RUNX1-induced upregulation of PTGS2 enhances cell growth, migration and invasion in colorectal cancer cells.

Colorectal cancer (CRC) arises via the progressive accumulation of dysregulation in key genes including oncogenes and tumor-suppressor genes. Prostaglandin-endoperoxide synthase 2 (PTGS2, also called COX2) acts as an oncogenic driver in CRC. Here, we explored the upstream transcription factors (TFs) responsible for elevating PTGS2 expression in CRC cells. The results showed that PTGS2 silencing repressed cell growth, migration and invasion in HCT116 and SW480 CRC cells. The two fragments (499-981 bp) and (1053-1434 bp) were confirmed as the core TF binding profiles of the PTGS2 promoter. PTGS2 expression positively correlated with RUNX1 level in colon adenocarcinoma (COAD) samples using the TCGA-COAD dataset. Furthermore, RUNX1 acted as a positive regulator of PTGS2 expression by promoting transcriptional activation of the PTGS2 promoter via the 1086-1096 bp binding motif. In conclusion, our study demonstrates that PTGS2 upregulation induced by the TF RUNX1 promotes CRC cell growth, migration and invasion, providing an increased rationale for the use of PTGS2 inhibitors in CRC prevention and treatment.

3D-Printed Liquid Metal-in-Hydrogel Solar Evaporator: Merging Spectrum-Manipulated Micro-Nano Architecture and Surface Engineering for Solar Desalination.

Solar desalination driven by interfacial heating is considered a promising technique to alleviate the freshwater shortage crisis. However, its further extension and application are confined by factors such as highlighted salt accumulation, inferior energy efficiency, and poor durability. Herein, a microsized eutectic gallium-indium (EGaIn) core-shell nanodroplet (denoted as LMTE) with photo-cross-linking and photothermal traits, stabilized by allyl glycidyl ether (AGE)-grafting tannic acid (TA), is explored as the solar absorber for broadband light absorbing and localized micro-nano heat channeling. The LMTE nanodroplets are formulated directly with highly hydrated polymers and photosensitive species to successfully develop a water-based photothermal ink suitable for digital light processing (DLP) 3D printing. As a demonstration, the LMTE composite hydrogel-forged milli-conical needle arrays with metal-phenolic network (MPN)-engineered wettability and photothermal enhancement can be printed by the digital light processing (DLP) technique and designed rationally via a bottom-up strategy. The 3D-printing hydrogel evaporator is composed of spectrum-tailored EGaIn nanodroplets for efficient photon harvesting and MPN-coated milli-cone arrays for water supplying with micro-nano channeling, which function cooperatively to bestow the 3D solar evaporator with superior solar-powered water evaporation (2.96 kg m-2 h-1, 96.93% energy efficiency) and excellent solar desalination (salt cycle and site-specific salt crystallization). Furthermore, a robust steam generating/collecting system of the 3D solar evaporator is demonstrated, providing valuable guidance for building a water-energy-agriculture nexus.

Synergistic Dual-Mechanism Localized Heat Channeling and Spectrum-Tailored Liquid Metal Hydrogels for Efficient Solar Water Evaporation and Desalination.

Photothermal hydrogels featuring broadband light absorption abilities and highly hydrated networks provide an appealing mass-energy transfer platform for water evaporation by using solar energy. However, the targeted delivery of solar heat energy to power the water evaporation process remains challenging. Herein, enlightened by metal-phenolic coordination chemistry and camouflaged architecture, photothermal hydrogels with dual-mechanism vaporization structure are tactfully designed via a rational interfacial engineering and integration strategy to enable near-µm heat confinement and highly efficient light-to-heat conversion ability. The spectrum-tailored liquid metal droplet (LMGAs-FeIII ) and optimized carbon-wrapped silver nanowire sponge (Ag@C750 ) are integrally built as photothermal promotors/channels and jointly embedded into a highly hydratable poly(vinyl alcohol) hydrogel, denoted as PALGH, to synergistically boost water molecule activation and interfacial vaporization behavior by triggering robust photothermal performance. As a result, under one sun irradiation, the all-embracing PALGH hydrogel evaporation system achieves a brine evaporation rate to a high level of 3.47 kg m-2 h-1 , and >19 L m-2 clean water of PALGH is ideally delivered daily when purifying natural seawater. This work offers not only a rational design principle to create sophisticated photothermal materials but also replenishes insight into solar heat generation and water transportation in a cross-media system.

Peptide encoded by lncRNA BVES-AS1 promotes cell viability, migration, and invasion in colorectal cancer cells via the SRC/mTOR signaling pathway.

Long non-coding RNAs (lncRNAs) have been revealed to harbor open reading frames (ORFs) that can be translated into small peptides. The peptides may participate in the pathogenesis of colorectal cancer (CRC). Herein, we investigated the role of a lncRNA BVES-AS1-encoded peptide in colorectal tumorigenesis. Through bioinformatic analysis, lncRNA BVES-AS1 was predicted to have encoding potential and to be associated with poor prognosis of patients with CRC. In CRC cells, BVES-AS1 was validated to encode a 50-aa-length micro-peptide, named BVES-AS1-201-50aa, through a western blotting method. BVES-AS1-201-50aa enhanced cell viability and promoted the migratory and invasive capacities of HCT116 and SW480 CRC cells in vitro, validated via CCK-8 assay and transwell assay, respectively. Immunofluorescence assay showed that BVES-AS1-201-50aa increased the expression of proliferating cell nuclear antigen (PCNA) and matrix metalloproteinase 9 (MMP9) in CRC cells. We further verified that BVES-AS1-201-50aa targeted and activated the Src/mTOR signaling pathway in CRC cells by co-immunoprecipitation (Co-IP) experiment, qualitative proteomic analysis, and western blotting. Our findings demonstrated that BVES-AS1 could encode a micro-peptide, which promoted CRC cell viability, migration, and invasion in vitro. Our current work broadens the diversity and breadth of lncRNAs in human carcinogenesis.

Non-invasive measurement of tumor immune microenvironment and prediction of survival and chemotherapeutic benefits from 18F fluorodeoxyglucose PET/CT images in gastric cancer.

Background: The tumor immune microenvironment could provide prognostic and predictive information. It is necessary to develop a noninvasive radiomics-based biomarker of a previously validated tumor immune microenvironment signature of gastric cancer (GC) with immunohistochemistry staining. Methods: A total of 230 patients (training (n = 153) or validation (n = 77) cohort) with gastric cancer were subjected to (Positron Emission Tomography-Computed Tomography) radiomics feature extraction (80 features). A radiomics tumor immune microenvironment score (RTIMS) was developed to predict the tumor immune microenvironment signature with LASSO logistic regression. Furthermore, we evaluated its relation with prognosis and chemotherapy benefits. Results: A 8-feature radiomics signature was established and validated (area under the curve=0.692 and 0.713). The RTIMS signature was significantly associated with disease-free survival and overall survival both in the training and validation cohort (all P<0.001). RTIMS was an independent prognostic factor in the Multivariate analysis. Further analysis revealed that high RTIMS patients benefitted from adjuvant chemotherapy (for DFS, stage II: HR 0.208(95% CI 0.061-0.711), p=0.012; stage III: HR 0.321(0.180-0.570), p<0.001, respectively); while there were no benefits from chemotherapy in a low RTIMS patients. Conclusion: This PET/CT radiomics model provided a promising way to assess the tumor immune microenvironment and to predict clinical outcomes and chemotherapy response. The RTIMS signature could be useful in estimating tumor immune microenvironment and predicting survival and chemotherapy benefit for patients with gastric cancer, when validated by further prospective randomized trials.

Integrating Dual-Interfacial Liquid Metal Based Nanodroplet Architectures and Micro-Nanostructured Engineering for High Efficiency Solar Energy Harvesting.

Broadband strong absorption of solar light over a wide range of angles, low heat loss, and excellent structural reliability are of significance for enhancing solar harvesting of photothermal materials; however, it remains a challenge to achieve these attributes simultaneously. Herein, a tailored photothermal composite nanodroplet (LMP-rGO) featured with dual-interface, which comprises liquid metal (LM) core with polydopamine (PDA) photothermal middle layer of tunable thickness and reduced graphene oxide (rGO) shell, is particularly prepared. Thermal-insulating PDA coating and light-absorbing carbonaceous shell allow it to synergistically suppress heat loss and reinforce photon absorptivity. To maximize photothermal conversion and photon harvesting yield on solar light, inspired by light trapping architecture, a three-dimensional (3D) stepped micropyramid grating array framework is tactfully designed to ameliorate light coupling. Utilizing the scalability and cost-effectiveness of the poly(vinyl alcohol) (PVA), the flexible 3D-structured PVA/LMP-rGO absorbers are successfully constructed via a controllable casting molding strategy. As a proof-of-concept, the developed micrograting absorber exhibits a desirable combination of strong broadband selective light absorption (94.9% for parallel to the grating direction and 97.3% for perpendicular to the grating direction), superior photothermal conversion effect (89.4%), high heat flux density, and fascinating mechanical properties. Also, an efficient and steady solar-driven thermoelectric generator (STEG) system for real-time solar-heat-electric conversion, with its high peak power density of 245.9 µW cm-2 under one sun irradiation, is further displayed, making an important step to rationally design LM-based nanocomposite droplets for solar energy harvesting.

Indirect comparison between powered and manual circular staplers for left-sided colorectal anastomoses: clinical and economic outcomes in China.

AIMS: This study aimed to examine the economic and clinical benefits of a new powered circular stapler for left-sided colorectal construction in China. METHODS: A decision analysis model was constructed for a cohort of adult patients who underwent left-sided colorectal anastomoses, using either the Echelon Circular Powered (ECP) stapler) or the conventional manual circular staplers (MCS). The complications rates and healthcare resource utilization in the ECP cohort were obtained from the single-arm ECP trial (NCT03326895). For the MCS cohort, retrospective data from 20 Chinese hospitals were analyzed. Listing prices were used to estimate the costs of the staplers in China. Propensity score matching (PSM) was employed to adjust for the imbalance between the two cohorts. Anastomotic leak rate, length of stay (LOS), 90-day readmission rate, and direct medical costs were used for the decision analysis model parameters. A budget impact analysis was conducted to compare the total hospitalization expenditure between ECP and manual circular staplers from the hospital's perspective in China. RESULTS: Assuming 100 procedures per year, the anastomotic leak rate was 1.79 and 29.76 per 100 procedures in the ECP and MCS cohorts, respectively. LOS was 1,426.91 days in the ECP cohort, compared to 1,702.38 days in the MCS cohort. The 90-day readmission rate was also lower in the ECP cohort than the MCS cohort (19.10 vs. 26.19 per 100 procedures). For the 100 procedures, the annual total hospitalization costs for left-sided colorectal anastomosis were reduced from ¥7,152,251 using manual circular staplers to ¥6,919,306 using ECP. Despite a higher acquisition cost of ECP compared to the manual staplers (¥711,200 vs. ¥441,700), an annual saving of ¥232,945in the total cost resulted from lower rates of complications and shorter LOS. Sensitivity analyses presented consistent savings using ECP, and the ECP cost and cost of the index hospitalization with anastomotic leak were found the most influencing factors. CONCLUSIONS: There were clinical and economic benefits of ECP, compared to manual circular staplers for left-sided colorectal anastomoses. Further direct comparative studies on the use of ECP in practice in Chinese hospital settings are warranted.

Sphingolipid metabolism plays a key role in diabetic peripheral neuropathy.

INTRODUCTION: As the most common chronic complication of diabetes mellitus (DM), diabetic peripheral neuropathy (DPN) seriously affects the quality of life of DM patients. So, it is of great significance for the diagnosis and treatment of DPN. In recent years, there have been numerous studies on pathogenesis and biomarkers of DM, but there are few studies on the biomarkers of DPN. OBJECTIVES: This research is intended to identify abnormal metabolic pathways, search for potential biomarkers of DPN, and provide a metabolic basis for the diagnosis and mechanism of DPN. METHODS: Serum samples from 23 healthy controls (HC), 42 DM patients and 30 DPN patients and urine samples from 42 HC, 40 DM patients, and 30 DPN patients were collected. UPLC-Q-TOF/MS was used to analyze the samples. Potential biomarkers were screened from principal component analysis (PCA) to orthogonal partial least squares discriminant analysis (OPLS-DA) and further evaluated by receiver operating characteristic analysis (ROC). The biomarkers were then enriched and pathway analyzed. RESULTS: 12 potential DPN biomarkers were identified from patient's serum. 11 potential DPN biomarkers were identified from the patient's urine. Among them, the diagnostic ability of gluconic acid, lipoic acid, sphinganine, bilirubin, sphingosine and 4-hydroxybenzoic acid was increased by ROC analysis. Potential biomarkers suggest that the disorder of DPN metabolism may be linked to sphingolipid metabolism. CONCLUSIONS: This research laid a theoretical foundation for the diagnosis and pathogenesis of DPN.

Intratumoral and Peritumoral Radiomics of Contrast-Enhanced CT for Prediction of Disease-Free Survival and Chemotherapy Response in Stage II/III Gastric Cancer.

BACKGROUND: We evaluated the ability of radiomics based on intratumoral and peritumoral regions on preoperative gastric cancer (GC) contrast-enhanced CT imaging to predict disease-free survival (DFS) and chemotherapy response in stage II/III GC. METHODS: This study enrolled of 739 consecutive stage II/III GC patients. Within the intratumoral and peritumoral regions of CT images, 584 total radiomic features were computed at the portal venous-phase. A radiomics signature (RS) was generated by using support vector machine (SVM) based methods. Univariate and multivariate Cox proportional hazards models and Kaplan-Meier analysis were used to determine the association of the RS and clinicopathological variables with DFS. A radiomics nomogram combining the radiomics signature and clinicopathological findings was constructed for individualized DFS estimation. RESULTS: The radiomics signature consisted of 26 features and was significantly associated with DFS in both the training and validation sets (both P<0.0001). Multivariate analysis showed that the RS was an independent predictor of DFS. The signature had a higher predictive accuracy than TNM stage and single radiomics features and clinicopathological factors. Further analysis showed that stage II/III patients with high scores were more likely to benefit from adjuvant chemotherapy. CONCLUSION: The newly developed radiomics signature was a powerful predictor of DFS in GC, and it may predict which patients with stage II and III GC benefit from chemotherapy.