Overexpression of COX7A1 Promotes the Resistance of Gastric Cancer to Oxaliplatin and Weakens the Efficacy of Immunotherapy.

Gastric cancer (GC) is one of the most common clinical malignant tumors worldwide, with high morbidity and mortality. Presently, the overall response rate to immunotherapy is low, and current methods for predicting the prognosis of GC are not optimal. Therefore, novel biomarkers with accuracy, efficiency, stability, performance ratio, and wide clinical application are needed. Based on public data sets, the chemotherapy cohort and immunotherapy cohort from Sun Yat-sen University Cancer Center, a series of bioinformatics analyses, such as differential expression analysis, survival analysis, drug sensitivity prediction, enrichment analysis, tumor immune dysfunction and exclusion analysis, single-sample gene set enrichment analysis, stemness index calculation, and immune cell infiltration analysis, were performed for screening and preliminary exploration. Immunohistochemical staining and in vitro experiments were performed for further verification. Overexpression of COX7A1 promoted the resistance of GC cells to Oxaliplatin. COX7A1 may induce immune escape by regulating the number of fibroblasts and their cellular communication with immune cells. In summary, measuring the expression levels of COX7A1 in the clinic may be useful in predicting the prognosis of GC patients, the degree of chemotherapy resistance, and the efficacy of immunotherapy.

Construction of a gene model related to the prognosis of patients with gastric cancer receiving immunotherapy and exploration of COX7A1 gene function.

BACKGROUND: GC is a highly heterogeneous tumor with different responses to immunotherapy, and the positive response depends on the unique interaction between the tumor and the tumor microenvironment (TME). However, the currently available methods for prognostic prediction are not satisfactory. Therefore, this study aims to construct a novel model that integrates relevant gene sets to predict the clinical efficacy of immunotherapy and the prognosis of GC patients based on machine learning. METHODS: Seven GC datasets were collected from the Gene Expression Omnibus (GEO) database, The Cancer Genome Atlas (TCGA) database and literature sources. Based on the immunotherapy cohort, we first obtained a list of immunotherapy related genes through differential expression analysis. Then, Cox regression analysis was applied to divide these genes with prognostic significancy into protective and risky types. Then, the Single Sample Gene Set Enrichment Analysis (ssGSEA) algorithm was used to score the two categories of gene sets separately, and the scores differences between the two gene sets were used as the basis for constructing the prognostic model. Subsequently, Weighted Correlation Network Analysis (WGCNA) and Cytoscape were applied to further screen the gene sets of the constructed model, and finally COX7A1 was selected for the exploration and prediction of the relationship between the clinical efficacy of immunotherapy for GC. The correlation between COX7A1 and immune cell infiltration, drug sensitivity scoring, and immunohistochemical staining were performed to initially understand the potential role of COX7A1 in the development and progression of GC. Finally, the differential expression of COX7A1 was verified in those GC patients receiving immunotherapy. RESULTS: First, 47 protective genes and 408 risky genes were obtained, and the ssGSEA algorithm was applied for model construction, showing good prognostic discrimination ability. In addition, the patients with high model scores showed higher TMB and MSI levels, and lower tumor heterogeneity scores. Then, it is found that the COX7A1 expressions in GC tissues were significantly lower than those in their corresponding paracancerous tissues. Meanwhile, the patients with high COX7A1 expression showed higher probability of cancer invasion, worse clinical efficacy of immunotherapy, worse overall survival (OS) and worse disease-free survival (DFS). CONCLUSIONS: The ssGSEA score we constructed can serve as a biomarker for GC patients and provide important guidance for individualized treatment. In addition, the COX7A1 gene can accurately distinguish the prognosis of GC patients and predict the clinical efficacy of immunotherapy for GC patients.

Progressive Facial Ulcer: A Case Report of Pyoderma gangrenosum.

Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis characterized by rapidly developing and painful skin ulcers with distinctive features. As far as we are concerned, there is no previous case report on facial PG in East-Asia. In this case, we describe a case of a 79-year-old man with a 3-month history of progressive painful ulcers on his cheek and upper lip. Initial suspicion of atypical mycobacterium infection led to an ineffective treatment regimen. Comprehensive infectious testing yielded negative results, and a positive pathergy test indicated a potential diagnosis of PG. A skin biopsy confirmed the diagnosis, and the patient showed significant improvement with intravenous methylprednisolone and oral cyclosporine treatment. After three months, complete resolution of the lesions was achieved without recurrence. The case highlights the diagnostic challenges associated with PG, which is often misdiagnosed due to its resemblance to other conditions. Thorough evaluation is crucial to exclude alternative diagnoses, particularly cutaneous infections. Clinical morphology, tissue biopsy, and culture are essential for accurate diagnosis. The presence of pathergy, the development of new lesions following minor trauma, can also be a diagnostic clue.

Orthogonal threading-through-ß-sheet design of lung cancer EGFR extracellular domain-derived peptidic mimotopes binding to anti-EGFR antibody.

Human epidermal growth factor receptor (EGFR) has been established as a therapeutic target of lung cancer and other diverse tumors. The antibody drug Cetuximab has been developed to target the third subdomain III (TSDIII) of EGFR extracellular domain (ECD) by competitively inhibiting epidermal growth factor binding. In this study, we performed systematic investigation on the crystal complex structure of EGFR ECD domain with Cetuximab to create a residue importance profile for the TSDIII subdomain, based on which a number of U-shaped, double-stranded linear peptides were derived and cyclized to orthogonally thread through most hotspot residues and many responsible residues within the TSDIII ß-sheet plane; they represent mimotopes of the key antibody-recognition site of TSDIII subdomain. Computational analyses revealed that these linear peptides cannot spontaneously fold to the desired conformation in free state due to their intrinsic flexibility. Cell-free assays confirmed that the stapling can considerably improve the binding affinity of linear peptides to Cetuximab by up to 18-fold. The cOrt1 [3-18] cyclic peptide was measured to have the highest affinity in all designed linear and cyclic peptides.

Clinical significance of half-hepatic blood flow occlusion technology in patients with hepatocellular carcinoma with cirrhosis.

BACKGROUND: Most patients with primary hepatocellular carcinoma (HCC) have a history of chronic hepatitis B and usually present with varying degrees of cirrhosis. Owing to the special nature of liver anatomy, the blood vessel wall in the liver parenchyma is thin and prone to bleeding. Heavy bleeding and blood transfusion during hepatectomy are independent risk factors for liver cancer recurrence and death. Various clinical methods have been used to reduce intraoperative bleeding, and the Pringle method is most widely used to prevent blood flow to the liver. AIM: To investigate the effect of half-hepatic blood flow occlusion after patients with HCC and cirrhosis undergo hepatectomy. METHODS: This retrospective study included 88 patients with HCC and liver cirrhosis who underwent hepatectomy in our hospital from January 2017 to September 2020. Patients were divided into two groups based on the following treatment methods: the research group (n = 44), treated with half-hepatic blood flow occlusion technology and the control group (n = 44), treated with total hepatic occlusion. Differences in operation procedure, blood transfusion, liver function, tumor markers, serum inflammatory response, and incidence of surgical complications were compared between the groups. RESULTS: The operation lasted longer in the research group than in the control group (273.0 ± 24.8 min vs 256.3 ± 28.5 min, P < 0.05), and the postoperative anal exhaust time was shorter in the research group than in the control group (50.0 ± 9.7 min vs 55.1 ± 10.4 min, P < 0.05). There was no statistically significant difference in incision length, surgical bleeding, portal block time, drainage tube indwelling time, and hospital stay between the research and control groups (P > 0.05). Before surgery, there were no significant differences in serum alanine transaminase (ALT), aspartate aminotransferase (AST), total bilirubin, and prealbumin levels between the research and control groups (P > 0.05). Conversely, 24 and 72 h after the operation the respective serum ALT (378.61 ± 77.49 U/L and 246.13 ± 54.06 U/L) and AST (355.30 ± 69.50 U/L and 223.47 ± 48.64 U/L) levels in the research group were significantly lower (P < 0.05) than those in the control group (ALT, 430.58 ± 83.67 U/L and 281.35 ± 59.61 U/L; AST, 416.49 ± 73.03 U/L and 248.62 ± 50.10 U/L). The operation complication rate did not significantly differ between the research group (15.91%) and the control group (22.73%; P > 0.05). CONCLUSION: Half-hepatic blood flow occlusion technology is more beneficial than total hepatic occlusion in reducing liver function injury in hepatectomy for patients with HCC and cirrhosis.

The role of Resolvin D1 in liver diseases.

The liver is a parenchymatous organ closely related to immunity, detoxification and metabolism of the three major nutrients. The inflammatory response is a protective mechanism of the body to eliminate harmful stimuli. However, continuous inflammatory stimulation leads to occurrence of many liver diseases and brings great social burden. Resolvin D1, a member of the specialized pro-resolving lipid mediators family, exerts anti-inflammatory, anti-oxidant stress, anti-fibrosis, anti-apoptotic, and anti-tumor effects by binding to ALX/FPR2 or GPR32. RvD1 plays an important role and has great therapeutic potential in liver diseases, which has been validated in multiple models of preclinical disease. This review will provide a detailed summary of the role of RvD1 in different liver diseases, including acute liver injury, liver ischemia/reperfusion injury, non-alcoholic fatty liver disease, liver fibrosis, and liver cancer, so as to help people have a more comprehensive understanding of RvD1 and promote its further research.

[Application of MRI Water-Fat Separation Technology in Patients with Multiple Myeloma].

OBJECTIVE: To explore the clinical significance of magnetic resonance imaging water-fat separation (Dixon) technique in patients with multiple myeloma. METHODS: A total of 41 newly diagnosed patients with multiple myeloma who underwent Dixon in The Affiliated Hospital of Qingdao University from April 2019 to April 2021 were included in this study. Patients were divided into observation group and control group according to whether Dixon performance was normal or not. The differences of clinical data and fat fraction (FF) between the two groups were compared. The correlation between FF and clinical data, disease stages and differences before and after treatment were also compared. The receiver operator characteristic curve of patients was drawn to analyze the diagnostic value of FF combined with serum alkaline phosphatase for bone destruction in patients with multiple myeloma. RESULTS: Among the 41 patients, there were 12 cases in the control group and 29 cases in the observation group. There was no significant difference in age and sex between the two groups. In the observation group, ß2-microglobulin concentration and M protein were significantly higher than those in the control group, while serum alkaline phosphatase and FF were lower (P<0.05). In all 41 patients included in the study, there was a significant negative correlation between FF value and ß2-microglobulin concentration (r=-0.57), and a significant positive correlation between FF value and serum alkaline phosphatase (r=0.31). After treatment, FF value increased, while myeloma cell percentage, ß2-microglobulin concentration and M protein decreased in 11 patients who completed 4 cycles of chemotherapy, and the differences before and after treatment were statistically significant (P<0.05). The value of serum alkaline phosphatase combined with FF value in predicting bone destruction is higher than that of FF value or serum alkaline phosphatase alone. CONCLUSION: Dixon's different imaging manifestations can reflect the severity of the disease. FF value is correlated with clinical examination results and R-ISS staging, and there is a significant difference before and after treatment. Serum alkaline phosphatase combined with FF value is better than two indicators alone in predicting bone destruction.

Formation and control of organic chloramines and disinfection by-products during the degradation of pyrimidines and purines by UV/chlorine process in water.

Pyrimidine and purine bases (adenine, cytosine, guanine and thymine) are important precursors of organic chloramines (OC) and disinfection by-products (DBPs) during chlor(am)ination. In this study, OC and DBP formation derived from pyrimidine and purine bases during chlor(am)ination, post-chlor(am)ination after pretreated by UV alone and UV/chlorination were systematically investigated with ultraviolet light-emitting diodes (UV-LEDs, 265 and 275 nm) and low pressure mercury lamp (LPUV, 254 nm). The results revealed that higher OC formation was observed during chlorination than that during chloramination of pyrimidine and purine bases. The degradation of pyrimidine and purine bases followed the pseudo-first-order kinetics. Both solution pH and UV wavelength played vital influence on the degradation of pyrimidine and purine bases. In terms of fluence-based rate constants (kobs), the degradation rates of pyrimidine and purine bases decreased in the order of 275 nm > 265 nm > 254 nm in alkaline conditions. The synergistic effects of kobs, chlorine,kobs, •OH and kobs, RCS contributed to the differences of pyrimidine and purine bases degradation at different pH values and UV wavelengths. A vital suppression of OC formation was observed during post-chlorination after pretreated by 275 nm UV-LED/chlorination. In addition, compared with LPUV (254 nm), less DBP formation was observed at UV-LED (275 nm), especially during the UV/chlorine process. The phenomena obtained in this study indicated that 275 nm UV-LED combined with chlorine could be a preferred method to promote pyrimidine and purine bases degradation and control OC and DBP formation in practical water treatment.

Clinical Applicable AI System Based on Deep Learning Algorithm for Differentiation of Pulmonary Infectious Disease.

Objective: To assess the performance of a novel deep learning (DL)-based artificial intelligence (AI) system in classifying computed tomography (CT) scans of pneumonia patients into different groups, as well as to present an effective clinically relevant machine learning (ML) system based on medical image identification and clinical feature interpretation to assist radiologists in triage and diagnosis. Methods: The 3,463 CT images of pneumonia used in this multi-center retrospective study were divided into four categories: bacterial pneumonia (n = 507), fungal pneumonia (n = 126), common viral pneumonia (n = 777), and COVID-19 (n = 2,053). We used DL methods based on images to distinguish pulmonary infections. A machine learning (ML) model for risk interpretation was developed using key imaging (learned from the DL methods) and clinical features. The algorithms were evaluated using the areas under the receiver operating characteristic curves (AUCs). Results: The median AUC of DL models for differentiating pulmonary infection was 99.5% (COVID-19), 98.6% (viral pneumonia), 98.4% (bacterial pneumonia), 99.1% (fungal pneumonia), respectively. By combining chest CT results and clinical symptoms, the ML model performed well, with an AUC of 99.7% for SARS-CoV-2, 99.4% for common virus, 98.9% for bacteria, and 99.6% for fungus. Regarding clinical features interpreting, the model revealed distinctive CT characteristics associated with specific pneumonia: in COVID-19, ground-glass opacity (GGO) [92.5%; odds ratio (OR), 1.76; 95% confidence interval (CI): 1.71-1.86]; larger lesions in the right upper lung (75.0%; OR, 1.12; 95% CI: 1.03-1.25) with viral pneumonia; older age (57.0 years ± 14.2, OR, 1.84; 95% CI: 1.73-1.99) with bacterial pneumonia; and consolidation (95.8%, OR, 1.29; 95% CI: 1.05-1.40) with fungal pneumonia. Conclusion: For classifying common types of pneumonia and assessing the influential factors for triage, our AI system has shown promising results. Our ultimate goal is to assist clinicians in making quick and accurate diagnoses, resulting in the potential for early therapeutic intervention.

Luminescence chronology for the Paleolithic site of Xinmiaozhuang Locality 1 (XMZ1) in the Nihewan Basin, northern China, and its paleoenvironmental and archaeological implications.

In contrast to the prevailing view that the Chinese Paleolithic has been dominated by the Mode 1 technology-with a slow and conservative development from the Early to the Late Pleistocene-recent discoveries indicate that the lithic technology might have developed into an 'advanced' phase in some parts of China, at least since the early Late Pleistocene. The Xinmiaozhuang Locality 1 (XMZ1), located on the southern edge of the Nihewan Basin in northern China, is one of the examples belonging to such an 'advanced' phase. Although the stone artifacts at this site still belong to the long-existing 'small-tool' industry (core-and-flake) in this basin, some 'advanced' traits, including discoidal cores, elongated flakes, and 'Mousterian-like' triangular points and scrapers, are present. We provide a dating of the XMZ1 using the multiple elevated temperatures (MET) post infrared (pIR) infrared stimulated luminescence (IRSL) procedure (MET-pIRIR) on both multigrained single aliquots and 'individual' grains of potassium-rich feldspars (K-feldspars). The consistency between the single-aliquot and single-grain K-feldspar equivalent dose results mutually confirmed the reliability of the obtained ages. Our chronology indicates that the cultural layer falls within the period of ca. 63-75 ka, corresponding to the early stage of the Marine Isotope Stage (MIS) 4. Based on the correlation of the cultural age to the environmental proxies of loess and stalagmites from China, we suggest that the site might have witnessed dramatic fluctuations of paleoclimate during the site formation. Additionally, based on the discoidal cores distribution, a potential corridor along the Xuefeng-Wu-Tainhang-Great Khingan Mountains for ancient humans migrating between South and North China is suggested. However, more archaeological and chronological studies are required to figure out the origin and the dispersal patterns of the discoidal core associated with lithic assemblage and the tool-makers in East Asia.

Acute myeloid leukemia with T lymphoblastic lymphoma: a case report and literature review.

Acute myeloid leukemia (AML) with T lymphoblastic lymphoma (T-LBL) is a hematologic tumor of two origins, myeloid and lymphoblastic, and is relatively rare in the same patient. We report a rare case of AML with T-LBL. After the patient was diagnosed, he received standard chemotherapy, which decreased the primitive bone marrow cell percentage from 84% to 5%; however, the enlarged superficial lymph nodes showed no obvious change in size. Immunohistochemistry revealed the following: cluster of differentiation (CD)3 (+), CD5 (+), CD7 (+), transmission disequilibrium test (TDT) (+), myeloperoxidase (MPO) (-), and lysozyme (Lys) (-). The lymph node morphology and immunohistochemical results indicated T-LBL. Therefore, the final diagnosis was AML with T-LBL, with both diseases occurring independently and concurrently.

The application of UV-C laser in persulfate activation for micropollutant removal: Case study with iodinated X-ray contrast medias.

A novel light source UV-C laser was applied in persulfate (PS) activation to effectively remove iodinated X-ray contrast medias (ICMs) including iohexol (IOX), iopamidol (IPM) and diatrizoate (DTZ) in this study. Significant ICMs degradation was observed in UV-C laser/PS systems with pseudo first-order rate constants of 0.022-0.067 s-1. Sulfate radicals (SO4•-) were the main active species in the three ICMs degradation, and the steady-state concentrations ([SO4•-]ss) were 3.629 × 10-11 M (IOX), 1.702 × 10-11 M (IPM) and 1.148 × 10-11 M (DTZ), respectively. Under the high intensity of UV-C laser, the optimal reaction efficiency was achieved at pH = 7.0 with PS concentration of 1.0 mM, and the degradation efficiency for IOX reached 93.8% within only 40 s. Both bicarbonate and chloride ions could inhibit the three ICMs degradation and the inhibition rate increased with the increase of ions concentration. The kinetic models were established and the steady-state concentrations of radicals were calculated. Density functional theory (DFT) calculations combined with experiments were used to derive the reaction pathways for three ICMs. Cyclic voltammetry measurements detected a lower redox potential peak in IOX degradation, revealing the existence of electron shuttles under the UV-C laser irradiation to promote the redox reaction. This study is the first report of UV-C laser activation of persulfate. It is a new advanced oxidation process mediated by very effective photolysis and active species formation.

Photodegradation pathway of iodate and formation of I-THMs during subsequent chloramination in iodate-iodide-containing water.

This study investigated the mechanisms of mixed IO3-/I- system under UV irradiation in drinking water and compared the iodinated trihalomethanes (I-THMs) formation of a mixed IO3-/I- system to that of single I- and IO3- systems during subsequent chloramination. The effects of initial I-/IO3- molar ratio, pH, and UV intensity on a mixed IO3-/I- system were studied. The introduction of I- enhanced the conversion rate of IO3- to reactive iodine species (RIS). Besides, IO3- degradation rate increased with the increase of initial I- concentration and UV intensity and the decrease of pH value. In a mixed IO3-/I- system, IO3- could undergo direct photolysis and photoreduction by hydrated electron (eaq-). Moreover, the enhancement of I-THM formation in a mixed IO3-/I- system during subsequent chloramination was observed. The I-THM yields in a mixed IO3-/I- system were higher than the sum of I-THMs produced in a single IO3- and I- systems at all the evaluated initial I- concentrations and pH values. The difference between I-THM formation in a mixed IO3-/I- system and the sum of I-THMs in a single IO3- and I- systems increased with the increase of initial I- concentration. As the initial pH decreased from 9 to 5, the difference of I-THM yields enhanced, while the total I-THM yield of a mixed IO3-/I- system and single I- and IO3- systems decreased slightly. Besides, IO3--I--containing water with DOC concentration of 2.5-4.5 mg-C/L, which mainly contained humic-acid substances, had a higher risk in I-THMs formation than individual I--containing and IO3--containing water.

Physiological and antioxidant responses of Euryale ferox salisb seedlings to microcystins.

Lake Taihu is the third largest freshwater lake located in eastern China. In recent years, it has experienced extensive cyanobacterial (Microcystis spp.) blooms that produce toxic microcystins (MCs), which may have acute and chronic hepatotoxic effects in animals and humans. Although the impact of MCs on both terrestrial and aquatic plants is well documented, the effects and underlying mechanisms of the harmful toxin MC-LR on Euryale ferox Salisb seedlings have rarely been reported. Thus, herein, the antioxidant response mechanisms and the biosynthesis of secondary metabolites during the exposure of E. ferox Salisb seedlings to varying MC-LR concentrations (0.05, 0.2, 1, and 5 µg/L) were thoroughly investigated after exposure periods (7, 14, 21 d). Our study revealed that the seedling growth was inhibited with increasing MC-LR exposure concentration that significantly induced at 1 µg/L and reached a maximum level at 5 µg/L, whereas the activity of the antioxidant enzymes catalase (CAT), superoxide dismutase (SOD), and peroxidase (POD) in the seedling cells increased gradually with increasing MC-LR concentration and longer exposure time. The maximum malondialdehyde (MDA) content was 4.3-fold higher than that of the control group under an MC-LR concentration of 5.0 µg/L after 7 days of exposure treatment. The study of the seedling detoxification mechanism revealed that the content of total glutathione (tGSH) and reduced glutathione (GSH), as well as the activities of GSH sparse transferase (GST) and glutathione reductase (GR), increased to varying degrees and reached a maximum level at 1 µg/L. Therefore, the exposure to MC-LR can promote the accumulation of secondary metabolites and increase the activities of secondary metabolic enzymes in the seedlings. Further investigation of these antioxidative mechanisms will provide additional information for the identification and development of bio-indicators to evaluate the environmental impact of MCs on aquatic ecosystems.

[High Risk Factors for Transformation into Acute myeloid Leukemia in Patients with Intermediate and High Risk Myelodysplastic syndrome].

OBJECTIVE: To study the high risk factors for the transformation into acute myeloid leukemia(AML) in patients with intermediate and high risk myelodysplastic syndrome(MDS) treated by decitabine-based regimen. METHODS: The clinical characterstics of 60 intermediate and high risk MDS patients and the factors of its transformed into AML were retrospectively analyzed. RESULTS: The overall response rate(ORR) of the patients suffered from intermediate and high risk MDS treated by decitabine-based regimen was 65.0％(39/60), among the 60 cases 17 achieved complete remission(CR), 5 achieved morrow complete remission(mCR), 4 achieved partial remission(PR) and 13 achieved hematologic improvement(HI). Twenty-one cases(35.0%) were transformed into AML among 60 cases of intermediate and high risk MDS treated by decitabine-based regimen. The median time of transformation from intermediate and high risk MDS into AML was 10.0 months(1.6-32.0). χ2 or Fisher's exact test showed that 2016 WHO MDS diagnostic subgrouping, myeloid hyperplasia markedly active, delayed interval of decitabine-based treatment associated with the transformation from intermediate to high risk MDS into AML (χ2=9.878，P=0.031；χ2=4.319，P=0.038；χ2=6406，P=0.011); Univariate analysis of Kaplan-Meier test showed that 2016 WHO MDS diagnostic subgroups, bone marrow blast cell ratio, bone marrow dysplasia coefficients, prolonged interval of decitabine-based treatment associated with the transformation from intermediate and high risk MDS into AML (P=0.015，P=0.008，P=0.012，P=0.032); multivariate analysis showed the bone marrow blast cell ratio and the bone marrow dysplasia coefficients were independent risk factors for the transformation from intermediate to high risk MDS into AML (P=0.022，P=0.018). CONCLUSION: The bone marrow blast cell ratio and the bone marrow dysplasia coefficients are independent risk factors of transformation into AML in the patients with intermediate and high risk MDS treated by decitabine-based regimen. The regular interval of dicitabine treatment is beneficial to maintain the stability of patients conditions.

Ginsenoside Rg1 Exerts Anti-inflammatory Effects via G Protein-Coupled Estrogen Receptor in Lipopolysaccharide-Induced Microglia Activation.

Neuroinflammation plays a pivotal role in the pathogenesis of Parkinson's disease. Ginsenoside Rg1, the most active ingredient of ginseng, has been reported to exert neuroprotective effects via estrogen and glucocorticoid receptors. The present study evaluated the involvement of the G protein-coupled estrogen receptor (GPER) in the anti-inflammatory effects of ginsenoside Rg1 against lipopolysaccharide (LPS)-induced microglia activation in the BV2 microglial cell line and ventral mesencephalic primary microglial culture. The pharmacological blockade and lentivirus-mediated small interfering RNA (siRNA) knockdown of GPER were used to study the underlying mechanism. Rg1 attenuated LPS-induced upregulation of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) mRNA and protein levels. The GPER antagonist G15 blocked the inhibitory effects of Rg1 and the GPER-specific agonist G1 on LPS-induced microglia activation. Rg1 mimicked the effects of G1 by inhibiting the LPS-induced activation of nuclear transcription factor-kappa B (NF-κB) and mitogen activated protein kinase signaling pathways, which was also blocked by G15. Moreover, lentivirus-mediated siRNA knockdown of GPER inhibited the anti-inflammatory effects of Rg1. Taken together, our results indicate that GPER is involved in the anti-inflammatory effects of Rg1 against LPS-induced microglia activation. These findings provide a new biological target of Rg1 for the treatment of neuroinflammatory disorders.

RETRACTED: LSAMP-AS1 binds to microRNA-183-5p to suppress the progression of prostate cancer by up-regulating the tumor suppressor DCN.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the editor after publication concerns were raised with respect to data presented in Figure 2. The journal contacted Southern Medical University, Guangzhou, Guangdong Province, China, who formed an Academic Committee to investigate. According to the "Academic Ethics and Implementation Rules" of Southern Medical University, the Committee reported evidence of improper preservation of original data and incorrect use of pictures, and recommended immediate withdrawal of the paper. Specifically, in the PC-3 group of Fig. 2H, the 'Control' cell migration image had been partially duplicated in the 'Empty vector' image. As per journal policy, original files used to create the entire figure were requested. Raw western blot images were not available for Figure 2 C+F, and experimental repeats yielded protein level discrepancies with the original published data. The editors therefore no longer have confidence in the integrity of these data.

[A Simple Medical Research Microdevice for Analyzing Three-dimensional Migration of Tumor Cells in Vitro].

Objective To develop and verify a medical microdevice for analyzing the three-dimensional(3D)migration of tumor cells in extracellular matrix. Methods The mold of the microdevice was made by precision machining,and then the medical microdevice based on polydimethylsiloxane(PDMS)-glass was obtained by PDMS casting,moulding,and bonding.During the analysis,the suspension of tumor cells and matrigel were mixed and then added into the migration channel of microdevice,and the controllable migration of tumor cells in matrigel was induced by establishing chemokine concentration gradient on both sides of the migration channel.Meanwhile,the migration process of tumor cells was recorded with the live cell dynamic imaging device. Results Breast cancer cell line MCF-7 was taken as an example to verify the feasibility of the microdevice to control and dynamically monitor the 3D migration process of tumor cells in vitro.Qualitative analysis of imaging data showed that the migration of MCF-7 cell lines in matrigel was determined by the concentration gradient distribution direction of chemokine and presented as the amoeboid-like migration mode.The proportion and migration velocity of MCF-7 cells could be quantified by the quantitative analysis of cell migration process.The inhibition ability of matrix metalloproteinase inhibitors(Batimastat)and adenosine triphosphatase inhibitors(Blebbistation)on the 3D migration behavior of MCF-7 cells was found to be different.Conclusion This device can be used for in-depth analysis of tumor cell migration and its mechanism and for evaluating the efficacy of anti-metastatic drugs.