Decarboxylative C−H functionalization reactions are highly attractive methods for forging carbon–carbon bonds considering their inherent step‐ and atom‐economical features and the pervasiveness of ...carboxylic acids and C−H bonds. An ideal approach to achieve these dehydrogenative transformations is through hydrogen evolution without using any chemical oxidants. However, effective couplings by decarboxylative carbon–carbon bond formation with proton reduction remain an unsolved challenge. Herein, we report an electrophotocatalytic approach that merges organic electrochemistry with photocatalysis to achieve the efficient direct decarboxylative C−H alkylation and carbamoylation of heteroaromatic compounds through hydrogen evolution. This electrophotocatalytic method, which combines the high efficiency and selectivity of photocatalysis in promoting decarboxylation with the superiority of electrochemistry in effecting proton reduction, enables the efficient coupling of a wide range of heteroaromatic bases with a variety of carboxylic acids and oxamic acids. Advantageously, this method is scalable to decagram amounts, and applicable to the late‐stage functionalization of drug molecules.
A broadly applicable electrophotocatalytic method for the direct decarboxylative C−H alkylation and carbamoylation of heteroarenes has been developed. This method combines the advantages of photocatalysis and electrochemistry to enable the functionalization of a broad range of substrates and to allow the decarboxylative C−H functionalization reactions to proceed by H2 evolution, obviating the need for oxidizing reagents and proton acceptors.
The methyltransferase like 3 （METTL3）-containing methyltransferase complex catalyzes the N6-methyladenosine （m6A） formation, a novel epitranscriptomic marker; however, the nature of this complex ...remains largely unknown. Here we report two new components of the human m6A methyltransferase complex, Wilms＇ tumor 1-associating protein （WTAP） and methyltransferase like 14 （METTL14）. WTAP interacts with METTL3 and METTL14, and is required for their localization into nuclear speckles enriched with pre-mRNA processing factors and for catalytic ac- tivity of the m6A methyltransferase in vivo. The majority of RNAs bound by WTAP and METTL3 in vivo represent mRNAs containing the consensus m6A motif. In the absence of WTAP, the RNA-binding capability of METTL3 is strongly reduced, suggesting that WTAP may function to regulate recruitment of the m6A methyltransferase complex to mRNA targets. Furthermore, transcriptomic analyses in combination with photoactivatable-ribonucleoside-en- hanced crosslinking and immunoprecipitation （PAR-CLIP） illustrate that WTAP and METTL3 regulate expression and alternative splicing of genes involved in transcription and RNA processing. Morpholino-mediated knockdown targeting WTAP and/or METTL3 in zebrafish embryos caused tissue differentiation defects and increased apoptosis. These findings provide strong evidence that WTAP may function as a regulatory subunit in the m6A methyltransferase complex and play a critical role in epitranscriptomic regulation of RNA metabolism.
Understanding the dynamics and underlying mechanism of carbon exchange between terrestrial ecosystems and the atmosphere is one of the key issues in global change research. In this study, we ...quantified the carbon fluxes in different terrestrial ecosystems in China, and analyzed their spatial variation and environmental drivers based on the long‐term observation data of ChinaFLUX sites and the published data from other flux sites in China. The results indicate that gross ecosystem productivity (GEP), ecosystem respiration (ER), and net ecosystem productivity (NEP) of terrestrial ecosystems in China showed a significantly latitudinal pattern, declining linearly with the increase of latitude. However, GEP, ER, and NEP did not present a clear longitudinal pattern. The carbon sink functional areas of terrestrial ecosystems in China were mainly located in the subtropical and temperate forests, coastal wetlands in eastern China, the temperate meadow steppe in the northeast China, and the alpine meadow in eastern edge of Qinghai‐Tibetan Plateau. The forest ecosystems had stronger carbon sink than grassland ecosystems. The spatial patterns of GEP and ER in China were mainly determined by mean annual precipitation (MAP) and mean annual temperature (MAT), whereas the spatial variation in NEP was largely explained by MAT. The combined effects of MAT and MAP explained 79%, 62%, and 66% of the spatial variations in GEP, ER, and NEP, respectively. The GEP, ER, and NEP in different ecosystems in China exhibited ‘positive coupling correlation’ in their spatial patterns. Both ER and NEP were significantly correlated with GEP, with 68% of the per‐unit GEP contributed to ER and 29% to NEP. MAT and MAP affected the spatial patterns of ER and NEP mainly by their direct effects on the spatial pattern of GEP.
Nasopharyngeal carcinoma (NPC) is an aggressive malignancy with extremely skewed ethnic and geographic distributions. Increasing evidence indicates that targeting the tumor microenvironment (TME) ...represents a promising therapeutic approach in NPC, highlighting an urgent need to deepen the understanding of the complex NPC TME. Here, we generated single-cell transcriptome profiles for 7581 malignant cells and 40,285 immune cells from fifteen primary NPC tumors and one normal sample. We revealed malignant signatures capturing intratumoral transcriptional heterogeneity and predicting aggressiveness of malignant cells. Diverse immune cell subtypes were identified, including novel subtypes such as CLEC9A
dendritic cells (DCs). We further revealed transcriptional regulators underlying immune cell diversity, and cell-cell interaction analyses highlighted promising immunotherapeutic targets in NPC. Moreover, we established the immune subtype-specific signatures, and demonstrated that the signatures of macrophages, plasmacytoid dendritic cells (pDCs), CLEC9A
DCs, natural killer (NK) cells, and plasma cells were significantly associated with improved survival outcomes in NPC. Taken together, our findings represent a unique resource providing in-depth insights into the cellular heterogeneity of NPC TME and highlight potential biomarkers for anticancer treatment and risk stratification, laying a new foundation for precision therapies in NPC.
Currently, there is no strong evidence of the well-established biomarkers for immune checkpoint inhibitors (ICIs) in nasopharyngeal carcinoma (NPC). Here, we aimed to reveal the heterogeneity of ...tumour microenvironment (TME) through virtual microdissection of gene expression profiles. An immune-enriched subtype was identified in 38% (43/113) of patients, which was characterized by significant enrichment of immune cells or immune responses. The remaining patients were therefore classified as a non-Immune Subtype (non-IS), which exhibited highly proliferative features. Then we identified a tumour immune evasion state within the immune-enriched subtype (18/43, 42%), in which high expression of exclusion- and dysfunction-related signatures was observed. These subgroups were designated the Evaded and Active Immune Subtype (E-IS and A-IS), respectively. We further demonstrated that A-IS predicted favourable survival and improved ICI response as compared to E-IS and non-IS. In summary, this study introduces the novel immune subtypes and demonstrates their feasibility in tailoring immunotherapeutic strategies.
ObjectiveTo investigate the relationship between job satisfaction, work stress, work–family conflict and turnover intention, and explore factors associated with turnover intention, among physicians ...in Guangdong Province, China.MethodsFrom August to October 2013, physicians completed questionnaires and scales with regard to their job satisfaction, work stress, work–family conflict, and turnover intention. Binary logistic regression and structural equation modelling (SEM) were used in data analysis.ResultsA total of 3963 physicians were approached, with 3563 completing the questionnaire. The mean score of the overall perception of turnover intention of physicians who worked in Guangdong was 2.71 on a scale ranging from 1 to 6. Hours worked per week, working in an urban/rural area, type of institution, and age significantly impacted on turnover intention. Turnover intention was directly and negatively related to job satisfaction, and it was directly, indirectly and positively related to work stress and work–family conflict.ConclusionJob satisfaction, work stress, work–family conflict, hours worked per week, working in an urban/rural area, types of institution and age are influencing factors of turnover intention. Reducing working hours, raising salary, providing more opportunities for career development and training, supporting and encouraging physicians by senior managers could potentially contribute to the reduction in turnover intention.
The coronavirus disease 2019 (COVID-19) outbreak impacts physical and mental health. The purpose of this study was to explore the association between the levels of social support and mental health ...among Chinese adolescents during the outbreak.
A total of 7,202 adolescents aged 14–18 years completed online survceys from March 8 to 15, 2020, in China. Researchers assessed the associations between depression symptoms (Patient Health Questionnaire-9), anxiety symptoms (Chinese version of the 7-item Generalized Anxiety Disorder scale), and social support (Social Support Rate Scale).
COVID-19 exposure was associated with a higher prevalence of depression symptoms (odds ratio OR = 1.38, 95% confidence interval CI: 1.14–1.66) and anxiety symptoms (OR = 1.26, 95% CI: 1.04–1.52). Only 24.6% of adolescents reported high levels of social support. Most adolescents (70%) reported medium levels of support, and 5.4% reported low support. Low support was associated with higher prevalence of depression (OR = 4.24, 95% CI: 3.38–5.33) and anxiety symptoms (OR = 3.18, 95% CI: 2.54–3.98), while controlling for gender, grade, living situation, and COVID-19 exposure; similarly, medium support was associated with higher prevalence of depression (OR = 2.79, 95% CI: 2.48–3.15) and anxiety (OR = 2.19, 95% CI: 1.94–2.48) symptoms.
This study indicates there is a higher prevalence of mental health problems among adolescents with medium and low levels of social support in China during the outbreak of COVID-19.
A convenient and rapid detection method for methanol in ethanol remains a major challenge due to their indistinguishable physical properties. Herein, a novel fluorescence probe based on perovskite ...was successfully designed to overcome this bottleneck. We report a new zero‐dimensional (0D) hybrid perovskite of MP2InxSb1−xCl7 ⋅ 6 H2O (MP=2‐methylpiperazine) displaying an unusual green light emission with near‐unity photoluminescence quantum yield. Remarkably, this 0D perovskite exhibits reversible methanol‐response luminescence switching between green and yellow color but fail in any other organic vapors. Even for blended alcohol solutions, the luminescent probe exhibits excellent sensing performance with multiple superiorities of rapid response time (30 s) and ultra‐low detection limit (40 ppm), etc. Therefore, this 0D perovskite can be utilized as a perfect fluorescence probe to detect traces of methanol from ethanol with ultrahigh sensitivity, selectivity and repeatability. To the best of our knowledge, this work represents the first perovskite as fluorescence probe for methanol with wide potential in environmental monitoring and methanol detection, etc.
0D hybrid lead‐free halide displays highly efficient broadband green light emission with a near‐unity photoluminescence quantum yield, and acts as a unique fluorescence sensor for methanol in ethanol with ultrahigh selectivity, sensitivity and repeatability as well as fast response time.
Background
Studies are trying to add immunotherapy to gemcitabine and cisplatin (GP) induction chemotherapy, the standard therapy, in nasopharyngeal carcinoma (NPC) patients with locoregionally ...advanced disease. However, how the immune system responds to GP remains unknown.
Method
We examined the dynamic changes of circulating immune cells and plasma cytokines in NPC patients administered with GP.
Result
After GP administration, immunosuppressive myeloid cells, including CD11b+CD14+ monocytes, CD33+ myeloid cells, CD33+CD11+ myeloid cells, total MDSCs (CD33+CD11+HLA‐DR−/low), monocytic MDSCs, and granulocytic MDSCs decreased significantly. The regulatory T cells and B cells, two important suppressive lymphocyte subpopulations, also decreased. On the other hand, the levels of CD3+ T cells, total B cells, central memory CD4+ T cells, and pro‐inflammatory cytokines (including Interleukin IL‐1β, IL‐6, IL‐2, IL‐5, and IL‐8) increased significantly after GP administration. Besides, GP chemotherapy did not weaken the cytotoxic activity and proliferative capacity of T cells.
Conclusion
Our results showed the immune modulation effect of GP induction chemotherapy in locoregionally advanced NPC, providing a solid basis for its combination with immunotherapy.
Through monitoring the dynamic changes in the peripheral immune cell populations and cytokines, we demonstrated that GP chemotherapy not only significantly decreased the immunosuppressive cells but also improved the T cell immunity in NPC patients. Our study provided a new insight into the anti‐tumor mechanism of gemcitabine and cisplatin chemotherapy. Furthermore, our findings offered solid basis for the combination of GP induction chemotherapy with immunotherapy in future studies.
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