Academic literature on the topic 'Zhong sheng jiao yu'

Electrochemical water splitting, an effective approach of generating high purity hydrogen in a clean way, is composed of two half reactions: hydrogen evolution reaction (HER) and oxygen evolution reaction (OER).[1] OER is the main rate-limiting half reaction for water splitting due to its sluggish four-electron transfer process.[2] , [3] An efficient electrocatalyst is indispensable to minimize the activation barrier for the reaction and achieve a high efficiency. Recently, two-dimensional (2D) layered double hydroxides (LDHs) have shown promises as one of the most effective electrocatalysts towards OER. However, the confined nanostructure with poor electronic conductivity inhibits their further enhanced catalytic performance towards OER. Herein, a 3D core-shell LDH structure is synthesized through a facile one-step reaction strategy, in which the terephthalic acid and urea is employed as the organic ligand for the metal organic framework (MOF) precursor and surface coordination buffer between LDH and MOF. Benefiting from the hierarchical 3D microstructure with uniformly nanosheets grown on the surface, the as prepared electrocatalyst exhibits rich edge active sites and enormous electrochemical surface area. The representative sample (namely, CoNi-LDH@BDC) achieves an excellent OER activity with a low overpotential of 280 mV at 100 mA cm-2 and robust cyclic stability. In addition, quasi-operando studies using X-ray absorption and X-ray photoelectron spectroscopy further elucidate that the Co-Ni dual metal sites act as the main active site while Ni of high valence state is a favorable site to oxygen for the O-O bond formation. The prominent OER performance is also attributed to the synergistic effect between different transition metal atoms. References [1] L. Yu, H. Zhou, J. Sun, F. Qin, F. Yu, J. Bao, Y. Yu, S. Chen, Z. Ren, Energy Environ. Sci. 2017, 10, 1820. [2] Y. Wang, C. Xie, Z. Zhang, D. Liu, R. Chen, S. Wang, Adv. Funct. Mater. 2018, 28, 1703363. [3] L. Zhuang, L. Ge, Y. Yang, M. Li, Y. Jia, X. Yao, Z. Zhu, Adv. Mater. 2017, 29, 1606793. [4] R. Frydendal, E. A. Paoli, B. P. Knudsen, B. Wickman, P. Malacrida, I. E. L. Stephens, I. Chorkendorff, ChemElectroChem 2014, 1, 2075. [5] Y. Lee, J. Suntivich, K. J. May, E. E. Perry, Y. Shao-Horn, Synthesis and activities of rutile IrO 2 and RuO 2 nanoparticles for oxygen evolution in acid and alkaline solutions, Vol. 3, American Chemical Society, 2012, pp. 399–404. [6] M. Gao, W. Sheng, Z. Zhuang, Q. Fang, S. Gu, J. Jiang, Y. Yan, J. Am. Chem. Soc. 2014, 136, 7077.

BackgroundColorectal cancer is a heterogeneous disease with complicated genetic alterations. Right colon and left colon have different features while right colon cancer displays an even worse prognosis. The randomized phase III FOxTROT trial demonstrated better downstaging effect with neoadjuvant plus adjuvant chemotherapy compared with adjuvant chemotherapy alone (P=0.04).1 Moreover, 2-year relapse rate was improved with neoadjuvant therapy, though the difference was not statistically significant. The NICHE study of neoadjuvant immunotherapy (maximum 6 weeks) showed that the pathological response was observed in 20/20 mismatch repair-deficient (dMMR) resectable colon cancers, with 19 major pathological responses and 12 pathological complete responses (pCRs).2 Recently, KEYNOTE-177 study showed improved progression-free survival with PD-1 inhibitor over chemotherapy (16.5 months vs. 8.2 months) in untreated microsatellite instability-high (MSI-H)/dMMR colon cancer patients, including 68% of right colon cancers.3 In addition, camrelizumab (PD-1 inhibitor) plus apatinib (vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor) demonstrated favorable antitumor effects and a manageable safety profile in advanced hepatocellular carcinoma and gastric cancer.4 5 This phase II trial aims to explore whether the combination of camrelizumab, apatinib and chemotherapy (mFOLFOX6) could significantly improve the pathological regression rate in locally advanced right colon cancer so as to bring considerable survival benefit for patients.MethodsEligible patients are aged 18–75 years, with locally advanced (T4 or T3 with extramural depth ≥5 mm, N0-2, M0, AJCC 8th) adenocarcinoma of right colon (including ileocecal area, ascending colon, and transverse colon to splenic flexion), and without prior systemic chemotherapy or immunotherapy. All patients will receive 5 cycles of camrelizumab (200 mg once every 2 weeks) plus mFOLFOX6 and 2 months of apatinib (250 mg orally once a day), followed by surgery and 7 cycles of adjuvant camrelizumab plus mFOLFOX6. The primary endpoint is the proportion of patients with tumor regression grade (TRG) 2–4 according to the Dworak criteria (TRG2: dominantly fibrotic changes with few tumor cells or groups; TRG3: very few tumor cells in fibrotic tissue; TRG4: no tumor cells). Secondary endpoints include downstaging rate, pCR rate, R0 resection rate, 2-year disease-free survival rate, 2-year event-free survival, overall survival, quality of life, and safety.ResultsTo date, three of planned 64 patients have been enrolled. Two patients have completed surgery. According to Dworak criteria, TRG ranked 4 (pathologic complete response) for the first patient and 3 (very few tumor cells in fibrotic tissue) for the second patient. No severe adverse events have been observed for all patients.Trial RegistrationThis trial has been registered at ClinicalTrials.gov (NCT04625803).ReferencesG. Foxtrot Collaborative. Feasibility of preoperative chemotherapy for locally advanced, operable colon cancer: the pilot phase of a randomised controlled trial. Lancet Oncol 13(11) (2012):1152–60.Chalabi M, Fanchi LF, Dijkstra KK, Van den Berg JG, Aalbers AG, Sikorska K, Lopez-Yurda M, Grootscholten C, Beets GL, Snaebjornsson P, Maas M, Mertz M, Veninga V, Bounova G, Broeks A, Beets-Tan RG, de Wijkerslooth TR, van Lent AU, Marsman HA, Nuijten E, Kok NF, Kuiper M, Verbeek WH, Kok M, Van Leerdam ME, Schumacher TN, Voest EE, Haanen JB. Neoadjuvant immunotherapy leads to pathological responses in MMR-proficient and MMR-deficient early-stage colon cancers. Nat Med 26(4) (2020):566–576.André T, Shiu KK, Kim TW, Jensen BV, Jensen LH, Punt C, Smith D, Garcia-Carbonero R, Benavides M, Gibbs P, de la Fouchardiere C, Rivera F, Elez E, Bendell J, Le DT, Yoshino T, Van Cutsem E, Yang P, Farooqui MZH, Marinello P, Diaz Jr LA. Pembrolizumab in microsatellite-instability-high advanced colorectal cancer. N Engl J Med 383(23) (2020):2207–2218.Xu J, Shen J, Gu S, Zhang Y, Wu L, Wu J, Shao G, Zhang Y, Xu L, Yin T, Liu J, Ren Z, Xiong J, Mao X, Zhang L, Yang J, Li L, Chen X, Wang Z, Gu K, Chen X, Pan Z, Ma K, Zhou X, Yu Z, Li E, Yin G, Zhang X, Wang S, Wang Q. Camrelizumab in combination with apatinib in patients with advanced hepatocellular carcinoma (RESCUE): a nonrandomized, open-label, phase II trial. Clin Cancer Res 27(4) (2021):1003–1011.Xu J, Shen J, Gu S, Zhang Y, Wu L, Wu J, Shao G, Zhang Y, Xu L, Yin T, Liu J, Ren Z, Xiong J, Mao X, Zhang L, Yang J, Li L, Chen X, Wang Z, Gu K, Chen X, Pan Z, Ma K, Zhou X, Yu Z, Li E, Yin G, Zhang X, Wang S, Wang Q, Xu J, Zhang Y, Jia R, Yue C, Chang L, Liu R, Zhang G, Zhao C, Zhang Y, Chen C, Wang Y, Yi X, Hu Z, Zou J, Wang Q. Camrelizumab in combination with apatinib in patients with advanced hepatocellular carcinoma (RESCUE): a nonrandomized, open-label, phase II trial anti-PD-1 antibody SHR-1210 combined with apatinib for advanced hepatocellular carcinoma, gastric, or esophagogastric junction cancer: an open-label, dose escalation and expansion study. Clin Cancer Res 27(4) (2021):1003–1011.Ethics ApprovalStudy protocol was approved by the Clinical Research Ethics Committee of the First Affiliated Hospital, College of Medicine, Zhejiang University (2020–119)ConsentWritten informed consent was obtained from the patient for publication of this abstract and any accompanying images. A copy of the written consent is available for review by the Editor of this journal.

Abstract BackgroundCurrently, BRAF inhibitors are primarily effective in LC patients with BRAF V600E mutation, while with limited benefit for patients with BRAF non-V600E mutation. Additionally, it is unclear whether immunotherapy is effective in LC patients with BRAF mutations, and the relationship between BRAF mutations and immune biomarkers, such as TMB, is also unclear. Here, we retrospectively investigated the relationship with BRAF mutation and TMB in Chinese LC patients.MethodsSamples were extracted from 3,136 our cohort samples of LC, which from OncoPanscan࣪ (Genetron Health) based sequencing of tissue. Because of the significantly different cohort characteristics, propensity score matching was used to resolve potential confounding by a nearest neighbor algorithm. The use of a multivariable logistic regression model to estimate the propensity score was based on age, sex, cancer type and detail panels. The samples after propensity score matching was used to investigate the relationship with TMB. ResultsIn our cohort, 171 samples had BRAF mutations and 2,965 samples had non-BRAF mutations. After propensity score analysis, 165 samples of BRAF mutations were screened with 165 paired samples of non-BRAF mutations.In the 165 samples of BRAF mutations, 83 samples of them had TMB information, while 83 samples of the 165 paired samples of non-BRAF mutations had TMB information. Patients with BRAF mutation had a higher median TMB than the patients with non-BRAF mutation (9.39 vs. 7.51 Muts/Mb, p=0.0545). Similarly, in these two groups, there was slightly higher ratio of samples with TMB ≥10muts/Mb (43.37% vs. 31.32%, P=0.0788). Among BRAF mutation group, when compared to BRAF V600E group (N=26), the median TMB was much higher in non-V600E group (N=57) (7.38 vs. 9.86 muts/Mb, P=0.0270). The proportion of TMB ≥10muts/Mb in BRAF non-V600E group was much higher than V600E group (49.12% vs. 30.77%, P=0.0094). Additionally, we analyzed the samples that had high TMB (TMB≥10 muts/Mb) and high PD-L1 (TPS≥50%). The BRAF mutation group had more proportion than non-BRAF mutation (14.46% vs.6.02%, p=0.0593), and the BRAF non-V600E group was higher than BRAF V600E group (15.79% vs. 11.54%, P=0.4150).ConclusionsCompared with non-BRAF mutation, BRAF mutation was associated with higher TMB, and it was also higher in BRAF non-V600E than BRAF V600E. These results suggested that patients with driver mutation of BRAF V600E had lower TMB and they always had good response to BRAF inhibitors. While LC patients with BRAF non-V600E always with higher TMB, thus, they may be more suitable for immunotherapy. However, more clinical research are needed to evaluate the effectiveness of immunotherapy. Citation Format: Jian Zhang, Yu Fang, Lei Sun, Hongling Yuan, Mao Shang, Xiaoyan Zhang, Honglin Zhu, Tonghui Ma. Investigating the potential relationship between BRAF mutations and tumor mutation burden (TMB) in lung cancer (LC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5292.

Исследована адсорбция аниона серина на гладком Pt и Pt(Pt)-электроде. Методом кривых заряжения получены стационарные и кинетические изотермы адсорбции. Установлено, что как на гладком, так и Pt(Pt)-электроде, кинетика исследуемых процессов подчиняется уравнению Рогинского-Зельдовича, а стационарное заполнение описывается изотермой Темкина. При этом адсорбция аниона серина на Pt(Pt) сопровождается диссоциацией адсорбата. Найдены основные термодинамические характеристики (константа адсорбционного и изменение свободной энергии Гиббса) процесса адсорбции аниона серина на обоих электродах. ЛИТЕРАТУРА Damaskin B., Petrii A. O., and Batrakar V.Adsorption of Organic Compounds on Electrodes. Plenum Press, New York, 1973. Sobkowski J., Juzkiewics-Herbish M. Metall/Solution Interface: an Experimental Approach, Modern Aspects of Electrochemistry, no. 31. Eds. by J. O¢ Bockris, R. E. White and B. E. Conway. Plenum Press, New York, London, 1997, p. 1. Frumkin A. N. 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Abstract BACKGROUND: Immune checkpoint inhibitors (ICIs) have revolutionized the cancer therapy landscape in recent years. Despite the success of the checkpoint blockade strategies targeting cytotoxic T lymphocyte antigen 4 (CTLA-4) and programmed death receptor 1 (PD-1), many cancer patients cannot benefit from these therapies. T cell immunoglobulin and mucin domain 3 (TIM-3) has emerged as one of the next generation ICI targets, with potentially lower toxicity and higher safety compared to CTLA-4 and PD-1 blockades. TIM-3 is widely expressed in different immune lineages playing various roles such as mediating immune tolerance and regulating innate immune response. However, the mechanism of action of TIM-3 inhibition in different malignancies is not completely understood. Whether the expression and genomic status of TIM-3 and its ligands, Ceacam-1, galectin-9, HMGB1 and phosphatidyl serine (PtdSer) are associated with clinical outcome or any indication would be essential for patient selection for TIM-3 targeting therapies. METHODS: Human PD-1/TIM-3 double-knock-in mice (PD-1/TIM-3 dKI HuGEMM™) engrafted with CT26.WT tumor model were used to test human PD-1 antibody (Keytruda) and TIM-3 antibody (MBG453). Immune phenotyping of blood, tumor draining lymph node (TDLN) and spleen tissues were assessed by flow cytometry at different time points after dosing. Cytokine levels in serum were measured by MSD assays at 48 hours post the 3rd dose and at study termination. Patient genomic and clinical data for various cancer types such as colorectal adenocarcinoma and pancreatic adenocarcinoma were collected for prognostic biomarker analysis. RESULTS: In the in vivo efficacy study of single and combination treatment with Keytruda and MBG453, we observed that NK cells were induced by anti-TIM-3 treatment, alone and in combination, in both blood and TDLN. This indicates TIM-3 blockade may lead to NK cell proliferation in the TME to enhance tumor killing. Transcriptomic analysis on thousands of patients from TCGA showed that high expression of TIM-3 was highly associated with MSI-H and MSI/CIMP subtypes of colorectal adenocarcinoma, suggesting the potential of Tim-3 target therapy in combination with PD-1 blockade in colorectal cancers. By survival analysis, we observe that one of the TIM-3 ligands, HMGB1, expression is associated with patient OS and PFS with pancreatic adenocarcinoma, but not in colorectal cancers. Furthermore, TIM-3 expression was associated with many immune cell signatures, including macrophages, dendritic cells, CD8+ memory T cells, CD4+ memory T cells and Tregs in both colorectal and pancreatic adenocarcinoma. CONCLUSIONS: Evaluation in preclinical model demonstrated that TIM-3 blockade may cause NK cell proliferation to enhance anti-tumor immunity. In addition, the expression and genomic alteration of TIM-3 and its ligand have prognostic values for certain cancers. Citation Format: Jia Xue, Yu Zhang, Xianfei He, Henry Q. Li, Sheng Guo. Tim-3 as an immune therapy target, mechanism and action, and prognostic values with its ligands in patient stratification [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 615.

Abstract Introduction: CD19 targeted autologous CAR-T therapies have been approved for the treatment of r/r B-ALL and greatly improved outcome. However, some patients may not be eligible to receive autologous CAR-T. TruUCAR™ GC502 is an allogeneic, universal CAR-T product with CD19/CD7 dual directed CAR. Preclinical data of GC502 were reported at ASH 2021 (Abstract 148500). Here, we report early clinical results from a phase I open-label, non-randomized, prospective investigator initiate trial (IIT) of GC502 in r/r B-ALL patients. Methods: GC502 is manufactured using leukopaks from HLA-unmatched healthy donors. It contains a 4-1BB based CD19/CD7 dual directing CAR, a T cell enhancer, and genetically disrupted TRAC and CD7 loci to avoid GvHD and fratricide. Patients (pts) with r/r B-ALL were enrolled and treated with one of two different formulations (A or B) in escalating dose levels ranging from 1.0x107 (DL1) to 1.5x107 (DL2) cells/kg. Prior to infusion of GC502, pts received a Flu/Cy based lymphodepletion regimen. Adverse events, disease response and expansion kinetics were evaluated in this study. Results: To date, 4 pts (15-34 yrs) were enrolled from Sep. 2021 to Jan. 2022. All patients were heavily pretreated, and had received either autologous or donor derived CD19 or CD19-CD22 targeted CAR-T therapy. Baseline marrow blast levels ranged from 19.5% to 92% (median 48.1%). 1 pt had extramedullary involvement. At data cut-off (Jan. 28, 2022), all patients had received a single dose of GC502: 1 pt at DL 1 1.0x107cells/kg and 3 patients at DL 2 1.5x107cells/kg. At day 28 post CAR-T infusion, 2 out of 3 response evaluable patients had achieved CR/CRi; 1 pt achieved PR at month 1 and subsequently received HSCT on day 39. TEAEs presented as Gr 3 febrile neutropenia (2/3), Gr 4 thrombocytopenia (1/3) and Gr 3 anemia (3/3). All TEAE resolved after treatment with SOC. Non-hematological TEAE presented as Gr≤3 γ-GT increase (3/3), Gr≤3 AST increase (2/3) and Gr≤3 ALT increase (3/3). CRS presented as Gr 2 in 2 patients with formulation B. 2 pts received formulation A and experienced Gr 3 CRS with a duration of 7 and 10 days respectively (CRS was graded according ASTCT Consensus Grading). CRS in all pts was manageable and resolved after treatment with Ruxolitinib, SOC and supportive care. No ICANS or aGvHD were observed. The pt treated in DL 1 did not show adequate GC502 cellular expansion. Peak expansions of GC502 in peripheral blood were observed between week 1-2 in DL 2. Median peak CAR copies were 149,945 copies/ug DNA (range 10,849-195,400). Conclusions: TruUCAR™ GC502 demonstrated promising early results with a manageable safety profile. Robust CAR-T cell expansion was observed in DL2 at 1.5x107cells/kg in heavily pretreated r/r B-ALL patients, including those previously treated with CD19 CAR-T therapies. The study is ongoing and continues accruing patients. Citation Format: Shiqi Li, Xinxin Wang, Zhongtao Yuan, Lin Liu, Yu Li, Jia Liu, Jiaping He, Zhimin Li, Wei Zhao, Jianning Ge, Yajin Ni, Lianjun Shen, Wei Cao, Xi Zhang, Martina Sersch, Sanbin Wang. Early results of a safety and efficacy study of allogeneic TruUCAR™ GC502 in patients with relapsed/refractory B-cell acute lymphoblastic leukemia (r/r B-ALL) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT196.

Thesis (M.Phil.)--Hong Kong University of Science and Technology, 2004.
Includes bibliographical references (leaves 323-342). Also available in electronic version. Access restricted to campus users.