Discovery of Cyclic Peptide Inhibitors Targeted on TNFα-TNFR1 from Computational Design and Bioactivity Verification.

Activating tumor necrosis factor receptor 1 (TNFR1) with tumor necrosis factor alpha (TNFα) is one of the key pathological mechanisms resulting in the exacerbation of rheumatoid arthritis (RA) immune response. Despite various types of drugs being available for the treatment of RA, a series of shortcomings still limits their application. Therefore, developing novel peptide drugs that target TNFα-TNFR1 interaction is expected to expand therapeutic drug options.

Assessing physical fitness adaptations in collegiate male soccer players through training load parameters: a two-arm randomized study on combined small-sided games and running-based high-intensity interval training.

Objective: To evaluate the effects of a 4-week intervention combining small-sided games (SSGs) and high-intensity interval training (HIIT) on physical fitness in collegiate male soccer players.

Methods: Twenty-one soccer players were randomly assigned to either the HIIT + SSGs group (n = 11) or a control group (n = 10). Physical fitness was assessed at baseline and 1-week post-intervention, including countermovement jump (CMJ), change of direction (COD) test, sprint test, repeated sprint ability (RSA) test, and 30-15 Intermittent Fitness Test (30-15IFT).

Hot Workability and Microstructure Evolution of Homogenized 2050 Al-Cu-Li Alloy during Hot Deformation.

For this article, hot compression tests were carried out on homogenized 2050 Al-Cu-Li alloys under different deformation temperatures and strain rates, and an Arrhenius-type constitutive model with strain compensation was established to accurately describe the alloy flow behavior. Furthermore, thermal processing maps were created and the deformation mechanisms in different working regions were revealed by microstructural characterization. The results showed that most of the deformed grains orientated toward <101>//CD (CD: compression direction) during the hot compression process, and, together with some dynamic recovery (DRV), dynamic recrystallization (DRX) occurred.

Associations between cardiorespiratory fitness and executive function in Chinese adolescents.

Executive function (EF) has a significant impact on career achievement in adolescence and later adulthood, and there are many factors that influence EF. Cardiorespiratory fitness (CRF) is an important factor in the physical fitness of adolescents and is of great significance to healthy development. However, the current association between CRF and EF in Chinese adolescents is still unclear.

Unilateral Plyometric Jump Training Shows Significantly More Effective than Bilateral Training in Improving Both Time to Stabilization and Peak Landing Force in Single-Leg Lend and Hold Test: A Randomized Multi-Arm Study Conducted Among Young Male Basketball Players.

Enhancing peak landing forces and ensuring faster stabilization in the lower limbs during jumping activities can significantly improve performance and decrease the risk of injury among basketball players. This study aimed to compare the effects of unilateral (uPJT) and bilateral plyometric jump training (bPJT) programs on various performance measures, including countermovement jump (CMJ), squat jump (SJ), and single-leg land and hold (SLLH) test outcomes, assessed using force plates. A randomized multi-arm study design was employed, comprising two experimental groups (n = 25; uPJT and n = 25; bPJT) and one control group (n = 25), conducted with youth male regional-level basketball players (16.

Higher final speed in 30-15 intermittent fitness tests correlates with soccer's locomotor demands, not heart rate responses in small-sided soccer games.

This study aimed to achieve two objectives: firstly, to analyze the relationships between aerobic fitness, as represented by the VIFT, and the heart rate and locomotor responses of youth male soccer players across various teams; and secondly, to compare players with lower and higher VIFT in terms of performance outcomes extracted during small-sided games (SSGs). A total of twenty-six youth male soccer players, aged 16.5 ± 0.

Correction: Antimicrobial peptide-modified silver nanoparticles for enhancing the antibacterial efficacy.

[This corrects the article DOI: 10.1039/D0RA05640E.].

Targeted delivery of NO donor and ROS scavenger for synergistic treatment of rheumatoid arthritis.

Rheumatoid arthritis (RA) is characterized by high level of reactive oxygen species (ROS) and proinflammatory cytokines, which facilitate the activation of the inflammatory signaling such as NF-κB pathway and exacerbate the development of inflammation. Herein, we designed a nanodrug by encapsulating the NO donor S-nitrosoglutathione (GSNO) into an emulsion and coating the surface with a polydopamine (PDA) layer to yield GSNO@PDA, which simultaneously scavenged the extra ROS and suppressed NF-κB signaling for potent RA treatment. To enhance the cellular uptake and NO generation efficiency, dextran sulfate (DS) and Cu were anchored on the surface of GSNO@PDA to obtain the final formulation GSNO@PDA@DS.

Effects of small-sided games training programs on physiological and physical adaptations of youth basketball players: A systematic review.

The primary objective of this study was to systematically investigate the physiological and physical fitness adaptations resulting from small-sided games (SSGs) training programs in basketball players competing at youth competitive levels, as compared to other training approaches and/or control groups. To achieve this, we conducted a literature search on PubMed, Scopus, SPORTDiscus, and Web of Science, adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. From the initial 626 studies retrieved, five were considered eligible for the current study.

Dual-targeting inhibition of TNFR1 for alleviating rheumatoid arthritis by a novel composite nucleic acid nanodrug.

Selective suppression of tumor necrosis factor (TNF) α-TNF receptor 1 (TNFR1) signaling is a potent solution for rheumatoid arthritis (RA). Herein, novel composite nucleic acid nanodrugs that simultaneously restrain TNF α binding and TNFR1 multimerization were designed to reinforce inhibition of TNF α-TNFR1 signaling for RA therapy. Towards this end, a novel peptide Pep4-19 that suppresses TNFR1 clustering was extracted from TNFR1.

Palladium/Silver Cocatalyzed Divergent Dimerization of 2-Azirines for Regioselective Synthesis of Tetrasubstituted Pyrroles and Pyrimidines.

The unprecedented dimerizations of 2-azirines have been developed under the catalysis of palladium and silver. Upon changing the reaction conditions, the fully aryl-substituted pyrrole and pyrimidine derivatives were furnished in moderate yields with regiospecificity, respectively. Control experiments uncovered distinct catalytic effects of two transition metals, and the proposed catalytic cycles plausibly rationalized the chemodivergence and regioselectivity.

Modular Synthesis of Tetrasubstituted Pyrroles via an Annulative Migration Reaction of Allenyl Ketones and -Toluenesulfonylmethyl Isocyanide.

The metal-free cyclization of allenyl ketones and -toluenesulfonylmethyl isocyanide (TosMIC), promoted by CsCO, provides a convenient access to tetrasubstituted pyrroles in which an acyl group undergoes 1,2-migration. This tandem Michael addition/annulative migration synthetic strategy is general and high-yielding for various substituted allenyl ketones. Moreover, a phosphoryl or ester moiety is also a suitable functionality to enable such migration.

Association between Dairy Consumption and Psychological Symptoms: Evidence from a Cross-Sectional Study of College Students in the Yangtze River Delta Region of China.

Background: Assessing the dairy consumption and psychological symptoms of Chinese college students as a reference for the mental health of Chinese college students.

Methods: A three-stage stratified whole-group sampling method was used to investigate dairy consumption and psychological symptoms among 5904 (2554 male students, accounting for 43.3% of the sample) college students in the Yangtze River Delta region.

Targeting Tumor Necrosis Factor Receptor 1 with Selected Aptamers for Anti-Inflammatory Activity.

Tumor necrosis factor-α (TNFα) inhibitors are widely used in treating autoimmune diseases like rheumatoid arthritis (RA). These inhibitors can presumably alleviate RA symptoms by blocking TNFα-TNF receptor 1 (TNFR1)-mediated pro-inflammatory signaling pathways. However, the strategy also interrupts the survival and reproduction functions conducted by TNFα-TNFR2 interaction and causes side effects.

Electron transfer-based antioxidant nanozymes: Emerging therapeutics for inflammatory diseases.

Inflammatory diseases are usually featured with relatively high level of reactive oxygen species (ROS). The excess ROS facilitate the polarization of microphages into proinflammatory M1 phenotype, and cause DNA damage, protein carbonylation, and lipid peroxidation, resulting in further deterioration of inflammatory diseases. Therefore, alleviating oxidative stress by ROS scavenging has been an effective strategy for reversing inflammation.

Stimulus-responsive and dual-target DNA nanodrugs for rheumatoid arthritis treatment.

Tumor necrosis factor receptor-1 (TNFR1) and DEK are closely associated with the development of rheumatoid arthritis (RA). Taking advantage of the high adenosine triphosphate (ATP) in RA microenvironment and the interactions of DNA aptamers with their targets, an ATP-responsive DNA nanodrug was constructed that simultaneously targets TNFR1 and DEK for RA therapy. To this end, DEK target aptamer DTA and TNFR1 target aptamer Apt1-67 were equipped with sticky ends to hybridize with ATP aptamer (Apt) and fabricated DNA nanodrug DAT.

Catalytic DNA-Assisted Mass Production of Arbitrary Single-Stranded DNA.

Synthetic single-stranded (ss) DNA is a cornerstone for life and materials science, yet the purity, quantity, length, and customizability of synthetic DNA are still limiting in various applications. Here, we present PECAN, paired-end cutting assisted by DNAzymes (DNA enzymes or deoxyribozymes), which enables mass production of ssDNA of arbitrary sequence (up to 7000 nucleotides, or nt) with single-base precision. At the core of PECAN technique are two newly identified classes of DNAzymes, each robustly self-hydrolyzing with minimal sequence requirement up- or down-stream of its cleavage site.

PBA functionalized single-atom Fe for efficient therapy of multidrug-resistant bacterial infections.

The abuse of antibiotics has led to the emergence of multidrug-resistant bacterial strains worldwide, which greatly threatens human health. In the present work, we developed single-atom catalysts (SACs) with atomically dispersed Fe as catalytic sites (Fe-SACs) to combat multidrug-resistant bacteria by elevating cellular reactive oxygen species (ROS). Our intensive studies confirmed that Fe-SACs were successfully prepared and exhibited excellent catalase (CAT)-, oxidase (OXD)-, and peroxidase (POD)-like activities.

Protein DEK and DTA Aptamers: Insight Into the Interaction Mechanisms and the Computational Aptamer Design.

By blocking the DEK protein, DEK-targeted aptamers (DTAs) can reduce the formation of neutrophil extracellular traps (NETs) to reveal a strong anti-inflammatory efficacy in rheumatoid arthritis. However, the poor stability of DTA has greatly limited its clinical application. Thus, in order to design an aptamer with better stability, DTA was modified by methoxy groups (DTA_OMe) and then the exact DEK-DTA interaction mechanisms were explored through theoretical calculations.

Dual-Drug Loaded Separable Microneedles for Efficient Rheumatoid Arthritis Therapy.

Although the inhibitors of the interleukin-6 receptor (IL-6R) and tumor necrosis factor-α (TNF-α) have achieved a certain success in the clinical treatment of rheumatoid arthritis (RA), great effort should be made to overcome side effects and to improve patient compliance. The present research aimed to address these problems by the co-delivery of tocilizumab (TCZ)-an inhibitor of IL-6R-and an aptamer Apt1-67, which specifically inhibits TNF receptor 1 via separable microneedles (MN). MN were featured with a sustained release of TCZ from needle tips and a rapid release of Apt1-67 from needle bodies by using methacrylate groups grafted hyaluronic acid as the fillings of needle tips and polyvinyl alcohol/polyvinyl pyrrolidone as the fillings of needle bodies.

Co-delivery of triamcinolone acetonide and verapamil for synergistic treatment of hypertrophic scars via carboxymethyl chitosan and Bletilla striata polysaccharide-based microneedles.

Hypertrophic scar (HS) is a frequently diagnosed skin disease that is difficult to treat. HS is usually associated with itching and pain and causes both physical and psychological issues. In this study, a safe, convenient, and efficient therapy for HS is developed.

Synthesis of Trisubstituted Furans via Copper(I)-Catalyzed Strain-Driving Cycloisomerization/Annulative Fragmentation.

The formed furan-fused cyclobutenes via Cu(I)-catalyzed cycloisomerization of readily available allenyl ketones bearing a cyclopropyl moiety are a highly reactive and powerful species, which undergo annulative fragmentation with terminal ynones to afford a wide variety of functional furans in moderate to high yields. This ring-distortion protocol features an unprecedented strain-controlled cycloisomerization/Diels-Alder/retro-Diels-Alder (CDRD) sequence under mild conditions.

Nucleic Acids for Potential Treatment of Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a common systemic inflammatory autoimmune disease that severely affects the life quality of patients. Current therapeutics in clinic mainly focus on alleviating the development of RA or relieving the pain of patients. The emerging biological disease-modifying antirheumatic drugs (DMARDs) require long-term treatment to achieve the expected efficacy.

DNA nanotechnology-facilitated ligand manipulation for targeted therapeutics and diagnostics.

Ligands, mostly binding to proteins to form complexes and catalyze chemical reactions, can serve as drug and probe molecules, as well as sensing elements. DNA nanotechnology can integrate the high editability of DNA nanostructures and the biological activity of ligands into functionalized DNA nanostructures in a manner of controlled ligand stoichiometry, type, and arrangement, which provides significant advantages for targeted therapeutics and diagnostics. As therapeutic agents, multiple- and multivalent-ligands functionalized DNA nanostructures increase ligand-receptor affinity and activate multivalent ligand-receptor interactions, enabling improved regulation of cell signaling and enhanced control of cell behavior.