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Crystalline borates have received great attention due to their various structures and wide applications. For a long time, the corner-sharing B–O unit is considered a basic rule in borate structural chemistry. The Dy4B6O15 synthesized under high-pressure is the first oxoborate with edge-sharing [BO4] tetrahedra, while the KZnB3O6 is the first ambient pressure borate with the edge-sharing [BO4] tetrahedra. The edge-sharing connection modes greatly enrich the structural chemistry of borates and are expected to expand new applications in the future. In this review, we summarize the recent progress in crystalline borates with edge-sharing [BO4] tetrahedra. We discuss the synthesis, fundamental building blocks, structural features, and possible applications of these edge-sharing borates. Finally, we also discuss the future perspectives in this field.

Background The tumor microenvironment is characterized by inflammation-like and immunosuppression situations. Although cancer-associated fibroblasts (CAFs) are among the major stromal cell types in various solid cancers, including colon cancer, the interactions between CAFs and immune cells remains largely uncharacterized. Pentraxin 3 (PTX3) is responsive to proinflammatory cytokines and modulates immunity and tissue remodeling, but its involvement in tumor progression appears to be context-dependent and is unclear. Methods Open-access databases were utilized to examine the association of PTX3 expression and the fibroblast signature in colon cancer. Loss-of-function assays, including studies in tamoxifen-induced Ptx3 knockout mice and treatment with an anti-PTX3 neutralizing antibody (WHC-001), were conducted to assess the involvement of PTX3 in colon cancer progression as well as its immunosuppressive effect. Finally, bioinformatic analyses and in vitro assays were performed to reveal the downstream effectors and decipher the involvement of the CREB1/CEBPB axis in response to PTX3 and PTX3-induced promotion of M2 macrophage polarization. Results Clinically, higher PTX3 expression was positively correlated with fibroblasts and inflammatory response signatures and associated with a poor survival outcome in colon cancer patients. Blockade of PTX3 significantly reduced stromal cell-mediated tumor development. The decrease of the M2 macrophage population and an increase of the cytotoxic CD8 + T-cell population were observed following PTX3 inactivation in allografted colon tumors. We further revealed that activation of cyclic AMP-responsive element-binding protein 1 (CREB1) mediated the PTX3-induced promotion of M2 macrophage polarization. Conclusions PTX3 contributes to stromal cell-mediated protumor immunity by increasing M2-like macrophage polarization, and inhibition of PTX3 with WHC-001 is a potential therapeutic strategy for colon cancer.

Background Nitric oxide-releasing drugs are used for cardiovascular diseases; however, their effects on the tumor immune microenvironment are less clear. Therefore, this study explored the impact of nitric oxide donors on tumor progression in immune-competent mice. Methods The effects of three different nitric oxide-releasing compounds (SNAP, SNP, and ISMN) on tumor growth were studied in tumor-bearing mouse models. Three mouse tumor models were used: B16F1 melanoma and LL2 lung carcinoma in C57BL/6 mice, CT26 colon cancer in BALB/c mice, and LL2 lung carcinoma in NOD/SCID mice. After nitric oxide treatment, splenic cytokines and lymphocytes were analyzed by cytokine array and flow cytometry, and tumor-infiltrating lymphocytes in the TME were analyzed using flow cytometry and single-cell RNA sequencing. Results Low doses of three exogenous nitric oxide donors inhibited tumor growth in two immunocompetent mouse models but not in NOD/SCID immunodeficient mice. Low-dose nitric oxide donors increase the levels of splenic cytokines IFN-γ and TNF-α but decrease the levels of cytokines IL-6 and IL-10, suggesting an alteration in Th2 cells. Nitric oxide donors increased the number of CD8 + T cells with activation gene signatures, as indicated by single-cell RNA sequencing. Flow cytometry analysis confirmed an increase in infiltrating CD8 + T cells and dendritic cells. The antitumor effect of nitric oxide donors was abolished by depletion of CD8 + T cells, indicating the requirement for CD8 + T cells. Tumor inhibition correlated with a decrease in a subtype of protumor macrophages and an increase in a subset of Arg1-positive macrophages expressing antitumor gene signatures. The increase in this subset of macrophages was confirmed by flow cytometry analysis. Finally, the combination of low-dose nitric oxide donor and cisplatin induced an additive cancer therapeutic effect in two immunocompetent animal models. The enhanced therapeutic effect was accompanied by an increase in the cells expressing the gene signature of NK cell. Conclusions Low concentrations of exogenous nitric oxide donors inhibit tumor growth in vivo by regulating T cells and macrophages. CD8 + T cells are essential for antitumor effects. In addition, low-dose nitric oxide donors may be combined with chemotherapeutic drugs in cancer therapy in the future.

Achalasia is a rare motility disorder of the esophagus caused by the gradual degeneration of myenteric neurons. Immune-mediated ganglionitis has been proposed to underlie the loss of myenteric neurons. Here, we measure the immune cell transcriptional profile of paired lower esophageal sphincter (LES) tissue and blood samples in achalasia and controls using single-cell RNA sequencing (scRNA-seq). In achalasia, we identify a pattern of expanded immune cells and a specific transcriptional phenotype, especially in LES tissue. We show C1QC + macrophages and tissue-resident memory T cells (T RM ), especially ZNF683 + CD8 + T RM and XCL1 + CD4 + T RM , are significantly expanded and localized surrounding the myenteric plexus in the LES tissue of achalasia. C1QC + macrophages are transcriptionally similar to microglia of the central nervous system and have a neurodegenerative dysfunctional phenotype in achalasia. T RM also expresses transcripts of dysregulated immune responses in achalasia. Moreover, inflammation increases with disease progression since immune cells are more activated in type I compared with type II achalasia. Thus, we profile the immune cell transcriptional landscape and identify C1QC + macrophages and T RM as disease-associated immune cell subsets in achalasia. Achalasia is a rare motility disorder of the esophagus resulting from abnormal immune responses, but the immunologic mechanism is unclear. Here the authors use scRNA-seq of PBMC and esophageal lower sphincter tissue and find C1QC + macrophages and tissue-resident memory T cells with expanded compositions and altered transcriptional profiles in achalasia.

Linear stability of braneworld models constructed with multi-scalar fields is very different from that of single-scalar field models. It is well known that both the tensor and the scalar perturbations of the latter are stable at linear level. However, in general there is no effective method to deal with the stability problem of the scalar perturbations for braneworld models constructed with non-minimally coupled multi-scalar fields. In this work we present a systematic covariant approach to deal with the scalar perturbations. By introducing the orthonormal bases in field space and making the Kaluza–Klein decomposition, we get a set of coupled Schrödinger-like equations of the scalar perturbation modes. Using the nodal theorem, we show that the result is model-dependent. For superpotential derived brane models, the scalar perturbations are stable, but there exist normalizable scalar zero modes, which will result in unacceptable fifth force on the brane. We also use this method to analyze the f(R) braneworld model with an explicit solution and find that the scalar perturbations are stable and the scalar zero modes cannot be localized on the brane, which ensures that there is no extra long-range force and the Newtonian potential on the brane can be recovered.

Background An increasing number of studies have been conducted on the use of endoscopic ultrasound (EUS)-guided needle sampling for upper gastrointestinal subepithelial lesions (SEL). However, reported diagnostic efficacy varies greatly. Objective To summarize up current evidences on the diagnostic efficacy of EUS-guided needle sampling for upper GI SEL. Method A reproducible strategy was used to search four databases. Search results were evaluated for eligibility, and the quality of eligible studies was assessed by QUADAS-2. Pooled efficacy of EUS-guided needle sampling in upper GI SEL was calculated. Procedure-related complications, diagnostic errors, and independent factors related to a higher success rate were also recorded and analyzed. Results Seventeen studies, comprising 978 attempts of EUS-guided needle sampling, were included in a meta-analysis. Pooled diagnostic rate of EUS-guided needle sampling was 59.9 %, with a heterogeneity I 2 of 55.2 %. Subgroup analysis showed no difference in diagnostic rate among fine needle aspiration (FNA), trucut needle biopsy (TCB), and fine needle biopsy (FNB), or among 19-, 22-, and 25-G needles. Subgroup analysis and meta-regression suggested that the cell block method might be correlated with a higher diagnostic rate. Few severe complications were reported. Diagnosis errors were rare. Conclusion EUS-guided needle sampling is a safe, but only moderately effective method for pathology diagnosis of upper GI SEL. Choice of FNA/TCB/FNB, or 19 G/22 G/25 G does not seem to alter the overall diagnostic rate.

Background This study was designed to evaluate the clinical efficacy, safety, and feasibility of endoscopic full-thickness resection (EFR) for gastric submucosal tumors (SMTs) originated from the muscularis propria. Methods Twenty-six patients with gastric SMTs originated from the muscularis propria were treated by EFR between July 2007 and January 2009. EFR technique consists of five major procedures: (1) injecting normal saline into the submucosa and precutting the mucosal and submucosal layer around the lesion; (2) a circumferential incision as deep as muscularis propria around the lesion by the endoscopic submucosal dissection (ESD) technique; (3) incision into serosal layer around the lesion with Hook knife; (4) completion of full-thickness incision to the tumor including the serosal layer with Hook, IT, or snare by gastroscopy without laparoscopic assistance; (5) closure of the gastric-wall defect with metallic clips. Results EFR was successfully performed in all 26 patients without laparoscopic assistance. The complete resection rate was 100%, and the mean operation time was 105 (range, 60–145) min. The mean resected lesion size was 2.8 (range, 1.2–4.5) cm. Pathological diagnosis of these lesions included gastrointestinal stromal tumors (GISTs) (16/26), leiomyomas (6/26), glomus tumors (3/26), and Schwannoma (1/26). No gastric bleeding, peritonitis sign, or abdominal abscess occurred after EFR. No lesion residual or recurrence was found during the follow-up period (mean, 8 months; range, 6–24 months). Conclusions EFR seems to be an efficacious, safe, and minimally invasive treatment for patients with gastric SMT, which makes it possible to resect deep gastric lesion and provide precise pathological diagnosis of it. With the development of EFR, the indication of endoscopic resection may be expanded.

BackgroundThe endoscopic resection of gastrointestinal mesenchymal tumors (GIMTs) is widely accepted because of its minimal invasiveness. However, one major concern is the high rate of positive microscopic margins remaining following endoscopic resection, which was thought to be related to a higher risk of recurrence. This study aimed to determine whether positive margins affect the recurrence rate of gastric GIMTs and the factors associated with positive margins.MethodsPatients with gastric GIMTs were recruited retrospectively from January 2008 to December 2013. Clinical and pathological features, endoscopic procedure information, and follow-up data were collected and analyzed.ResultsThe study included 777 patients. All tumors were removed along with the pseudocapsule without macroscopic residual (ER0), and the median tumor size was 15.2 mm (range 3–100 mm). Pathological evaluation revealed 371(47.7%) GISTs. The rate of microscopic R1 resection rate was 47.0% (443/777). In a stepwise multivariate analysis, a significantly increased incidence of R1 resection was recorded for the GISTs (OR 11.13, 95% CI 3.00–41.37). In a subgroup analysis of GISTs, a univariate analysis revealed that EFTR achieved a higher rate of R0 resection (OR 0.56, 95% CI 0.31–1.00), but it was proven insignificant in a stepwise multivariate analysis. Local recurrence occurred in two patients (0.3%) during a mean follow-up time of 34.2 months. Differences in the recurrence rates between the R0 and R1 groups were statistically insignificant (P = 0.841).ConclusionsR1 resection for gastric GIMTs is not related to a higher recurrence rate than R0 resection, and ER0 resection is sufficient for gastric GIMTs.

(Bleeker, 1849) is common in China, belongs to the family Butidae within the order Gobiiformes. The complete mitochondrial genome of was sequenced and characterized for the first time. The circular genome is 16,521 bp in length, comprising 13 protein-coding genes, 22 transfer RNA genes, two ribosomal RNA genes and one control region. The phylogenetic reconstruction based on the mitochondrial genome sequences revealed as sister to . This study could be beneficial for systematic studies on family Butidae.

Patients with clear cell renal cell carcinoma (ccRCC) are often diagnosed with both von Hippel-Lindau (VHL) mutations and the constitutive activation of hypoxia-inducible factor-dependent signaling. In this study, we investigated the effects of long-term hypoxia in 786-O, a VHL-defective renal cell carcinoma cell line, to identify potential genes and microRNAs associated with tumor malignancy. The transcriptomic profiles of 786-O under normoxia, short-term hypoxia and long-term hypoxia were analyzed using next-generation sequencing. The results showed that long-term hypoxia promoted the ability of colony formation and transwell migration compared to normoxia. In addition, the differentially expressed genes induced by long-term hypoxia were involved in various biological processes including cell proliferation, the tumor necrosis factor signaling pathway, basal cell carcinoma and cancer pathways. The upregulated (L1CAM and FBN1) and downregulated (AUTS2, MAPT, AGT and USH1C) genes in 786-O under long-term hypoxia were also observed in clinical ccRCC samples along with malignant grade. The expressions of these genes were significantly correlated with survival outcomes in patients with renal cancer. We also found that long-term hypoxia in 786-O resulted in decreased expressions of hsa-mir-100 and hsa-mir-378 and this effect was also observed in samples of metastatic ccRCC compared to samples of non-metastatic ccRCC. These findings may provide a new direction for the study of potential molecular mechanisms associated with the progression of ccRCC.