The Gut Microbiota Impacts Gastrointestinal Cancers through Obesity, Diabetes, and Chronic Inflammation.

The gut microbiota's pivotal role in human health is increasingly evident, particularly in chronic conditions like obesity, diabetes, and inflammatory diseases. This intricate symbiotic relationship influences metabolic balance and immune responses. Notably, gut microbial dysbiosis is linked to obesity's metabolic disruption and chronic low-grade inflammation.

A phase III study to access the safety and efficacy of prolgolimab 250 mg fixed dose administered every 3 weeks versus prolgolimab 1 mg/kg every 2 weeks in patients with metastatic melanoma (FLAT).

Background: Prolgolimab is the first Russian PD-1 inhibitor approved for the first-line treatment of unresectable or metastatic melanoma and advanced non-small cell lung cancer. It was approved in two weight-based regimens of 1 mg/kg Q2W and 3 mg/kg Q3W, but because of re-evaluation of weight-based dosing paradigm, studying of a fixed-dose regimen was considered perspective.

Methods: We conducted a multicenter, single-arm, open-label efficacy, pharmacokinetics, and safety study to obtain data that would allow the approval of the new flat dosing regimen of prolgolimab in patients with previously untreated unresectable or metastatic melanoma (BCD-100-8/FLAT, NCT05783882).

Maternal Age at Menarche Genes Determines Fetal Growth Restriction Risk.

We aimed to explore the potential link of maternal age at menarche (mAAM) gene polymorphisms with risk of the fetal growth restriction (FGR). This case (FGR)-control (FGR free) study included 904 women (273 FGR and 631 control) in the third trimester of gestation examined/treated in the Departments of Obstetrics. For single nucleotide polymorphism (SNP) multiplex genotyping, 50 candidate loci of mAAM were chosen.

Neural machine translation of clinical text: an empirical investigation into multilingual pre-trained language models and transfer-learning.

Clinical text and documents contain very rich information and knowledge in healthcare, and their processing using state-of-the-art language technology becomes very important for building intelligent systems for supporting healthcare and social good. This processing includes creating language understanding models and translating resources into other natural languages to share domain-specific cross-lingual knowledge. In this work, we conduct investigations on clinical text machine translation by examining multilingual neural network models using deep learning such as Transformer based structures.

Polymorphism rs143384 GDF5 reduces the risk of knee osteoarthritis development in obese individuals and increases the disease risk in non-obese population.

Background: We investigated the effect of obesity on the association of genome-wide associative studies (GWAS)-significant genes with the risk of knee osteoarthritis (KOA).

Methods: All study participants (n = 1,100) were divided into 2 groups in terms of body mass index (BMI): BMI ≥ 30 (255 KOA patients and 167 controls) and BMI < 30 (245 KOA and 433 controls). The eight GWAS-significant KOA single nucleotide polymorphisms (SNP) of six candidate genes, such as LYPLAL1 (rs2820436, rs2820443), SBNO1 (rs1060105, rs56116847), WWP2 (rs34195470), NFAT5 (rs6499244), TGFA (rs3771501), GDF5 (rs143384), were genotyped.

Sex-Hormone-Binding Globulin Gene Polymorphisms and Breast Cancer Risk in Caucasian Women of Russia.

In our work, the associations of GWAS (genome-wide associative studies) impact for sex-hormone-binding globulin (SHBG)-level SNPs with the risk of breast cancer (BC) in the cohort of Caucasian women of Russia were assessed. The work was performed on a sample of 1498 women (358 BC patients and 1140 control (non BC) subjects). SHBG correlated in previously GWAS nine polymorphisms such as rs780093 , rs17496332 , rs3779195 , rs10454142 , rs7910927 , rs4149056 , rs440837 , rs12150660 , and rs8023580 have been genotyped.

Maternal Age at Menarche Gene Polymorphisms Are Associated with Offspring Birth Weight.

In this study, the association between maternal age at menarche (AAM)-related polymorphisms and offspring birth weight (BW) was studied. The work was performed on a sample of 716 pregnant women and their newborns. All pregnant women underwent genotyping of 50 SNPs of AAM candidate genes.

High peak power and energy scaling in the mid-IR chirped-pulse oscillator-amplifier laser systems.

The paper introduces a new route towards the ultrafast high laser peak power and energy scaling in a hybrid mid-IR chirped pulse oscillator-amplifier (CPO-CPA) system, without sacrificing neither the pulse duration nor energy. The method is based on using a CPO as a seed source allowing the beneficial implementation of a dissipative soliton (DS) energy scaling approach, coupled with a universal CPA technique. The key is avoiding a destructive nonlinearity in the final stages of an amplifier and compressor elements by using a chirped high-fidelity pulse from CPO.

Atmospheric dispersion management in mid-IR mode-locked oscillators.

The atmospheric dispersion in the mid-infrared transparency windows presents an important albeit often neglected factor when developing ultrashort-pulsed lasers. We show that it can amount to hundreds of fs in 2-3 µm window with typical laser round-trip path lengths. Using the Cr:ZnS ultrashort-pulsed laser as a test-bed, we demonstrate the atmospheric dispersion influence on femtosecond and chirped-pulse oscillator performance and show that the humidity fluctuations can be compensated by an active dispersion control, greatly improving stability of mid-IR few-optical cycle laser sources.

Curcumin and Its Supramolecular Complex with Disodium Glycyrrhizinate as Potential Drugs for the Liver Fluke Infection Caused by .

Opisthorchiosis is a parasitic liver disease found in mammals that is widespread throughout the world and causes systemic inflammation. Praziquantel remains the drug of choice for the treatment of opisthorchiosis, despite its many adverse effects. An anthelmintic effect is attributed to the main curcuminoid of L.

A Study of a Protein-Folding Machine: Transient Rotation of the Polypeptide Backbone Facilitates Rapid Folding of Protein Domains in All-Atom Molecular Dynamics Simulations.

Molecular dynamics simulations of protein folding typically consider the polypeptide chain at equilibrium and in isolation from the cellular components. We argue that in order to understand protein folding as it occurs in vivo, it should be modeled as an active, energy-dependent process, in which the cellular protein-folding machine directly manipulates the polypeptide. We conducted all-atom molecular dynamics simulations of four protein domains, whose folding from the extended state was augmented by the application of rotational force to the C-terminal amino acid, while the movement of the N-terminal amino acid was restrained.

Risk Effects of rs1799945 Polymorphism of the Gene and Intergenic Interactions of GWAS-Significant Loci for Arterial Hypertension in the Caucasian Population of Central Russia.

The aim of this case-control replicative study was to investigate the link between GWAS-impact for arterial hypertension (AH) and/or blood pressure (BP) gene polymorphisms and AH risk in Russian subjects (Caucasian population of Central Russia). AH (n = 939) and control (n = 466) cohorts were examined for ten GWAS AH/BP risk loci. The genotypes/alleles of these SNP and their combinations (SNP-SNP interactions) were tested for their association with the AH development using a logistic regression statistical procedure.

Sex-Specific Features of the Correlation between GWAS-Noticeable Polymorphisms and Hypertension in Europeans of Russia.

The aim of the study was directed at studying the sex-specific features of the correlation between genome-wide association studies (GWAS)-noticeable polymorphisms and hypertension (HTN). In two groups of European subjects of Russia ( = 1405 in total), such as men ( = 821 in total: = 564 HTN, = 257 control) and women ( = 584 in total: = 375 HTN, = 209 control), the distribution of ten specially selected polymorphisms (they have confirmed associations of GWAS level with blood pressure (BP) parameters and/or HTN in Europeans) has been considered. The list of studied loci was as follows: () rs932764 A > G, () rs1173771 G > A, () rs7302981 G > A, () rs1799945 C > G, () rs4387287 C > A, () rs805303 G > A, () rs167479 T > G, () rs633185 C > G, () rs8068318 T > C, and () rs2681472 A > G.

Intergenic Interactions of , and Determine the Susceptibility to Knee Osteoarthritis among Europeans of Russia.

This study was conducted to examine the associations between genome-wide association studies (GWAS)-important single nucleotide polymorphisms (SNPs) and knee osteoarthritis (KOA) among Europeans of Russia. The present replicative study ("patient-control" design has been used) was carried out on 1000 DNA samples from KOA ( = 500) and KOA-free ( = 500) participants. Ten GWAS-important for KOA SNPs of eight candidate genes () were studied.

Modeling of Benign Prostatic Hyperplasia in Rats with a High Dose of Testosterone.

In order to optimize the testosterone model of benign prostatic hyperplasia, we studied the effect of castration and different doses of testosterone on the induction of the proliferative process in the prostate of Wistar rats. It was shown that 4-week subcutaneous administration of testosterone propionate in a dose of 20 mg/kg causes pronounced proliferative and hemodynamic disorders in the dorsolateral gland morphologically similar in castrated and non-castrated males. Administration of testosterone in a dose of 3 mg/kg had no significant effect on the dynamics of the pathological process in non-operated rats and normalized the structure of the gland in castrated animals.

Clinical and Genetic Characteristics of Preeclampsia.

Preeclampsia (PE) is a severe complication of pregnancy accompanied by arterial hypertension, edema, or proteinuria with impaired functioning of various organs and systems. It is also an important medical and social problem, which has been one of the leading causes of maternal and perinatal mortality and morbidity worldwide. Despite the achievements of modern medicine, the etiology of this pathology is still unknown.

Conjugates of Lupane Triterpenoids with Arylpyrimidines: Synthesis and Anti-inflammatory Activity.

Semisynthetic triterpenoid betulonic acid is of significant interest due to its biological activity and synthetic application. In this study, we report the synthesis of hybrid compounds, containing betulonic acid carboxamide and arylpyrimidine fragments. A total of 15 conjugates were prepared using the cyclocondensation reaction of new terpenoid alkynyl ketones with amidinium salts.

Efficient high-energy Raman soliton generation in a Tm:doped large mode area fiber amplifier.

We report the Tm-doped all-fiber MOPA based on a LMA active fiber generating Raman solitons tunable in the range 1970-2300 nm directly from the LMA fiber. By tuning the chirp of the input pulse we reached more than 90 % energy transfer efficiency to Raman soliton. Solitons with 125 fs duration and up to 24 nJ energy are demonstrated in LMA fiber amplifier.

Is Protein Folding a Thermodynamically Unfavorable, Active, Energy-Dependent Process?

The prevailing current view of protein folding is the thermodynamic hypothesis, under which the native folded conformation of a protein corresponds to the global minimum of Gibbs free energy . We question this concept and show that the empirical evidence behind the thermodynamic hypothesis of folding is far from strong. Furthermore, physical theory-based approaches to the prediction of protein folds and their folding pathways so far have invariably failed except for some very small proteins, despite decades of intensive theory development and the enormous increase of computer power.

Cascade Transformations of 1-R-Ethynyl-9,10-anthraquinones with Amidines: Expanding Access to Isoaporphinoid Alkaloids.

The interaction of acetamidine and phenylamidine with peri-R-ethynyl-9,10-anthraquinones in refluxing n-butanol leads to the formation of cascade transformations products: addition/elimination/cyclization-2-R-7-dibenzo[,]quinolin-7-ones and(or) 2-R-3-aroyl-7-dibenzo[,]quinolin-7-ones. The anti-inflammatory and antitumor properties of the new 2-R-7H-dibenzo[]quinolin-7-ones were investigated in vivo, in vitro, and in silico. The synthesized compounds exhibit high anti-inflammatory activity at dose 20 mg/kg (intraperitoneal injection) in the models of exudative (histamine-induced) and immunogenic (concanavalin A-induced) inflammation.

Energy-dependent protein folding: modeling how a protein folding machine may work.

Proteins fold robustly and reproducibly , but many cannot fold in isolation from cellular components. Despite the remarkable progress that has been achieved by the artificial intelligence approaches in predicting the protein native conformations, the pathways that lead to such conformations, either or , remain largely unknown. The slow progress in recapitulating protein folding pathways may be an indication of the fundamental deficiencies in our understanding of folding as it occurs in nature.

Candidate Genes for Age at Menarche Are Associated With Uterine Leiomyoma.

Age at menarche (AAM) is an important marker of the pubertal development and function of the hypothalamic-pituitary-ovarian system. It was reported as a possible factor for a risk of uterine leiomyoma (UL). However, while more than 350 loci for AAM have been determined by genome-wide association studies (GWASs) to date, no studies of these loci for their association with UL have been conducted so far.

[Gene-environment interactions between polymorphic loci of MMPs and obesity in essential hypertension in women.].

Background: The prevalence of essential hypertension (ЕH) is increasing every year, both in Russia and around the world. Genetic and environmental risk factors are involved in the development of hypertension, and obesity plays an important role. Therefore, the study of gene-ecological interactions in the development of hypertension seems to be relevant.

Candidate genes for age at menarche are associated with endometriosis.

Research Question: Are the candidate genes for age at menarche associated with a risk of endometriosis?

Design: Fifty-two candidate single nucleotide polymorphisms (SNP) for age at menarche, their gene-gene and gene-environment interactions were analysed for possible association with endometriosis in a sample of 395 patients and 981 controls. Association of the polymorphisms was analysed using logistic regression according to three main genetic models (additive, recessive and dominant). The gene-gene and gene-environment interactions were analysed for the second-, third- and fourth-order models with adjustment for covariates and multiple comparisons with subsequent cross-validation.