Phosphorylation-driven epichaperome assembly is a regulator of cellular adaptability and proliferation.

The intricate network of protein-chaperone interactions is crucial for maintaining cellular function. Recent discoveries have unveiled the existence of specialized chaperone assemblies, known as epichaperomes, which serve as scaffolding platforms that orchestrate the reconfiguration of protein-protein interaction networks, thereby enhancing cellular adaptability and proliferation. This study explores the structural and regulatory aspects of epichaperomes, with a particular focus on the role of post-translational modifications (PTMs) in their formation and function.

Combination of MDM2 and Targeted Kinase Inhibitors Results in Prolonged Tumor Control in Lung Adenocarcinomas With Oncogenic Tyrosine Kinase Drivers and Amplification.

Purpose: MDM2, a negative regulator of the TP53 tumor suppressor, is oncogenic when amplified. amplification (MDM2amp) is mutually exclusive with mutation and is seen in 6% of patients with lung adenocarcinoma (LUAD), with significant enrichment in subsets with receptor tyrosine kinase (RTK) driver alterations. Recent studies have shown synergistic activity of MDM2 and MEK inhibition in patient-derived LUAD models with MDM2amp and RTK driver alterations.

Combined inhibition of KRAS and mTORC1 kinase is synergistic in non-small cell lung cancer.

Current KRAS (OFF) inhibitors that target inactive GDP-bound KRAS cause responses in less than half of patients and these responses are not durable. A class of RAS (ON) inhibitors that targets active GTP-bound KRAS blocks ERK signaling more potently than the inactive-state inhibitors. Sensitivity to either class of agents is strongly correlated with inhibition of mTORC1 activity.

Diet induced insulin resistance is due to induction of PTEN expression.

Type 2 Diabetes (T2D) is a condition that is often associated with obesity and defined by reduced sensitivity of PI3K signaling to insulin (insulin resistance), hyperinsulinemia and hyperglycemia. Molecular causes and early signaling events underlying insulin resistance are not well understood. Insulin activation of PI3K signaling causes mTOR dependent induction of PTEN translation, a negative regulator of PI3K signaling.

Phosphorylation-Driven Epichaperome Assembly: A Critical Regulator of Cellular Adaptability and Proliferation.

The intricate protein-chaperone network is vital for cellular function. Recent discoveries have unveiled the existence of specialized chaperone complexes called epichaperomes, protein assemblies orchestrating the reconfiguration of protein-protein interaction networks, enhancing cellular adaptability and proliferation. This study delves into the structural and regulatory aspects of epichaperomes, with a particular emphasis on the significance of post-translational modifications in shaping their formation and function.

Charge carrier transport in PbS films doped with iodine.

The results of the measurements of electrical and Hall resistivities on polycrystalline PbS films doped with iodine obtained through hydrochemical deposition are presented. The analysis of the temperature dependence of resistivity points out the crossover from the hopping mechanism due to thermal delocalization in the impurity band to the variable range hopping mechanism. The increase in the iodine content in the films leads to an increase in the impurity ionization energy.

Vilsmeier-Haack-Initiated Formylative Rearrangement of Spirodioxo-lan-5-ones into Functionalized 4,5,6,7-Tetrahydrobenzofurans.

Pharmaceutically relevant bicyclic furans can be synthesized in a single step from substituted dioxolan-5-ones by reacting with Vilsmeier-Haack reagents. These reagents are generated from POCl or PBr and DMF. The reaction cascade is mechanistically complex and involves deoxyhalogenation, iminomethylation, and electrophilic rearrangement steps, which are facilitated by the DMF solvent.

Over-expression of N-acetylaspartate synthase exacerbates pathological energetic deficit and accelerates cognitive decline in the 5xFAD mouse.

N-acetylaspartate (NAA) is an abundant central nervous system amino acid derivative that is tightly coupled to mitochondria and energy metabolism in neurons. A reduced NAA signature is a prominent early pathological biomarker in multiple neurodegenerative diseases and becomes progressively more pronounced as disease advances. Because NAA synthesis requires aspartate drawn directly from mitochondria, we argued that this process is in direct competition with oxidative phosphorylation for substrate and that sustained high levels of NAA synthesis would be incompatible with pathological energy crisis.

Optimizing quantum noise-induced reservoir computing for nonlinear and chaotic time series prediction.

Quantum reservoir computing is strongly emerging for sequential and time series data prediction in quantum machine learning. We make advancements to the quantum noise-induced reservoir, in which reservoir noise is used as a resource to generate expressive, nonlinear signals that are efficiently learned with a single linear output layer. We address the need for quantum reservoir tuning with a novel and generally applicable approach to quantum circuit parameterization, in which tunable noise models are programmed to the quantum reservoir circuit to be fully controlled for effective optimization.

First 24-Membered Macrocyclic 1,10-Phenanthroline-2,9-Diamides-An Efficient Switch from Acidic to Alkaline Extraction of -Elements.

A reaction of acyl chlorides derived from 1,10-phenanthroline-2,9-dicarboxylic acids with piperazine allows the preparation of the corresponding 24-membered macrocycles in good yield. The structural and spectral properties of these new macrocyclic ligands were thoroughly investigated, revealing promising coordination properties towards f-elements (Am, Eu). It was shown that the prepared ligands can be used for selective extraction of Am(III) from alkaline-carbonate media in presence of Eu(III) with an SF up to 40.

Combination Therapy With MDM2 and MEK Inhibitors Is Effective in Patient-Derived Models of Lung Adenocarcinoma With Concurrent Oncogenic Drivers and MDM2 Amplification.

Introduction: Although targeted therapies have revolutionized the therapeutic landscape of lung adenocarcinomas (LUADs), disease progression on single-agent targeted therapy against known oncogenic drivers is common, and therapeutic options after disease progression are limited. In patients with MDM2 amplification (MDM2amp) and a concurrent oncogenic driver alteration, we hypothesized that targeting of the tumor-suppressor pathway (by means of restoration of p53 using MDM2 inhibition) and simultaneous targeting of co-occurring MAPK oncogenic pathway might represent a more durably effective therapeutic strategy.

Methods: We evaluated genomic next-generation sequencing data using the Memorial Sloan Kettering Cancer Center-Integrated Mutation Profiling of Actionable Cancer Targets platform to nominate potential targets for combination therapy in LUAD.

Improvement of Work Ability After Weight Loss Surgery: Results of a Longitudinal Study of Patients Suffering from Extreme Obesity Before and 4 Years After Bariatric Surgery.

Purpose: Body mass index (BMI) is directly associated with employment status. Our longitudinal prospective study is aimed at ascertaining whether work ability index (WAI) 4 years after surgery remains improved, such as 1 year after surgery, or changes and whether socio-demographic or psycho-social factors influence changes in work ability.

Materials And Methods: 197 bariatric surgery candidates were recruited.

A regioselective step-by-step CCl functionalization approach affords a novel family of CArTh'Th''H fullerene derivatives with promising antiviral properties.

We report a novel reaction of the recently discovered family of fullerene derivatives -CArTh' with thiophene derivatives Th''H yielding a previously unknown family of -CArTh'Th''H compounds with three different types of functional aromatic addends attached to the carbon cage. The discovered reaction paves a way to the synthesis of novel C fullerene derivatives with promising antioxidant and antiviral properties.

Fused-Pentagon Carbon Cages in Chloro and Trifluoromethyl Derivatives of C: Non-IPR CCl, C(CF), and Nonclassical C()Cl.

High-temperature chlorination of conventional IPR C can produce chloro derivatives of non-IPR C by skeletal transformations via Stone-Wales rearrangements (SWRs) of the carbon cage. We report the synthesis and structure elucidation of non-IPR CCl and nonclassical C()Cl. The present isolation of CCl hints at the possibility that the same product in the previously reported chlorine-doped arc-discharge synthesis could have, likewise, resulted from the initially formed IPR C.

The influence of iodide addition on the composition, morphology, crystal structure, and semiconductor and photoelectric properties of PbS films.

The concentration conditions for the deposition of lead sulfide and hydroxide in a citrate-ammonia reaction system by varying the pH value and the concentration of the ammonium iodide dopant are calculated. Kinetic studies of the process of conversion of lead salt into sulfide by varying the concentration of NHI in solution within the range of 0.0-0.

Changes in Work Ability after Weight-Loss Surgery: Results of a Longitudinal Study of Persons with Morbid Obesity before and after Bariatric Surgery.

Introduction: Bariatric surgery is a life-changing treatment, but knowledge of its influence on changes in work ability is still limited. We hypothesized that self-reported work ability improves in response to surgery-induced weight loss and sociodemographical variables (e.g.

Primary Sleeve Gastrectomy and Leaks: The Impact of Fundus-Wall Thickness and Staple Heights on Leakage-An Observational Study of 500 Patients.

The most feared complication of laparoscopic sleeve gastrectomy (LSG) is staple-line leakage. Staple height and fundus-wall thickness might influence such leakage, and this study examined their possible impact on leak incidence. Factors including gender, age, comorbidities, and reinforcement of the staple line were also investigated.

Water-Promoted Reaction of CArCl Compounds with Thiophenes Delivers a Family of Multifunctional Fullerene Derivatives with Selective Antiviral Properties.

Here we report a reaction of the fullerene derivatives CArCl, which enables the substitution of Cl with thiophene residues and the formation of the novel family of -symmetrical C fullerene derivatives with six functional addends CArTh. The discovered reaction provided a straightforward approach to the synthesis of previously inaccessible multifunctional water-soluble fullerene derivatives, including the compounds with antiviral activity against human immunodeficiency and influenza viruses.

Impact of microvascular injury various types on function of left ventricular in patients with primary myocardial infarction with ST segment elevation.

Aim: To analyze the long-term effect of microvascular injury various types on the structural and functional parameters of the left ventricle assessed by echocardiography in patients with primary ST-segment elevation myocardial infarction (STEMI).

Materials And Methods: The study included 60 patients with primary STEMI admitted within the first 12 hours after the onset of disease who underwent stenting of the infarct-associated coronary artery. Each patient included in the study underwent CMR imaging on the second day post-STEMI.

A nonlinear evolution of the structure, morphology, and optical properties of PbS-CdS films with cadmium nitrate in the reaction mixture.

Herein, we describe the nonlinear processes for the formation of thin films of the PbS-CdS system using chemical bath deposition with a gradual change in the cadmium nitrate content in the reaction mixture. The morphology of films was studied via scanning electron microscopy and atomic force microscopy. The mechanism for the formation of thin-film compounds can be considered as cluster-particle aggregation (diffusion-limited aggregation).

Synthesis and crystal structures of nickel(ii) and palladium(ii) complexes with o-carboranyl amidine ligands.

A number of new nido-carboranyl amidines 10-R(CH)NHC(Et)[double bond, length as m-dash]HN-7,8-CBH (n = 2, R = OH, OMe, and NMe; n = 3, R = OH) were synthesized by the nucleophilic addition of amino alcohols and N,N-dimethylethylenediamine to the highly activated -C[triple bond, length as m-dash]N- triple bond of the 10-propionitrilium derivative of nido-carborane. A similar reaction of 10-EtC[triple bond, length as m-dash]N-7,8-CBH with ethylenediamine unexpectedly resulted in the cleavage of the C[triple bond, length as m-dash]N bond to form the ammonium derivative 10-HN-7,8-CBH. The complexation of the synthesized carboranyl amidines 10-MeO(CH)NHC(Et)[double bond, length as m-dash]HN-7,8-CBH and 10-MeN(CH)NHC(Et)[double bond, length as m-dash]HN-7,8-CBH with nickel and palladium phosphine complexes [(PhP)MCl] (M = Ni, Pd) was studied.

Trifluoromethyl derivatives of pentagon-fused C: C(CF) (n = 10, 12, 14, 16).

The carbon cage of buckminsterfullerene I-C, obeying the Isolated-Pentagon Rule (IPR), can be transformed to the non-IPR C-C cage by a single Stone-Wales rearrangement (SWR) in the course of high-temperature chlorination of C with SbCl. The following high-temperature trifluoromethylation of the chlorination products with CFI afforded non-IPR CF derivatives, C(CF). X-ray diffraction studies of C(CF) (n = 10, 12, 14, 16) revealed that the sites of pentagon-pentagon fusions on the carbon cage are preferentially occupied by CF groups.

Estimating the Impact of Economic Fluctuations on Unemployment in Russian Regions Based on the Okun Model.

Based on the modified Okun's model, the article evaluates the impact of changes in production volumes on the dynamics of unemployment in Russia and three regional clusters differing in the unemployment rate and behavioral responses to economic shocks. Assessing the specifications of the basic Okun model on the data of 2010-2020 made it possible to identify a cyclical reaction of the unemployment rate in heterogeneous regional clusters to changes in output volumes.