The outbreak of Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2), has thus far killed over 3,000 people and infected over 80,000 in ...China and elsewhere in the world, resulting in catastrophe for humans. Similar to its homologous virus, SARS-CoV, which caused SARS in thousands of people in 2003, SARS-CoV-2 might also be transmitted from the bats and causes similar symptoms through a similar mechanism. However, COVID-19 has lower severity and mortality than SARS but is much more transmissive and affects more elderly individuals than youth and more men than women. In response to the rapidly increasing number of publications on the emerging disease, this article attempts to provide a timely and comprehensive review of the swiftly developing research subject. We will cover the basics about the epidemiology, etiology, virology, diagnosis, treatment, prognosis, and prevention of the disease. Although many questions still require answers, we hope that this review helps in the understanding and eradication of the threatening disease.
Northern Hemisphere forests changed drastically in the early Eocene with the diversification of the oak family (Fagaceae). Cooling climates over the next 20 million years fostered the spread of ...temperate biomes that became increasingly dominated by oaks and their chestnut relatives. Here we use phylogenomic analyses of nuclear and plastid genomes to investigate the timing and pattern of major macroevolutionary events and ancient genome-wide signatures of hybridization across Fagaceae. Innovation related to seed dispersal is implicated in triggering waves of continental radiations beginning with the rapid diversification of major lineages and resulting in unparalleled transformation of forest dynamics within 15 million years following the K-Pg extinction. We detect introgression at multiple time scales, including ancient events predating the origination of genus-level diversity. As oak lineages moved into newly available temperate habitats in the early Miocene, secondary contact between previously isolated species occurred. This resulted in adaptive introgression, which may have further amplified the diversification of white oaks across Eurasia.
AbstractObjectiveTo investigate the association between weight changes across adulthood and mortality.DesignProspective cohort study.SettingUS National Health and Nutrition Examination Survey ...(NHANES) 1988-94 and 1999-2014.Participants36 051 people aged 40 years or over with measured body weight and height at baseline and recalled weight at young adulthood (25 years old) and middle adulthood (10 years before baseline).Main outcome measuresAll cause and cause specific mortality from baseline until 31 December 2015.ResultsDuring a mean follow-up of 12.3 years, 10 500 deaths occurred. Compared with participants who remained at normal weight, those moving from the non-obese to obese category between young and middle adulthood had a 22% (hazard ratio 1.22, 95% confidence interval 1.11 to 1.33) and 49% (1.49, 1.21 to 1.83) higher risk of all cause mortality and heart disease mortality, respectively. Changing from obese to non-obese body mass index over this period was not significantly associated with mortality risk. An obese to non-obese weight change pattern from middle to late adulthood was associated with increased risk of all cause mortality (1.30, 1.16 to 1.45) and heart disease mortality (1.48, 1.14 to 1.92), whereas moving from the non-obese to obese category over this period was not significantly associated with mortality risk. Maintaining obesity across adulthood was consistently associated with increased risk of all cause mortality; the hazard ratio was 1.72 (1.52 to 1.95) from young to middle adulthood, 1.61 (1.41 to 1.84) from young to late adulthood, and 1.20 (1.09 to 1.32) from middle to late adulthood. Maximum overweight had a very modest or null association with mortality across adulthood. No significant associations were found between various weight change patterns and cancer mortality.ConclusionsStable obesity across adulthood, weight gain from young to middle adulthood, and weight loss from middle to late adulthood were associated with increased risks of mortality. The findings imply that maintaining normal weight across adulthood, especially preventing weight gain in early adulthood, is important for preventing premature deaths in later life.
Objective
The study aimed to identify BMI‐related lipids and to explore the role of lipids linking BMI and gestational diabetes mellitus (GDM).
Methods
Plasma lipidome, height, and weight were ...measured in early pregnancy among 1008 women. Pearson correlation analyses and least absolute shrinkage and selection operator regression (LASSO) were performed to identify BMI‐associated lipids. Based on these lipids, a lipid score was created using LASSO, and its association with GDM risk was evaluated by conditional logistic regression. The causal relationships between BMI and lipids were tested by Mendelian randomization analysis with genotyping data. Mediation analysis was conducted to evaluate the mediating effect of lipids on the association of BMI with GDM.
Results
Of 366 measured lipids, BMI was correlated with 28 lipids, which mainly belong to glycerophospholipids and glycerolipids. A total of 10 lipid species were associated with BMI, and a lipid score was established. A causal relationship between BMI and lysophosphatidylcholine 14:0 was observed. The lipid score was associated with a 1.69‐fold increased risk of GDM per 1‐point increment (95% CI: 1.33‐2.15). Furthermore, BMI‐associated lipids might explain 66.4% of the relationship between BMI and GDM.
Conclusions
Higher BMI in early pregnancy was associated with altered lipid metabolism that may contribute to the increased risk of GDM.
The efficacy of osimertinib was compromised by the development of resistance mechanisms, such as EGFR C797S. In vitro study proved that cells harboring EGFR C797S in trans with T790M are sensitive to ...a combination of first- and third-generation EGFR tyrosine kinase inhibitors. However, this has not been reported clinically.
We performed capture-based sequencing on longitudinal plasma samples obtained at various treatment milestones from a patient with advanced lung adenocarcinoma who was undergoing targeted therapy.
At the development of resistance to osimertinib, the patient’s plasma sample revealed EGFR C797S located in trans with T790M. He achieved partial response accompanied by undetectable C797S after commencement of a combinatorial treatment consisting of erlotinib and osimertinib. After 3 months of progression-free survival, he experienced progressive disease with emergence of EGFR C797S located in cis to T790M.
We report the first clinical evidence of efficacy generated by combination therapy consisting of first- and third-generation EGFR tyrosine kinase inhibitors targeting concomitant EGFR T790M and C797S in trans. We also reveal that the clonal progression of C797S from in trans to in cis at disease progression may serve as a potential resistance mechanism.
Identification of non-diabetic renal disease (NDRD) in patients with type 2 diabetes mellitus (T2DM) may help tailor treatment. Intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) is a ...promising tool to evaluate renal function but its potential role in the clinical differentiation between diabetic nephropathy (DN) and NDRD remains unclear.
To investigate the added role of IVIM-DWI in the differential diagnosis between DN and NDRD in patients with T2DM.
Prospective.
Sixty-three patients with T2DM (ages: 22-69 years, 17 females) confirmed by renal biopsy divided into two subgroups (28 DN and 35 NDRD).
3 T/ T2 weighted imaging (T
WI), and intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI).
The parameters derived from IVIM-DWI (true diffusion coefficient D, pseudo-diffusion coefficient D*, and pseudo-diffusion fraction f) were calculated for the cortex and medulla, respectively. The clinical indexes related to renal function (eg cystatin C, etc.) and diabetes (eg diabetic retinopathy DR, fasting blood glucose, etc.) were measured and calculated within 1 week before MRI scanning. The clinical model based on clinical indexes and the IVIM-based model based on IVIM parameters and clinical indexes were established and evaluated, respectively.
Student's t-test; Mann-Whitney U test; Fisher's exact test; Chi-squared test; Intraclass correlation coefficient; Receiver operating characteristic analysis; Hosmer-Lemeshow test; DeLong's test. P < 0.05 was considered statistically significant.
The cortex D*, DR, and cystatin C values were identified as independent predictors of NDRD in multivariable analysis. The IVIM-based model, comprising DR, cystatin C, and cortex D*, significantly outperformed the clinical model containing only DR, and cystatin C (AUC = 0.934, 0.845, respectively).
The IVIM parameters, especially the renal cortex D* value, might serve as novel indicators in the differential diagnosis between DN and NDRD in patients with T2DM.
2 TECHNICAL EFFICACY: Stage 2.
Summary
Natural selection shapes genome‐wide patterns of diversity within species and divergence between species. However, quantifying the efficacy of selection and elucidating the relative ...importance of different types of selection in shaping genomic variation remain challenging.
We sequenced whole genomes of 101 individuals of three closely related oak species to track the divergence history, and to dissect the impacts of selective sweeps and background selection on patterns of genomic variation.
We estimated that the three species diverged around the late Neogene and experienced a bottleneck during the Pleistocene. We detected genomic regions with elevated relative differentiation (‘FST‐islands’). Population genetic inferences from the site frequency spectrum and ancestral recombination graph indicated that FST‐islands were formed by selective sweeps. We also found extensive positive selection; the fixation of adaptive mutations and reduction neutral diversity around substitutions generated a signature of selective sweeps. Prevalent negative selection and background selection have reduced genetic diversity in both genic and intergenic regions, and contributed substantially to the baseline variation in genetic diversity.
Our results demonstrate the importance of linked selection in shaping genomic variation, and illustrate how the extent and strength of different selection models vary across the genome.
Inspired by the photosynthesis process of natural plants, multifunctional transistors based on natural biomaterial chlorophyll and organic semiconductors (OSCs) are reported. Functions as ...photodetectors (PDs) and light‐stimulated synaptic transistors (LSSTs) can be switched by gate voltage. As PDs, the devices exhibit ultrahigh photoresponsivity up to 2 × 106 A W−1, detectivity of 6 × 1015 Jones, and Iphoto/Idark ratio of 2.7 × 106, which make them among the best reported organic PDs. As LSSTs, important synaptic functions similar to biological synapses are demonstrated, together with a dynamic learning and forgetting process and image‐processing function. Significantly, benefiting from the ultrahigh photosensitivity of chlorophyll, the lowest operating voltage and energy consumption of the LSSTs can be 10−5 V and 0.25 fJ, respectively. The devices also exhibit high flexibility and long‐term air stability. This work provides a new guide for developing organic electronics based on natural biomaterials.
Bioinspired multifunctional organic transistors based on natural chlorophyll and organic semiconductors are fabricated. Phototdetection and light‐stimulated synaptic transistor function can be realized by the single device under gate‐voltage control. The devices show excellent photoresponsivity up to 2 × 106 A W−1 as photodetectors and ultralow operating voltage of 10–5 V as synaptic devices.
Chirality, with its intrinsic symmetry‐breaking feature, is frequently utilized in the creation of acentric crystalline functional materials that exhibit intriguing optoelectronic properties. On the ...other hand, the development of chiral crystals from achiral molecules offers a solution that bypasses the need for enantiopure motifs, presenting a promising alternative and thereby expanding the possibilities of the self‐assembly toolkit. Nevertheless, the rational design of achiral molecules that prefer spontaneous symmetry breaking during crystallization has so far been obscure. In this study, we present a series of six achiral molecules, demonstrating that when these conformationally flexible molecules adopt a cis‐conformation and engage in multiple non‐covalent interactions along a helical path, they collectively self‐assemble into chiral superstructures consisting of single‐handed supramolecular columns. When these homochiral supramolecular columns align in parallel, they form polar crystals that exhibit intense luminescence upon grinding or scraping. We therefore demonstrate our molecular design strategy could significantly increase the likelihood of symmetry breaking in achiral molecular synthons during self‐assembly, offering a facile access to novel chiral crystalline materials with unique optoelectronic properties.
We designed a library of six achiral pyrene‐containing molecules and two counterexamples to demonstrate the powerful strategy for spontaneous symmetry breaking. When the polarity of the crystals resulting from symmetry breaking is coupled with the intrinsic photophysical property of pyrene moieties, the three polar crystals exhibit intense mechanoluminescence.
Objective
To investigate the association between mitochondrial DNA copy number (mtDNAcn) and semen quality.
Design
A cross‐sectional study.
Setting
Hubei Province Human Sperm Bank of China (from ...April 2017 to July 2018).
Population
A total of 1164 healthy male sperm donors with 5739 specimens.
Main outcome measures
Real‐time quantitative polymerase chain reaction (RT‐PCR) was used to measure sperm mtDNAcn. We also determined semen volume, concentration and motility parameters (progressive motility, nonprogressive motility and immotility).
Methods
Mixed‐effect models and general linear models were uses.
Results
After adjusting for relevant confounding factors, mixed‐effect models revealed diminished sperm motility (progressive and total), concentration, and total count across the quartiles of mtDNAcn (all P < 0.05). Compared with men in the lowest quartile, men in the highest quartile of mtDNAcn had lower progressive sperm motility, total motility, concentration and total count of −8.9% (95% CI −12.7% to −5.0%), −8.0% (95% CI −11.6% to −4.4%), −42.8% (95% CI −47.7% to −37.4%), and − 44.3% (95% CI −50.1% to −37.7%), respectively. These inverse dose–response relationships were further confirmed in the cubic spline models, where mtDNAcn was modelled as a continuous variable.
Conclusions
We found that mtDNAcn was inversely associated with semen quality in a dose‐dependent manner. Our results provide novel clues that sperm mtDNAcn may serve as a useful predictor of human semen characteristics.
Tweetable
Sperm mitochondrial DNA copy number was markedly associated with diminished sperm motility (progressive and total), concentration and total count.
Tweetable
Sperm mitochondrial DNA copy number was markedly associated with diminished sperm motility (progressive and total), concentration and total count.
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