Browse Articles
Discover research articles across all indexed journals
DFT-based insights into novel Ga6N6 nanoring for pollutant gas adsorption: energetics and electronic modulations
Biosynthesis of fatty aldehydes and alcohols in the eye and their role in meibogenesis
Single atom engineering for radiotherapy-activated immune agonist prodrugs
Abstract Immunotherapy has revolutionized cancer treatment by leveraging the body’s immune system to combat malignancies. However, on-target, off-tumour (OTOT) toxicity poses significant challenges, often leading to the failure of clinical trials for the development of immunotherapeutic drugs. The molecular engineering of clinically relevant, tumour-selective prodrugs, activated in a targeted way, could help minimize systemic toxicity while maximizing anti-tumour efficacy. Here, we propose a Single Atom Engineering for Radiotherapy-Activated Prodrug (SAE-RAP) technique for the development of radiotherapy-activatable small-molecule immune agonist prodrugs. We show that introducing a single oxygen atom into the TLR7/8 agonist R848 significantly reduces the EC50 value by over 4000-fold, hence mitigating severe side effects following systemic administration. In preclinical tumour mouse models, exposure to radiotherapy removes the protective mask provided by the oxygen atom and locally rescues the activity of the prodrugs, triggering anti-tumour immunity and limiting the growth of primary and distal tumours. The SAE-RAP technique may be further utilized for developing radiotherapy-activated prodrugs for next-generation combination therapies that transcend traditional limitations.
Highly pathogenic avian influenza H5N1 clade 2.3.4.4b genotype B3.13 is highly virulent for mice, rapidly causing acute pulmonary and neurologic disease
Abstract The highly pathogenic avian influenza (HPAI) A(H5N1) clade 2.3.4.4b viruses, responsible for the current outbreak in dairy cows in the United States, pose a significant animal and public health threat. In this study, we compare disease progression and pathology of three recent clade 2.3.4.4b isolates derived from a cow, a mountain lion, and a mink to a human HPAI A(H5N1) isolate from Vietnam in mice. Inoculating C57BL/6J and BALB/c mice with all four HPAI A(H5N1) isolates results in comparable levels of virus replication in the lung inducing significant local pro-inflammatory cytokine responses and severe respiratory disease. Infecting C57BL/6J mice with the bovine isolate yields high viral titers in the brain, a significant pro-inflammatory cytokine response and neurologic disease. Our findings suggest the recent bovine isolate possesses enhanced neuroinvasive/neurovirulent disease causing fatal respiratory and neurologic disease in C57BL/6J mice.
The capacity limits of moving objects in the imagination
A simple preprocessing approach for improving semantic segmentation in unsupervised domain adaptation
Simulation and experiment research on heat treatment of micro and nano BN particles modified casting aluminum copper alloys
A virtual reality game for older adults’ immersive learning
Abstract This article presents a feasibility study that assessed the effectiveness of a virtual reality (VR) game in training older adults’ cognitive and independent living skills. A home-like virtual environment, comprising six mini-games, each designed to target a specific type of learning, was created to enhance the gamified experience. A qualitative approach was used to evaluate the feasibility of the gamified approach, involving semi-structured interviews with older adults (N = 30) who had played the VR game. Findings revealed positive feedback on the VR game’s effectiveness in facilitating learning among older adults, including ease of use and perceived usefulness which informed their acceptance of the technology, as well as the competency and cognitive developments afforded by the VR game. The gaming experience also offers varying degrees of stimulation and engagement, although some negative experiences, such as cybersickness and anxiety, were identified that may require further attention. The study’s findings offer insights into the feasibility of employing digital game-based learning for older adults within an immersive learning environment and provide best practices for designing VR games that promote the development of cognitive and independent living skills.
Characterisation of gut microbiota in Malaysian cancer patients using V3-V4 region of 16S rRNA gene sequencing
Abstract Recent studies suggested a potential connection between gut microbiota changes and cancer onset. However, conflicting results make it challenging to understand the role of gut microbiota dysbiosis in cancer, particularly in underrepresented populations like those in Southeast Asia. To address this gap, we analysed the diversity and composition of gut microbiota in 65 faecal samples, which included 48 from cancer patients with various malignancies and 17 from healthy controls. Patients were categorised into four groups: symptomatic patients undergoing cancer treatment, asymptomatic pre-treatment and during cancer treatment, and healthy controls. Genomic DNA was extracted, and the V3-V4 region of the 16 S rRNA gene was sequenced. Our findings revealed significant differences in the alpha diversity ( p ≤ 0.05) between cancer patients and controls. Asymptomatic patients under treatment showed slightly lower alpha diversity than pre-treatment patients, but this difference was not statistically significant ( p = 0.06). We identified 13 genera with over 20% difference in abundance between patient groups and controls. Asymptomatic patients receiving treatment and pre-treatment patients exhibited enrichment in Enterococcus , whereas Prevotella , Faecalibacterium , Brevundimonas , and Pseudomonas were significantly reduced compared to controls. Symptomatic patients had higher levels of Enterococcus and Staphylococcus , while Ruminococcus was enriched in asymptomatic patients. These underscore the distinct differences in gut microbiota composition between cancer patients and healthy individuals, particularly in symptomatic cases with potential biomarkers such as Enterococcus , Prevotella , and Faecalibacterium . Our study suggests that cancer treatment may not significantly alter the gut profile of cancer patients. Further research is needed to comprehend the implications of these findings fully.