Publications by authors named "Wei Guan"

388 Publications

Four new polyacetylenes from the roots of .

Nat Prod Res 2021 Jan 10:1-8. Epub 2021 Jan 10.

Key Laboratory of Chinese Materia Medica (Ministry of Education), Heilongjiang University of Chinese Medicine, Harbin, P.R. China.

Four new polyacetylene substances, sadivaethynes A-D, were isolated from the ethanol extract of the roots of (Turcz.) Schischk using repeated column chromatography. Structural elucidation of compounds was established by 1D and 2D NMR spectra referring to the literature, together with high-resolution mass spectrometric analysis. All compounds were evaluated for cytotoxicity against two human cancer cell lines (MGC-803, Ishikawa) .
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http://dx.doi.org/10.1080/14786419.2020.1869973DOI Listing
January 2021

Three-Year Outcomes of Sleeve Gastrectomy Plus Jejunojejunal Bypass: a Retrospective Case-Matched Study with Sleeve Gastrectomy and Gastric Bypass in Chinese Patients with BMI ≥35 kg/m.

Obes Surg 2021 Apr 16. Epub 2021 Apr 16.

Department of General surgery, the First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, Jiangsu, China.

Background: Sleeve gastrectomy plus jejunojejunal bypass (SG+JJB) is a novel bariatric procedure. In this study, we compared the 3-year outcomes of SG+JJB to those of sleeve gastrectomy (SG) and gastric bypass (RYGB).

Methods: This retrospective study included 113 patients (SG, N=31; RYGB, N=33; SG+JJB, N=49) with a preoperative BMI≥35 kg/m. Among them, 31 pairs of patients who underwent SG+JJB/SG and 33 pairs who underwent SG+JJB/RYGB were matched by sex, age (±2 years), and BMI (±2 kg/m). Postoperative weight loss, diabetes remission, and patient complaints at the 3-year follow-up were compared.

Results: SG+JJB yielded higher 3-year total weight loss (TWL) than SG alone (35.5±9.1% vs 31.5±7.3%, P=0.031) and equivalent 3-year %TWL to RYGB. The diabetes remission rate of SG+JJB was similar to that of SG or RYGB. SG+JJB resulted in a higher incidence of malodorous flatus than SG (25.8% vs 0, P<0.05). Compared to RYGB, SG+JJB resulted in a higher incidence of postoperative de novo gastroesophageal reflux disease (GERD) symptoms (30.3% vs 0, P<0.05).

Conclusions: In the present study, we found that SG+JJB yielded higher weight loss than SG and similar weight loss to RYGB at the 3-year follow-up. SG+JJB increased the risk of malodorous flatus compared to SG and de novo GERD symptoms compared to RYGB.
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http://dx.doi.org/10.1007/s11695-021-05411-zDOI Listing
April 2021

Profiling of somatic mutations and fusion genes in acute myeloid leukemia patients with FLT3-ITD or FLT3-TKD mutation at diagnosis reveals distinct evolutionary patterns.

Exp Hematol Oncol 2021 Apr 9;10(1):27. Epub 2021 Apr 9.

Department of Hematology, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853, China.

Background: The receptor tyrosine kinase FLT3 with internal tandem duplications within the juxtamembrane domain (FLT3-ITD) is a poor prognostic factor; however, the prognostic significance of missense mutation in the tyrosine kinase domain (FLT3-TKD) is controversial. Furthermore, the accompanying mutations and fusion genes with FLT3 mutations are unclear in acute myeloid leukemia (AML).

Methods: We investigated FLT3 mutations and their correlation with other gene mutations and gene fusions through two RNA-seq based next-generation sequencing (NGS) method and prognostic impact in 207 de novo AML patients.

Results: FLT3-ITD mutations were positive in 58 patients (28%), and FLT3-TKD mutations were positive in 20 patients (9.7%). FLT3-ITD was associated with a higher white blood cell count (WBC, mean 72.9 × 10/L vs. 24.2 × 10/L, P = 0.000), higher bone marrow blasts (mean 65.9% vs. 56.0%, P = 0.024), and NK-AML (normal karyotype) (64.8% vs. 48.4%, P = 0.043). NPM1 and DNMT3A mutations were enriched in FLT3-ITD (53.5% vs. 15.3%, P = 0.000; 34.6% vs. 13%, P = 0.003). However, the mutations of CEBPA were excluded in FLT3-AML (3.8% vs. 0% vs. 19.8%, P = 0.005). Mutations of Ras and TP53 were unlikely associated with FLT3-ITD (1.9% vs. 20.6%, P = 0.006; 0% vs. 6.1%, P = 0.04). The common fusion genes (> 10%) in FLT3-ITD had MLL-rearrangement and NUP98-rearrangement, while the common fusion genes in FLT3-TKD had AML1-ETO and MLL-rearrangement. Two novel fusion genes PRDM16-SKI and EFAN2-ZNF238 were identified in FLT3-ITD patients. Gene fusions and NPM1 mutation were mutually excluded in FLT3-ITD and FLT3-TKD patients. Their patterns of mutual exclusivity and cooperation among mutated genes suggest that additional driver genetic alterations are required and reveal two evolutionary patterns of FLT3 pathogenesis. Patients with FLT3-ITD had a lower CR (complete remission) rate, lower 3-year OS (overall survival), DFS (disease-free survival), and EFS (event-free survival) compared to FLT3AML. NK-AML with FLT3-ITD had a lower 3-year OS, DFS, and EFS than those without, while FLT3-TKD did not influence the survival in whole cohort and NK-AML. Besides, we found that FLT3-ITD/TET2 bimutation defined a poor prognostic subgroup.

Conclusions: Our study offers deep insights into the molecular pathogenesis and biology of AML with FLT3-ITD and FLT3-TKD by providing the profiles of concurrent molecular alterations and the clinical impact of FLT3-ITD and FLT3-TKD on AML patients.
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http://dx.doi.org/10.1186/s40164-021-00207-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8033687PMC
April 2021

Sirtuin 1 alleviates neuroinflammation-induced apoptosis after traumatic brain injury.

J Cell Mol Med 2021 May 8;25(9):4478-4486. Epub 2021 Apr 8.

Department of Neurosurgery, The Second Affiliated Hospital, Fujian Medical University, Quanzhou, China.

Sirtuin 1 (SIRT1) plays a very important role in a wide range of biological responses, such as metabolism, inflammation and cell apoptosis. Changes in the levels of SIRT1 have been detected in the brain after traumatic brain injury (TBI). Further, SIRT1 has shown a neuroprotective effect in some models of neuronal death; however, its role and working mechanisms are not well understood in the model of TBI. This study aimed to address this issue. SIRT1-specific inhibitor (sirtinol) and activator (A3) were introduced to explore the role of SIRT1 in cell apoptosis. Results of the study suggest that SIRT1 plays an important role in neuronal apoptosis after TBI by inhibiting NF-κB, IL-6 and TNF-α deacetylation and the apoptotic pathway sequentially, possibly by alleviating neuroinflammation.
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http://dx.doi.org/10.1111/jcmm.16534DOI Listing
May 2021

Evaluation of acute myeloid leukemia blast percentage on MethylC-Capture Sequencing results.

Exp Hematol Oncol 2021 Mar 31;10(1):26. Epub 2021 Mar 31.

Department of Hematology and Oncology, International Cancer Center, Shenzhen Key Laboratory of Precision Medicine for Hematological Malignancies, Shenzhen University General Hospital, Shenzhen University Clinical Medical Academy, Shenzhen University Health Science Center, Shenzhen University, Xueyuan AVE 1098, Nanshan District, Shenzhen, Guangdong, 518000, People's Republic of China.

Aberrant DNA methylation is often related to the diagnosis, prognosis, and therapeutic response of acute myeloid leukemia (AML); however, relevant studies on the relationship between bone marrow myeloblast percentage and the DNA methylation level in AML have not been reported. We evaluated the effects of AML blast percentage on DNA methylation level using the MethylC-capture sequencing (MCC-Seq) approach based on next-generation sequencing (NGS) and found that the methylation level of both genome-wide and promoter regions significantly increased when the percentage of AML blasts reached ≥ 40%, indicating that an accurate DNA methylation level in cancer cells can be obtained when the bone marrow samples of AML patients have more than 40% myeloblasts.
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http://dx.doi.org/10.1186/s40164-021-00219-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8011402PMC
March 2021

Androgen receptor splice variant 7 detected by immunohistochemical is an independent poor prognostic marker in men receiving adjuvant androgen-deprivation therapy after radical prostatectomy.

Biomark Res 2021 Mar 31;9(1):23. Epub 2021 Mar 31.

Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.

Background: To evaluate the predictive value of AR-V7 expression detected by immunohistochemical (IHC) in the prognosis of prostate cancer patients receiving adjuvant hormonal therapy (AHT) following radical prostatectomy (RP).

Methods: We retrospectively collected data of 110 patients with prostate cancer receiving RP, followed by AHT, from Tongji hospital. IHC analysis of AR-V7 expression was performed in a retrospective cohort.

Results: In total, 110 patients were enrolled, of whom 21 patients (19.1%) were AR-V7-positive and 89 patients (80.9%) were AR-V7-negative. No significant differences in baseline characteristics were found between the two groups. AR-V7-positive patients had shorter progression-free survival (PFS) (HR: 4.26; 95% CI, 1.55 to 11.68; P = 0.003), shorter cancer-special survival (CSS) (HR: 22.47; 95% CI, 2.912 to 173.4; P = 0.003) and shorter overall survival (OS) (HR: 6.61; 95% CI, 1.40 to 31.20; P = 0.017) compared to AR-V7-negative patients. In multivariate analysis, AR-V7 is an independent risk factor for shorter PFS (HR, 3.76; 95% CI, 1.63 to 8.70; P = 0.002), shorter CSS (HR: 9.17; 95% CI, 1.48 to 55.56; P = 0.017) and shorter OS (HR: 4.81; 95% CI, 1.28 to 17.86; P = 0.020).

Conclusion: The presence of AR-V7 in prostate cancer tissue is independently associated with an unfavorable prognosis for PFS, OS and CSS in patients who received AHT.
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http://dx.doi.org/10.1186/s40364-021-00276-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8011087PMC
March 2021

Comparison of Thulium Laser Resection of Bladder Tumors and Conventional Transurethral Resection of Bladder Tumors for Non-Muscle-Invasive Bladder Cancer.

Urol Int 2021 Mar 30:1-6. Epub 2021 Mar 30.

Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Introduction: The thulium laser resection of bladder tumors (TmLRBT) was increasingly used in the treatment of non-muscle-invasive bladder cancer (NMIBC) recently, and here we report the relevant outcomes of our institution to evaluate its efficacy and safety.

Methods: We retrospectively collected the data of NMIBC patients who underwent either TmLRBT or transurethral resection of bladder tumor (TURBT). The baseline characteristics and perioperative outcomes were compared in these 2 groups.

Results: The TmLRBT had a higher rate of detrusor identification than TURBT (97.4 vs. 87.6%, p = 0.001). After screening, 134 patients who underwent TmLRBT and 152 patients who received TURBT were enrolled in the analysis, and their baseline characteristics were similar. During the TURBT, 24 (15.8%) obturator nerve reflexes and 9 (5.9%) bladder perforations occurred, while none happened during the TmLRBT. After surgery, TmLRBT patients had fewer postoperative gross hematuria (38.1 vs. 96.7%, p < 0.001) and postoperative irrigation (27.6 vs. 92.7%, p < 0.001), and its irrigation duration was significantly shorter (2.3 vs. 3.3 day, p < 0.001). During the follow-up, no significant difference in the recurrence rate was detected (p = 0.315).

Conclusions: TmLRBT is a safer technique than conventional TURBT in the treatment of NMIBC, and it could offer better specimens for pathologic assessment while the cancer control was not compromised.
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http://dx.doi.org/10.1159/000514042DOI Listing
March 2021

Transcriptomic and functional analyses reveal roles of AclR, a luxR-type global regular in regulating motility and virulence of .

Mol Plant Microbe Interact 2021 Mar 29. Epub 2021 Mar 29.

Chinese Academy of Agricultural Sciences Institute of Plant Protection, 243827, Beijing, Beijing, China;

LuxR-type transcriptional regulators are essential for many physiological processes in bacteria, including pathogenesis. Acidovorax citrulli is a seedborne bacterial pathogen responsible for bacterial fruit blotch, which causes great losses in melon and watermelon worldwide. However, the LuxR-type transcriptional factors in A. citrulli have not been well studied, except the previously reported LuxR-type regulatory protein, AcrR, involved inregulating virulence and motility. Here, we characterized a second LuxR-type regulator, AclR, in the group II strain Aac-5 of A. citrulli by mutagenesis, virulence and motility assays, and transcriptomic analysis. Deletion of aclR resulted in impaired twitching and swimming motility and flagellar formation and diminished virulence but increased biofilm formation. Transcriptomic analysis revealed that 1379 genes were differentially expressed in the aclR-mutant strain, including 29 genes involved in flagellar assembly and 3 involved in pili formation, suggesting a regulatory role for AclR in multiple important biological functions of A. citrulli. Together, our results not only indicate that AclR plays a global role in transcriptional regulation in A. citrulli influencing motility, biofilm formation, and virulence, but also provide perspective regarding the regulatory network of biological functions in A. citrulli.
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http://dx.doi.org/10.1094/MPMI-01-21-0020-RDOI Listing
March 2021

Three new sesquiterpenoid alkaloids from the roots of and its cytotoxicity.

Nat Prod Res 2021 Mar 26:1-9. Epub 2021 Mar 26.

Key Laboratory of Chinese Materia Medica, Heilongjiang University of Chinese Medicine, Ministry of Education, Harbin, People's Republic of China.

Three new sesquiterpenoid alkaloids, cangorin K (), dimacroregelines C () and D (), as well as two known sesquiterpenoids (-), were isolated from the roots of The structures of new compounds were characterised by extensive 1D and 2D NMR spectroscopic analyses, as well as HRESIMS data, and the known compounds were established by 1 D NMR spectra referring to the literatures. Cytotoxicity evaluation of these compounds against two human tumour lines (SMMC7721, LN229) was investigated by CCK-8 assay and displayed that compounds - showed potent cytotoxicity against SMMC7721 cell with IC value in the range of 0.26-9.67 μΜ and compounds - showed potent cytotoxicity against LN-229 cell with IC values in the range of 0.50-7.38 μΜ.
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http://dx.doi.org/10.1080/14786419.2021.1903460DOI Listing
March 2021

Genus Stathmopoda Herrich-Schäffer, 1853 (Lepidoptera: Stathmopodidae) from China: Descriptions of ten new species.

Zootaxa 2021 Jan 18;4908(4):zootaxa.4908.4.1. Epub 2021 Jan 18.

College of Life Sciences, Nankai University, Tianjin 300071, China.

Ten new species of the genus Stathmopoda are described: S. basirotata sp. nov., S. bicoloriptera sp. nov., S. bucera sp. nov., S. hamulata sp. nov., S. ochricolorata sp. nov., S. octacantha sp. nov., S. pyriformis sp. nov., S. rhombica sp. nov., S. tetracantha sp. nov. and S. tristriata sp. nov. Also, three species: S. citrinella Sinev, 1995, S. orbiculata Meyrick, 1913 and S. tecticochlea Terada, 2016 are newly recorded for China. Images of both adults and genitalia for the species are provided, along with a map showing the distribution of them in China.
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http://dx.doi.org/10.11646/zootaxa.4908.4.1DOI Listing
January 2021

High Expression of CLEC11A Predicts Favorable Prognosis in Acute Myeloid Leukemia.

Front Oncol 2021 2;11:608932. Epub 2021 Mar 2.

Department of Hematology, Chinese People's Liberation Army General Hospital, Beijing, China.

Background: Acute myeloid leukemia (AML) is a heterogeneous disease of the hematopoietic system, for which identification of novel molecular markers is potentially important for clinical prognosis and is an urgent need for treatment optimization.

Methods: We selected C-type lectin domain family 11, member A (CLEC11A) for study several public databases, comparing expression among a variety of tumors and normal samples as well as different organs and tissues. To investigated the relationship between CLEC11A expression and clinical characteristics, we derived an AML cohort from The Cancer Genome Atlas (TCGA); we also investigated the Bloodspot and HemaExplorer databases. The Kaplan-Meier method and log-rank test were used to evaluate the associations between CLEC11A mRNA expression, as well as DNA methylation, and overall survival (OS), event-free survival (EFS), and relapse-free survival (RFS). DNA methylation levels of CLEC11A from our own 28 AML patients were assessed and related to chemotherapeutic outcomes. Bioinformatics analysis of CLEC11A was carried out using public databases.

Results: Multiple public databases revealed that CLEC11A expression was higher in leukemia. The TCGA data revealed that high CLEC11A expression was linked with favorable prognosis (OS -value = 2e-04; EFS -value = 6e-04), which was validated in GSE6891 (OS -value = 0; EFS -value = 0; RFS -value = 2e-03). Methylation of CLEC11A was negatively associated with CLEC11A expression, and high CLEC11A methylation level group was linked to poorer prognosis (OS -value = 1e-02; EFS -value = 2e-02). Meanwhile, CLEC11A hypermethylation was associated with poor induction remission rate and dismal survival. Bioinformatic analysis also showed that CLEC11A was an up-regulated gene in leukemogenesis.

Conclusion: CLEC11A may be used as a prognostic biomarker, and could do benefit for AML patients by providing precise treatment indications, and its unique gene pattern should aid in further understanding the heterogeneous AML mechanisms.
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http://dx.doi.org/10.3389/fonc.2021.608932DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7966831PMC
March 2021

Recurrent Sepsis Exacerbates CD4 T Cell Exhaustion and Decreases Antiviral Immune Responses.

Front Immunol 2021 25;12:627435. Epub 2021 Feb 25.

College of Pulmonary and Critical Care Medicine, Chinese People's Liberation Army (PLA) General Hospital, Beijing, China.

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to an infection. It is a disease with a high incidence, mortality, and recurrence rate and frequently results in its survivors requiring readmission into hospitals. The readmission is mainly due to recurrent sepsis. Patients with recurrent sepsis are more susceptible to secondary infections partly due to immune dysfunction, leading to a higher mortality in the long term. However, there remains a gap in the understanding of immunological characteristics and underlying mechanisms of recurrent sepsis. In this study, we used mouse models of acute and recurrent sepsis to investigate their different immunological characteristics. And then we subjected the two mouse models to a secondary influenza A virus (H1N1) infection and characterized the different immune responses. Here, we demonstrated that CD4 T cells present an exacerbated exhaustion phenotype in response to recurrent sepsis as illustrated by the decreased frequency of CD4 T cells, reduced co-stimulatory CD28 and increased inhibitory PD-1 and Tim-3 expression on CD4 T cells, increased frequency of regulatory T cells, and reduced MHC-II expression on antigen-presenting cells. Moreover, we showed that antiviral immune responses decrease in the recurrent sepsis mouse model subjected to a secondary infection as illustrated by the reduced pathogen clearance and inflammatory response. This may be a consequence of the exacerbated CD4 T cell exhaustion. In summary, recurrent sepsis exacerbates CD4 T cell exhaustion and decreases antiviral immune responses, contributing to significant morbidity, increased late mortality, and increased health care burden in recurrent sepsis patients.
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http://dx.doi.org/10.3389/fimmu.2021.627435DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7946831PMC
February 2021

Two new terpenes from the aerial parts of Osbeck.

Nat Prod Res 2021 Feb 22:1-8. Epub 2021 Feb 22.

Key Laboratory of Chinese Materia Medica, Heilongjiang University of Chinese Medicine, Ministry of Education, Harbin, People's Republic of China.

Two new acyclic sesquiterpenoids () and fourteen known monocyclic monoterpenoids () were isolated from the aerial parts of Osbeck. All compounds were isolated from for the first time. The structures of all compounds were characterized by spectroscopic methods (1 D, 2 D NMR and HRESIMS). In-vitro cytotoxic activity against two human cancer cell lines (MGC-803 and Ishikawa) of all the compounds were evaluated by CCK-8 assay.
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http://dx.doi.org/10.1080/14786419.2021.1889541DOI Listing
February 2021

Ophiopogonin A Alleviates Hemorrhagic Shock-Induced Renal Injury via Induction of Nrf2 Expression.

Front Physiol 2020 1;11:619740. Epub 2021 Feb 1.

Department of Orthopaedics, Affiliated Hospital of Nantong University, Nantong, China.

Ophiopogonin, including Ophiopogonin A, B, C, D, is an effective active component of traditional Chinese medicine which has a wide range of pharmacological effects such as protecting myocardial ischemia, resisting myocardial infarction, immune regulation, lowering blood glucose, and anti-tumor. However, the functions of ophiopogonin A on hemorrhagic shock (HS)-induced renal injury remain unclear. First, this study constructed an HS rat model and hypoxia HK-2 cell model to assess the effects of ophiopogonin A and . , HE and TUNEL staining show that ophiopogonin A dose-dependently inhibits HS-induced tissue damage and apoptosis. Moreover, ophiopogonin A dose-dependently downregulates the levels of blood urea nitrogen (BUN), creatinine (Cr), KIM-1, NGAL, iNOS, TNF-α, IL-1β, and IL-6 in HS rats kidney tissues, and decreases the number of MPO-positive cells. , we get similar results that ophiopogonin A dose-dependently improves hypoxia-induced HK-2 cell apoptosis and damage. In addition, ophiopogonin A dose-dependently increases the expression of NF E2-related factor 2 (Nrf2), while knockdown of Nrf2 reverses the functions of ophiopogonin A and . Furthermore, ophiopogonin A dose-dependently promotes the phosphorylation of ERK in HS kidney tissues and hypoxia-treated HK-2 cells, suggesting that ophiopogonin A functions via the p-ERK/ERK signaling pathway.
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http://dx.doi.org/10.3389/fphys.2020.619740DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7882626PMC
February 2021

Clinicopathological characteristics and survival in lung signet ring cell carcinoma: a population-based study.

Bosn J Basic Med Sci 2021 Feb 15. Epub 2021 Feb 15.

Department of Thoracic surgery, Daping Hospital, Army Medical University, Chongqing, China.

Lung signet ring cell carcinoma (LSRCC) is a very rare type of lung cancer, the clinical characteristics, and prognosis of which remain to be clarified. In order to explore the clinicopathological and survival-related factors associated with LSRCC, we performed a large population-based cohort analysis of data included in the Surveillance, Epidemiology, and End Results (SEER) registry from 2001- 2015. A total of 752 LSRCC and 7518 lung mucinous adenocarcinoma (LMAC) patients were incorporated into our analysis, with respective mean ages of 63.8 and 67.5 years at the time of diagnosis. LSRCC patients were significantly more likely than LMAC patients to have distant-stage disease (72.1% vs. 45.8%, p<0.0001), tumors of a high pathological grade (40.6% vs. 10.8%, p<0.0001), have undergone chemotherapy (62.1% vs. 39.9%, p<0.0001), be male (52.7% vs. 48.5%, p=0.03), and be < 40 years old (3.3% vs. 1.3%, p=0.022), whereas they were less likely to have undergone surgical treatment (52.4% vs. 77.0%, p<0.0001). LSRCC and LMAC patients exhibited median overall survival (OS) duration of 8 and 18 months (p<0.0001), respectively, although these differences were not significant after adjusting for confounding variables. Independent factors associated with a favorable patient prognosis included a primary site in the middle or lower lung lobe, underwent surgery and underwent chemotherapy. However, age ≥ 80 years, higher grade, distant summary stage disease, and T4 stage disease were linked to poor prognosis. Patient age, tumor grade, primary tumor site, summary stage, T stage, surgery, and chemotherapy were all significantly associated with LSRCC patient prognosis.
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http://dx.doi.org/10.17305/bjbms.2020.5454DOI Listing
February 2021

Androgen Receptor Splice Variant 7 Predicts Shorter Response in Patients with Metastatic Hormone-sensitive Prostate Cancer Receiving Androgen Deprivation Therapy.

Eur Urol 2021 Feb 10. Epub 2021 Feb 10.

Department of Urology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Institute of Urology of Hubei Province, Wuhan, China. Electronic address:

Background: Whether AR-V7 expression can predict the response in patients with metastatic hormone-sensitive prostate cancer (mHSPC) who receive androgen deprivation therapy (ADT) remains to be explored.

Objective: To evaluate the predictive value of AR-V7 expression in the prognosis of mHSPC patients receiving ADT.

Design, Setting, And Participants: In this multicenter prospective cohort study, 310 mHSPC patients commencing ADT were enrolled. Standard immunohistochemical staining was used to assess AR-V7 protein expression in biopsy tissues collected before initiation of ADT.

Outcome Measurements And Statistical Analysis: Kaplan-Meier survival estimates and Cox regression analyses were used to evaluate associations of AR-V7 status (positive vs negative) with progression-free survival (PFS) and overall survival (OS).

Results And Limitations: Sixty-four (21%) patients were AR-V7-positive and 246 (79%) patients were AR-V7-negative. The median follow-up for patients not confirmed dead was 25 mo (interquartile range 10-30). Compared to AR-V7-negative patients, AR-V7-positive patients had significantly shorter PFS (hazard ratio [HR] 47.39, 95% confidence interval [CI] 25.83-86.94) and OS (HR 3.57, 95% CI 1.46-8.72). In multivariable analysis, AR-V7 was an independent predictive factor (HR 7.61, 95% CI 5.24-11.06) for shorter PFS. Limitations include the sample size and follow-up period.

Conclusions: AR-V7 expression in primary cancer tissue is correlated with poor prognosis for mHSPC patients receiving ADT.

Patient Summary: In this study of men with metastatic hormone-sensitive prostate cancer, AR-V7 protein expression in primary cancer tissue was associated with poor outcomes on androgen deprivation therapy.
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http://dx.doi.org/10.1016/j.eururo.2021.01.037DOI Listing
February 2021

Autophagy Plays a Protective Role in Sodium Hydrosulfide-Induced Acute Lung Injury by Attenuating Oxidative Stress and Inflammation in Rats.

Chem Res Toxicol 2021 Mar 4;34(3):857-864. Epub 2021 Feb 4.

College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China.

Sodium hydrosulfide (NaHS), as an exogenous hydrogen sulfide (HS) donor, has been used in various pathological models. NaHS is usually considered to be primarily protective, however, the toxic effect of NaHS has not been well elucidated. The aim of this study was to investigate whether NaHS (1 mg/kg) can induce acute lung injury (ALI is a disease process characterized by diffuse inflammation of the lung parenchyma) and define the mechanism by which NaHS-induced ALI involves autophagy, oxidative stress, and inflammatory response. Wistar rats were randomly divided into three groups (control group, NaHS group, and 3-MA + NaHS group), and samples from each group were collected from 2, 6, 12, and 24 h. We found that intraperitoneal injection of NaHS (1 mg/kg) increased the pulmonary levels of HS and oxidative stress-related indicators (reactive oxygen species, myeloperoxidase, and malondialdehyde) in a time-dependent manner. Intraperitoneal injection of NaHS (1 mg/kg) induced histopathological changes of ALI and inhibition of autophagy exacerbated the lung injury. This study demonstrates that administration of NaHS (1 mg/kg) induces ALI in rats and autophagy in response to ROS is protective in NaHS-induced ALI by attenuating oxidative stress and inflammation.
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http://dx.doi.org/10.1021/acs.chemrestox.0c00493DOI Listing
March 2021

The Selective SIK2 Inhibitor ARN-3236 Produces Strong Antidepressant-Like Efficacy in Mice via the Hippocampal CRTC1-CREB-BDNF Pathway.

Front Pharmacol 2020 14;11:624429. Epub 2021 Jan 14.

Department of Pharmacology, School of Pharmacy, Nantong University, Nantong, China.

Depression is a widespread chronic medical illness affecting thoughts, mood, and physical health. However, the limited and delayed therapeutic efficacy of monoaminergic drugs has led to intensive research efforts to develop novel antidepressants. ARN-3236 is the first potent and selective inhibitor of salt-inducible kinase 2 (SIK2). In this study, a multidisciplinary approach was used to explore the antidepressant-like actions of ARN-3236 in mice. Chronic social defeat stress (CSDS) and chronic unpredictable mild stress (CUMS) models of depression, various behavioral tests, high performance liquid chromatography-tandem mass spectrometry, stereotactic infusion, viral-mediated gene transfer, western blotting, co-immunoprecipitation and immunofluorescence were used together. It was found that ARN-3236 could penetrate the blood-brain barrier. Repeated ARN-3236 administration induced significant antidepressant-like effects in both the CSDS and CUMS models of depression, accompanied with fully preventing the stress-enhanced SIK2 expression and cytoplasmic translocation of cyclic adenosine monophosphate response element binding protein (CREB)-regulated transcription coactivator 1 (CRTC1) in the hippocampus. ARN-3236 treatment also completely reversed the down-regulating effects of CSDS and CUMS on the hippocampal brain-derived neurotrophic factor (BDNF) system and neurogenesis. Moreover, we demonstrated that the hippocampal CRTC1-CREB-BDNF pathway mediated the antidepressant-like efficacy of ARN-3236. Collectively, ARN-3236 possesses strong protecting effects against chronic stress, and could be a novel antidepressant beyond monoaminergic drugs.
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http://dx.doi.org/10.3389/fphar.2020.624429DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7840484PMC
January 2021

Proteome-wide analyses reveal diverse functions of acetylation proteins in Neurospora crassa.

Proteomics 2021 Mar 23;21(6):e2000212. Epub 2021 Feb 23.

State Key Laboratory Breeding Base of Dao-di Herbs, National Resource Center for Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China.

Quantitative acetyl-proteomics, a newly identified post-translational modification, is known to regulate transcriptional activity in different organisms. Neurospora crassa is a model ascomycete fungus maintained for biochemistry and molecular biology research; however, extensive studies of the functions of its acylation proteins have yet to be performed. In this study, using LC-MS/MS qualitative proteomics strategies, we identified 1909 modification sites on 940 proteins in N. crassa and analysed the functions of these proteins using GO enrichment, KEGG pathway, and subcellular location experiments. We classified the acetylation protein involvement in diverse pathways, and protein-protein interaction (PPI) network analysis further demonstrated that these proteins participate in diverse biological processes. In summary, our study comprehensively profiles the crosstalk of modified sites, and PPI among these proteins may form a complex network with both similar and distinct regulatory mechanisms, providing improved understanding of their biological functions in N. crassa.
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http://dx.doi.org/10.1002/pmic.202000212DOI Listing
March 2021

Can staple line reinforcement eliminate the major early postoperative complications after sleeve gastrectomy?

Asian J Surg 2021 Jan 20. Epub 2021 Jan 20.

Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, Jiangsu, China. Electronic address:

Background: Staple line reinforcement (SLR) is widely used to reduce major complications such as bleeding and leak after sleeve gastrectomy (SG). The present study aims to compare the running suture of SLR with a hybrid method by purse string suture of His angle, continuous inverted suture of proximal staple line and oversewing of distal staple line with omental coverage.

Methods: This single center retrospective study included 914 patients underwent SG. Their surgical videos were reviewed. The patients were divided into two groups according to the SLR methods, including hybrid suture and running suture. The postoperative major complications, including bleeding, leak and obstruction, were evaluated.

Results: Among 914 patients, 384 had hybrid suture while 530 had running suture of SLR. The overall incidence of staple line bleeding and disruption was 39.2% and 4.9% after stomach transection. Hybrid suture exhibited slightly shorter SLR suture time, and required less extra suture for the hemostasis of suture site bleeding after staple line reinforcement compared to running suture. The incidence of postoperative bleeding was significantly lower after hybrid suture than after running suture (0 vs 1.3%, P = 0.02). Two patients in running suture group were complicated with postoperative leak. There was no postoperative obstruction within all patients. 1-year excessive weight loss was similar between two groups.

Conclusion: Despite surgical complexity, hybrid suture seemed to be able to decrease the incidence of postoperative bleeding compared to running suture. However, its role on leak and obstruction requires further clinical validation.
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http://dx.doi.org/10.1016/j.asjsur.2020.12.036DOI Listing
January 2021

SHP2 blockade enhances anti-tumor immunity via tumor cell intrinsic and extrinsic mechanisms.

Sci Rep 2021 Jan 14;11(1):1399. Epub 2021 Jan 14.

Oncology Disease Area, Novartis Institutes for BioMedical Research, 250 Massachusetts Avenue, Cambridge, MA, 02139, USA.

SHP2 is a ubiquitous tyrosine phosphatase involved in regulating both tumor and immune cell signaling. In this study, we discovered a novel immune modulatory function of SHP2. Targeting this protein with allosteric SHP2 inhibitors promoted anti-tumor immunity, including enhancing T cell cytotoxic function and immune-mediated tumor regression. Knockout of SHP2 using CRISPR/Cas9 gene editing showed that targeting SHP2 in cancer cells contributes to this immune response. Inhibition of SHP2 activity augmented tumor intrinsic IFNγ signaling resulting in enhanced chemoattractant cytokine release and cytotoxic T cell recruitment, as well as increased expression of MHC Class I and PD-L1 on the cancer cell surface. Furthermore, SHP2 inhibition diminished the differentiation and inhibitory function of immune suppressive myeloid cells in the tumor microenvironment. SHP2 inhibition enhanced responses to anti-PD-1 blockade in syngeneic mouse models. Overall, our study reveals novel functions of SHP2 in tumor immunity and proposes that targeting SHP2 is a promising strategy for cancer immunotherapy.
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http://dx.doi.org/10.1038/s41598-021-80999-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7809281PMC
January 2021

Five new sesquiterpenoids from the fruits of Acanthopanax senticosus (Rupr. & Maxim.) Harms.

Fitoterapia 2021 Mar 8;149:104827. Epub 2021 Jan 8.

Key Laboratory of Chinese Materia Medica, Heilongjiang University of Chinese Medicine, Ministry of Education, Harbin 150040, People's Republic of China. Electronic address:

Five new sesquiterpenoids named acasenterpene A-E (1-5) were isolated from the fruits of Acanthopanax senticosus. The structures of all compounds were elucidated by extensive spectroscopic data analyses (1D, 2D NMR, and HR-ESI-MS) combined with physico-chemical analysis methods (enzyme hydrolysis, optical rotation, and CD). The cytotoxicity of all compounds in vitro against four human cancer cell lines (MGC-803, Ishikawa, LN-229 and SMMC-7721) were evaluated by CCK-8 assay.
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http://dx.doi.org/10.1016/j.fitote.2021.104827DOI Listing
March 2021

Valproic Acid Enhanced Apoptosis by Promoting Autophagy Via Akt/mTOR Signaling in Glioma.

Cell Transplant 2020 Jan-Dec;29:963689720981878

Department of Neurosurgery, The Third Affiliated Hospital of Soochow University, Changzhou, China.

Glioma is the most common malignant tumor in the central nervous system with a poor median survival. Valproic acid (VPA), a widely used antiepileptic drug, has been found to have antitumor effects on gliomas, but its role still has not been determined. In this study, we investigated VPA-induced apoptotic and autophagic effects on human U251 and SNB19 cells by cell counting kit-8 assay, flow cytometry, terminal deoxynucleotidyl transferase-mediated nick end labeling staining, western blots, and immunofluorescence assay in vitro, and then we further explored the role of autophagy in apoptosis by using the selective antagonist MHY1485. The data showed that VPA inhibited U251 and SNB19 glioma cells viability in a dose-dependent and time-dependent manner and induced apoptosis through the mitochondria-dependent pathway in vitro. In addition, VPA activated the Akt/mTOR pathway by decreasing their protein phosphorylation to promote cellular apoptosis. Surprisingly, the mTOR agonist MHY1485, causing a strong elevation of mTOR activity, partially reduced apoptosis ratio, which supposing that the autophagy of VPA is involved in the regulation of apoptosis. These findings suggest that VPA enhanced apoptosis by promoting autophagy via Akt/mTOR signaling in glioma, which could be further evaluated as a reliable therapy for glioma.
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http://dx.doi.org/10.1177/0963689720981878DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7873763PMC
December 2020

Ultrasonic Interfacial Engineering of Red Phosphorous-Metal for Eradicating MRSA Infection Effectively.

Adv Mater 2021 Feb 22;33(5):e2006047. Epub 2020 Dec 22.

School of Materials Science & Engineering, The Key Laboratory of Advanced Ceramics and Machining Technology by the Ministry of Education of China, Tianjin University, Tianjin, 300072, China.

Sonodynamic therapy (SDT) is considered to be a potential treatment for various diseases including cancers and bacterial infections due to its deep penetration ability and biosafety, but its SDT efficiency is limited by the hypoxia environment of deep tissues. This study proposes creating a potential solution, sonothermal therapy, by developing the ultrasonic interfacial engineering of metal-red phosphorus (RP), which has an obviously improved sonothermal ability of more than 20 °C elevation under 25 min of continuous ultrasound (US) excitation as compared to metal alone. The underlying mechanism is that the mechanical energy of the US activates the motion of the interfacial electrons. US-induced electron motion in the RP can efficiently transfer the US energy into phonons in the forms of heat and lattice vibrations, resulting in a stronger US absorption of metal-RP. Unlike the nonspecific heating of the cavitation effect induced by US, titanium-RP can be heated in situ when the US penetrates through 2.5 cm of pork tissue. In addition, through a sonothermal treatment in vivo, bone infection induced by multidrug-resistant Staphylococcus aureus (MRSA) is successfully eliminated in under 20 min of US without tissue damage. This work provides a new strategy for combating MRSA by strong sonothermal therapy through US interfacial engineering.
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http://dx.doi.org/10.1002/adma.202006047DOI Listing
February 2021

Superiority of Iridium Photocatalyst and Role of Quinuclidine in Selective α-C(sp)-H Alkylation: Theoretical Insights.

J Org Chem 2021 Jan 9;86(1):484-492. Epub 2020 Dec 9.

Institute of Functional Material Chemistry, Faculty of Chemistry, Northeast Normal University, Changchun 130024, Jilin, P. R. China.

Recent experimental work reported that visible-light photoredox catalysis coupled with primary sulfonamides and electron-deficient alkenes could efficiently construct C-C bonds at the α-position of primary amine derivatives under mild conditions. Here, a systematic study was conducted to explore the non-negligible excited-state single-electron-transfer (SET) processes and the catalytic cycle. Hydrogen atom transfer (HAT) catalysis containing different site-selective functionalization, involved as a critical process during the reaction, was computationally characterized. The superiorities of iridium-based photoredox catalysts in terms of photoabsorption properties, phosphorescence rates, and electron-transfer rates for SET processes were focused on. In addition, the function of quinuclidine in the entire photocatalytic reaction was also probed. These intrinsic properties and detailed insights into the mechanism are supposed to be helpful to the understanding of the C-C bond functionalization reaction and the future application of the iridium-based photoredox catalyst.
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http://dx.doi.org/10.1021/acs.joc.0c02227DOI Listing
January 2021

[The NOXA promoter could function as an active enhancer to regulate the expression of BCL2 in the apoptosis response].

Yi Chuan 2020 Nov;42(11):1110-1121

Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University, Nanjing 211166, China.

The transcription of eukaryotic genes is regulated by both proximal promoters and distal enhancers. Some promoters also have enhancer activity. NOXA and BCL2 are pro-apoptotic and anti-apoptotic members of the BCL2 family of protein, respectively. Our previous study has found that the NOXA gene promoter and the BCL2 gene promoter interact at the level of three-dimensional chromatin structure. Moreover, the NOXA gene promoter region displays histone modifications characteristic of both promoters and enhancers. This study aimed to explore whether and when the NOXA promoter could act as an active enhancer to regulate BCL2 expression. Based on the apoptosis model of MCF-7 cells induced by camptothecin, we used chromosome conformation capture (3C), quantitative real-time PCR (qRT-PCR) and the luciferase reporter gene technology to demonstrate that the NOXA promoter could function as an active enhancer and physically interact with the BCL2 promoter through chromatin looping. The regulatory properties of the NOXA promoter were closely related to the strength of the apoptosis stimulation. Under weak apoptotic stimulation (1 μmol/L camptothecin treatment), the NOXA promoter mainly functioned as an enhancer; with the enhancement of apoptotic stimulation (10 μmol/L camptothecin treatment), the NOXA promoter activity increased and mainly regulated the expression of the gene itself to promote apoptosis. Chromatin immunoprecipitation (ChIP) confirmed that the dynamic changes of the promoter activity and enhancer activity in the NOXA promoter region are consistent with its histone modification marks. This study provides new clues for further exploring the mechanism underlying cooperative response of BCL2 family member to apoptosis stimuli.
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http://dx.doi.org/10.16288/j.yczz.20-213DOI Listing
November 2020

AML1-ETO inhibits acute myeloid leukemia immune escape by CD48.

Leuk Lymphoma 2021 04 21;62(4):937-943. Epub 2020 Nov 21.

Department of Hematology-Oncology, International Cancer Center, Shenzhen University General Hospital, Shenzhen University Health Science Center, Shenzhen, China.

The t(8;21)(q22;q22) translocation is the most common chromosomal translocation in acute myeloid leukemia (AML), and it gives rise to acute myeloid gene 1 (AML1)-myeloid transforming gene 8 (ETO)-positive AML, which has a relatively favorable prognosis. CD48 is a favorable prognosis factor that is downregulated in AML patients. AML can escape immunosurveillance of natural killer (NK) cells by decreasing CD48 expression. The correlation between AML1-ETO and CD48-mediated immune evasion is not well understood. Here, we show that AML1-ETO can increase CD48 expression, which is regulated by AML1-ETO/P300-mediated acetylation. AML1-ETO can inhibit AML immune escape from NK cell recognition and killing by increasing CD48 expression. This study describes a novel mechanism by which AML1-ETO can inhibit AML immune escape by increasing CD48 acetylation, thereby providing new evidence about AML patients with AML1-ETO oncogene infusion having better clinical outcomes.
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http://dx.doi.org/10.1080/10428194.2020.1849680DOI Listing
April 2021

Epigenetic silencing of miR564 contributes to the leukemogenesis of t(8;21) acute myeloid leukemia.

Clin Sci (Lond) 2020 12;134(23):3079-3091

Department of Hematology and Oncology, International Cancer Center, Shenzhen University General Hospital, Shenzhen University Health Science Center, Xueyuan AVE 1098, Nanshan District, Shenzhen, Guangdong 518000, P.R. China.

The AML1-ETO oncoprotein, which results from t(8;21) translocation, is considered an initial event of t(8;21) acute myeloid leukemia (AML). However, the precise mechanisms of the oncogenic activity of AML1-ETO is yet to be fully determined. The present study demonstrates that AML1-ETO triggers the heterochromatic silencing of microRNA-564 (miR564) by binding at the AML1 binding site along the miR564 promoter region and recruiting chromatin-remodeling enzymes. Suppression of miR564 enhances the oncogenic activity of the AML1-ETO oncoprotein by directly inhibiting the expression of CCND1 and the DNMT3A genes. Ectopic expression of miR564 can induce retardation of G1/S transition, reperform differentiation, promote apoptosis, as well as inhibit the proliferation and colony formation of AML1-ETO+ leukemia cells in vitro. Enhanced miR564 levels can significantly inhibit the tumor proliferation of t(8;21)AML in vivo. We first identify an unexpected and important epigenetic circuitry of AML1-ETO/miR564/CCND1/DNMT3A that contributes to the leukemogenesis in vitro/vivo of AML1-ETO+ leukemia, indicating that miR564 enhancement could provide a potential therapeutic method for AML1-ETO+ leukemia.
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http://dx.doi.org/10.1042/CS20200786DOI Listing
December 2020

Lipidomic analyses reveal enhanced lipolysis in planthoppers feeding on resistant host plants.

Sci China Life Sci 2020 Nov 5. Epub 2020 Nov 5.

State Key Laboratory of Hybrid Rice, College of Life Sciences, Wuhan University, Wuhan, 430072, China.

The brown planthopper (BPH) (Nilaparvata lugens Stål) is a highly destructive pest that seriously damages rice (Oryza sativa L.) and causes severe yield losses. To better understand the physiological and metabolic mechanisms through which BPHs respond to resistant rice, we combined mass-spectrometry-based lipidomics with transcriptomic analysis and gene knockdown techniques to compare the lipidomes of BPHs feeding on either of the two resistant (NIL-Bph6 and NIL-Bph9) plants or a wild-type, BPH susceptible (9311) plant. Insects that were fed on resistant rice transformed triglyceride (TG) to phosphatidylcholine (PC) and digalactosyldiacylglycerol (DGDG), with these lipid classes showing significant alterations in fatty acid composition. Moreover, the insects that were fed on resistant rice were characterized by prominent expression changes in genes involved in lipid metabolism processes. Knockdown of the NlBmm gene, which encodes a lipase that regulates the mobilization of lipid reserves, significantly increased TG content and feeding performance of BPHs on resistant plants relative to dsGFP-injected BPHs. Our study provides the first detailed description of lipid changes in BPHs fed on resistant and susceptible rice genotypes. Results from BPHs fed on resistant rice plants reveal that these insects can accelerate TG mobilization to provide energy for cell proliferation, body maintenance, growth and oviposition.
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http://dx.doi.org/10.1007/s11427-020-1834-9DOI Listing
November 2020

A theoretical mechanistic study of Ir/Cu-metallaphotoredox catalyzed asymmetric radical decarboxylative cyanation.

Dalton Trans 2020 Nov;49(43):15276-15286

Faculty of Chemistry, Institute of Functional Material Chemistry, Northeast Normal University, Changchun 130024, P. R. China.

Visible-light-induced asymmetric metallaphotoredox catalysis has become a powerful strategy in synthetic organic chemistry. IrIII/CuI dual asymmetric catalysis has been developed to achieve enantioselective decarboxylative cyanation. However, detailed mechanisms, such as catalytic cycles for dual catalysts and the role of a chiral ligand, remain obscure in these reactions. In this study, the catalytic cycle of this reaction is systematically investigated by DFT calculations to clarify the quenching mechanism of the photocatalyst and the origin of the excellent enantioselectivity. Interestingly, the radical mechanism merging oxidative quenching (IrIII-*IrIII-IrIV-IrIII) and copper catalytic cycles (CuI-CuII-CuIII-CuI) is favourable. It consists of five major processes: single-electron oxidation of *IrIII by N-hydroxy-phthalimide (NHP) esters followed by decarboxylation to generate benzyl radical, oxidation of CuI by IrIVvia a single-electron transfer (SET) process, cyanide exchange, radical capture by CuII, and C-CN reductive elimination from CuIII. The cyanide exchange is the rate-determining step, whereas the C-CN reductive elimination is the enantio-determining step of the reaction. In addition, the origin of the high enantioselectivity was analyzed from the steric and electronic effects. This study will hopefully benefit the future understanding of such photoredox-mediated dual catalyzed asymmetric synthesis.
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http://dx.doi.org/10.1039/d0dt02630aDOI Listing
November 2020