3-dependent AKT activation.

Orthodenticle homeobox (OTX1) is reported to be involved in numerous cancers, but the expression level and molecular function of OTX1 in gallbladder cancer (GBC) remain unknown. Here, we found the elevated level of OTX1 associated with poor prognosis in human gallbladder cancer. In vitro and in vivo studies of human gallbladder cancer cell lines demonstrated that overexpression of OTX1 promoted cell proliferation, whereas the downregulation inhibited it. Additionally, we found a tight correlation between the serum level of taurodeoxycholic acid (TDCA) and OTX1 expression. TDCA-induced activation of YAP1 by phosphorylation inhibition contributed to the transcriptional activation of OTX1. Mechanistically, we identified that OTX1 activated AKT signaling pathway by transactivating the expression of IFITM3 and thus promoted the proliferation of GBC cells. Taken together, our results showed that TDCA-YAP1-dependent expression of OTX1 regulated IFITM3 and affected GBC proliferation via the AKT signaling pathway. Our experiments also suggested that OTX1 is a novel therapeutic target for GBC.

Identification and development of a novel risk model based on cuproptosis-associated RNA methylation regulators for predicting prognosis and characterizing immune status in hepatocellular carcinoma.

BACKGROUND: Cuproptosis, a novel cell death caused by excess copper, is quite obscure in hepatocellular carcinoma (HCC) and needs more investigation. METHODS: RNA-seq and clinical data of HCC patients TCGA database were analyzed to establish a predictive model through LASSO Cox regression analysis. External dataset ICGC was used for the verification. GSEA and CIBERSORT were applied to investigate the molecular mechanisms and immune microenvironment of HCC. Cuproptosis induced by elesclomol was confirmed via various in vitro experiments. The expression of prognostic genes was verified in HCC tissues using qRT-PCR analysis. RESULTS: Initially, 18 cuproptosis-associated RNA methylation regulators (CARMRs) were selected for prognostic analysis. A nine-gene signature was created by applying the LASSO Cox regression method. Survival and ROC assays were carried out to validate the model using TCGA and ICGC database. Moreover, there exhibited obvious differences in drug sensitivity in terms of common drugs. A higher tumor mutation burden was shown in the high-risk group. Additionally, significant discrepancies were found between the two groups in metabolic pathways and RNA processing via GSEA analysis. Meanwhile, CIBERSORT analysis indicated different infiltrating levels of various immune cells between the two groups. Elesclomol treatment caused a unique form of programmed cell death accompanied by loss of lipoylated mitochondrial proteins and Fe-S cluster protein. The results of qRT-PCR indicated that most prognostic genes were differentially expressed in the HCC tissues. CONCLUSION: Overall, our predictive signature displayed potential value in the prediction of overall survival of HCC patients and might provide valuable clues for personalized therapies.

Tastin promotes non-small-cell lung cancer progression through the ErbB4, PI3K/AKT, and ERK1/2 pathways.

Tastin might be involved in tumorigenesis, but its role in non-small-cell lung cancer (NSCLC) has not been adequately explored. This work aimed to examine tastin's role in NSCLC and to explore the underlying mechanism. The Gene Expression Omnibus (GEO), Gene Expression Database of Normal and Tumor tissues (GENT), and Cancer Genome Atlas (TCGA) databases were used. Four GEO datasets (GSE81089, GSE40419, GSE74706, and GSE19188) containing gene expression data for NSCLC and normal tissue samples were analyzed for tastin mRNA expression. Tastin expression levels in different tissues were compared using the GENT website. TCGA biolinks were used to download gene expression quantification (n = 594) and overall survival data (n = 535). In total, 30 lung adenocarcinoma and 25 lung squamous cell carcinoma cases were enrolled. In addition, four-week-old male BALB/c nude mice (n = 9/group) were used to establish xenograft mouse models. Furthermore, cultured HEK293T, A549, and NCI-H226 cells assessed. Immunoblot, hematoxylin and eosin (H&E) staining, immunohistochemistry, real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR), fluorescence microscopy, flow cytometry, lentiviral transduction, and MTT, colony formation, wound healing, and Transwell assays were carried out. Tastin expression levels were markedly increased in NSCLC tumor tissue specimens and correlated with a poorer prognosis. Silencing of tastin inhibited the proliferative and migratory abilities of NSCLC cells. Bioinformatic analysis suggested that tastin interacts with ErbB4. The PI3K/AKT and ERK1/2 downstream pathways were suppressed in tastin-deficient cells. In conclusion, tastin might be involved in NSCLC growth and invasion and is a potential therapeutic target in NSCLC.

Cell membrane-coated human hair nanoparticles for precise disease therapies.

Precision medicine is the ultimate goal for current disease therapies, including tumor and infection. The lack of specific targeted drugs for liver cancer and the lack of specific anti-infective drugs in the treatment of diabetic foot ulcer with infection (DFI) are the representative obstacles in those 2 major diseases currently plaguing human beings. Inventing natural biocompatible polymers derived from natural materials is one of the main development directions of current bio-medical materials. Though previous studies have demonstrated the potential application values of human black hair-derived nanoparticles (HNP) in cancer, methicillin-resistant Staphylococcus aureus (MRSA) infection, and thrombosis scenarios treatments, it still has not solved the problem of low local therapeutic concentration and general targeting ability. Here, we firstly modified the HNP with membrane encapsulations, which endowed these dual-pure natural bio-fabricated materials with better targeting ability at the disease sites with no reduction in photothermal therapy (PTT) effect. HNP coated by red blood cell membrane loaded with DSPE-PEG-cRGD peptide for the therapeutic application of liver cancer greatly prolonged in vivo circulation time and enhanced local targeting efficacy as well as low toxicity; HNP coated by the murine macrophage cell membrane (RAWM) for the DFIs treatment greatly promoted the adhesive ability of HNP on the bacteria and thereby improved the killing effect. Briefly, the appropriate cell membranes camouflaged HNP nanomedicine has the characteristics of excellent photothermal effect, an all-natural source with excellent biocompatibility and easy access, which is expected to have huge potential in both benign and malignant diseases.

NIR-II and visible fluorescence hybrid imaging-guided surgery via aggregation-induced emission fluorophores cocktails.

Fluorescence imaging-guided surgery is one of important techniques to realize precision surgery. Although second near-infrared window (NIR-II) fluorescence imaging has the advantages of high resolution and large penetration depth in surgical navigation, its major drawback is that NIR-II images cannot be detected by our naked eyes, which demands a high hand-eye coordination for surgeons and increases the surgical difficulty. On the contrary, visible fluorescence can be observed by our naked eyes but has poor penetration. Here, we firstly propose a kind of NIR-II and visible fluorescence hybrid navigation surgery assisted via a cocktail of aggregation-induced emission nanoparticles (AIE NPs). NIR-II imaging helps to locate deep targeted tissues and judge the residual, and visible fluorescence offers an easily surgical navigation. We apply this hybrid navigation mode in different animals and systems, and verify that it can accelerate surgical process and compatible with a visible fluorescence endoscopy. To deepen the understanding of lymph node (LN) labelling, the distribution of NPs in LNs after local administration is initially analyzed by NIR-II fluorescence wide-filed microscopy, and two fates of the NPs are summarized. An alternative strategy which combines indocyanine green and berberine is also reported as a compromise for rapidly clinical translation.

Primary malignant melanoma in gastroesophageal junction with 36 months' recurrence-free: a case report.

Background: Melanoma is a sinister malignant tumor originates from melanocytes and is characterized by the presence of black pigmentation in the tissue. The vast majority of melanomas are cutaneous melanomas, and primary mucosal melanomas originating from the esophagus are extremely rare. Primary malignant melanoma of esophagus (PMME) accounts for 0.1% to 0.2% of all primary esophageal malignancies. PMME possess high invasiveness but are insensitive to various treatments, so the prognosis is disappointing. Most literature reported that patients are prone to death from complications of tumor metastasis soon, even they undergo radical surgery. Case Description: In this case report, we admitted a 67-year-old female patient with recurrent chest tightness for 2 years and chest pain for 15 days on October 4, 2017. Preoperative imaging examinations, including computerized tomography (CT) and upper gastrointestinal examination by barium revealed stenosis of the lower esophagus and the fundus of the stomach, with mucosa destruction and lymph node metastasis in the hepatic-gastric space. A laparoscope assisted total gastrectomy with D2 lymph node resection and Roux-en-Y anastomosis was performed without adjuvant immunotherapy or targeted therapies. Postoperative pathological examination and immunohistochemical staining indicated malignant melanoma. Meanwhile we did not find a cutaneous lesion, this patient was therefore diagnosed with a rare PMME. There was no sign of recurrence or metastasis during the latest follow-up of 36 months after the operation, which also exceeded the median recurrence-free survival time in the existing cases worldwide. Conclusions: Therefore, we recommend early radical surgery, which may be beneficial to the PMME patient.

C8orf76 Modulates Ferroptosis in Liver Cancer via Transcriptionally Up-Regulating SLC7A11.

Hepatocellular carcinoma (HCC) is a common malignant tumor worldwide. Chromosome 8 open reading frame 76 (C8orf76), a novel gene located in the nucleus, is highly expressed in many tumor types. However, the specific mechanisms and functions of C8orf76 in HCC remain unclear. Here, we reported for the first time that C8orf76 gene expression levels were frequently upregulated in liver cancer and significantly correlated with HCC development. C8orf76 downregulation induced G1-S arrest and inhibited cell proliferation. Intriguingly, C8orf76 deficiency could accelerate erastin or sorafenib-induced ferroptosis through increasing lipid reactive oxygen species (ROS) levels. Moreover, although C8orf76 overexpression did not affect tumorigenesis under normal conditions, it increased resistance to lipid disturbance and ferroptosis triggered by erastin or sorafenib, which further facilitated HCC cell growth and tumor progression. Mechanistically, C8orf76 bound to the promoter region of the solute carrier family 7 member 11 (SLC7A11) gene and upregulated SLC7A11 transcriptionally. SLC7A11-dependent cystine import led to sufficient GSH synthesis and lipid peroxidation inhibition, thus accelerating tumor growth. Our study indicated that C8orf76 could be a novel marker for HCC diagnosis. In addition, a better comprehensive understanding of the potential role of C8orf76 in HCC helped us develop novel therapeutic strategies for this intractable cancer.

ESR1 Regulates the Obesity- and Metabolism-Differential Gene MMAA to Inhibit the Occurrence and Development of Hepatocellular Carcinoma.

Obesity is often regarded as a factor that promotes tumorigenesis, but the role of obesity in promoting hepatocellular carcinoma (HCC) is still controversial. We compared the trend change of 14 obesity-related genes in the formation and development of HCC in normal, adjacent, and HCC tissues. Mendelian randomization (MR) analysis was used to verify the relationship between obesity and HCC occurrence. Metabolism of cobalamin-associated A (MMAA) was discovered as an obesity- and metabolism-differential gene, and its function in HCC was tested in vitro and in vivo. Finally, we explored how obese female patients with an originally high expression of female estrogen receptor (ESR1) directly upregulated MMAA to interfere with the progression of HCC. Fourteen obesity-related genes were downregulated in adjacent and tumoral tissues compared with normal liver tissues, which indicated that obesity may be inversely related to the occurrence of HCC and was consistent with the results of MR analysis. We also discovered that MMAA is a metabolic gene closely related to the occurrence and development of HCC by mining the TCGA database, and it functioned an anti-tumor-promoting role in HCC by damaging the mitochondrial function and preserving the redox balance. We further verified that obese females with a high expression of ESR1 can regulate MMAA to protect HCC from progression. This study elucidates that obesity might be a protective factor for female HCC patients, as they originally highly expressed ESR1, which could upregulate MMAA to suppress tumor growth and participate in metabolic reprogramming.