Sequence Diversity in the 3' Untranslated Region of Alphavirus Modulates IFIT2-Dependent Restriction in a Cell Type-Dependent Manner.

Alphaviruses (family Togaviridae) are a diverse group of positive-sense RNA (+ssRNA) viruses that are transmitted by arthropods and are the causative agent of several significant human and veterinary diseases. Interferon (IFN)-induced proteins with tetratricopeptide repeats (IFITs) are a family of RNA-binding IFN-stimulated genes (ISGs) that are highly upregulated following viral infection and have been identified as potential restrictors of alphaviruses. The mechanism by which IFIT1 restricts RNA viruses is dependent on self and non-self-discrimination of RNA, and alphaviruses evade this recognition via their 5' untranslated region (UTR).

Medication experiences in the treatment of opioid use disorders: Insights from Reddit.

Background And Aims: Better understanding the challenges faced by patients on medications for opioid use disorder (MOUD), including methadone and buprenorphine, is critical to increasing their use/retention. Social media platforms such as Reddit offer a space for patients to share their experiences with medications. We aimed to identify and characterize challenges faced by patients taking MOUD through analysis of discussions from the r/Methadone and r/suboxone subreddits.

Orchestrating Intracellular Calcium Signaling Cascades by Phosphosite-Centric Regulatory Network: A Comprehensive Analysis on Kinases CAMKK1 and CAMKK2.

Intracellular calcium signaling is a cornerstone in cell biology and a key molecular target for human health and disease. Calcium/calmodulin dependent protein kinase kinases, CAMKK1 and CAMKK2 are serine/threonine kinases that contribute to the regulation of intracellular calcium signals in response to diverse stimuli. CAMKK1 generally has stable dynamics, whereas CAMKK2 dysregulation triggers oncogenicity and neurological disorders.

3,5-Disubstituted pyrazoline as a promising core for anticancer agents: mechanisms of action and therapeutic potentials.

The rapidly growing interest in the literature about the anticancer activity of 3,5-disubstituted pyrazolines and their promising therapeutic potentials/pharmacological properties, supported by the number of pyrazoline derivatives currently in clinical use or clinical trials, encouraged us to review the antiproliferative effects and biochemical investigations of probable mechanisms of action. Nevertheless, many reported pyrazoline-bearing compounds have anticancer activity without an explored mode of action, which opens new research avenues to examine their biochemical profiles further. Therefore, 3,5-disubstituted pyrazoline is a promising core that can be used to design new derivatives with anticancer activity based on the structure-activity relationship summarized in this review to obtain higher potency and selectivity.

Treat-And-Extend Versus Pro Re Nata Regimen of Intravitreal Conbercept Injection for Neovascular Age-Related Macular Degeneration: Results from COCOA, a Prospective, Open-Label, Multicenter, Randomized Phase IV Clinical Trial.

Purpose: To evaluate and contrast the effectiveness and safety of two conbercept treatment protocols-a three-dose treat-and-extend (3+T&E) regimen and a three-dose pro re nata (3+PRN) regimen-in Chinese patients diagnosed with neovascular age-related macular degeneration (nAMD).

Methods: Eligible patients, who had not undergone anti-VEGF intraocular injections within 3 months prior to enrollment, were randomly assigned to either the 3+T&E or 3+PRN regimen. The 3+T&E group received at least three monthly injections, with subsequent visit intervals extended based on disease activity assessment.

Harnessing Intelligence from Brain Cells In Vitro.

Harnessing intelligence from brain cells in vitro requires a multidisciplinary approach integrating wetware, hardware, and software. Wetware comprises the in vitro brain cells themselves, where differentiation from induced pluripotent stem cells offers ethical scalability; hardware typically involves a life support system and a setup to record the activity from and deliver stimulation to the brain cells; and software is required to control the hardware and process the signals coming from and going to the brain cells. This review provides a broad summary of the foundational technologies underpinning these components, along with outlining the importance of technology integration.

Femtosecond laser-ablative aqueous synthesis of multi-drug antiviral nanoparticles.

Background: Nanomedicine offers a number of innovative strategies to address major public health burdens, including complex respiratory illnesses. In this work, we introduce a multi-drug nanoparticle fabricated using femtosecond laser ablation for the treatment of influenza, SARS-CoV-2, and their co-infections.

Methods: The SARS-CoV-2 antiviral, remdesivir; the influenza antiviral, baloxavir marboxil; and the anti-inflammatory, dexamethasone, were co-crystalized and then ablated in aqueous media using a femtosecond pulsed laser and subsequently surface modified with the cationic polymer, chitosan, or poly-d-lysine.

Should Older Patients Accept a High KDPI Kidney or Wait? A National Data Analysis of Matched Cohorts.

Objective: This study addressed whether kidney transplant (KTx) candidates, ages 60+, should accept a high KDPI kidney and differences when considering a high (>85% vs low (<85%) KDPI KTx.

Summary/background Data: To date, there is limited survival data to guide decision-making for patients aged 60 years and older who are faced with the choice of accepting a high KDPI kidney or remaining on the waitlist.

Methods: Propensity-matched cohort study using data from United Network on Organ Sharing (2014-2021).

Postoperative outcome of palatine tonsillectomy by tonsil pillar suture with knot-free suture.

Background: Postoperative haemorrhage following palatine tonsillectomy occurs in 5-14% of cases. Since 2021, our department has used knot suturing with 3-0 Vicryl, and from 2023, continuous suturing with the V-Loc closure device to reduce suture time. While knot suturing is reported to reduce postoperative bleeding and pain, no studies have compared outcomes between different suture methods.

Loss of N-6 adenine-specific DNA methyltransferase 1 leads to meiotic prophase abnormalities and male sub-fertility in mice.

Mammalian sexual reproduction critically relies on the generation of haploid gametes following a specialized cell division process known as meiosis. Here, we demonstrate that N-6 Adenine-Specific DNA methyltransferase 1 (N6AMT1) plays a crucial role in the progression of meiosis during spermatogenesis, as follows. N6AMT1 was expressed in germ cells throughout the entire process of spermatogenesis, with a peak in mRNA levels in spermatocytes at the prophase I stage of meiosis.

March2 Alleviates Aortic Aneurysm/Dissection by Regulating PKM2 Polymerization.

Background: Aortic aneurysm/dissection (AAD) is a life-threatening disease lacking effective pharmacological treatment. Protein ubiquitination plays a pivotal role in cardiovascular diseases. However, the possible contribution of the E3 ubiquitin ligase March2 (membrane-associated RING finger protein 2) to the cause of AAD remains elusive.

Role of Perivascular Adipose Tissue in Vein Remodeling.

Perivascular adipose tissue (PVAT) plays a crucial, yet underexplored, role in vein remodeling, which occurs after bypass surgery using a venous graft or creation of arteriovenous fistulae for hemodialysis access. PVAT exhibits significant heterogeneity in phenotype and tissue composition depending on the vascular bed, as well as its anatomic location within the vasculature. Through the excretion of adipokines, cytokines, and chemokines, PVAT can shape the vascular response to local and systemic perturbations.

Murine Aortic Valve Cell Heterogeneity at Birth.

Background: Heart valve function requires a highly organized ECM (extracellular matrix) network that provides the necessary biomechanical properties needed to withstand pressure changes during each cardiac cycle. Lay down of the valve ECM begins during embryogenesis and continues throughout postnatal stages when it is remodeled into stratified layers and arranged according to blood flow. Alterations in this process can lead to dysfunction and, if left untreated, heart failure.

Role of Immune Cells in Perivascular Adipose Tissue in Vascular Injury in Hypertension.

Hypertension is associated with vascular injury characterized by vascular dysfunction, remodeling, and stiffening, which contributes to end-organ damage leading to cardiovascular events and potentially death. Innate (macrophages and dendritic cells), innate-like (γδ T cells) and adaptive immune cells (T and B cells) play a role in hypertension and vascular injury. Perivascular adipose tissue that is the fourth layer of the blood vessel wall is an important homeostatic regulator of vascular tone.

Recommendations for Design, Execution, and Reporting of Studies on Experimental Thoracic Aortopathy in Preclinical Models.

There is a recent dramatic increase in research on thoracic aortic diseases that includes aneurysms, dissections, and rupture. Experimental studies predominantly use mice in which aortopathy is induced by chemical interventions, genetic manipulations, or both. Many parameters should be deliberated in experimental design in concert with multiple considerations when providing dimensional data and characterization of aortic tissues.

Efficient estimation of the cox model when incorporating the subgroup restricted mean survival time.

The restricted mean survival time has been widely used in the field of medical research because of its clear physical and simple clinical interpretation. In this paper, we propose an efficient estimation that incorporates the auxiliary restricted mean survival information into the estimation of the proportional hazard (PH) model. Compared to conventional models that do not incorporate available auxiliary information, the proposed method improves efficiency in estimating regression parameters by utilizing the double empirical likelihood method.

Evaluation of Nutritional Values of Defatted Black Soldier Fly (Hermetia illucens) Larvae Meal Using the Precision-Fed Cecectomized Rooster Assay.

The use of insects, such as black soldier fly (Hermetia illucens) larvae meal (BSFLM), as an alternative protein source for pet food has gained attention due to their high nutritional value. The objective of this study was to determine the chemical composition, amino acid digestibility, and protein quality of defatted BSFLM of two distinct substrates (wheat and corn, BSFLM-W and BSFLM-C). Whole egg powder (WEP) and chicken meal (CM) were used as reference protein sources commonly used in pet foods.

Combining integral equation closures with force density functional theory for the study of inhomogeneous fluids.

Classical density functional theory (DFT) is a powerful framework to study inhomogeneous fluids. Its standard form is based on the knowledge of a generating free energy functional. If this is known exactly, then the results obtained by using standard DFT or its alternative, recently developed version, force-DFT, are the same.

A population-based cohort study of perinatal mental illness following traumatic brain injury.

Aims: To examine the risk of perinatal mental illness, including new diagnoses and recurrent use of mental healthcare, comparing women with and without traumatic brain injury (TBI), and to identify injury-related factors associated with these outcomes among women with TBI.

Methods: We conducted a population-based cohort study in Ontario, Canada, of all obstetrical deliveries to women in 2012-2021, excluding those with mental healthcare use in the year before conception. The cohort was stratified into women with no remote mental illness history (to identify new mental illness diagnoses between conception and 365 days postpartum) and those with a remote mental illness history (to identify recurrent illnesses).

Amino Acid Digestibility of Yellow Mealworm-Based Ingredients using the Precision-Fed Cecectomized Rooster Assay.

Yellow mealworms (Tenebrio molitor) serve as an alternative protein source. Because the amino acid (AA) concentrations, AA digestibility, and protein quality of ingredients may vary depending on their husbandry, harvest and processing procedures, and other factors, each should be evaluated separately. The objective of this study was to measure the AA composition, AA digestibility, and protein quality of yellow mealworm-based ingredients using the precision-fed cecectomized rooster assay.

Ethical issues surrounding the implementation of long-acting injectable antiretroviral therapy in sub-Saharan Africa.

Background: This article discusses the ethical issues surrounding the integration of long-acting injectable antiretroviral therapy (LA-ART) in the programmatic management of human immunodeficiency virus (HIV). As the medical landscape evolves, implementing LA-ART introduces many ethical issues that should be considered for the success of scale-up in diverse settings.

Methods: This article examines key issues such as bioethical concerns around the rollout of LA-ART, including regulatory requirements, a person's autonomy, informed consent, privacy and confidentiality; the societal implications of providing LA-ART, including the impact on stigma and discrimination; ethics around who receives LA-ART, financial accessibility, equitable access, inclusive decision-making and cultural sensitivity; and the ethics of providing an expensive intervention, including cost-effectiveness, supply chain sustainability and resource allocation.

Photocatalyzed Aerobic Oxidation of Thiols to Disulfides Using CuO Polyhedra.

To further demonstrate semiconductor facet effect to photocatalytic organic transformations and address a lack of using simple polyhedral semiconductor particles for disulfide bond formation, CuO cubes, octahedra, and rhombic dodecahedra were used to photocatalyze aerobic oxidation of 4-methylbenzenethiol. After reaction condition optimization, CuO crystals and ,,','-tetramethylethylenediamine (TMEDA) were added to 4-methylbenzenethiol in ethanol for thiol oxidation to 1,2-di--tolyldisulfane under 390 nm light-emitting diode (LED) lamp irradiation for just 5 min. Rhombic dodecahedra gave the highest product yield, followed by octahedra, cubes, and commercial CuO powder.

Development of a Calreticulin-targeting Glycan Ligand Based on a Hybrid Binding Concept.

Calreticulin (CRT), a chaperone that possesses both lectin and chaperone domains, is localized in the endoplasmic reticulum (ER). CRT has diverse functions and localizations; thus, CRT is a multifunctional protein. Particularly in the ER, CRT mainly aids in the proper folding of nascent glycoproteins as lectin chaperones.

Potential of enterocin from MF5 in controlling species.

This research paper presents the characterization of an enterocin-producing MF5 isolate and the determination of the in vitro antilisterial activity of enterocin produced by this isolate, named Ent-MF5. PCR-based screening for bacteriocin biosynthetic genes revealed that MF5 harbors multiple enterocin-encoding genes ( A, B, P and X), classified as class II bacteriocins and enterocin-P of (sharing up to 99% similarity at the genetic level). MF5 is sensitive to eight clinically important antibiotics and does not possess cytolysin activator -A, gelatinase -E and hyaluronidase -lA virulence genes.

Assessment of compliance with tetracycline eye ointment treatment to accelerate the elimination of trachoma in Yobe State, Nigeria.

Background: Trachoma, a neglected tropical disease, remains a significant public health concern in many regions, particularly in sub-Saharan Africa and in Yobe State, Nigeria. One approach for elimination involves administering tetracycline eye ointment (TEO) to children <6 months of age as part of annual mass drug administration (MDA), aligning with the World Health Organization's 'A' component of the SAFE (Surgery, Antibiotics, Facial hygiene and Environmental sanitation) strategy for elimination of trachoma as a public health problem. However, suboptimal compliance rates in affected populations pose challenges, potentially serving as a reservoir for reinfection and hindering progress toward trachoma elimination.