Titanium Dioxide (TiO) Incorporation into Poly(ether sulfone) (PES) Hollow Fiber Membranes (HFMs) Improves Biocompatibility and Separation Performance for Bioartificial Kidney (BAK) and Hemodialysis Applications.

Hemodialysis and bioartificial kidney (BAK), which mimic both physical and biological functions, can significantly impact chronic kidney disease (CKD) patients. Here we report on Hollow fiber membranes (HFMs) with enhanced separation of uremic toxins along with enhanced hemocompatibility and biocompatibility that also promote the growth of kidney cells. The improvement arises from the addition of titanium dioxide (0.

Assessment of surface roughness and microbiological retention on custom abutments produced by different techniques and materials.

The aims of this study were twofold: first, to investigate the surface roughness of different abutment materials prepared using various manufacturing methods; and, second, to evaluate colonization by Streptococcus mutans and Candida albicans according to abutment material and manufacturing method. Six material/manufacturing method combinations were investigated in this study, namely chromium-cobalt (Cr-Co) (prepared using casting, milling, and laser sintering) and titanium, zirconia, and anodized titanium (all prepared using milling); titanium (stock) abutments were used as the control group. Surface roughness of seven specimens from each group was evaluated using atomic force microscopy and scanning electron microscopy.

The conformational landscape of human transthyretin revealed by cryo-EM.

Transthyretin (TTR) is a natively tetrameric thyroxine transporter in blood and cerebrospinal fluid whose misfolding and aggregation causes TTR amyloidosis. A rational drug design campaign identified the small molecule tafamidis (Vyndamax) as a stabilizer of the native TTR fold, and this aggregation inhibitor is regulatory agency approved for the treatment of TTR amyloidosis. Here we used cryo-EM to investigate the conformational landscape of this 55 kDa tetramer in the absence and presence of one or two ligands, revealing inherent asymmetries in the tetrameric architecture and previously unobserved conformational states.

Private and well drinking water are reservoirs for antimicrobial resistant bacteria.

Water quality testing does not recognise antimicrobial resistance (AMR) and is often limited to indicators of faecal contamination Escherichia coli and Enterococcus species. In Europe, data on AMR in drinking water is scarce. In Ireland, as in many countries, household drinking water is supplied via mains or via private wells or water schemes.

Identification and characterisation of two functional antibiotic MATE efflux pumps in the archaeon Halorubrum amylolyticum.

Multidrug efflux pumps have been found to play a crucial role in drug resistance in bacteria and eukaryotes. In this study, we investigated the presence of functional multidrug and toxic compound extrusion (MATE) efflux pumps, inferred from whole genome sequencing, in the halophilic archaeon Halorubrum amylolyticum CSM52 using Hoechst 33342 dye accumulation and antimicrobial sensitivity tests in the presence and absence of efflux pump inhibitors (EPIs). The whole genome sequence of H.

Unlocking the potential of experimental evolution to study drug resistance in pathogenic fungi.

Exploring the dynamics and molecular mechanisms of antimicrobial drug resistance provides critical insights for developing effective strategies to combat it. This review highlights the potential of experimental evolution methods to study resistance in pathogenic fungi, drawing on insights from bacteriology and innovative approaches in mycology. We emphasize the versatility of experimental evolution in replicating clinical and environmental scenarios and propose that incorporating evolutionary modelling can enhance our understanding of antifungal resistance evolution.

Rapid resistance profiling of SARS-CoV-2 protease inhibitors.

Resistance to nirmatrelvir (Paxlovid) has been shown by multiple groups and may already exist in clinical SARS-CoV-2 isolates. Here a robust cell-based assay is used to determine the relative potencies of nirmatrelvir, ensitrelvir, and FB2001 against a panel of SARS-CoV-2 main protease (M) variants. The results reveal that these three drugs have at least partly distinct resistance mutation profiles and raise the possibility that the latter compounds may be effective in some instances of Paxlovid resistance and vice versa.

Antimicrobial peptide glatiramer acetate targets Pseudomonas aeruginosa lipopolysaccharides to breach membranes without altering lipopolysaccharide modification.

Antimicrobial peptides (AMPs) are key components of innate immunity across all domains of life. Natural and synthetic AMPs are receiving renewed attention in efforts to combat the antimicrobial resistance (AMR) crisis and the loss of antibiotic efficacy. The gram-negative pathogen Pseudomonas aeruginosa is one of the most concerning infecting bacteria in AMR, particularly in people with cystic fibrosis (CF) where respiratory infections are difficult to eradicate and associated with increased morbidity and mortality.

Study on the correlation between serum IgG4/IgG levels and the development of Graves' ophthalmopathy.

Graves' ophthalmopathy (GO) with elevated IgG4 levels has different characteristics from patients with GO who do not have elevated IgG4 levels, but the study findings are contradictory. The goal of this study was first to investigate the relationship between IgG4/IgG and IgG4 levels and the occurrence of GO and then to investigate the clinical and laboratory characteristics of patients with GO who had elevated IgG4 levels. This study control group consisted of 57 Graves' disease(GD)patients with no complicated ocular disease and a median followup of 54.

Detection and genomic characterisation of foot-and-mouth disease virus serotypes circulating in Cameroon using environmental sampling.

Foot-and-mouth disease virus (FMDV) is a highly contagious, economically important disease of livestock and wildlife species. Active monitoring and understanding the epidemiology of FMDV underpin the foundations of control programmes. In many endemic areas, however, veterinary resources are limited, resulting in a requirement for simple sampling techniques to increase and supplement surveillance efforts.

Triple-negative breast cancer modifies the systemic immune landscape and alters neutrophil functionality.

Cancer disrupts intratumoral innate-adaptive immune crosstalk, but how the systemic immune landscape evolves during breast cancer progression remains unclear. We profiled circulating immune cells in stage I-III and stage IV triple-negative breast cancer (TNBC) patients and healthy donors (HDs). Metastatic TNBC (mTNBC) patients had reduced T cells, dendritic cells, and differentiated B cells compared to non-metastatic TNBC patients and HDs, partly linked to prior chemotherapy.

The left amygdala is genetically sexually-dimorphic: multi-omics analysis of structural MRI volumes.

Brain anatomy plays a key role in complex behaviors and mental disorders that are sexually divergent. While our understanding of the sex differences in the brain anatomy remains relatively limited, particularly of the underlying genetic and molecular mechanisms that contribute to these differences. We performed the largest study of sex differences in brain volumes (N = 33,208) by examining sex differences both in the raw brain volumes and after controlling the whole brain volumes.

Microglia modulate the cerebrovascular reactivity through ectonucleotidase CD39.

Microglia and the border-associated macrophages contribute to the modulation of cerebral blood flow, but the mechanisms have remained uncertain. Here, we show that microglia regulate the cerebral blood flow baseline and the responses to whisker stimulation or intra-cisternal magna injection of adenosine triphosphate, but not intra-cisternal magna injection of adenosine in mice model. Notably, microglia repopulation corrects these cerebral blood flow anomalies.

Mechanism of sensor kinase CitA transmembrane signaling.

Membrane bound histidine kinases (HKs) are ubiquitous sensors of extracellular stimuli in bacteria. However, a uniform structural model is still missing for their transmembrane signaling mechanism. Here, we used solid-state NMR in conjunction with crystallography, solution NMR and distance measurements to investigate the transmembrane signaling mechanism of a paradigmatic citrate sensing membrane embedded HK, CitA.

A dataset of Antarctic ecosystems in ice-free lands: classification, descriptions, and maps.

Antarctica, Earth's least understood and most remote continent, is threatened by human disturbances and climate-related changes, underscoring the imperative for biodiversity inventories to inform conservation. Antarctic ecosystems support unique species and genetic diversity, deliver essential ecosystem services and contribute to planetary stability. We present Antarctica's first comprehensive ecosystem classification and map of ice-free lands, which host most of the continent's biodiversity.

Use of climate smart agriculture technologies in West Africa peri-urban Sahel in Niger.

Climate change affects peri-urban agricultural systems. However, most studies on Climate-Smart Agriculture (CSA) often focused on climate-smart villages in the Sahel region. This study investigated peri-urban farming systems in West African Sahel cities.

Lentinan's effect on gut microbiota and inflammatory cytokines in 5-FU-induced mucositis mice.

Chemotherapeutic therapies for cancer are frequently associated with cytotoxic side effects that can be harmful to human health, including the development of intestinal mucositis (IM). It mostly affects the gastrointestinal tract, causing ulceration, inflammation, and the formation of lesions in the colon. Surprisingly, despite the frequency of IM, therapeutic choices remain restricted.

Shoulder Aesthetics: A Novel Synergy of Hyaluronic Acid Fillers and Neuromodulators.

The pursuit of aesthetically pleasing shoulder contours, particularly those characterised by a sharp, angular definition, has gained significant traction in Southeast Asia. Traditionally, neuromodulators have been used to achieve these results by inducing muscle atrophy, particularly in the trapezius muscles. However, this approach can carry potential risks, such as compromised muscle function and spinal instability.

Genetic insights into CRP levels in Indian adolescents: confirming adult genetic associations.

CRP is a biomarker of acute inflammation linked to metabolic complications. Given the rising prevalence of these conditions in India, we investigated the genetic basis of CRP levels in Indian adolescents, an underrepresented group in genetic studies, to identify early markers of metabolic risk. We performed a two-phased genome-wide association study (GWAS; N = 5052) and an independent Exome-wide association study (ExWAS; N = 4547), to identify both common and rare genetic variants associated with CRP levels.

Endocannabinoid contributions to the perception of socially relevant, affective touch in humans.

Social relationships are central to well-being. A subgroup of afferent nerve fibers, C-tactile (CT) afferents, are primed to respond to affective, socially relevant touch and may mitigate the effects of stress. The endocannabinoid ligand anandamide (AEA) modulates both social reward and stress.

A game of hide-and-seek: how extracellular vesicles evade the immune system.

Extracellular vesicles (EVs) are heterogeneously sized, cell-derived nanoparticles operating as proficient mediators of intercellular communication. They are produced by normal as well as diseased cells and carry a variety of cargo. While the molecular details of EV biology have been worked out over the past two decades, one question that continues to intrigue many is how are EVs able to evade the phagocytic immune cells while also being effectively internalized by the target cell or tissue.

How to combine multiple tools for the genetic diagnosis work-up of pediatric B-cell acute lymphoblastic leukemia.

This study investigated the importance of comprehensive genetic diagnosis in pediatric B-cell acute lymphoblastic leukemia (B-ALL). We analyzed 175 B-ALL employing karyotyping, FISH, MLPA, targeted next-generation sequencing (t-NGS), and Optical Genome Mapping (OGM). This approach achieved an 83% classification rate, identifying 17 distinct genetic subtypes.

Development and In-Vitro Tuning of Piperine Containing Solid Lipid Microparticles for the Treatment of Rheumatoid Arthritis.

The current project was designed to develop piperine-loaded solid lipid microparticles (SLMs) to assess the anti-arthritic potential of piperine (PIP). Variable proportions of carnauba wax, beeswax, and tween 80 were employed for preparing SLMs by using the solvent evaporation technique. The developed formulations were subjected to particle size measurements, entrapment efficiency (EE), and zeta potential (ZP) determination.

Mitochondrial NAD deficiency in vascular smooth muscle impairs collagen III turnover to trigger thoracic and abdominal aortic aneurysm.

Thoracic and abdominal aortic aneurysm poses a substantial mortality risk in adults, yet many of its underlying factors remain unidentified. Here, we identify mitochondrial nicotinamide adenine dinucleotide (NAD)⁺ deficiency as a causal factor for the development of aortic aneurysm. Multiomics analysis of 150 surgical aortic specimens indicated impaired NAD salvage and mitochondrial transport in human thoracic aortic aneurysm, with expression of the NAD transporter SLC25A51 inversely correlating with disease severity and postoperative progression.

Emerging roles of exosomes in diagnosis, prognosis, and therapeutic potential in ovarian cancer: a comprehensive review.

Ovarian cancer is a leading cause of cancer-related deaths in women, and the development of chemoresistance remains a major challenge during and after its treatment. Exosomes, small extracellular vesicles involved in intercellular communication, have emerged as potential biomarkers and therapeutic targets in ovarian cancer. This review summarizes the current literature on differences in exosomal protein/gene expression between chemosensitive and chemoresistant ovarian cancer, and the effects of exosomal modifications on chemotherapeutic response.