Highly-dispersed nickel species on nitrogen-doped porous carbon: Significant local pH-buffering capacity and favorable CO desorption for efficient and robust electro-reduction of CO2.

Electrocatalytic reduction of CO2 (CO2RR) to value-added fuels and chemicals can potentially serve as a promising strategy to curb CO2 accumulation and carbon neutral cycle, but is still plagued by sluggish kinetics, poor selectivity and weak durability. Herein, we developed highly-dispersed nickel species on the nitrogen-doped carbon materials (Ni/NC) via the double solvent method (DSM), followed by the pyrolysis. The as-prepared Ni/NC possesses high CO2-to-CO selectivity of 93.2%∼98.6% at broad potential range (0.57 âˆ¼ 0.97 VRHE), decent jCO of 57.9 mAcm-2 at -1.07 VRHE, and significant robustness (retaining 96.3% of the initial faradaic efficiency for CO formation after 50 h electrolysis). As manifested by the rotating ring-disk electrode (RRDE) tests, the DSM-based Ni/NC possesses more significant pH-buffering capacity than Ni nanoparticles, thus promotes the CO2-to-CO. DFT calculations unveil that Ni/NC exhibits relatively lower d-band center, hence resulting in favorable desorption of CO from the catalyst surface that intrinsically boost the CO2-to-CO compared with the nanoparticle catalyst. These results suggest that the DSM-derived Ni/NC catalysts is a promising candidate towards large-scale application of CO2-to-CO.

The Effect of Low-Dose Esketamine on Postoperative Neurocognitive Dysfunction in Elderly Patients Undergoing General Anesthesia for Gastrointestinal Tumors: A Randomized Controlled Trial.

Purpose: This study aims to evaluate the effects of the intraoperative application of low-dose esketamine on postoperative neurocognitive dysfunction (PND) in elderly patients undergoing general anesthesia for gastrointestinal tumors. Methods: Sixty-eight elderly patients were randomly allocated to two groups: the esketamine group (group Es) (0.25 mg/kg loading, 0.125mg/kg/h infusion) and the control group (group C) (received normal saline). The primary outcome was the incidence of delayed neurocognitive recovery (DNR). The secondary outcomes were intraoperative blood loss, the total amount of fluid given during surgery, propofol and remifentanil consumption, cardiovascular adverse events, use of vasoactive drugs, operating and anesthesia time, the number of cases of sufentanil remedial analgesia, the incidence of postoperative delirium (POD), the intraoperative hemodynamics, bispectral index (BIS) value at 0, 1, 2 h after operation and numeric rating scale (NRS) pain scores within 3 d after surgery. Results: The incidence of DNR in group Es (16.13%) was lower than in group C (38.71%) (P <0.05). The intraoperative remifentanil dosage and the number of cases of dopamine used in group Es were lower than in group C (P <0.05). Compared with group C, DBP was higher at 3 min after intubation, and MAP was lower at 30 min after extubation in group Es (P<0.05). The incidence of hypotension and tachycardia in group Es was lower than in group C (P <0.05). The NRS pain score at 3 d after surgery in group Es was lower than in group C (P <0.05). Conclusion: Low-dose esketamine infusion reduced to some extent the incidence of DNR in elderly patients undergoing general anesthesia for gastrointestinal tumors, improved intraoperative hemodynamics and BIS value, decreased the incidence of cardiovascular adverse events and the intraoperative consumption of opioids, and relieved postoperative pain.

Acinar Cell-Derived Extracellular Vesicle MiRNA-183-5p Aggravates Acute Pancreatitis by Promoting M1 Macrophage Polarization Through Downregulation of FoxO1.

Acute pancreatitis (AP) is a common cause of a clinically acute abdomen. Crosstalk between acinar cells and leukocytes (especially macrophages) plays an important role in the development of AP. However, the mechanism mediating the interaction between acinar cells and macrophages is still unclear. This study was performed to explore the role of acinar cell extracellular vesicles (EVs) in the crosstalk between acinar cells and macrophages involved in the pathogenesis of AP. EVs derived from caerulein-treated acinar cells induced macrophage infiltration and aggravated pancreatitis in an AP rat model. Further research showed that acinar cell-derived EV miR-183-5p led to M1 macrophage polarization by downregulating forkhead box protein O1 (FoxO1), and a dual-luciferase reporter assay confirmed that FoxO1 was directly inhibited by miR-183-5p. In addition, acinar cell-derived EV miR-183-5p reduced macrophage phagocytosis. Acinar cell-derived EV miR-183-5p promoted the pancreatic infiltration of M1 macrophages and increased local and systemic damage in vivo. Subsequently, miR-183-5p overexpression in macrophages induced acinar cell damage and trypsin activation, thus further exacerbating the disease. In clinical samples, elevated miR-183-5p levels were detected in serum EVs and positively correlated with the severity of AP. EV miR-183-5p might play an important role in the development of AP by facilitating M1 macrophage polarization, providing a new insight into the diagnosis and targeted management of pancreatitis. Graphical abstract of the present study. In our caerulein-induced AP model, miR-183-5p was upregulated in injured acinar cells and transported by EVs to macrophages. miR-183-5p could induce M1 macrophage polarization through downregulation of FoxO1 and the release of inflammatory cytokines, which could aggravate AP-related injuries. Therefore, a vicious cycle might exist between injured ACs and M1 macrophage polarization, which is fulfilled by EV-transported miR-183-5p, leading to sustainable and progressive AP-related injuries.

SIRT1 ameliorated septic associated-lung injury and macrophages apoptosis via inhibiting endoplasmic reticulum stress.

BACKGROUND: The inappropriate apoptosis of macrophages plays an important role in the pathogenesis of sepsis-induced acute lung injury, however, the detailed regulatory mechanisms remain largely unknown. As an endogenous apoptosis pathway, endoplasmic reticulum (ER) stress plays an important role in cell damage in patients with sepsis. Clarifying the ER stress response and its effect on macrophages during the development of sepsis is helpful to explore new strategies for the prevention and treatment of ALI in sepsis. METHODS: The mouse model and the RAW264.7 inflammation model were stimulated with LPS to establish in vivo and in vitro. We explored the effects of different expression levels of silent information regulator factor 2-related enzyme 1 (SIRT1) on the ER stress response and apoptosis of macrophages in the sepsis-related injury model. RESULTS: Our studies found that the increased expression of SIRT1 can significantly improve sepsis-related lung injury and relieve lung inflammation. SRT1720, a SIRT1 activator, can significantly inhibit the ER stress response of lung tissue and macrophages, inhibit the expression of pro-apoptotic proteins, promote the expression of anti-apoptotic proteins, and reduce macrophages of apoptosis. While the EX527, an inhibitor of SIRT1, had the opposite effect. CONCLUSION: SIRT1 can significantly improve sepsis-associated lung injury and LPS-induced macrophage apoptosis. This protective effect is closely related to its inhibition of the ER stress response via the PERK/eIF2-α/ATF4/CHOP pathway.

Comprehensive Analysis of Necroptosis in Pancreatic Cancer for Appealing its Implications in Prognosis, Immunotherapy, and Chemotherapy Responses.

Objective: Necroptosis represents a new target for cancer immunotherapy and is considered a form of cell death that overcomes apoptosis resistance and enhances tumor immunogenicity. Herein, we aimed to determine necroptosis subtypes and investigate the roles of necroptosis in pancreatic cancer therapy. Methods: Based on the expression of prognostic necroptosis genes in pancreatic cancer samples from TCGA and ICGC cohorts, a consensus clustering approach was implemented for robustly identifying necroptosis subtypes. Immunogenic features were evaluated according to immune cell infiltrations, immune checkpoints, HLA molecules, and cancer-immunity cycle. The sensitivity to chemotherapy agents was estimated using the pRRophetic package. A necroptosis-relevant risk model was developed with a multivariate Cox regression analysis. Results: Five necroptosis subtypes were determined for pancreatic cancer (C1∼C5) with diverse prognosis, immunogenic features, and chemosensitivity. In particular, C4 and C5 presented favorable prognosis and weakened immunogenicity; C2 had high immunogenicity; C1 had undesirable prognosis and high genetic mutations. C5 was the most sensitive to known chemotherapy agents (cisplatin, gemcitabine, docetaxel, and paclitaxel), while C4 displayed resistance to aforementioned agents. The necroptosis-relevant risk model could accurately predict prognosis, immunogenicity, and chemosensitivity. Conclusion: Our findings provided a conceptual framework for comprehending necroptosis in pancreatic cancer biology. Future work is required for evaluating its relevance in the design of combined therapeutic regimens and guiding the best choice for immuno- and chemotherapy.

Extracellular Vesicle/Macrophage Axis: Potential Targets for Inflammatory Disease Intervention.

Extracellular vesicles (EVs) can regulate the polarization of macrophages in a variety of inflammatory diseases by mediating intercellular signal transduction and affecting the occurrence and development of diseases. After macrophages are regulated by EVs, they mainly show two phenotypes: the proinflammatory M1 type and the anti-inflammatory M2 type. A large number of studies have shown that in diseases such as mastitis, inflammatory bowel disease, Acute lung injury, and idiopathic pulmonary fibrosis, EVs promote the progression of the disease by inducing the M1-like polarization of macrophages. In diseases such as liver injury, asthma, and myocardial infarction, EVs can induce M2-like polarization of macrophages, inhibit the inflammatory response, and reduce the severity of the disease, thus indicating new pathways for treating inflammatory diseases. The EV/macrophage axis has become a potential target for inflammatory disease pathogenesis and comprehensive treatment. This article reviews the structure and function of the EV/macrophage axis and summarizes its biological functions in inflammatory diseases to provide insights for the diagnosis and treatment of inflammatory diseases.

Nickel-Based High-Entropy Intermetallic as a Highly Active and Selective Catalyst for Acetylene Semihydrogenation.

Acetylene semihydrogenation is a key technology for producing polymer-grade ethylene from crude ethylene. Ni-based catalysts are promising alternatives to noble-metals for this process. However, achieving high catalytic activity and selectivity remains a big challenge. We report a novel catalyst design based on high-entropy intermetallics (HEI), which provide thermally stable isolated Ni without excess counterpart metals and achieve exceptionally high performance. Intermetallic NiGa was multi-metalized to a (NiFeCu)(GaGe), where the Ni and Ga sites were partially substituted with Fe/Cu and Ge, respectively, without altering the parent CsCl-type structure. The NiFeCuGaGe/SiO2 HEI catalyst completely inhibited ethylene overhydrogenation even at complete acetylene conversion, and exhibited five-times higher activity than other 3d-transition-metal-based catalysts. The DFT study showed that the surface energy decreased by multi-metallization, which drastically weakened ethylene adsorption.

Characterization of Modification Patterns, Biological Function, Clinical Implication, and Immune Microenvironment Association of m6A Regulators in Pancreatic Cancer.

Objective: N6-methyladenosine (m6A) modification may modulate various biological processes. Nonetheless, clinical implications of m6A modification in pancreatic cancer are undefined. Herein, this study comprehensively characterized the m6A modification patterns in pancreatic cancer based on m6A regulators. Methods: Genetic mutation and expression pattern of 21 m6A regulators and their correlations were assessed in pancreatic cancer from TCGA dataset. m6A modification patterns were clustered using unsupervised clustering analysis in TCGA and ICGC datasets. Differences in survival, biological functions and immune cell infiltrations were assessed between modification patterns. A m6A scoring system was developed by principal component analysis. Genetic mutations and TIDE scores were compared between high and low m6A score groups. Results: ZC3H13 (11%), RBM15B (9%), YTHDF1 (8%), and YTHDC1 (6%) frequently occurred mutations among m6A regulators. Also, most of regulators were distinctly dysregulated in pancreatic cancer. There were tight crosslinks between regulators. Two m6A modification patterns were constructed, with distinct prognoses, immune cell infiltration and biological functions. Furthermore, we quantified m6A score in each sample. High m6A scores indicated undesirable clinical outcomes. There were more frequent mutations in high m6A score samples. Lower TIDE score was found in high m6A score group, with AUC = 0.61, indicating that m6A scores might be used for predicting the response to immunotherapy. Conclusion: Collectively, these data demonstrated that m6A modification participates pancreatic cancer progress and ornaments immune microenvironment, providing an insight into pancreatic cancer pathogenesis and facilitating precision medicine development.

GYY4137 alleviates sepsis-induced acute lung injury in mice by inhibiting the PDGFRß/Akt/NF-κB/NLRP3 pathway.

AIMS: GYY4137 [GYY, morpholin-4-ium-4-methoxyphenyl (morpholino) phosphinodithioate] is a novel and perfect hydrogen sulfide (H2S) donor that is stable in vivo and in vitro. H2S, along with CO and NO, has been recognized as the third physiological gas signaling molecule that plays an active role in fighting various lung infections. However, the mechanism by which GYY4137 affects cecal ligation and puncture (CLP)-induced acute lung injury (ALI) is not understood. This study aimed to investigate whether GYY4137 inhibits the activation of the pyrin domain-containing protein 3 (NLRP3) inflammasome by inhibiting the PDGFRß/Akt/NF-κB pathway. MAIN METHODS: The model of CLP-induced ALI was established in vivo. The mice were subsequently treated with GYY4137 (25 µg/g and 50 µg/g) to simulate the realistic conditions of pathogenesis. Western blotting and immunohistochemical staining were used to examine protein expression, hematoxylin and eosin staining was used for the histopathological analysis, and the levels of inflammatory factors were determined using enzyme-linked immunosorbent assays (ELISAs). KEY FINDINGS: GYY4137 significantly increased the 7-day survival of mice with septic peritonitis and protected against CLP-induced ALI, including decreasing neutrophil infiltration, improving sepsis-induced lung histopathological changes, diminishing lung tissue damage, and attenuating the severity of lung injury in mice. The protective effect of GYY4137 was undoubtedly dose-dependent. We discovered that GYY4137 reduced the levels of the p-PDGFRß, p-NF-κB, ASC, NLRP3, caspase-1, and p-Akt proteins in septic mouse lung tissue. Akt regulates the generation of proinflammatory cytokines in endotoxemia-associated ALI by enhancing the nuclear translocation of NF-κB. SIGNIFICANCE: These results indicate a new molecular mechanism explaining the effect of GYY4137 on the treatment of CLP-induced ALI in mice.

Evaluation of surgical risk and prognosis between thyroid nodules of size <1 and ≥1 cm.

BACKGROUND: The objective of this study was to evaluate the surgical risk and prognosis between thyroid nodules of size <1 and ≥1 cm and to explore whether it is reasonable generally to ignore the diagnosis and treatment of thyroid nodules and thyroid carcinoma <1 cm in wide areas of China. METHODS: A retrospective observational study included all first-time thyroid surgery patients between January 2005 and December 2016 of the First Affiliated Hospital of Harbin Medical University. All patients were divided into two groups (group A: <1 cm, group B: ≥1 cm) according to the maximum diameter of the nodules and demographics, surgery procedure, pathology, postoperative complications, morbidity, and mortality were analyzed. RESULTS: A total of 6,317 patients were reviewed and 3,424 (54.20%) of them were malignant; 2,128 patients in group A and 4,189 in group B. Patients in group A had better pathological diagnosis, inferior extent of lymph node metastasis, less surgical complexity, fewer postoperative complications, and longer disease-free survival (DFS). CONCLUSIONS: Thyroid operations were safer and involved fewer postoperative complications when thyroid nodules were <1 cm and patients who were diagnosed with malignant thyroid disease had superior prognoses. Underdeveloped regions of China should diagnose and treat thyroid nodules <1 cm early.