LP-98 is a lipopeptide HIV fusion inhibitor showing strong treatment and pre-exposure prophylaxis efficacies in non-human primates. In this study, we further characterized its pharmacokinetics, long-lasting antiviral activity, and post-exposure prophylaxis (PEP) efficacy using 62 macaques. In cynomolgus macaques, LP-98 achieved high concentrations (C) with a half-life (T) of ∼31 h, and sustained an effective therapeutic concentration for two weeks post-injection.
View Article and Find Full Text PDFObjective: To design and fabricate a universal donor tooth model for autotransplantation and evaluate its clinical application efficacy.
Methods: CBCT data of 1003 third molars were collected as donor tooth data and classified after preprocessing. Multi-point cloud registration was performed for each classified dataset, and the registered point clouds were fused to obtain the distribution of point clouds under a unified reference.
Objective: The dried succulent stem of (Schenk) Wight has long been used as herbal medicine in China and other regions of Asia for its tonifying properties. This study aimed to elucidate the pharmacological mechanisms of the total glycosides from (GCT) in ameliorating cognitive decline, with a focus on gut microbiota remodeling and metabolic regulation.
Methods: Six-month-old APP/PS1 double-transgenic mice received oral GCT at three doses or donepezil for 60 days.
Antifouling paints can effectively prevent marine organisms from biofouling. However, the release of antifouling paint particles (APPs) and their toxic additives has emerged as a significant source of marine contamination, posing potential threats to marine biota. Hence, this study investigated the release kinetics and bioaccessibility of heavy metals from APPs in simulated digestive fluids, mimicking the gastrointestinal conditions of marine polychaete, fish, and seabird.
View Article and Find Full Text PDFTo achieve the non-destructive identification of millet origin, near-infrared spectroscopy was used to collect the raw spectral data of the millet. Considering the issues of high-dimensional redundancy and spectral peak overlap in near-infrared spectral data, feature wavelengths were selected using the Competitive Adaptive Reweighted Sampling (CARS) algorithm, the Uninformative Variable Elimination (UVE) algorithm, and the Whale Optimization Algorithm (WOA), resulting in 26, 158, and 123 feature wavelengths, respectively. To further improve feature extraction effectiveness, strategies such as chaotic mapping were integrated into the Whale Optimization Algorithm (IWOA), reducing the selected feature wavelengths from 123 to 27 variables.
View Article and Find Full Text PDFMol Ther Methods Clin Dev
September 2025
Precise assessment of the cytotoxic activity of engineered immune cell therapeutics, such as chimeric antigen receptor-engineered T (CAR-T) cells, is essential for their development and quality control. However, luciferase (Luc)-based viability assays, which evaluate target cell viability by overexpressing Luc tags and measuring chemiluminescent signals, may yield biased results depending on the promoter driving Luc expression. This study demonstrates that CAR-T cells can enhance cytomegalovirus (CMV) promoter-driven transcription in target cells via the interferon-gamma (IFN-γ)/nuclear factor κB (NF-κB) signaling pathway, leading to elevated Luc expression and a discrepancy between chemiluminescent signals and actual target cell death.
View Article and Find Full Text PDFMicroplastics have been recognized as a global marine environmental issue, but their sources, particularly the contribution of atmospheric transport, remain obscure. Here, we determine the transport efficiency of atmospheric microplastics (AMPs) from land to sea using multimedia observations from both sea and land in the South China Sea in conjunction with atmospheric trajectory modelling. Furthermore, we extrapolate AMP inputs to the ocean at a global scale.
View Article and Find Full Text PDFResistance to multi-tyrosine kinase inhibitors (TKI) is a major clinical concern in advanced hepatocellular carcinoma (HCC). Herein, we aimed to uncover the mechanisms underlying pan-TKI resistance and to identify potential therapeutic targets. We used multiple TKI-resistant HCC cell lines to identify caveolin-1 (CAV1) as a key driver of therapeutic resistance.
View Article and Find Full Text PDFThe estuarine environment is a complex and dynamic ecosystem in the transition zone where rivers meet the sea. However, information on the distribution, fate, and risks of novel organic ultraviolet filters and stabilizers (OUVs) in estuaries remains limited. In this study, the occurrence of benzotriazole (BT) and benzothiazole (BTH) derivatives in seawater, suspended particulate matter (SPM) and sediments in the Pearl River Estuary (PRE) was analysed.
View Article and Find Full Text PDFBackground: "Study With Me (SWM)," a popular trend among Generation Z college students, enabling self-directed learning through livestreams or prerecorded videos and offering peer support in virtual settings. However, its impact on learning outcomes remains underexplored.
Purpose: This study examines how peer support impacts learning satisfaction and engagement in SWM, focusing on intrinsic motivation, extrinsic motivation, test anxiety, and self-efficacy as mediators, comparing livestreams and prerecorded formats.
Developing alloys with both ultrahigh strength and ductility remains a formidable scientific challenge, primarily due to the inherent strength-ductility tradeoff. Here, we present an approach to enhance the ductility and strength of a medium-entropy alloy (MEA) featuring a fully recrystallized face-centered cubic/hexagonal close-packed dual-phase ultrafine-grained architecture. This is achieved by activating unusual non-basal slips in the ordered hexagonal close-packed superlattice nanoprecipitates, resulting in this MEA that exhibits remarkable uniform elongation (ε) and ultrahigh yield strength (σ) across a wide temperature range, particularly at cryogenic temperatures (σ ~ 2100 MPa, ε ~ 15%).
View Article and Find Full Text PDFDuring chronic HIV-1 infection, the upregulation of immune checkpoints (ICs) on lymphocytes contributes to persistent immune dysfunction, T-cell exhaustion, and inadequate virological control, highlighting the potential role of ICs in HIV functional cure strategy. Despite extensive research on ICs, the expression dynamics and immunological impact of ICs in natural HIV/SHIV infection, particularly among antiretroviral therapy (ART)-free elite controllers (ECs), remain poorly understood. In this study, we monitored a cohort of SHIV-infected rhesus macaques (RMs), identifying four ECs and four progressors (PGs) through longitudinal evaluation.
View Article and Find Full Text PDFWhat Is Already Known About This Topic?: As an indicator of aortic stiffening, elevated pulse pressure (PP) has been established as a marker of poor clinical outcomes.
What Is Added By This Report?: Compared with the lowest quartile of PP (<40 mmHg), mortality risk increased by 9.8%-23.
Emerging contaminants (ECs) have attracted significant attention due to their adverse effects on aquatic ecosystems and human health. Compared with traditional technologies, biocatalytic membranes (BCMs) combine membrane separation with enzymatic reactions, showing potential for ECs treatment. However, natural enzymes are susceptible to environmental impacts.
View Article and Find Full Text PDFAims: Individuals with abnormal glucose metabolism are at a significantly higher risk of developing heart failure (HF). However, strategies for early identification of HF in this high-risk population remain inadequate. This study aimed to identify plasma protein biomarkers associated with HF development and construct predictive models to identify at-risk individuals.
View Article and Find Full Text PDFThe emergence of rubber-derived chemicals (RDCs) has garnered significant environmental attention, particularly N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine quinone (6PPD-Q) linked to acute mortality in salmonids. However, the trophic transfer of RDCs within marine ecosystems is notably sparse. Here, we investigated RDCs in the Nandu River estuary near China's largest rubber production region through an integrated targeted and non-targeted approach.
View Article and Find Full Text PDFThe human intestinal floras play an important role in human microecosystem, accounting for more than 1,500 species and consisting of beneficial, harmful and neutral bacteria, which take part in regulating the progression of various malignant tumors. Meanwhile, the cell death is a physiological process maintaining biological development and internal environmental homeostasis, including cuproptosis, ferroptosis, disulfidptosis, immunogenic cell death, necroptosis, anoikis, autophagy, pyroptosis and so on. A variety of cell deaths and their related genes have been reported to regulate many malignant tumors.
View Article and Find Full Text PDFGastric cancer (GC) is a major public health issue due to its high morbidity and mortality rates. The role of long noncoding RNAs (lncRNAs) in GC progression has received extensive attention. However, the underlying mechanisms by which lncRNAs mediates GC development remain poorly characterized.
View Article and Find Full Text PDFGastrointestinal (GI) cancers are a leading cause of cancer morbidity and mortality worldwide. Despite advances in treatment, cancer relapse remains a significant challenge, necessitating novel therapeutic strategies. In this study, we engineered nanobody-based chimeric antigen receptor (CAR) natural killer (NK) cells targeting cadherin 17 (CDH17) for the treatment of GI tumors.
View Article and Find Full Text PDFObjective: Gastric cancer is a serious human chronic disease. The gastric signet ring cell carcinoma (GSRCC) is the most-dangerous subtype with several acute complications, including gastrointestinal hemorrhage, gastric perforation, pyloric obstruction and so on. This study aimed to compare the predictive efficiency of positive lymph nodes (PLN) and log odds of positive lymph nodes (LODDS) for survival and to establish a LODDS-based nomogram model in stage III-IV GSRCC.
View Article and Find Full Text PDFBackground: Patient-centered care is a healthcare priority, particularly in diverse settings like the United Arab Emirates. Understanding the factors influencing its delivery is essential for effective care.
Objective: This study examines the association between cultural sensitivity, technology, and patient empowerment with patient-centered care in UAE rehabilitation healthcare centers.
Monticola rufiventris belongs to the order Passeriformes and the family Muscicapidae. As the largest group of birds, the phylogenetic relationships within Passeriformes have been a hot topic of research; however, studies on the genus Monticola within Passeriformes are relatively limited. This study presents the first comprehensive sequencing and analysis of the mitochondrial genome of M.
View Article and Find Full Text PDFResistance to tyrosine kinase inhibitors (TKIs, e.g., sorafenib and lenvatinib) presents a significant hurdle for hepatocellular carcinoma (HCC) treatment, underscoring the need to decipher the underlying mechanisms for improved therapeutic strategies.
View Article and Find Full Text PDFFront Pharmacol
April 2025
Acute kidney injury (AKI) refers to clinical syndromes culminating in rapidly reduced renal function associated with inflammation and the demise of renal tubular epithelial cells. Current research aims to develop strategies which prevent tubular cell death. Here, based on the involvement of histone deacetylases (HDACs) in renal physiology and their established role in renal fibrosis, we investigated the mechanistic contributions of HDACs using a mouse model together with studies employing human renal epithelial cells.
View Article and Find Full Text PDFChimeric antigen receptor (CAR) T cells offered a potential cure for malignancies, however, their outcomes and dynamics across different anatomical sites remained inadequately characterized. Monitoring the bio-distribution and tumor-homing of CAR-T cells in vivo is crucial, as it provides patient-specific data that might inform on treatment success, potential failure, and off-target toxicities. Herein, an Aptamer A3 by Cell-SELEX (systematic evolution of ligands by exponential enrichment) is generated, which can bind with CAR-T cells with nanomolar affinity.
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