Basic Mechanisms Research Articles

Pathology and pathobiology of pulmonary hypertension: current insights and future directions.

In recent years, major advances have been made in the understanding of the cellular and molecular mechanisms driving pulmonary vascular remodelling in various forms of pulmonary hypertension, including pulmonary arterial hypertension, pulmonary hypertension associated with left heart disease, pulmonary hypertension associated with chronic lung disease and hypoxia, and chronic thromboembolic pulmonary hypertension. However, the survival rates for these different forms of pulmonary hypertension remain unsatisfactory, underscoring the crucial need to more effectively translate innovative scientific knowledge into healthcare interventions. In these proceedings of the 7th World Symposium on Pulmonary Hypertension, we delve into recent developments in the field of pathology and pathophysiology, prioritising them while questioning their relevance to different subsets of pulmonary hypertension. In addition, we explore how the latest omics and other technological advances can help us better and more rapidly understand the myriad basic mechanisms contributing to the initiation and progression of pulmonary vascular remodelling. Finally, we discuss strategies aimed at improving patient care, optimising drug development, and providing essential support to advance research in this field.

Pathophysiology of the right ventricle and its pulmonary vascular interaction.

The right ventricle and its stress response is perhaps the most important arbiter of survival in patients with pulmonary hypertension of many causes. The physiology of the cardiopulmonary unit and definition of right heart failure proposed in the 2018 World Symposium on Pulmonary Hypertension have proven useful constructs in subsequent years. Here, we review updated knowledge of basic mechanisms that drive right ventricular function in health and disease, and which may be useful for therapeutic intervention in the future. We further contextualise new knowledge on assessment of right ventricular function with a focus on metrics readily available to clinicians and updated understanding of the roles of the right atrium and tricuspid regurgitation. Typical right ventricular phenotypes in relevant forms of pulmonary vascular disease are reviewed and recent studies of pharmacological interventions on chronic right ventricular failure are discussed. Finally, unanswered questions and future directions are proposed.

Quantum–Classical Hybrid Dynamics: Coupling Mechanisms and Diffusive Approximation

In this paper we demonstrate that any Markovian master equation defining a completely positive evolution for a quantum–classical hybrid state can always be written in terms of four basic coupling mechanisms. Each of them is characterized by a different “backaction” on each subsystem. On this basis, for each case, we find the conditions under which a diffusive limit is approached, that is, the time evolution can be approximated in terms of the first and second derivatives of the hybrid state with respect to a classical coordinate. In this limit, the restricted class of evolutions that guaranty the positivity of the hybrid state at all times (quantum Fokker-Planck master equations) emerges when the coupling mechanisms lead to infinitesimal (non-finite) changes in both the quantum and classical subsystems. A broader class of diffusive evolutions is obtained when positivity is only granted after a transient time or alternatively is granted after imposing an initial finite width on the state of the classical subsystem. A set of representative examples support these results.

Unbiased discovery of cancer pathways and therapeutics using Pathway Ensemble Tool and Benchmark.

Correctly identifying perturbed biological pathways is a critical step in uncovering basic disease mechanisms and developing much-needed therapeutic strategies. However, whether current tools are optimal for unbiased discovery of relevant pathways remains unclear. Here, we create "Benchmark" to critically evaluate existing tools and find that most function sub-optimally. We thus develop the "Pathway Ensemble Tool" (PET), which outperforms existing methods. Deploying PET, we identify prognostic pathways across 12 cancer types. PET-identified prognostic pathways offer additional insights, with genes within these pathways serving as reliable biomarkers for clinical outcomes. Additionally, normalizing these pathways using drug repurposing strategies represents therapeutic opportunities. For example, the top predicted repurposed drug for bladder cancer, a CDK2/9 inhibitor, represses cell growth in vitro and in vivo. We anticipate that using Benchmark and PET for unbiased pathway discovery will offer additional insights into disease mechanisms across a spectrum of diseases, enabling biomarker discovery and therapeutic strategies.

Nuclear receptor 4A1 ameliorates renal fibrosis by inhibiting vascular endothelial growth factor A induced angiogenesis in UUO rats

IntroductionAngiogenesis is closely related to renal fibrosis; however, its basic mechanism remains unclear. In our study, we found that nuclear receptor 4A1 (NR4A1) inhibits vascular endothelial growth factor A (VEGFA)-induced angiogenesis, ameliorating renal fibrosis. MethodsWe prepared a renal fibrosis animal model with unilateral ureteral obstruction (UUO) and NR4A1 knockdown UUO mice model, Using Human umbilical vein endothelial cells (HUVECs) to conduct all in vitro experiments. We then detected and analyzed the expression levels of NR4A1 and other genes related to angiogenesis and fibrosis. ResultsThe angiogenesis related genes, such as VEGFA, vascular endothelial growth factor receptor-2 (VEGFR-2), endoglin (CD105), as well as the expression of fibrosis related genes that included, α-smooth muscle actin (α-SMA), Vimentin, and Collagen I are all significantly increased in the UUO rat model. In addition, the expression of NR4A1 of the kidney tissue of UUO rats was significantly reduced. Therefore, according to the above results, we speculated that angiogenesis may exacerbate renal fibrosis and NR4A1 may repress renal fibrosis by inhibiting angiogenesis. To further verify the above results, we used VEGFA to stimulate HUVECs with (or without) overexpression or knockdown of NR4A1. The results showed that with prolonged stimulation using VEGFA, the expression of NR4A1 decreases. Overexpression of NR4A1 significantly inhibits the expression of related indicators of angiogenesis and renal fibrosis. Furthermore, knockdown of NR4A1 induces endothelial cell proliferation and migration; therefore, exacerbating angiogenesis and fibrosis. Finally, the results of NR4A1 knockdown UUO mice showed that knockdown of NR4A1 can aggravating kidney damage and induce the expression of angiogenesis and renal fibrosis related indicators, while UUO can significantly induce kidney damage, angiogenesis and renal fibrosis. When knockdown of NR4A1, renal kidney damage, angiogenesis and fibrosis becomes more severe than UUO. Thus, all of these results indicate that NR4A1 can ameliorate renal fibrosis by inhibiting angiogenesis. ConclusionsNR4A1 can inhibit angiogenesis to ameliorate renal fibrosis.

Biocatalytic Carbenoid N-H Insertions Via Engineered Myoglobins: A Systematic Reaction Mechanism Study

Recently engineered myoglobins have demonstrated excellent biocatalytic activities for a broad range of carbenoid N-H insertion reactions with up to >99% yield. Such biocatalysts offer various tuning points beyond protein residues, such as metal center, and axial ligand, to regulate different chemical reactivities. However, there is no computational mechanistic study to reveal its basic reaction mechanism, which could be utilized to study effects of different catalyst component for rational biocatalyst design. The reported computational mechanistic papers of other heme protein catalyzed N-H insertion have limited information without a careful comparison of all possible pathways and just focused on certain steps. Building on our group’s recent mechanistic work on a number of heme carbene transfer reactions, we performed a quantum chemical study to systematically study all possible reaction pathways for myoglobin catalyzed N-H insertions, which starts from the reactants to final released products and thus constitute a complete reaction pathway study. We examined ylide (proton transfer), hydrogen atom transfer, and hydride transfer pathways. In the favored ylide pathways, we calculated the direct proton transfer from amine to carbene and indirect paths with both concerted and stepwise proton transfer and dissociation components. For the indirect pathways in which the proton resides on the carbonyl oxygen of the original carbene substituent, subsequent water-assisted proton transfer from this carbonyl oxygen to carbene’s carbon to form the final product was also investigated. The most favorable pathway from this systematic reaction mechanism study was further supported by new experimental work from our collaborators, the original developer of myoglobin-based biocatalysts. These novel mechanistic results provide important mechanistic information for future biocatalyst design with enhanced reactivities.

Development of Ceria Slurry for Enhanced Chemical Mechanical Polishing (CMP) Performance

As the semiconductor device is shrinking and gets complicated, the chemical mechanical polishing (CMP) process has become important. Various types of abrasive particles are used as CMP slurry, and among them, ceria slurry is in the spotlight due to its high material removal rate (MRR) and selectivity on oxide CMP process. It is known that the ceria abrasives form Ce-O-Si chemical bonds with oxide film, which makes it possible to achieve a high CMP performance.To further advance the performance of ceria slurry, we conducted a series of researches on ceria. A study was conducted on scanning mobility particle sizer (SMPS) measurement to accurately evaluate particle size distribution along with the basic polishing mechanism of monodisperse ceria nanoparticles. In addition, an optimization study was conducted considering the CMP performance according to the abrasive concentration of ceria slurry and the influence of ceria nanoparticles remaining on the wafer surface before the post-CMP cleaning process. Furthermore, research on synthesis method and surface modification of ceria was also conducted to improve the polishing performance. Ce3+ ions on the surface of ceria form Ce-O-Si chemical bond with the silicon dioxide film. Therefore, an important key point is to increase the concentration of Ce3+ ions to improve polishing performance. To achieve high Ce3+ ion concentration, ceria nanoparticles were synthesized through a hydrothermal method, and this performance was improved through lanthanide doping. On the other hand, methods to enhance Ce3+ ion concentration by inducing a reduction reaction on the surface of ceria nanoparticles were also proposed. First, the polishing performance was improved by adding trace metals (FeCl2, CrCl2) to induce a reduction reaction of ceria nanoparticles. Next, the reduction reaction of ceria was induced by applying an eco-friendly method which did not add chemical agents. Ultraviolet (UV) irradiation and hydrogen-gas reduction methods showed sufficient reduction reaction to improve the polishing performance of ceria slurry, and maintained physical properties without causing CMP defects such as poor surface roughness and micro-scratches.As with previous polishing studies, post-CMP cleaning is also important to decease defects. While ceria nanoparticles exhibit great polishing performance for silicon dioxide due to their ability to form chemical bonds, however, they also have the disadvantage of being difficult to remove during the post-CMP cleaning process. To efficiently remove ceria nanoparticles from the wafer surface during the post-CMP cleaning process, various methods have been studied. First, the buff cleaning process was studied in which a deionized water-based cleaning solution is injected instead of slurry after the CMP process. Since the buff cleaning process must simultaneously minimize damage of wafer surface and maximize cleaning performance, optimization research on the properties of the physical factors and cleaning solution is important. For an environmentally friendly cleaning method, we proposed controlling the viscosity of deionized water or using gas-dissolved water. It has been proven that physical factors of cleaning solutions (viscosity, micro bubbles, etc.) can be effective in removing ceria nanoparticles. Especially, hydrogen gas in gas-dissolved water induced a reduction reaction, breaking Ce-O-Si bonds and improving the cleaning performance. Limited to the bulk ceria CMP process, we also studied the improvement of cleaning performance of remained ceria nanoparticles using the tangential flow filtration (TFF) method before CMP process. We focused that small contaminant particles are difficult to remove during the cleaning process, and through the TFF method, small abrasive particles in the slurry are filtered in advance while maintaining the polishing performance.

Decomposition Mechanism of Lithium Methyl Carbonate with Electrolyte in the Solid Electrolyte Interphase to Elucidate the Early Stages of Thermal Runaway in Lithium-Ion Batteries

With the growing demand for electric vehicles, the safety of lithium-ion batteries has been greatly emphasized. Thermal runaway caused by the continuous side reactions inside the battery makes it difficult to extinguish fires caused by abnormal activity. The temperature at which a typical thermal runaway begins is around 100°C, the temperature at which several elements in the solid electrolyte interphase (SEI) layer on the anode surface experience thermal decomposition reactions (causing gas generation and heat production). Therefore, to understand the first stage of thermal runaway and increase battery safety, it is necessary to describe the thermal decomposition process of the SEI layer.To investigate the thermal decomposition process of the SEI layer, it is necessary to understand the various organic components. During the initial charging phase, the reduction reaction between the lithium ions and the electrolyte produces a series of components that make up the SEI layer. On the surface of the anode active material, the SEI layer is a thin layer with an overall thickness of 10-50 nm. It is composed of various organic (inner layer) and inorganic (outer layer) elements. Under thermal stress, the unstable organic SEI layer decomposes into an inorganic SEI layer due to its low stability in the presence of heat and gas generation, which is mostly caused by the decomposition of lithium carbonate (ROCOOLi). It is important to note that the most used electrolytes in batteries today are ethylene carbonate and ethyl methyl carbonate (EMC) dissolved in salts based on lithium hexafluorophosphate. Due to the application of EMC, lithium methyl carbonate (LMC) accounts for more than 50% of the SEI layer in the ROCOOLi compounds.This study used both theoretical and experimental techniques to fully elucidate the pyrolysis process of high-purity synthesized LMC with the electrolyte. First, LMC was chemically synthesized using a nucleophilic substitution reaction. Then, in-situ thermogravimetry analysis (TGA)-mass spectrometer(MS), attenuated total reflectance (ATR)- fourier transform infrared (FTIR), and nuclear magnetic resonance (NMR) results along with bond dissociation energy (BDE)/spectral analysis/energy diagrams obtained by density functional theory (DFT) calculations were analyzed to propose the elementary reaction steps involved in the pyrolysis reaction. We propose six elementary reaction steps for the pyrolysis reaction of LMC. To verify the validity of the proposed basic reaction mechanisms, chain reactions involving radicals generated during pyrolysis were finally calculated using GRI-MECH 3.0, and the calculated results were compared with the composition of the actual gas. We hope to utilize the techniques used in this study to obtain the reaction steps of additional SEI components (LEMC, Li2CO3, etc.). The precise mechanisms obtained through modeling studies can be used to predict the self-heating phase of thermal runaway and to develop materials that can stop the SEI decomposition reaction.

Design and Characterization of Printed Flexible Humidity Sensor

The development of humidity sensors is essential for applications in the environmental, agriculture, medical and semiconductor industries [1-2]. The basic mechanism of humidity sensors is explained by a Grotthuss chain reaction, which is usually simplified as a proton-hopping process [3]. This refers to a dynamic charge transfer process at a certain relative humidity (RH). The humidity sensors can be of different types such as capacitive type, resistive, colorimetric and surface acoustic wave [4-7]. Capacitive type sensors are linear, require less complex circuitry and can operate for a wide range of humidity [8]. A typical capacitive type humidity sensor uses hydrophilic films as sensing layers which are stable at higher humidity levels [9]. Polymers that are being used for the fabrication of capacitive type humidity sensors include poly (2-hydroxyethyl methacrylate) (pHEMA) [9], cellulose acetate butyrate (CAB) [10], polyimide [11] and polymethyl methacrylate (PMMA) [12]. In this work, a humidity sensor has been fabricated on glass and flexible substrates.The design of humidity sensor consists of printed pattern of a conductor such as silver and a spin coated dielectric such as polymer poly (2-hydroxyethyl methacrylate) (p-HEMA) and polyimide. The printing of conductor was done in an interdigitated pattern as shown in figure 1. The thickness of sensitive materials was controlled by varying the spin time from 10 to 30 seconds. A thick solution of sensitive materials was prepared by adding a 3 gm of polymer in 50 mL ethanol in the case of p-HEMA. Currently we are preparing one more set of samples using polyimide and we will present a comparison of two humidity sensors- one with p-HEMA and another with polyimide. A humidity sensor that employs interdigitated capacitors (IDC) printed with silver on a glass and flexible substrate was successfully fabricated using p-HEMA and polyimide at spin speed of 2000 rpm for 20 seconds. Our goal is to integrate the humidity sensor into a robotic arm to perform real-time object characterization in agricultural applications via comprehensive understanding of the operations of harvesting robots in various crop types and environmental conditions.

Exploration on Advanced Intelligent Algorithms of Artificial Intelligence for Verb Recognition in Machine Translation

This article aimed to address the problems of word order confusion, context dependency, and ambiguity in traditional machine translation (MT) methods for verb recognition. By applying advanced intelligent algorithms of artificial intelligence, verb recognition can be better processed and the quality and accuracy of MT can be improved. Based on Neural machine translation (NMT), basic attention mechanisms, historical attention information, dynamically obtain information related to the generated words, and constraint mechanisms were introduced to embed semantic information, represent polysemy, and annotate semantic roles of verbs. This article used the Workshop on MT (WMT), British National Corpus (BNC), Gutenberg, Reuters Corpus, and OpenSubtitles corpus, and enhanced the data in the corpora. The improved NMT model was compared with traditional NMT models, Rule-Based MT (RBMT), and Statistical MT (SMT). The experimental results showed that the average verb semantic matching degree of the improved NMT model in five corpora was 0.85, and the average Bilingual Evaluation Understudy (BLEU) score in five corpora was 0.90. The improved NMT model in this article can effectively improve the accuracy of verb recognition in MT, providing new methods for verb recognition in MT.

Formation of human kinship structures depending on population size and cultural mutation rate

How does social complexity depend on population size and cultural transmission? Kinship structures in traditional societies provide a fundamental illustration, where cultural rules between clans determine people's marriage possibilities. Here, we propose a simple model of kinship interactions that considers kin and in-law cooperation and sexual rivalry. In this model, multiple societies compete. Societies consist of multiple families with different cultural traits and mating preferences. These values determine interactions and hence the growth rate of families and are transmitted to offspring with mutations. Through a multilevel evolutionary simulation, family traits and preferences are grouped into multiple clans with interclan mating preferences. It illustrates the emergence of kinship structures as the spontaneous formation of interdependent cultural associations. Emergent kinship structures are characterized by the cycle length of marriage exchange and the number of cycles in society. We numerically and analytically clarify their parameter dependence. The relative importance of cooperation versus rivalry determines whether attraction or repulsion exists between families. Different structures evolve as locally stable attractors. The probabilities of formation and collapse of complex structures depend on the number of families and the mutation rate, showing characteristic scaling relationships. It is now possible to explore macroscopic kinship structures based on microscopic interactions, together with their environmental dependence and the historical causality of their evolution. We propose the basic causal mechanism of the formation of typical human social structures by referring to ethnographic observations and concepts from statistical physics and multilevel evolution. Such interdisciplinary collaboration will unveil universal features in human societies.

From irregular to regular eutectic growth in the Al-Al3Ni system: In situ observations during directional solidification

We investigate the irregular eutectic growth dynamics of the Al-Al3 alloy, in which one of the solid phases (Al3Ni) grows faceted from the liquid. Leveraging in situ optical microscopy and synchrotron transmission x-ray microscopy, we address the question of the degree of coupling between Al and Al3Ni at the growth front and that of the shape of the microstructures left behind in the bulk solid during directional solidification. Real-time optical observations bring evidence for a morphological transition from a eutectic-grain dependent, irregular eutectic growth at low solidification velocity V (typically 1μms−1), to a weakly anisotropic, regular growth at higher V (reaching 10μms−1). Unprecedented x-ray nano-imaging of the solid-liquid interface, and 3D characterization of the growth patterns, were made possible by a new DS setup at Brookhaven National Laboratory’s NSLS-II. At low V, the leading tips of partly faceted Al3Ni crystals are observed to grow not far ahead of the Al growth front. Correlating in situ images and postmortem 3D tomographic reconstructions reveals that the presence of faceted and non-faceted regions of Al3Ni crystals in the solid is a direct consequence of coupling and decoupling during DS, respectively. Upon increasing V, the lead distance of Al3Ni vanishes, and the shape of Al3Ni ceases to be governed by faceted growth. These observations cast light onto the basic mechanisms (faceted growth, diffusive coupling, and the dynamics of trijunctions) governing a faceted to rod-like transition upon increasing V in the Al3Ni system, with broad implications to a large class of irregular eutectics.

Analysis and numerical simulation of a generalized compressible Cahn-Hilliard-Navier-Stokes model with friction effects

We propose a new generalized compressible diphasic Navier-Stokes Cahn-Hilliard model that we name G-NSCH. This new G-NSCH model takes into account important properties of diphasic compressible fluids such as possible non-matching densities and contrast in mechanical properties (viscosity, friction) between the two phases of the fluid. the model also comprises a term to account for possible exchange of mass between the two phases. Our G-NSCH system is derived rigorously and satisfies basic mechanics of fluids and thermodynamics of particles. Under some simplifying assumptions, we prove the existence of global weak solutions. We also propose a structure preserving numerical scheme based on the scalar auxiliary variable method to simulate our system and present some numerical simulations validating the properties of the numerical scheme and illustrating the solutions of the G-NSCH model.

Asthma Pathogenesis: Phenotypes, Therapies, and Gaps: Summary of the Aspen Lung Conference 2023.

Although substantial progress has been made in our understanding of asthma pathogenesis and phenotypes over the nearly 60-year history of the Aspen Lung Conferences on asthma, many ongoing challenges exist in our understanding of the clinical and molecular heterogeneity of the disease and an individual patient's response to therapy. This report summarizes the proceedings of the 2023 Aspen Lung Conference, which was organized to review the clinical and molecular heterogeneity of asthma and to better understand the impact of genetic, environmental, cellular, and molecular influences on disease susceptibility, heterogeneity, and severity. The goals of the conference were to review new information about asthma phenotypes, cellular processes, and cellular signatures underlying disease heterogeneity and treatment response. The report concludes with ongoing gaps in our understanding of asthma pathobiology and provides some recommendations for future research to better understand the clinical and basic mechanisms underlying disease heterogeneity in asthma and to advance the development of new treatments for this growing public health problem.

A new assembled experimental device for fluid mechanics

Fluid mechanics is one of the important branches of basic mechanics education of science and technology in higher education, and its corresponding teaching experiments are numerous. However, there are great similarities among some components of most traditional hydrodynamics experimental devices. If an independent experimental device is designed for a specific experiment, it will result in a great waste of resources and space. Therefore, based on the full investigation on the similar components of some certain experimental devices, this study redesigned and integrated them, and innovatively proposed a new type of assembled hydrodynamics comprehensive experimental device. This experimental device can be utilized to carry out Reynolds experiment, Nozzle outflow experiment, Karman vortex street experiment, etc. based on different combinations. The corresponding results show that this assembled hydrodynamics comprehensive experimental device has the advantages of multiple functions, small occupied space, low cost, good stability, high corrosion resistance, strong expandability, and so on.

Theoretical Investigation of Laser Ablation Propulsion Using Micro-Scale Fluid in Atmosphere

Laser ablation propulsion based on liquid propellants is a type of propulsion technology with a high specific impulse and good controllability that can be applied to space thrusters, gas metal arc welding, and extreme ultraviolet light. However, its basic mechanisms, such as flow evolution and thrust formation, have not yet been described in detail. In this study, the laser ablation of micro-scale fluid in the atmosphere was investigated. Flow evolution with different laser energy and fluid mass was observed using a schlieren system. According to the characteristic of flow evolution, a theoretical model of laser ablation propulsion in the atmosphere was established. For the first time, a theoretical hypothesis was proposed that the laser energy is divided into two parts, which act on fluid and air respectively. The model indicates that the impulses generated by fluids and air follow power laws with the laser energy, while the exponentials are 0.5 and 1, respectively. In the atmosphere, due to the shielding effect of a laser-maintained detonation wave on laser, the energy absorbed by the fluid is basically unchanged, while only the energy absorbed by the air changes. Significantly, the theoretical model is consistent with the impulse experiment and current studies.

The influence of representations on task difficulty in organic chemistry: an exploration using a novel paired-items test instrument

ABSTRACT The intricate relationship between representational competence and content knowledge in organic chemistry has been widely debated, and the ways in which representations contribute to task difficulty, particularly in assessment, remain unclear. This paper presents a multiple-choice test instrument for assessing individuals’ knowledge of fundamental concepts – such as nomenclature and basic reaction mechanisms – in organic chemistry using item pairs with and without representations. We conducted a pilot test of the instrument with 55 undergraduate students and administered the final version to 357 undergraduate chemistry students from seven German universities. We used the Rasch methodology for psychometric analysis to identify sound and reliable test properties. A task-difficulty comparison revealed no differences between the item pairs with and those without representations. Hierarchical regression suggests that the complexity and cognitive processes involved in a task influence its difficulty. Our data suggest that the relationship between representational competence and content knowledge may not be disentangled when item difficulty is considered. We argue that representational competence and content knowledge might not represent separate constructs, which is in line with the literature on representational dilemmas: representations cannot be taught without content knowledge, and content knowledge cannot be taught without the use of representations.

Clinical application of live biotherapeutic products in infectious diseases

Live biotherapeutics products (LBP) are a novel range of therapeutic options in medicine. In this review, authors discuss basic composition and mechanism of action of LBP, provide a comprehensive focused overview of published in vitro and in vivo studies on efficacy of LBP for prevention and treatment of infectious diseases such as viral (HIV, COVID-19), bacterial (C.difficile infection, bacterial vaginosis, multi-drug resistant organisms) and fungal (Candida) organisms. This review should be of interest to clinicians to understand the broad application of LBP in infectious diseases world beyond recurrent C.difficile infection and to researchers on unexplored prospects of LBP and the need for further investigation in this emerging field to improve its clinical application.

Cell-Based Therapy and Genome Editing as Emerging Therapeutic Approaches to Treat Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation of the joints. Although much remains unknown about the pathogenesis of RA, there is evidence that impaired immune tolerance and the development of RA are related. And it is precisely the restoration of immune tolerance at the site of the inflammation that is the ultimate goal of the treatment of RA. Over the past few decades, significant progress has been made in the treatment of RA, with higher rates of disease remission and improved long-term outcomes. Unfortunately, despite these successes, the proportion of patients with persistent, difficult-to-treat disease remains high, and the task of improving our understanding of the basic mechanisms of disease development and developing new ways to treat RA remains relevant. This review focuses on describing new treatments for RA, including cell therapies and gene editing technologies that have shown potential in preclinical and early clinical trials. In addition, we discuss the opportunities and limitations associated with the use of these new approaches in the treatment of RA.

INNOVATSION TEXNOLOGIYALARDAN FOYDALANISHNING RIVOJLANISH TENDENSIYALARI

This article states that one of the important pedagogical tasks is to educate young people who are knowledgeable, mature in all aspects, creative, diverse in teaching methods, who are able to competently choose modern pedagogical technologies, and study the basic mechanisms of methods and technologies based on a creative approach emphasized