Lipid droplets-related Perilipin-3: potential immune checkpoint and oncogene in oral squamous cell carcinoma.

BACKGROUND: Lipid droplets (LDs) as major lipid storage organelles are recently reported to be innate immune hubs. Perilipin-3 (PLIN3) is indispensable for the formation and accumulation of LDs. Since cancer patients show dysregulated lipid metabolism, we aimed to elaborate the role of LDs-related PLIN3 in oral squamous cell carcinoma (OSCC). METHODS: PLIN3 expression patterns (n = 87), its immune-related landscape (n = 74) and association with B7-H2 (n = 51) were assessed by immunohistochemistry and flow cytometry. Real-time PCR, Western blot, Oil Red O assay, immunofluorescence, migration assay, spheroid-forming assay and flow cytometry were performed for function analysis. RESULTS: Spotted LDs-like PLIN3 staining was dominantly enriched in tumor cells than other cell types. PLIN3high tumor showed high proliferation index with metastasis potential, accompanied with less CD3+CD8+ T cells in peripheral blood and in situ tissue, conferring immunosuppressive microenvironment and shorter postoperative survival. Consistently, PLIN3 knockdown in tumor cells not only reduced LD deposits and tumor migration, but benefited for CD8+ T cells activation in co-culture system with decreased B7-H2. An OSCC subpopulation harbored PLIN3highB7-H2high tumor showed more T cells exhaustion, rendering higher risk of cancer-related death (95% CI 1.285-6.851). CONCLUSIONS: LDs marker PLIN3 may be a novel immunotherapeutic target in OSCC.

Kv1.3 Blockade Alleviates White Matter Injury through Reshaping M1/M2 Phenotypes via the NF-κB Signaling Pathway after Intracerebral Hemorrhage.

BACKGROUND: White matter injury (WMI) in basal ganglia usually induces long-term disability post intracerebral hemorrhage (ICH). Kv1.3 is an ion channel expressed in microglia and induces neuroinflammation after ICH. Here, we investigated the functions and roles of Kv1.3 activation-induced inflammatory response in WMI and the Kv1.3 blockade effect on microglia polarization after ICH. METHODS: Mice ICH model was constructed by autologous blood injection. The expression of Kv1.3 was measured using immunoblot, real-time quantitative polymerase chain reaction (RT-qPCR), and immunostaining assays. Then, the effect of administration of 5-(4-Phenoxybutoxy) psoralen (PAP-1), a selectively pharmacological Kv1.3 blocker, was investigated using open field test (OFT) and basso mouse score (BMS). RT-qPCR, immunoblot, and enzyme-linked immunosorbent assay (ELISA) were taken to elucidate the expression of pro-inflammatory or anti-inflammatory factors around hematoma. PAP-1's function in regulating microglia polarization was investigated using immunoblot, RT-qPCR, and immunostaining assays. The downstream PAP-1 signaling pathway was determined by RT-qPCR and immunoblot. RESULTS: Kv1.3 expression was increased in microglia around the hematoma significantly after ICH. PAP-1 markedly improved neurological outcomes and the WMI by reducing pro-inflammatory cytokine accumulation and upregulating anti-inflammatory factors. Mechanistically, PAP-1 reduces NF-κB p65 and p50 activation, thus facilitating microglia polarization into M2-like microglia, which exerts this beneficial effect. CONCLUSIONS: PAP-1 reduced pro-inflammatory cytokines accumulation and increased anti-inflammatory factors by facilitating M2-like microglia polarization via the NF-κB signaling pathway. Thus, the current study shows that the Kv1.3 blockade is capable of ameliorating WMI by facilitating M2-like phenotype microglia polarization after ICH.

Disseminated Hypertrophic Discoid Lupus Erythematosus in a Patient with Vitiligo: A Case Report and Literature Review.

Vitiligo has been reported to occur in association with lupus erythematosus (LE) and other autoimmune diseases. However, it remains unclear whether this association occurs because of shared immunopathogenesis. We hereby describe a case of discoid lupus erythematosus (DLE) in a 51-year-old man with a 3 years history of skin lesions on his face, arms, and the V zone of the neck, and with the coexistence of vitiligo for 12 years, who developed from DLE to hypertrophic discoid lupus erythematosus (HDLE) after 10 months. We reviewed the previously reported cases to summarize the clinical characteristics of these patients and hope it may provide a reference for dermatologists.

Nanomaterial-Based Strategies for Preventing Tumor Metastasis by Interrupting the Metastatic Biological Processes.

Tumor metastasis is the primary cause of cancer-related deaths. The prevention of tumor metastasis has garnered notable interest and interrupting metastatic biological processes is considered a potential strategy for preventing tumor metastasis. The tumor microenvironment (TME), circulating tumor cells (CTCs), and premetastatic niche (PMN) play crucial roles in metastatic biological processes. These processes can be interrupted using nanomaterials due to their excellent physicochemical properties. However, most studies have focused on only one aspect of tumor metastasis. Here, the hypothesis that nanomaterials can be used to target metastatic biological processes and explore strategies to prevent tumor metastasis is highlighted. First, the metastatic biological processes and strategies involving nanomaterials acting on the TME, CTCs, and PMN to prevent tumor metastasis are briefly summarized. Further, the current challenges and prospects of nanomaterials in preventing tumor metastasis by interrupting metastatic biological processes are discussed. Nanomaterial-and multifunctional nanomaterial-based strategies for preventing tumor metastasis are advantageous for the long-term fight against tumor metastasis and their continued exploration will facilitate rapid progress in the prevention, diagnosis, and treatment of tumor metastasis. Novel perspectives are outlined for developing more effective strategies to prevent tumor metastasis, thereby improving the outcomes of patients with cancer.

Normal Reorientation for Scene Consistency.

With the remarkable progress of 3D scanning technique, the captured indoor scenes appear increasingly in last decade. Generating orientation-consistent normals for indoor point clouds is a fundamental and important task. The existing orientation rectification methods pay more attention to object-level targets with connected surface. However, it is challenging to compute consistent surface orientation for real scanned indoor point clouds. In this paper, we analyze the causes of this difficulty and propose a new normal reorienting framework for indoor scene consistency, namely NRSC. It first estimates normals for an indoor point cloud and extracts all the connected regions. We then design and construct an abstract orientation bridging tree (OBT) to organize the extracted regions in a hierarchical way. For all node regions, NRSC iteratively implements a set of orientation propagations to generate locally orientation-consistent regions. Moreover, we define an auxiliary viewpoint set for each pairwise parent-child node regions and introduce a voting mechanism to rectify the region orientation of child node according to its parent. After processing all the child node regions along OBT, we finally eliminate the orientation inconsistencies between related regions. Multi-groups of experimental results on both fused indoor scenes and single-view-scenes show that our method generates globally consistent orientation for indoor point clouds.

Immune checkpoint CD161/LLT1-associated immunological landscape and diagnostic value in oral squamous cell carcinoma.

An active host adaptive response is characterized by the existence of programmed cell death protein 1 (PD-1)+ /IFN-γ+ cytotoxic T cells and IFN-γ-induced PD-L1+ tumor cells (TCs), which predicts high response rate to anti-PD-1/L1 therapy. Recently, CD161 and its ligand LLT1 (CLEC2D) have been identified as an emerging checkpoint for immunotherapy. Clarifying its heterogeneous clinical expression pattern and its immune landscape is a prerequisite for maximizing the response rate of CD161 blockade therapy in a specific population of oral squamous cell carcinoma (OSCC) patients. Here, we investigated the expression pattern of CD161/LLT1 and its association with major immunocytes (T cells, B cells, NK cells, and macrophages) by multiplex immunofluorescence, immunohistochemistry, and flow cytometry in 109 OSCC tissues and 102 peripheral blood samples. TCs showed higher LLT1 levels than tumor infiltrating lymphocytes (TILs), whereas CD161 was highly expressed in CD8+ T cells at the tumor front, which was decreased in paracancerous tissue. High expression of TC-derived LLT1 (LLT1TC ) conferred poor clinical outcomes, whereas higher CD161+ and LLT1+ TILs were associated with better prognosis. Meanwhile, patients with high LLT1TC showed a decreased ratio of CD8+ /Foxp3+ T cells in situ, but CD161+ TILs correlated with more peripheral CD3+ T cells. Interestingly, treatment of OSCC patients with nivolumab (anti-PD-1) could restore tumoral CD161/LLT1 signal. Furthermore, an OSCC subgroup characterized by high LLT1+ TCs and low CD161+ CD8+ T cells showed fewer peripheral T cells and a higher risk of lymph node metastasis, leading to a shorter 5-year survival time (29%). More LLT1TC at the invasive front was another risk characteristic of exhausted T cells. In conclusion, in view of this heterogeneity, the LLT1/CD161 distribution pattern should be determined before CD161-based immunotherapy.

Association Between Serum Zinc and Non-Alcoholic Fatty Liver Disease and Advanced Liver Fibrosis: NHANES 2011-2016.

Limited and inconclusive evidence exists regarding the correlation between serum zinc levels and non-alcoholic fatty liver disease (NAFLD) and advanced fibrosis. The objective of this cross-sectional study was to investigate the association between serum zinc concentration and both NAFLD and advanced liver fibrosis among the United States (US) adults. 3398 subjects from National Health and Nutrition Examination Survey (NHANES) 2011-2016 were included. Serum zinc concentration was measured by inductively coupled plasma dynamic reaction cell mass spectrometry (ICP-DRC-MS). NAFLD was diagnosed with Hepatic Steatosis Index (HSI), and advanced fibrosis risk was assessed by NAFLD Fibrosis Score (NFS). Weighted logistic regression and restricted cubic splines (RCS) were used to examine the association between serum zinc concentration and NAFLD and advanced fibrosis. Linear trend tests were conducted by incorporating the median of serum zinc quartiles as a continuous variable in the models. We employed sensitivity analysis and subgroup analysis to enhance the robustness of our results. The results from the RCS regression revealed no evident nonlinear relationship between serum zinc concentration and the presence of NAFLD and advanced fibrosis (p-nonlinear > 0.05). Compared with those in the lowest quartile (Q1) of serum zinc concentrations, the odds ratios (95% confidence intervals) of NAFLD were 1.49 (0.89,2.49) in Q2, 0.99 (0.68,1.45) in Q3, and 2.00 (1.40,2.86) in Q4 (p-trend = 0.002). Similarly, the odds ratios (95% confidence intervals) for advanced fibrosis in Q2-4 compared to Q1 were 0.86 (0.50,1.47), 0.60 (0.26,1.39), and 0.41 (0.21,0.77), respectively (p-trend = 0.006). Subgroup analyses and sensitivity analyses reinforce the same conclusion. The investigation revealed a positive linear relationship between serum zinc concentrations and the probability of developing NAFLD. Conversely, an inverse correlation was observed between serum zinc concentrations and the incidence of advanced liver fibrosis among individuals diagnosed with NAFLD.

Comparison of laparoscopic papillary dilation and Endoscopic sphincterotomy with small incision treating fine stones in common bile duct with stricture of oddi sphincter / 中国内镜杂志

Objective Analyze and compare the clinical data of patients with choledocholithiasis combined with benign biliary stricture and Oddi sphincter received laparoscopic percutaneous endoscopic dilation of duodenal papilla and endoscopic sphincterotomy, to explore the clinical experience and investigate the safety and superiority of laparoscopic papillary dilatation and the clinical value in extending the first phase suturing.. Methods From January 2016 to January 2017, 60 patients with choledocholithiasis combined with Oddi sphincter received laparoscopic nipple expansion (30 cases, Group L) and the others received endoscopic sphincterotomy (30 cases, Group E). All the patients clinical data was retrospectively compared and analyzed to explore the clinical experience. Results All operation were successfully performed with no perioperative deaths occurred.. By comparison of the clinical data before and after surgery, we learned that the changes of alanine aminotransferase (ALT), aspartate transaminase (AST), direct bilirubin and postoperative biliary tract bleeding has no statistically significant difference (P > 0.05), while the operation time, the changes of blood amylase and lipase, postoperative gastrointestinal symptoms, postoperative pancreatitis, gastrointestinal function recovery time has statistically significant differences (P < 0.05). There has one self-healing bile leakage case in Group L thanks to routine placement of abdominal drainage tube intraoperatively. The patients gastrointestinal function recovered quick and not suffered pancreatitis because of there's no incision of nipple sphincter. Conclusion Laparoscopic papillary dilation reflects its superiority for not increase postoperative liver function damage, DBIL abnormalities, residual stones, biliary tract bleeding and biliary stricture, while can effectively decrease the incidence of complications such as postoperative pancreatitis, bile reflux and gastrointestinal symptoms. It is safe and effective with less postoperative complications in appropriately application in treatment of fine diameter common bile duct stones with sphincter of Oddi stenosis.

Comparison of laparoscopic papillary dilation and Endoscopic sphincterotomy with small incision treating fine stones in common bile duct with stricture of oddi sphincter / 中国内镜杂志

Objective Analyze and compare the clinical data of patients with choledocholithiasis combined with benign biliary stricture and Oddi sphincter received laparoscopic percutaneous endoscopic dilation of duodenal papilla and endoscopic sphincterotomy, to explore the clinical experience and investigate the safety and superiority of laparoscopic papillary dilatation and the clinical value in extending the first phase suturing.. Methods From January 2016 to January 2017, 60 patients with choledocholithiasis combined with Oddi sphincter received laparoscopic nipple expansion (30 cases, Group L) and the others received endoscopic sphincterotomy (30 cases, Group E). All the patients clinical data was retrospectively compared and analyzed to explore the clinical experience. Results All operation were successfully performed with no perioperative deaths occurred.. By comparison of the clinical data before and after surgery, we learned that the changes of alanine aminotransferase (ALT), aspartate transaminase (AST), direct bilirubin and postoperative biliary tract bleeding has no statistically significant difference (P > 0.05), while the operation time, the changes of blood amylase and lipase, postoperative gastrointestinal symptoms, postoperative pancreatitis, gastrointestinal function recovery time has statistically significant differences (P < 0.05). There has one self-healing bile leakage case in Group L thanks to routine placement of abdominal drainage tube intraoperatively. The patients gastrointestinal function recovered quick and not suffered pancreatitis because of there's no incision of nipple sphincter. Conclusion Laparoscopic papillary dilation reflects its superiority for not increase postoperative liver function damage, DBIL abnormalities, residual stones, biliary tract bleeding and biliary stricture, while can effectively decrease the incidence of complications such as postoperative pancreatitis, bile reflux and gastrointestinal symptoms. It is safe and effective with less postoperative complications in appropriately application in treatment of fine diameter common bile duct stones with sphincter of Oddi stenosis.