Synergistic use of electrochemistry and organometallic catalysis has emerged as a powerful tool for site-selective C–H functionalization, yet this type of transformation has thus far mainly been ...limited to arene C–H functionalization. Herein, we report the development of electrochemical vinylic C–H functionalization of acrylic acids with alkynes. In this reaction an iridium catalyst enables C–H/O–H functionalization for alkyne annulation, affording α-pyrones with good to excellent yields in an undivided cell. Preliminary mechanistic studies show that anodic oxidation is crucial for releasing the product and regeneration of an Ir(III) intermediate from a diene-Ir(I) complex, which is a coordinatively saturated, 18-electron complex. Importantly, common chemical oxidants such as Ag(I) or Cu(II) did not give significant amounts of the desired product in the absence of electrical current under otherwise identical conditions.
Cancer cells undergo metabolic reprogramming such as enhanced aerobic glycolysis, mutations in the tricarboxylic acid cycle enzymes, and upregulation of de novo lipid synthesis and glutaminolysis. ...These alterations are pivotal to the development and maintenance of the malignant phenotype of cancer cells in unfavorable tumor microenvironment or metastatic sites. Although mitochondrial fatty acid β-oxidation (FAO) is a primary bioenergetic source, it has not been generally recognized as part of the metabolic landscape of cancer. The last few years, however, have seen a dramatic change in the view of cancer relevance of the FAO pathway. Many recent studies have provided significant evidence to support a “lipolytic phenotype” of cancer. FAO, like other well-defined metabolic pathways involved in cancer, is dysregulated in diverse human malignancies. Cancer cells rely on FAO for proliferation, survival, stemness, drug resistance, and metastatic progression. FAO is also reprogrammed in cancer-associated immune and other host cells, which may contribute to immune suppression and tumor-promoting microenvironment. This article reviews and puts into context our current understanding of multi-faceted roles of FAO in oncogenesis as well as anti-cancer therapeutic opportunities posed by the FAO pathway.
•FAO emerges as a new aspect of metabolic transformation in cancer.•Cancer cells rely on FAO for growth, stemness, drug resistance and metastasis.•FAO is reprogrammed in cancer and cancer-associated immune and other host cells.•FAO is druggable given the differential dependence of cancer and normal tissues.•FAO inhibitors including those for other ailments offer new anti-cancer therapies.
The Tibetan Plateau (TP), the highest and largest plateau in the world, with complex and competing cryospheric‐hydrologic‐geodynamic processes, is particularly sensitive to anthropogenic warming. The ...quantitative water mass budget in the TP is poorly known. Here we examine annual changes in lake area, level, and volume during 1970s–2015. We find that a complex pattern of lake volume changes during 1970s–2015: a slight decrease of −2.78 Gt yr−1 during 1970s–1995, followed by a rapid increase of 12.53 Gt yr−1 during 1996–2010, and then a recent deceleration (1.46 Gt yr−1) during 2011–2015. We then estimated the recent water mass budget for the Inner TP, 2003–2009, including changes in terrestrial water storage, lake volume, glacier mass, snow water equivalent (SWE), soil moisture, and permafrost. The dominant components of water mass budget, namely, changes in lake volume (7.72 ± 0.63 Gt yr−1) and groundwater storage (5.01 ± 1.59 Gt yr−1), increased at similar rates. We find that increased net precipitation contributes the majority of water supply (74%) for the lake volume increase, followed by glacier mass loss (13%), and ground ice melt due to permafrost degradation (12%). Other term such as SWE (1%) makes a relatively small contribution. These results suggest that the hydrologic cycle in the TP has intensified remarkably during recent decades.
Key Points
Lake area, level, and volume vary in three stages: slight decrease (1970s–1995), rapid increase (1996–2010), and recent slowdown (2011–2015)
Lake and groundwater storage both increased at similar rates in Tibetan Plateau's endorheic basin over 2003–2009
Increased precipitation contributes a major water supply (74%) for lake volume increase, followed by glacier melting (13%) in 2003–2009
Leaf area index (LAI) is an important vegetation biophysical variable and has been widely used for crop growth monitoring and yield estimation, land-surface process simulation, and global change ...studies. Several LAI products currently exist, but most have limited temporal coverage. A long-term high-quality global LAI product is required for greatly expanded application of LAI data. In this paper, a method previously proposed was improved to generate a long time series of Global LAnd Surface Satellite (GLASS) LAI product from Advanced Very High Resolution Radiometer (AVHRR) and Moderate Resolution Imaging Spectroradiometer (MOD!S) reflectance data. The GLASS LAI product has a temporal resolution of eight days and spans from 1981 to 2014. During 1981-1999, the LAI product was generated from AVHRR reflectance data and was provided in a geographic latitude/longitude projection at a spatial resolution of 0.05°. During 2000-2014, the LAI product was derived from MODIS surface-reflectance data and was provided in a sinusoidal projection at a spatial resolution of 1 km. The GLASS LAI values derived from MODIS and AVHRR reflectance data form a consistent data set at a spatial resolution of 0.05°. Comparison of the GLASS LAI product with the MODIS LAI product (MOD15) and the first version of the Geoland2 (GEOV1) LAI product indicates that the global consistency of these LAI products is generally good. However, relatively large discrepancies among these LAI products were observed in tropical forest regions, where the GEOV1 LAI values were clearly lower than the GLASS and MOD15 LAI values, particularly in January. A quantitative comparison of temporal profiles shows that the temporal smoothness of the GLASS LAI product is superior to that of the GEOV1 and MODIS LAI products. Direct validation with the mean values of high-resolution LAI maps demonstrates that the GLASS LAI values were closer to the mean values of the high-resolution LAI maps (RMSE = 0.7848 and R 2 = 0.8095) than the GEOV1 LAI values (RMSE = 0.9084 and R 2 = 0.7939) and the MOD15 LAI values (RMSE = 1.1173 and R 2 = 0.6705).
To determine distribution of severe acute respiratory syndrome coronavirus 2 in hospital wards in Wuhan, China, we tested air and surface samples. Contamination was greater in intensive care units ...than general wards. Virus was widely distributed on floors, computer mice, trash cans, and sickbed handrails and was detected in air ≈4 m from patients.
•Medical staff experience mental health disturb during the COVID-19 pandemic.•Direct and indirect exposure to COVID-19 affects the mental health profoundly.•Psychological materials and resources ...provide some protection.•Interventions with appropriate level are urgent.
The severe 2019 outbreak of novel coronavirus disease (COVID-19), which was first reported in Wuhan, would be expected to impact the mental health of local medical and nursing staff and thus lead them to seek help. However, those outcomes have yet to be established using epidemiological data. To explore the mental health status of medical and nursing staff and the efficacy, or lack thereof, of critically connecting psychological needs to receiving psychological care, we conducted a quantitative study. This is the first paper on the mental health of medical and nursing staff in Wuhan. Notably, among 994 medical and nursing staff working in Wuhan, 36.9% had subthreshold mental health disturbances (mean PHQ-9: 2.4), 34.4% had mild disturbances (mean PHQ-9: 5.4), 22.4% had moderate disturbances (mean PHQ-9: 9.0), and 6.2% had severe disturbance (mean PHQ-9: 15.1) in the immediate wake of the viral epidemic. The noted burden fell particularly heavily on young women. Of all participants, 36.3% had accessed psychological materials (such as books on mental health), 50.4% had accessed psychological resources available through media (such as online push messages on mental health self-help coping methods), and 17.5% had participated in counseling or psychotherapy. Trends in levels of psychological distress and factors such as exposure to infected people and psychological assistance were identified. Although staff accessed limited mental healthcare services, distressed staff nonetheless saw these services as important resources to alleviate acute mental health disturbances and improve their physical health perceptions. These findings emphasize the importance of being prepared to support frontline workers through mental health interventions at times of widespread crisis.
The global pandemic of coronavirus disease 2019 (COVID-19) is a disaster for human society. A convenient and reliable neutralization assay is very important for the development of vaccines and novel ...drugs. In this study, a G protein-deficient vesicular stomatitis virus (VSVdG) bearing a truncated spike protein (S with C-terminal 18 amino acid truncation) was compared to that bearing the full-length spike protein of SARS-CoV-2 and showed much higher efficiency. A neutralization assay was established based on VSV-SARS-CoV-2-Sdel18 pseudovirus and hACE2-overexpressing BHK21 cells (BHK21-hACE2 cells). The experimental results can be obtained by automatically counting the number of EGFP-positive cells at 12 h after infection, making the assay convenient and high-throughput. The serum neutralizing titer measured by the VSV-SARS-CoV-2-Sdel18 pseudovirus assay has a good correlation with that measured by the wild type SARS-CoV-2 assay. Seven neutralizing monoclonal antibodies targeting the receptor binding domain (RBD) of the SARS-CoV-2 S protein were obtained. This efficient and reliable pseudovirus assay model could facilitate the development of new drugs and vaccines.
Exploiting radio frequency signals is promising for locating and tracking objects. Prior works focus on per-tag localization, in which each object is attached with one tag. In this paper, we propose ...a comprehensive localization and tracking scheme by attaching two RFID tags to one object. Instead of using per-tag localization pattern, adding one-more RFID tag to the object exhibits several benefits: 1) providing rich freedom in RFID reader's antenna spacing and placement; 2) supporting accurate calibration of the reader's antenna location and spacing, and 3) enabling fine-grained calculation on the orientation of the tags. All of these advantages ultimately improve the localization/tracking accuracy. Our extensive experimental results demonstrate that the average errors of localization and orientation of target tags are 6.415 cm and 1.330°, respectively. Our results also verify that the reader's antenna geometry does have impact on tag positioning performance.
COVID-19 has spread globally. Epidemiological susceptibility to COVID-19 has been reported in patients with cancer. We aimed to systematically characterise clinical features and determine risk ...factors of COVID-19 disease severity for patients with cancer and COVID-19.
In this multicentre, retrospective, cohort study, we included all adult patients (aged ≥18 years) with any type of malignant solid tumours and haematological malignancy who were admitted to nine hospitals in Wuhan, China, with laboratory-confirmed COVID-19 between Jan 13 and March 18, 2020. Enrolled patients were statistically matched (2:1) with patients admitted with COVID-19 who did not have cancer with propensity score on the basis of age, sex, and comorbidities. Demographic characteristics, laboratory examinations, illness severity, and clinical interventions were compared between patients with COVID-19 with or without cancer as well as between patients with cancer with non-severe or severe COVID-19. COVID-19 disease severity was defined on admission on the basis of the WHO guidelines. Univariable and multivariable logistic regression, adjusted for age, sex, comorbidities, cancer type, tumour stage, and antitumour treatments, were used to explore risk factors associated with COVID-19 disease severity. This study was registered in the Chinese Clinical Trial Register, ChiCTR2000030807.
Between Jan 13 and March 18, 2020, 13 077 patients with COVID-19 were admitted to the nine hospitals in Wuhan and 232 patients with cancer and 519 statistically matched patients without cancer were enrolled. Median follow-up was 29 days (IQR 22–38) in patients with cancer and 27 days (20–35) in patients without cancer. Patients with cancer were more likely to have severe COVID-19 than patients without cancer (148 64% of 232 vs 166 32% of 519; odds ratio OR 3·61 95% CI 2·59–5·04; p<0·0001). Risk factors previously reported in patients without cancer, such as older age; elevated interleukin 6, procalcitonin, and D-dimer; and reduced lymphocytes were validated in patients with cancer. We also identified advanced tumour stage (OR 2·60, 95% CI 1·05–6·43; p=0·039), elevated tumour necrosis factor α (1·22, 1·01–1·47; p=0·037), elevated N-terminal pro-B-type natriuretic peptide (1·65, 1·03–2·78; p=0·032), reduced CD4+ T cells (0·84, 0·71–0·98; p=0·031), and reduced albumin–globulin ratio (0·12, 0·02–0·77; p=0·024) as risk factors of COVID-19 severity in patients with cancer.
Patients with cancer and COVID-19 were more likely to deteriorate into severe illness than those without cancer. The risk factors identified here could be helpful for early clinical surveillance of disease progression in patients with cancer who present with COVID-19.
China National Natural Science Foundation.