Circular RNAs (circRNAs) have emerged as critical regulators in cancer progression. This study aimed to investigate the role of circ_0003266 in bladder cancer (BCa) and elucidate its underlying molecular mechanisms. The expression levels of circ_0003266, miR-503-5p, and SMAD7 in BCa tissues and cell lines were determined using bioinformatics analysis, clinical data, and quantitative real-time PCR (qPCR). Cellular phenotypes were evaluated through proliferation, migration, and apoptosis assays. RNA pull-down and luciferase reporter assays were conducted to validate the molecular interactions among circ_0003266, miR-503-5p, and SMAD7. The involvement of the TGF-β signaling pathway was assessed by Western blotting and co-immunoprecipitation (Co-IP) analysis. Circ_0003266 expression was significantly downregulated in BCa tissues and cell lines, and its low expression was clinically correlated with larger tumor size and advanced disease stage, including poor differentiation and higher TNM classification. Upregulation of circ_0003266 inhibited BCa cell proliferation and migration while promoting apoptosis. Mechanistic analyses revealed that miR-503-5p is a direct target of circ_0003266, and that circ_0003266-mediated regulation of miR-503-5p subsequently modulates SMAD7 expression. SMAD7, a well-established inhibitor of the TGF-β pathway, was shown to mediate the tumor-suppressive effects of circ_0003266. In vivo experiments confirmed that overexpression of circ_0003266 attenuated tumor growth and suppressed TGF-β signaling activity. Our findings demonstrate that circ_0003266 exerts tumor-suppressive functions in BCa by modulating the miR-503-5p/SMAD7/TGF-β axis, highlighting its potential as a novel therapeutic target for bladder cancer intervention.

Background This study aimed to compare low Hartmann’s procedure (LHP) with abdominoperineal resection (APR) for rectal cancer (RC) regarding postoperative complications. Method RC patients receiving radical LHP or APR from 2015 to 2019 in our center were retrospectively enrolled. Patients’ demographic and surgical information was collected and analyzed. Propensity score matching (PSM) was used to balance the baseline information. The primary outcome was the incidence of major complications. All the statistical analysis was performed by SPSS 22.0 and R. Results 342 individuals were primarily included and 134 remained after PSM with a 1:2 ratio (50 in LHP and 84 in APR). Patients in the LHP group were associated with higher tumor height ( P < 0.001). No significant difference was observed between the two groups for the incidence of major complications (6.0% vs. 1.2%, P = 0.290), and severe pelvic abscess (2% vs. 0%, P = 0.373). However, the occurrence rate of minor complications was significantly higher in the LHP group (52% vs. 21.4%, P < 0.001), and the difference mainly lay in abdominal wound infection (10% vs. 0%, P = 0.006) and bowel obstruction (16% vs. 4.8%, P = 0.028). LHP was not the independent risk factor of pelvic abscess in the multivariate analysis. Conclusion Our data demonstrated a comparable incidence of major complications between LHP and APR. LHP was still a reliable alternative in selected RC patients when primary anastomosis was not recommended.

Background: Tumor is a complex and dynamic ecosystem formed by the interaction of numerous diverse cells types and the microenvironments they inhabit. Determining how cellular states change and develop distinct cellular communities in response to the tumor microenvironment is critical to understanding cancer progression. Tumour-associated macrophages (TAMs) are an important component of the tumour microenvironment and play a crucial role in cancer progression. This study was designed to identify cellstate-specific M2 macrophage markers associated with gastric cancer (GC) prognosis through integrative analysis of single-cell RNA sequencing (scRNA-seq) and bulk RNA-seq data using a machine learning framework named EcoTyper. Results: The results showed that TAMs were classified into M1 macrophages, M2 macrophages, monocytes, undefined macrophages and dendritic cells, with M2 macrophages predominating. EcoTyper assigned macrophages to different cell states and ecotypes. A total of 168 cell-state-specific M2 macrophage markers were obtained by integrative analysis of scRNA-seq and bulk RNA-seq data. These markers could categorize GC patients into two clusters (clusters A and B) with different survival and M2 macrophages infiltration abundance. Cell adhesion molecules, cytokine-cytokine receptor interaction, JAK/STAT pathway, MAPK pathway were significantly enriched in cluster A, which had worse survival and higher M2 macrophages infiltration. Conclusion: In conclusion, this study profiles a single-cell atlas of intratumor heterogeneity and defines the cell states and ecotypes of TAMs in GC. Furthermore, we have identified prognostically relevant cell-state-specific M2 macrophage markers. These findings provide novel insights into the tumor ecosystem and cancer progression.

Deep cutaneous infections pose formidable challenges for conventional topical treatments due to limited drug transdermal efficiency and inadequate antifungal properties. This paper presents a rational engineering approach to develop biodegradable and multifunctional microneedles (MNs) that can be easily tailored for the co-delivery of both hydrophilic and hydrophobic drugs, aimed at the combined treatment of cutaneous infections. Polymyxin B (PB)-loaded Polyvinyl pyrrolidone (PVP) is casted to fabricate microneedle array, then followed by an electrospray coating of curcumin (CUR)-loaded poly(lactic-co-glycolic acid) (PLGA) particles, affording the resultant PB-PVP-MN@CUR-PLGA. Rational coating of hydrophobic PLGA shell can significantly withstand humidity, wound exudate, and pus. Comprehensive moisture resistance tests verify the sustained mechanical strength of the multifunctional MNs, even after one hour of storage at 85% relative humidity, the multifunctional MNs still maintain the potency to effectively penetrate skin tissues. In vitro and in vivo explorations confirm sustained drug release and efficient antimicrobial treatment. The promising outcomes of current multifunctional MNs lay a solid foundation for clinical translation to treat deep skin-related diseases.

Immune checkpoints inhibitors are effective but it needs more precise biomarkers for patient selection. We explored the biological significance of LINC00862 in pan-cancer by bioinformatics. And we studied its regulatory mechanisms using chromatin immunoprecipitation and RNA immunoprecipitation assays etc. TCGA and single-cell sequencing data analysis indicated that LINC00862 was overexpressed in the majority of tumor and stromal cells, which was related with poor prognosis. LINC00862 expression was related with immune cell infiltration and immune checkpoints expression, and had a high predictive value for immunotherapy efficacy. Mechanistically, LINC00862 competitively bound to miR-29c-3p to unleash SIRT1’s tumor-promoting function. SIRT1 inhibitor-EX527 were screened by virtual screening and verified by in vitro and vivo assays. Notably, acetyltransferase P300-mediated super-enhancer activity stimulated LINC00862 transcription. Collectively, LINC00862 could be a diagnostic and prognostic biomarker. LINC00862 could also be a predictive biomarker for immunotherapy efficacy. Super-enhancer activity is the driver for LINC00862 overexpression in cervical cancer and gastric cancer.

Supplementary Figure S2 PDF file 861K, Confirmation of h4D5 and D4(508-577) interaction by immunoprecipitation

Supplementary Figure S1 PDF file 1270K, Structural model of FcR - IgG Fc - domain B triple complex

PurposeThis study aimed to evaluate the impact of type 2 diabetes mellitus (T2DM) on the short-term outcomes and long-term survival of patients with colorectal cancer (CRC) who underwent curative resection.MethodsThis study retrospectively included 136 patients (T2DM group) with resectable CRC and T2DM from Jan 2013 to Dec 2017. Propensity score-matched control group consisting of 136 patients (non-T2DM group) were selected from 1143 CRC patients without T2DM. The short-term outcomes and prognosis were compared between the T2DM and non-T2DM group.ResultsA total of 272 patients (136 patients for each group) were included in this study. Patients in T2DM group had higher body mass index (BMI), higher proportion of hypertension and cerebrovascular diseases (P<0.05). T2DM group had more overall complications (P=0.001), more major complications (P=0.003) and higher risk of reoperation (P=0.007) when compared with non-T2DM patients. T2DM patients had longer hospitalization time than non-T2DM (20.7 ± 10.2 vs. 17.5 ± 6.2, P=0.002). As for the prognosis, T2DM patients had worse 5-year overall survival (OS) (P=0.024) and 5-year disease-free survival (DFS) (P=0.019) in all stage. Moreover, T2DM and TNM stage were the independent predictors of OS and DFS for CRC patients.ConclusionsT2DM increases overall complications and major complications, and prolongs the hospitalization time after CRC surgery. In addition, T2DM indicates the poor prognosis of CRC patients. A prospective study with large sample size is required to confirm our findings.

Supplementary Information PDF file - 77K, Additional information on the HER2 Domain 4 sequence, methods and figure legends for supplemental figures

Thermocapillary convection of nanofluid with evaporating phase change interface occurs in a variety of industrial processes such as micro/nano fabrication, ink-jet printing, thin film coatings, etc. Previous studies have mostly focused on the phenomena of thermocapillary convection in pure fluids without phase change. This paper reports the first fundamental experimental work on the thermocapillary flow of a thin nanofluid layer under the effect of evaporation. This research focuses on the behavior of a volatile thin nanofluid layer in a rectangular test cell under the effects of horizontal temperature gradient. The buoyancy effect can be neglected inside this thin liquid layer as in microgravity conditions. HEE7200 and HFE7200-Al 2 O 3 nanofluid are used as working fluids to analyze the effect of nanoparticle addition. The results indicate that the linear relationship between the thickness of the liquid layer and the duration of evaporation is not changed by nanoparticles. HFE7200-Al 2 O 3 nanofluid always has a higher evaporation rate than its base fluid with the temperature ranging from 2.98 °C to 13.92 °C. The critical Marangoni number for the nanofluid is lower than that of the pure fluid, which indicates that the addition of nanoparticles promotes the flow pattern transition.

Supplementary Figure S4 PDF file 583K, In vivo activity of h4D5 in the T6-17 model

It was with great interest that we read the article by Buisman et al. [ [1] Buisman F.E. Giardiello D. Kemeny N.E. et al. Predicting 10-year survival after resection of colorectal liver metastases; an international study including biomarkers and perioperative treatment. Eur J Cancer. 2022; 168: 25-33https://doi.org/10.1016/j.ejca.2022.01.012 Abstract Full Text Full Text PDF PubMed Scopus (17) Google Scholar ] entitled "Predicting 10-year survival after resection of colorectal liver metastases; an international study including biomarkers and perioperative treatment". In this study, the authors included a colorectal liver metastasis (CRLM) population from two centres that underwent complete resection and attempted to develop a model to predict 10-year overall survival (OS) of CRLM following resection based on patient, tumour and treatment characteristics. Through regression analysis, the authors successfully developed a prediction model including 15 independent factors that accurately predicted 10-year OS of CRLM after resection. In addition, the authors developed a simplified risk score that predicts the probability of 10-year OS. This impressive study has significant clinical importance, and we commend the authors for their contribution. However, there are still several points that deserve to be addressed. Predicting 10-year survival after resection of colorectal liver metastases; an international study including biomarkers and perioperative treatmentEuropean Journal of CancerVol. 168PreviewThe aim of this study was to develop a prediction model for 10-year overall survival (OS) after resection of colorectal liver metastasis (CRLM) based on patient, tumour and treatment characteristics. Full-Text PDF Open Access

Our laboratory has identified and developed a unique human-engineered domain (HED) structure that was obtained from the human Alpha-2-macroglobulin receptor-associated protein based on the three-dimensional structure of the Z-domain derived from Staphylococcal protein A. This HED retains µM binding activity to the human IgG1CH2-CH3 elbow region. We determined the crystal structure of HED in association with IgG1’s Fc. This demonstrated that HED preserves the same three-bundle helix structure and Fc-interacting residues as the Z domain. HED was fused to the single chain variable fragment (scFv) of mAb 4D5 to produce an antibody-like protein capable of interacting with the p185Her2/neu ectodomain and the Fc of IgG. When further fused with murine IFN-γ (mIFN-γ) at the carboxy terminus, the novel species exhibited antitumor efficacy in vivo in a mouse model of human breast cancer. The HED is a novel platform for the therapeutic utilization of engineered proteins to alleviate human disease.

Supplementary Figure S3 PDF file 1739K, Binding of antibodies to D4(508-577) by SPR analysis

目的 探讨阴性切缘(R0)胃肠道间质瘤(GIST)患者原癌基因酪氨酸蛋白激酶kit(C-kit)的基因突变特征与术后复发的关系.方法 选择行R0切除术的GIST患者66例作为研究对象,采用第一代Sanger测序法对组织样本进行基因检测,并收集患者的临床病理特征[年龄、性别、原发部位、肿瘤最大径、核分裂像数目、瘤体破裂、簇分化抗原117(CD117)、胃肠道间质瘤1的标记物(DOG1)、簇分化抗原34(CD34)、增殖标记蛋白Ki-67(Ki-67)、危险度分级、肿瘤淋巴结转移(TNM)分期、C-kit突变类型、手术方式及术后靶向治疗情况];取手术后GIST患者的切除肿瘤及周围组织,常规术后病理检测、C-kit突变类型及其突变位点检测;采用改良美国国立研究院(NIH)标准评估GIST患者的危险度,对低危患者每6个月随访1次、中高危患者每3个月随访1次,收集腹部电子计算机断层扫描(CT)或磁共振成像(MRI)检查结果判断是否复发,并计算3年无病生存期(DFS);采用Kaplan-Meier法和log-rank检验分别构建和分析GIST患者术后3年DFS生存曲线,采用多因素Cox回归分析影响GIST患者术后3年预后的相关因素.结果 Sanger测序显示,GIST患者C-kit突变主要发生在11号外显子,其次为9号外显子;肿瘤最大径、核分裂像计数、肿瘤是否破裂、Ki-67增值指数、NIH分级、TNM分期、C-kit突变类型与GIST患者术后3年DFS有相关性(P<0.05);Cox回归模型结果显示,肿瘤最大径≥5 cm、核分裂像计数≥5个/50高倍视野、肿瘤破裂、Ki-67增值指数≥5、中高危NIH分级、TNM分期Ⅱ和Ⅲ期、C-kit 9及11号外显子突变是R0切除GIST患者术后3年内复发的独立危险因素(P<0.05);生存曲线结果表明,3年DFS由低到高依次为外显子9、11、13、17.结论 C-kit基因突变与R0切除GIST患者术后复发相关,其中9、11号外显子突变是3年内复发的独立危险因素.

This letter to the editor raises concerns with the methodology of a recently published study that analyzed the role of vitamin D levels in survival outcomes in patients with pancreatic cancer.

The effects of phase change on the stability of a horizontally heated liquid layer are studied experimentally in this paper. Results are obtained for two volatile liquids with similar Prandtl numbers in a rectangular geometry with different temperature differences. Three different flow states occur with the variation of the liquid depth, namely oscillating multicellular convection, hydrothermal waves and steady flow. The critical conditions for the transition between the different flow states are identified and discussed. In addition, the presence of evaporation at the interface plays an essential role in the flow instabilities. The results show that evaporation at the surface and associated surface deformation tend to inhibit the development of a hydrothermal wave but conversely promote the transition of oscillating multicellular convection. Furthermore, the transient nature of HTWs is shown to be little affected by the phase change.

利用实践十号返回式科学实验卫星蒸发对流箱,开展了三相线处于钉扎状态且接触半径大于毛细长度的无水乙醇大滴在加热PTFE表面蒸发的地基科学实验.实验发现,液滴体积随时间线性递减,但钉扎大液滴蒸发过程中没有出现恒定接触角(CCA)阶段.与小液滴蒸发的恒定接触半径(CCR)阶段相同,大液滴的平均蒸发速率也与初始体积无关,表明受重力影响明显的大液滴蒸发主要发生在三相线附近区域.瞬时蒸发速率经历了迅速上升和之后的长时间内保持稳定两个阶段.与数值模拟结果对比分析发现,准静态扩散模型低估了三相线处于钉扎状态的大液滴瞬时蒸发速率,而同时考虑蒸气扩散与空气中自然对流经验模型的准确性取决于实验所用工质.

Overdosage of antibiotics used to prevent bacterial infections in the human and animal gastrointestinal tract would result in disturbing of intestinal barrier, significant misbalancing effects of intestinal microflora and persuading bacterial resistance. The main objective of the present investigation is to design and develop novel combinations of organic curcumin (Cur) and antimicrobial peptide (Amp) loaded chitosan nanoformulations (Cur/Amp@CS NPs) to improve significant effects on antibacterial action, immune response, intestine morphology, and intentional microflora. The antibacterial efficiency of the prepared nanoformulations was evaluated using Escherichia coli (E. coli) induced bacterial infections in GUT of Rat models. Further, we studied the cytocompatibility, inflammatory responses, α-diversity, intestinal morphology, and immune responses of treated nanoformulations in rat GUT models. The results indicated that Cur/Amp@CS NPs are greatly beneficial for intestinal microflora and could be a prodigious alternative of antibiotics.

Lately, long non-coding RNA (lncRNA) is recognized as a key regulator of gastric cancer (GC) which has aroused great interest in the fields of medicine, toxicology, and functional food. Studies related to LncRNA expression microarray data indicate that BX357664 is down-regulated in GC specimens. However, the expression pattern and molecular mechanism of BX357664 in GC have not been studied so far. The purpose of this study was to investigate the expression of lncRNA BX357664 in GC and its function in GC cell lines. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect the level of BX357664 in 50 pairs of cancer tissues and adjacent non-cancer tissues collected from GC patients. It was found that BX357664 level was lowered in cancer specimens than adjacent non-cancer tissues and correlated with tumor size and TNM stage. Also, we used cell counting kit 8 (CCK8), cell clone formation assay and transwell assay, which affirmed that up-regulation of BX357664 inhibited the proliferation, migration, and invasion of GC cells, but promoted apoptosis. In the dual-luciferase report analysis, BX357664 acted as a miR-183-3p ceRNA to target and regulate the expression of PTEN and affect the PI3K/AKT pathway. These results indicate that BX357664 can inhibit the proliferation and metastasis of GC through the miR-183-3p/PTEN/PI3K/AKT pathway, which may serve as potential targets for the treatment of GC in the future.