Miracle-dz/UniFAR-FTUs huggingface dataset:
Secondary contact between diverged host lineages entails ecological speciation in a European hantavirus

The diversity of viruses probably exceeds biodiversity of eukaryotes, but little is known about the origin and emergence of novel virus species. Experimentation and disease outbreak investigations have allowed the characterization of rapid molecular virus adaptation. However, the processes leading to the establishment of functionally distinct virus taxa in nature remain obscure. Here, we demonstrate that incipient speciation in a natural host species has generated distinct ecological niches leading to adaptive isolation in an RNA virus. We found a very strong association between the distributions of two major phylogenetic clades in Tula orthohantavirus (TULV) and the rodent host lineages in a natural hybrid zone of the European common vole (Microtus arvalis). The spatial transition between the virus clades in replicated geographic clines is at least eight times narrower than between the hybridizing host lineages. This suggests a strong barrier for effective virus transmission despite frequent dispersal and gene flow among local host populations, and translates to a complete turnover of the adaptive background of TULV within a few hundred meters in the open, unobstructed landscape. Genetic differences between TULV clades are homogenously distributed in the genomes and mostly synonymous (93.1%), except for a cluster of nonsynonymous changes in the 5′ region of the viral envelope glycoprotein gene, potentially involved in host-driven isolation. Evolutionary relationships between TULV clades indicate an emergence of these viruses through rapid differential adaptation to the previously diverged host lineages that resulted in levels of ecological isolation exceeding the progress of speciation in their vertebrate hosts.
Boron-doped graphene quantum dots: an efficient photoanode for a dye sensitized solar cell

Boron-doped graphene quantum dots (B-GQDs) have been synthesized via a microwave reactor assisted process from bulk boron carbide (B4C) crystals and they are shown to exhibit enhanced photoactivity. The B-GQDs are found to have an average lateral width of ∼6 ± 2 nm, and thickness of ∼0.2–0.3 nm. Nano ZnO is incorporated into these B-GQDs to prepare a B-GQDs-ZnO composite based high-performance photo-anode for Dye-Sensitized Solar Cells (DSSCs). The results showed the highest power conversion efficiency of ∼3.7% with these new composite based DSSCs, showing the potential of this composite in real cell applications.
Convergent perturbation of the human domain-resolved interactome by viruses and mutations inducing similar disease phenotypes

An important goal of systems medicine is to study disease in the context of genetic and environmental perturbations to the human interactome network. For diseases with both genetic and infectious contributors, a key postulate is that similar perturbations of the human interactome by either disease mutations or pathogens can have similar disease consequences. This postulate has so far only been tested for a few viral species at the level of whole proteins. Here, we expand the scope of viral species examined, and test this postulate more rigorously at the higher resolution of protein domains. Focusing on diseases with both genetic and viral contributors, we found significant convergent perturbation of the human domain-resolved interactome by endogenous genetic mutations and exogenous viral proteins inducing similar disease phenotypes. Pan-cancer, pan-oncovirus analysis further revealed that domains of human oncoproteins either physically targeted or structurally mimicked by oncoviruses are enriched for cancer driver rather than passenger mutations, suggesting convergent targeting of cancer driver pathways by diverse oncoviruses. Our study provides a framework for high-resolution, network-based comparison of various disease factors, both genetic and environmental, in terms of their impacts on the human interactome.
Regulation of Nitric Oxide Production in the Developmental Programming of Hypertension and Kidney Disease

Development of the kidney can be altered in response to adverse environments leading to renal programming and increased vulnerability to the development of hypertension and kidney disease in adulthood. By contrast, reprogramming is a strategy shifting therapeutic intervention from adulthood to early life to reverse the programming processes. Nitric oxide (NO) is a key mediator of renal physiology and blood pressure regulation. NO deficiency is a common mechanism underlying renal programming, while early-life NO-targeting interventions may serve as reprogramming strategies to prevent the development of hypertension and kidney disease. This review will first summarize the regulation of NO in the kidney. We also address human and animal data supporting the link between NO system and developmental programming of hypertension and kidney disease. This will be followed by the links between NO deficiency and the common mechanisms of renal programming, including the oxidative stress, renin–angiotensin system, nutrient-sensing signals, and sex differences. Recent data from animal studies have suggested that interventions targeting the NO pathway could be reprogramming strategies to prevent the development of hypertension and kidney disease. Further clinical studies are required to bridge the gap between animal models and clinical trials in order to develop ideal NO-targeting reprogramming strategies and to be able to have a lifelong impact, with profound savings in the global burden of hypertension and kidney disease.
Transport and Optical Gaps in Amorphous Organic Molecular Materials

The standard procedure to identify the hole- or electron-acceptor character of amorphous organic materials used in OLEDs is to look at the values of a pair of basic parameters, namely, the ionization potential (IP) and the electron affinity (EA). Recently, using published experimental data, the present authors showed that only IP matters, i.e., materials with IP > 5.7 (<5.7) showing electron (hole) acceptor character. Only three materials fail to obey this rule. This work reports ab initio calculations of IP and EA of those materials plus two materials that behave according to that rule, following a route which describes the organic material by means of a single molecule embedded in a polarizable continuum medium (PCM) characterized by a dielectric constant ε. PCM allows to approximately describe the extended character of the system. This “compound” system was treated within density functional theory (DFT) using several combinations of the functional/basis set. In the preset work ε was derived by assuming Koopmans’ theorem to hold. Optimal ε values are in the range 4.4–5.0, close to what is expected for this material family. It was assumed that the optical gap corresponds to the excited state with a large oscillator strength among those with the lowest energies, calculated with time-dependent DFT. Calculated exciton energies were in the range 0.76–1.06 eV, and optical gaps varied from 3.37 up to 4.50 eV. The results are compared with experimental data.
Examining individual and geographic factors associated with social isolation and loneliness using Canadian Longitudinal Study on Aging (CLSA) data

Background A large body of research shows that social isolation and loneliness have detrimental health consequences. Identifying individuals at risk of social isolation or loneliness is, therefore, important. The objective of this study was to examine personal (e.g., sex, income) and geographic (rural/urban and sociodemographic) factors and their association with social isolation and loneliness in a national sample of Canadians aged 45 to 85 years. Methods The study involved cross-sectional analyses of baseline data from the Canadian Longitudinal Study on Aging that were linked to 2016 census data at the Forward Sortation Area (FSA) level. Multilevel logistic regression analyses were conducted to examine the association between personal factors and geographic factors and social isolation and loneliness for the total sample, and women and men, respectively. Results The prevalence of social isolation and loneliness was 5.1% and 10.2%, respectively, but varied substantially across personal characteristics. Personal characteristics (age, sex, education, income, functional impairment, chronic diseases) were significantly related to both social isolation and loneliness, although some differences emerged in the direction of the relationships for the two measures. Associations also differed somewhat for women versus men. Associations between some geographic factors emerged for social isolation, but not loneliness. Living in an urban core was related to increased odds of social isolation, an effect that was no longer significant when FSA-level factors were controlled for. FSAs with a higher percentage of 65+ year old residents with low income were consistently associated with higher odds of social isolation. Conclusion The findings indicate that socially isolated individuals are, to some extent, clustered into areas with a high proportion of low-income older adults, suggesting that support and resources could be targeted at these areas. For loneliness, the focus may be less on where people live, but rather on personal characteristics that place individuals at risk.
Increasing atmospheric CO2 and canopy temperature induces anatomical and physiological changes in leaves of the C4 forage species Panicum maximum

Changes in leaf anatomy and ultrastructure are associated with physiological performance in the context of plant adaptations to climate change. In this study, we investigated the isolated and combined effects of elevated atmospheric CO2 concentration ([CO2]) up to 600 μmol mol-1 (eC) and elevated temperature (eT) to 2°C more than the ambient canopy temperature on the ultrastructure, leaf anatomy, and physiology of Panicum maximum Jacq. grown under field conditions using combined free-air carbon dioxide enrichment (FACE) and temperature free-air controlled enhancement (T-FACE) systems. Plants grown under eC showed reduced stomatal density, stomatal index, stomatal conductance (gs), and leaf transpiration rate (E), increased soil-water content (SWC) conservation and adaxial epidermis thickness were also observed. The net photosynthesis rate (A) and intrinsic water-use efficiency (iWUE) were enhanced by 25% and 71%, respectively, with a concomitant increase in the size of starch grains in bundle sheath cells. Under air warming, we observed an increase in the thickness of the adaxial cuticle and a decrease in the leaf thickness, size of vascular bundles and bulliform cells, and starch content. Under eCeT, air warming offset the eC effects on SWC and E, and no interactions between [CO2] and temperature for leaf anatomy were observed. Elevated [CO2] exerted more effects on external characteristics, such as the epidermis anatomy and leaf gas exchange, while air warming affected mainly the leaf structure. We conclude that differential anatomical and physiological adjustments contributed to the acclimation of P. maximum growing under elevated [CO2] and air warming, improving the leaf biomass production under these conditions.
Drug Sensitivity Screening and Targeted Pathway Analysis Reveal a Multi-Driver Proliferative Mechanism and Suggest a Strategy of Combination Targeted Therapy for Colorectal Cancer Cells

Treatment of colorectal cancer mostly relies on traditional therapeutic approaches, such as surgery and chemotherapy. Limited options of targeted therapy for colorectal cancer narrowly focus on blocking cancer-generic targets VEGFR and EGFR. Identifying the oncogenic drivers, understanding their contribution to proliferation, and finding inhibitors to block such drivers are the keys to developing targeted therapy for colorectal cancer. In this study, ten colorectal cancer cell lines were screened against a panel of protein kinase inhibitors blocking key oncogenic signaling pathways. The results show that four of the 10 cell lines did not respond to any kinase inhibitors significantly, the other six were mildly inhibited by AZD-6244, BMS-754807, and/or dasatinib. Mechanistic analyses demonstrate that these inhibitors independently block the MAP kinase pathway, IR/IGF-1R/AKT pathway, and Src kinases, suggesting a multi-driver nature of proliferative signaling in these cells. Most of these cell lines were potently and synergistically inhibited by pair-wise combinations of these drugs. Furthermore, seven of the 10 cell lines were inhibited by the triple combination of AZD-6244/BMS-754807/dasatinib with IC50’s between 10 and 84 nM. These results suggest that combination targeted therapy may be an effective strategy against colorectal cancer.
Pulp Temperature Rise Induced by Light-Emitting Diode Light-Curing Units Using an Ex Vivo Model

The aim of this research was to compare the pulp temperature (PT) rise induced by four light-emitting diode light-curing units (LED LCUs) (Bluephase 20i, Demi Ultra, SPEC 3, and Valo) in different curing modes. Immediately after extraction, the pulp chamber of 11 premolars was accessed from the palatal cervical third of the crown for insertion of fiber Bragg grating (FBG) sensors for temperature measurement and kept in a 37.0° water bath. The teeth were then submitted to a random sequence of curing modes with four irradiations at 30 s intervals. Care was taken to ensure complete pulp temperature reset between curing modes. The curing modes were classified as high-energy (above 80 J/cm2) or low-energy (below 40 J/cm2) according to the total energy density delivered. Statistical analysis was performed with repeated ANOVA measures and Pearson’s correlation for the association between energy density and temperature variation. The significance level was set to 0.05. All curing units promoted a statistically significant PT rise (p < 0.01). After four emissions, the PT rise was higher than 5.0 °C for the high-energy curing modes. The low-energy modes induced approximately a 2.5 °C rise. A strong positive correlation was found between energy density and PT increase (R = 0.715; p = 0.01). Exposure of intact premolars to LED LCUs induced significant and cumulative PT rise. Curing modes emitting high energy densities produced higher PT variations. Radiant exposure was positively correlated to PT variation.
Preparative Separation of Diterpene Lactones and Flavones from Andrographis paniculate Using Off-Line Two-Dimensional High-Speed Counter-Current Chromatography

Seven diterpene lactones, andrographolide (1), isoandrographolide (2), neo-andrographolide (3), 14-deoxy-11,12-didehydroandrographolide (4), 14-deoxyandrographiside (5), 14-deoxy-11,12-didehydroandrographiside (6), 3,14-dideoxyandrographolide (10), and three flavones, andrographidine C (7), andrographidine A (8), 5-hydroxy-7,8-dimethoxyflavanone (9) have been successfully and efficiently isolated from A. paniculata using an off-line two dimensional (2D) high-speed counter-current chromatography (HSCCC) method for the first time. For the first dimension HSCCC separation, petroleum ether-ethyl acetate-methanol-water 3:7:5:5 (v/v) was employed to isolate 14.4 mg of compound 1, 3.1 mg of compound 2, 7.8 mg of compound 3, and 18.0 mg of compound 4 from 200 mg of the A. paniculata extract. For the second dimension HSCCC separation, petroleum ether-ethyl acetate-methanol-water 2:8:1:9 (v/v) and 5:5:6:4 (v/v) were employed to isolate the collected fractions ranged from 55 to 79 min and the flow out fraction, respectively, which led to 5.1 mg of compound 5, 4.4 mg of compound 6, 2.4 mg of compound 7, 3.3 mg of compound 8, 4.0 mg of compound 9, 7.0 mg of compound 10. The structures of these diterpene lactones and flavones were elucidated by extensive spectroscopic methods.
Short email with attachment versus long email without attachment when contacting authors to request unpublished data for a systematic review: a nested randomised trial

Objective Systematic reviews often rely on the acquisition of unpublished analyses or data. We carried out a nested randomised trial comparing two different approaches for contacting authors to request additional data for a systematic review. Participants Participants were authors of published reports of prevention or treatment trials in stroke in which there was central adjudication of events. A primary and secondary research active author were selected as contacts for each trial. Interventions Authors were randomised to be sent either a short email with a protocol of the systematic review attached (‘Short’) or a longer email that contained detailed information and without the protocol attached (‘Long’). A maximum of two emails were sent to each author to obtain a response. The unit of analysis was trial, accounting for clustering by author. Primary and secondary outcome measures The primary outcome was whether a response was received from authors. Secondary outcomes included time to response, number of reminders needed before a response was received and whether authors agreed to collaborate. Results 88 trials with 76 primary authors were identified in the systematic review, and of these, 36 authors were randomised to Short (trials=45) and 40 to Long (trials=43). Responses were received for 69 trials. There was no evidence of a difference in response rate between trial arms (Short vs Long, OR 1.10, 95% CI 0.36 to 3.33). There was no evidence of a difference in time to response between trial arms (Short vs Long, HR 0.91, 95% CI 0.55 to 1.51). In total, 27% of authors responded within a day and 22% of authors never responded. Conclusions There was no evidence to suggest that email format had an impact on the number of responses received when acquiring data for a systematic review involving stroke trials or the time taken to receive these responses.
Quantification and discovery of sequence determinants of protein‐per‐mRNA amount in 29 human tissues

Despite their importance in determining protein abundance, a comprehensive catalogue of sequence features controlling protein-to-mRNA (PTR) ratios and a quantification of their effects is still lacking. Here we quantified PTR ratios for 11,575 proteins across 29 human tissues using matched transcriptomes and proteomes. We analyzed the contribution of known sequence determinants of protein synthesis and degradation and 15 novel mRNA and protein sequence motifs that we found by association testing. While the dynamic range of PTR ratios spans more than 2 orders of magnitude, our integrative model predicts PTR ratios at a median precision of 3.2-fold. A reporter assay provided significant functional support for two novel UTR motifs and a proteome-wide competition-binding assay identified motif-specific bound proteins for one motif. Moreover, our direct comparison of protein to RNA levels led to a new metrics of codon optimality. Altogether, this study shows that a large fraction of PTR ratio variance across genes can be predicted from sequence and identified many new candidate post-transcriptional regulatory elements in the human genome.
Innovative Biomaterials for Bone Regrowth

The regenerative medicine, a new discipline that merges biological sciences and the fundamental of engineering to develop biological substitutes, has greatly benefited from recent advances in the material engineering and the role of stem cells in tissue regeneration. Regenerative medicine strategies, involving the combination of biomaterials/scaffolds, cells, and bioactive agents, have been of great interest especially for the repair of damaged bone and bone regrowth. In the last few years, the life expectancy of our population has progressively increased. Aging has highlighted the need for intervention on human bone with biocompatible materials that show high performance for the regeneration of the bone, efficiently and in a short time. In this review, the different aspects of tissue engineering applied to bone engineering were taken into consideration. The first part of this review introduces the bone cellular biology/molecular genetics. Data on biomaterials, stem cells, and specific growth factors for the bone regrowth are reported in this review.
Chlamydia trachomatis infection among patients attending sexual and reproductive health clinics: A cross-sectional study in Bao'an District, Shenzhen, China

This study aimed to estimate the prevalence of chlamydial trachomatis (CT) infection and explore its risk factors among patients attending sexual and reproductive health clinics in Shenzhen, China. We collected demographic and clinical information from attendees (aged 18–49). CT and Neisseria gonorrhoeae (NG) infection was determined by nucleic acid amplification test (NAAT) on self-collected urine specimens. Of 1,938 participants recruited, 10.3% (95% confidence interval [CI]: 9.6%-11.0%) tested positive for CT. Prevalence was similar between men (10.6% [85/804]; 95% CI, 9.5%–11.7%) and women (10.1% [115/1134]; 95% CI: 9.2%–11.0%). Being 18–25 years old (adjusted odds ratio [aOR] = 2.52; 95%CI:1.35–4.71), never tested for CT before (aOR = 2.42; 95%CI: 1.05–5.61) and infected with NG(aOR = 3.87; 95%CI: 2.10–7.10) were independently associated with CT infection. We found that CT infection is prevalent among patients attending sexual and reproductive health clinics in Shenzhen, China. A comprehensive program including CT screening, surveillance and treatment is urgently needed.
High Temperatures and Kidney Disease Morbidity: A Systematic Review and Meta-analysis

Objectives In recent years, serious concerns have been raised regarding the impacts of rising temperatures on health. The present study was conducted to investigate the relationship between elevated temperatures and kidney disease through a systematic review and meta-analysis. Methods In October 2017, 2 researchers independently searched related studies in PubMed and Embase. A meta-analysis was conducted using a random-effects model, including only studies that presented odds ratios, relative risks, or percentage changes, along with 95% confidence intervals (CIs). The characteristics of each study were summarized, and the Egger test and funnel plots were used to evaluate publication bias. Results Eleven studies that met the criteria were included in the final analysis. The pooled results suggest an increase of 30% (95% CI, 20 to 40) in kidney disease morbidity with high temperatures. In a disease-specific subgroup analysis, statistically significant results were observed for both renal colic or kidney stones and other renal diseases. In a study design–specific subgroup analysis, statistically significant results were observed in both time-series analyses and studies with other designs. In a temperature measure–specific subgroup analysis, significant results were likewise found for both studies using mean temperature measurements and studies measuring heat waves or heat stress. Conclusions Our results indicate that morbidity due to kidney disease increases at high temperatures. We also found significant results in subgroup analyses. However, further time-series analyses are needed to obtain more generalizable evidence.