Analysis of glutamate-dependent mechanism and optimization of fermentation conditions for poly-gamma-glutamic acid production by Bacillus subtilis SCP017-03.

Poly-gamma-glutamic acid (γ-PGA) is mainly synthesized by glutamate-dependent strains in the manufacturing industry. Therefore, understanding glutamate-dependent mechanisms is imperative. In this study, we first systematically analyzed the response of Bacillus subtilis SCP017-03 to glutamate addition by comparing transcriptomics and proteomics.

Potential Azo-8-hydroxyquinoline derivatives as multi-target lead candidates for Alzheimer's disease: An in-depth in silico study of monoamine oxidase and cholinesterase inhibitors.

Cognitive dysfunction in Alzheimer's disease results from a complex interplay of various pathological processes, including the dysregulation of key enzymes such as acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), and monoamine oxidase B (MAO-B). This study proposes and designs a series of novel molecules derived from 8-hydroxyquinoline (Azo-8HQ) as potential multi-target lead candidates for treating AD. An exhaustive in silico analysis was conducted, encompassing docking studies, ADMET analysis, density functional theory (DFT) studies, molecular dynamics simulations, and subsequent MM-GBSA calculations to examine the pharmacological potential of these molecules with the specific targets of interest.

Amino acid stable carbon isotopes in nail keratin illuminate breastfeeding and weaning practices of mother - infant dyads.

Compound-specific stable carbon isotope analysis of amino acids (CSIA-AA) is widely used in ecological studies to analyze food-webs and is gaining use in archaeology for investigating past diets. However, its use in reconstructing breastfeeding and weaning practices is not fully understood. This study evaluates the efficacy of stable carbon isotope analysis of amino acids in early life diet reconstruction by analyzing keratin from fingernail samples of three mother-infant pairs during late gestation and early postpartum periods.

Accuracy of two-compartment modelling of gas exchange with ventilation-perfusion mismatch in inhalational anesthesia.

Background: Multi-compartment computer models of heterogeneity in alveolar ventilation-perfusion ratios (VA/Q scatter) across the lung explain the significant alveolar-arterial (A-a) partial pressure gradients and associated alveolar dead-space fractions (VDA/VA) seen in anesthetized patients for both carbon dioxide and for anesthetic gases of different blood solubilities. However, the accuracy of a simpler two-compartment model of VA/Q scatter to do this has not been tested or compared to calculations from the traditional Riley model with "ideal", unventilated (shunt) and unperfused (deadspace) compartments.

Methods: Measurements of gas partial pressures in inspired and expired gas and arterial and mixed venous blood from 29 patients undergoing inhalational general anesthesia for cardiac surgery was used to compare the accuracy of two simple models of VA/Q scatter and lung gas exchange in predicting measured alveolar and arterial partial pressure differences, and associated alveolar dead-space calculations for the modern anesthetic gases isoflurane, sevoflurane and desflurane.

Cryo-EM structure of AAV2 Rep68 bound to integration site AAVS1: insights into the mechanism of DNA melting.

The Rep68 protein from Adeno-Associated Virus (AAV) is a multifunctional SF3 helicase that performs most of the DNA transactions necessary for the viral life cycle. During AAV DNA replication, Rep68 assembles at the origin of replication, catalyzing the DNA melting and nicking reactions during the hairpin rolling replication process to complete the second-strand synthesis of the AAV genome. We report the cryo-electron microscopy structures of Rep68 bound to the adeno-associated virus integration site 1 in different nucleotide-bound states.

Web-Based Exercise and Nutrition Intervention to Improve Leg Muscle Strength and Physical Functioning in Older Adults: Pre-Post Pilot Study.

Background: The lifestyle intervention ProMuscle, which combines resistance exercise and an increased protein intake, was effective in improving muscle strength, muscle mass, and physical functioning in older adults. However, due to a growing shortage of health care professionals, the rapidly growing aging population cannot be personally guided in the future. Therefore, Uni2Move, a scalable web-based variant of ProMuscle, was designed to reach larger groups of older adults without putting additional burden on health care professionals.

Linking Adherence to Effectiveness in Family-Based Adolescent ADHD Academic Training and Medication Decision-Making Protocols.

Objective: Changing Academic Support in the Home for Adolescents with ADHD (CASH-AA) and Medication Integration Protocol (MIP) are two family-based behavioral protocols designed to promote family solutions to academic problems and medication decision-making. Building on a randomized control trial examining these protocols, the current study examined how protocol dose, an indicator of treatment adherence, was associated with treatment outcomes.

Method: The sample consisted of 145 adolescent clients (M age = 14.

Pathogenesis and regenerative therapy in vitiligo and alopecia areata: focus on hair follicle.

Vitiligo is an autoimmune disease characterized by the loss of functional melanocytes in the hair follicles and epidermis, leading to white patches on the skin and mucous membranes. Alopecia areata (AA) is a common immune-mediated condition in which autoimmune attack on hair follicles cause non-scarring hair loss. Both diseases significantly impact patients's physical and mental health.

Effects of vitamin D and L-cysteine cosupplementation on circulating bioavailable and total 25-hydroxy-vitamin D, the free/total testosterone ratio and inflammatory biomarkers in healthy vitamin D-deficient African Americans: a placebo-controlled double-blind clinical trial.

Background: Subjects with metabolic syndrome and obesity have higher levels of inflammation with depression of the vitamin D (VD) hydroxylase/metabolising genes () required to convert VD consumed in the diet into 25(OH)VD. Compared with total 25(OH)VD levels, measurement of bioavailable 25(OH)VD is a better method to determine the beneficial effect of VD.

Objective: This study investigates whether cosupplementation with VD and L-cysteine (LC), which downregulates inflammation and upregulates VD-regulating genes, provides a better therapeutic benefit than supplementation with VD-alone in African Americans (AA).

Prevalence and predictive factors of testosterone-induced erythrocytosis: a retrospective single center study.

Aim: This study analyzes the prevalence and predictive factors of testosterone-induced erythrocytosis (TIE) in patients receiving testosterone replacement therapy (TRT).

Methods: Retrospective single-center observational study.

Results: 247 patients were included; median age was 47.

Auricular Acupuncture for Perioperative Pain Management: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Purpose: We conducted a more comprehensive systematic review and meta-analysis to evaluate the effectiveness of auricular acupuncture (AA) in perioperative pain management.

Methods: Randomized controlled trials (RCTs) findings were retrieved from the Embase, Cochrane Central Register of Controlled Trials, PubMed, Web of Science, Chinese Biomedical Literature Database, Wanfang, VIP, and China National Knowledge Infrastructure databases from their inception to March 2024 using the search terms "pain", "auriculotherapy", and "randomized controlled trial". The experimental group was treated with AA alone or in combination with analgesic drugs, whereas the control group was treated with sham auricular acupuncture, placebo, conventional treatment, or no treatment.

Identification of the AHP family reveals their critical response to cytokinin regulation during adventitious root formation in apple rootstock.

Adventitious root (AR) formation is a bottleneck for vegetative proliferation. In this study, 13 AHP genes (MdAHPs) were identified in the apple genome. Phylogenetic analysis grouped them into 3 clusters (I, II, III), with 4, 4, and 5 genes respectively.

Evidence for a shared cognitive mechanism underlying relative rhythmic and melodic perception.

Musical melodies and rhythms are typically perceived in a relative manner: two melodies are considered "the same" even if one is shifted up or down in frequency, as long as the relationships among the notes are preserved. Similar principles apply to rhythms, which can be slowed down or sped up proportionally in time and still be considered the same pattern. We investigated whether humans perceiving rhythms and melodies may rely upon the same or similar mechanisms to achieve this relative perception.

Real-world treatment patterns and survival outcomes in men with metastatic castration-resistant prostate cancer in Finland: a national, population-based cohort study.

Background: Metastatic castration-resistant prostate cancer (mCRPC) treatment is advancing yet Nordic, real-world evidence for its use is scarce. In this population-based cohort study, we describe characteristics of patients with mCRPC, and their treatment patterns and survival outcomes in Finland.

Methods: Incident patients with mCRPC diagnosed during 2013-2021 were identified from data lakes in two large and representative, Finnish hospital districts, and linked to data on drug purchases and causes of death from national registries.

Evaluation of Lyso-Gb1 as a biomarker for Gaucher disease treatment outcomes using data from the Gaucher Outcome Survey.

Background: Patients with Gaucher disease (GD) require continual monitoring; however, lack of specific disease biomarkers was a significant challenge in the past. Glucosylsphingosine (lyso-Gb1) has been shown to be a reliable, key, specific, and sensitive biomarker for diagnosis, prognosis, and treatment response in clinical studies of patients with GD. We evaluated the change in lyso-Gb1 concentration over time following enzyme replacement therapy in patients with confirmed GD using real-world data from the Gaucher Outcome Survey disease registry.

N7-methylguanosine modification in cancers: from mechanisms to therapeutic potential.

N7-methylguanosine (m7G) is an important RNA modification involved in epigenetic regulation that is commonly observed in both prokaryotic and eukaryotic organisms. Their influence on the synthesis and processing of messenger RNA, ribosomal RNA, and transfer RNA allows m7G modifications to affect diverse cellular, physiological, and pathological processes. m7G modifications are pivotal in human diseases, particularly cancer progression.

Dioscin pretreatment ameliorates ferroptosis in cardiomyocytes after myocardial infarction via inhibiting endoplasmic reticulum stress.

Background: Myocardial infarction (MI) remains a leading cause of mortality globally, often resulting in irreversible damage to cardiomyocytes. Ferroptosis, a recently identified form of regulated cell death driven by iron-dependent lipid peroxidation, has emerged as a significant contributor to post-MI cardiac injury. The endoplasmic reticulum (ER) stress response has been implicated in exacerbating ferroptosis.

Effects of thermal aging on the performance of ordinary and novel superhydrophobic and oleophobic ultra-fine dry powder extinguishing agent.

Powder-based fire extinguishing agents have become a kind of promising substitutes for halon extinguishing agents in civil aircrafts. However, their storage lifespan, significantly influenced by the thermal aging, emerges as a crucial yet overlooked aspect for aviation use. This study investigates the effects of thermal aging cycles on various parameters of ordinary dry powder extinguishing agent (ODPEA) and novel superhydrophobic and oleophobic ultra-fine dry powder extinguishing agent (SHOU DPEA), including surface microscopic morphology, D90 (the diameter at which 90% of the cumulative volume of particles are equal to or smaller than this value), chemical structure, hydrophobic and oleophobic angles, flowability, extinguishing time and effectiveness.

The question of strains in AA amyloidosis.

The existence of transmissible amyloid fibril strains has long intrigued the scientific community. The strain theory originates from prion disorders, but here, we provide evidence of strains in systemic amyloidosis. Human AA amyloidosis manifests as two distinct clinical phenotypes called common AA and vascular AA.

Triaging mammography with artificial intelligence: an implementation study.

Purpose: Many breast centers are unable to provide immediate results at the time of screening mammography which results in delayed patient care. Implementing artificial intelligence (AI) could identify patients who may have breast cancer and accelerate the time to diagnostic imaging and biopsy diagnosis.

Methods: In this prospective randomized, unblinded, controlled implementation study we enrolled 1000 screening participants between March 2021 and May 2022.

Acute appendicitis and its treatment: a historical overview.

Purpose: Acute appendicitis (AA) is the leading cause of acute abdomen worldwide, with an incidence of 90-100 cases per 100,000 individuals annually and a lifetime risk of 7-12%. Despite its prevalence, historical accounts of AA are limited, particularly when compared to conditions like haemorrhoids, likely due to the appendix's internal location. This article traces the historical evolution of AA treatment from ancient times to the present, highlighting key contributions.

A neural network for long-term super-resolution imaging of live cells with reliable confidence quantification.

Super-resolution (SR) neural networks transform low-resolution optical microscopy images into SR images. Application of single-image SR (SISR) methods to long-term imaging has not exploited the temporal dependencies between neighboring frames and has been subject to inference uncertainty that is difficult to quantify. Here, by building a large-scale fluorescence microscopy dataset and evaluating the propagation and alignment components of neural network models, we devise a deformable phase-space alignment (DPA) time-lapse image SR (TISR) neural network.

Medical management pathways for Cushing's disease in pituitary tumors centers of excellence (PTCOEs).

Purpose: A recent update of consensus guidelines for the management of Cushing's disease (CD) included indications for medical therapy. However, there is limited evidence regarding their implementation in clinical practice. This study aimed to evaluate current medical therapy approaches by expert pituitary centers through an audit conducted to validate the criteria of Pituitary Tumors Centers of Excellence (PTCOEs) and provide an initial standard of medical care for CD.

Four Neurotoxic Insecticides Impair Partner and Host Finding in the Parasitoid Leptopilina heterotoma and Bioactive Doses Can Be Taken up Via the Host.

In modern agriculture, control of insect pests is achieved by using insecticides that can also have lethal and sublethal effects on beneficial non-target organisms. Here, we investigate acute toxicity and sublethal effects of four insecticides on the males' sex pheromone response and the female host finding ability of the Drosophila parasitoid Leptopilina heterotoma. The nicotinic acetylcholine receptor antagonists acetamiprid, flupyradifurone and sulfoxaflor, as well as the acetylcholinesterase inhibitor dimethoate were applied topically as acetone solutions.