Enhancing Bioactivity of Titanium-Based Materials Through Chitosan Based Coating and Calcitriol Functionalization.

Titanium (Ti)-based materials are favored for hard tissue applications, yet their bioinertness limits their success. This study hypothesizes that functionalizing Ti materials with chitosan nano/microspheres and calcitriol (VD) will enhance their bioactivity by improving cellular activities and mineralization. To test this, chitosan particles were applied uniformly onto Ti surfaces using electrophoretic deposition (EPD) at 20 V for 3 minutes.

A bioinformatic approach to characterize the vitellogenin receptor and the low density lipoprotein receptor superfamily in the newt Cynops orientalis.

The Low Density Lipoprotein receptors (LDLRs) gene family includes 15 receptors: very low-density lipoprotein receptor (VLDLR), LDLR, Sorting-related receptor with A-type repeats (SORLA), and 12 LDL receptor-related proteins (LRPs): LRP1, LRP1B, LRP2, LRP3, LRP4, LRP5, LRP6, LRP8, LRP10, LRP11, LRP12, LRP13. Most of these are involved in the transduction of key signals during embryonic development and in the regulation of cholesterol homeostasis. In oviparous animals, the VLDL receptor is also known as VTGR since it facilitates the uptake of vitellogenin in ovary.

The southern house mosquito Culex quinquefasciatus in Abu Dhabi, UAE, is developing resistance to deltamethrin insecticide.

Culex quinquefasciatus is a widely spread mosquito species that poses a significant public health threat in many countries. This insect vector is present in the United Arab Emirates (UAE), yet no studies have been conducted on its resistance to any insecticide group. Research shows that controlling mosquitoes is crucial to eliminating mosquito-borne diseases, but when these vectors develop insecticide resistance, the situation can escalate dangerously out of control.

Plasma membrane-associated ARAF condensates fuel RAS-related cancer drug resistance.

RAF protein kinases are major RAS effectors that function by phosphorylating MEK. Although all three RAF isoforms share a conserved RAS binding domain and bind to GTP-loaded RAS, only ARAF uniquely enhances RAS activity. Here we uncovered the molecular basis of ARAF in regulating RAS activation.

Piezoelectric biosensor with dissipation monitoring enables the analysis of bacterial lytic agent activity.

Antibiotic-resistant strains of Staphylococcus aureus pose a significant threat in healthcare, demanding urgent therapeutic solutions. Combining bacteriophages with conventional antibiotics, an innovative approach termed phage-antibiotic synergy, presents a promising treatment avenue. However, to enable new treatment strategies, there is a pressing need for methods to assess their efficacy reliably and rapidly.

Exploration of alcohol dehydrogenase EutG from Bacillus tropicus as an eco-friendly approach for the degradation of polycyclic aromatic compounds.

Polycyclic aromatic compounds (PACs) are pervasive environmental contaminants derived from diverse sources including pyrogenic (e.g., combustion processes), petrogenic (e.

Patients with neurological or psychiatric complications of COVID-19 have worse long-term functional outcomes: COVID-CNS-A multicentre case-control study.

It is established that patients hospitalised with COVID-19 often have ongoing morbidity affecting activity of daily living (ADL), employment, and mental health. However, little is known about the relative outcomes in patients with COVID-19 neurological or psychiatric complications. We conducted a UK multicentre case-control study of patients hospitalised with COVID-19 (controls) and those who developed COVID-19 associated acute neurological or psychiatric complications (cases).

A compendium of Amplification-Related Gain Of Sensitivity genes in human cancer.

While the effect of amplification-induced oncogene expression in cancer is known, the impact of copy-number gains on "bystander" genes is less understood. We create a comprehensive map of dosage compensation in cancer by integrating expression and copy number profiles from over 8000 tumors in The Cancer Genome Atlas and cell lines from the Cancer Cell Line Encyclopedia. Additionally, we analyze 17 cancer open reading frame screens to identify genes toxic to cancer cells when overexpressed.

Short-term evolutionary implications of an introgressed size-determining supergene in a vulnerable population.

The Thorny Skate (Amblyraja radiata) is a vulnerable species displaying a discrete size-polymorphism in the northwest Atlantic Ocean (NWA). We conducted whole genome sequencing of samples collected across its range. Genetic diversity was similar at all sampled sites, but we discovered a ~ 31 megabase bi-allelic supergene associated with the size polymorphism, with the larger size allele having introgressed in the last ~160,000 years B.

Utilizing TP53 hotspot mutations as effective predictors of gemcitabine treatment outcome in non-small-cell lung cancer.

TP53 mutations are recognized to correlate with a worse prognosis in individuals with non-small cell lung cancer (NSCLC). There exists an immediate necessity to pinpoint selective treatment for patients carrying TP53 mutations. Potential drugs were identified by comparing drug sensitivity differences, represented by the half-maximal inhibitory concentration (IC50), between TP53 mutant and wild-type NSCLC cell lines using database analysis.

Genetic coupling of enhancer activity and connectivity in gene expression control.

Gene enhancers often form long-range contacts with promoters, but it remains unclear if the activity of enhancers and their chromosomal contacts are mediated by the same DNA sequences and recruited factors. Here, we study the effects of expression quantitative trait loci (eQTLs) on enhancer activity and promoter contacts in primary monocytes isolated from 34 male individuals. Using eQTL-Capture Hi-C and a Bayesian approach considering both intra- and inter-individual variation, we initially detect 19 eQTLs associated with enhancer-eGene promoter contacts, most of which also associate with enhancer accessibility and activity.

Splicing accuracy varies across human introns, tissues, age and disease.

Alternative splicing impacts most multi-exonic human genes. Inaccuracies during this process may have an important role in ageing and disease. Here, we investigate splicing accuracy using RNA-sequencing data from >14k control samples and 40 human body sites, focusing on split reads partially mapping to known transcripts in annotation.

A role for mitochondria-ER crosstalk in amyotrophic lateral sclerosis 8 pathogenesis.

Protein aggregates in motoneurons, a pathological hallmark of amyotrophic lateral sclerosis, have been suggested to play a key pathogenetic role. ALS8, characterized by ER-associated inclusions, is caused by a heterozygous mutation in VAPB, which acts at multiple membrane contact sites between the ER and almost all other organelles. The link between protein aggregation and cellular dysfunction is unclear.

Comparative impact of tertiary lymphoid structures and tumor-infiltrating lymphocytes in cholangiocarcinoma.

Background: Cholangiocarcinoma is a challenging malignancy with limited responses to conventional therapies, particularly immune checkpoint inhibitor therapy. Tumor-infiltrating lymphocytes (TILs) and tertiary lymphoid structures (TLSs) are key components of the tumor microenvironment (TME) and have been implicated in the immune response to cancer. However, the role and difference of TLSs and TILs in patients with cholangiocarcinoma remains unclear.

Strengthening advanced therapy for sickle cell disease in Africa: experience from sickle cell disease centre in Dar es Salaam, Tanzania.

Despite progress in healthcare services for individuals living with sickle cell disease (SCD) in Africa, substantial gaps remain in advanced treatments for SCD. To help address this burden, Tanzania has established one of the largest single-centre SCD programmes in the world and developed an advanced therapy programme for SCD focused on patient engagement and advocacy, clinical activities involving exchange blood transfusion (ExBT) and haematopoietic stem cell transplant (HSCT), gene therapy (GT) preparedness, and enabling partnerships. This report describes the programme's genesis, structure and progress achieved.

The multifaceted roles of retinoids in eye development, vision, and retinal degenerative diseases.

Vitamin A (all-trans-retinol; at-Rol) and its derivatives, known as retinoids, have been adopted by vertebrates to serve as visual chromophores and signaling molecules, particularly in the eye/retina. Few tissues rely on retinoids as heavily as the retina, and the study of genetically modified mouse models with deficiencies in specific retinoid-metabolizing proteins has allowed us to gain insight into the unique or redundant roles of these proteins in at-Rol uptake and storage, or their downstream roles in retinal development and function. These processes occur during embryogenesis and continue throughout life.

microbiota model recapitulates and predicts individualised sensitivity to dietary emulsifier.

Background: Non-absorbed dietary emulsifiers, including carboxymethylcellulose (CMC), directly disturb intestinal microbiota, thereby promoting chronic intestinal inflammation in mice. A randomised controlled-feeding study (Functional Research on Emulsifiers in Humans, FRESH) found that CMC also detrimentally impacts intestinal microbiota in some, but not all, healthy individuals.

Objectives: This study aimed to establish an approach for predicting an individual's sensitivity to dietary emulsifiers via their baseline microbiota.

The Autonomic Nervous System and Inflammation in Chronic Kidney Disease.

The autonomic nervous system plays a crucial role in regulating physiological processes and maintaining homeostasis through its two branches: the sympathetic nervous system (SNS) and the parasympathetic nervous system. Dysregulation of the autonomic system, characterized by increased sympathetic activity and reduced parasympathetic tone, is a common feature in chronic kidney disease (CKD) and cardiovascular disease. This imbalance contributes to a pro-inflammatory state, exacerbating disease progression and increasing the risk for cardiovascular events.

Optimized Scaffold-Free Human 3D Adipose Tissue Organoid Culture for Obesity and Disease Modeling.

Obesity and type 2 diabetes (T2D) are strongly linked to abnormal adipocyte metabolism and adipose tissue (AT) dysfunction. However, existing adipose tissue models have limitations, particularly in the stable culture of fat cells that maintain physiologically relevant phenotypes, hindering a deeper understanding of adipocyte biology and the molecular mechanisms behind differentiation. Current model systems fail to fully replicate in vivo metabolism, posing challenges in adipose research.

Prospective analysis of biomarkers associated with successful faecal microbiota transplantation in recurrent Clostridioides difficile Infection.

Objectives: Faecal microbiota transplantation (FMT) is an established treatment for recurrent Clostridioides difficile infection (R-CDI). This study aimed to identify calprotectin and microbiome characteristics as potential biomarkers of FMT success.

Methods: We conducted a prospective study of patients who underwent oral FMT (single dose of 4-5 capsules) for R-CDI (January 2018 to December 2022).

Uncovering the naturally occurring covalent inhibitors of SARS-CoV-2 M from the Chinese medicine sappanwood and deciphering their synergistic anti-M effects.

Ethnopharmacological Relevance: The Chinese medicine sappanwood is primarily sourced from the dried heartwood of the medicinal plant Caesalpinia sappan Linn., which has been found with a variety of valuable properties including anti-inflammatory, anti-oxidant, and anti-viral effects. Preliminary investigations have demonstrated that sappanwood showed strong anti-SARS-CoV-2 M effects, but the key constituents responsible for SARS-CoV-2 M inhibition and their anti-M mechanisms have not been uncovered.

Biochemical, structural, and cellular characterization of S-but-3-yn-2-ylglycine as a mechanism-based covalent inactivator of the flavoenzyme proline dehydrogenase.

The mitochondrial flavoenzymes proline dehydrogenase (PRODH) and hydroxyproline dehydrogenase (PRODH2) catalyze the first steps of proline and hydroxyproline catabolism, respectively. The enzymes are targets for chemical probe development because of their roles in cancer cell metabolism (PRODH) and primary hyperoxaluria (PRODH2). Mechanism-based inactivators of PRODH target the FAD by covalently modifying the N5 atom, with N-propargylglycine (NPPG) being the current best-in-class of this type of probe.

NKAP: a new m6A RNA binding protein predicts prognosis and immunotherapy response in head and neck squamous cell carcinoma.

Objective: This study aimed to investigate whether NKAP (nuclear factor κB activating protein) serves as a prognostic marker and predictive biomarker for immunotherapy response in head and neck squamous cell carcinoma (HNSCC).

Methods: A retrospective cohort study combined with in vitro analyses was conducted. NKAP mRNA expression levels were assessed in 520 HNSCC tumor tissues and 44 normal tissues from the TCGA dataset and validated in a clinical cohort (n=32).

Bioimpedance Measurements of Fibrotic and Acutely Injured Lung Tissues.

In injured and diseased tissues, changes in molecular and cellular compositions, as well as tissue architecture, lead to alterations in both physiological and physical characteristics. Notably, the electrical properties of tissues, which can be characterized as bioelectrical impedance (bioimpedance), are closely linked to the health and pathological conditions of the tissues. This highlights the significant role of quantitatively characterizing these electrical properties in improving the accuracy and speed of diagnosis and prognosis.