RNA Technology to Regenerate and Repair Alveolar Bone Defects.

microRNA-200a (miR-200a) targets multiple signaling pathways that are involved in osteogenic differentiation and bone development. However, its therapeutic function in osteogenesis and bone regeneration remains unknown. In this study, we use in vitro and in vivo models to investigate the molecular function of miR-200a overexpression and miR-200a inhibition using a plasmid-based miR inhibitor system (PMIS) on osteogenic differentiation and bone regeneration. Inhibition of miR-200a using PMIS-miR-200a significantly increased osteogenic biomarkers of human embryonic palatal mesenchyme cells and promoted bone regeneration in rat tooth socket defects. In rat maxillary M1 molar extractions, the supporting tooth structures were removed with an implant drill to yield a 3-mm defect in the alveolar bone. A collagen sponge was inserted into the open alveolar defect and PMIS-miR-200a plasmid DNA was added to the sponge and the wound sutured to protect the sponge and close the defect. It was important to remove the existing tooth supporting structure, which can influence alveolar bone regeneration. The alveolar bone was regenerated in 4 wk. The collagen sponge acts to stabilize and deliver the PMIS-miR-200a DNA to cells entering the sponge in the bone defect. We show that mesenchymal stem cells expressing CD90 and Stro-1 enter the sponges, take up the DNA, and express PMIS-miR-200a. PMIS-miR-200a initiates a bone regeneration program in transformed cells in vivo. In vitro inhibition of miR-200a was found to upregulate Wnt and BMP signaling activity as well as Runx2, OCN, Lef-1, Msx2, and Dlx5 associated with osteogenesis. Liver and blood toxicity testing of PMIS-miR-200a-treated rats showed no increase in several biomarkers of liver disease. These results demonstrate the therapeutic function of PMIS-miR-200a for rapid bone regeneration. Furthermore, the studies were designed to demonstrate the ease of use of PMIS-miR-200a in solution and applied using a syringe in the clinic through a simple one-time application.

[Distribution characteristics of tumor infiltrating lymphocytes in EBV-associated lymphoepithelioma-like carcinoma and their clinical significance].

Objective: To investigate the association between the distribution of tumor infiltrating lymphocytes (TIL) in EBV associated lymphoepitheliomatoid carcinoma (LELC) and the pathological subtypes of LELC, as well as the clinical significance of TIL distribution. Methods: The LELC patients with sufficient tumor tissues, complete clinical data and positive EBER, who visited Zhejiang Cancer Hospital, Hangzhou, China from January 2006 to October 2018, were selected. Various immunohistochemical markers (CD20, CD138, CD4, CD8, CD56 and FOXP3) were examined for TIL typing. Two pathologists reviewed the hematoxylin and eosin (HE) staining sections and interpreted the immunohistochemical results. Correlation analysis was used to evaluate the relationship between the distribution of TIL subgroups and LELC's pathological characteristics. Survival analyses were conducted to study the prognostic values of TIL subgrouping. Results: A total of 102 patients with EBV related LELC were included. 46 of them were classic LELC (c-LELC) with rich interstitial TIL, and 56 were non-classic LELC (n-LELC) with relatively fewer interstitial TIL. The results of TIL analysis showed that all subtypes of c-LELC were rich in TIL, with B lymphocytes as the dominant subgroup. The number of TIL in n-LELC was fewer than that in c-LELC, with T lymphocytes as the dominant subgroup. There was no significant difference in the distribution of plasma cells between the two groups. Survival analysis showed that the total number of TIL, and the infiltrations of CD20+B cells, CD4+T cells, and FOXP3+Treg cells were associated with better overall survivals (P=0.004, 0.003, 0.008 and 0.025, respectively) and disease-free survivals (P=0.011, 0.003, 0.038 and 0.041, respectively) in patients with LELC. Conclusions: The morphologic subtypes of EBV-related LELC have different tumor immune characteristics. The total number of TIL in the stroma of c-LELC is significantly higher than that of n-LELC. Interestingly, B lymphocytes are the dominant TIL in c-LELC, while T lymphocytes are the dominant TIL in n-LELC. The infiltration of TIL, CD20+B cells, CD4+T cells and FOXP3+Treg cells in LELC may suggest a better prognosis.

[Advancements in corneal sensory reconstruction for the treatment of neurotrophic keratopathy].

Neurotrophic corneal disease is a degenerative eye condition that occurs due to damage to the trigeminal nerve. This condition presents as a persistent corneal epithelial defect, corneal ulceration, or even perforation, and the main cause is a loss of corneal nerve function. While traditional treatments mainly focus on supportive measures to repair corneal damage, they cannot cure the condition completely. A new surgical treatment option called corneal sensory reconstruction surgery can rebuild the corneal nerve, slow down the progression of the corneal disease, promote corneal epithelial repair, and improve vision. This article reviews the surgical techniques used in corneal sensory reconstruction, including direct nerve repositioning and indirect nerve transplantation, and discusses their treatment outcomes and future prospects.

[Relationship between onco-immunological and morphologic characteristics of lymphoepithelioma-like carcinoma and lymphocyte subtypes of peripheral blood].

Objective: To study the relationship between the onco-immunological and morphologic characteristics of lymphoepithelioma-like carcinoma (LELC) and peripheral blood lymphocyte subtypes and its clinical significance. Methods: The pathologic and clinical data of 117 LELC patients who were admitted to the Tumor Hospital of the University of Chinese Academy of Sciences from 2006 to 2018 were collected. The histological classification was based on previously reported morphological classification method. The onco-immunological and morphologic characteristics of the tumors such as lymphoid follicle formation and interstitial fibrous hyperplasia, patient's peripheral blood lymphocyte subtypes and prognosis data were collected. The relationship between various factors and their impact on prognosis were analyzed. Results: There were 117 patients, including 61 females and 56 males. The male to female ratio was 0.9∶1.0. The age of onset was 24-89 years (median 52 years). Primary sites included head and neck (68 cases), lungs (26 cases), stomach (15 cases), and others (eight cases). Morphologically, 54 cases were type Ⅰ, 62 cases were type Ⅱ, and one case could not be classified. The onco-immunological and morphologic features of the LELC tumors showed a continuous spectrum. Interstitial TILs were noted from focally to diffuse, and the interstitial fibrous tissues were from hardly visible to obvious sclerotic. Formation of lymphoid follicles was seen in 42 patients; obvious fibrosis was seen in 31 cases. Data of peripheral blood lymphocyte subtyping by flow cytometry were available in 73 cases. These data included CD3+total T cells, CD3+CD4+helper T cells, CD3+CD8+cytotoxic T cells, CD3-CD56+natural killer (NK) cells, CD3-CD19+B cells, CD4+CD45RA-T helper induction subgroup, CD4+CD45RA+ T suppression induction subgroup, CD4+CD45RO+memory T cell subgroup, CD45RA+CD45RO+activated T cell subgroup, CD8+CD38+activated cytotoxic T cell, and CD25+lymphocytes and CD44+lymphocyte. The proportion of lymphocytes of each subtype was normal in most patients, but the proportion of CD44+lymphocytes in 61 cases (83.6%) was increased; the proportion of T cell suppression induced subgroups was decreased in 53 cases (72.6%). Correlation analysis found a significant correlation between clinical stage and NK cells (P=0.023); tumor histologic type and cytotoxic T cells were significantly positively correlated (P=0.012); while tumor cell morphologic differentiation was significantly related to total T cells (P=0.003) and NK cells (P=0.026); Formation of interstitial lymphoid follicles was positively correlated with memory T cell subsets (P=0.025); Tumor interstitial fibrosis was significantly positively correlated with T suppression-induced subpopulations (P=0.004), and was significantly negatively correlated with total T cells (P=0.023) and with the expression of CD44 adhesion molecules (P=0.003). Survival analysis found that lymphoid follicle formation was a favorable prognostic factor for LELC (P=0.001). Conclusions: The onco-immunological and morphologic features in LELC show a continuous spectrum; the tumor clinicopathological characteristics and onco-immunological morphology are closely related to peripheral blood T lymphocyte subtypes, and the formation of interstitial lymphoid follicles is a favorable prognostic factor for LELC.

A spectral CT-based nomogram for predicting the response to induction chemotherapy in nasopharyngeal carcinoma.

AIM: To establish a spectral computed tomography (CT)-based nomogram for predicting the response to induction chemotherapy (ICT) in nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: Fifty-four patients with NPC who underwent spectral CT examination before ICT were enrolled prospectively. Patients were assigned to response and non-response groups according to response evaluation. The predictive indicators were spectral CT parameters of venous phase, including iodine concentration (IC), normalised IC (NIC), slope of the spectral attenuation curve in Hounsfield units (λHU), effective atomic number (Eff-Z), and water concentration. Multivariate logistic regression was used to construct a predictive model. The receiver operating characteristic (ROC) and calibration curves were used to evaluate the robustness of model, while the bootstrap method was used for internal validation. The Hosmer-Lemeshow test was used to test the goodness of fit of the discriminant model. RESULTS: Multivariate logistic regression analysis showed that NIC, λHU, and Eff-Z were the potential predictors, and the three indicators were further used to establish a predictive model. The nomogram was evaluated to have good predictive performance, the area under the ROC curve was 0.909 (95% confidence interval [CI]: 0.799-0.970), and the model was well calibrated (χ2 = 8.149, p=0.419). CONCLUSIONS: The spectral CT nomogram has potential clinical value in predicting response to ICT in NPC and may help guide individualised treatment decisions.

[Primary ovarian squamous cell carcinoma: clinicopathological features and prognostic analysis of fifteen cases].

Objective: To assess the clinical features and treatment outcomes in patients with primary ovarian squamous cell carcinoma (POSCC). Methods: Fifteen patients with primary ovarian squamous cell carcinoma diagnosed from January 2009 to December 2018 in Cancer Hospital of the University of Chinese Academy of Sciences were collected. The expression of p16, hMLH1, hMSH2, hMSH6 and PMS2 in POSCC was detected by immunohistochemistry, and the status of high-risk human papillomavirus (HPV) by RNAscope test. Results: Squamous cell carcinoma with different degrees of differentiation was found in 15 cases, including three cases with high differentiation and 12 cases with medium to low differentiation. There were four cases with in situ squamous cell carcinoma, four cases with teratoma, one case with endometrial carcinoma/atypical hyperplasia, and one case with endometriosis. p16 was expressed in five cases (5/15), indicating coexisting high-risk HPV infection. There was no high-risk HPV infection in the remaining 10 cases, and p16 staining was negative. There was no deficient mismatch repair protein in all cases. The overall survival time (P=0.038) and progression free survival (P=0.045) of patients with high-risk HPV infection were longer than those without HPV infection. Conclusions: POSCC is more commonly noted in postmenopausal women and often occurs unilaterally. Elevated serological indexes CA125 and SCC are the most common finding. Morphologically, the tumors show variable degrees of differentiation, but the current data suggest that the degree of differentiation cannot be used as an independent prognostic index. High-risk HPV infection may be associated with the occurrence of POSCC, and that the prognosis of POSCC patients with HPV infection is better than that of patients without infection.

Cholesterol loading suppresses the atheroinflammatory gene polarization of human macrophages induced by colony stimulating factors.

In atherosclerotic lesions, blood-derived monocytes differentiate into distinct macrophage subpopulations, and further into cholesterol-filled foam cells under a complex milieu of cytokines, which also contains macrophage-colony stimulating factor (M-CSF) and granulocyte-macrophage-colony stimulating factor (GM-CSF). Here we generated human macrophages in the presence of either M-CSF or GM-CSF to obtain M-MØ and GM-MØ, respectively. The macrophages were converted into cholesterol-loaded foam cells by incubating them with acetyl-LDL, and their atheroinflammatory gene expression profiles were then assessed. Compared with GM-MØ, the M-MØ expressed higher levels of CD36, SRA1, and ACAT1, and also exhibited a greater ability to take up acetyl-LDL, esterify cholesterol, and become converted to foam cells. M-MØ foam cells expressed higher levels of ABCA1 and ABCG1, and, correspondingly, exhibited higher rates of cholesterol efflux to apoA-I and HDL2. Cholesterol loading of M-MØ strongly suppressed the high baseline expression of CCL2, whereas in GM-MØ the low baseline expression CCL2 remained unchanged during cholesterol loading. The expression of TNFA, IL1B, and CXCL8 were reduced in LPS-activated macrophage foam cells of either subtype. In summary, cholesterol loading converged the CSF-dependent expression of key genes related to intracellular cholesterol balance and inflammation. These findings suggest that transformation of CSF-polarized macrophages into foam cells may reduce their atheroinflammatory potential in atherogenesis.

LINC00261 regulates EBF1 to suppress malignant progression of thyroid cancer.

OBJECTIVE: We aimed to explore the role of LINC00261 in thyroid cancer (TC) and the potential regulatory mechanism. PATIENTS AND METHODS: 40 cases of tumor tissues and adjacent tissues of TC patients were collected, and the expressions of LINC00261 and EBF1 were detected by quantitative real-time polymerase chain reaction (qRT-PCR), and the relationship between LINC00261 and the clinical pathological indicators and prognosis of TC patients were analyzed. Next, LINC00261 overexpression and knockdown cell models were constructed in TC cell lines BPH5-16 and K1, respectively. Cell counting kit-8 (CCK-8) and transwell migration were used to detect the impact of LINC00261 overexpression or silencing on cell proliferative and migration ability. The bioinformatics website was used to screen the possible target gene of LINC00261. RESULTS: qRT-PCR analysis showed that LINC00261 level was markedly reduced in TC tumor tissues, as well as corresponding cell lines. Retrospective analysis showed that low expression of LINC00261 was in positive correlation with the pathological stage, lymphatic and distant metastasis in patients with TC, meanwhile, the expression of LINC00261 was also in positive correlation with overall survival rate of TC patients. Bioinformatics analysis suggested that LINC00261 could target EBF1. Luciferase reporter gene experiment and qRT-PCR analysis suggested that LINC00261 could target EBF1 and that their expressions showed a negative correlation in TC tumor tissues and cells. Cell functional experiments confirmed that LINC00261 can inhibit the proliferative and migration ability of TC cells. Subsequently, the recovery experiment also suggested that silencing EBF1 could reverse the promotion effect of LINC00261 knockdown on the proliferative and migration ability of TC cells; while EBF1 overexpression could reverse the inhibition of LINC00261 on the proliferative and migration ability of TC cells. CONCLUSIONS: LINC00261 was markedly downregulated in TC tissues and cells. In addition, the level of LINC00261 was closely related to lymph node and distant metastasis, as well as the prognosis in TC patients. Moreover, LINC00261 could negatively regulate EBF1, thereby promoting the malignant progression of TC.

Screening key genes and biomarkers in gastrointestinal metaplasia that progress to gastric cancer by integrated bioinformatics analysis.

This study aimed to screen the potential candidate genes and relevant biological markers associated with gastrointestinal metaplasia that progresses to gastric cancer (GIM-GC). Microarray datasets (GSE78523) were downloaded from the GEO database. Differentially expressed genes (DEGs) between GIM-GC samples and healthy controls were identified. GO and KEGG pathway enrichment analyses were performed. STRING and Cytoscape were used to identify significant module and hub genes. Survival analysis was applied to identify key genes. A Venn diagram was built to find hub DEGs that differed in all three relevant comparisons (GIM-GC vs. healthy controls vs. GIM-NoGC). The clinical characteristics of the hub DEGs were evaluated using the Cancer Genome Atlas dataset. The study found 257 DEGs (217 upregulated and 40 downregulated). The upregulated DEGs were enriched in regulation of microvillus length and phospholipid binding and were components of the apical plasma membrane. Downregulated DEGs were involved in digestion and hormone activity and were found in the extracellular space. Fat digestion and absorption as well as gastric acid secretion were the pathways enrichment. The most important gene modules related mainly to O-glycan processing, extracellular exosome, hormone activity, and vitamin and fat digestion and absorption. Eleven hub genes were identified, of which APOB, FABP1, CDX2, GCG, HNF4A, SLC26A3, CFTR, MUC5AC, OLFM4, and SI were related to the prognosis. Olfactomedin-4 (OLFM4) was the most relevant DEG to identify GIM-GC. In conclusion: DEGs and hub genes are helpful to understand the molecular mechanisms of GIM-GC. OLFM4 may be a biological marker for GIM-GC.

[Analysis on clinical efficacy, safety and economy of Shaobei injection and elastic band ligation in the treatment of grade II or III hemorrhoids].

Objective: Currently, various treatments such as hemorrhoidectomy, ligation and sclerotherapy injection can be applied in grade II or III hemorrhoids. This study aims to compare the clinical efficacy, safety and economy between Shaobei injection and elastic band ligation in treating patients with grade II or grade III hemorrhoids. Methods: A retrospective cohort study was used. Clinical data of 60 patients with grade II or grade III hemorrhoids at Department of Anorectal Surgery of the Sixth Affiliated Hospital, Sun Yat-sen University between January 2019 and October 2019 were collected. Patients were divided into two groups according to surgical methods. Patients in the Shaobei group received Shaobei injection (n=28), and those in the ligation group received elastic band ligation (n=32). Inclusion criteria: (1) diagnosis of grade II or III hemorrhoid; (2) application of Shaobei injection or elastic band ligation; (3) age between 18-75 years old. Exclusion criteria: (1) comorbidity with anal fissure, anal fistula, anal sinusitis or other perianal diseases; (2) patients with mental disorder or poor compliance; (3) incomplete clinical or follow-up data. Recurrent rate, postoperative pain, anal edema, anal distension, total cost of hospitalization, length of hospitalization, and postoperative life quality EQ-5D-3L score were compared between the two groups at postoperative 6-month. Results: No significant difference was observed in the baseline data (including Nystrom hemorrhoid symptom score) between the two groups (all P>0.05), except gender ratio [male proportion: Shaobei 75% (21/28) vs. ligation 37.5%(12/32), χ(2)=8.485, P=0.004]. No significant difference in recurrent rate was found between the two groups [14.3% (4/28) vs. 9.4% (3/32), χ(2)=0.035, P=0.851]. Compared to the ligation group, Shaobei group showed less pain at postoperative day 1 [VAS median (range): 2 (1-6) vs. 3 (1-7), Z=2.814, P=0.005] and postoperative day 7 [VAS median (range): 0 (0-2) vs. 1 (0-4), Z=3.149, P=0.002]; lower anal edema ratio at postoperative day 1 [10.7% (3/28) vs. 34.4% (11/32), Z=4.673, P=0.037]; lower anal distension ratio at postoperative day 1 [7.1% (2/28) vs. 28.1% (9/32), Z=4.391, P=0.048]; less hospitalization cost [(6343.5±1444.1) yuan vs. (10 587.1± 1719.0) yuan, t=12.515, P<0.001] and shorter postoperative hospital stay [median (range): 1 (1-5) days vs. 3 (1-6) days, Z=5.879, P<0.001]. The EQ-5D-3L scores of two groups were significantly improved six months after treatment [Shaobei group: (0.90±0.16) vs. (0.73±0.14); ligation group: (0.91±0.13) vs. (0.74±0.10); both P<0.001], while there was no statistically significant difference between the two groups (t=0.130, P=0.897). No complications such as massive hemorrhage, infection, iatrogenic anal fistula, rectal stricture and local induration occurred after the injection. Conclusions: Shaobei injection is effective and safe in treating grade II or III hemorrhoids. Compared with elastic band ligation, it can reduce morbidity of complications and hospitalization expenses.

[XBP1 modulates hypoxia/reoxygenation injury in mouse renal tubular epithelial cells through TXNIP-NLRP3 signaling pathway].

Objective: To investigate the role and regulation mechanism of X box binding protein 1 (XBP1) for hypoxia/reoxygenation(H/R) injury in mouse renal tubular epithelial cells (TCMK-1) through thioredoxin interacting protein (TXNIP)-nucleotide-binding domain (NOD)-like receptor protein (TXNIP-NLRP3) signaling pathway. Methods: The cells were divided into 4 groups: si-NC group transfected with negative control siRNA (si-NC), si-XBP1 group transfected with siRNA targeting XBP1 (si-XBP1), si-NC+H/R group transfected with si-NC and exposed to H/R, and si-XBP1+H/R group transfected with si-XBP1 and exposed to H/R. The Annexin Ⅴ/PI double-staining method was used to detect cell apoptosis; The mitochondrial membrane potential (MMP) was determined by using JC-1 dye; The mitochondrial reactive oxygen species (mROS) was assessed by using MitoSOX™ dye. The interference efficiency of XBP1 was tested by Western blotting and quantitative real-time polymerase chain reaction. The expression levels of TXNIP, NLRP3 and IL-1ß protein were detected by Western blotting. The colocalization of mitochondria and TXNIP was detected by double-labeling immunofluorescent staining. The intergroup difference was compared by using an independent samples t-test. Results: Compared with the si-NC group, more mROS, apoptosis and lower MMP were observed in si-NC+H/R group. Compared with the si-NC+H/R group, less apoptosis (12.08±0.51 vs 19.01±1.80, P<0.05), mROS (34.63±0.64 vs 48.17±1.84, P<0.01) and higher MMP (1.03±0.11 vs 0.45±0.08, P<0.05) were observed in si-XBP1+H/R group. Down-regulation of XBP1U (protein: 1.31±0.18 vs 0.23±0.02, P<0.01; mRNA: 1.12±0.07 vs 0.38±0.01, P<0.001) and XBP1S (protein: 1.13±0.17 vs 0.28±0.07, P<0.01; mRNA: 8.39±0.63 vs 2.45±0.22, P<0.001) inhibited expression of TXNIP (0.15±0.02 vs 0.04±0.01, P<0.01), NLRP3 (1.13±0.12 vs 0.51±0.12, P<0.05) and IL-1ß (1.02±0.04 vs 0.19±0.06, P<0.001) during H/R. Meanwhile, TXNIP exhibited significantly much less colocalization with mitochondria in the si-XBP1+H/R group. Conclusion: Supression of XBP1 expression can effectively alleviate H/R-induced TCMK-1 cells injury, whose mechanism may be inhibition of TXNIP-induced NLRP3 inflammasome activation.

Research on sleeve gastrectomy for the treatment of rats with type 2 diabetes mellitus and the regulation of ghrelin and intestinal lesions.

OBJECTIVE: To explore the effect of sleeve gastrectomy on type 2 diabetes mellitus (T2DM) in regulating ghrelin and intestinal lesions. MATERIALS AND METHODS: Specific pathogen free (SPF) Wistar rats were injected with streptozotocin (STZ) after giving a high-sugar and high-fat diet, to establish a T2DM rat model. The rats were randomly divided into a sleeve gastric excision group, a non-surgical group and a fake surgical group, with 10 rats in each group. The weight, blood glucose, glucose tolerance and ghrelin hormone of rats were compared. The feces of rats in each group at the 8th week after surgery were collected, to extract the total bacterial deoxyribonucleic acid (DNA). The bacterial 16S universal primer was used to expand the 16SrRNA V46 conserved region. The total Polymerase Chain Reaction (PCR) products were sequenced by PE101-bp to classify the gene and genera. RESULTS: The weight of the rats after sleeve gastrectomy significantly decreased (p <0.05). The area under the blood glucose curve and the area under the insulin curve were significantly smaller than those in the non-surgical group and the fake surgical group (p <0.05). Compared with the sleeve gastric excision group, the abundance of Phylum Firmicutes was higher, that of Bacteroidetes was lower. Compared with the sleeve gastric excision group, there were more genera in the fake surgical group and the non-surgical group. The genera with higher abundance in the three groups were Lactobacillus and Bacteroidetes. Compared with the sleeve gastric excision group, the fake surgical group and the non-surgical group had higher abundance of Phylum Firmicutes (p <0.05) and lower abundance of Bacteroidetes (p <0.05). CONCLUSIONS: To sum up, sleeve gastrectomy can reduce the weight of rats in T2DM rat model, lower blood glucose levels of rats in the model and improve insulin resistance levels. The related mechanism may be related to the upregulation of ghrelin and intestinal flora.

MiR-543 inhibits proliferation and metastasis of human colorectal cancer cells by targeting PLAS3.

OBJECTIVE: Colorectal cancer (CRC) has a very high morbidity and mortality worldwide. Related studies have shown that microRNA-543 (miR-543) is involved in the development of many cancers, including CRC. The purpose of this study was to explore the potential molecular mechanism of miR-543's involvement in the development of CRC. PATIENTS AND METHODS: QRT-PCR and Western blot were used to detect the expression of proliferation and migration-related proteins, signal transduction and transcriptional activator 3 and protein inhibitor of activated signal transducer and activators of transcription 3 (PIAS3). Cell proliferation and metastasis were measured by MTT, transwell and Western blot. The binding sites of miR-543 and PIAS3 were predicted by TargetScan database and verified by double-luciferase report experiment. RESULTS: The expression of miR-543 was high in CRC tissues and cell lines, while the mRNA and protein levels of PIAS3 were decreased. Meanwhile, a negative correlation between miR-543 and PIAS3 was also observed in CRC tissues. Moreover, the downregulation of miR-543 led to the inhibition of viability and the expression of proliferation and migration related proteins. Subsequently, miR-543 depletion also blocked cell migration and invasion. MiR-543 inhibits the expression of PISA3. Furthermore, downregulation of PIAS3 undermined the miR-543 depletion-mediated suppression effect on SW480 and LOVO cells. Notably, loss of miR-543 downregulated STAT3 activity, which was rescued by PIAS3 ablation. CONCLUSIONS: MiR-543 participated in cell proliferation and metastasis by targeting PIAS3 in CRC.

Atomically dispersed Ni in cadmium-zinc sulfide quantum dots for high-performance visible-light photocatalytic hydrogen production.

Catalysts with a single atom site allow highly tuning of the activity, stability, and reactivity of heterogeneous catalysts. Therefore, atomistic understanding of the pertinent mechanism is essential to simultaneously boost the intrinsic activity, site density, electron transport, and stability. Here, we report that atomically dispersed nickel (Ni) in zincblende cadmium-zinc sulfide quantum dots (ZCS QDs) delivers an efficient and durable photocatalytic performance for water splitting under sunlight. The finely tuned Ni atoms dispersed in ZCS QDs exhibit an ultrahigh photocatalytic H2 production activity of 18.87 mmol hour-1 g-1. It could be ascribed to the favorable surface engineering to achieve highly active sites of monovalent Ni(I) and the surface heterojunctions to reinforce the carrier separation owing to the suitable energy band structures, built-in electric field, and optimized surface H2 adsorption thermodynamics. This work demonstrates a synergistic regulation of the physicochemical properties of QDs for high-efficiency photocatalytic H2 production.

The significance of Siglec-15 expression in resectable non-small cell lung cancer.

Siglec-15 (S15) is another important mechanism of tumor immune escape besides the PD-L1/PD-1 pathway and represents a new kind of immune checkpoint inhibitor. However, the associations of tumor Siglec-15 expression with clinicopathological characteristics and outcomes of non-small cell lung cancer (NSCLC), and tumor-infiltrating lymphocytes (TILs) in a tumor microenvironment (TME) have so far been unclear. A total of 324 NSCLC surgical samples on tumor microarray were used in this study for investigating the association of S15 expression with clinicopathological characteristics and overall survival (OS) as well as correlation with TILs using multiplex immunofluorescence staining and PD-L1. Results showed that the expression of S15 in adenocarcinoma was significantly higher than that in squamous cell carcinoma. S15 expression was positively correlated with CD8+ T cell density in the stroma. The expression rate of PD-L1 in lung squamous cell carcinoma was higher than that in lung adenocarcinoma. S15 expression was not associated with the prognosis of early NSCLC. The pathological mechanism of the co-expression of S15 and PD-L1 in resectable NSCLC remains to be further studied.

Effect of clinical signs, endocrinopathies, timing of surgery, hyperlipidemia, and hyperbilirubinemia on outcome in dogs with gallbladder mucocele.

Gallbladder mucocele (GBM) is a common extra-hepatic biliary syndrome in dogs with death rates ranging from 7 to 45%. Therefore, the aim of this study was to identify the association of survival with variables that could be utilized to improve clinical decisions. A total of 1194 dogs with a gross and histopathological diagnosis of GBM were included from 41 veterinary referral hospitals in this retrospective study. Dogs with GBM that demonstrated abnormal clinical signs had significantly greater odds of death than subclinical dogs in a univariable analysis (OR, 4.2; 95% CI, 2.14-8.23; P<0.001). The multivariable model indicated that categorical variables including owner recognition of jaundice (OR, 2.12; 95% CI, 1.19-3.77; P=0.011), concurrent hyperadrenocorticism (OR 1.94; 95% CI, 1.08-3.47; P=0.026), and Pomeranian breed (OR, 2.46; 95% CI 1.10-5.50; P=0.029) were associated with increased odds of death, and vomiting was associated with decreased odds of death (OR, 0.48; 95% CI, 0.30-0.72; P=0.001). Continuous variables in the multivariable model, total serum/plasma bilirubin concentration (OR, 1.03; 95% CI, 1.01-1.04; P<0.001) and age (OR, 1.17; 95% CI, 1.08-1.26; P<0.001), were associated with increased odds of death. The clinical utility of total serum/plasma bilirubin concentration as a biomarker to predict death was poor with a sensitivity of 0.61 (95% CI, 0.54-0.69) and a specificity of 0.63 (95% CI, 0.59-0.66). This study identified several prognostic variables in dogs with GBM including total serum/plasma bilirubin concentration, age, clinical signs, concurrent hyperadrenocorticism, and the Pomeranian breed. The presence of hypothyroidism or diabetes mellitus did not impact outcome in this study.

Retraction Note to: miR-200 Regulates Epithelial-Mesenchymal Transition in Anaplastic Thyroid Cancer via EGF/EGFR Signaling.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.