Efficient and Rapid Enrichment of Extracellular Vesicles Using DNA Nanotechnology-Enabled Synthetic Nano-Glue.

Swift and efficient enrichment and isolation of extracellular vesicles (EVs) are crucial for enhancing precise disease diagnostics and therapeutic strategies, as well as elucidating the complex biological roles of EVs. Conventional methods of isolating EVs are often marred by lengthy and laborious processes. In this study, we introduce an innovative approach to enrich and isolate EVs by leveraging the capabilities of DNA nanotechnology.

Doxazosin Attenuates Development of Testosterone Propionate-induced Prostate Growth by regulating TGF-β/Smad Signaling Pathway, Prostate-specific Antigen Expression and Reversing Epithelial-mesenchymal Transition in Mice and Stroma Cells.

Background: Finasteride and doxazosin are used for the treatment of benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS). Epithelial-mesenchymal transition (EMT) plays an important role in BPH, little is known about the growth inhibition and anti-fibrosis effects of doxazosin on the regulation of EMT and morphology in the prostate.

Objectives: The present study examined the effects of doxazosin on testosterone propionate (TP)-induced prostate growth in vivo and in vitro and its impact on the EMT and TGF-β/Smad signaling pathway.

Probing Deep Hydrogen Polysulfides Fluctuations In Vivo by Engineering Activatable Fluorescence Reporters with Second Near-Infrared Window Emission.

Deep and comprehensive understanding of the intricate biochemical processes mediated by HS ( ≥ 1), but not HS, is of paramount importance. A few fluorescent probes have been developed with the intention of addressing this issue. However, there is currently no evidence of any activatable NIR-II fluorescent probes for HS-specific imaging over HS.

Morpho-molecular analysis of two new species and in Agaricales from Mount Tianmu, China.

Two new species of Agaricales, and , are described from Mount Tianmu, Zhejiang Province, Eastern China. Two new species are distinct and monophyletic based on morphology and phylogenetic analyses. differs from other species in that the pileus is brow shallow in the center and stipe with yellowish white fibrils, scatted on litter under coniferous and broad-leaved mixed forest at 1162 m.

Digital technology and psychological happiness: the mediating roles of interpersonal relationships and employment situations.

Psychological happiness represents the ultimate pursuit of human beings, and the impact of digital technology on psychological happiness is becoming increasingly significant in the era of the digital economy. Based on data from 2020 China Family Panel Studies (CFPS), this study constructs an empirical model that examines the effect and mechanism of digital technology on happiness. Additionally, this study investigates the heterogeneity and robustness of the impact of digital technology on happiness.

Porphyrin-based-MOF nanocomposite hydrogels for synergistic sonodynamic and gas therapy against tumor.

The glioma is one of the most aggressive tumors in humans, which is difficult to eradicate clinically. Therefore, we devised a porphyrin-based metal-organic frameworks (MOFs) crosslinking hyaluronic acid (HA) hydrogel nanocomposite through double-network (Cu-MOF-S-S-HA-Gel, CSSH-Gel), which is tumor responsive for enhanced gas therapy and sonodynamic therapy (SDT). Firstly, the hydrogels show extraordinary injectability and biocompatibility, which enables intratumor administration to circumvent the danger associated with surgery.

Coevolution of specific gut microbiota of Min pig with host cold adaptation through enhanced vitamin B1 synthesis.

Min pigs exhibit remarkable cold tolerance, where vitamin B1 synthesis by gut microbiota is crucial for the host's energy metabolism. However, the role of this synthesis in cold adaptation of Min pigs are not yet fully understood. This study utilized 16S rRNA amplicon and metagenomic sequencing to examine seasonal variations in the gut microbiota of Min pigs.

Design, Synthesis, and Bioevaluation of Novel NLRP3 Inhibitor with IBD Immunotherapy from the Virtual Screen.

NLRP3, a crucial member of the NLRP family, plays a pivotal role in immune regulation and inflammatory modulation. Here, we report a potent and specific NLRP3 inhibitor obtained though docking-based virtual screening and structure-activity relationship studies with an IC of 0.26 μM in THP-1 cells and 0.

Biodegradable Zwitterionic Polymers as PEG Alternatives for Drug Delivery.

Poly(ethylene glycol) (PEG) is a highly biocompatible and water-soluble polymer that is widely utilized for biomedical applications. Unfortunately, the immunogenicity and antigenicity of PEG severely restrict the biomedical efficacy of pegylated therapeutics. As emerging PEG alternatives, biodegradable zwitterionic polymers (ZPs) have attracted significant interest in recent years.

Plasmonic Radiation from Spin-Momentum Locking.

Chiral light emission plays a key role in sensing, tomography, quantum communication, among others. Whereas, achieving highly pure, tunable chirality emission across a broad spectrum currently presents significant challenges. Free-electron radiation emerges as a promising solution to surpass these barriers, especially in hard-to-reach regimes.

Vacancy-engineered Mn-doped iron oxide nano-crystals for enhanced sonodynamic therapy through self-supplied oxygen.

Sonodynamic therapy (SDT) is a minimally invasive therapeutic approach, that uses ultrasound activating sonosensitizers to generate reactive oxygen species (ROS) for inducing the tumor cell death. However, the SDT is always limited by the dissatisfactory performance of sonosensitizers and hypoxic tumor microenvironment (TME). Nano iron oxide is a narrow bandgap semiconductor material with good biocompatibility.

Advanced seismic resilient performance of steel MRF equipped with viscoelastic friction dampers.

This paper demonstrates the enhanced resilience performance of steel structures with viscoelastic friction dampers (VEFDs) based on numerical simulations of building responses. Velocity-dependent dampers, which are widely used to increase seismic resilience, may increase the axial force of the column under strong earthquake conditions because the generated force depends on the interstory velocity. This often leads to plastic hinges being placed on the columns of the structure, which can lead to structural collapse via weak-layer failure.

Dynamic measurement for the impact of project portfolio synergy.

Measuring the impact of project portfolio synergy (PPSI) is crucial for making informed decisions to improve the strategic realization of a project portfolio. However, the literature has failed to measure PPSI effectively from the perspective of project element flow and to explore the differences in synergy relationships between homogeneous and heterogeneous projects. Consequently, this study proposes a framework for measuring PPSI from the perspective of project element flow.

Development and evaluation of immunological effects of a DNA vaccine encoding phosphoketolase family protein against Nocardia seriolae in hybrid snakehead.

Fish nocardiosis is a chronic disease mainly caused by Nocardia seriolae, which occurs in a variety of economically cultured freshwater and marine fish. Studies have shown that DNA vaccine is an effective treatment to protect fish from bacterial infection. In our previous experiment, an in vivo-induced gene of N.

Screening of potentially active compounds against rheumatoid arthritis in the Juan-Bi decoction using systems pharmacology and animal experiments.

The Juan-Bi decoction (JBD) is a classic traditional Chinese medicines (TCMs) prescription for the treatment of rheumatoid arthritis (RA). However, the active compounds of the JBD in RA treatment remain unclear. The aim of this study is to screen effective compounds in the JBD for RA treatment using systems pharmacology and experimental approaches.

FOXCUT regulates the malignant phenotype of triple-negative breast Cancer via the miR-337-3p/ANP32E Axis.

Background: The lack of specific molecular targets and the rapid spread lead to a worse prognosis of triple-negative breast cancer (TNBC). Therefore, identifying new therapeutic and prognostic biomarkers helps to develop effective treatment strategies for TNBC.

Methods: Through preliminary bioinformatics analysis, FOXCUT was found to be significantly overexpressed in breast cancer, especially in TNBC.

The role and mechanism of SUMO modification in liver disease.

Liver disease affects millions of people in the world, and China has the highest prevalence of liver disease in the world. Small ubiquitin-related modifier (SUMO) modification is a highly conserved post-translational modification of proteins. They are widely expressed in a variety of tissues, including the heart, liver, kidney and lung.

Discovery of autophagy-tethering compounds as potent NLRP3 degraders for IBD Immunotherapy.

Nucleotide-binding oligomerization domain-like receptor pyrin domain containing 3 (NLRP3) constitutes an essential inflammasome sensor protein, pivotal in the orchestration of innate immunity. Given its paramount role, NLRP3 has recently emerged as an enticing therapeutic target for disorders associated with inflammation. In this study, we embarked on the design and synthesis of two series of compounds, endowed with the capacity to induce NLRP3 degradation via autophagy-tethering compounds (ATTECs)-an innovative targeted protein degradation technology.

External stakeholder risk response strategies selection in project portfolio.

To improve the effectiveness of external stakeholder risks (ESRs) management in project portfolios (PPs), a portfolio-wide risk response approach is required. However, current research is inadequate to effectively identify response strategies for ESRs, which brings challenges to managing ESRs in PPs. In this context, the purpose of this study is to select an appropriate combination of response strategies for ESRs by considering interactions among ESRs, projects, and response strategies in the PP.

Depletion and Downregulation of Hydrogen Sulfide Using an Activatable Probe for Promoting Photothermal Therapy toward Colorectal Cancers.

Since hydrogen sulfide (HS) is an important endogenous gaseous mediator, therapeutic manipulation of HS is promising for anticancer treatment. In this work, we develop a novel theranostic nanoplatform with HS-specific and photocontrolled synergistic activation for imaging-guided HS depletion and downregulation along with promoted photothermal therapy. Such a nanoplatform is fabricated by integration of a HS-responsive molecule probe that can generate a cystathionine-β-synthase (CBS) inhibitor AOAA and a photothermal transducer into an NIR-light-responsive container.

The promise and challenges of combination therapies with antibody-drug conjugates in solid tumors.

Antibody-drug conjugates (ADCs) represent an important class of cancer therapies that have revolutionized the treatment paradigm of solid tumors. To date, many ongoing studies of ADC combinations with a variety of anticancer drugs, encompassing chemotherapy, molecularly targeted agents, and immunotherapy, are being rigorously conducted in both preclinical studies and clinical trial settings. Nevertheless, combination therapy does not always guarantee a synergistic or additive effect and may entail overlapping toxicity risks.

Spatiotemporal Quantification of HER2-targeting Antibody-Drug Conjugate Bystander Activity and Enhancement of Solid Tumor Penetration.

Purpose: Antibody-drug conjugate (ADC) has had a transformative effect on the treatment of many solid tumors, yet it remains unclear how ADCs exert bystander activity in the tumor microenvironment.

Experimental Design: Here, we directly visualized and spatiotemporally quantified the intratumor biodistribution and pharmacokinetics of different ADC components by developing dual-labeled fluorescent probes.

Results: Mechanistically, we found that tumor penetration of ADCs is distinctly affected by their ability to breach the binding site barrier (BSB) in perivascular regions of tumor vasculature, and bystander activity of ADC can only partially breach BSB.

Targeted Degradation of PCSK9 In Vivo by Autophagy-Tethering Compounds.

Proprotein convertase subtilisin/kexin type-9 (PCSK9), a secreted protein that is synthesized and spontaneously cleaved in the endoplasmic reticulum, has become a hot lipid-lowering target chased by pharmaceutical companies in recent years. Autophagosome-tethering compounds (ATTECs) represent a new strategy to degrade targeted biomolecules. Here, we designed and synthesized PCSK9·ATTECs that are capable of lowering PCSK9 levels via autophagy in vivo, providing the first report of the degradation of a secreted protein by ATTECs.

RSS and ROS Sequentially Activated Carbon Monoxide Release for Boosting NIR Imaging-Guided On-Demand Photodynamic Therapy.

Carbon monoxide shows great therapeutic potential in anti-cancer. In particular, the construction of multifunctional CO delivery systems can promote the precise delivery of CO and achieve ideal therapeutic effects, but there are still great challenges in design. In this work, a RSS and ROS sequentially activated CO delivery system is developed for boosting NIR imaging-guided on-demand photodynamic therapy.