Application of enhanced recovery after surgery during the perioperative period in children with Meckel's diverticulum-a single-center prospective clinical trial.

Background: Enhanced recovery after surgery (ERAS) has been widely used in adult surgery. However, few studies have reported the efficacy of ERAS in paediatric patients with Meckel's diverticulum (MD), the aim of the study was to prospectively evaluate the safety and efficacy of ERAS in treating MD. Methods: A prospective randomised controlled study of children with MD admitted to our hospital from Jan 1, 2021 to Dec 31, 2023 were conducted, we developed and implemented an ERAS program for this patients. All cases were strictly selected according to the inclusion and exclusion criteria. Among these patients, they were randomly assigned to the ERAS group or the traditional (TRAD) group with random number table row randomization. The main observational indicators were operation time, intraoperative hemorrhage, FLACC pain scale results on 2 h, 6 h, 12 h, 24 h after surgery, length of postoperative stay (LOPS), time to first defecation, time to first eating after surgery, time to discontinuation of intravenous infusion, total treatment cost, incidence of postoperative complications, 30-day readmission rate and parental satisfaction rate. Results: A total of 50 patients underwent Meckel's diverticulectomy during this period, 7 patients were excluded, 23 patients were assigned to the ERAS group and 20 patients were assigned to the TRAD group. There were no significant differences in demographic data and operation time, intraoperative hemorrhage. The FLACC pain scale results on 2 h, 6 h, 12 h, 24 h after surgery were significantly lower in the ERAS group. The LOPS was 6.17 ± 0.89 days in the ERAS group and 8.30 ± 1.26 days in the TRAD group, resulting in a significantly shorter LOPS in ERAS group. ERAS could also reduce the first postoperative defecation time, the time to first eating after surgery and the time to discontinuation of intravenous infusion. The treatment cost was decreased in the ERAS group. The rate of complications and 30-day readmission were not significantly different between the two groups. Conclusions: In this single-center study, the ERAS protocol for patients with MD requiring surgery was safe and effective.

Transarterial chemoembolization plus lenvatinib with or without a PD-1 inhibitor for advanced and metastatic intrahepatic cholangiocarcinoma: a retrospective real-world study.

OBJECTIVES: Most patients with intrahepatic cholangiocarcinoma (ICC) present with locally advanced or metastatic disease. We report the combined potency of transarterial chemoembolization (TACE), lenvatinib and programmed cell death-1 (PD-1) inhibitors in patients with advanced and metastatic ICC. METHODS: This retrospective study enrolled 32 patients with advanced or metastatic ICC between January 2017 and August 2021. Eligible patients had received gemcitabine-based TACE combined with lenvatinib with or without PD-1 inhibitor in any line of treatment. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method. Risk factors associated with OS were assessed using univariate and multivariate Cox regression analyses. RESULTS: Eighteen patients received a combination of TACE and lenvatinib (TL group) and 14 patients received TACE and lenvatinib plus aPD-1 inhibitor (TLP group). The median follow-up time was 19.8 months (range 1.8-37.8). The median OS was 25.3 months (95% CI 18.5-32.1) and the median PFS was 7.3 months (95% CI 4.9-9.7). Partial response was achieved in 10 patients (31.3%), and stable disease in 13 (40.6 %) with disease control rate of 71.9%. The median OS was comparable in the TL and TLP groups (22.4 vs 27.3 months, respectively; hazard ratio: 1.245, 95% CI 0.4245-3.653; p = 0.687). The regression analysis revealed that, regardless of treatment group, a favorable independent prognostic factor for OS was HBV/HCV infection (HR: 0.063, 95% CI 0.009-0.463; p = 0.007). There were no treatment-related deaths and 81.3% of study participants experienced adverse events (AEs), the majority of which were of moderate severity (71.8% Grade 1-2). CONCLUSIONS: Gemcitabine-based TACE plus lenvatinib with or without aPD-1 inhibitor was well tolerated and provided promising therapeutic outcomes for patients with advanced and metastatic ICC. ADVANCES IN KNOWLEDGE: Monotherapy with TACE, or Lenvatinib, or PD-1 inhibitors has shown limited efficacy over standard first-line chemotherapy in advanced and metastatic ICC. This work suggested the combined potency of these treatments and well-tolerance.

Laser Shock Peening Improves the Corrosion Resistance of an E690 High-Strength Steel Cladding Layer.

To investigate the effect of laser shock peening parameters on the corrosion resistance of an E690 high-strength steel cladding layer, NVE690 high-strength steel powder was selected for testing at various power densities of pulse lasers. The surface roughness and residual stress of the treated samples were measured, and the microstructure morphology of the sample surface was observed. The electrochemical corrosion tests were conducted with an electrochemical workstation to measure the electrometer polarization, obtain the impedance curve, and observe the electrochemical corrosion. As the laser power density increased, the surface grains of the E690 high-strength steel cladding layer continued to refine until nanocrystals formed, and the residual compressive stress on the surface increased. The residual compressive stress on the surface rendered the passivation film stable and dense; furthermore, the refinement of surface grains inhibited the initiation and propagation of microcracks. The positive shift of the corrosion potential increased from -1.004 to -0.771 V, the corrosion current density decreased from 114.5 to 5.41 µA/cm2, the radius of the impedance spectrum curve increased, and the peeling pits, as well as corrosion micropores on the surface, gradually became no longer evident after electrochemical corrosion. After laser shock treatment, the corrosion resistance of the cladding layer sample was substantially improved.

[Use a leaflet flap of foot to severed multi-finger with segmental injury].

OBJECTIVE: To explore asurgical methods for replantation of severed finger. METHODS: From January 2018 to November 2022, 8 amputated-finger patients were performed surgical reconstructions by using polyfoliate free flaps with the first dorsal metatarsal artery, including 7 males and 1 female, aged from 20 to 55 years old, and defect areas ranged from (1.0 to 2.0) cm×(3.0 to 4.5) cm. Finger pulp sensation, shape and other relevant parameters were assessed following the upper extremity functional evaluation standard, which was put forward by Hand Surgery Branch of Chinese Medical Association. And maryland foot functional score was used to evaluate foot function. RESULTS: Amputated fingers and flaps of all the 8 patients were survived. All patients were followed up for 4 to 20 months, their finger color and temperature tured to normal, with good wear-resistance and cold-resistance. According to Hand Surgery Branch of Chinese Medical Association, functional score ranged 61 to 92;4 patients got excellent result and 4 good. Maryland foot functional score ranged from 93 to 100;and 8 patients got excellent result. CONCLUSION: It is feasible to repair severed fingers with soft tissue defects using polyfoliate free flaps that driven by the flippers of the first and second toes of the foot. This method ccould bridge blood vessels, increase soft tissue volume of the injured finger, and avoid finger shortening, with high patient satisfaction.

A novel tetraspanin-related gene signature for predicting prognosis and immune invasion status of lung adenocarcinoma.

BACKGROUND: Lung adenocarcinoma (LUAD), the most common subtype of lung cancer, is the primary contributor to cancer-linked fatalities. Dysregulation in the proliferation of cells and death is primarily involved in its development. Recently, tetraspanins, a group of transmembrane proteins, have gained increasing attention for their potential role in the progression of LUAD. Hence, our endeavor involved the development of a novel tetraspanin-based model for the prognostication of lung cancer. METHODS: A comprehensive set of bioinformatics tools was utilized to evaluate the expression of tetraspanin-related genes and assess their significance regarding prognosis. Hence, a robust risk signature was established through machine learning. The prognosis-predictive value of the signature was evaluated in terms of clinical application, functional enrichment, and the immune landscape. RESULTS: The research first identified differential expression of tetraspanin genes in patients with LUAD via publicly available databases. The resulting data were indicative of the value that nine of them held regarding prognosis. Five distinct elements were utilized in the establishment of a tetraspanin-related model (TSPAN7, TSPAN11, TSPAN14, UPK1B, and UPK1A). Furthermore, as per the median risk scores, the participants were classified into high- and low-risk groups. The model was validated using inner and outer validation sets. Notably, consensus clustering and prognostic score grouping analysis revealed that tetraspanin-related features affect tumor prognosis by modulating tumor immunity. A nomogram based on the tetraspanin gene was constructed with the aim of enhancing the poor prognosis of high-risk groups and facilitating clinical application. CONCLUSION: Through machine learning algorithms and in vitro experiments, a novel tetraspanin-associated signature was developed and validated for survival prediction in patients with LUAD that reflects tumor immune infiltration. This could potentially provide new and improved measures for diagnosis and therapeutic interventions for LUAD.

Visible-light-driven photoreforming of poly(ethylene terephthalate) plastics via carbon nitride porous microtubes.

It is highly desirable but challenging to realize efficient photoreforming of plastic waste over metal-free semiconductors. Here, we synthesized metal-free carbon nitride porous microtube (CNxPM) photocatalysts by carrying out a pyrolysis of the supramolecular assembly formed by the self-assembly of L-arginine (L-Arg) and melamine, the modification of L-Arg rationally engineering the microstructure and electronic structure of the CNxPM system for efficient visible-light-driven photoreforming of poly(ethylene terephthalate) (PET) to hydrogen (H2) and high-value chemicals. In particular, the amount of formate converted from PET substrate under visible light was highest in metal-free semiconductors without any co-catalyst reported so far, presenting the first example of visible-light-driven photoreforming of PET over a completely metal-free single-component semiconductor without any co-catalyst.

Effect of Multi-Element Microalloying on the Structure and Properties of High Chromium Cast Iron.

High chromium cast iron (HCCI) has been widely used as wear-resistant material in the industry. Alloying is an effective way to improve the microstructure and mechanical properties of HCCI. This paper added multi-component V-Fe-Ti-Nb-C-Zr-B alloy (VFC) to HCCI, showing a significant synergistic solution-strengthening effect. The results show that the added V-Ti-Nb-B are dissolved in M7C3 carbide to form the (Cr, Fe, V, Ti, Nb)7(C, B)3 alloy carbide, and a small amount of V and all Zr are dissolved in austenite and martensite. Adding VFC into HCCI improved the hardenability of HCCI, decreased the residual austenite content from 6.0 wt% to 0.9 wt%, increased the martensite content from 70.7 wt% to 82.5 wt%, and changed the structure and content of M7C3 carbide. These changes increased the hardness of as-cast and heat-tread HCCI by 1.4% and 4.1%, increased the hardness of austenite and martensite by 7.9% and 7.0%, increased the impact toughness by 16.9%, and decreased the friction coefficient and wear loss by 2.3 % and 7.0 %, respectively. Thus, the hardness, toughness, wear resistance, and friction resistance of HCCI alloy are improved simultaneously.

HLA complex P5 upregulation is correlated with poor prognosis and tumor progression in esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is a deadly malignant tumor that threatens human health. Long noncoding RNA (lncRNA) is widely expressed in eukaryotes and is closely associated with human disease progression. However, its role in ESCC remains incompletely understood. In this study, we analyzed the results of three gene expression omnibus (GEO) databases containing lncRNA expression data of ESCC and normal tissues. The results showed that HCP5 was significantly overexpressed in ESCC tissues, which was further verified in our collected ESCC samples. The functional study suggested that HCP5 knockdown inhibited ESCC cell proliferation and invasion. Regarding the mechanism, HCP5 was able to directly interact with YTHDF1, a N6-methyladenosine (m6A) reader, enhancing the binding of YTHDF1 to m6A-modified HK2 mRNA, leading to increasing HK2 stability, thereby promoting the Warburg effect (aerobic glycolysis) of ESCC cells. The nude mice model showed that the knockdown of HCP5 in vivo remarkably reduced tumor size. Clinically, high HCP5 was positively correlated with larger tumor volume, higher TNM stage and lymph node metastasis. Moreover, ESCC patients with high HCP5 exerted shorter survival time than patients with low HCP5. These findings uncover the importance of HCP5 in human ESCC progression; the turbulence of HCP5/YTHDF1/HK2 axis may be responsible for ESCC carcinogenicity.

Effect and Mechanism of the Lenvatinib@H-MnO2-FA Drug Delivery System in Targeting Intrahepatic Cholangiocarcinoma.

BACKGROUND: To investigate the effects of the Lenvatinib@H-MnO2-FA administration system on the proliferation and apoptosis of Intrahepatic cholangiocarcinoma (ICC) and the underlying molecular mechanism. MATERIALS AND METHODS: In this research, hollow MnO2 (H-MnO2) was synthesized via the modified Stöber method, and H-MnO2 was modified with polyethylene glycol-bis (Amine) (NH2-PEG-NH2) and folic acid (FA) to obtain H-MnO2-PEG-FA (H-MnO2-FA). Lenvatinib was coated in the hollow cavity of H-MnO2-PEG-FA to further form a nanometre drug-carrying system (Lenvatinib@H-MnO2-PEG-FA). Lenvatinib@H-MnO2-FA was characterized through transmission electron microscopy (TEM) and scanning electron microscopy (SEM). Fourier transform infrared spectroscopy (FT-IR) was used to verify that Lenvatinib was loaded on nanoparticles. Functionally, confocal laser scanning microscopy (CLSM), 2-(4-Amidinophenyl)-6-indolecarbamidine dihydrochloride (DAPI) staining, and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay were performed to determine the effect of Lenvatinib@H-MnO2-FA on the proliferation and apoptosis of ICC cells (9810 cells). Finally, the protein levels of Raf-1MEK1/2-ERK1/2 signalling pathway components were detected through Western blotting analysis. RESULTS: We successfully synthesised a Lenvatinib@H-MnO2-PEG-FA administration system. The resulting nanomaterials had excellent biological stability and improved targeting effects. Functionally, Lenvatinib@ H-MnO2-FA inhibited the proliferation of 9810 cells. The Bcl-2 protein level was significantly downregulated, and the caspase-3 protein level was significantly upregulated, indicating that Lenvatinib@H-MnO2- PEG- FA promoted the apoptosis of 9810 cells. Mechanistically, Lenvatinib@H-MnO2-FA increased the phosphorylation levels of Raf, MEK1/2, and ERK1/2. CONCLUSION: H-MnO2-FA can more effectively deliver Lenvatinib to inhibit proliferation and promote apoptosis in ICC, which could be the promising drug delivery nano-vehicles for delivery drugs.

Biothiol-Functionalized Cuprous Oxide Sensor for Dual-Mode Sensitive Hg2+ Detection.

Hg2+ ions are one of the highly poisonous heavy metal ions in the environment, so it is urgent to develop rapid and sensitive detection platforms for detecting Hg2+ ions. In this work, a novel electrochemical and photoelectrochemical dual-mode sensor (l-Cys-Cu2O) was successfully fabricated, and the sensor exhibits a satisfactory detection limit (0.2 and 0.01 nM) for the detection of Hg2+, which is far below the dangerous limit of the U.S. Environmental Protection Agency. The linear ranges of dual-mode Hg2+ detections were 0.33-3.3 and 0.17-1.33 µM, respectively. Moreover, the sensor shows desirable stability, selectivity, and reproducibility for detecting Hg2+ ions. For river water samples, the recoveries of 96.6-101.4% (electrochemical data) and 93.0-105.6% (photoelectrochemical data) were obtained, indicating that the sensor could be successfully applied in the determination of Hg2+ ions in environmental water. Therefore, the designed sensor has a potential in the trace-level detection of Hg2+ ions.

Phosphorus doped nickel selenide for full device water splitting.

The lack of high active and stable electrocatalysts has impeded the development of electrochemical water splitting device, which is promising technique for renewable energy conversion system. Here, we report a one-step protocol to synthesize P doped NiSe2 (P-NiSe2) by selenylation process derived from nickel foam with assistant of NaH2PO2 and Se powder. The P-NiSe2 could be directly used as working electrode and shows the superior electrochemical activity, offering current density of 10 mA cm-2 with overpotential of 270 mV for OER and 71 mV for HER. The enhanced electrochemical activity can be ascribed to the P atom doping. The P atom doping leads to the high valence state of Ni active sites, which have high catalytic ability towards OER. Moreover, the P doping makes the d-band center of Ni atoms in P-NiSe2 move close to Fermi level, facilitating the HER kinetics with respect to proton adsorption and hydrogen desorption. When employed P-NiSe2 as both anodic and cathodic electrode in alkaline water electrolyzer, a current density of 10 mA cm-2 can be achieved at 1.58 V. Our work highlights the importance of P doping in determining the surface electron configuration for full device water splitting and the facile synthesis protocol would be promising for realistic applications.

NUCB1 Suppresses Growth and Shows Additive Effects With Gemcitabine in Pancreatic Ductal Adenocarcinoma via the Unfolded Protein Response.

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer with poor patient prognosis. A cellular stress response mechanism called the unfolded protein response (UPR) has been implicated in PDAC progression. More recently, nucleobindin 1 (NUCB1), a calcium-binding protein, has been shown to control the UPR but its precise role in PDAC has not been explored. Here, we found that downregulation of NUCB1 was associated with poor prognosis in patients with PDAC. Functionally, NUCB1 overexpression suppressed pancreatic cancer cell proliferation and showed additive effects with gemcitabine (GEM) in vitro and in vivo. Moreover, by controlling ATF6 activity, NUCB1 overexpression suppressed GEM-induced UPR and autophagy. Last but not least, we uncovered METTL3-mediated m6A modification on NUCB1 5'UTR via the reader YTHDF2 as a mechanism for NUCB1 downregulation in PDAC. Taken together, our study revealed crucial functions of NUCB1 in suppressing proliferation and enhancing the effects of gemcitabine in pancreatic cancer cells and identified METTL3-mediated m6A modification as a mechanism for NUCB1 downregulation in PDAC.

CMTM8 as an LPA1-associated partner mediates lysophosphatidic acid-induced pancreatic cancer metastasis.

BACKGROUND: Lysophosphatidic acid (LPA) is known to promote cancer cell invasiveness through LPA1, but the downstream signaling cascades are still not fully clarified. The CKLF-like MARVEL transmembrane domain-containing (CMTM) family regulates aggressive phenotype in many cancers. METHODS: We performed LPA1 co-immunoprecipitation combined with mass spectrometry to search for LPA1-associated proteins. The role of CMTM8 in mediating the pro-invasive activity of LPA was investigated in pancreatic cancer. RESULTS: We identified CMTM8 as an LPA1-interacting protein. LPA1 and CMTM8 were co-localized in pancreatic cancer cells. LPA treatment led to stabilization of CMTM8 protein, which was impaired by knockdown of LPA1. Depletion of CMTM8 significantly suppressed the migration and invasion of pancreatic cancer cells. Conversely, ectopic expression of CMTM8 enhanced the migratory and invasive capacity of pancreatic cancer cells. CMTM8 depletion blocked the formation of metastatic lesions in the lung. Knockdown of CMTM8 attenuated LPA-induced migration and invasion in pancreatic cancer cells. CMTM8 overexpression stimulated ß-catenin activation through reduction of GSK3ß. In addition, knockdown of ß-catenin dramatically antagonized CMTM8-mediated migration and invasion in pancreatic cancer cells. CONCLUSIONS: CMTM8 serves as a key mediator of LPA-induced invasiveness in pancreatic cancer. The interaction between CMTM8 and LPA1 leads to activation of oncogenic ß-catenin signaling. CMTM8 represents a potential therapeutic target for pancreatic cancer.

Fam83D promotes tumorigenesis and gemcitabine resistance of pancreatic adenocarcinoma through the Wnt/ß-catenin pathway.

BACKGROUND: Elevated expression of family with sequence similarity 83 member D (Fam83D) has been found in various cancers; however, its role in pancreatic adenocarcinoma (PDAC) remains unclear. The current study was designed to elucidate the roles of Fam83D in pancreatic cancer. METHOD: The level of Fam83D was detected in PDAC tissues and adjacent no-tumorous tissues. Effects of Fam83D on proliferation, glycolysis and gemcitabine (GEM) sensitivity of pancreatic cancer cells were examined. RESULTS: Fam83D was overexpressed in PDAC and associated with clinical stage, metastatic status and survival rates of PDAC patients. Function study showed that Fam83D knockdown (KD) caused inhibited proliferation, suppressed mitochondrial respiration capacity, reduced aerobic glycolysis, and down-regulation of nuclear ß-catenin, proto-oncogene C-Myc, and lactate dehydrogenase A (LDHA). Fam83D KD enhanced the sensitivity of PDAC cells to GEM in vitro and in vivo. On the contrary, Fam83D overexpression displayed reverse effects on PDAC cells. Moreover, the Wnt/ß-catenin inhibitor abolished the effects of Fam83D overexpression in PDAC cells. CONCLUSIONS: the current data suggest that enhanced Fam83D expression contributes to PDAC progression and the development of chemoresistance through the Wnt/ß-catenin signaling.

Bone marrow-derived mesenchymal stem cells microvesicles stabilize atherosclerotic plaques by inhibiting NLRP3-mediated macrophage pyroptosis.

Rupture of atherosclerotic plaques constitutes the major cause of thrombosis and acute ischemic coronary syndrome. Bone marrow-derived mesenchymal stem cells microvesicles (BMSCs-MVs) are reported to promote angiogenesis. This study investigated the role of BMSCs-MVs in stabilizing atherosclerotic plaques. BMSCs-MVs in mice were isolated and identified. The mouse model of atherosclerosis was established, and mice were injected with BMSCs-MVs via the tail vein. The macrophage model with high glucose and oxidative damage was established and then incubated with BMSCs-MVs. Nod-like receptor protein 3 (NLRP3) expression, pyroptosis-related proteins, and inflammatory factors were detected. Actinomycin D was used to inhibit the secretion of BMSCs-MVs to verify the source of microRNA-223 (miR-223). The binding relationship between miR-223 and NLRP3 was predicted and verified. BMSCs-MVs with knockdown of miR-223 were cocultured with bone marrow-derived macrophages with knockdown of NLRP3, and then levels of miR-223, NLRP3, pyroptosis-related proteins, and inflammatory factors were detected. BMSCs-MVs could reduce the vulnerability index of atherosclerotic plaques and intima-media thickness in mice, and inhibit pyroptosis and inflammation. BMSCs-MVs inhibited pyroptosis and inflammatory factors in macrophages. BMSCs-MVs carried miR-223 to inhibit NLRP3 expression and reduce macrophage pyroptosis, thereby stabilizing the atherosclerotic plaques.

Self-supported nickel sulfide derived from nickel foam for hydrogen evolution and oxygen evolution reaction: effect of crystal phase switching.

Designing and fabricating economically viable, high active and stable electrocatalysts play an important role for hydrogen evolution reaction (HER) and oxygen evolution reaction (OER). Crystal phase is the crucial factor that governs the electrochemical property and electrocatalytic reaction pathways. Here, a one-step nickel foam derived sulfidation method was presented to synthesize self-supported NiS2 and Ni3S2. The crystal phase-dependent chemical properties related to electrocatalytic behavior were evaluated by a series of advanced characterization and density functional theory calculations. Overall, the self-supported Ni3S2 shows high electrochemical activity towards both HER and OER in alkaline conditions, which afford the current density of 10 mA cm-2 with overpotentials of 245 mV for OER and 123 mV for HER, respectively. When employed the self-supported Ni3S2 as the bifunctional electrocatalysts for overall water splitting, the entire device provides the current density of 10 mA cm-2 at 1.61 V. These results indicate that the electrocatalytic properties can be exert greater improved by controlling the crystal phase, offering the prospect for advanced materials design and development.

A NIR-Responsive Phytic Acid Nickel Biomimetic Complex Anchored on Carbon Nitride for Highly Efficient Solar Hydrogen Production.

A challenge in photocatalysis consists in improving the efficiency by harnessing a large portion of the solar spectrum. We report the design and realization of a robust molecular-semiconductor photocatalytic system (MSPS) consisting of an earth-abundant phytic acid nickel (PA-Ni) biomimetic complex and polymeric carbon nitride (PCN). The MSPS exhibits an outstanding activity at λ=940 nm with high apparent quantum efficiency (AQE) of 2.8 %, particularly λ>900 nm, as it outperforms all reported state-of-the-art near-infrared (NIR) hybrid photocatalysts without adding any noble metals. The optimum hydrogen (H2 ) production activity was about 52 and 64 times higher with respect to its pristine counterpart under the AM 1.5 G and visible irradiation, respectively, being equivalent to the platinum-assisted PCN. This work sheds light on feasible avenues to prepare highly active, stable, cheap NIR-harvesting photosystems toward sustainable and scalable solar-to-H2 production.

Holey Cobalt-Iron Nitride Nanosheet Arrays as High-Performance Bifunctional Electrocatalysts for Overall Water Splitting.

Designing efficient metal nitride electrocatalysts with advantageous nanostructures toward overall water splitting is of great significance for energy conversion. In this work, holey cobalt-iron nitride nanosheet arrays grown on Ni foam substrate (CoFeNx HNAs/NF) are prepared via a facile hydrothermal and subsequent thermal nitridation method. This unique HNA architecture can not only expose abundant active sites but also facilitate the charge/mass transfer. Resulting from these merits, the CoFeNx HNAs/NF exhibits high catalytic performance with overpotentials of 200 and 260 mV at 10 mA cm-2 for the hydrogen evolution reaction (HER) and 50 mA cm-2 for the oxygen evolution reaction (OER), respectively. Furthermore, when using CoFeNx-500 HNAs/NF as both anode and cathode, the alkaline electrolyzer could afford a current density of 10 mA cm-2 at 1.592 V, higher than many other metal nitride-based electrocatalysts. This work signifies a simple approach to prepare holey metal nitride nanosheet arrays, which can be applied in various fields of energy conversion and storage.

FBXL6 governs c-MYC to promote hepatocellular carcinoma through ubiquitination and stabilization of HSP90AA1.

BACKGROUND: Heat shot protein 90 (HSP90) AA1 functions as an onco-protein to regulate the assembly, manipulation, folding and degradation of its client proteins, including c-MYC. However, little is known about the mechanism of HSP90AA1 regulation. METHODS: Transcriptome RNA-sequencing data of hepatocellular carcinoma (HCC) samples were used to detect the mRNA expression of FBXL6. Immunoprecipitation/Mass Spectrum (IP/MS) method was used to identify the interacting proteins of FBXL6. The co-immunoprecipitation assay was used to determine the interaction between FBXL6 and HSP90AA1. The in vivo ubiquitination assay was performed to determine the regulation of HSP90AA1 by FBXL6. Luciferase reporter and chromatin immunoprecipitation (ChIP) assays were used to determine the transcriptional regulation of FBXL6 by c-MYC. Immunohistochemical (IHC) staining was performed to study the correlation of FBXL6 and HSP90AA1 protein expression in 87 HCC samples. Cell counting and colony formation assays were implemented to detect the biological effects of FBXL6 on the growth of HCC cells in vitro. The effect of FBXL6 on HCC tumor growth in vivo was studied in a tumor xenograft model in mice. RESULTS: Here, we identified the orphan F-box protein FBXL6, a substrate recognition subunit of an SCF (Skp1-Cul1-F-box protein) complex, as the ubiquitin ligase for HSP90AA1. FBXL6 promoted K63-dependent ubiquitination of HSP90AA1 to stabilize it. Through analysis of the TCGA dataset, we found that FBXL6 was significantly increased in HCC tissues and positively correlated with c-MYC pathway. FBXL6 accumulation in HCC causes the stabilization and activation of c-MYC by preventing HSP90AA1 degradation. The activated c-MYC directly binds to the promoter region of FBXL6 to induce its mRNA expression. CONCLUSION: Collectively, our data revealed an unknown FBXL6-HSP90AA1-c-MYC axis which might contribute to the oncogenesis of HCC, and we propose that inhibition of FBXL6 might represent an effective therapeutic strategy for HCC treatment. Video abstract.

Exploration of prognostic index based on immune-related genes in patients with liver hepatocellular carcinoma.

The present study aimed to screen the immune-related genes (IRGs) in patients with liver hepatocellular carcinoma (LIHC) and construct a synthetic index for indicating the prognostic outcomes. The bioinformatic analysis was performed on the data of 374 cancer tissues and 50 normal tissues, which were downloaded from TCGA database. We observed that 17 differentially expressed IRGs were significantly associated with survival in LIHC patients. These LIHC-specific IRGs were validated with function analysis and molecular characteristics. Cox analysis was applied for constructing a RiskScore for predicting the survival. The RiskScore involved six IRGs and corresponding coefficients, which was calculated with the following formula: RiskScore = [Expression level of FABP5 *(0.064)] + [Expression level of TRAF3 * (0.198)] + [Expression level of CSPG5 * (0.416)] + [Expression level of IL17D * (0.197)] + [Expression level of STC2 * (0.036)] + [Expression level of BRD8 * (0.140)]. The RiskScore was positively associated with the poor survival, which was verified with the dataset from ICGC database. Further analysis revealed that the RiskScore was independent of any other clinical feature, while it was linked with the infiltration levels of six types of immune cells. Our study reported the survival-associated IRGs in LIHC and then constructed IRGs-based RiskScore as prognostic indicator for screening patients with high risk of short survival. Both the screened IRGs and IRGs-based RiskScore were clinically significant, which may be informative for promoting the individualized immunotherapy against LIHC.