Coupling cellular drug-target engagement to downstream pharmacology with CeTEAM.

Cellular target engagement technologies enable quantification of intracellular drug binding; however, simultaneous assessment of drug-associated phenotypes has proven challenging. Here, we present cellular target engagement by accumulation of mutant as a platform that can concomitantly evaluate drug-target interactions and phenotypic responses using conditionally stabilized drug biosensors. We observe that drug-responsive proteotypes are prevalent among reported mutants of known drug targets.

Artificial neural network inference analysis identified novel genes and gene interactions associated with skeletal muscle aging.

Background: Sarcopenia is an age-related muscle disease that increases the risk of falls, disabilities, and death. It is associated with increased muscle protein degradation driven by molecular signalling pathways including Akt and FOXO1. This study aims to identify genes, gene interactions, and molecular pathways and processes associated with muscle aging and exercise in older adults that remained undiscovered until now leveraging on an artificial intelligence approach called artificial neural network inference (ANNi).

Acute responses of strength-related gene expressions to maximum strength and force sense acuity.

Background/aim: Although high muscle strength worsens the sense of force, it is unknown whether there is a relationship between this deterioration and the underlying molecular mechanisms. This study examined the relationship between decreased force sense (FS) acuity and strength-related gene expressions.

Materials And Methods: Maximal voluntary isometric contraction (MVIC) and FS (50% MVIC) tests were performed on the knee joints of twenty-two subjects.

Microstructural analysis of verbal fluency performance in relapsing-remitting multiple sclerosis based on the impact of disability level.

Verbal fluency (VF) evaluates language and cognitive abilities. This study compared VF in Relapsing-Remitting Multiple Sclerosis (RRMS) and healthy controls (HC), examining variables including correct responses (CR), mean cluster size (MCS), switches (S), and fluency difference score (FDS). RRMS participants were subgrouped by Expanded Disability Status Scale (EDSS), to explore the relationship between MS severity and VF.

Chemical Characterization, DNA-Damage Protection, Antiproliferative Activity and in Silico Studies of the Essential Oils from Perralderia coronopifolia Coss.

In this study, for the first time, we analyzed the chemical composition of essential oils (EOs) steam-distilled from the flowers and leaves of Perralderia coronopifolia by GC-FID/MS. The objective was to explore new anticancer and antioxidant bioactive substances and understand their mechanisms of action through the use of plant-derived natural products. The major chemical components characterizing the EOs were cis-chrysanthenyl acetate 1, 6-oxocyclonerolidol 2, cis-8-acetoxychrysanthenyl acetate 3, and 6α-hydroxycyclonerolidol 4, respectively.

Promising Outcomes in Acromegaly Patients Receiving CyberKnife Stereotactic Hypofractionated Radiotherapy.

Background: The primary treatment for patients with acromegaly has traditionally been transsphenoidal surgery, with decreasing reliance on radiotherapy (RT) due to advancements in pharmacotherapy (PT). Despite these advancements, a substantial portion of patients still face persistent acromegaly, necessitating novel treatment approaches. This study investigates the role of CyberKnife Stereotactic Hypofractionated Radiotherapy (CK-HFRT) in persistent acromegaly.

Emergence and Progression of Behavioral Motor Deficits and Skeletal Muscle Atrophy across the Adult Lifespan of the Rat.

The facultative loss of muscle mass and function during aging (sarcopenia) poses a serious threat to our independence and health. When activities of daily living are impaired (clinical phase), it appears that the processes leading to sarcopenia have been ongoing in humans for decades (preclinical phase). Here, we examined the natural history of sarcopenia in male outbred rats to compare the occurrence of motor behavioral deficits with the degree of muscle wasting and to explore the muscle-associated processes of the preclinical and clinical phases, respectively.

Energy-Efficient Hardware Implementation of Fully Connected Artificial Neural Networks Using Approximate Arithmetic Blocks.

In this paper, we explore efficient hardware implementation of feedforward artificial neural networks (ANNs) using approximate adders and multipliers. Due to a large area requirement in a parallel architecture, the ANNs are implemented under the time-multiplexed architecture where computing resources are re-used in the multiply accumulate (MAC) blocks. The efficient hardware implementation of ANNs is realized by replacing the exact adders and multipliers in the MAC blocks by the approximate ones taking into account the hardware accuracy.

Cisplatin-docetaxel induction chemotherapy for patients with nasopharyngeal carcinoma in a non-endemic cohort.

This is the report on our clinic's 15 years of experience (2004-2018) on nasopharyngeal carcinoma (NPC), treated with induction chemotherapy (IC) and subsequent concomitant chemoradiotherapy (CCRT), comprising population characteristics and treatment outcomes of 203 patients with non-metastatic NPC. IC comprised docetaxel (75 mg/m) and cisplatin (75 mg/m) combination (TP). Concurrent cisplatin (P) was applied either weekly (40 mg/m, 32 cases) or every-3-week (100 mg/m, 171 cases).

Point-of-care testing: a disposable label-free electrochemical CA125 and HE4 immunosensors for early detection of ovarian cancer.

Cancer antigen 125 (CA125) and human epididymal secretory protein 4 (HE4) are critical biomarkers for ovarian cancer diagnosis and progression monitoring; therefore, sensitive determination of their levels in body fluids is crucial. In recent study, label-free CA125 and HE4 immunosensors were prepared using disposable screen-printed carbon electrodes modified with reduced graphene oxide, polythionine, and gold nanoparticles for the sensitive, fast, and practical determination of CA125 and HE4. Differential pulse voltammetry, square wave voltammetry, and electrochemical impedance spectroscopy methods were used for the electrochemical determination of antigens in four different linear ranges (1-100 pg mL, 0.

Monkeypox Detection Using CNN with Transfer Learning.

Monkeypox disease is caused by a virus that causes lesions on the skin and has been observed on the African continent in the past years. The fatal consequences caused by virus infections after the COVID pandemic have caused fear and panic among the public. As a result of COVID reaching the pandemic dimension, the development and implementation of rapid detection methods have become important.

A label-free dual immunosensor for the simultaneous electrochemical determination of CA125 and HE4 biomarkers for the early diagnosis of ovarian cancer.

The blood levels of cancer antigen 125 (CA125) and human epididymal secretory protein 4 (HE4) are measured in the diagnosis and progression monitoring of ovarian cancer (OC), and the Risk of Ovarian Malignancy Algorithm (ROMA) score% values are calculated for cancer risk assessment. For the first time, disposable dual screen-printed carbon electrodes modified with reduced graphene oxide, polythionine, and gold nanoparticles were used to fabricate label-free electrochemical dual CA125-HE4 immunosensors for the sensitive, fast, and practical simultaneous determination of CA125 and HE4. DPV and SWV methods were used to simultaneously determine antigens in two different linear ranges (1-100 pg mL and 1-50 ng mL).

Single-cell sequencing deconvolutes cellular responses to exercise in human skeletal muscle.

Skeletal muscle adaptations to exercise have been associated with a range of health-related benefits, but cell type-specific adaptations within the muscle are incompletely understood. Here we use single-cell sequencing to determine the effects of exercise on cellular composition and cell type-specific processes in human skeletal muscle before and after intense exercise. Fifteen clusters originating from six different cell populations were identified.

Evaluation of different nutrient limitation strategies for the efficient production of poly(hydroxybutyrate-co-hydroxyvalerate) from waste frying oil and propionic acid in high cell density fermentations of H16.

Because of its application potential and biodegradability, poly(3-hydroxybutyrate-co-3-hydroxyvalerate;PHBV), a member of the polyhydroxyalkanoates (PHA) biopolymer family, is one of the most extensively studied PHA. High PHBV productivity with a significant amount of hydroxyvalerate (HV) content is very appealing for commercial scale production. The goal of this study was to investigate the efficiency of various defined limitation strategies, namely nitrogen, phosphorus, and oxygen-limitation, for high yield PHBV production by H16 with increased HV unit using waste frying vegetable oil (WFO) and propionic acid (PA) in a high cell density culture (5 L bioreactor).

Determination of chemical compositions and antibacterial effects of selected essential oils against human pathogenic strains.

Increasing the rates of drug resistant bacteria, having adverse effects and also high costs of antibiotics lead to essential oils (EOs) with antibacterial properties have gained importance. The present study was predicted to evaluate antibacterial activity of cinnamon, lavender, tea tree, lemon, coconut, oregano, mint, laurel and eucalyptus EOs alone and in combination. Chemical components of effective EOs were examined through gas chromatography/mass spectrometry (GC/MS).

Three new iridoids from the aerial parts of Willd. and antiproliferative activities of extracts.

The aerial parts of Willd. were extracted with the solvents of different polarities. The antiproliferative activities of the extracts were evaluated against rat brain tumor (C6) and human cervix carcinoma (HeLa) cell lines.

Inhibition of the ubiquitin-proteasome system by an NQO1-activatable compound.

Malignant cells display an increased sensitivity towards drugs that reduce the function of the ubiquitin-proteasome system (UPS), which is the primary proteolytic system for destruction of aberrant proteins. Here, we report on the discovery of the bioactivatable compound CBK77, which causes an irreversible collapse of the UPS, accompanied by a general accumulation of ubiquitylated proteins and caspase-dependent cell death. CBK77 caused accumulation of ubiquitin-dependent, but not ubiquitin-independent, reporter substrates of the UPS, suggesting a selective effect on ubiquitin-dependent proteolysis.

The Correlation between Selenium-Dependent Glutathione Peroxidase Activity and Oxidant/Antioxidant Balance in Sera of Diabetic Patients with Nephropathy.

Background: Oxidative stress is an imbalance between free radical's production and the body's ability to counteract or detoxify their harmful effects through neutralization by antioxidants, oxidative stress is thought to be involved in the pathogenesis of diabetic nephropathy. One of the key enzymatic antioxidants is glutathione peroxidase (GPx), which plays an important protective function in diabetes complications, by reducing the rising state of oxidative stress and removing toxicity from peroxides and converting them into a non-toxic substance. The objective of this research was to evaluate the rule of glutathione peroxidase in regulate oxidants/antioxidants levels diabetic patients with nephropathy.

Nasopharyngeal carcinoma in children: Multimodal treatment and long-term outcome of 92 patients in a single center over a 28-year period.

Objectives: The aim of the study was to evaluate the long-term outcome and late effects in pediatric patients with nasopharyngeal carcinoma (NPC) treated with neoadjuvant chemotherapy (NACT), followed by radiotherapy (RT).

Methods: Ninety-two children (65 male, 27 female) diagnosed with NPC between 1989 and 2017 in the Istanbul University, Institute of Oncology were evaluated retrospectively. NACT consisted of three cycles of cisplatin-containing regimen every 3 weeks, followed by RT.

The exon-junction complex helicase eIF4A3 controls cell fate via coordinated regulation of ribosome biogenesis and translational output.

Eukaryotic initiation factor 4A-III (eIF4A3), a core helicase component of the exon junction complex, is essential for splicing, mRNA trafficking, and nonsense-mediated decay processes emerging as targets in cancer therapy. Here, we unravel eIF4A3's tumor-promoting function by demonstrating its role in ribosome biogenesis (RiBi) and p53 (de)regulation. Mechanistically, eIF4A3 resides in nucleoli within the small subunit processome and regulates rRNA processing via R-loop clearance.

The isolation of secondary metabolites from Rheum ribes L. and the synthesis of new semi-synthetic anthraquinones: Isolation, synthesis and biological activity.

Rheum ribes L. (Rhubarb) is one of the most important edible medicinal plants in the Eastern Anatolia region and is called "Işkın" by local people. Resveratrol and 6-O-methylalaternin were isolated from the Rhubarb for the first time in addition to well-known secondary metabolites including emodin, aloe-emodin, β-sitosterol and rutin.

Involvement of Autophagy in Levodopa-Induced Dyskinesia.

Background: Autophagy is intensively studied in cancer, metabolic and neurodegenerative diseases, but little is known about its role in pathological conditions linked to altered neurotransmission. We examined the involvement of autophagy in levodopa (l-dopa)-induced dyskinesia, a frequent motor complication developed in response to standard dopamine replacement therapy in parkinsonian patients.

Methods: We used mouse and non-human primate models of Parkinson's disease to examine changes in autophagy associated with chronic l-dopa administration and to establish a causative link between impaired autophagy and dyskinesia.