Mechanical Imbalance Research Articles

Promoted coagulant activity and disrupted blood-brain barrier depending on phosphatidylserine externalization of red blood cells exposed to ZnO nanoparticles

Zinc oxide nanoparticles (ZnO-NPs) are nanomaterials mainly produced and used worldwide. They translocate to circulatory systems from various exposure routes. While blood and endothelial cells are persistently exposed to circulating ZnO-NPs, the potential risks posed by ZnO-NPs to the cardiovascular system are largely unknown. Our study identified the potential risk of thrombosis and disturbance of the blood-brain barrier (BBB) by coagulant activity on red blood cells (RBCs) caused by ZnO-NPs. ZnO-NPs promoted the externalization of phosphatidylserine and the generation of microvesicles through an imbalance of intracellular mechanisms regulating procoagulant activity in human RBCs. The coagulation cascade leading to thrombin generation was promoted in ZnO-NPs-treated human RBCs. Combined with human RBCs, ZnO-NPs caused coagulant activity on isolated rat RBCs and rat venous thrombosis models. We identified the erythrophagocytosis of RBCs into brain endothelial cells via increased PS exposure induced by ZnO-NPs. Excessive erythrophagocytosis contributes to disrupting the BBB function of endothelial cells. ZnO-NPs increased the procoagulant activity of RBCs, causing venous thrombosis. Excessive erythrophagocytosis through ZnO-NPs-treated RBCs resulted in the dysfunction of BBB. Our study will help elucidate the potential risk ZnO-NPs exert on the cardiovascular system.

Mechanical imbalance between normal and transformed cells drives epithelial homeostasis through cell competition.

Cell competition in epithelial tissue eliminates transformed cells expressing activated oncoproteins to maintain epithelial homeostasis. Although the process is now understood to be of mechanochemical origin, direct mechanical characterization and associated biochemical underpinnings are lacking. Here, we employ tissue-scale stress and compressibility measurements and theoretical modeling to unveil a mechanical imbalance between normal and transformed cells, which drives cell competition. In the mouse intestinal epithelium and epithelial monolayer, transformed cells get compacted during competition. Stress microscopy reveals an emergent compressive stress at the transformed loci leading to this compaction. A cell-based self-propelled Voronoi model predicts that this compressive stress originates from a difference in the collective compressibility of the competing populations. A new collective compressibility measurement technique named gel compression microscopy then elucidates a two-fold higher compressibility of the transformed population than the normal population. Mechanistically, weakened cell-cell adhesions due to reduced junctional abundance of E-cadherin in the transformed cells render them collectively more compressible than normal cells. Taken together, our findings unveil a mechanical basis for epithelial homeostasis against oncogenic transformations with implications in epithelial defense against cancer.

Seawater‐degradable poly(ethylene adipate‐co‐terephthalate) copolyester: Synthesis, properties, and degradation behavior

AbstractThe application and promotion of biodegradable plastics are hindered by the imbalance between their mechanical and degradation performance imbalance, as well as high costs. Herein, a series of poly(ethylene adipate‐co‐terephthalate) (PEAT) copolyesters with excellent mechanical and degradation properties are synthesized by one‐step melt polycondensation. The influence of the proportion of aliphatic groups in the molecular chain on the structure and properties, especially the degradation performance, of the copolyesters was studied. The molecular chain flexibility and degradability of PEAT increases with increasing of adipic acid content and decreasing of ET fragment length (LET). The comprehensive mechanical properties of PEAT60 can be comparable to traditional packaging material poly(butylene adipateco‐terephthalate) (PBAT). The degradation performance of PEAT can be adjusted the molecular chain structure. PEAT with LET < 3 exhibit degradation performance, and PEAT with LET < 2.2 exhibit significant degradation acceleration. The excellent mechanical and degradable properties of PEAT copolyester make it expected to be used in degradable packaging and other fields to help solve plastic pollution, while its lower cost will aid in the promotion of degradable materials.

Percutaneous kyphoplasty in the treatment of Kümmell disease in lumbar scoliosis: A case report

BACKGROUND Due to mechanical imbalance in the spine, elderly scoliosis patients tend to develop vertebral fracture nonunion, i.e. , Kümmell disease, when osteoporotic vertebral compression fractures occur. However, accompanying vertebral rotational deformities make surgical procedures challenging risky. Such patients are usually compelled to undergo conservative treatment and there are very few reports on minimally invasive surgeries for them. We first-time report a patient with Kümmell disease and lumbar scoliosis treated with percutaneous kyphoplasty (PKP) under O-arm guidance. CASE SUMMARY An 89-year-old female was admitted to the hospital due to delayed low back pain after a fall. She was diagnosed with Kümmell disease based on physical and radiologic examinations. The patient experienced severe scoliosis and subsequently underwent O-arm-guided kyphoplasty, resulting in a significant alleviation of low back pain. CONCLUSION PKP has good efficacy in treating Kümmell disease. However, surgical risks are elevated in scoliosis patients with Kümmell disease due to the abnormal anatomical structure of the spine. O-arm assisted operations play a crucial role in decreasing surgical risks.

In vivo evaluation of hyaluronic acid–polyethylene glycol amended PMMA bone cement for orthopaedic application

The utilization of polymethyl methacrylate (PMMA) bone cement is employed for the purpose of stabilizing fractured vertebral bodies. The existence of a mechanical imbalance in hard polymethylmethacrylate (PMMA) bone cement has the potential to increase the likelihood of a fracture occurring in the neighbouring vertebral body. In order to reduce potential difficulties, the primary goal of this study is to investigate the potential benefits of increasing PMMA bone cement’s bioactivity and lowering its elastic modulus. The incorporation of a 10% volume fraction of hyaluronic acid (HyA) and polyethylene glycol (PEG) into the bone cement led to an improvement in the bioactivity and decreasing of elastic modulus of polymethylmethacrylate (PMMA). The integration of HyPE gel phase presents several advantages over pure PMMA bone cement, including enhanced setting parameters, improved degradability, and increased biocompatibility. The gel phase is additionally accountable for a reduction in the elastic modulus of polymethylmethacrylate (PMMA) bone cement. In addition, the existence of a porous structure that arises from the degradation of the HyPE gel phase delivers a significant amount of room, thereby enhancing the process of bone regeneration when implanted in the femur of rabbits. The utilization of HyPE in PMMA has been shown through comprehensive µ-CT analysis to enhance bone formation, thereby promoting osteointegration at the implantation site. Furthermore, the histological analysis demonstrated the existence of osteogenic activity in the PMMA polyethylene glycol supplemented with 10% HyA and 10% PEG after a 2-month period subsequent to implantation.

Establishing Standardization Guidelines For Finite-Element Optomechanical Simulations of Refractive Laser Surgeries: An Application to Photorefractive Keratectomy.

Computational models can help clinicians plan surgeries by accounting for factors such as mechanical imbalances or testing different surgical techniques beforehand. Different levels of modeling complexity are found in the literature, and it is still not clear what aspects should be included to obtain accurate results in finite-element (FE) corneal models. This work presents a methodology to narrow down minimal requirements of modeling features to report clinical data for a refractive intervention such as PRK. A pipeline to create FE models of a refractive surgery is presented: It tests different geometries, boundary conditions, loading, and mesh size on the optomechanical simulation output. The mechanical model for the corneal tissue accounts for the collagen fiber distribution in human corneas. Both mechanical and optical outcome are analyzed for the different models. Finally, the methodology is applied to five patient-specific models to ensure accuracy. To simulate the postsurgical corneal optomechanics, our results suggest that the most precise outcome is obtained with patient-specific models with a 100 µm mesh size, sliding boundary condition at the limbus, and intraocular pressure enforced as a distributed load. A methodology for laser surgery simulation has been developed that is able to reproduce the optical target of the laser intervention while also analyzing the mechanical outcome. The lack of standardization in modeling refractive interventions leads to different simulation strategies, making difficult to compare them against other publications. This work establishes the standardization guidelines to be followed when performing optomechanical simulations of refractive interventions.

Cardiac resident macrophages: The core of cardiac immune homeostasis

Cardiac resident macrophages (CRMs) are essential in maintaining the balance of the immune homeostasis in the heart. One of the main factors in the progression of cardiovascular diseases, such as myocarditis, myocardial infarction(MI), and heart failure(HF), is the imbalance in the regulatory mechanisms of CRMs. Recent studies have reported novel heterogeneity and spatiotemporal complexity of CRMs, and their role in maintaining cardiac immune homeostasis and treating cardiovascular diseases. In this review, we focus on the functions of CRMs, including immune surveillance, immune phagocytosis, and immune metabolism, and explore the impact of CRM's homeostasis imbalance on cardiac injury and cardiac repair. We also discuss the therapeutic approaches linked to CRMs. The immunomodulatory strategies targeting CRMs may be a therapeutic approach for the treatment of cardiovascular disease.

Extracellular Vesicles Functional “Brick‐Cement” Bio‐Integrated System for Annulus Fibrosus Repair

AbstractDue to the deficiency of mechanical supporting after discectomy and weak proliferative capacity of annulus fibrosus (AF) cells, the AF defect repair remains a clinical challenge. Herein, a myofibroblasts derived extracellular vesicles (M‐EVs) functional “brick‐cement” bio‐integrated system (M‐EVs@PGBgel) is developed to repair AF defect. The modified Poly(glycerol‐sebacate) (PGBS), “bio‐brick” layer, exhibited excellent support features on account of its elastomeric mechanical properties. The loaded M‐EVs in the “bio‐cement” layer activated ITGA6/PI3K/AKT pathway, regulated M2 macrophage polarization, thus synergistically promoting AF cell proliferation and migration. The “bio‐cement” layer integrated PGBS and remnant tissue at the defect through the Schiff base reaction and aided M‐EVs’ sustained release. This study demonstrated that M‐EVs@PGBgel significantly improved the disc's biological and mechanical properties in the AF defect microenvironments and promoted AF regeneration in vivo. The M‐EVs@PGBgel shows promise as an effective strategy to simultaneously address the mechanical imbalance and biological disruptions resulting from AF defect.

Oral microbiota-host interaction: the chief culprit of alveolar bone resorption.

There exists a bidirectional relationship between oral health and general well-being, with an imbalance in oral symbiotic flora posing a threat to overall human health. Disruptions in the commensal flora can lead to oral diseases, while systemic illnesses can also impact the oral cavity, resulting in the development of oral diseases and disorders. Porphyromonas gingivalis and Fusobacterium nucleatum, known as pathogenic bacteria associated with periodontitis, play a crucial role in linking periodontitis to accompanying systemic diseases. In periodontal tissues, these bacteria, along with their virulence factors, can excessively activate the host immune system through local diffusion, lymphatic circulation, and blood transmission. This immune response disruption contributes to an imbalance in osteoimmune mechanisms, alveolar bone resorption, and potential systemic inflammation. To restore local homeostasis, a deeper understanding of microbiota-host interactions and the immune network phenotype in local tissues is imperative. Defining the immune network phenotype in periodontal tissues offers a promising avenue for investigating the complex characteristics of oral plaque biofilms and exploring the potential relationship between periodontitis and associated systemic diseases. This review aims to provide an overview of the mechanisms underlying Porphyromonas gingivalis- and Fusobacterium nucleatum-induced alveolar bone resorption, as well as the immunophenotypes observed in host periodontal tissues during pathological conditions.

Vibration Qualification Campaign on Main Landing Gear System for High-Speed Compound Helicopter

Vibrations in helicopters have strong implications for their performance and safety, leading to the increased fatigue of components and reduced operational efficiency. As helicopters are designed to land on several types of surfaces, the landing gear system dissipates the impact on the ground and maintains stability during landing and take-off. These vibrations can arise from a variety of sources, such as aerodynamic loads, mechanical imbalances, and engine instabilities. In the present work, the authors describe the vibration qualification process of the main landing gear tailored to fast helicopters within the Clean Sky 2 Racer program. The method entails devising preliminary load sets that deform the structure in its key excited mode shapes to assess stresses and address the experimental campaign. A full-scale prototype model is then tested for sine sweep and random vibrations as per the Airbus Helicopter requirements in order to reach the final qualification and acceptance stage. Although the discussion centers on a landing gear structure, the described process could be extended to other critical equipment as well.

GSTP1 rs4147581 C>G and NLRP3 rs3806265 T>C as Risk Factors for Chronic Obstructive Pulmonary Disease: A Case-Control Study.

Chronic obstructive pulmonary disease (COPD) is a chronic respiratory ailment influenced by a blend of genetic and environmental factors. Inflammatory response and an imbalance in oxidative-antioxidant mechanisms constitute the primary pathogenesis of COPD. Glutathione S-transferase P1(GSTP1) plays a pivotal role as an antioxidant enzyme in regulating oxidative-antioxidant responses in the pulmonary system. The activation of the NOD-like receptor thermal protein domain (NLRP3) inflammatory vesicle can trigger an inflammatory response. Several investigations have implicated GSTP1 and NLRP3 in the progression of COPD; nonetheless, there remains debate regarding this mechanism. Employing a case-control study design, 312 individuals diagnosed with COPD and 314 healthy controls were recruited from Gansu Province to evaluate the correlation between GSTP1 (rs4147581C>G and rs1695A>G) and NLRP3 (rs3806265T>C and rs10754558G>C) polymorphisms and the susceptibility to COPD. The presence of the GSTP1 rs4147581G allele substantially elevated the susceptibility to COPD (CGvs.CC:OR=3.11,95% CI=1.961-4.935, P<0.001;GGvs.CC:OR=2.065,95% CI=1.273-3.350, P=0.003; CG+GGvs.CC:OR=2.594,95% CI=1.718-3.916, P<0.001). Similarly, the NLRP3rs3806265T allele significantly increased the susceptibility to COPD (TC:TT:OR=0.432,95% CI=0.296-0.630; TC+CCvs.TT:OR=2.132,95% CI=1.479-3.074, P<0.001). However, no statistically significant association was discerned between the rs1695A>G and rs10754558G>C polymorphisms and COPD susceptibility (P>0.05). In summary, this study ascertained that the GSTP1 rs4147581C>G polymorphism is associated with increased COPD susceptibility, with the G allele elevating the risk of COPD. Similarly, the NLRP3 rs3806265T>C polymorphism is linked to elevated COPD susceptibility, with the T allele heightening the risk of COPD.

A Critical Interpretive Synthesis of the Role of Arecoline in Oral Carcinogenesis: Is the Local Cholinergic Axis a Missing Link in Disease Pathophysiology?

Arecoline is the primary active carcinogen found in areca nut and has been implicated in the pathogenesis of oral squamous cell carcinoma (OSCC) and oral submucous fibrosis (OSF). For this study, we conducted a stepwise review process by combining iterative scoping reviews with a post hoc search, with the aim of identifying the specific mechanisms by which arecoline initiates and promotes oral carcinogenesis. Our initial search allowed us to define the current trends and patterns in the pathophysiology of arecoline-induced OSF and OSCC, which include the induction of cell proliferation, facilitation of invasion, adhesion, and migration, increased collagen deposition and fibrosis, imbalance in immune and inflammatory mechanisms, and genotoxicity. Key molecular pathways comprise the activation of NOTCH1, MYC, PRDX2, WNT, CYR61, EGFR/Pl3K, DDR1 signaling, and cytokine upregulation. Despite providing a comprehensive overview of potential pathogenic mechanisms of OSF, the involvement of molecules functioning as areca alkaloid receptors, namely, the muscarinic and nicotinic acetylcholine receptors (AChRs), was not elucidated with this approach. Accordingly, our search strategy was refined to reflect these evidence gaps. The results of the second round of reviews with the post hoc search highlighted that arecoline binds preferentially to muscarinic AChRs, which have been implicated in cancer. Consistently, AChRs activate the signaling pathways that partially overlap with those described in the context of arecoline-induced carcinogenesis. In summary, we used a theory-driven interpretive review methodology to inform, extend, and supplement the conventional systematic literature assessment workflow. On the one hand, the results of this critical interpretive synthesis highlighted the prevailing trends and enabled the consolidation of data pertaining to the molecular mechanisms involved in arecoline-induced carcinogenesis, and, on the other, brought up knowledge gaps related to the role of the local cholinergic axis in oral carcinogenesis, thus suggesting areas for further investigation.

Cylindrospermopsin exposure promotes redox unbalance and tissue damage in the liver of Poecilia reticulata, a neotropical fish species

ABSTRACT There is a growing concern regarding the adverse risks exposure to cylindrospermopsin (CYN) might exert on animals and humans. However, data regarding the toxicity of this cyanotoxin to neotropical fish species are scarce. Using the fish species Poecilia reticulata, the influence of CYN concentrations equal to and above the tolerable for drinking water may produce on liver was determined by assessing biomarkers of antioxidant defense mechanisms and correlated to qualitative and semiquantitative histopathological observations. Adult females were exposed to 0.0 (Control); 0.5, 1 and 1.5 μg/L pure CYN for 24 or 96 hr, in triplicate. Subsequently the livers were extracted for biochemical assays and histopathological evaluation. Catalase (CAT) activity was significantly increased only by 1.5 μg/L CYN-treatment, at both exposure times. Glutathione -S-transferase (GST) activity presented a biphasic response for both exposure times. It was markedly decreased after exposure by 0.5 μg/L CYN treatment but significantly elevated by 1.5 μg/L CYN treatment. All CYN treatments produced histopathological alterations, as evidenced by hepatocyte cords degeneration, steatosis, inflammatory infiltration, melanomacrophage centers, vessel congestion, and areas with necrosis. Further, an IORG >35 was achieved for all treatments, indicative of the presence of severe histological alterations in P. reticulata hepatic parenchyma and stroma. Taken together, data demonstrated evidence that CYN-induced hepatotoxicity in P. reticulata appears to be associated with an imbalance of antioxidant defense mechanisms accompanied by histopathological liver alterations. It is worthy to note that exposure to low environmentally-relevant CYN concentrations might constitute a significant risk to health of aquatic organisms.

The role of dysmetabolic iron overload syndrome in non-alcoholic fatty liver disease and carbohydrate metabolism disorders induction

Iron affects the pathogenesis and clinical course of several chronic metabolic diseases such as obesity, atherosclerosis, non-alcoholic fatty liver disease and type 2 diabetes mellitus. High pro-oxidant iron activity is physiologically controlled by mechanisms regulating entry, recycling, and loss of body iron. These mechanisms include the interplay of iron with ferritin, transferrin, hepcidin, insulin, as well as with adipokines and proinflammatory molecules. An imbalance of these regulatory mechanisms results in both systemic and parenchymal siderosis. Iron overload has a toxic effect on the major tissues involved in lipid and glucose metabolism — pancreatic β cells, liver, muscle, and adipose tissue — as well as the organs affected by chronic hyperglycemia — brain, retina and kidneys. Hyperferremia leads to a decrease in insulin secretion, the formation of insulin resistance and increased liver gluconeogenesis. Molecular mechanisms for these effects are diverse. Elucidating them will implicate both for carbohydrate metabolism disorders prevention and for the pathogenesis of other diseases that are, like diabetes mellitus type 2, associated with nutrition, aging and iron. The literature review presents data from world studies on the mutual influence of glucose metabolism and iron overload, and discusses the differences between hereditary and acquired disorders of iron metabolism from the standpoint of their influence on carbohydrate metabolism.

Monitoring Changes in Plasma Proteome in AML Patients Receiving Blood Transfusion Products

Background: Hemato-oncological patients, and in particular patients with acute myeloid leukemia (AML) in the remission induction treatment phase frequently receive transfusion products. These products include platelet- and red blood cell- concentrates and are administered in order to prevent and treat bleeding complications and anemia. During this treatment, patients are constantly monitored by clinical laboratory tests, however, additional studies could add nuanced information about the patients' status. Different studies have shown that plasma proteins change and their patterns' characteristics could be key to illustrate the patients' healthy and/or disease status. Importantly, changes in the plasma proteome in AML patients receiving transfusion products have not yet been studied. Thus, defining protein profiles during this phase is vital to use as a point of reference prior to tracing patients' treatments and their responses. Aim: In light of this, we aim to delineate the baseline plasma proteome in AML patients during their treatment phase. Methods: We employed unbiased mass spectrometry (MS)-based proteomics to gain insight in treatment-induced changes of the plasma proteome (Figure 1A). We included samples derived from 11 healthy donors and 11 AML patients who received chemotherapy and platelet, and red blood cell transfusions. AML patients without a previous transplant or platelet transfusion were included in this study. Results: We identified over 400 proteins in each plasma sample and found associations between proteins and clinical laboratory data, exemplified by a high correlation between Pro-Platelet Basic Protein (PPBP) and platelet incounts (r = 0.7, p-value &amp;lt; 0.001). We observed 169 significantly different proteins between AML patients and healthy controls, amongst the most significant changes we captured a strong signature of inflammation with an increased abundance of proteins involved in the acute-phase response pathway (i.e. SAA1 and CRP) and a decreased abundance of proteins involved in innate immune response (i.e. DEF1 and CAMP). Interestingly, we also found an increased abundance of proteins from the complement pathway (i.e. C9 and CFHR) and decreased abundance in proteins enriching for plasma lipoprotein particle remodeling (i.e. APOA1 and PON1) (Figure 1B). Furthermore, by building correlation networks we analyzed differences in the dynamics of plasma proteins in AML patients compared to healthy controls. This analysis showed several changes in associations between proteins, including alterations in known interactions such as the gain of correlation between APOA1 and GPLD1 as well as a loss of correlation between PLG and KNG1. Conclusion: These results highlight an imbalance in lipid metabolism and innate defense mechanisms, such as the coagulation pathway and complement system, in AML patients during their transfusion-dependent window. The plasma proteome studied in this pilot can serve as the basis to further explore changes induced in specific subgroups of patients, for example patients with and without bleeding complications. Follow up studies to analyze the changes observed here in larger cohorts are currently running (ALPHABET, trial registration NL9204) and they would be key to explore their potential association with clinical outcome in AML patients receiving transfusion products. Figure 1.- Exploring proteome changes in AML patients during their transfusion treatment phase. A) Graphical summary of the study, and B) Proteins with contrasting dynamics when comparing AML patients in treatment phase to healthy controls. Box plots depict median with its upper and lower limits representing the first (25th) and third (75th) percentiles, respectively. Box plot whiskers extend up to the highest or lowest value within 1.5 x IQR.

Multi-Locational Based Comparative Antioxidant Study of Some Commonly Consumed Fruits and Vegetables in a Part of Eastern India

The oxidative compounds at a certain level positively affect the body's immune functions; however, inappropriate lifestyles and dietary habits can trigger an imbalance in the body's antioxidant defense mechanisms and the production of free radicles, can cause molecular damages which can be observed through different biomarkers. These free radicles can cause undesirable health, leading to different degenerative diseases and pathogenesis. Antioxidants are highly effective in reducing the frequent occurrence of such chronic diseases. FAV (fruits and vegetables) and food plants have been well known for its antioxidant contain. This study interprets to determine the total phenolic content which ranges from 8.6 μg (Tomato of Cuttack) to 27.8 μg (Amla of Jajpur) of gallic acid equivalents per 100 gm of extract. Flavonoid content ranges from 3.6-34.2 μg of quercetin equivalents per 100 gm of the extract, with Karela of Jajpur having the maximal (34.2 μg) content, with banana (3.6 μg) being the least of Cuttack. Antioxidant content ranges from 5.1-10.8 μg/ml. Banana of Jajpur has maximal IC50 value through DPPH based scavenging assay method, with Amla of Angul, Cuttack and Dhenkanal as the lowest capacity. The significant output of the research will convey the habitant of these localities and the selection as well as the inclusion of the finest fruits and vegetables in their day to day regular diet. The researchers may utilize the data for geographical based epidemiological studies where the intake of reported foods can be used to measure their antioxidant values, which may further be utilized to verify the impact of antioxidants and their synergistic effect on the cell. Animal based experimental studies or human based clinical trials may interpret the role of dietary phytochemical based antioxidants in preventing different chronic and degenerative diseases.

Imbalance of immunoregulatory molecular cellular mechanisms as a cause of recurrent miscarriage

Introduction. Recurrent pregnancy loss (RPL) is an early spontaneous termination of pregnancy before 20 weeks, which is defined as two or more miscarriages. Most of the known causes associated with the pathophysiology of RPL include endocrine disorders, antiphospholipid syndrome, intrauterine infection, anatomical defects of the uterus, etc. However, in approximately 50% of cases, the cause of the pathogenesis of RPL remains unclear and may be associated with a violation of immune mechanisms, such as maternal tolerance to fetal alloantigens and controlled inflammation, which play a decisive role in successful pregnancy. Purpose of the review. To summarize current knowledge about the molecular cellular immune mechanisms that ensure the induction and maintenance of maternal-fetal tolerance and highlight the association between impaired immunoregulation and the development of RPL. Methods. The materials were the results of research on the topic over the past 23 years. Publications included in the Pubmed and eLibrary.ru databases were analyzed. Results. This review provides information about the immune regulation of pregnancy, which is carried out through the interaction of molecular mediators and effector cells of the innate and adaptive immunity. Current evidence points to a key role of the immune system in the pathophysiology of RPL. Successful pregnancy requires a finely regulated and tightly controlled balance between immune activation and tolerance to fetal antigens. Conclusion. The main events occur in the uteroplacental zone, where trophoblast cells and maternal lymphocytes come into close contact. The search for biomarkers for pregnancy complications is the focus of scientists.

Effects of Varied Planar Dimensions of IPMC on Simulated Actuation using COMSOL

This study focuses on mechatronic systems and their use of bending smart materials, specifically the ionic polymer metal composite (IPMC), for compliant actuation. The advantages of IPMC actuators, such as low power consumption and high flexibility, are highlighted. The actuation mechanism of IPMCs involving ion migration, water transport, and mechanical stress imbalance is discussed. The influence of geometric parameters, specifically length and width, on IPMC performance is investigated through simulations. Results show a positive correlation between IPMC lengths exceeding 30 mm and displacement, with longer lengths leading to higher displacements. The relationship between width and maximum displacement is attributed to factors like increased active area, larger polymer volume, and potential effects on mechanical properties. Further electromechanical analysis is needed for a comprehensive understanding of these mechanisms.

IMMUNOREACT 6: weak immune surveillance characterizes early-onset rectal cancer.

Colon cancer in young patients is often associated with hereditary syndromes; however, in early-onset rectal cancer, mutations of these genes are rarely observed. The aim of this study was to analyse the features of the local immune microenvironment and the mutational pattern in early-onset rectal cancer. Commonly mutated genes were analysed within a rectal cancer series from the University Hospital of Padova. Mutation frequency and immune gene expression in a cohort from The Cancer Genome Atlas ('TCGA') were compared and immune-cell infiltration levels in the healthy rectal mucosa adjacent to rectal cancers were evaluated in the IMMUNOlogical microenvironment in REctal AdenoCarcinoma Treatment 1 and 2 ('IMMUNOREACT') series. In the authors' series, the mutation frequency of BRAF, KRAS, and NRAS, as well as microsatellite instability frequency, were not different between early- and late-onset rectal cancer. In The Cancer Genome Atlas series, among the genes with the most considerable difference in mutation frequency between young and older patients, seven genes are involved in the immune response and CD69, CD3, and CD8β expression was lower in early-onset rectal cancer. In the IMMUNOlogical microenvironment in REctal AdenoCarcinoma Treatment 1 and 2 series, young patients had a lower rate of CD4+ T cells, but higher T regulator infiltration in the rectal mucosa. Early-onset rectal cancer is rarely associated with common hereditary syndromes. The tumour microenvironment is characterized by a high frequency of mutations impairing the local immune surveillance mechanisms and low expression of immune editing-related genes. A constitutively low number of CD4 T cells associated with a high number of T regulators indicates an imbalance in the immune surveillance mechanisms.

Physiological and pathophysiological mechanisms of the molecular and cellular biology of angiogenesis and inflammation in moyamoya angiopathy and related vascular diseases.

The etiology and pathophysiological mechanisms of moyamoya angiopathy (MMA) remain largely unknown. MMA is a progressive, occlusive cerebrovascular disorder characterized by recurrent ischemic and hemorrhagic strokes; with compensatory formation of an abnormal network of perforating blood vessels that creates a collateral circulation; and by aberrant angiogenesis at the base of the brain. Imbalance of angiogenic and vasculogenic mechanisms has been proposed as a potential cause of MMA. Moyamoya vessels suggest that aberrant angiogenic, arteriogenic, and vasculogenic processes may be involved in the pathophysiology of MMA. Circulating endothelial progenitor cells have been hypothesized to contribute to vascular remodeling in MMA. MMA is associated with increased expression of angiogenic factors and proinflammatory molecules. Systemic inflammation may be related to MMA pathogenesis. This literature review describes the molecular mechanisms associated with cerebrovascular dysfunction, aberrant angiogenesis, and inflammation in MMA and related cerebrovascular diseases along with treatment strategies and future research perspectives. References were identified through a systematic computerized search of the medical literature from January 1, 1983, through July 29, 2022, using the PubMed, EMBASE, BIOSIS Previews, CNKI, ISI web of science, and Medline databases and various combinations of the keywords "moyamoya," "angiogenesis," "anastomotic network," "molecular mechanism," "physiology," "pathophysiology," "pathogenesis," "biomarker," "genetics," "signaling pathway," "blood-brain barrier," "endothelial progenitor cells," "endothelial function," "inflammation," "intracranial hemorrhage," and "stroke." Relevant articles and supplemental basic science articles almost exclusively published in English were included. Review of the reference lists of relevant publications for additional sources resulted in 350 publications which met the study inclusion criteria. Detection of growth factors, chemokines, and cytokines in MMA patients suggests the hypothesis of aberrant angiogenesis being involved in MMA pathogenesis. It remains to be ascertained whether these findings are consequences of MMA or are etiological factors of MMA. MMA is a heterogeneous disorder, comprising various genotypes and phenotypes, with a complex pathophysiology. Additional research may advance our understanding of the pathophysiology involved in aberrant angiogenesis, arterial stenosis, and the formation of moyamoya collaterals and anastomotic networks. Future research will benefit from researching molecular pathophysiologic mechanisms and the correlation of clinical and basic research results.