In December 2019, coronavirus disease 2019 (COVID-19), which is caused by the new coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was identified in Wuhan (Hubei province, ...China)
; it soon spread across the world. In this ongoing pandemic, public health concerns and the urgent need for effective therapeutic measures require a deep understanding of the epidemiology, transmissibility and pathogenesis of COVID-19. Here we analysed clinical, molecular and immunological data from 326 patients with confirmed SARS-CoV-2 infection in Shanghai. The genomic sequences of SARS-CoV-2, assembled from 112 high-quality samples together with sequences in the Global Initiative on Sharing All Influenza Data (GISAID) dataset, showed a stable evolution and suggested that there were two major lineages with differential exposure history during the early phase of the outbreak in Wuhan. Nevertheless, they exhibited similar virulence and clinical outcomes. Lymphocytopenia, especially reduced CD4
and CD8
T cell counts upon hospital admission, was predictive of disease progression. High levels of interleukin (IL)-6 and IL-8 during treatment were observed in patients with severe or critical disease and correlated with decreased lymphocyte count. The determinants of disease severity seemed to stem mostly from host factors such as age and lymphocytopenia (and its associated cytokine storm), whereas viral genetic variation did not significantly affect outcomes.
The cytoskeleton plays a pivotal role in maintaining the epithelial phenotype and is vital to several hallmark processes of cancer. Over the past decades, researchers have identified the epithelial ...protein lost in neoplasm (EPLIN, also known as LIMA1) as a key regulator of cytoskeletal dynamics, cytoskeletal organization, motility, as well as cell growth and metabolism. Dysregulation of EPLIN is implicated in various aspects of cancer progression, such as tumor growth, invasion, metastasis, and therapeutic resistance. Its altered expression levels or activity can disrupt cytoskeletal dynamics, leading to aberrant cell motility and invasiveness characteristic of malignant cells. Moreover, the involvement of EPLIN in cell growth and metabolism underscores its significance in orchestrating key processes essential for cancer cell survival and proliferation. This review provides a comprehensive exploration of the intricate roles of EPLIN across diverse cellular processes in both normal physiology and cancer pathogenesis. Additionally, this review discusses the possibility of EPLIN as a potential target for anticancer therapy in future studies.
Summary Background On March 30, a novel influenza A subtype H7N9 virus (A/H7N9) was detected in patients with severe respiratory disease in eastern China. Virological factors associated with a poor ...clinical outcome for this virus remain unclear. We quantified the viral load and analysed antiviral resistance mutations in specimens from patients with A/H7N9. Methods We studied 14 patients with A/H7N9 disease admitted to the Shanghai Public Health Clinical Centre (SPHCC), China, between April 4, and April 20, 2013, who were given antiviral treatment (oseltamivir or peramivir) for less than 2 days before admission. We investigated the viral load in throat, stool, serum, and urine specimens obtained sequentially from these patients. We also sequenced viral RNA from these specimens to study the mutations associated with resistance to neuraminidase inhibitors and their association with disease outcome. Findings All patients developed pneumonia, seven of them required mechanical ventilation, and three of them further deteriorated to become dependent on extracorporeal membrane oxygenation (ECMO), two of whom died. Antiviral treatment was associated with a reduction of viral load in throat swab specimens in 11 surviving patients. Three patients with persistently high viral load in the throat in spite of antiviral therapy became ECMO dependent. An Arg292Lys mutation in the virus neuraminidase (NA) gene known to confer resistance to both zanamivir and oseltamivir was identified in two of these patients, both also received corticosteroid treatment. In one of them, wild-type sequence Arg292 was noted 2 days after start of antiviral treatment, and the resistant mutant Lys292 dominated 9 days after start of treatment. Interpretation Reduction of viral load following antiviral treatment correlated with improved outcome. Emergence of NA Arg292Lys mutation in two patients who also received corticosteroid treatment led to treatment failure and a poor clinical outcome. The emergence of antiviral resistance in A/H7N9 viruses, especially in patients receiving corticosteroid therapy, is concerning, needs to be closely monitored, and considered in pandemic preparedness planning. Funding National Megaprojects of China for Infectious Diseases, Shanghai Municipal Health and Family Planning Commission, the National Key Basic Research Program of China, Ministry of Science and Technology, and National Natural Science Foundation of China.
Cancer cells are characterized by a higher rate of protein turnover and greater demand for protein homeostasis compared to normal cells. In this scenario, the ubiquitin-proteasome system (UPS), which ...is responsible for the degradation of over 80% of cellular proteins within mammalian cells, becomes vital to cancer cells, making the UPS a critical target for the discovery of novel cancer therapeutics. This review systematically categorizes all current reported small molecule inhibitors of the various essential components of the UPS, including ubiquitin-activating enzymes (E1s), ubiquitin-conjugating enzymes (E2s), ubiquitin ligases (E3s), the 20S proteasome catalytic core particle (20S CP) and the 19S proteasome regulatory particles (19S RP), as well as their mechanism/s of action and limitations. We also discuss the immunoproteasome which is considered as a prospective therapeutic target of the next generation of proteasome inhibitors in cancer therapies.
Crystal orientations in multiple orders correlate to the properties of polycrystalline materials, and it is critical to manipulate these microstructural arrangements to enhance device performance. ...Herein, we report a controllable approach to manipulate the facet orientation within the ABX
hybrid perovskites polycrystalline films by cation cascade doping at A-site. Two-dimensional synchrotron radiation grazing incidence wide-angle X-ray scattering is employed to probe the crystal orientations in multiple orders in mixed perovskites thin films, revealing a general pattern to guide crystal planes stacking upon extrinsic doping during crystallization. Different from previous studies, this method enables to adjust the crystal stacking mode of certain crystallographic planes in polycrystalline perovskites. Moreover, the preferred facet orientation is found to facilitate photocarrier transport across the absorber and pertaining interface in the resultant PV device, which provides an exemplary paradigm for further explorations that relate to the microstructures of hybrid perovskite materials and relevant optoelectronics.
The application of biological nitrification inhibitors (BNIs) is considered an important new strategy to mitigate nitrogen losses from agricultural soils. 1,9-decanediol was recently identified as a ...new BNI in rice root exudates and was shown to inhibit nitrification in bioassays using Nitrosomonas. However, the effect of this compound on nitrification and ammonia oxidizers in soils remained unknown. In this study, three typical agriculture soils were collected to investigate the impact of 1,9-decanediol on nitrification and ammonia oxidizers in a 14-day microcosm incubation. High doses of 1,9-decanediol showed strong soil nitrification inhibition in all three agricultural soils, with the highest inhibition of 58.1% achieved in the acidic red soil, 37.0% in the alkaline fluvo-aquic soil, and 35.7% in the neutral paddy soil following 14 days of incubation. Moreover, the inhibition of 1,9-decanediol was superior to the widely used synthetic nitrification inhibitor, dicyandiamide (DCD) and two other BNIs, methyl 3-(4-hydroxyphenyl) propionate (MHPP) and α-linolenic acid (LN), in all three soils. The abundance of ammonia-oxidizing bacteria (AOB) and ammonia-oxidizing archaea (AOA) was significantly inhibited by 1,9-decanediol addition across the three soils. All AOB sequences fell within the Nitrosospira group, and the dominant AOA sequences belonged to the Nitrososphaera cluster in all three soils. Changes in the community composition of AOB were more pronounced than AOA after the application of 1,9-decanediol. The AOB community structure shifted from Nitrosospira cluster 2 and cluster 3a toward Nitrosospira clusters 8a and 8b. As for AOA, no significant impact on the proportion of the dominant Nitrososphaera cluster was observed in the fluvo-aquic soil and paddy soil while only the Nitrosopumilus cluster decreased in the red soil. 1,9-decanediol could also significantly reduce soil N2O emissions, especially in acidic red soil. Our results provide evidence that 1,9-decanediol is capable of suppressing nitrification in agricultural soils through impeding both AOA and AOB rather than affecting soil NH4+ availability. 1,9-decanediol holds promise as an effective biological nitrification inhibitor for soil ammonia-oxidizing bacteria and archaea.
•1,9-decanediol can inhibit soil nitrification.•The inhibition of 1,9-decanediol is superior to that of DCD and two other BNIs.•1,9-decanediol inhibits nitrification by impeding both AOA and AOB.•1,9-decanediol can reduce N2O emissions, especially in acidic red soils.
Quiescent cancer cells (QCCs) are nonproliferating cells arrested in the G0 phase, characterized by ki67
and p27
. QCCs avoid most chemotherapies, and some treatments could further lead to a higher ...proportion of QCCs in tumors. QCCs are also associated with cancer recurrence since they can re-enter a proliferative state when conditions are favorable. As QCCs lead to drug resistance and tumor recurrence, there is a great need to understand the characteristics of QCCs, decipher the mechanisms that regulate the proliferative-quiescent transition in cancer cells, and develop new strategies to eliminate QCCs residing in solid tumors. In this review, we discussed the mechanisms of QCC-induced drug resistance and tumor recurrence. We also discussed therapeutic strategies to overcome resistance and relapse by targeting QCCs, including (i) identifying reactive quiescent cancer cells and removing them via cell-cycle-dependent anticancer reagents; (ii) modulating the quiescence-to-proliferation switch; and (iii) eliminating QCCs by targeting their unique features. It is believed that the simultaneous co-targeting of proliferating and quiescent cancer cells may ultimately lead to the development of more effective therapeutic strategies for the treatment of solid tumors.
Loss of heterozygosity (LOH) is a common genetic event in the development of cancer. In certain tumor types, LOH can affect more than 20% of the genome, entailing loss of allelic variation in ...thousands of genes. This reduction of heterozygosity creates genetic differences between tumor and normal cells, providing opportunities for development of novel cancer therapies. Here, we review and summarize (1) mutations associated with LOH on chromosomes which have been shown to be promising biomarkers of cancer risk or the prediction of clinical outcomes in certain types of tumors; (2) loci undergoing LOH that can be targeted for development of novel anticancer drugs as well as (3) LOH in tumors provides up-and-coming possibilities to understand the underlying mechanisms of cancer evolution and to discover novel cancer vulnerabilities which are worth a further investigation in the near future.
High levels of air pollution in China may contribute to the urban population's reported low level of happiness
. To test this claim, we have constructed a daily city-level expressed happiness metric ...based on the sentiment in the contents of 210 million geotagged tweets on the Chinese largest microblog platform Sina Weibo
, and studied its dynamics relative to daily local air quality index and PM
concentrations (fine particulate matter with diameters equal or smaller than 2.5 μm, the most prominent air pollutant in Chinese cities). Using daily data for 144 Chinese cities in 2014, we document that, on average, a one standard deviation increase in the PM
concentration (or Air Quality Index) is associated with a 0.043 (or 0.046) standard deviation decrease in the happiness index. People suffer more on weekends, holidays and days with extreme weather conditions. The expressed happiness of women and the residents of both the cleanest and dirtiest cities are more sensitive to air pollution. Social media data provides real-time feedback for China's government about rising quality of life concerns.
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