Is San Diego California on Track to Reach HCV Elimination? A Modeling Analysis of Combination Prevention Strategies.

In 2020, the in the county of San Diego (COSD) was launched, a private-public joint endeavor between the COSD and the American Liver Foundation. We use epidemic modeling to assess whether the COSD is on track to reach its elimination targets (80% reduction in incidence, 65% reduction in hepatitis C virus (HCV)-related mortality by 2030 compared to 2015) and what intervention scale-up may be required. We adapted a previously developed dynamic, deterministic model of HCV transmission and disease progression among adults in the COSD, stratified by risk, age, gender, and human immunodeficiency virus (HIV) status.

Cell-Cultured Influenza Vaccine Enhances IFN-γ+ T Cell and Memory T Cell Responses Following A/Victoria/2570/2019 IVR-215 (A/H1N1) Infection.

Background: Influenza remains a significant public health challenge, with vaccination being a substantial way to prevent it. Cell-cultured influenza vaccines have emerged to improve on the drawbacks of egg-based vaccines, but there are few studies focusing on T cell immunity with both types of vaccines. Therefore, we studied the following 2022-2023 seasonal influenza vaccines with a standard dose and high dose: cell-based (C_sd and C_hd) and egg-based (E_sd and E_hd) vaccines.

Heterotropic Activation of Cytochrome P450 3A4 by Perillyl Alcohol.

: Perillyl alcohol (POH), a monoterpene natural product derived from the essential oils of plants such as perilla (), is currently in phase I and II clinical trials as a chemotherapeutic agent. In this study, we investigated the effect of POH on cytochrome P450 (CYP) activity for evaluating POH-drug interaction potential. : The investigation was conducted using pooled human liver microsomes (HLMs), recombinant CYP3A4 (rCYP3A4) enzymes, and human pluripotent stem cell-derived hepatic organoids (hHOs) employing liquid chromatography-tandem mass spectrometry.

Buccal Absorption of Biopharmaceutics Classification System III Drugs: Formulation Approaches and Mechanistic Insights.

Buccal drug delivery emerges as a promising strategy to enhance the absorption of drugs classified under the Biopharmaceutics Classification System (BCS) Class III, characterized by high solubility and low permeability. However, addressing the absorption challenges of BCS Class III drugs necessitates innovative formulation strategies. This review delves into optimizing buccal drug delivery for BCS III drugs, focusing on various formulation approaches to improve absorption.

Exploring Orodispersible Films Containing the Proteolysis Targeting Chimera ARV-110 in Hot Melt Extrusion and Solvent Casting Using Polyvinyl Alcohol.

Background/objectives: This project aims to provide valuable insights into the formulation of orodispersible films (ODFs) for the delivery of PROTAC ARV-110. The primary objective of this drug delivery formulation is to enhance the solubility of PROTAC ARV-110, which faces significant challenges due to the low solubility of this active pharmaceutical ingredient, as it belongs to a molecular class that is considered to exceed the "Rule of Five".

Methods: We employed the concept of developing a rapidly disintegrating ODF to enhance the solubility of PROTAC ARV-110, utilizing polyvinyl alcohol as the polymer of choice.

Combination of Inulin and Resistant Dextrin Has Superior Prebiotic Effects and Reduces Gas Production During In Vitro Fermentation of Fecal Samples from Older People.

Background: Older people are more susceptible to deterioration of the gut microbiota. Prebiotics help improve the gut microbiota. Inulin, a major prebiotic, stimulates the growth of ; however, it produces a large amount of gas, which leads to abdominal symptoms.

(-)-Syringaresinol Exerts an Antidepressant-like Activity in Mice by Noncompetitive Inhibition of the Serotonin Transporter.

Background: Durazz. is one of the most popular herbs used for depression treatment, but the molecular basis for its mechanism of action has not been fully addressed. Previously, we isolated and identified two lignan glycoside derivatives that were shown to noncompetitively inhibit serotonin transporter (SERT) activity but with a relatively low inhibitory potency compared with those of conventional antidepressants.

Enhancement of the Thermostability of Esterase by Combinatorial Rational Design.

The esterase EstSIT01 from can catalyze the asymmetric hydrolysis of -dimethyl ester to produce the crucial chiral intermediate (4, 5)-hemimethyl ester for -biotin synthesis. Despite its high yields and stereoselectivity, the low thermostability of EstSIT01 limits its practical application. Herein, two kinds of rational strategies were combined to enhance the thermostability of EstSIT01.

Mining and Characterization of Amylosucrase from for Synthesis of α-Arbutin Using Sucrose.

α-Arbutin is the fourth generation whitening factor in the field of cosmetics, which can block the synthesis of melanin in epidermal cells and has the advantages of good stability and less toxic side effects. Moreover, α-arbutin has potential application value in food, medicine, and other fields. However, the extraction yield from plant tissues is relatively low, which restricts its application value.

Ticagrelor Induces Angiogenesis in Progenitor and Mature Endothelial Cells In Vitro: Investigation of the Possible Role of Adenosine.

Ticagrelor, a reversible platelet P2Y receptor antagonist, exerts various pleiotropic actions, some of which are at least partially mediated through adenosine. We studied the ticagrelor and adenosine effect on the angiogenic properties of progenitor CD34-derived endothelial colony-forming cells (ECFCs). Angiogenesis studies were performed in vitro using capillary-like tube formation and spheroid-based angiogenesis assays.

The Impact of Comorbid Sleep-Disordered Breathing on Hospitalization Risk Related to Diabetes and Atherosclerotic Disease: A Retrospective Cohort Analysis.

To determine the relationship between comorbid sleep-disordered breathing (SDB) and hospitalization rates related to diabetes mellitus (DM) and atherosclerotic disease (AD). This study used a retrospective cohort design from a large medical claims database with 5 years of data between 2018 and 2022. The presences of SDB, DM, and AD were identified using International Classification of Diseases (ICD-10) and relevant Current Procedural Terminology (CPT) codes.

Meta-Analysis of MINIject vs. Two iStents as Standalone Treatment for Glaucoma with 24 Months of Follow-Up.

This study compares the long-term intraocular pressure (IOP)-lowering efficacy of standalone MINIject (iSTAR Medical, Belgium) suprachoroidal implantation and two iStent (Glaukos, CA, USA) trabecular bypass implantation using a systematic review and meta-analysis. Systematic review of standalone implantation of MINIject or iStent inject with at least 24 months of follow up. The mean and standard deviation of IOP and the number of IOP-lowering medications at baseline and at 24 months were extracted.

Effects of Oral Ingestion of L-Ornithine on Mental Stress and Fatigue Based on the Trier Social Stress Test in Healthy Humans: A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Trial.

With changes in the social environment typified by COVID-19, an increasing number of people are suffering from mental stress in interpersonal relationships and the resulting fatigue in recent years. L-ornithine oral ingestion reportedly suppresses the secretion of cortisol, a stress marker, through the hypothalamic-pituitary-adrenal (HPA) axis. However, there is insufficient research to determine whether L-ornithine exerts an ameliorative effect on social stress.

Reassessing Pulmonary Hypertension Classification: Utilizing Criteria for Heart Failure with Preserved Ejection Fraction Instead of Pulmonary Arterial Wedge Pressure.

: The current classification of pulmonary hypertension (PH) distinguishes between pre-capillary (PAWP ≤ 15 mmHg) and post-capillary (PAWP > 15 mmHg) forms, with left heart disease, especially heart failure with preserved ejection fraction (HFpEF), being a common cause of PH. We investigated the suitability of an HFpEF diagnosis instead of PAWP in diagnosing PH associated with HFpEF. : In a retrospective, single-center analysis, we reviewed diagnoses from our database, focusing on patients initially diagnosed with idiopathic pulmonary arterial hypertension (IPAH) or PH associated with HFpEF (PH-HFpEF) based on their PAWP.

Identification of Novel Inhibitors of Starch Excess 4 (SEX4).

This study identified several inhibitors of Starch Excess 4 (SEX4), an enzyme in plants' starch decomposition. Our research aims to inhibit starch breakdown by SEX4 with its potential to significantly impact food security, leading to starch accumulation in plants such as potatoes, sweet potatoes, and significant crops like grains and rice. We recognized potential candidates by screening approximately 1840 chemical compounds using the phosphatase assay against NPP.

Obinutuzumab in Combination with Alternative Chlorambucil Schedules in Front-Line Treatment of Chronic Lymphocytic Leukemia: A Study by KroHem, the Croatian Cooperative Group for Hematologic Diseases.

Obinutuzumab was approved for front-line treatment of chronic lymphocytic leukemia in combination with chlorambucil pulses administered every 2 wks. Alternative schedules of chlorambucil enable the administration of higher total chlorambucil doses, and have better antileukemia activity. So far, evidence on the feasibility of combining obinutuzumab with alternative chlorambucil schedules is lacking.

A Novel Ginsenoside-Transforming α-L-Rhamnosidase from : Screening, Characterization and Application.

Despite the rapid advancement of glycosidase biotechnology, ginsenoside-transforming rhamnosidases remain underexplored due to a lack of research. In this study, we aimed to bridge this gap by evaluating eight putative rhamnosidases for their ability to transform ginsenosides. Among them, a novel rhamnosidase (C118) from was identified as being efficient at hydrolyzing ginsenoside Re.

Differential Regulation of Hyaluronan Synthesis by Three Isoforms of Hyaluronan Synthases in Mammalian Cells.

Hyaluronan (HA) is one of the crucial components of the extracellular matrix in vertebrates and is synthesized by three hyaluronan synthases (HASs), namely HAS1, HAS2, and HAS3. The low expression level of HASs in normal keratinocytes and other various types of cells presents a recognized challenge, impeding biological and pathological research on their localization. In this study, the human proteins HAS1, HAS2, and HAS3 with fused maltose-binding protein (MBP) tags were successfully expressed at high levels and purified for the first time in HEK293F cells.

Anchorage Accurately Assembles Anchor-Flanked Synthetic Long Reads.

Modern sequencing technologies allow for the addition of short-sequence tags, known as anchors, to both ends of a captured molecule. Anchors are useful in assembling the full-length sequence of a captured molecule as they can be used to accurately determine the endpoints. One representative of such anchor-enabled technology is LoopSeq Solo, a synthetic long read (SLR) sequencing protocol.

α-Cyclodextrin supplementation improves endurance exercise performance and reduces post-exercise fatigue in human males: a randomized, double-blind, placebo-controlled, parallel-group study.

α-Cyclodextrin (αCD), a cyclic hexasaccharide composed of six glucose units, is not digested in the small intestine but is completely fermented by gut microbes. Recently, we have reported that αCD supplementation for nonathlete men improved their 10 km biking times. However, the beneficial effects of αCD on exercise are not yet fully understood.

Autogene cevumeran with or without atezolizumab in advanced solid tumors: a phase 1 trial.

Effective targeting of somatic cancer mutations to enhance the efficacy of cancer immunotherapy requires an individualized approach. Autogene cevumeran is a uridine messenger RNA lipoplex-based individualized neoantigen-specific immunotherapy designed from tumor-specific somatic mutation data obtained from tumor tissue of each individual patient to stimulate T cell responses against up to 20 neoantigens. This ongoing phase 1 study evaluated autogene cevumeran as monotherapy (n = 30) and in combination with atezolizumab (n = 183) in pretreated patients with advanced solid tumors.

Burn-induced mitochondrial dysfunction in hepatocytes: The role of methylation-controlled J protein silencing.

Background: Burn injuries trigger a systemic hyperinflammatory response, leading to multiple organ dysfunction, including significant hepatic damage. The liver plays a crucial role in regulating immune responses and metabolism after burn injuries, making it critical to develop strategies to mitigate hepatic impairment. This study investigates the role of methylation-controlled J protein (MCJ), an inner mitochondrial protein that represses complex I in burn-induced oxidative stress and mitochondrial dysfunction, using an in vitro Alpha Mouse Liver 12 cell model.

Identification of cellular signatures associated with chinese hamster ovary cell adaptation for secretion of antibodies.

The secretory capacity of Chinese hamster ovary (CHO) cells remains a fundamental bottleneck in the manufacturing of protein-based therapeutics. Unconventional biological drugs with complex structures and processing requirements are particularly problematic. Although engineered vector DNA elements can achieve rapid and high-level therapeutic protein production, a high metabolic and protein folding burden is imposed on the host cell.