Within-host evolution of a transcriptional regulator contributes to the establishment of chronic Pseudomonas aeruginosa infection.

As an opportunistic pathogen, Pseudomonas aeruginosa can cause both acute and chronic infections that are notoriously difficult to treat. However, the mechanism underlying acute or chronic P. aeruginosa infection remains unclear.

Biocompatible autonomous self-healing PVA-CS/TA hydrogels based on hydrogen bonding and electrostatic interaction.

The biocompatible autonomous self-healing hydrogels have great potential in biomedical applications. However, the fairly weak tensile strength of the hydrogels seriously hinders their application. Here, we introduced chitosan (CS) into the polyvinyl alcohol (PVA)-tannic acid (TA) hydrogel and investigated the effects of the CS content, as CS can not only form reversible H bonds with PVA and TA but also form reversible electrostatic interactions with TA.

Research progress on the performance of expandable systems for long-term gastric retention.

Gastroretentive systems have gained attention due to their prolonged retention time in the human body, and they have the potential to improve treatment effects, simplify treatment regimens, and improve patient compliance. Among these systems, expandable gastroretentive systems (EGRSs) have emerged as an important type of carrier that can reside in the stomach for a desired period through on-demand expansion for drug delivery, obesity intervention, and medical diagnosis. As the physiological environment significantly influences the performance of EGRSs, here, the physiological factors such as the stomach's physiological structure and activity pattern, and the character of gastric juice are summarized.

Advances in structure-based allosteric drug design.

The identification of allosteric binding sites forms a critical connection between structural and computational biology, substantially advancing the discovery of allosteric drugs. However, the prevailing strategies for allosteric drug development predominantly rely on high-throughput screening, which suffers from high failure rates due to a limited understanding of allosteric mechanisms. This review collects insights from case studies on allosteric mechanisms, protein structure databases and computation algorithm developments, aiming to enhance our comprehension of allostery and guide more effective allosteric drug development.

Diagnostic Value of the Ovarian-Adnexal Reporting and Data System Ultrasound in Ovarian Masses: A Two-Center Study.

Objective: This study aimed to assess the diagnostic efficacy of the Ovarian-Adnexal Reporting and Data System (O-RADS) and Ultrasound (US) and its sub-classification system for distinguishing ovarian masses.

Methods: O-RADS US was used for the retrospective analysis of 606 ovarian masses of Chinese from two medical centers by two gynecologic sonographers with varying experience. The O-RADS 4 categories masses were further sub-classified into O-RADS 4a and O-RADS 4 b through three different approaches(O-RADS A1/A2/A3).

Chitosan/polyvinyl alcohol-based magnetic hydrogel microspheres with controlled retention and regulated drug release for intravesical instillation.

As a clinically effective treatment for bladder cancer (BC), intravesical instillation still suffers from the debilitating efficacy triggered by frequent urination. Herein, the magnetic hydrogel microspheres (DOX-mMSs) with the incorporation of magnetic nanoparticles (MNPs) and doxorubicin (DOX) into polyvinyl alcohol (PVA)/chitosan (CS) are developed for intravesical instillation. The magnetic force initiated by the applied magnetic field (AMF) enables the long-term retention of DOX-mMSs in the bladder, and the convenient injection and excretion from the bladder can be accomplished in virtue of the micron size of the DOX-mMSs.

NPR1 promotes cisplatin resistance by inhibiting PARL-mediated mitophagy-dependent ferroptosis in gastric cancer.

Cisplatin-based chemotherapy serves as the standard of care for individuals with advanced stages of gastric cancer. Nevertheless, the emergence of chemoresistance in GC has detrimental impacts on prognosis, yet the underlying mechanisms governing this phenomenon remain elusive. Level of mitophagy and ferroptosis of GC cells were detected by fluorescence, flow cytometry, GSH, MDA, Fe assays, and to explore the specific molecular mechanisms between NPR1 and cisplatin resistance by performing western blot and coimmunoprecipitation (co-IP) assays.

A rising star involved in tumour immunity: Lactylation.

In recent years, continuous exploration worldwide has revealed that some metabolites produced during cellular and tissue metabolism can act as signalling molecules to exert different effects on the human body. These metabolites may act as cofactors for proteases or as post-translational modifications linked to proteins. Lactate, a traditional metabolite, is found at high levels in the tumour microenvironment (TME).

Hydrogel Sensors in an IoT System for Self-Monitoring and Remote Monitoring of Massage Pressure.

The effectiveness of massage can be enhanced if the pressure applied can be monitored continuously. In this study, we described an Internet-of-Things (IoT) system based on hydrogel sensors, which allows for self-monitoring and remote monitoring of massage pressure. The piezoresistive hydrogel with the compressive energy loss coefficient of 15.

Electrical Stimulation Promotes Endocytosis of Magnetic Nanoparticles by Cancer Cells.

Nanomaterials are increasingly used in biomedical imaging and cancer therapy, and how to improve the endocytosis of nanomaterials by cells is a key issue. The application of alternating current (AC) electrical stimulation to osteosarcoma cells (MG-63) here can increase the cellular endocytosis of FeO nanoparticles (diameter: 50 nm) by 52.46% via macropinocytosis.

Thermo-Mechanical Properties and Phase-Separated Morphology of Warm-Mix Epoxy Asphalt Binders with Different Epoxy Resin Concentrations.

The performance and phase-separated microstructures of epoxy asphalt binders greatly depend on the concentration of epoxy resin or bitumen. In this paper, the effect of the epoxy resin (ER) concentration (10-90%) on the viscosity, thermo-mechanical properties, and phase-separated morphology of warm-mix epoxy asphalt binders (WEABs) was investigated using the Brookfield rotational viscometer, differential scanning calorimetry (DSC), dynamic mechanical analysis (DMA) and laser scanning confocal microscopy (LSCM). Due to the high reactivity of epoxy resin, the viscosity of WEABs increases with time.

Polyphenol-mediated hyaluronic acid/tannic acid hydrogel with short gelation time and high adhesion strength for accelerating wound healing.

Wound healing is a complex process involving a complicated interplay between numerous cell types and vascular systems. Hyaluronic acid (HA)-based hydrogel facilitates wound healing, and is involved in all processes. However, slow gelation speed and weak adhesion strength limit its ability to form a stable physical barrier quickly.

Performance and Morphology of Waterborne Polyurethane Asphalt in the Vicinity of Phase Inversion.

Waterborne polyurethane asphalt emulsion (WPUA) is an environmentally friendly bituminous material, whose performance is highly dependent on the phase structure of the continuous phase. In this paper, WPUAs in the vicinity of phase inversion were prepared using waterborne polyurethane (WPU) and asphalt emulsion. The chemical structures, thermal stability, dynamic mechanical properties, phase-separated morphology and mechanical performance of WPUAs were studied.

Design of novel triply periodic minimal surface (TPMS) bone scaffold with multi-functional pores: lower stress shielding and higher mass transport capacity.

The bone repair requires the bone scaffolds to meet various mechanical and biological requirements, which makes the design of bone scaffolds a challenging problem. Novel triply periodic minimal surface (TPMS)-based bone scaffolds were designed in this study to improve the mechanical and biological performances simultaneously. The novel bone scaffolds were designed by adding optimization-guided multi-functional pores to the original scaffolds, and finite element (FE) method was used to evaluate the performances of the novel scaffolds.

TLTNet: A novel transscale cascade layered transformer network for enhanced retinal blood vessel segmentation.

Extracting global and local feature information is still challenging due to the problems of retinal blood vessel medical images like fuzzy edge features, noise, difficulty in distinguishing between lesion regions and background information, and loss of low-level feature information, which leads to insufficient extraction of feature information. To better solve these problems and fully extract the global and local feature information of the image, we propose a novel transscale cascade layered transformer network for enhanced retinal blood vessel segmentation, which consists of an encoder and a decoder and is connected between the encoder and decoder by a transscale transformer cascade module. Among them, the encoder consists of a local-global transscale transformer module, a multi-head layered transscale adaptive embedding module, and a local context(LCNet) module.

Design, Synthesis, and Biological Evaluation of 1,2,4-Oxadiazole Derivatives Containing an Aryl Carboxylic Acid Moiety as Potent Sarbecovirus Papain-like Protease Inhibitors.

Papain-like protease (PLpro) is a promising therapeutic target for its pivotal role in the life cycle of SARS-CoV-2. A series of 1,2,4-oxadiazole derivatives was designed and synthesized via a ring formation strategy based on SARS-CoV-2 PLpro-GRL0617 complex structure. Systematic structure-activity relationship studies revealed that introducing oxadiazole and aryl carboxylic acid moieties to GRL0617 enhanced the enzymatic inhibition activity, affinity, and deubiquitination capacity toward PLpro.

A role for the C. elegans Argonaute protein CSR-1 in small nuclear RNA 3' processing.

The Integrator is a multi-subunit protein complex that catalyzes the maturation of snRNA transcripts via 3' cleavage, a step required for snRNA incorporation with snRNP for spliceosome biogenesis. Here we developed a GFP based in vivo snRNA misprocessing reporter as a readout of Integrator function and performed a genome-wide RNAi screen for Integrator regulators. We found that loss of the Argonaute encoding csr-1 gene resulted in widespread 3' misprocessing of snRNA transcripts that is accompanied by a significant increase in alternative splicing.

Chemical Genetics in Identifies Anticancer Mycotoxins Chaetocin and Chetomin as Potent Inducers of a Nuclear Metal Homeostasis Response.

(clear-localized etal-esponsive) is an identical gene pair encoding a nuclear protein previously shown to be activated by cadmium and disruption of the integrator RNA metabolism complex. We took a chemical genetic approach to further characterize regulation of this novel metal response by screening 41,716 compounds and extracts for activation. The most potent activator was chaetocin, a fungal 3,6-epidithiodiketopiperazine (ETP) with promising anticancer activity.

Cerastecins inhibit membrane lipooligosaccharide transport in drug-resistant Acinetobacter baumannii.

Carbapenem-resistant Acinetobacter baumannii infections have limited treatment options. Synthesis, transport and placement of lipopolysaccharide or lipooligosaccharide (LOS) in the outer membrane of Gram-negative bacteria are important for bacterial virulence and survival. Here we describe the cerastecins, inhibitors of the A.

NAMPT/NAD/PARP1 Pathway Regulates CFA-Induced Inflammatory Pain via NF-κB Signaling in Rodents.

Emerging evidence has implicated nicotinamide adenine dinucleotide (NAD) metabolism in various inflammatory diseases. In the study, the role of NAD metabolism in Complete Freund's Adjuvant (CFA)-evoked inflammatory pain and the underlying mechanisms are investigated. The study demonstrated that CFA induced upregulation of nicotinamide phosphoribosyltransferase (NAMPT) in dorsal root ganglia (DRG) without significant changes in the spinal cord.