Molecular characterization and clinical relevance of metabolic signature subtypes in gastric cancer.

Metabolic reprogramming dictates tumor molecular attributes and therapeutic potentials. However, the comprehensive metabolic characteristics in gastric cancer (GC) remain obscure. Here, metabolic signature-based clustering analysis identifies three subtypes with distinct molecular and clinical features: MSC1 showed better prognosis and upregulation of the tricarboxylic acid (TCA) cycle and lipid metabolism, combined with frequent TP53 and RHOA mutation; MSC2 had moderate prognosis and elevated nucleotide and amino acid metabolism, enriched by intestinal histology and mismatch repair deficient (dMMR); and MSC3 exhibited poor prognosis and enhanced glycan and energy metabolism, accompanied by diffuse histology and frequent CDH1 mutation. The Shandong Provincial Hospital (SDPH) in-house dataset with matched transcriptomic, metabolomic, and spatial-metabolomic analysis also validated these findings. Further, we constructed the metabolic subtype-related prognosis gene (MSPG) scoring model to quantify the activity of individual tumors and found a positive correlation with cuproptosis signaling. In conclusion, comprehensive recognition of the metabolite signature can enhance the understanding of diversity and heterogeneity in GC.

Tumor microenvironment characteristics association with clinical outcome in patients with resected intestinal-type gastric cancer.

BACKGROUND: Tumor microenvironment (TME) characteristics including tumor stroma ratio (TSR), tumor budding (TB), and tumor-infiltrating lymphocytes (TILs) were examined in resected gastric cancer. These TME features have been shown to indicate metastatic potential in colon cancer, and intestinal-type gastric cancer (IGC) has pathological similarities with that malignancy. METHODS: TSR, TB, and TILs were quantified in routine histological sections from 493 patients with IGC who underwent radical resection at 2 university hospitals in China from 2010 to 2016. TME variables were dichotomized as follows: TSR (50%), TILs (median), TB per international guidelines (4 buds/0.785mm2), and platelet-lymphocyte ratio (PLR) per survival ROC. Association of TME features with patient clinicopathological characteristics, time-to-recurrence (TTR), and cancer-specific-survival (CSS) were examined using univariate and multivariate analysis, including a relative contribution analysis by Cox regression. RESULTS: Patients whose tumors showed high TSR or high TB or low TILs were each significantly associated with increased T and N stage, higher histological grade, and poorer TTR and CSS at 5 years. Only TSR and N stage were independently associated with TTR and CSS after adjustment for covariates. PLR was only independently associated with TTR after adjustment for covariates. Among the variables examined, only TSR was significantly associated with both TTR (HR 1.72, 95% CI, 1.14-2.60, P = .01) and CSS (HR 1.62, 95% CI, 1.05-2.51, P = .03) multivariately. Relative contribution to TTR revealed that the top 3 contributors were N stage (45.1%), TSR (22.5%), and PLR (12.9%), while the top 3 contributors to CSS were N stage (59.9%), TSR (14.7%), and PLR (10.9%). CONCLUSIONS: Among the examined TME features, TSR was the most robust for prognostication and was significantly associated with both TTR and CSS. Furthermore, the relative contribution of TSR to patient TTR and CSS was second only to nodal status.

Prussian blue analogue-derived CoP nanocubes supported on MXene toward an efficient bifunctional electrode with enhanced overall water splitting.

The exploration of bifunctional catalyst with economic, durable, and efficient performance plays a crucial role to boost both hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) in overall water splitting. Herein, we report a feasible strategy to design effective heterostructure between CoP and Ti3C2Tx MXene (denoted as CoP/Ti3C2Tx). This approach allows for the growth of CoP nanoparticles with uniform size of 5 nm on the Ti3C2Tx MXene, further enhancing the water electrolysis efficiency. The CoP/Ti3C2Tx bifunctional catalyst demonstrates an exceptional HER activity with a satisfactory overpotential of 103 mV at 10 mA cm-2, and also can drive 10 mA cm-2 for OER with the overpotential of 312 mV in 1.0 M KOH. Moreover, the CoP/Ti3C2Tx-based electrolyzer exhibits high electrochemical stability for 24 h with a low required voltage of 1.66 V at 10 mA cm-2. The density functional theory (DFT) calculations reveal that the introduction of Ti3C2Tx MXene significantly adjusts d-band center towards Fermi level and expand total density of states, resulting in great electrical conductivity, enhanced water adsorption, and activation. This study provides an available mode for effective design and construction of non-noble-metal-based dual-functional catalyst toward practical energy conversion.

Pan-cancer analysis of the tumorigenic role of Fanconi anemia complementation group D2 (FANCD2) in human tumors.

Monoubiquitination of FANCD2 is a central step in the activation of the Fanconi anemia (FA) pathway after DNA damage. Defects in the FA pathway centered around FANCD2 not only lead to genomic instability but also induce tumorigenesis. At present, few studies have investigated FANCD2 in tumors, and no pan-cancer research on FANCD2 has been conducted. We conducted a comprehensive analysis of the role of FANCD2 in cancer using public databases and other published studies. Moreover, we evaluated the role of FANCD2 in the proliferation, migration and invasion of lung adenocarcinoma cells through in vitro and in vivo experiments, and explored the role of FANCD2 in cisplatin chemoresistance. We investigated the regulatory effect of FANCD2 on the cell cycle of lung adenocarcinoma cells by flow cytometry, and verified this effect by western blotting. FANCD2 expression is elevated in most TCGA tumors and shows a strong positive correlation with poor prognosis in tumor patients. In addition, FANCD2 expression shows strong correlations with immune infiltration, immune checkpoints, the tumor mutation burden (TMB), and microsatellite instability (MSI), which are immune-related features, suggesting that it may be a potential target of tumor immunotherapy. We further found that FANCD2 significantly promotes the proliferation, invasion, and migration abilities of lung adenocarcinoma cells and that its ability to promote cancer cell proliferation may be achieved by modulating the cell cycle. The findings indicate that FANCD2 is a potential biomarker and therapeutic target in cancer treatment by analyzing the oncogenic role of FANCD2 in different tumors.

Surface-Enhanced Raman Spectroscopy for Boosting Electrochemical CO2 Reduction on Amorphous-Surfaced Tin Oxide Supported by MXene.

Amorphous materials disrupt the intrinsic linear scalar dependence seen in their crystalline counterparts, typically exhibiting enhanced catalytic characteristics. Nevertheless, substantial obstacles remain in terms of boosting their stability, enhancing their conductivity, and elucidating distinct catalytic mechanisms. Herein, a core-shell catalyst, comprising a crystalline SnO2 core and an amorphous SnOx shell supported on MXene (denoted as SnO2@SnOx/MXene), was prepared utilizing hydrothermal and solution reduction methods. The SnO2@SnOx/MXene catalyst excels in the electrocatalytic conversion of CO2 to formate, yielding a Faradaic efficiency (FE) as high as 93% for formate production at -1.17 V vs RHE and demonstrating exceptional durability. Both density functional theory (DFT) calculations and experimental results indicate that the SnOx shell bolsters formate formation by fine-tuning the adsorption energy of the *OCHO intermediate. In SnO2@SnOx/MXene, MXene plays a vital role in enhancing the conductivity and stability of the amorphous shell and especially amplifying Raman signals of catalyst components. The ex/in situ surface-enhanced Raman scattering (SERS) application further confirms the formation of amorphous SnOx and further enables the direct detection of the formation of the intermediate species. This work provides the basis for the application of amorphous materials in practical electrocatalytic reduction of CO2 reduction.

Double-Heterostructured Nickel Phosphate-Phosphides as High-Activity Electrocatalyst for Ammonia Borane Electrooxidation.

The direct electrooxidation reaction of ammonia borane (ABOR) as the anodic reaction of direct ammonia borane fuel cells (DABFCs) is greatly dependent on the properties of electrocatalysts. Both the active sites and charge/mass transfer characteristics are the key to promoting the processes of kinetics and thermodynamics, which can further improve the electrocatalytic activity. Hence, the catalyst double-heterostructured Ni2 P/Ni2 P2 O7 /Ni12 P5 (d-NPO/NP) with the optimistic redistribution of electrons and active sites is prepared for the first time. The d-NPO/NP-750 catalyst obtained after pyrolysis at 750 °C shows the outstanding electrocatalytic activity toward ABOR with an onset potential of -0.329 V vs RHE which is better than all the published catalysts. The density functional theory (DFT) computations illustrate that the Ni2 P2 O7 /Ni2 P acts as the activity enhancement heterostructure with a high d-band center (-1.60 eV) and the low activation energy barrier, while the Ni2 P2 O7 /Ni12 P5 acts as the conductivity enhancement heterostructure with the highest density of valence electrons.

Porous carbon framework decorated with carbon nanotubes encapsulating cobalt phosphide for efficient overall water splitting.

Exploration of catalysts for water splitting is critical for advancing the development of energy conversion field, but designing bifunctional catalysts remains a major challenge. Herein, we demonstrate the N-doped carbon nanotube (NCNT)-grafted N-doped carbon (NC) framework embedding CoP nanoparticles (CoP@NC/NCNT) as hydrogen and oxygen evolution reaction (HER and OER) catalysts for water splitting. As a result, the CoP@NC/NCNT electrode requires the overpotentials of 106 and 177 mV at 10 mA cm-2 in 0.5 M H2SO4 and 1.0 M KOH solutions for HER, respectively. Moreover, an overpotential of 324 mV for OER can drive 10 mA cm-2 in 1.0 KOH. The CoP@NC/NCNT-based electrolyzer derives a current density of 10 mA cm-2 at a low voltage of 1.72 V in 1.0 M KOH and remains stable for 10 h. The outstanding electrocatalytic performance is mainly attributed to the hierarchical structure with rich branches and highly active component of CoP. The intimate contacts between hierarchical porous NC frameworks by cross-linked NCNTs create a 3D conductive network, which facilitates electron or mass transfer and activates CoP. This work offers a novel route for preparing hierarchical carbon framework encapsulated metal phosphide particles for potential applications in energy conversion field.

Anaplastic lymphoma kinase fusion protein expression is associated with a favorable prognosis in resected invasive mucinous lung adenocarcinoma: A retrospective study from two Chinese tertiary hospitals.

Background: Invasive mucinous adenocarcinoma (IMA) is a distinct variant of lung adenocarcinoma, which typically has a worse survival. However, its pathogenesis is potentially associated with a high degree of molecular heterogeneity, which might determine its different prognosis. Methods: We retrospectively analyzed 2207 consecutive lung adenocarcinoma patients who underwent radical resection at Qilu Hospital of Shandong University and Shandong Provincial Hospital from 2013 to 2019. Anaplastic lymphoma kinase (ALK) fusion protein expression was routinely detected by immunohistochemistry. The clinicopathological characteristics and treatment outcomes of IMA patients were retrieved, and compared between ALK-positive and ALK-negative IMA patients as well as between pure IMA and mixed IMA patients. The last follow-up was on December 31, 2020, and the median follow-up was 42 months. Results: A total of 98 patients (4.4%) were diagnosed with IMA. ALK protein expression was positive in 24.5% of IMAs, which was significantly higher than that of non-IMA lung adenocarcinomas (4.7%, P < 0.001). ALK-positive and ALK-negative IMA, as well as pure IMA and mixed IMA, showed similar distribution in terms of patients' age, gender and smoking history, stage, and primary tumor location, except for a higher rate of lymph node metastasis in mixed IMA (22.0% vs. 46.2%, P = 0.012). Five cases (20.8%) of ALK-positive IMAs and 28 cases (40.6%) of ALK-negative IMAs experienced recurrence. Multivariable-adjusted Cox regression analysis demonstrated that ALK expression was a favorable prognostic factor for both disease-free survival (hazard ratio [HR]: 0.354; 95% confidence interval [CI]: 0.131-0.960; P = 0.041) and overall survival (HR: 0.138; 95% CI: 0.029-0.658; P = 0.013) in resected IMA. No difference in disease-free survival (HR: 0.524; 95% CI: 0.237-1.157; P = 0.110) and OS (HR: 0.553; 95% CI: 0.199-1.537; P = 0.256) was observed between pure IMA and mixed IMA. Conclusion: Invasive mucinous lung adenocarcinoma showed higher ALK protein expression, which was a favorable prognostic factor for survival in early resected patients.

A New Role for Conivaptan in Ulcerative Colitis in Mice: Inhibiting Differentiation of CD4+T Cells into Th1 Cells.

BACKGROUND: Conivaptan, a nonselective antagonist of vasopressin receptors V1a and V2, is the first drug of this class to be used for treating euvolemic and hypervolemic hyponatremia. Recently, increasing evidence supports the involvement of vasopressin in immune responses. AIMS: In this study, we investigated the effect of conivaptan on the modulation of CD4+ T cell homeostasis and the progression of experimental colitis. METHODS: The expression of the V1a receptor on CD4+ T cells was detected by immunofluorescence and western blot. The subset of isolated CD4+ T cells were examined after arginine vasopressin (AVP) incubation. CD4+ T cells were injected into DNBS-induced mice through the tail vein. The severity of colitis was evaluated according to weight, disease activity index (DAI), and morphological injury. Intracellular Ca2+ ([Ca2+]i) signaling in CD4+ T cells was measured using the Fluo-3 AM loading method. T-bet and IFN-γ mRNAs in the colon were detected by real-time polymerase chain reaction (qPCR). RESULTS: We found that CD4+ T cells expressed the V1a receptor. Activation of the V1a receptor significantly promoted the differentiation of CD4+ T cells into T helper 1 (Th1) cells. This process was blocked by conivaptan treatment. However, the activation of the V1a receptor did not evoke an increase in [Ca2+]i in CD4+ T cells. Notably, conivaptan markedly alleviated body weight loss, pathological damage, and expression of T-bet and IFN-γ in the colon of DNBS-treated mice. CONCLUSIONS: For the first time, we report that conivaptan attenuated colitis by inhibiting the differentiation of CD4+ T cells into Th1 cells. Mechanistically, the anti-inflammatory role of conivaptan is independent of [Ca2+]i.

Isolated synchronous Virchow lymph node metastasis of sigmoid cancer: A case report.

BACKGROUND: Colorectal cancer (CRC) is one of the most common malignant tumors of the digestive tract. Lymphatic metastases of this tumor are mostly confined to the regional lymph nodes, and distant supraclavicular lymph node metastases are very rare. CASE SUMMARY: In this report, we describe a patient with sigmoid carcinoma and isolated synchronous supraclavicular lymph node metastases. A 56-year-old male presented with a left cervical mass that was confirmed as a lymph node metastasis from sigmoid cancer by several auxiliary examinations. After 6 cycles of chemotherapy with the 5-fluorouracil, leucovorin and oxaliplatin + cetuximab regimen, the sigmoid colon tumor and Virchow's lymph node metastasis were significantly smaller than before treatment, and no new metastatic sites were observed. Considering the effects of chemotherapy on quality of life, resection of the primary tumor was performed followed by 4 cycles of chemotherapy with the original chemotherapy regimen. Virchow's lymph node dissection was selected by mutual consultation between the patient and us. After the second surgery, the patient received capecitabine and cetuximab chemotherapy and did not experience recurrence or metastasis during follow-up. CONCLUSION: In conclusion, supraclavicular lymph node metastasis without any other solid organ metastasis is a potential metastatic pathway for CRC. In addition, after resection of the primary lesion, postoperative chemotherapy combined with supraclavicular lymph node dissection is feasible for the treatment of patients with CRC and isolated synchronous Virchow's lymph node metastases.

Clinicopathological characteristics and longterm survival of patients with synchronous multiple primary gastrointestinal stromal tumors: A propensity score matching analysis.

BACKGROUND: Multiple gastrointestinal stromal tumors (MGISTs) are specific and rare. Little is known about the impact of MGISTs on the survival of patients with gastrointestinal stromal tumors (GIST). The diagnosis, treatment and follow-up strategies of MGISTs is not specifically described in guidelines. AIM: To compare the clinicopathological characteristics and prognosis of MGISTs and solitary GISTs (SGISTs). METHODS: Patients diagnosed with primary GISTs from March 2010 to January 2020 were included. Due to the inhomogeneous distribution of several baseline characteristics and uneven MGIST and SGIST group sizes, propensity score matching was performed according to comorbidities, body mass index, tumor location, mitotic index, sex, age and American Society of Anesthesiologists score. Differences in clinicopathological characteristics and prognosis between patients with MGISTs and patients with SGISTs were compared. RESULTS: Among the entire cohort of 983 patients, the incidence of MGISTs was 4.17%. Before matching, patients with MGISTs and those with SGISTs had disparities in body mass index, surgical approach, tumor size and mitotic index. After 1:4 ratio matching, the clinical baseline data were comparable. The 5-year progression-free survival rate was 52.17% in the MGIST group and 75.00% in the SGIST group (P = 0.031). On multivariate analysis, tumor location, tumor size, mitotic index, imatinib treatment and MGISTs (hazard ratio = 2.431, 95% confidence interval = 1.097-5.386, P = 0.029) were identified as independent prognostic factors of progression-free survival. However, overall survival was similar between the SGIST and MGIST groups. CONCLUSION: Patients with MGISTs had poorer progression-free survival than patients with SGISTs. Risk criteria and diagnostic and treatment strategies should be developed to achieve personalized precision therapy and maximize the survival benefit.

A practical screening strategy for Lynch syndrome and Lynch syndrome mimics in colorectal cancer.

OBJECTIVES: The objective of the study is to provide an efficient and practical screening strategy to distinguish a broader spectrum of Lynch syndrome (LS) and LS mimics-associated colorectal cancer (CRC), including Lynch-like syndrome (LLS), constitutional mismatch repair-deficiency, familial CRC type X (FCCTX), and polymerase proofreading-associated polyposis syndrome. MATERIALS AND METHODS: 1294 cases of CRC samples were detected mismatch repair (MMR) status using immunohistochemistry (IHC) staining, in which the cases with MLH1-deficient CRC underwent BRAF mutation analysis by IHC. Following the personal and/or family history survey, next-generation sequencing (NGS) was used to detect gene variants. RESULTS: 1294 CRC patients were dichotomized into tumors caused by a deficient MMR (dMMR) system and a proficient MMR (pMMR) system after MMR status analysis. 45 patients with suspected sporadic dMMR CRC were then separated from MLH1-deficient CRC though BRAF mutation status analysis by IHC. Following the personal and/or family history survey for 1294 patients, as well as germline genetic testing by NGS, 34 patients were diagnosed as LS (8 cases), SLS (13 cases), LLS ( 6 cases), FCCTX (3 cases), and sporadic CRC (4 cases). CONCLUSIONS: Our screening strategy, which consists of clinical and molecular analyses, is expected to improve the screening efficiency and management for the LS and LS mimics.

A new practical classification of desmoplastic reaction in endoscopic forceps biopsy of colorectal cancer.

BACKGROUND: The histopathological discrepancy between endoscopic forceps biopsy (EFB) and post-resection specimens is considered a practical clinical problem. This retrospective study aimed to determine the current diagnostic concordance between the EFB and surgical specimens of colorectal cancer (CRC) and then investigated the useful factors in EFB diagnosis. METHODS: We used the representative pathological data of 2188 CRCs. The comparison of histopathological discrepancy between EFB and the related surgical specimens was performed. Furthermore, 418 biopsy specimen slides in our hospital were reviewed to determine the classification of intratumor desmoplastic reaction (DR). RESULTS: Among the 2188 patients, the positive sensitivity of EFB for adenocarcinoma was 82.7%. The discrepancy rate between the EFB and surgical specimens was 10.8-40.0% corresponding to different T stages. On the basis of DR classification, 32, 131, and 255 tumors were categorized as little, moderate and extensive, respectively. The correlation between DR classification and tumor invasion based on T stage was significant (Spearman's rho= 0.112; p<0.05). The extensive DR provided better estimates for advanced tumors than the little and moderate DR (χ²= 3.977, p=0.046). Besides DR, factors including deeper cutting the slides and histological types were significantly associated with "adenocarcinoma" diagnosis in EFB of CRCs (p<0.05). CONCLUSION: To the best of our knowledge, this is the first time that a DR classification specifically for EFB specimens was proposed. It might contribute to improve the accuracy of biopsy-based diagnosis of CRC.

Prognostic role of tumour-infiltrating lymphocytes assessed by H&E-stained section in gastric cancer: a systematic review and meta-analysis.

OBJECTIVES: Some studies have identified tumour-infiltrating lymphocytes (TILs) in H&E-stained sections of gastric cancer, but the prognostic and clinicopathological significance of this remains unclear. The objective of this study is to evaluate the associations between H&E-based TIL density and prognosis and clinicopathological characteristics of patients with gastric cancer. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Cochrane Library, PubMed and Embase databases were searched through 25 February 2020. ELIGIBILITY CRITERIA: Studies evaluating the correlations between TILs assessed by H&E-stained sections and prognosis and clinicopathological characteristics of gastric cancer were included. DATA EXTRACTION AND SYNTHESIS: Relevant data were extracted and risks of bias were assessed independently by two reviewers. HR and relative risk (RR) with 95% CI were pooled by random-effect models to estimate the associations between TIL density and overall survival (OS) and clinicopathological characteristics, respectively. RESULTS: We enrolled nine studies including 2835 cases for the present meta-analysis. High TILs were associated with superior OS (HR=0.68, 95% CI 0.52 to 0.87, p=0.003) compared with low TILs. High TILs were significantly associated with lower depth of invasion (T3-T4 vs T1-T2) (RR=0.58, 95% CI 0.50 to 0.66, p<0.001), less lymph node involvement (presence vs absence) (RR=0.68, 95% CI 0.56 to 0.81, p<0.001) and earlier TNM (tumour, node, metastasis) stage (III-IV vs I-II) (RR=0.68, 95% CI 0.55 to 0.83, p<0.001). TIL density was not associated with age, gender, Lauren classification or histological grade. The methodology for evaluating TIL and its cut-off value varied across different studies, which might affect the results of our meta-analysis. CONCLUSIONS: Our meta-analysis suggests that H&E-based TIL density is a reliable biomarker to predict the clinical outcomes of patients with gastric cancer. Multicentre, prospective studies are needed to further confirm our findings. PROSPERO REGISTRATION NUMBER: CRD42020169877.

Comparison of Multi-Gene Testing Data Between Fresh and Formalin-Fixed Specimens From Core Needle Biopsy in Patients With NSCLC.

Purpose: Currently, formalin-fixed paraffin-embedded (FFPE) tissue specimens are the conventional material for gene testing for non-small cell lung cancer (NSCLC) patients. In our study, we aimed to develop a quick gene testing procedure using fresh core needle biopsy samples from NSCLC patients. Methods: In total, 77 fresh NSCLC samples obtained from core needle biopsy were evaluated by frozen section examination. If the NSCLC diagnosis and adequate tumor cell counts were confirmed by histopathology, the fresh tissues were used to extract DNA and subsequent gene testing by ARMS-PCR. Meanwhile, the paired FFPE core needle biopsy samples from 30 NSCLC patients also underwent gene testing. Results: In total, 77 fresh samples showed an EGFR mutation rate of 61.0%, higher than the levels in the Asian. Following a comparison of gene testing results with fresh tissues and paired FFPE tissues from the 30 patients, no significant difference in the DNA concentration extracted from fresh tissues and FFPE tissues was found. However, DNA purity was significantly higher in fresh tissues than that in FFPE tissues. Gene testing detected the same gene mutations in 93.3% of cases in fresh tissues and paired FFPE tissues. The gene testing procedure using fresh biopsy samples greatly shortens the waiting time of patients. Conclusion: The multi-gene mutation testing using fresh core needle biopsy samples from NSCLC patients is a reasonable, achievable, and quick approach. Fresh tissues may serve as a potential alternative to FFPE tissues for gene testing in NSCLC patients.

[Summary of Fault Maintenance Experience of Multifunctional Digital Flat Plate Radiography System-Carestream DR7500].

This paper is a summary of the three types of faults that have occurred in the recent years in the Carestream DR7500:hardware failure, software failure, and communication failure. The specific cases of three types of faults are introduced in a case-by-case basis.

High salt-induced weakness of anti-oxidative function of natriuretic peptide receptor-C and podocyte damage in the kidneys of Dahl rats.

BACKGROUND: Atrial natriuretic peptide (ANP) and its natriuretic peptide receptors A (NPR-A) and C (NPR-C) are involved in the regulation of physiological and pathophysiological process of blood pressure. The present study aimed to determine the role of NPR-C in the development of salt-sensitive hypertension. METHODS: The Dahl salt-sensitive (DS) and salt-resistant (DR) rats were used in this study. Animals were matched according to their age and weight, and then placed on either a high-salt (HS, 8%) or a normal-salt (NS, 0.4%) diet for 6 weeks randomly using random number table. The systolic blood pressure (SBP), plasmatic sodium concentration (PLNa), urinary sodium excretion (UVNa), and serum creatinine concentration (Scr) were measured. The concentration of ANP in blood and tissues (heart and kidney) was detected by enzyme-linked immunosorbent assay. The expression of ANP, NPR-A, and NPR-C in kidney was evaluated with western blot analysis. Regarding renal redox state, the concentration changes in malondialdehyde (MDA), lipofuscin, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (Nox), and nitric oxide synthase (NOS) in kidney were detected by a spectrophotometric method. The kidney damage was evaluated using pathological techniques and the succinodehydrogenase (SDHase) examination. Furthermore, after an intra-peritoneal injection of C-atrial natriuretic peptide (ANP)4-23 (C-ANP4-23), an NPR-C receptor agonist, the SBP, biochemical values in blood and urine, and renal redox state were evaluated. The paired Student's t test and analysis of variance followed by the Bonferroni test were performed for statistical analyses of the comparisons between two groups and multiple groups, respectively. RESULTS: The baseline SBP in all groups was within the normal range. At the end of the 6-week experiment, HS diet significantly increased the SBP in DS rats from 116.63 ±â€Š2.90 mmHg to 162.25 ±â€Š2.15 mmHg (t = -10.213, P < 0.001). The changes of SBP were not significant in DS rats on an NS diet and DR rats on an NS diet or on an HS diet (all P > 0.05). The significant increase of PLNa, UVNa, and Scr related to an HS diet was found in both DS and DR rats (all P < 0.05). However, significant changes in the concentration (t = -21.915, P < 0.001) and expression of renal ANP (t = -3.566, P = 0.016) and the expression of renal NPR-C (t = 5.864, P = 0.002) were only observed in DS hypertensive rats. The significantly higher desmin immunochemical staining score (t = -5.715, P = 0.005) and mitochondrial injury score (t = -6.325, P = 0.003) accompanied by the lower SDHase concentration (t = 3.972, P = 0.017) revealed mitochondrial pathologic abnormalities in podocytes in DS rats with an HS diet. The distinct increases of MDA (t = -4.685, P = 0.009), lipofuscin (t = -8.195, P = 0.001), and Nox (t = -12.733, P < 0.001) but not NOS (t = -0.328, P = 0.764) in kidneys were also found in DS hypertensive rats. C-ANP4-23 treatment significantly decreased the SBP induced by HS in DS rats (P < 0.05), which was still higher than NS groups with the vehicle or C-ANP4-23 treatment (P < 0.05). Moreover, the HS-induced increase of MDA, lipofuscin, Nox concentrations, and Nox4 expression in DS rats was significantly attenuated by C-ANP4-23 treatment as compared with those with HS diet and vehicle injection (all P < 0.05). CONCLUSIONS: The results indicated that the renal NPR-C might be involved in the salt-sensitive hypertension through the damage of mitochondria in podocytes and the reduction of the anti-oxidative function. Hence, C-ANP4-23 might serve as a therapeutic agent in treating salt-sensitive hypertension.

Phosphorus-triggered synergy of phase transformation and chalcogenide vacancy migration in cobalt sulfide for an efficient oxygen evolution reaction.

Introduction of surface defects and phase control engineering in the electrocatalytic system of overall water splitting has played a crucial role in significantly enhancing its electrocatalytic activity toward the hydrogen evolution reaction (HER) and the oxygen evolution reaction (OER) in water splitting, but the relationship between structure and electrocatalysis is still elusive. Herein, we report a solid-liquid method to induce surface reorganization (formation of a chalcogenide layer with rich chalcogenide vacancies) and phase transformation (Co9S8-to-Co3S4) simultaneously on cobalt chalcogenide. Featuring a uniform 2D morphology and the in situ formation of sulfur (S) vacancies, in a 0.1 M KOH solution, it exhibits a low overpotential of 288 mV vs. RHE at 10 mA cm-2, a low Tafel slope of 43.4 mV dec-1, and strong cycling stability (35 h), outperforming commercial RuO2 and most reported OER electrocatalysts. In addition, we also investigate the OER activity of the Co-S-P electrode in 1.0 M KOH solutions. Co0.37S0.38P0.02 NSs only need 257 mV to reach a current density of 10 mA cm-2. Meanwhile, the Tafel slope of Co0.37S0.38P0.02 NSs (44.0 mV dec-1) is lower than those of other recently reported electrocatalysts. Also, it shows high HER electrocatalytic activity in alkaline and acidic solutions. Finally, the Co0.37S0.38P0.02 electrode is used as a cathode and anode simultaneously for overall water splitting, which merely requires a cell voltage of 1.59 V at 10 mA cm-2 with excellent stability (40 h).

Case report of ascending colon cancer and multiple jejunal GISTs in a patient with neurofibromatosis type 1 (NF1).

BACKGROUND: NF1(Neurofibromatosis type 1) is an autosomal dominant genetic disorder. Patients with NF1 have an increased risk of developing benign or malignant tumours, such as gastrointestinal stromal tumours (GISTs). However, the coexistence of NF1, GIST and colon cancer is very rare, and few cases have been reported in the literature. CASE PRESENTATION: We admitted a case of a 64-year-old man with type 1 neurofibromatosis, GISTs, and ascending colon cancer. This case was characterized by café-au-lait macules, discrete cutaneous neurofibromas, nodular neurofibromas, multiple jejunal tumours, and ascending colon cancer. Laparoscopic exploration revealed ascending colon cancer and multiple jejunal tumours. Laparoscopic right hemicolectomy and local excision of the jejunal tumours were performed successfully. The pathological results confirmed moderate differentiated adenocarcinoma of the ascending colon with multiple jejunal GISTs (low risk, very low risk). Moreover, the immunohistochemistry results of multiple jejunal GISTs suggest that NF1 is positive. Whole-exome sequencing (WES) of colon cancer revealed mutations in more than 20 genes, including KRAS, PIK3CA, APC, SMAD4, etc. The results of whole-exome sequencing (WES) of jejunal GISTs revealed an NF1 mutation and no KIT or PDGFR gene mutation. CONCLUSION: We report a rare case of simultaneous NF1, GIST and colon adenocarcinoma. For patients with NF1, benign and/or malignant tumours are often combined. Therefore, these patients should undergo regular physical examinations so that early detection and early treatment can be achieved.

Clinical characteristics of early neuroendocrine carcinoma in stomach: A case report and review of literature.

INTRODUCTION: Gastric neuroendocrine carcinoma (NEC) is rare. It is considered to be aggressive and has a poor prognosis since the diagnosis is usually made at its advanced stage. However, the survival rate is increased in some early gastric NECs. This study showed a case and reviewed the clinical characteristics of early NECs in stomach. PATIENT CONCERNS: A 38-year-old man displayed no symptoms and underwent the gastric endoscopy test for his health examination, which showed a red slightly depressed lesion 1.0 cm in size on the lesser curvature of gastric cardia. Magnifying endoscopy with narrow-band imaging (NBI) revealed a clear demarcation and an irregular mesh in vessels within the depressed area. The background mucosa was negative for atrophic gastritis and Helicobacter Pylori infection. A contrast-enhanced computed tomography (CT) scan disclosed no obvious thickening of stomach and lymphadenopathy. Blood tests and physical examination were unremarkable. He had not received any surgical treatment and denied a family history of cancer and any genetic disorders. The pathologic result of biopsy from the lesion was suspicious of superficial carcinoma. Then endoscopic submucosal dissection (ESD) was performed. DIAGNOSIS: Gastric NEC G3 in the early stage (T1aN0M0). INTERVENTIONS: Concerning this patient's situation, we considered the ESD as a curable treatment. And no radical surgery or adjuvant chemotherapy was arranged. OUTCOMES: The patient is doing well and displays no recurrence for 11 months, who is still in follow-up. LESSONS SUBSECTIONS AS PER STYLE: The early diagnosis and effective treatment by endoscopy would contribute to improve the prognosis of gastric NECs.