H3K4me3-related lncRNAs signature and comprehensive analysis of H3K4me3 regulating tumor immunity in lung adenocarcinoma.

BACKGROUD: The role of epigenetic modifications in tumorigenesis has been widely reported. However, the role and mechanism of H3K4me3 modification in lung adenocarcinoma (LUAD) are rarely reported systematically. We, therefore, sought to analyze the characteristics of LUAD associated with H3K4me3 modification, build an H3K4me3-lncRNAs score model to predict the prognosis of patients with LUAD and clarify the potential value of H3K4me3 in immunotherapy of LUAD. METHODS: We evaluated H3K4me3-lncRNA patterns and H3K4me3-lncRNA scores of 477 LUAD samples based on 53 lncRNAs closely correlated to H3K4me3 regulators and comprehensive analyzed the role of these patterns in tumorigenesis and tumor immunity. Using Gene set variation analysis (GSVA), we systematically evaluated the H3K4me3 level of every sample and deeply analyzed the effect of H3K4me3 on the prognosis of LUAD. In addition, we included two independent immunotherapy cohorts to study the impact of high H3K4me3 score on the prognosis of patients. We also used an independent cohort with 52 matched paraffin specimens of LUAD to verify the impact of high H3K3me3 expression on the prognosis of patients. RESULTS: We identified three H3K4me3-lncRNA patterns that exhibited specific immune characteristics. Characterized by immunosuppressive and increased TGFß-mediated epithelial-mesenchymal transition (EMT), patients with high H3K4me3-lncRNA score had a poor overall survival and decreased H3K4me3 score. H3K4me3 score was significantly positively correlated with CD4+T-cell and CD8+T-cell activation, programmed cell death and immune checkpoints (ICs) expression, and was negatively correlated with MYC pathway, TP53 pathway, and cell proliferation. Patients with high H3K4me3 score showed elevated expression of ICs, potentiated CD4 T-cell and CD8 T-cell activation, increased programmed cell death, and suppressed cell proliferation and TGFß-mediated EMT. Patients with high H3K4me3 score and high expression of CTLA4, ICOS, TIGIT, PDCD1LG2, IDO1, CD274, PDCD1, LAG3, or HAVCR2 had the best survival advantage. Two independent immunotherapy cohorts verified that patients with high H3K4me3 score showed an increased inflamed tumor microenvironment (TME) phenotype and enhanced anti-PD-1/L1 immunotherapy response. Immunohistochemistry (IHC) data from 52 matched paraffin specimens of LUAD confirmed that the protein level of H3K4me3 in tumor was significantly lower than that of paracancerous tissues and H3K4me3 brought significant survival benefits to patients with LUAD. CONCLUSIONS: We build an H3K4me3-lncRNAs score model to predict the prognosis of patients with LUAD. More importantly, this study revealed characteristics of H3K4me3 modification in LUAD and clarified the important potential role of H3K4me3 on tumor immunotherapy and patients' survival.

Risk and prognosis of secondary thoracic cancers after radiation therapy for esophageal cancer.

BACKGROUND AND AIM: Radiation therapy (RT) is a crucial modality for the local control of esophageal cancer (EC), but the effect of RT on the development of secondary thoracic malignancies is still unclear. This study aims to identify the association between RT for the treatment of primary EC and subsequent secondary thoracic cancer (STC). METHODS: The primary EC patients were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. Fine-Gray competing risk regression and standardized incidence ratio (SIR) were used to evaluate the radiotherapy-associated cancer risk. Overall survival (OS) was compared by Kaplan-Meier analysis. RESULTS: A total of 40 255 EC patients from the SEER database were identified, of which 17 055 patients (42.37%) did not receive radiotherapy (NRT) and 23 200 patients (57.63%) had been treated with RT. After 12 months of latency, 162 patients (0.95%) in the NRT group and 272 patients (1.17%) in the RT group developed STC. The incidences of the RT group were significantly higher than the NRT group. Patients who have primary EC were at an increased risk of developing STC (SIR = 1.79, 95% CI: 1.63-1.96). The SIR of STC was 1.37 (95% CI: 1.16-1.60) in the NRT group and 2.10 (95% CI: 1.87-2.34) in the RT group. The OS of STC patients in the RT group was significantly lower than the NRT group (P = 0.006). CONCLUSION: The RT for primary EC was associated with higher risks of developing STC than patients unexposed to radiotherapy. The EC patients treated with RT, especially young patients, require long-term monitoring of the risk of STC.

Sustainable synthesis of hydroxyl-functional porous organic framework as novel adsorbent for effective removal of organic micropollutants from water.

Organic micropollutants (OMPs) in water resources are a growing threat to aquatic ecosystems and human health. Efficient removal of polar OMPs is very challenging because of their high hydrophility. Synthesizing novel adsorbent capable of high-efficiently removing hydrophilic and hydrophobic micropollutants is highly desirable for water remediation. Here, using natural proanthocyanidin as building units, a novel hydroxyl-functional porous organic framework (denoted as PC-POF) with amphiphilic feature was synthesized through facile azo coupling reaction. Five sulfonamide antibiotics were selected as model OMPs for adsorption study. Adsorption experiments demonstrated a more rapid and efficient sulfonamides capture ability of the PC-POF than that of the most reported adsorbents due to strong hydrogen bonding, π stacking and electrostatic interactions. The PC-POF can be easily recovered and reused at least 5 times without obvious decline in adsorption performance. Moreover, experiments conducted at environmentally relevant concentrations (µg L-1) further confirmed a notable adsorption performance of the PC-POF even when the sulfonamides solution was rapidly passed through the PC-POF packed column. The PC-POF also showed good adsorption performance for other micropollutants like neonicotinoid insecticides, nitroimidazole antibiotics and triazine herbicides, indicating a promising prospect. This work provides a new strategy to construct amphiphilic adsorbent by using renewable resources for pollutants removal.

[Modeling of Abdominal Wall-Cecum Injury Adhesion and the Anti-adhesion Mechanism of mXG].

OBJECTIVE: To construct the adhesion model of abdominal wall-cecum injury and explore the prevention and treatment effect of modified xyloglucan (mXG) thermosensitive hydrogel on abdominal wall-cecal injury adhesion. METHODS: SD rats were used to construct the abdominal wall-cecal injury adhesion model. Model mice were randomly divided into blank control group (Control), commercial chitosan membrane Control group (Film) and mXG thermosensitive hydrogel group (Hydrogel), each group contained 16 rats.In the Hydrogel group, 1 mL 4% (m/V) mXG solution was smeared on the wound surface of abdominal wall and the cecum, then closed the abdomen after gel was formed (3 min).In the Film group, 2 cm×3 cm chitosan anti-adhesion Film was applied onto the wound surface of the abdominal wall before abdominal closure.In the Control group, 1 mL normal saline was applied onto the wound surface of abdominal wall and the cecum before abdominal closure.On 7 and 14 d after the operation, rats'abdominal cavity was opened by surgery to examine and score the adhesion grade between the abdominal wall and the cecum, with double-blind design.Meanwhile, the adhesion tissue or wound tissue was taken and stained by HE, Masson and Van Gieson to histological evaluate the anti-adhesion effect.The expression of transforming growth factor-ß1 (TGF-ß1) and connective tissue growth factor (CTGF) was determined by immunohistochemical staining as well. Another group of 12 SD rat models were subjected to mXG thermosensitive hydrogel intervention.At the 1 and 6 weeks postoperation, rats main organs such as heart, liver, spleen, lung and kidney were taken for histological examination with HE staining for the purpose of evaluation the toxicity of mXG in vivo. RESULTS: Adhesion grade evaluation results showed that Film group rats occurred mild adhesion, Control group rats occurred severe adhesion, while in Hydrogel group hardly rats occured adhesion, and the differences were statistically significant(P < 0.05). Histological results showed that the Hydrogel group rats recovered well at 7 d after surgery.In healing wound tissue, no mutated tissue was observed, but a certain degree of inflammatory cell infiltration was still existed. At 14 d after surgery, the inflammation cells in the wound were significantly reduced, and the healing tissue containing only a small amount of collagen fibers under the neonatal mesothelial layer.But the other two groups showed different degrees of adhesion at the 7 and 14 d post surgery.Immunohistochemical staining showed that the expression of TGF-ß1 and CTGF in the Hydrogel group were both weaker than those in the other groups, and the difference was statistically significant (P < 0.05). In vivo toxicity tests did not show significant changes in the structure of the organs of mXG gel intervention rats at different time points. CONCLUSION: mXG thermosensitive hydrogel plays a good role in physical isolation during the key period of adhesion formation and effectively prevent the occurrence of cecum-abdominal adhesion.

A Comprehensive Comparison of CT, MRI, Positron Emission Tomography or Positron Emission Tomography/CT, and Diffusion Weighted Imaging-MRI for Detecting the Lymph Nodes Metastases in Patients with Cervical Cancer: A Meta-Analysis Based on 67 Studies.

OBJECT: In recent times, many published papers reported the diagnostic performance of CT, MRI, positron emission tomography (PET) using 2-[18F] fluoro-2-deoxy-D-glucose (FDG) and diffusion-weighted magnetic resonance imaging (DW-MRI) for detecting the lymph nodes (LNs) metastases in patients with cervical cancer. This study is aimed at assessing and comparing the diagnostic value of those non-invasive modalities in detecting the LNs metastases in cervical cancer patients. METHODS: Studies on the non-invasive modalities for the detection of metastatic LNs were searched in PubMed, Medline, Web of Science, Cochrane Library and Embase databases. Pooled positive likelihood ratios and negative likelihood ratios, diagnostic OR, area under curve (AUC), summary receiver operating characteristics were calculated as evaluation indices. RESULTS: In region- or node-based analysis, the AUC of DWI-MRI (0.92) and PET or PET/CT (0.90) were better than CT (0.83), and the difference was significant (DWI-MRI vs. CT: Z = 4.61, p < 0.001; PET or PET/CT vs. CT: Z = 3.61, p = 0.001). CONCLUSION: Among the 4 non-invasive modalities, the PET or PET/CT has the highest specificity, and DWI-MRI has the highest sensitivity.

One-step preparation of carboxyl-functionalized porous organic polymer as sorbent for enrichment of phenols in bottled water, juice and honey samples.

Herein, a novel carboxyl-functionalized porous organic polymer (COOH-POP) was prepared as sorbent. Due to multiple hydrogen bonds and π-π interactions between COOH-POP and phenols, COOH-POP shows good enrichment ability and very fast adsorption rate for phenols. Then, an analytical method was developed for determination of five phenols (2-chlorophenol, bisphenol A, 2,6-dichlorophenol, 2,4-dichlorophenol and p-tert-butylphenol) in bottled water, lemon juice, peach juice and honey samples using COOH-POP as solid phase extraction sorbent in combination with high performance liquid chromatography. Under optimal conditions, the COOH-POP based method gave the detection limits (S/N = 3) of 0.02-0.10 ng mL-1 for bottled water, 0.03-0.12 ng mL-1 for lemon juice, 0.03-0.25 ng mL-1 for peach juice and 0.7-1.5 ng g-1 for honey samples. The recoveries for spiked samples ranged from 84.0 % to 119.0 % with relative standard deviation less than 7.6 %. This study provides a new yet effective method for enrichment of phenols by designing carboxyl-functionalized porous organic polymer as sorbent.

Novel magnetic porous organic polymer containing amino and triazine bifunctional groups for efficient adsorption of nitroimidazoles.

In this paper, a novel magnetic hyper-crosslinked polymer with amino and triazine bifunctional groups (M-NH2-THCP) was developed. M-NH2-THCP has strong nitroimidazoles (NDZs) enrichment effect, and therefore it was used as an adsorbent to extract five NDZs from lake water, catfish and shrimp meat prior to HPLC. Polar interaction, π-π stacking interaction, hydrogen bond and Lewis acid-base interaction were attested to be the major adsorption mechanism. The method has a good linearity in the range of 0.1-100 ng mL-1 for lake water, 10-400 ng g-1 for catfish and shrimp muscle with R2 > 0.9964. The limits of detection of NDZs were 0.03-0.04 ng mL-1 for lake water, 1.0-2.0 ng g-1 for catfish and 2.0-2.5 ng g-1 for shrimp, which is superior to most reported method. The method recoveries were 87.6-119 %, and relative standard deviations were less than 8.7 %. M-NH2-THCP holds great application potential in pollutants enrichment, separation and removal.

Fabrication of chitin based hydrophilic hyper-crosslinked porous polymer for efficiently removing bisphenol A from water.

Water pollution caused by bisphenol A (BPA) has become the world problem. Designing and preparing cost-effective and biodegradable sorbents for the effectively adsorptive removal of bisphenol A from wastewater is of immense significance. Herein, a natural polysaccharide (chitin) was used as raw materials to be grafted with styrene (GS), then crosslinked with α,α'-dichloro-p-xylene (DCX) to form the hyper-crosslinked polymer (labeled as CGS@DCX). The CGS@DCX showed high adsorptive affinity for bisphenol A, with adsorption capacity of 441 mg g-1. Various studies gave an insight into the adsorption process, demonstrating that the highly efficient adsorption of BPA by the CGS@DCX is mainly based on the π-π stacking, hydrogen-bond interaction, polar interaction and pore adsorption. Moreover, the CGS@DCX had high chemical stability, good reusability (9 cycles) and fast adsorption kinetics (10 min) for adsorption of BPA. This work provides a promising strategy for the design and synthesis of novel yet eco-friendly sorbents to solve environmental problems.

MnO2 nanoflowers based colorimetric and fluorescent dual-mode aptasensor for sensitive detection of aflatoxin B1 in milk.

Aflatoxin B1 (AFB1) with tremendous toxic effects has caused a serious threat to food security. Accurate quantification of AFB1 in food can effectively prevent the risk of human intake of AFB1. Herein, a colorimetric and fluorescent dual-mode aptasensor for accurate and sensitive detection of AFB1 has been developed based on MnO2 nanoflowers (MnO2NFs) for the first time. MnO2NFs could catalyze the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) into blue oxidation product (TMBox) by H2O2, which would be used for visible detection of AFB1. Simultaneously, MnO2NFs can be served as a signal amplifier and reduced by ascorbic acid to generate lots of Mn2+ which would quench the fluorescence of calcein for fluorescent detection of AFB1. Both colorimetric and fluorescent methods have been successfully applied for determination of AFB1 in milk samples with satisfactory results. The proposed dual-mode detection method with high detection sensitivity and accuracy showed great promise for monitoring AFB1 in food.

Predictive Value of the Neutrophil-Lymphocyte Ratio for Tumor Regression Grade and Prognosis of Local Advanced Rectal Cancer Patients Undergoing Neoadjuvant Chemoradiotherapy.

PURPOSE: Numerous indicators can be used to predict tumor patients' prognosis and tumor regression grade (TRG). The role of the neutrophil-lymphocyte ratio (NLR) among individuals with locally advanced rectal cancer (LARC) following neoadjuvant chemoradiotherapy (nCRT) hasn't been studied, nevertheless. This study aims to explore the predictive value of the NLR before nCRT (pre-NLR) in TRG and prognosis of LARC patients undergoing nCRT.. METHODS: In this retrospective investigation, 326 LARC patients receiving nCRT in total were included. The link between the pre-NLR and TRG was examined using a logistic regression analysis. A Cox-based nomogram was created in the meanwhile to forecast overall survival (OS). With the use of calibration plots and receiver operating characteristic (ROC) curves, we evaluated the nomogram's predictive capabilities. RESULTS: The median pre-NLR across 326 patients was 2.2 (interquartile range, IQR: 1.7-2.7). In the logistic regression analysis, only the pre-NLR for TRG in LARC patients receiving nCRT was statistically significant (odds ratio, OR = 0.62, 95% CI: 0.47-0.80, P < 0.001). Pre-NLR, nCRT with surgery interval, ypTNM stage, TRG, vascular invasion, adjuvant chemotherapy, and carbohydrate antigen 19-9 before nCRT were revealed to be OS predictors in the Cox multivariate analysis. According to calibration plots and ROC curves, the predictive nomogram demonstrated high statistical performance on internal validation. CONCLUSION: This study demonstrated that a lower pre-NLR was probably associated with a greater rate of TRG in LARC patients undergoing nCRT. Furthermore, the pre-NLR was credibly correlated with OS in LARC patients undergoing nCRT. Meanwhile, we constructed a nomogram for predicting the prognosis in LARC patients undergoing nCRT.

Differences in clinical characteristics and prognosis between breast neuroendocrine carcinoma and breast invasive ductal carcinoma: A multicentre population-based study from China.

AIM: We constructed a multicentre cohort in China to analyse the differences in clinical characteristics, treatment strategies and prognoses between breast neuroendocrine carcinoma (NEC) and invasive ductal carcinoma (IDC) of the breast. METHODS: All patients with early-stage breast cancer who attended three hospitals in Beijing from 2000 to 2018 were included in the study. We used propensity score matching to make a 1:3 match between NEC and IDC. RESULTS: After propensity score matching, 153 patients with IDC and 51 patients with NEC were analysed. Multivariate Cox regression showed that compared to patients with IDC, patients with NEC had a worse disease-free survival (HR = 2.94, 95% CI: 1.69-5.12, p < 0.001). CONCLUSION: NEC patients have a worse disease-free survival than IDC patients.

Fluorine-Functionalized Triazine-Based Porous Organic Polymers for the Efficient Adsorption of Aflatoxins.

Food safety issue caused by aflatoxins has aroused widespread concern in society. Herein, a novel fluorine-functionalized triazine-based porous organic polymer (F-POP) was developed for the first time by the simple condensation polymerization of 2,2'-bis(trifluoromethyl)benzidine and cyanuric chloride. With in-built fluorine functional group (F) and imine group (-NH-), F-POP displayed significantly superior adsorption ability for aflatoxins, outperforming fluorine-free POP due to the multiple interaction mechanisms of hydrogen bond, F-O interaction, π-π interaction, F-π interaction, and hydrophobic interaction. Thus, magnetic F-POP was prepared by introducing Fe3O4 into F-POP and then utilized as a magnetic sorbent for the extraction of trace aflatoxins in peanut and rice samples prior to high-performance liquid chromatography-fluorescence detection. Under the optimal conditions, the proposed method presented high sensitivity with the limit of detections at 0.005-0.15 ng g-1. F-POP also exhibited outstanding adsorption capability for many other organic pollutants, revealing its great potential for analysis or adsorption applications.

Synthesis of phosphate-functionalized magnetic porous organic polymer: A sorbent for sensitive determination of neonicotinoid insecticides in water and lemon juice.

There is an urgent need to prepare advanced functional materials for extraction and enrichment of trace organic pollutants from different samples. In this work, two novel phosphate-functionalized porous organic polymers (DBP-POP and DPP-POP) were synthesized for the first time. Compared with phosphate-free counterpart, both phosphate-functionalized POPs showed excellent adsorption performance for the neonicotinoids due to the hydrogen bonding, π-π interaction and hydrophobic interaction. For ease of separating the sorbent from solution, magnetic DBP-POP (M-DBP-POP) was further prepared as sorbent to extract neonicotinoids from environmental water and lemon juice samples prior to their determination by high performance liquid chromatography-ultraviolet detection. Under optimal conditions, the detection limits (S/N = 3) of the method were 0.01-0.08 ng mL-1 for water and 0.03-0.10 ng mL-1 for lemon juice. The recoveries were in the range of 80.0% to 113.0% with relative standard deviation less than 10.6%. This work demonstrated the feasibility of phosphate-functionalized POPs for adsorption applications.

Carboxyl functionalized sorbent based solid-phase extraction for sensitive determination of endocrine disrupting chemicals in bottled water, juice and milk.

Endocrine disrupting chemicals (EDCs) pose a serious threat to human health even at extremely low concentration. Three carboxyl functionalized porous polymers (PDA-DPBP, PTCDA-DPBP and ODPA-DPBP) were synthesized for the first time and employed as solid-phase extraction sorbent to enrich phenolic EDCs at trace level. Compared with PTCDA-DPBP, ODPA-DPBP and corresponding carboxyl-free counterpart (PC-DPBP), PDA-DPBP delivered superior enrichment efficiency for the phenolic EDCs, which can be ascribed to the strong hydrogen bonding, pore filling, hydrophobic interaction and π-π interaction between PDA-DPBP and phenolic EDCs. Coupled with high performance liquid chromatography, phenolic EDC residues in bottled water, juice and milk samples were enriched and determined. At the optimum conditions, the PDA-DPBP based method provided a good linear response in the range of 0.04-100ng mL-1 for bottled water, 0.07-100ng mL-1 for juice and 0.15-500ng mL-1 for milk samples. The detection limits (S/N=3) were 0.01-0.04, 0.02-0.06 and 0.05-0.10ng mL-1 for bottled water, juice and milk, respectively. The method recoveries were in the range from 81.6% to 116%, with RSDs ≤ 7.7%. This work provides an attractive and reliable alternative method for sensitive determination of phenolic EDCs.

Diabetes and Colorectal Cancer Risk: Clinical and Therapeutic Implications.

Several epidemiological studies have identified diabetes as a risk factor for colorectal cancer (CRC). The potential pathophysiological mechanisms of this association include hyperinsulinemia, insulin-like growth factor (IGF) axis, hyperglycemia, inflammation induced by adipose tissue dysfunction, gastrointestinal motility disorder, and impaired immunological surveillance. Several studies have shown that underlying diabetes adversely affects the prognosis of patients with CRC. This review explores the novel anticancer agents targeting IGF-1R and receptor for advanced glycation end products (RAGE), both of which play a vital role in diabetes-induced colorectal tumorigenesis. Inhibitors of IGF-1R and RAGE are expected to become promising therapeutic choices, particularly for CRC patients with diabetes. Furthermore, hypoglycemic therapy is associated with the incidence of CRC. Selection of appropriate hypoglycemic agents, which can reduce the risk of CRC in diabetic patients, is an unmet issue. Therefore, this review mainly summarizes the current studies concerning the connections among diabetes, hypoglycemic therapy, and CRC as well as provides a synthesis of the underlying pathophysiological mechanisms. Our synthesis provides a theoretical basis for rational use of hypoglycemic therapies and early diagnosis and treatment of diabetes-related CRC.

Predictive value of indirect bilirubin before neoadjuvant chemoradiotherapy in evaluating prognosis of local advanced rectal cancer patients.

BACKGROUND: Many biomarkers have predictive value for overall survival (OS) and disease-free survival (DFS) in tumor patients. However, the role of indirect bilirubin (IBIL) in local advanced rectal cancer (LARC) patients treated with neoadjuvant chemoradiotherapy (nCRT) has not been studied. AIM: To explore the predictive value of IBIL before nCRT (pre-IBIL) for the OS and DFS of LARC patients treated with nCRT. METHODS: A total of 324 LARC patients undergoing nCRT with total mesorectal excision (TME) were enrolled. Preoperative clinical features and postoperative pathological characteristics were collected. Cox regression analysis was performed, and a Cox-based nomogram was developed to predict OS and DFS. We also assessed the predictive performance of the nomogram with calibration plots and receiver operating characteristic (ROC) curves. RESULTS: Among 324 patients, the median pre-IBIL was 6.2 µmol/L (interquartile range: 4.6 µmol/L-8.4 µmol/L). In the Cox multivariate regression analysis, we found that pre-IBIL, smoking history, tumor regression grade (TRG), vascular invasion, and carbohydrate antigen 19-9 before nCRT (pre-CA19-9) were predictors of OS. Additionally, pre-IBIL, body mass index (BMI), nCRT with surgery interval, TRG, and vascular invasion were predictors of DFS. Predictive nomograms were developed to predict 5-year OS and 5-year DFS with area under the ROC curve values of 0.7518 and 0.7355, respectively. Good statistical performance on internal validation was shown by calibration plots and ROC curves. CONCLUSION: This study demonstrated that pre-IBIL was an independent prognostic factor for OS and DFS in LARC patients treated with nCRT followed by TME. Nomograms incorporating pre-IBIL, BMI, smoking history, nCRT with surgery interval, TRG, vascular invasion, and pre-CA19-9 could be helpful to predict OS and DFS.

A Novel Biomarker, FKBP10, for Poor Prognosis Prediction in Patients with Clear Cell Renal Cell Carcinoma.

Objective: To screen genes associated with poor prognosis of clear cell renal cell carcinoma (CcRCC) from the public databases HPA (Human Protein Atlas), UALCAN, and GEPIA (Gene Expression Profiling Interactive Analysis) and to investigate the expression of FKBP10 in CcRCC and the effect on prognosis of the patients and the biological behavior of CcRCC cells. Methods: The tumor tissues and adjacent noncancerous tissues of 42 patients with CcRCC diagnosed and treated in our hospital were collected, and the general information of the patients was recorded. FKBP10 expression in the tissues was determined by qRT-PCR and western blot, and its relationship with general information and prognosis of patients was analyzed. Knockdown or overexpression experiments were carried out with the human proximal tubule epithelial cell line HK-2 and CcRCC cell lines Caki-1, 786-O, ACHN, and A498 to verify the relationship between FKBP10 expression and cell proliferation and adhesion ability using MTT assay and fibronectin adhesion assay, respectively. Western blot was utilized to examine the protein expression level of c-Myc, cyclin D1, and Bcl-2 in the cells. Results: FKBP10 was highly expressed in CcRCC tissues and cells and was correlated with poor prognosis. In addition, FKBP10 expression was positively correlated with CcRCC tumor size and staging and negatively correlated with tumor differentiation. Moreover, knockdown of FKBP10 significantly inhibited the proliferation of CcRCC cells, notably declined the protein expression of c-Myc, cyclin D1, and Bcl-2, and promoted cell adhesion. Conclusion: FKBP10 is highly expressed in CcRCC tissues and cells and is associated with poor prognosis in patients. FKBP10 participated in the occurrence and development of CcRCC by promoting cell proliferation and inhibiting apoptosis and adhesion.

CCL20 promotes lung adenocarcinoma progression by driving epithelial-mesenchymal transition.

C-C motif chemokine ligand 20 (CCL20) participates in multiple oncogenic processes, but its role in lung adenocarcinoma (LUAD) is unclear. Herein, we explored the mechanism by which CCL20 works in LUAD progression. We performed bioinformatical analyses based on the complete transcriptome sequencing data from 1544 LUAD cases in 4 independent cohorts to evaluate signaling pathways regulated by CCL20. We established A549 and H358 cell lines with CCL20 knockdown to explore how CCL20 promotes tumor progression in vitro and in vivo experiments. Using another independent cohort of 348 urothelial carcinoma patients treated with the anti-PD-L1 agent (atezolizumab), we explored the synergistic effect of CCL20 and TGF-ß on immunotherapy efficacy. High CCL20 expression is a poor prognostic marker for LUAD patients, and is associated with enhanced epithelial-mesenchymal transition (EMT), inflammatory response, and activated TNF pathway in LUAD. CCL20 knockdown restrained the EMT process and cell proliferation of LUAD cells in vitro and in vivo. Low CCL20 expression blocked the detrimental effects of high TGF-ß on survival and effectively improved patients' response to anti-PD-L1 therapy. Collectively, we revealed the underlying mechanisms by which CCL20 promotes LUAD progression based on the largest sample size. The synergistic inhibitory effect of CCL20 and TGF-ß on immune-checkpoint blockade therapy efficacy provides new views of immunotherapy resistance.

A Number of the N-terminal RASSF Family: RASSF7

The Ras association domain family 7 (RASSF7, also named HRC1), a potential tumor-related gene, located on human chromosome 11p15, has been identified as an important member of the N-terminal RASSF family. Whereas, the molecular biological mechanisms of RASSF7 in tumorigenesis remain to be further established. We perform a systematic review of the literature and assessment from PUBMED and MEDLINE databases in this article. RASSF7 plays a significant role in mitosis, microtubule growth, apoptosis, proliferation and differentiation. Many research literature shows that the RASSF7 could promote the occurrence and advance of human tumors by regulating Aurora B, MKK4, MKK7, JNK, YAP, MEK, and ERK, whereas, it might inhibit c-Myc and thus lead to the suppression of tumorigenesis. The pregulation of RASSF7 often occurs in various malignancies such as lung cancer, neuroblastoma, thyroid neoplasm, hepatocellular cancer, breast cancer and gastric cancer. The expression stage of RASSF7 is positively correlated with the tumor TNM stage. In this review, we primarily elaborate on the acknowledged structure and progress in the various biomechanisms and research advances of RASSF7, especially the potential relevant signaling pathways. We hope that RASSF7 , a prospective therapeutic target for human malignancies, could play an available role in future anti-cancer treatment.

Facile synthesis of BiOI/MXene heterostructure as a superior photoelectrochemical sensor for sensitive detection of glucose.

A MXene-based heterostructure (BiOI/Ti3C2TX) was synthesized via simple hydrothermal synthesis strategy. The BiOI/Ti3C2TX exhibited distinctly enhanced photoelectrochemical (PEC) activity, excellent durability and high selectivity because the introduction of Ti3C2TX could facilitate the separation of photogenerated electron-hole pairs. Since the redox process of glucose resulted in a decreasing photocurrent of BiOI/Ti3C2TX, a BiOI/Ti3C2TX based signal-off PEC sensing platform was constructed to sensitively determine glucose for the first time. Under the optimal conditions, the BiOI/Ti3C2TX sensor displayed a good linearity ranging from 0.03 µΜ to 1500 µΜ with the limit of detection down to 0.02 µΜ. The sensor was successfully applied for the glucose detection in human urine with satisfactory accuracy and repeatability, confirming its practical applicability and good serviceability. Moreover, the BiOI/Ti3C2TX sensor also exhibited superb selectivity and stability, providing a great potential application in the development of glucose sensor.