Design, Synthesis, and Biological Evaluation of Thieno[3,2-]pyrimidine Derivatives as the First Bifunctional PI3Kδ Isoform Selective/Bromodomain and Extra-Terminal Inhibitors.

The concomitant inhibition of PI3Kδ and bromodomain and extra-terminal (BET) that exerts a synergistic effect on the B-cell receptor signaling pathway provides a new strategy for the treatment of aggressive diffuse large B-cell lymphoma (DLBCL). Herein, a merged pharmacophore strategy was utilized to discover a series of thieno[3,2-]pyrimidine derivatives as the first-in-class bifunctional PI3Kδ-BET inhibitors. Through optimization, a highly potent compound () was identified to possess excellent and balanced activities against PI3Kδ [inhibitory concentration (IC) = 112 ± 8 nM] and BRD4-BD1 (IC = 19 ± 1 nM) and exhibited strong antiproliferative activities in DLBCL cells.

Whey Protein-Based Hydrogel Microspheres for Endovascular Embolization.

Transarterial embolization (TAE) is an image-guided, minimally invasive procedure for treating various clinical conditions by delivering embolic agents to occlude diseased arteries. Conventional embolic agents focus on vessel occlusion but can cause unintended long-term inflammation and ischemia in healthy tissues. Next-generation embolic agents must exhibit biocompatibility, biodegradability, and effective drug delivery, yet some degradable microspheres degrade too quickly, leading to the potential migration of fragments into distal blood vessels causing off-target embolization.

Tumor burden with AFP improves survival prediction for TACE-treated patients with HCC: An international observational study.

Background & Aims: Current prognostic models for patients with hepatocellular carcinoma (HCC) undergoing transarterial chemoembolization (TACE) are not extensively validated and widely accepted. We aimed to develop and validate a continuous model incorporating tumor burden and biology for individual survival prediction and risk stratification.

Methods: Overall, 4,377 treatment-naive candidates for whom TACE was recommended, from 39 centers in five countries, were enrolled and divided into training, internal validation, and two external validation datasets.

Synergistic Phase and Structural Engineering for Enhanced Zinc Storage in VO@N-Doped Carbon Nanofibers.

Vanadium-based oxide cathodes are promising energy-storage systems for aqueous zinc-ion batteries (AZIBs) because of their high energy density and safety, and low cost. However, their limited ion/electron transfer rates and rapid capacity decay pose challenges to their practical application. To overcome these limitations, VO nanoparticles are developed with surface oxygen vacancies integrated with N-doped carbon nanofibers (VO@NCNFs), using an electrospinning method combined with an in situ oxidation/reduction strategy.

Exploring interactive effects of environmental and microbial factors on food waste anaerobic digestion performance: Interpretable machine learning models.

Biogas yield in anaerobic digestion (AD) involves continuous and complex biological reactions. The traditional linear models failed to quantitatively assess the interactive effects of these factors on AD performance. To further explore the internal relationship between target variables and AD performance, this study developed four machine learning models to predict biogas yield and consider the interaction among various factors.

Application of multimodal deep learning and multi-instance learning fusion techniques in predicting STN-DBS outcomes for Parkinson's disease patients.

Parkinson's Disease (PD) is a progressive neurodegenerative disorder with substantial impact on patients' quality of life. Subthalamic nucleus deep brain stimulation (STN-DBS) is an effective treatment for advanced PD, but patient responses vary, necessitating predictive models for personalized care. Recent advancements in medical imaging and machine learning offer opportunities to enhance predictive accuracy, particularly through deep learning and multi-instance learning (MIL) techniques.

WuYou decoction effectively reduces neuronal damage, synaptic dysfunction, and Aβ production in rats exposed to chronic sleep deprivation by modulating the Aβ-related enzymes and SIRT1/Nrf2/NF-κB pathway.

Ethnopharmacological Relevance: Chronic sleep deprivation (CSD) can result in neuronal damage, synaptic dysfunction, Aβ production, neuroinflammation, and ultimately cognitive deterioration. WuYou Decoction (WYD), a contemporary prescription, has shown promise in enhancing sleep quality and cognitive performance in individuals with insomnia. However, the specific molecular mechanisms responsible for the neuroprotective effects of WYD on CSD remain incompletely understood.

Multi-category sorting of plastic waste using Swin Transformer: A vision-based approach.

Sorting out plastic waste (PW) from municipal solid waste (MSW) by material type is crucial for reutilization and pollution reduction. However, current automatic separation methods are costly and inefficient, necessitating an advanced sorting process to ensure high feedstock purity. This study introduces a Swin Transformer-based model for effectively detecting PW in real-world MSW streams, leveraging both morphological and material properties.

Protocatechualdehyde inhibits iron overload-induced bone loss by inhibiting inflammation and oxidative stress in senile rats.

The accumulating evidence has made it clear that iron overload is a crucial mechanism in bone loss. Protocatechualdehyde (PCA) has also been used to prevent osteoporosis in recent years. Whether PCA can reverse the harmful effects of iron overload on bone mass in aged rats is still unknown.

Ganoderic Acid A prevents bone loss in lipopolysaccharide-treated male rats by reducing oxidative stress and inflammatory.

Ganoderic Acid A (GAA) has demonstrated beneficial effects in anti-inflammatory and anti-oxidative stress studies. However, it remains unknown whether GAA exerts positive impacts on bone loss induced by lipopolysaccharide (LPS). This study aims to investigate the influence of GAA on bone loss in LPS-treated rats.

Non-Classical Swine Leukocyte Antigens SLA-6, -7, and -8, Are Xenoantigens for Some Waitlisted Patients.

Attack of donor tissues by pre-formed anti-pig antibodies is well known to cause graft failure in xenotransplantation. Genetic engineering of porcine donors to eliminate targets of these pre-formed antibodies coupled with advances in immunosuppressive medicines have now made it possible to achieve extended survival in the pre-clinical pig-to-non-human primate model. Despite these improvements, antibodies remain a risk over the lifetime of the transplant, and many patients continue to have pre-formed donor-specific antibodies even to highly engineered pigs.

attenuates the intestinal permeability, oxidative stress and endoplasmic reticulum stress: transcriptome and microbiome analyses in weaned piglets.

Endoplasmic reticulum (ER) stress is related to oxidative stress (OS) and leads to intestinal injury. SC06 (SC06) can regulate OS, but its roles in intestinal ER stress remains unclear. Using a 2 × 2 factorial design, 32 weaned piglets were treated by two SC06 levels (0 or 1 × 10 CFU/g), either with or without diquat (DQ) injection.

Integrating Experimental and Computational Analyses for Mechanical Characterization of Titanium Carbide/Aluminum Metal Matrix Composites.

This study investigates the mechanical properties of titanium carbide/aluminum metal matrix composites (AMMCs) using both experimental and computational methods. Through accumulative roll bonding (ARB) and cryorolling (CR) processes, AA1050 alloy surfaces were reinforced with TiCp particles to create the Al-TiCp composite. The experimental analysis shows significant improvements in tensile strength, yield strength, elastic modulus, and hardness.

Constructing 3D Zincophilic Skeleton in Nitrogen-Doped Carbon Hybrid Fibers for Dendrite-Free Zn Anodes.

The Zn dendrite growth and side reactions are two major issues for the practical use of Zn metal anodes (ZMAs). Herein, an N-doped carbon-based hybrid fiber with the 3D porous skeleton and the zincophilic Cu nanoparticles (denoted as Cu@HLCF) is developed for stable ZMAs. The zincophilic Cu particles in the skeleton work as the active sites to facilitate uniform Zn nucleation.

A comparative study of stereo-dependent SSVEP targets and their impact on VR-BCI performance.

Steady-state visual evoked potential brain-computer interfaces (SSVEP-BCI) have attracted significant attention due to their ease of deployment and high performance in terms of information transfer rate (ITR) and accuracy, making them a promising candidate for integration with consumer electronics devices. However, as SSVEP characteristics are directly associated with visual stimulus attributes, the influence of stereoscopic vision on SSVEP as a critical visual attribute has yet to be fully explored. Meanwhile, the promising combination of virtual reality (VR) devices and BCI applications is hampered by the significant disparity between VR environments and traditional 2D displays.

Microstructure and Mechanical Properties of AA1050/AA6061 Laminated Composites Fabricated through Three-Cycle Accumulative Roll Bonding and Subsequent Cryorolling.

In this study, AA1050/AA6061 laminated composites were prepared by three-cycle accumulative roll bonding (ARB) and subsequent rolling. The effects of the rolling process on the microstructure evolution and mechanical properties of AA1050/AA6061 laminated composites were systematically investigated. The results indicate that the mechanical properties of the laminated composites can be effectively improved by cryorolling compared with room-temperature rolling.

Optimization of the morphological, structural, and physicochemical properties of maize starch using straw returning and nitrogen fertilization in Northeast China.

The combination of straw returning and nitrogen (N) fertilization is a popular tillage mode and essential strategy for achieving stable yield and high quality. However, the optimal combination strategy and the influence of tillage mode on the morphological, crystalline, and molecular structures of maize starch remain unclear. We conducted a long-term field experiment over 7 years in Northeast China using two tillage modes, rotary tillage with straw returning (RTS) and plow tillage with straw returning (PTS), and four N application rates.

Mi-2β promotes immune evasion in melanoma by activating EZH2 methylation.

Recent development of new immune checkpoint inhibitors has been particularly successfully in cancer treatment, but still the majority patients fail to benefit. Converting resistant tumors to immunotherapy sensitive will provide a significant improvement in patient outcome. Here we identify Mi-2β as a key melanoma-intrinsic effector regulating the adaptive anti-tumor immune response.

Segmenting tourists' motivations via online reviews: An exploration of the service strategies for enhancing tourist satisfaction.

Tourism motivation and satisfaction are classic themes in tourism research. This study combines latent Dirichlet allocation (LDA) and the Censydiam motivation model to analyze online reviews of tourism in Qinghai, China. The aim of this research is to explore tourist motivation through online reviews and provide innovative service suggestions to improve tourist satisfaction.