WS2 as a saturable absorber for ultrafast photonic applications of mode-locked and Q-switched lasers

Two-dimensional (2D) nanomaterials, especially the transition metal sulfide semiconductors, have drawn great interests due to their potential applications in viable photonic and optoelectronic devices, such as saturable absorbers (SAs) and optical switches, etc. In this work, tungsten disulfide (WS2) based SA for ultrafast photonic applications was demonstrated. WS2 nanosheets were prepared using liquid-phase exfoliation method and embedded in polyvinyl alcohol (PVA) thin film for the practical usage. Saturable absorption was observed in the WS2-PVA SA at the telecommunication waveband near 1550 nm. By incorporating WS2-PVA SA into a fiber laser cavity, both stable mode locking operation and Q-switching operation were achieved. In the mode locking operation, the laser obtained femtosecond output pulse width and high spectral purity in the radio frequency spectrum. In the Q-switching operation, the laser had tunable repetition rate and output pulse energy of a few tens of nano joule. Our findings suggest that few-layer WS2 nanosheets embedded in PVA thin film are promising nonlinear optical materials for ultrafast photonic applications as a mode locker or Q-switcher.Comment: 15 pages, 6 figure

Structural implication of splicing stochastics

Even though nearly every human gene has at least one alternative splice form, very little is so far known about the structure and function of resulting protein products. It is becoming increasingly clear that a significant fraction of all isoforms are products of noisy selection of splice sites and thus contribute little to actual functional diversity, and may potentially be deleterious. In this study, we examine the impact of alternative splicing on protein sequence and structure in three datasets: alternative splicing events conserved across multiple species, alternative splicing events in genes that are strongly linked to disease and all observed alternative splicing events. We find that the vast majority of all alternative isoforms result in unstable protein conformations. In contrast to that, the small subset of isoforms conserved across species tends to maintain protein structural integrity to a greater extent. Alternative splicing in disease-associated genes produces unstable structures just as frequently as all other genes, indicating that selection to reduce the effects of alternative splicing on this set is not especially pronounced. Overall, the properties of alternative spliced proteins are consistent with the outcome of noisy selection of splice sites by splicing machinery

Evasion of anti-growth signaling: a key step in tumorigenesis and potential target for treatment and prophylaxis by natural compounds

The evasion of anti-growth signaling is an important characteristic of cancer cells. In order to continue to proliferate, cancer cells must somehow uncouple themselves from the many signals that exist to slow down cell growth. Here, we define the anti-growth signaling process, and review several important pathways involved in growth signaling: p53, phosphatase and tensin homolog (PTEN), retinoblastoma protein (Rb), Hippo, growth differentiation factor 15 (GDF15), AT-rich interactive domain 1A (ARID1A), Notch, insulin-like growth factor (IGF), and Krüppel-like factor 5 (KLF5) pathways. Aberrations in these processes in cancer cells involve mutations and thus the suppression of genes that prevent growth, as well as mutation and activation of genes involved in driving cell growth. Using these pathways as examples, we prioritize molecular targets that might be leveraged to promote anti-growth signaling in cancer cells. Interestingly, naturally-occurring phytochemicals found in human diets (either singly or as mixtures) may promote anti-growth signaling, and do so without the potentially adverse effects associated with synthetic chemicals. We review examples of naturally-occurring phytochemicals that may be applied to prevent cancer by antagonizing growth signaling, and propose one phytochemical for each pathway. These are: epigallocatechin-3-gallate (EGCG) for the Rb pathway, luteolin for p53, curcumin for PTEN, porphyrins for Hippo, genistein for GDF15, resveratrol for ARID1A, withaferin A for Notch and diguelin for the IGF1-receptor pathway. The coordination of anti-growth signaling and natural compound studies will provide insight into the future application of these compounds in the clinical setting

Global, regional, and national incidence of six major immune-mediated inflammatory diseases: findings from the global burden of disease study 2019

BACKGROUND: The causes for immune-mediated inflammatory diseases (IMIDs) are diverse and the incidence trends of IMIDs from specific causes are rarely studied. The study aims to investigate the pattern and trend of IMIDs from 1990 to 2019. METHODS: We collected detailed information on six major causes of IMIDs, including asthma, inflammatory bowel disease, multiple sclerosis, rheumatoid arthritis, psoriasis, and atopic dermatitis, between 1990 and 2019, derived from the Global Burden of Disease study in 2019. The average annual percent change (AAPC) in number of incidents and age standardized incidence rate (ASR) on IMIDs, by sex, age, region, and causes, were calculated to quantify the temporal trends. FINDINGS: In 2019, rheumatoid arthritis, atopic dermatitis, asthma, multiple sclerosis, psoriasis, inflammatory bowel disease accounted 1.59%, 36.17%, 54.71%, 0.09%, 6.84%, 0.60% of overall new IMIDs cases, respectively. The ASR of IMIDs showed substantial regional and global variation with the highest in High SDI region, High-income North America, and United States of America. Throughout human lifespan, the age distribution of incident cases from six IMIDs was quite different. Globally, incident cases of IMIDs increased with an AAPC of 0.68 and the ASR decreased with an AAPC of −0.34 from 1990 to 2019. The incident cases increased across six IMIDs, the ASR of rheumatoid arthritis increased (0.21, 95% CI 0.18, 0.25), while the ASR of asthma (AAPC = −0.41), inflammatory bowel disease (AAPC = −0.72), multiple sclerosis (AAPC = −0.26), psoriasis (AAPC = −0.77), and atopic dermatitis (AAPC = −0.15) decreased. The ASR of overall and six individual IMID increased with SDI at regional and global level. Countries with higher ASR in 1990 experienced a more rapid decrease in ASR. INTERPRETATION: The incidence patterns of IMIDs varied considerably across the world. Innovative prevention and integrative management strategy are urgently needed to mitigate the increasing ASR of rheumatoid arthritis and upsurging new cases of other five IMIDs, respectively. FUNDING: The Global Burden of Disease Study is funded by the Bill and Melinda Gates Foundation. The project funded by Scientific Research Fund of Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital (2022QN38)

Computational chemistry for graphene-based energy applications: progress and challenges

YesResearch in graphene-based energy materials is a rapidly growing area. Many graphene-based energy applications involve interfacial processes. To enable advances in the design of these energy materials, such that their operation, economy, efficiency and durability is at least comparable with fossil-fuel based alternatives, connections between the molecular-scale structure and function of these interfaces are needed. While it is experimentally challenging to resolve this interfacial structure, molecular simulation and computational chemistry can help bridge these gaps. In this Review, we summarise recent progress in the application of computational chemistry to graphene-based materials for fuel cells, batteries, photovoltaics and supercapacitors. We also outline both the bright prospects and emerging challenges these techniques face for application to graphene-based energy materials in future.vesk

Joint analysis of three genome-wide association studies of esophageal squamous cell carcinoma in Chinese populations

We conducted a joint (pooled) analysis of three genome-wide association studies (GWAS) 1-3 of esophageal squamous cell carcinoma (ESCC) in ethnic Chinese (5,337 ESCC cases and 5,787 controls) with 9,654 ESCC cases and 10,058 controls for follow-up. In a logistic regression model adjusted for age, sex, study, and two eigenvectors, two new loci achieved genome-wide significance, marked by rs7447927 at 5q31.2 (per-allele odds ratio (OR) = 0.85, 95% CI 0.82-0.88; P=7.72x10−20) and rs1642764 at 17p13.1 (per-allele OR= 0.88, 95% CI 0.85-0.91; P=3.10x10−13). rs7447927 is a synonymous single nucleotide polymorphism (SNP) in TMEM173 and rs1642764 is an intronic SNP in ATP1B2, near TP53. Furthermore, a locus in the HLA class II region at 6p21.32 (rs35597309) achieved genome-wide significance in the two populations at highest risk for ESSC (OR=1.33, 95% CI 1.22-1.46; P=1.99x10−10). Our joint analysis identified new ESCC susceptibility loci overall as well as a new locus unique to the ESCC high risk Taihang Mountain region

Global, regional, and national incidence of six major immune-mediated inflammatory diseases : findings from the global burden of disease study 2019

DATA SHARING STATEMENT : Data used for the analyses are publicly available from the Institute of Health Metrics and Evaluation (http://www.healthdata.org/; http:// ghdx.healthdata.org/gbd-results-tool).BACKGROUND : The causes for immune-mediated inflammatory diseases (IMIDs) are diverse and the incidence trends of IMIDs from specific causes are rarely studied. The study aims to investigate the pattern and trend of IMIDs from 1990 to 2019. METHODS : We collected detailed information on six major causes of IMIDs, including asthma, inflammatory bowel disease, multiple sclerosis, rheumatoid arthritis, psoriasis, and atopic dermatitis, between 1990 and 2019, derived from the Global Burden of Disease study in 2019. The average annual percent change (AAPC) in number of incidents and age standardized incidence rate (ASR) on IMIDs, by sex, age, region, and causes, were calculated to quantify the temporal trends. FINDINGS : In 2019, rheumatoid arthritis, atopic dermatitis, asthma, multiple sclerosis, psoriasis, inflammatory bowel disease accounted 1.59%, 36.17%, 54.71%, 0.09%, 6.84%, 0.60% of overall new IMIDs cases, respectively. The ASR of IMIDs showed substantial regional and global variation with the highest in High SDI region, High-income North America, and United States of America. Throughout human lifespan, the age distribution of incident cases from six IMIDs was quite different. Globally, incident cases of IMIDs increased with an AAPC of 0.68 and the ASR decreased with an AAPC of −0.34 from 1990 to 2019. The incident cases increased across six IMIDs, the ASR of rheumatoid arthritis increased (0.21, 95% CI 0.18, 0.25), while the ASR of asthma (AAPC = −0.41), inflammatory bowel disease (AAPC = −0.72), multiple sclerosis (AAPC = −0.26), psoriasis (AAPC = −0.77), and atopic dermatitis (AAPC = −0.15) decreased. The ASR of overall and six individual IMID increased with SDI at regional and global level. Countries with higher ASR in 1990 experienced a more rapid decrease in ASR. INTERPRETATION : The incidence patterns of IMIDs varied considerably across the world. Innovative prevention and integrative management strategy are urgently needed to mitigate the increasing ASR of rheumatoid arthritis and upsurging new cases of other five IMIDs, respectively.The Global Burden of Disease Study is funded by the Bill and Melinda Gates Foundation. Support from Scientific Research Fund of Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital; Shaqra University; the School of Pharmacy, University of Botswana; the Indian Council of Medical Research (ICMR); an Australian National Health and Medical Research Council (NHMRC) Investigator Fellowship; the Italian Center of Precision Medicine and Chronic Inflammation in Milan; the Department of Environmental Health Engineering of Isfahan University of Medical Sciences, Isfahan, Iran; National Health and Medical Research Council (NHMRC), Australia; Jazan University, Saudi Arabia; the Clinician Scientist Program of the Clinician Scientist Academy (UMEA) of the University Hospital Essen; AIMST University, Malaysia; the Department of Community Medicine, Kasturba Medical College, Mangalore, Manipal Academy of Higher Education, Manipal, India; a Kornhauser Research Fellowship at The University of Sydney; the National Research, Development and Innovation Office Hungary; Taipei Medical University; CREATE Hope Scientific Fellowship from Lung Foundation Australia; the National Institute for Health and Care Research Manchester Biomedical Research Centre and an NIHR Clinical Lectureship in Respiratory Medicine; Kasturba Medical College, Mangalore and Manipal Academy of Higher Education, Manipal; Author Gate Publications; the Cleveland Clinic Foundation and Nassau University Medical center; the Italian Ministry of Health (RRC); King Abdulaziz University (DSR), Jeddah, and King Abdulaziz City for Science & Technology (KACSAT), Saudi Arabia, Science & Technology Development Fund (STDF), and US-Egypt Science & Technology joint Fund: The Academy of Scientific Research and Technology (ASRT), Egypt; partially supported by the Centre of Studies in Geography and Spatial Planning; the International Center of Medical Sciences Research (ICMSR), Islamabad Pakistan; Ain Shams University and the Egyptian Fulbright Mission Program; the Belgian American Educational Foundation; Health Data Research UK; the Spanish Ministry of Science and Innovation, Institute of Health Carlos III, CIBERSAM, and INCLIVA; the Clinical Research Development Unit, Imam Reza Hospital, Mashhad University of Medical Sciences; Shaqra University; Saveetha Institute of Medical and Technical Sciences and SRM Institute of Science and Technology; University of Agriculture, Faisalabad-Pakistan; the Chinese University of Hong Kong Research Committee Postdoctoral Fellowship Scheme; the institutional support of the Department of Microbiology and Immunology, Faculty of Pharmacy, Zagazig University, Egypt; the European (EU) and Developing Countries Clinical Trials Partnership, the EU Horizon 2020 Framework Programme, UK-National Institute for Health and Care Research, the Mahathir Science Award Foundation and EU-EDCTP.http://www.thelancet.comam2024School of Health Systems and Public Health (SHSPH)SDG-03:Good heatlh and well-bein

HOST FACTOR AND ANTIVIRAL DISCOVERY FOR HUMAN ENTEROVIRUS 71

Ph.DDOCTOR OF PHILOSOPHY (SOM

Vascular underpinning of COVID-19

COVID-19 management guidelines have largely attributed critically ill patients who develop acute respiratory distress syndrome, to a systemic overproduction of pro-inflammatory cytokines. Cardiovascular dysfunction may also represent a primary phenomenon, with increasing data suggesting that severe COVID-19 reflects a confluence of vascular dysfunction, thrombosis and dysregulated inflammation. Here, we first consolidate the information on localized microvascular inflammation and disordered cytokine release, triggering vessel permeability and prothrombotic conditions that play a central role in perpetuating the pathogenic COVID-19 cascade. Secondly, we seek to clarify the gateways which SARS-CoV-2, the causative COVID-19 virus, uses to enter host vascular cells. Post-mortem examinations of patients' tissues have confirmed direct viral endothelial infection within several organs. While there have been advances in single-cell RNA sequencing, endothelial cells across various vascular beds express low or undetectable levels of those touted SARS-CoV-2 entry factors. Emerging studies postulate alternative pathways and the apicobasal distribution of host cell surface factors could influence endothelial SARS-CoV-2 entry and replication. Finally, we provide experimental considerations such as endothelial polarity, cellular heterogeneity in organoids and shear stress dynamics in designing cellular models to facilitate research on viral-induced endothelial dysfunctions. Understanding the vascular underpinning of COVID-19 pathogenesis is crucial to managing outcomes and mortality.Published versio