The causal effects of atopic dermatitis on the risk of skin cancers: A two-sample Mendelian randomization study.

BACKGROUND: Observational and epidemiological studies show conflicting results on the relationship between atopic dermatitis and skin cancer. Additionally, observational studies are susceptible to the reverse causation and confounders, thus, may not interpret true causal relationships. The causal effects of atopic dermatitis on the risk of skin cancers remains unclear. OBJECTIVES: To investigate the causal relationship between atopic dermatitis and skin cancer including cutaneous malignant melanoma, cutaneous squamous cell carcinoma, basal cell carcinoma and actinic keratosis. METHODS: We performed a two-sample Mendelian randomization analysis based on summary datasets of public genome-wide association studies of European ancestry. The inverse variance-weighted approach was applied as the main analysis. MR-Egger and weighted median methods were used to complement the inverse variance-weighted results. A series of sensitivity analyses were used to ensure the robustness of the causality estimates. RESULTS: Inverse variance-weighted method showed that genetically predicted dermatitis patients were significantly associated with an increased incidence of basal cell carcinoma (OR, 1.20; 95% CI, 1.10-1.31; p = 4.07E-05) and cutaneous squamous cell carcinoma (OR, 1.14; 95% CI, 1.10-1.19; p = 1.05E-11). However, we did not find a significant causality for atopic dermatitis on melanoma neither did we find actinic keratosis. Subsequent sensitive analyses supported these results. CONCLUSIONS: Our study identified the causality between atopic dermatitis basal cell carcinoma and squamous cell carcinoma. Accordingly, regular skin cancer screening is recommended for patients with atopic dermatitis.

Mercury adsorption study and DFT calculations of sulfur-containing biomass composites prepared by inverse vulcanization.

This study introduces an innovative and cost-effective biomass adsorbent, the sulfur/cardanol/potato starch composite (SCP), synthesized through inverse vulcanization for the remediation of mercury-contaminated waters. The SCP was characterized using Scanning Electron Microscopy/Energy Dispersive Spectroscopy (SEM/EDS), Fourier Transform Infrared Spectroscopy (FT-IR), Thermogravimetric Analysis (TGA) and X-ray Diffraction (XRD) to confirm its composition, morphology, and properties. The adsorption capacity of SCP for Hg(II) was 246.88 mg/g with a removal rate of 98.75 %. Adsorption kinetics followed a pseudo-second-order model, indicating chemisorption as the dominant mechanism, while adsorption isotherms were best described by the Langmuir model. Thermodynamic studies confirmed the adsorption process as spontaneous and endothermic. Density Functional Theory (DFT) calculations further elucidate the interaction mechanisms between mercury and the adsorbent, revealing that the thiyl radicals play a crucial role in the adsorption process. The SCP also exhibited a high selectivity for Hg(II) over other co-existing ions and maintains an adsorption capacity over 223.93 mg/g after five regeneration cycles, thus promising practical applications in environmental mercury management.

Comparative efficacy and safety of JAK/TYK2 inhibitors and other oral drugs for moderate-to-severe plaque psoriasis: Systematic review and network meta-analysis.

Background Janus kinase (JAK)/tyrosine kinase 2 (TYK2) inhibitors are novel treatments for moderate-to-severe plaque psoriasis. Objective To perform a network meta-analysis to compare the efficacy and safety of TYK2 inhibitors with other oral drugs in moderate-to-severe psoriasis. Methods Eligible randomised clinical trials (RCTs) were identified from public databases (published before November 2, 2023). Random-effect frequentist network meta-analysis was performed with ranking based on the surface under the cumulative ranking curve (SUCRA) of Physician's Global Assessment of "clear" or "almost clear" (PGA 0/1), 75% reduction from baseline in Psoriasis Area and Severity Index (PASI-75). Results Twenty RCTs containing 7,564 patients with moderate-to-severe psoriasis were included. Deucravacitinib at all dose levels (except for 3 mg every other day) and tofacitinib (10 mg BID) ranked best in achieving PGA 0/1 and PASI-75 at 12- 16 weeks. Tofacitinib (10 mg BID) was considered the most unsafe. Analysis of Ranking according to efficacy and safety showed deucravacitinib (3 mg QD and 3 mg BID) was the best treatment. Analysis of Ranking according to efficacy and safety showed deucravacitinib (3 mg QD and 3 mg BID) was the best treatment. Limitation Insufficiency of eligible data and no long-term follow-up data. Conclusion Deucravacitinib showed superior efficacy and safety for treating moderate-to-severe psoriasis over other included drugs.

High Performance and Reprocessable In Situ Generated Nanofiber Reinforced Composites Based on Liquid Crystal Polyarylate.

Polymers are playing important roles in the rapid development of triboelectric nanogenerators (TENGs); However, most polymers cannot meet the high requirements of thermomechanical performance; Thus, various polymeric composites are developed for triboelectric layer. These composites are hardly recycled since their reinforcements are unevenly distributed after reprocessing, which limits the sustainable development of TENGs. To solve the above challenges, in situ generated nanofiber reinforced composites (NFRCs) based on single-component liquid crystal polyarylate (LCP) are designed and prepared via a one-step polycondensation. Nonlinear naphthalene (NDA) widens the processing window of LCP without destabilizing the liquid crystal phase. The NDA-rich domains act as a matrix while the NDA-poor domains with higher rigidity form oriented nanofibers to achieve self-reinforcement. The resultant NFRCs possess high glass transition temperature (Tg > 220 °C) and storage modulus (E' = 0.1 GPa at 350 °C), which are far beyond existing triboelectric polymers, typically Tg < 110 °C and E' < 0.1 MPa (flowable) at 350 °C. Furthermore, NFRC-based TENG exhibits superior electrical output performance and retention rate (>90%) after reprocessing; Overall, this work offers a new design principle to prepare self-reinforced composites, which paves a way to explore high performance materials.

V4RIN: visual analysis of regional industry network with domain knowledge.

The regional industry network (RIN) is a type of financial network derived from industry networks that possess the capability to describe the connections between specific industries within a particular region. For most investors and financial analysts lacking extensive experience, the decision-support information provided by industry networks may be too vague. Conversely, RINs express more detailed and specific industry connections both within and outside the region. As RIN analysis is domain-specific and current financial network analysis tools are designed for generalized analytical tasks and cannot be directly applied to RINs, new visual analysis approaches are needed to enhance information exploration efficiency. In this study, we collaborated with domain experts and proposed V4RIN, an interactive visualization analysis system that integrates predefined domain knowledge and data processing methods to support users in uploading custom data. Through multiple views in the system panel, users can comprehensively explore the structure, geographical distribution, and spatiotemporal variations of the RIN. Two case studies were conducted and a set of expert interviews with five domain experts to validate the usability and reliability of our system.

The cAMP receptor protein gene contributes to growth, stress resistance, and colonization of Actinobacillus pleuropneumoniae.

Porcine infectious pleuropneumonia (PCP) is a severe disease of porcine caused by Actinobacillus pleuropneumoniae (APP). The spread of PCP remains a threat to the porcine farms and has been known to cause severe economic losses. The cAMP receptor protein (CRP) serves as a pivotal player in helping bacteria adapt to shifts in their environment, particularly when facing the challenges posed by bacterial infections. In this study, we investigated the role of CRP in APP. Our results revealed that crp mutant (Δcrp) strains were more sensitive to acidic and osmotic stress resistance and had lower biofilm formation ability than wild-type (WT) strains. Furthermore, the Δcrp strains showed deficiencies in anti-phagocytosis, adhesion, and invasion upon interaction with host cells. Mice infected with the Δcrp strains demonstrated reduced bacterial loads in their lungs compared to those infected with the WT strains. This study reveals the pivotal role of crp gene expression in regulating pleuropneumonia growth, stress resistance, iron utilization, biofilm formation, phagocytosis, adhesion, invasion and colonization. Our discoveries offer novel perspectives on understanding the development and progression of APP infections.

Undetectable off-target effects induced by FokI catalytic domain in mouse embryos.

The FokI catalytic domain can be fused to various DNA binding architectures to improve the precision of genome editing tools. However, evaluation of off-target effects is essential for developing these tools. We use Genome-wide Off-target analysis by Two-cell embryo Injection (GOTI) to detect low-frequency off-target editing events in mouse embryos injected with FokI-based architectures. Specifically, we test FokI-heterodimers fused with TALENs, FokI homodimers fused with RYdCas9, or FokI catalytic domains alone resulting in no significant off-target effects. These FokI genome editing systems exhibit undetectable off-target effects in mouse embryos, supporting the further development of these systems for clinical applications.

Successful treatment of classic Kaposi sarcoma with Trichophyton rubrum-infected onychomycosis and tinea pedis utilizing combination of oral itraconazole and thalidomide.

Kaposi sarcoma (KS) is a vascular proliferative tumor caused by human herpesvirus 8. At present, the treatment of KS is difficult and refractory. Here, we report a 68-year-old man who was diagnosed with a classical KS with tinea pedis and onychomycosis, infected by Trichophyton rubrum, and treated with itraconazole and thalidomide after locational excision of several bigger nodules. The lesions were relieved during treatment, and recurred after discontinuation. Retreatment still achieved good effect and the therapy was tapered down after control. After the whole course of treatment, the skin lesions subsided significantly without obvious adverse reactions, which showed that itraconazole combined with thalidomide may be another effective and safe treatment for KS in some cases.

Integrated proteomic and metabolomic profiling of urine of renal anemia patients uncovers the molecular mechanisms of roxadustat.

Roxadustat (FG-4592) is a hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) prescribed to patients with low hemoglobin associated with chronic kidney disease. Due to the various HIF-mediated adaptive responses, FG-4592 has attracted significant interest for therapeutic use against various diseases. However, the clinical application of Roxadustat remains limited due to a lack of understanding of its underlying mechanisms. Herein, we performed label-free quantitative liquid chromatography with tandem mass spectrometry (LC-MS-MS) proteomics and un-targeted metabolomics to study the protein and metabolite alterations in the urine of renal anemia patients before and after Roxadustat therapy. The results were validated by parallel reaction monitoring (PRM). A total of 46 proteins (including 15 upregulated and 31 downregulated proteins) and 207 metabolites were significantly altered after Roxadustat treatment in urine samples obtained from renal anemia patients. Then, the altered proteins were further validated by PRM. Finally, proteomics combined with metabolomics analysis revealed that the Ras signalling pathway, cysteine and methionine metabolism, arginine and proline metabolism, and cholesterol metabolism were the main pathways altered by Roxadustat treatment. The multi-omics analysis revealed that Roxadustat could alter the protein expression and reverse the potential metabolic changes to exert hypotensive, lipid metabolic regulation, and renoprotective effects in clinical practice.

High-Performance Liquid Crystalline Polymer for Intrinsic Fire-Resistant and Flexible Triboelectric Nanogenerators.

Flammability is a great challenge in the fields of electronics. The emergence of triboelectric nanogenerators (TENGs) provides a safe way to harvest environmentalally friendly energy and convert it into more secure power sources. Especially, polymer-based TENGs significantly accelerate the practical application of self-powered flexible electronics. However, most of the existing polymeric materials for TENGs are easily flammable and melt, dripping, in a fire scenario, and cannot be reused after combustion, which greatly limits the application of TENGs under extreme conditions. Herein, a fire-resistant TENG based on all-aromatic liquid crystalline poly(aryl ether ester) (LCPAEE ) synthesized via simple and efficient one-pot melt polycondensation is reported. The highly rigid main chain of LCPAEE endows the LCP-TENG with outstanding anti-dripping, temperature- and fire-resistance. The resultant LCP-TENG exhibits excellent electrical output performance, which is attributed to the high dielectric constant (ε' = 4.8) and fibrous-structured morphology of LCPAEE . The device can maintain over 65% of open-circuit voltage even after 16 s combustion (≈520 °C). Consequently, this work offers a novel strategy for tailoring the TENGs toward a secure power generator and electronics with fire hazard reduction, and potential application in firefighting, personal protection, and other extreme temperature environments.