Multiwavelength highly transient stimulated Raman scattering on dual Raman modes in Sr(MoO4)0.8(WO4)0.2 and Sr(MoO4)0.4(WO4)0.6.

For the first time to our knowledge, multiwavelength, highly transient, single-pass stimulated Raman scattering with a low wavelength spacing on dual (stretching and bending) Raman modes in Sr(MoO4)0.8(WO4)0.2 and Sr(MoO4)0.4(WO4)0.6 solid solutions in a range of 1000-1300 nm (transparence window of biological tissue) under ultrafast chirped pulse laser pumping is comparatively investigated in the interests of multicolor two-photon imaging of a living tissue. For both the solid solutions, the optimum range (1-5 ps) of chirped pump pulse durations for multiwavelength Raman conversion on dual Raman modes was wider than for SrMoO4 (2-3 ps) due to the higher integral cross section of the bending Raman mode. Higher efficient SRS conversion took place at negative chirping of the pump pulse with its stretching from 0.25 ps up to 5 ps due to the compensation of a positive chirp caused by nonlinear phase modulation with total Raman conversion efficiency of up to 36% for Sr(MoO4)0.8(WO4)0.2 and 49% for Sr(MoO4)0.4(WO4)0.6. The highest number (five) of Stokes components in the desired range (1000-1300 nm) was observed in the optimum Sr(MoO4)0.4(WO4)0.6 solid solution, which has the Raman modes with comparable intensities.

The "Doorstop Pocket" In Thioredoxin Reductases─An Unexpected Druggable Regulator of the Catalytic Machinery.

Pyridine nucleotide-disulfide oxidoreductases are underexplored as drug targets, and thioredoxin reductases (TrxRs) stand out as compelling pharmacological targets. Selective TrxR inhibition is challenging primarily due to the reliance on covalent inhibition strategies. Recent studies identified a regulatory and druggable pocket in Schistosoma mansoni thioredoxin glutathione reductase (TGR), a TrxR-like enzyme, and an established drug target for schistosomiasis. This site is termed the "doorstop pocket" because compounds that bind there impede the movement of an aromatic side-chain necessary for the entry and exit of NADPH and NADP+ during enzymatic turnover. This discovery spearheaded the development of new TGR inhibitors with efficacies surpassing those of current schistosomiasis treatment. Targeting the "doorstop pocket" is a promising strategy, as the pocket is present in all members of the pyridine nucleotide-disulfide oxidoreductase family, opening new avenues for exploring therapeutic approaches in diseases where the importance of these enzymes is established, including cancer and inflammatory and infectious diseases.

Development of Graphene-Based Materials with the Targeted Action for Cancer Theranostics.

The review summarises the prospects in the application of graphene and graphene-based nanomaterials (GBNs) in nanomedicine, including drug delivery, photothermal and photodynamic therapy, and theranostics in cancer treatment. The application of GBNs in various areas of science and medicine is due to the unique properties of graphene allowing the development of novel ground-breaking biomedical applications. The review describes current approaches to the production of new targeting graphene-based biomedical agents for the chemotherapy, photothermal therapy, and photodynamic therapy of tumors. Analysis of publications and FDA databases showed that despite numerous clinical studies of graphene-based materials conducted worldwide, there is a lack of information on the clinical trials on the use of graphene-based conjugates for the targeted drug delivery and diagnostics. The review will be helpful for researchers working in development of carbon nanostructures, material science, medicinal chemistry, and nanobiomedicine.

Enhanced Performance and Stability of Perovskite Solar Cells Through Surface Modification with Benzocaine Hydrochloride.

Current development of inverted p-i-n perovskite solar cells (PSCs), with nickel oxide as the hole transport layer, is progressing toward lower net costs, higher efficiencies, and superior stabilities. Unfortunately, the high density of defect-based traps on the surface of perovskite films significantly limits the photoelectric conversion efficiency and operational stability of perovskite solar cells. Finding cost-effective interface modifiers is crucial for the further commercial development of p-i-n PSCs. In the present work, we report a passivation strategy using a multifunctional molecule, benzocaine hydrochloride (BHC), which is shown to reduce defect density and enhance the photovoltaic performance and stability of the resultant p-i-n PSCs. It has been revealed that BHC strongly interacts with perovskite precursor components and triggers the evolution of the perovskite absorber film morphology and enables improved surface energy level alignment, thus promoting charge carrier transport and extraction. These properties are beneficial for improving open-circuit voltage (VOC) and fill factor (FF). Our results show that the photoelectric conversion efficiency (PCE) of p-i-n PSCs with nickel oxide as the hole transport layer increased from an initial 20.0% to 22.1% after being passivated with BHC, and these passivated devices also exhibited improved stability. DFT calculations reveal the unusual ability of the BHC passivant to improve band alignment while also preventing the accumulation of holes at the interface. In this work, the advantages of BHC passivation are demonstrated by linking theoretical calculations with optical and electrical characterizations.

Quantum chemical package Jaguar: A survey of recent developments and unique features.

This paper is dedicated to the quantum chemical package Jaguar, which is commercial software developed and distributed by Schrödinger, Inc. We discuss Jaguar's scientific features that are relevant to chemical research as well as describe those aspects of the program that are pertinent to the user interface, the organization of the computer code, and its maintenance and testing. Among the scientific topics that feature prominently in this paper are the quantum chemical methods grounded in the pseudospectral approach. A number of multistep workflows dependent on Jaguar are covered: prediction of protonation equilibria in aqueous solutions (particularly calculations of tautomeric stability and pKa), reactivity predictions based on automated transition state search, assembly of Boltzmann-averaged spectra such as vibrational and electronic circular dichroism, as well as nuclear magnetic resonance. Discussed also are quantum chemical calculations that are oriented toward materials science applications, in particular, prediction of properties of optoelectronic materials and organic semiconductors, and molecular catalyst design. The topic of treatment of conformations inevitably comes up in real world research projects and is considered as part of all the workflows mentioned above. In addition, we examine the role of machine learning methods in quantum chemical calculations performed by Jaguar, from auxiliary functions that return the approximate calculation runtime in a user interface, to prediction of actual molecular properties. The current work is second in a series of reviews of Jaguar, the first having been published more than ten years ago. Thus, this paper serves as a rare milestone on the path that is being traversed by Jaguar's development in more than thirty years of its existence.

Enantioselective Transfer Hydrogenation of α-Methoxyimino-ß-keto Esters.

α-Methoxyimino-ß-keto esters are reported to undergo highly enantioselective catalytic transfer hydrogenation using the Noyori-Ikariya complex RuCl(p-cymene)[(S,S)-Ts-DPEN] in a mixture of formic acid-triethylamine and dimethylformamide at 25 °C. The experimental study performed on over 25 substrates combined with computational analysis revealed that a Z-configured methoxyimino group positioned alpha to a ketone carbonyl leads to higher reactivity and mostly excellent enantioselectivity within this substrate class. Density functional theory calculations of competing transition states were used in rationalizing the origins of enantioselectivity and the possible role of the methoxyimino group in the reaction outcome.

Photodynamic therapy with Photoditazine increases microviscosity of cancer cells membrane in cellulo and in vivo.

Photodynamic therapy (PDT) is a minimally invasive method for cancer treatment, one of the effects of which is the oxidation of membrane lipids. However, changes in biophysical properties of lipid membranes during PDT have been poorly explored. In this work, we investigated the effects of PDT on membrane microviscosity in cancer cells in the culture and tumor xenografts. Membrane microviscosity was visualized using fluorescence lifetime imaging microscopy (FLIM) with a viscosity-sensitive rotor BODIPY2. It was found that PDT using chlorine e6-based photosensitizer Photoditazine caused a quick, steady elevation of membrane microviscosity both in cellulo and in vivo. The proposed mechanisms responsible for the increase in microviscosity was lipid peroxidation by reactive oxygen species that resulted in a decrease of phosphatidylcholine and the fraction of unsaturated fatty acids in the membranes. Our results suggest that the increased microviscosity is an important factor that contributes to tumor cell damage during PDT.

KVX-053, a Protein Tyrosine Phosphatase 4A3 inhibitor, ameliorates SARS-CoV-2 Spike protein subunit 1 - induced acute lung injury in mice.

The Acute Respiratory Distress Syndrome (ARDS), often preceded by acute lung injury (ALI), is characterized by the accumulation of inflammatory fluid in the lung alveoli, leaky alveolar epithelium and endothelium, and overexpression of pro-inflammatory cytokines. This progression from ALI to ARDS is a major contributor to the high mortality observed in COVID-19 patients. The Spike protein of SARS-CoV-2 binds to lung ACE2 and, in addition to facilitating viral cell entry, it plays an important role in the development of ALI and ARDS, especially in the later phases of COVID-19 as well as long COVID. Protein tyrosine phosphatase (PTP) 4A3 is a key mediator of ARDS pathology. This study tested the hypothesis that targeting PTP4A3 would prevent COVID-19 associated ALI. Intratracheal administration of SARS-CoV-2 Spike protein Subunit 1 to K18-hACE2 transgenic mice expressing human ACE2 elicited pulmonary and systemic inflammation, leaky alveoli, overexpression of cytokines, structural lung injury and lung dysfunction; all these symptoms were ameliorated by the selective, allosteric inhibitor of PTP4A3, KVX-053. These findings provide the first evidence supporting a role for PTP4A3 in the development of SARS-CoV-2- mediated ALI. Significance Statement This study tested the hypothesis that targeting PTP4A3 would prevent COVID-19 associated ALI/ARDS. Intratracheal administration of SARS-CoV-2 Spike protein Subunit 1 to K18-hACE2 transgenic mice expressing human ACE2 elicited pulmonary and systemic inflammation, leaky alveoli, overexpression of cytokines and chemokines, structural lung injury and lung dysfunction; all these symptoms were ameliorated by the selective, allosteric inhibitor of PTP4A3, KVX-053. These findings suggest that this novel PTP4A3 inhibitor may be useful against COVID-19 and potentially other viral-induced ARDS.

Knowledge Base Prototype Creating with Using Interdisciplinary Metathesaurus.

This article presents our experience in development an ontological model can be used in clinical decision support systems (CDSS) creating. We have used the largest international biomedical terminological metathesaurus the Unified Medical Language System (UMLS) as the basis of our model. This metathesaurus has been adapted into Russian using an automated hybrid translation system with expert control. The product we have created was named as the National Unified Terminological System (NUTS). We have added more than 33 million scientific and clinical relationships between NUTS terms, extracted from the texts of scientific articles and electronic health records. We have also computed weights for each relationship, standardized their values and created symptom checker in preliminary diagnostics based on this. We expect, that the NUTS allow solving task of named entity recognition (NER) and increasing terms interoperability in different CDSS.