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The bioactivity of interferon-γ (IFN-γ) in cancer cells in the tumor microenvironment (TME) is not well understood in the current immunotherapy era. We found that IFN-γ has an immunosuppressive effect on colorectal cancer (CRC) cells. The tumor volume in immunocompetent mice was significantly increased after subcutaneous implantation of murine CRC cells followed by IFN-γ stimulation, and RNA sequencing showed high expression of B7 homologous protein 4 (B7H4) in these tumors. B7H4 promotes CRC cell growth by inhibiting the release of granzyme B (GzmB) from CD8 + T cells and accelerating apoptosis in CD8 + T cells. Furthermore, interferon regulatory factor 1 (IRF1), which binds to the B7H4 promoter, is positively associated with IFN-γ stimulation-induced expression of B7H4. The clinical outcome of patients with CRC was negatively related to the high expression of B7H4 in cancer cells or low expression of CD8 in the microenvironment. Therefore, B7H4 is a biomarker of poor prognosis in CRC patients, and interference with the IFN-γ/IRF1/B7H4 axis might be a novel immunotherapeutic method to restore the cytotoxic killing of CRC cells., (© 2024. The Author(s).)

Currently, the market demand of the non-animal-derived cholesterol is increasing. A novel synthetic route of producing cholesterol was developed through multiple reactions from plant-sourced and commercially available bisnoralcohol (BA). The key reaction conditions, including solvents, reaction temperatures, bases and reducing agents of the route were investigated and optimized. In this straightforward synthetic pathway of cholesterol, most of the reaction steps possess high conversions with average yields of 94%, and the overall yield is up to 74% (5 steps) from the BA. The epicholesterol and were also synthesized. This promising route offers economical and efficient strategies for potential large-scale production of plant-derived cholesterol., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Microscopic indications of malignancy and hallmark molecules of cancer are pivotal to determining cancer patient prognosis and subsequent medical intervention. Here, we found that compared to apical expression of Cdc42, which indicated that basal expression of Cdc42 occurred at the migrating cell front, glandular basal expression of Cdc42 (cell division cycle 42) in tissues indicated poorer prognoses for colorectal cancer (CRC) patients. The current study shows that activated Cdc42 was rapidly recruited to the migrating CRC cell front after VEGF stimulation through engagement of membrane-anchored neuropilin-1 (NRP1). When VEGF signalling was blocked with NRP1 knockdown or ATWLPPR (A7R, antagonist of VEGF/NRP1 interaction), Cdc42 activation and relocation to the cell front was attenuated, and filopodia and invadopodia formation was inhibited. The VEGF/NRP1 axis regulates directional migration, invasion, and metastasis through Cdc42 activation and relocation resulting from actin filament polymerisation of the extensions of membrane protrusions. Collectively, the immuno-micromorphological pattern of subcellular Cdc42 at the cell front indicated aggressive behaviours and predicted poor prognosis in CRC patients. Disruption of the intra- and extracellular interactions of the VEGF/NRP1 axis or Cdc42 relocation could be performed in clinical practice because it might inhibit cancer cell motility and metastasis.

Background: DNA-Dependent Protein Kinase Catalytic Subunit (PRKDC), a key component of the DNA damage repair pathway, is associated with chemotherapy resistance and tumor progression., Methods: Here we analyzed transcriptome data of ~2,000 breast cancer patients and performed functional studies in vitro to investigate the function of PRKDC in breast cancer., Results: Our results revealed overexpression of PRKDC in multiple breast cancer subtypes. Consistent with patients' data, overexpression of PRKDC was also observed in breast cancer cell lines compared to normal breast epithelial cells. Knockdown of PRKDC in MCF-7 and T47D breast cancer cell lines resulted in proliferation inhibition, reduced colony formation and G2/M cell cycle arrest. Furthermore, we showed that PRKDC knockdown induced proliferation inhibition through activation of p38 MAPK, but not ERK MAPK, signaling pathway in breast cancer cells. Blockage of p38 MAPK signaling could largely rescue proliferation inhibition and cell cycle arrest induced by PRKDC knockdown. Moreover, we analyzed gene expression and clinical data from six independent breast cancer cohorts containing ~1,000 patients. In all cohorts, our results consistently showed that high expression of PRKDC was significantly associated with poor survival in both treated and untreated breast cancer patients., Conclusion: Together, our results suggest that high expression of PRKDC facilitates breast cancer cell growth via regulation of p38 MAPK signaling, and is a prognostic marker for poor survival in breast cancer patients., (© 2019 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.)

A hallmark of gastric cancer is the high rate of genomic instability associated with deregulation of DNA damage repair pathways. DNA-Dependent Protein Kinase Catalytic Subunit (PRKDC) is a key component of the non-homologous end-joining (NHEJ) pathway. By reanalyzing transcriptome data of 80 pairs of gastric cancer tumors and the adjacent normal tissues from non-treated patients, we identified PRKDC as the top upregulated DNA damage repair genes in gastric cancer. High expression of PRKDC is associated with poor survival of gastric cancer patients, and genomic amplification of the gene is frequently observed across most gastric cancer subtypes. Knockdown of PRKDC in gastric cell lines resulted in reduced proliferation and cell cycle arrest. Furthermore, we showed that loss of PRKDC induced DNA damage and enhanced gastric cancer cell chemosensitivity to DNA-damaging reagents. Together, our results suggest that PRKDC is a prognostic marker of poor survival and is a putative target to overcome chemoresistance in gastric cancer., (Copyright © 2019 Elsevier GmbH. All rights reserved.)

Rationale and Objectives: As an extension of the conventional diffusion weighted imaging, diffusion kurtosis imaging (DKI) is based on the non-Gaussian diffusion model that can inherently account for restricted water diffusion within the complex microstructure of most tissues. This study aimed to investigate association of liver DKI derived parameter with stage of liver fibrosis., Materials and Methods: Fifty-six healthy New Zealand white rabbits were enrolled into this study, among which 48 rabbits were randomly given carbon tetrachloride to model liver fibrosis, and 8 rabbits treated with normal saline served as control subjects. All rabbits underwent liver DKI followed by biopsy to stage fibrosis (stages F0-F4) on 6th, 8th, 10th, and 12th weekends after initiation of modeling fibrosis. Mean kurtosis (MK), fractional anisotropy (FA), and mean diffusion (MD) were derived from DKI data. Statistical analysis was to evaluate association of DKI derived parameter with stage of fibrosis., Results: FA (r = 0.512) and MK (r = 0.567) increased, and MD (r = -0.574) decreased with increasing stage of fibrosis from F0 to F4 (all p values < 0.05). Significant differences were found in all parameters between F0 and F3 or F4, F1 and F4, F0 and F1-4, and F0-1 and F2-4 (all p values < 0.05). FA and MD could distinguish between F0 from F2, MD, and MK could distinguish F1 from F3, F0-2 from F3-4, and F1-2 from F3-4, and MK and FA could distinguish F2 from F4, and F0-3 from F4 (all p values < 0.05). According to receiver operating characteristic analysis, MK could best predict stage ≥F1, ≥F2, ≥F3, and F4, and discriminate F1-2 from F3-4 with areas under receiver operating characteristic curve of 0.766-0.930., Conclusion: DKI derived parameters can help stage fibrosis., (Copyright © 2018 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Nasal glioma is a rare congenital malformation in maxillofacial region. It is sluggish, benign, non-tumorous and with low recurrence rate. It is important to evaluate whether there is any intracranial connection before the operation through CT or MRI to avoid the serious intracranial complications. We reported a case of a adult with a nasal glioma in sphenoid sinus, and discuss clinical characteristics, diagnosis, and pathology., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

Fluorescence polarization microscopy (FPM) aims to detect the dipole orientation of fluorophores and to resolve structural information for labeled organelles via wide-field or confocal microscopy. Conventional FPM often suffers from the presence of a large number of molecules within the diffraction-limited volume, with averaged fluorescence polarization collected from a group of dipoles with different orientations. Here, we apply sparse deconvolution and least-squares estimation to fluorescence polarization modulation data and demonstrate a super-resolution dipole orientation mapping (SDOM) method that resolves the effective dipole orientation from a much smaller number of fluorescent molecules within a sub-diffraction focal area. We further apply this method to resolve structural details in both fixed and live cells. For the first time, we show that different borders of a dendritic spine neck exhibit a heterogeneous distribution of dipole orientation. Furthermore, we illustrate that the dipole is always perpendicular to the direction of actin filaments in mammalian kidney cells and radially distributed in the hourglass structure of the septin protein under specific labelling. The accuracy of the dipole orientation can be further mapped using the orientation uniform factor, which shows the superiority of SDOM compared with its wide-field counterpart as the number of molecules is decreased within the smaller focal area. Using the inherent feature of the orientation dipole, the SDOM technique, with its fast imaging speed (at sub-second scale), can be applied to a broad range of fluorescently labeled biological systems to simultaneously resolve the valuable dipole orientation information with super-resolution imaging.

Objective: To study the correlation between the angle of the pancreaticobiliary junction (APJ) and the prevalence of acute pancreatitis using magnetic resonance cholangiopancreatography (MRCP)., Materials and Methods: From February 2014 to October 2014, thirty two subjects with normal pancreas (group A) and 40 patients with acute pancreatitis (group B) who underwent MRCP were enrolled into our study. The type of biliary duct and main pancreatic duct joining the duodenal wall was reviewed and divided into V, B-P and P-B type. The V type is the pancreatic duct and biliary duct joining the duodenal wall without a common channel; the B-P type is the biliary duct draining into the pancreatic duct and forming a common channel; and the P-B type is the pancreatic duct draining into the biliary duct and forming a common channel. APJ was measured on MRCP. The correlation between the APJ and the prevalence of acute pancreatitis was analyzed., Results: The APJ in group A was smaller than in group B (51.45°±13.51° vs. 65.76°±15.61°, P<0.05). According to the type of biliary duct and main pancreatic duct joining the duodenal wall, the prevalence of acute pancreatitis in the V type and in the B-P type was higher than in the P-B type (12/17 vs. 10/29, or 18/26 vs. 10/29, respectively, all P<0.05), whereas there were no significant difference for the prevalence of acute pancreatitis between the V type and B-P type (P>0.05). The APJ were 59.32°±20.04°, 60.22°±11.06°, 57.13°±17.27°, respectively in V type, B-P type and P-B type joining of main pancreatic duct (P>0.05)., Conclusions: A larger APJ is related to a higher prevalence of acute pancreatitis.

Background and Objective: To determine associations of patterns of portosystemic collaterals and diameters of portal venous system in cirrhotic patients with hepatitis B on magnetic resonance (MR) imaging with Child-Pugh classification., Materials and Methods: Eighty-eight consecutive patients with cirrhosis resulting from chronic hepatitis B graded by Child-Pugh classifications were recruited and undergone MR portography. Patterns of the collaterals (presented as no collateral, isolated esophageal varices, and esophageal varices combined with other shunts), and diameters of portal venous system including portal vein (PV), left portal vein (LPV), right portal vein (RPV), splenic vein (SV) and superior mesenteric vein (SMV) were assessed statistically to determine associations of patterns of collaterals and diameters of the portal veins with Child-Pugh classification., Results: From no collateral, to isolated esophageal varices, and to the varices combined with other shunts, the Child-Pugh classifications tended to increase (r=0.516, P<0.001). Diameters of PV, LPV, RPV, SV and SMV tended to increase from Child-Pugh A to B but decrease from B to C. Differences in diameter of LPV and SV were significant between Child-Pugh A-B and C (all P<0.05) while no differences in diameters of other portal veins were found (all P>0.05). For discriminating Child-Pugh A-B from C, either a cut-off LPV diameter of 8.98mm or SV diameter of 9.10mm achieved a sensitivity of 67%-70%, specificity of 51%-53%., Conclusion: Patterns of portosystemic collaterals and diameters of LPV and SV tend to be associated with Child-Pugh classifications of cirrhosis., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

We have developed a quantum dot-based microRNA nanosensor for point mutation assays using primer generation-mediated rolling circle amplification. The proposed method exhibits high sensitivity with a detection limit of as low as 50.9 aM and a large dynamic range of 7 orders of magnitude from 0.1 fM to 1 nM. Importantly, this method can be further applied to analyze the point mutation of mir-196a2 in the lung tissues of non small-cell lung cancer patients.

Objective: To study MRI findings of abdominal wall edema (AWE) in acute pancreatitis as well as correlations between AWE and the severity of acute pancreatitis according to the MR severity index (MRSI) and the Acute Physiology And Chronic Healthy Evaluation III (APACHE III) scoring system., Materials and Methods: A total of 160 patients with AP admitted to our institution between December 2009 and March 2011 were included in this study. MRI was performed within 48 h after admission. MRI findings of acute pancreatitis were noted, including AWE on the MRI. The abdominal wall area was divided into quarters, and each area involved was recorded as 1 point to score the severity of AWE. The severity of acute pancreatitis was studied using both the MRSI and the APACHE III scoring system. Spearman correlation of AWE with the MRSI and the APACHE III scoring system was analyzed., Results: In 160 patients with acute pancreatitis, 53.8% had AWE on MRI. The average AWE score was 1.2±1.4 points. The prevalence of AWE was 30.5%, 64.5% and 100% in mild, moderate and severe AP, respectively, according to MRSI. AWE on MRI was correlated with MRSI scores (r=0.441, p=0.000). According to APACHE III scores, the averages were 2.0±1.1 and 2.6±1.1 points in mild AP and severe AP, respectively (P=0.016). AWE was slightly correlated with the APACHE III scores (r=0.222, p=0.005)., Conclusion: AWE on MRI in acute pancreatitis is common, which may be a supplementary indicator in determining the severity of AP., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Objectives: To study the prevalence and characteristics of renal and perirenal space involvement and its relation to the severity of acute pancreatitis (AP) using MRI., Methods: 115 patients with AP who underwent MRI with the clinical kidney function test were retrospectively analyzed in this study. MRI sequences included conventional and diffusion weighted imaging (DWI) sequences. The renal and perirenal space involvement in AP was noted on MRI. The renal apparent diffusion coefficient (ADC) on DWI was measured for each kidney. The severity of AP on MRI was graded using MR severity index (MRSI). The relationships among the renal and perirenal space involvement on MRI, the renal ADC, MRSI and the results of the kidney function test were analyzed., Results: In the 115 patients with AP, the renal and perirenal space abnormalities detected included renal parenchymal abnormalities (0.8%), abnormalities of the renal collecting system (2.6%), renal vascular abnormalities (1.7%), thickened renal fascia (99%), perirenal stranding (62%) and perirenal fluid collection (40%). The prevalence of perirenal space abnormalities was correlated with the severity of AP based on MRSI (P<0.05). The renal ADC values were lower in patients with abnormal kidney function than in those without kidney injury (P<0.05). The prevalence of kidney function abnormalities was 9.4%, 32% and 100% in mild, moderate, and severe AP cases, respectively (P=0.00)., Conclusion: Perirenal space involvement is much more than renal parenchymal involvement in AP. The prevalence of perirenal space involvement in AP on MRI has a positive correlation with the severity of AP according to MRSI., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

In the crystal structure of the title compound, C(9)H(8)F(3)N(3)S, all atoms except for two of the F atoms are located on a mirror plane. In the crystal, the molecules are connected by N-H⋯S hydrogen bonds, forming a mol-ecular tape along the a axis.

The weak inclusion complex of cyclomaltoheptaose (beta-cyclodextrin, betaCD) with p-nitrobenzoic acid was investigated in the solid state. Crystallography shows that two betaCD molecules co-crystallize with two p-nitrobenzoic acids and 28.5 water molecules [2(C(42)H(70)O(35))x2(C(7)H(5)NO(4))x28.5H(2)O] in the triclinic system.

An inclusion complex formed by beta-cyclodextrin and quinine has been investigated in solution and in the solid state, in which the quinoline ring and the aliphatic ring locate in different hydrophobic cavities, respectively. The study on the inclusion geometry and weak interactions shows that the difference in conformation for this complex is a result of three main packing arrangement considerations, which can provide an ideal model mimicking enzyme-substrate interactions.

The mono-modified beta-cyclodextrin derivative, 6(I)-O-(3-nitrophenyl)cyclomaltoheptaose{mono[6-O-(3-nitrophenyl)]-beta-cyclodextrin} was synthesized, and its crystal structure was determined by single-crystal X-ray analysis. The crystal structure suggests that the 3-nitrophenyl substituent group is inserted into the adjacent beta-cyclodextrin cavity from the secondary hydroxyl side, and the molecules are stacked along the twofold screw axis to form an infinite one-dimensional polymeric chain.