Copper-Mediated Cyclization of Terminal Alkynes with CF3-Imidoyl Sulfoxonium Ylides To Construct 5-Trifluoromethylpyrroles.

A copper-mediated [3 + 2] cyclization of CF3-imidoyl sulfoxonium ylides and terminal alkynes has been demonstrated. This work provides a practical approach for assembling 5-trifluoromethylpyrroles with the merits of a broad substrate scope, good functional tolerance, and mild reaction conditions. Control experiments and DFT studies indicate that this reaction may involve the addition of π-bonds of terminal alkynes by copper-carbene radicals and hydrogen migration.

Estimating the Risk of Death from COVID-19 in Adult Cancer Patients.

AIMS: During the coronavirus disease 2019 (COVID-19) pandemic, organisations have produced management guidance for cancer patients and the delivery of cytotoxic chemotherapy, but none has offered estimates of risk or the potential impact across populations. MATERIALS AND METHODS: We combined data from four countries to produce pooled age-banded case fatality rates, calculated the sex difference in survival and used data from four recent studies to convert case fatality rates into age/sex-stratified infection fatality rates (IFRs). We estimated the additional risk of death in cancer patients and in those receiving chemotherapy. We illustrate the impact of these by considering the impact on a national incident cancer cohort and analyse the risk-benefit in some clinical scenarios. RESULTS: We obtained data based on 412 985 cases and 41 854 deaths. The pooled estimate for IFR was 0.92%. IFRs for patients with cancer ranged from 0 to 29% and were higher in patients receiving chemotherapy (0.01-46%). The risk was significantly higher with age and in men compared with women. 37.5% of patients with a new diagnosis of cancer in 2018 had an IFR ≥5%. Survival benefits from adjuvant chemotherapy ranged from 5 to 10% in some common cancers, compared with the increased risk of death from COVID-19 of 0-3%. CONCLUSIONS: Older male patients are at a higher risk of death with COVID-19. Patients with cancer are also at a higher risk, as are those who have recently received chemotherapy. We provide well-founded estimates to allow patients and clinicians to better balance these risks and illustrate the wider impact in a national incident cohort.

Differential effects of sevoflurane on the metastatic potential and chemosensitivity of non-small-cell lung adenocarcinoma and renal cell carcinoma in vitro.

BACKGROUND: Increasing evidence suggests that perioperative factors including anaesthetics influence cancer recurrence and metastasis after surgery. This study investigated the influence of sevoflurane on the response of lung and renal cancer cells to cisplatin, with focus on transforming growth factor-beta (TGF-ß) and osteopontin (OPN) that are both closely associated with cancer tumorigenesis and metastasis. METHODS: Non-small cell lung adenocarcinoma (A549) and renal cell carcinoma (RCC4) cells were exposed to 3.6% sevoflurane for two hrs. Malignant potential represented by cell viability, migration, chemosensitivity to cisplatin was evaluated. Expression of OPN, TGF-ß1, TGF-ß receptor type II (TGF-ßRII) and the canonical downstream effector Smad3 was assessed. SiRNA knockdown of TGF-ß1 and OPN and chemical inhibition of TGF-ßRI/II was performed. RESULTS: Sevoflurane reduced cell viability (0.394) versus control (0.459) (P < 0.01), enhanced chemosensitivity but had no effect on migration of A549 cells. It enhanced viability (0.467) versus control (0.347) (P < 0.001), chemoresistance and migration of RCC4. In A549, there was enhanced nuclear Smad3. In RCC4, TGF-ßRII and OPN were upregulated, while TGF-ß1 was over- expressed with reduced nuclear Smad3. TGF-ßRII inhibition and OPN knockdown abolished sevoflurane-mediated viability, and migration, respectively, in RCC4. CONCLUSIONS: Sevoflurane promotes the metastatic potential of renal carcinoma, but not of non-small cell lung cancer. This may be associated with its differential effect on cellular signalling including TGF-ß. Our findings indicate that sevoflurane may have different effects on the metastatic potential and chemosensitivity of different tumour types.

Phytochrome and Ethylene Signaling Integration in Arabidopsis Occurs via the Transcriptional Regulation of Genes Co-targeted by PIFs and EIN3.

Plant seedlings germinating under the soil are challenged by rough soil grains that can induce physical damage and sudden exposure to light, which can induce photobleaching. Seedlings overcome these challenges by developing apical hooks and by suppressing chlorophyll precursor biosynthesis. These adaptive responses are, respectively, regulated by the phytochrome and ethylene signaling pathways via the PHYTOCHROME-INTERACTING FACTORs (PIFs) and the ETHYLENE INSENSITIVE 3 (EIN3)/EIN3-LIKE transcription factors. Although many processes downstream of phytochrome and ethylene signaling are similar, it remains unclear if and where these pathways converge. Here, we show PIFs and EIN3 induce similar changes in the transcriptome without robustly regulating each other's signaling pathways. PIFs and EIN3 target highly overlapped gene promoters and activate subsets of the co-target genes either interdependently or additively to induce plant responses. For chlorophyll biosynthesis, PIFs and EIN3 target and interdependently activate the expression of HOOKLESS1. HOOKLESS1, in turn, represses chlorophyll synthesis genes to prevent photobleaching. Thus, our results indicate an integration of the phytochrome and ethylene signaling pathways at the level of transcriptional gene regulation by two core groups of transcription factors, PIFs and EIN3.

KLF2 mutation is the most frequent somatic change in splenic marginal zone lymphoma and identifies a subset with distinct genotype.

To characterise the genetics of splenic marginal zone lymphoma (SMZL), we performed whole exome sequencing of 16 cases and identified novel recurrent inactivating mutations in Kruppel-like factor 2 (KLF2), a gene whose deficiency was previously shown to cause splenic marginal zone hyperplasia in mice. KLF2 mutation was found in 40 (42%) of 96 SMZLs, but rarely in other B-cell lymphomas. The majority of KLF2 mutations were frameshift indels or nonsense changes, with missense mutations clustered in the C-terminal zinc finger domains. Functional assays showed that these mutations inactivated the ability of KLF2 to suppress NF-κB activation by TLR, BCR, BAFFR and TNFR signalling. Further extensive investigations revealed common and distinct genetic changes between SMZL with and without KLF2 mutation. IGHV1-2 rearrangement and 7q deletion were primarily seen in SMZL with KLF2 mutation, while MYD88 and TP53 mutations were nearly exclusively found in those without KLF2 mutation. NOTCH2, TRAF3, TNFAIP3 and CARD11 mutations were observed in SMZL both with and without KLF2 mutation. Taken together, KLF2 mutation is the most common genetic change in SMZL and identifies a subset with a distinct genotype characterised by multi-genetic changes. These different genetic changes may deregulate various signalling pathways and generate cooperative oncogenic properties, thereby contributing to lymphomagenesis.

[Studies on inapparent infection of epidemic hemorrhagic fever in population of Shanxi Province].

Detection for IgG antibody to virus of epidemic hemorrhagic fever (EHF) in sera from healthy people in Shanxi province were carried out by IFAT. Two hundred thirty eight of 4873 serum samples were antibody-positive. Total positive rate was 4.88%. The inapparent infection rate of EHF in residents of endemic areas was 5.48%. There was a statistically significant difference of epidemic strength among different counties. Based on the analysis of antibody titers of positive sera, value of upper limit (P95) of antibody titre for inapparent infection was 1:315. It was suggested that the antibody titre of 1:320 by IFAT in a single sample of serum from patient with clinical manifestations of EHF might be used as a criteria for specific diagnosis of EHF.