The chemotactic cytokine fractalkine (FKN, chemokine CX3CL1) has unique properties resulting from the combination of chemoattractants and adhesion molecules. The soluble form (sFKN) has chemotactic properties and potently attracts T cells and monocytes. The membrane-bound form (mFKN) facilitates diapedesis and is responsible for cell-to-cell adhesion, especially by promoting the strong adhesion of leukocytes (monocytes) to activated endothelial cells with the subsequent formation of an extracellular matrix and angiogenesis. FKN signaling occurs via CX3CR1, which is the only known member of the CX3C chemokine receptor subfamily. Signaling within the FKN-CX3CR1 axis plays an important role in many processes related to inflammation and the immune response, which often occur simultaneously and overlap. FKN is strongly upregulated by hypoxia and/or inflammation-induced inflammatory cytokine secretion, and it may act locally as a key angiogenic factor in the highly hypoxic tumor microenvironment. The importance of the FKN/CX3CR1 signaling pathway in tumorigenesis and cancer metastasis results from its influence on cell adhesion, apoptosis and cell migration. This review presents the role of the FKN signaling pathway in the context of angiogenesis in inflammation and cancer. The mechanisms determining the pro- or anti-tumor effects are presented, which are the cause of the seemingly contradictory results that create confusion regarding the therapeutic goals.

Angiogenesis is a critical physiological response to ischemia but becomes pathological when dysregulated and driven excessively by inflammation. We recently identified a novel angiogenic role for tripartite-motif-containing protein 2 (TRIM2) whereby lentiviral shRNA-mediated TRIM2 knockdown impaired endothelial angiogenic functions in vitro. This study sought to determine whether these effects could be translated in vivo and to determine the molecular mechanisms involved. CRISPR/Cas9-generated Trim2–/– mice that underwent a periarterial collar model of inflammation-induced angiogenesis exhibited significantly less adventitial macrophage infiltration relative to wildtype (WT) littermates, concomitant with decreased mRNA expression of macrophage marker Cd68 and reduced adventitial proliferating neovessels. Mechanistically, TRIM2 knockdown in endothelial cells in vitro attenuated inflammation-driven induction of critical angiogenic mediators, including nuclear HIF-1α, and curbed the phosphorylation of downstream effector eNOS. Conversely, in a hindlimb ischemia model of hypoxia-mediated angiogenesis, there were no differences in blood flow reperfusion to the ischemic hindlimbs of Trim2–/– and WT mice despite a decrease in proliferating neovessels and arterioles. TRIM2 knockdown in vitro attenuated hypoxia-driven induction of nuclear HIF-1α but had no further downstream effects on other angiogenic proteins. Our study has implications for understanding the role of TRIM2 in the regulation of angiogenesis in both pathophysiological contexts.

Neuroimmune semaphorin 4A (Sema4A), a member of semaphorin family of transmembrane and secreted proteins, is an important regulator of neuronal and immune functions. In the nervous system, Sema4A primarily regulates the functional activity of neurons serving as an axon guidance molecule. In the immune system, Sema4A regulates immune cell activation and function granting a fine tuning of immune response. Recent studies have shown a dysregulation of Sema4A expression in several types of cancer such as hepatocellular carcinoma, colorectal and breast cancers. Cancers have been associated with abnormal angiogenesis. The function of Sema4A in angiogenesis and cancer is not defined. Recent studies have demonstrated Sema4A expression and function in endothelial cells. However, the results of these studies are controversial as they report either pro – or anti-angiogenic Sema4A effects depending on the experimental settings. In this mini-review, we discuss these findings as well as our data on Sema4A regulation of inflammation and angiogenesis, which both are important pathologic processes underlining tumorigenesis and tumor metastasis. Understanding the role of Sema4A in those processes may guide the development of improved therapeutic treatments for cancer.

Exercise induced bronchoconstriction (EIB) is a common complication of athletes and individuals who exercise regularly. It is estimated that about 90% of patients with underlying asthma experience EIB. Sex differences in the prevalence of asthma have been widely reported, with higher rates in boys vs. girls before puberty, and higher rates in women than men after puberty. Because atopy has been reported to occur at higher rates in athletes than in non-athletes, in this study we investigated sex differences in EIB and atopy in athletes. A systematic literature review identified 60 studies evaluating EIB and/or atopy in post-pubertal adult athletes (n=7501). Collectively, these studies reported: 1) a 23% prevalence of EIB in athletes; 2) a higher prevalence of atopy in male athletes vs. females; 3) a higher prevalence of atopy in athletes with EIB; and 4) a significantly higher rate of atopic EIB in male vs. female athletes. Our analysis indicates that the physiological changes that occur during exercise may differentially affect male and female athletes, and suggest an interaction between male sex, exercise, and atopic status in the course of EIB. Understanding these sex differences is important to provide personalized management plans to athletes with underlying asthma and/or atopy.

Background: Despite the existence of a wide variety of anti-inflammatory drugs, the vast majority are classified as steroidal or non-steroidal. Both classes with many side effects that limit usage. Thus, the search for new molecules with anti-inflammatory potential is still important. Methods: Five phenylbenzohydrazides were synthetized and evaluated in pre-clinical models of acute inflammation in vivo and in vitro. Results: Substances significantly reduced cell migration induced by carrageenan. It was also observed an intense inhibition in protein extravasation and cytokines (IL-6, IL-1β, and TNF-α) production as well as nitric oxide reduction. INL-11 demonstrated to be the most potent since the reduction was significant even when compared with dexamethasone. In vitro INLs also reduced cytokines and NO production and iNOS activity. INL-11 was the most effective in reducing cell migration in vitro. Conclusions: our data suggest that these substances are suitable for further development to new series of compounds that could lead to new hits and future drug prototypes for anti-inflammatory conditions.

Pregnancy-induced hypertension and preeclampsia are associated with significant maternal and fetal mortality. A better understanding of those diseases, delineation of molecular pathomechanism, and efficient treatment development are some of the most urgent tasks in obstetrics and gynecology. Recent findings indicate a crucial role of inflammation in the development of hypertension and preeclampsia. Although the mechanism is very complex and needs further explanation, it appears that high levels of cholesterol, urate, and glucose activates NLRP3 inflammasome, which produces IL-1β, IL-18 and gasdermin D. Production of these proinflammatory chemokines is a beginning of local and general inflammation, what results in sympathetic outflow, angiotensin II production, proteinuria, hemolysis, liver damage, immunothrombosis, and coagulopathy. NLRP3 inflammasome is a critical complex in the mediation of inflammatory response, which makes it crucial for the development of pregnancy-induced hypertension and preeclampsia, as well as its complications, such as placental abruption and HELLP syndrome. Herein presented the article delineate molecular mechanisms of those processes, indicating directions of future advance.

Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, is a complex gastrointestinal disorder with a multifactorial etiology, including environmental triggers, autoimmune mechanisms, and genetic predisposition. Despite advancements in therapeutic strategies for IBD, its associated mortality rate continues to rise, which is often attributed to unforeseen side effects of conventional treatments. In this context, we explored the potential of Ecklonia cava extract (ECE) derived from an edible marine alga known for its anti-inflammatory and antioxidant properties in mitigating IBD. This study investigated the effectiveness of ECE as a preventive agent in a murine model of dextran sulfate sodium (DSS)-induced colitis. Our findings revealed that pretreatment with ECE significantly ameliorated colitis severity as evidenced by increased colon length, reduced spleen weight, and histological improvements demonstrated by immunohistochemical analysis. Furthermore, ECE significantly attenuated the upregulation of inflammatory cytokines and mediators and the infiltration of immune cells known to be prominent features of colitis in mice. Notably, ECE restored dysbiosis of intestinal microflora and aided in the recovery of damaged intestinal mucosa. Mechanistically, ECE exhibited protective effects against pathogenic colitis by inhibiting the NLRP3/NF-κB pathway known to be pivotal regulators in the inflammatory signaling cascade. These compelling results suggest that ECE holds promise as a potential candidate for IBD prevention. It might be developed into a functional food for promoting gastrointestinal health. This research sheds light on the preventive potential of natural compounds like ECE in the management of IBD, offering a safer and more effective approach to combating this challenging disease.

Movement disorders can be associated with various drugs and systemic diseases, posing diagnostic challenges for clinicians. This review explores the spectrum of movement disorders associated with pharmacological agents and medical conditions. Drug-induced movement disorders encompass a broad range of conditions resulting from exposure to medications that affect several neurotransmitters. Neuroleptic medications can lead to tardive dyskinesia, characterized by involuntary, repetitive movements. Antipsychotics and antiemetics, including metoclopramide, may induce acute dystonic reactions. Other drugs, such as dopamine receptor-blocking agents, can contribute to drug-induced parkinsonism. Beyond medications, movement disorders can also arise secondary to systemic diseases. Metabolic disorders like Wilson's disease, characterized by copper accumulation, may manifest as chorea or dystonia. Inflammatory conditions such as rheumatoid arthritis and systemic lupus erythematosus can result in secondary movement disorders due to autoimmune-mediated processes affecting the central nervous system. Movement disorders linked to drugs or systemic diseases often necessitate a thorough clinical evaluation, including detailed medication histories and comprehensive systemic assessments. Neuroimaging, laboratory investigations, and, in some cases, cerebrospinal fluid analyses and electrodiagnostic studies help in establishing accurate diagnoses. Management involves addressing the underlying cause, modifying medications, and employing symptomatic treatments.

Chronic inflammation may have a detrimental impact on human health as it tends to result in cancer. In addition, it is often linked to different steps that participate in tumorigenesis, including cellular transformation, survival, promotion, invasion, proliferation, angiogenesis, and metastasis. Hence, inflammation predisposes cancer development and plays a vital role in promoting all tumorigenesis stages. Inflammation is caused by many factors, such as bacterial and viral infections, tobacco smoking, autoimmune diseases, obesity, asbestos exposure, and many others, increasing cancer risk. Moreover, cancer can be enhanced by mutations that proceed to cancer progression. Consequently, it leads to immunosuppression and provides a favorable background for tumor development. Although many studies address the question of relationships between inflammation and cancer development, little attention is paid to the link between inflammation and blood cancer. Therefore, the current study reviews the role of inflammation in cancer development, particularly in blood cancer. A meta-analysis research approach meets the research objective and answers the research question. The review results indicate that chronic inflammation directly relates to the development of many cancer types, blood cancer in particular.

Abstract: High-dose-rate interstitial brachytherapy (HDR-ISBT) has recently come to be considered one of the most effective treatments for oral cancer. On the other hand, it is important to note that radiation therapy has some side effects. Especially, radiation-induced malignancy is probably the most serious complication affecting long-term survivors. We report a case of a radiation-induced undifferentiated spindle cell sarcoma that developed following HDR-ISBT for tongue squamous cell carcinoma (SCC). A 39-year-old woman with right tongue SCC underwent HDR-ISBT (60 Gy, 10 fractions, 8 days) treatment. Five years and one month later, a tumor had developed at the primary site. Surgery was performed for the tumor, which was histopathologically diagnosed as an undifferentiated spindle cell sarcoma. That was distinct from the squamous cell origin of the primary cancer. According to recently established criteria for radiation-induced malignancy, this case was classified as a radiation-induced sarcoma. A search of the literature revealed no previous report of radiation-induced malignancy following HDR-ISBT for tongue cancer.

Toll-like receptors (TLRs) are a class of pattern recognition receptors (PRRs) family that identify pathogen-associated molecular patterns derived from microbes and activate immune cell response. Following TLRs ligation, different adaptor and transcription molecules such as myeloid differentiation primary response gene 88 (MyD88) and nuclear factor kappa B (NF-kB) are recruited that initiate inflammatory signaling pathways. The human Toll-like receptor 10 (hTLR10) is a novel member of the PRRs family with a regulatory function of immune responses because of unique cytoplasmic domains which lead to induction of both inflammatory and anti-inflammatory properties. Recent studies have reported the association of TLR10 polymorphisms with many inflammatory diseases and human cancer. Engagement of TLR10 on the surface of the epithelium and macrophages leads to the production of proinflammatory cytokines and chemokines, while other studies have proven an anti-inflammatory role of TLR10. Accordingly, TLR10 suppresses proinflammatory cytokine production via negative regulation of MyD88 and the Akt (protein kinase B) and MAPK (mitogen-activated protein kinase) signaling pathways. This review aimed to provide answers for these conflicting findings (Inflammatory and anti-inflammatory properties of TLR10) to further identify distinct biological functions of TLR10.

Chronic inflammatory diseases are considered the most significant cause of death worldwide. Current treatments for inflammatory diseases are limited due to the lack of understanding of the biological factors involved in early-stage disease progression. Nerve growth factor (NGF) is a neurotrophic factor directly associated with inflammatory and autoimmune diseases like osteoarthritis, multiple sclerosis, and rheumatoid arthritis. It has been shown that NGF levels are significantly upregulated at the site of inflammation and play a crucial role in developing a robust inflammatory response. However, little is known about NGF's temporal expression profile during the initial progressive phase of inflammation. This study aimed to determine the temporal expression pattern of NGF in rat skin during Adjuvant-Induced Arthritis (AIA). Sprague Dawley rats were randomly divided into control and Complete Freund's Adjuvant (CFA) treated groups. Levels of NGF were evaluated following unilateral AIA at different time points and it was found that peripheral inflammation due to AIA significantly upregulated the expression of NGF mRNA and Protein in a biphasic pattern. These results suggest that NGF signaling is crucial for initiating and maintaining peripheral neurogenic inflammation in rats during AIA.

Psychosis can be defined as a combination of psychopathological symptoms including delusions and/or hallucinations without insight. Psychotic disorders may configure a primary psychiatric illness or represent the result of a functional/structural brain damage induced by substance use, neurological diseases or other medical conditions. They are multifactorial disorders in which genetic, environmental and gene-environment interaction factors contribute to the expressiveness of the symptoms. Among the environmental factors, psychotropic substances represent the most important removable facilitators of psychosis. In our study, we compared the prevalence of substance induced psychosis between a sample of patients affected by cannabis use disorder and a sample of patients affected by cocaine use disorder analyzing retrospectively the data of outpatients with no personal or family history of psychiatric illnesses.

Drug induced liver injury (DILI) is the most common cause of acute liver failure and 5-10% of patients hospitalized for jaundice are diagnosed with DILI. For a diagnosis of DILI to be made, there should be exclusion of other etiologies of liver injury and the use of a precipitator drug, latency of symptoms, and resolution of liver injury once the offending drug is identified and discontinued. In our case report, we present a patient with idiosyncratic hepatocellular pattern DILI after two doses of ocrelizumab for treatment of multiple sclerosis. Ocrelizumab was given 16 and 27 days prior to the onset of icterus, jaundice, and fatigue, in a patient without the evidence of prior exposure to hepatitis B virus. At presentation labs revealed severe acute hepatocellular liver injury with R factor of 30.42, marked hyperbilirubinemia, and transient hypoalbuminemia. No evidence of latent or active hepatitis B infection was detected. Drug dechallenge led to return of liver chemistries to near-normal levels 31 days after the onset of her symptoms. This case indicates DILI diagnosis associated with the use of ocrelizumab, and warrants careful monitoring of liver functions in patients even in the absence of hepatitis B.

In resettlement planning literature, much has been written on economic, land valuation and compensation, infrastructure and services aspects of the land. Psychological risks and stresses of resettled communities, however, have been under-researched. The current research looks at the psychological risks of resettlers in a Development-Induced Displacement and Resettlement (DIDR) project in Sri Lanka. Focusing on the stages of resettlement planning process discussed by Scudder and Colson four-stage model (1980) and the psychological risks discussed by Cernea’s (1990) impoverishment risks and reconstruction (IRR) model. This study evaluates the significant level of the psychological risks faced by the communities in DIDR projects in Sri Lanka relating to before and after resettlement. Moragahakanda Resettlement Project (MRP) was selected as the case study which is located in Naula DS division of Matale District, Central Province, Sri Lanka. A questionnaire survey, documents and field observations were used to evaluate the current psychological risks. The responses received from multiple choice questions were analyzed by Significant Point (SP) index. The research findings point that there are no conspicuous changes of psychological risks related to before/after resettlement has occurred in re-settlers. The findings highlight that the psychological risk levels in transition stage have remained the same level in the potential development stage. This research provides a systematic guidance enabling the physical planners to prioritize the most significant psychological risks which should be considered in the decision-making process of DIDR projects.

Background: The morbidity of myocardial infarction is keeping raise in this decade. Because of high safety and operability , percutaneous coronary intervention(PCI) has been used to conquer this disease for more than 20 years.An important complication of PCI is contrast induced nephropathy(CIN), which raises our attention. Previously, we started a study to explore the correlation between acute kidney injury and myonecrosis after scheduled percutaneous coronary intervention. Our study showed that the rate of CI-AKI in patients with post-procedural myocardial injury and undergoing elective PCI was higher than that in patients free of injury. Methods: In this study,forty male rats were randomly divided into four groups: control group (n=8), CM group (n=12), AMI group (n=8) and AMI+CM group (n=12), then velocity of renal artery blood flow (VRABF), computer tomography (CT), serum creatinine(Scr), reactive oxidative species (ROS), periodic acid-Schiff (PAS) and TUNEL were used to estimate the injury of kidney. We analyzed 327 non-ST-segment elevation acute coronary syndrome subjects undertaking elective PCI. Serum levels of creatinine (SCr) and the eGFR before coronary angiography, and 24–72 h after contrast administration were recorded to assess the renal function. Results: The data showed that VRABF was lower in AMI+CM group than CM group from 0 minute to 24h and CT number in cortex was higher in AMI+CM group than CM group at 4-hour. As well as the level of Scr in AMI+CM group displayed a significantly increase at 24-hour compared with CM group. The histopathologic scores and percentage of tubular cell apoptosis were higher in AMI+CM group at 24-hour. In 327 patients, we found that CI-AKI occurred more often in subjects with post-procedural myonecrosis (PMN) than in those without PMN (20.8% versus 5.8%, respectively, P=0.001). Conclusion: Compared to the elective patient, the injury of CIN exhibited a higher severity in AMI patient.

Inflammation is widely acknowledged as a significant characteristic of cancer, playing a substantial function in both the initiation and advancement of cancers. In this research, we planned to investigate the comparison among pan-immune inflammation markers and other well-known markers (systemic immune inflammation index and neutrophil to lymphocyte ratio) to predict prognosis in individuals treated with radical cystectomy for bladder cancer. Methods: In this retrospective analysis, we focused on preoperative PIV, systemic immune inflammation index (SII), and neutrophil-lymphocyte ratio (NLR) in 193 individuals managed with radical cystectomy for bladder cancer between January 2016 and November 2022. Multivariable logistic regression assessments were perfomred to assess the predictive capabilities of PIV, SII, and NLR for infiltration of lymph nodes (N), aggressive tumor stage (pT3/pT4), and any non-organ limited disease at the time of RC. Multivariable Cox regression analyses were conducted to assess the predictive impact of PIV on Relapse-free survival (RFS), Cancer-specific survival (CSS), and Overall survival (OS). Results: Our individuals were divided into high PIV and low PIV cohorts using the optimal cut-off value (340.96 x 109/ L) based on receiver operating characteristic curve analysis for relapse-free survival. In multivariable preoperative logistic regression models, only SII and PIV correlated with the infiltration of lymph nodes, aggressive disease, and any non-organ confined disease. In multivariable Cox regression models considering presurgical clinicopathological variables, an higher PIV was associated with diminished RFS (p = 0.017) and OS (p = 0.029). In addition, in multivariable Cox regression models for postoperative outcomes, a high PIV correlated with both RFS ( p = 0.034) and OS ( p= 0.048). Conclusions: Our study suggests that PIV and SII are two very similar markers that may serve as an independent and significant predictor of aggressive disease and worse survival impacts on individuals undergoing radical cystectomy for bladder neoplasm.

The tension cable-supported power transmission structure (TC-PTS) is a new type of power transmission structure suitable for mountainous terrain, which is sensitive to wind load. In this regard, a nonlinear finite element analysis model of wind-induced vibration is proposed for the TC-PTS, and the wind-induced vibration response of the structure is analyzed. Firstly, the tangent stiffness matrix of the three-dimensional truss element for the supporting suspension cable and transmission line, considering the geometric nonlinearity of structures, is derived through the relationship between the element elastic energy and its displacement. Subsequently, the element mass matrix and damping matrix of the supporting suspension cable and transmission line, as well as the element nodal load vector obtained from wind load equivalence are given. Then, based on the nonlinear finite element theory, the nonlinear dynamic equation of wind-induced vibration is established for the TC-PTS and solved by Newmark-β method combined with Newton-Raphson iterative method. Furthermore, the rain-flow counting method and Miner's linear fatigue cumulative damage theory were used for wind induced fatigue damage assessment. Finally, a two-span TC-PTS is selected as an example, and the wind-induced nonlinear vibration and fatigue damage assessment are analyzed through the proposed model. The results show that the proposed model has high computational accuracy and efficiency. With the increase of wind speed and wind direction angle, the maximum lateral displacement and tension of the supporting suspension cable and transmission line increase, and their degree of increase shows a nonlinear trend. In terms of the wind-induced fatigue analysis results of TC-PTS, the fatigue damage at the end of the supporting-conductor suspension cable is greater than the fatigue damage at its midpoint. Compared to the fatigue damage at the midpoint of the conductor, the fatigue damage at the end of the conductor is less affected by wind direction angle, and both are more significantly affected by the wind speed.

This paper presents Mathematical Formulation for Neutrino-Fission of a heavy nuclei in Neutrino-environments. It has been proposed that neutrino fission is a dynamic two-process reaction, where more than one neutrino can be captured by target nucleus. A quantity named Neutrino-Zeta with units of eV^-1 has been defined to represent Neutrino-environments. Neutrino-zeta with assumed excited energy states for heavy nuclei A∼230-270 is estimated to be 0.0212 MeV^-1, with the probability of fission Barrier energy state P(E_x,f)= 0.169064014 with E_x,f =6MeV. P(E_x,f)=0.222664 is highest at zeta=0.1MeV^-1 . It has been shown that probabilities of certain excitation energy states and their corresponding decay reactions at those excitation energies can be equal for two neutrino-zetas. Neutron induced fission for different neutrinos hypothesize that probability of symmetric fission channels is higher at low neutrino-zetas, which can be tested experimentally.

The channels from the superfamily of transient receptor potential (TRP) activated by reactive oxygen species (ROS) are defined as redox channels. Those with the best exposure of the cysteine residues and hence the most sensitive to oxidative stress are TRPC4, TRPC5, TRPV1, TRPV4, and TRPA1, while others, such as TRPM2 and TRPM7 are indirectly activated by ROS. Activation by ROS has different effects on the tumorigenic process: some TRP channels may, upon activation, stimulate proliferation, apoptosis, or migration of cancer cells, while others inhibit these processes, depending on the cancer type, tumoral microenvironment and finally on the methods used for evaluation. Therefore, the use of these polymodal proteins as therapeutic targets is still an unmet need, despite their draggability and modulation by simple and mostly unharmful compounds. In this review, we intend to create some cellular models of the interaction between oxidative stress, TRP channels, and inflammation. Although the crosstalk between the three actors is rather theoretical, we intended to gather the recently published data and proposed pathways of cancer inhibition using modulators of TRP proteins, hoping that the experimental data corroborated with clinical information may finally bring the results from the bench to the bedside.

Fibrosis is an important health problem and its pathogenetic activation is still largely unknown. It can develop either spontaneously or, more frequently, as a consequence of various underlying diseases, such as chronic inflammatory autoimmune diseases. Fibrotic tissue is always characterized by mononuclear immune cells infiltration. The cytokine profile of these cells shows clear proinflammatory and profibrotic characteristics. Furthermore, the production of inflammatory mediators by non-immune cells, in response to several stimuli, can be involved in the fibrotic process. It is now established that defects in the abilities of non-immune cells to mediate immune regulation may be involved in the pathogenicity of a series of inflammatory diseases. The convergence of several, not yet well identified, factors results in the aberrant activation of non-immune cells, such as epithelial cells, endothelial cells and fibroblasts, that producing pro-inflammatory molecules, exacerbate the inflammatory condition leading to the excessive and chaotic secretion of extracellular matrix proteins. However, the precise cellular mechanisms involved in this process have not yet been fully elucidated. In this review we explore the latest discoveries on the mechanisms that initiate and perpetuate the vicious circle of abnormal communications between immune and non-immune cells, responsible for fibrotic evolution of inflammatory autoimmune diseases.

Spatially resolved, line-of-sight measurements of aluminum monoxide emission spectra in laser ablation plasma are used with Abel inversion techniques to extract radial plasma temperatures. Contour mapping of the radially deconvolved signal intensity shows a ring of AlO formation near the plasma boundary with the ambient atmosphere. Simulations of the molecular spectra were coupled with the line profile fitting routines. Temperature results are presented with simultaneous inferences from lateral, asymmetric radial, and symmetric radial AlO spectral intensity profiles. This analysis indicates that we measured shockwave phenomena in the radial profiles, including a temperature drop behind the blast wave created during plasma initiation.

Biomimetic design has recently received widespread attention. Inspired by the Terebridae structure, this paper provides a structural form for suppressing vortex-induced vibration (VIV) response. Four different structural forms are shown, including the traditional smooth cylinder (P0), the Terebridae-inspired cylinder with a helical angle of 30° (P30), the Terebridae-inspired cylinder with a helical angle of 60° (P60), and the Terebridae-inspired cylinder with a helical angle of 90° (P90). And computational fluid dynamics (CFD) method is adopted to solve the flow pass the Terebridae-inspired structures, and the vibration equation is solved using the Newmark-β method. The results show that the VIV responses are effectively controlled in the lock-in region for P30, P60, and P90, and P60 shows the best VIV suppression performance. The transverse amplitude and the downstream amplitude can be reduced by 82.67% and 91.43% respectively for P60 compared with that for P0, and the peak of the mean-drag coefficient is suppressed by 53.33%. The Q-criterion vortices of P30, P60, and P90 are destroyed, with irregular vortices shedding. It is also found that the boundary layer separation is located on the Terebridae-inspired ribs. The twisted ribs cause the separation point to constantly change along the spanwise direction, resulting in the development of the boundary layer separation being completely destroyed. The strength of the wake flow is significantly weakened for the Terebridae-inspired cylinder. In the lock-in region, the motion trajectory presents a typical 8-shaped for P0, while the motion trajectory of the Terebridae-inspired cylinder tends to be a flat 1-shaped.

Trichoderma spp. are widely used in plant disease control as biocontrol agents. Inducing plant disease resistance is an important biocontrol mechanism of Trichoderma. It is of great significance to explore the factors involved in the surface recognition and interaction of Trichoderma with plants. Hydrophobin is a small molecular protein rich in cysteine in higher filamentous fungi and has been found to participate in the morphogenesis and interaction of fungi with other organisms. In this study, the type II hydrophobic protein-coding gene Thfb6 from T. harzianum TH33 was cloned and heterologously expressed in Escherichia coli BL21 (DE3). The purified recombinant protein Thfb6 induced a hypersensitive response in tobacco leaves, a burst of reactive oxygen species, and an accumulation of callose, phenolic substances, and lignin in tobacco, indicating that Thfb6 can induce an early defense reaction in tobacco. Thfb6 also enhanced the systemic resistance of tobacco against tobacco mosaic virus. The rate of lesion number reduction by treatment with Thfb6 could be up to 36.02%. Thfb6 increased the activity of tobacco defense-related enzymes, including phenylalanine ammonia-lyase (PAL), polyphenol oxidase, and peroxidase, which were all more than three times the control after 3–5 days post treatment of Thfb6. The transcription of resistance-related genes, including the PAL gene, non-expresser of pathogenesis-related gene1 (NPR1), and basic pathogenesis-related gene 1 (PR1-b), were upregulated after Thfb6 treatment. The relative expression levels of the PAL and NPR1 genes were highest on the third and fourth days after Thfb6 treatment, at 5.5 times and 8.3 times that of the control, respectively. The relative expression level of PR1 on the sixth day after Thfb6 treatment was 5.3 times that of the control. These results indicate that the improvement of defense-related enzyme activity and the induced expression of disease-resistance-related genes were the main mechanisms by which Thfb6 induced systemic resistance in tobacco.

Fusarium wilt diseases severely influence the growth and productivity of numerous crop plants. The consortium of antagonistic rhizospheric Bacillus strains and quercetin were evaluated imperatively as a possible remedy to effectively manage the Fusarium wilt disease of tomato plants. The selection of Bacillus strains was made based on in-vitro antagonistic bioassays against Fusarium oxysporum f.sp. lycoprsici (FOL). Whereas, quercetin was selected after screening a library of phytochemicals during in-silico molecular docking analysis using tomato LysM receptor Kinases “SILKY12” based on its dual role in symbiosis and plant defense responses. After the selection of test materials, pot trials were conducted where tomato plants were provided consortium of Bacillus strains as soil drenching and quercetin as a foliar spray in different concentrations. The combined application of consortium () and quercetin (1.0 mM) reduced the Fusarium wilt disease index up to 69% also resulting in increased plant growth attributes. Likewise, the imperative application of the Bacillus consortium and quercetin (1.0 mM) significantly increased total phenolic contents and activities of the enzymes of the phenylpropanoid pathway. Non-targeted metabolomics analysis was performed to investigate the perturbation in metabolites. FOL pathogen negatively affected a range of metabolites including carbohydrates, amino acids, phenylpropanoids, and organic acids. Thereinto, combined treatment of Bacillus consortium and quercetin (1.0 mM) ameliorated the production of different metabolites in tomato plants. These findings prove the imperative use of Bacillus consortium and quercetin as an effective and sustainable remedy to manage Fusarium wilt disease of tomato plants and to promote the growth of tomato plants under pathogen stress conditions.

Land use/land cover (LULC) changes have a substantial influence on ecosystem services. The objective of this study is to estimate LULC dynamics induced ecosystem service values (ESV) changes in Western Ethiopia. Data were acquired from Landsat images of the area for four periods (1990-2020), and 221 sample households. The areas of LULC classes and the improved ESV coefficients of Costanza et al (1997) were used estimate ESV changes in 1990-2020. Forest provides diverse provisions, regulatory, supportive and cultural services. Analysis of the Landsat images showed that forest, farmland, settlement, water body and bare-land were the major LULC classes in the study area. While forest ESV had accounted 46.1% (US$ 4.95 million) of the ESV of Wayu-Tuka district in 1990, farmland ESV constituted the largest share (63.3%, US$ 5.21 million) of the ESV of the area after 30 years (2020). The ESV of forest and bare-land showed decreasing trends in three decades (1990-2020) but the farmland service value revealed an increasing trend in the same periods. Forest ecosystem exhibited the largest service value loss (US$ 3.91 million) in 1990-2020; whereas, the service value gain of farmland was only US$ 2.2 million although farmland was responsible for the conversion of the largest area size (9,766.5 ha) from other land covers in 30 years. LULC change induced net ESV loss of the district in three decades (1990-2020) was 23.4% (US$ 2.51 million). Land conversion due to expansion of farmland (by 9,766.5 ha) and settlement (by 4,061.3 ha) was the main cause for the LULC dynamics and the significant ESV loss in 1990-2020. Thus, the government and local people should cooperate so as to curb the steady degradation of forest and its ecosystem services in Wayu-Tuka district, Western Ethiopia.

A switchable and tunable terahertz (THz) metamaterial based on photosensitive silicon and Vanadium dioxide (VO2) was proposed. By using finite-difference time-domain (FDTD) method, the transmission and reflective properties of the metamaterial were investigated theoretically. The results imply that, the metamaterial can realize a dual electromagnetically induced transparency (EIT) or two narrow-band absorption depending on the temperature of the VO2. Additionally, the magnitude of the EIT and two narrow-band absorption can be tuned by varying the conductivity of photosensitive silicon (PSi) via pumping light. Correspondingly, the slow light effect accompanying the EIT can also be adjusted.

The plant immunity system is more and more revisited and new elements and roles are attributed to participate in the response to biotic stress. New terminology is also applied trying to identify different players in the whole scenario of immunity: Phytocytokines are one of those elements that are gaining more attention due the characteristics of processing and perception, and showing they are part of a big family of compounds that can amplify the immune response. This review aims to highlight the last findings about the role of phytocytokines in the whole immune response on biotic stress, including basal and adaptive immunity, and to expose the complexity in their action in plant perception and signaling events.

This study presents the developments regarding the time-domain-induced polarisation method, as a supporting tool for resistivity soundings during investigations of coastal detrital aquifers that are salinised by marine intrusion. The interpretation of resistivity measurements in such aquifers, which have variable hydrochemistry and lithology, involves uncertainties owing to the presence of low-resistivity lithologies, such as clays. To reduce these uncertainties, the use of other geophysical parameters is necessary; hence, this study focuses on induced polarisation, since it can be measured simultaneously with resistivity. In detail, we propose the determination of induced polarisation using 1D techniques, while developing a different algorithm for processing the induced polarisation data. The aim is to extend the results of this phenomenon, using instead of chargeability, the concepts of polarisability and decay time, which are extracted from the decay curve, given that they represent more intrinsic properties of the various analysed subsurface media. We present results obtained by applying this methodology to a Quaternary aquifer of the Costa del Sol in the SE Iberian Peninsula (in the province of Almería) during two different campaigns, one before and one after winter (i.e., in October and February, respectively). The results reveal the position of the saline front during each campaign, while reflecting the seasonal movement of the marine intrusion.

This paper develops the study of the effect of powerful ultrasound on the laser breakdown of liquids and a comparative study of the possibilities of acoustic and optical diagnostics of breakdown. The method of laser-induced breakdown spectroscopy (LIBS) for elemental analysis of liquids, along with high efficiency, continues to be less sensitive compared to traditional chemical methods. The paper develops a method of using additional ultrasound irradiation of the laser breakdown area in order to increase the efficiency of LIBS. Using the developed technique, spectral lines of chemical elements such as potassium, manganese, sodium, calcium, etc. were obtained for the first time depending on the frequency and power of ultrasound. It is shown that a sharp increase in the intensity of spectral lines of elements in water during laser breakdown is observed in the field of high-power ultrasound. It indicates an increase in the sensitivity of the combined method of ultrasonic LIBS. Along with the optical spectrum, the spectral and energy characteristics of acoustic emission were studied. An automated complex for hydrophysical and spectral studies is described, which was tested in the Sea of Japan during the voyage No. 81 of the research vessel RV "Professor Gagarinsky" in August 2022.

We have developed an unsteady and non-linear wind synopsis simulator called RIAM-COMPACT (Research Institute for Applied Mechanics, Kyushu University, COMputational Prediction of Airflow over Complex Terrain) in order to simulate the airflow on a microscale, i.e., a few tens of km or less. In RIAM-COMPACT, the large-eddy simulation (LES) has been adopted for turbulence modeling. LES is a technique in which the structures of relatively large eddies are directly simulated and smaller eddies are modeled using a sub-grid scale model. In the present study, we have conducted the numerical wind diagnoses for Taikoyama Wind Farm nacelle separation accident in Japan. The simulation results suggest that all six wind turbines at the Taikoyama Wind Farm are subject to significant influence from separated flow (terrain-induced turbulence) which is generated due to the topographic irregularities in the vicinity of the wind turbines. A proposal has been also made on reconstruction of the wind farm.

Diabetes may cause an increase blood levels of cytokines inducing a rising of C reactive protein (PCR) and fibrinogen stimulating a subclinical inflammation which lead to adhesive molecules expression and to endothelial disfunction. A comprehensive panel of type 1 diabetes mellitus (T1DM) interleukins polymorphisms is not provided yet. As chronic periodontitis (CP) is considered the sixth complication of DM, a clarification is needed about the inflammatory role managed by single nucleotides polymorphisms (SNPs). The goal of this review is to focus on the significant diversity of SNPs in T1DM patients with and without CP. After a digital search on PubMed and Scopus with reference to the last 5 years, 21 items were enrolled. Several ILs were analyzed. T1DM still needs to be thoroughly explored regarding the ILs polymorphisms panel, however the last 5 years have led to the increased independence of this condition, causing autonomous inflammatory effects which requires further investigations. CP and T1DM association in children and adolescents represents a severe gap in literature that should be filled, the scarce presence of studies also about adults serves as a motivation for ulterior clinical researches

In January and February 2001, El Salvador was hit by two strong earthquakes that triggered thousands of landslides, causing 1,259 fatalities and extensive damage. The analysis of aerial and SPOT-4 satellite images taken a few days after the events allowed us to map 6,491 coesismic landslides, which occurred in 14 study areas extending for about 400 km2. Four different Multivariate Adaptive Regression Splines (MARS) models were produced by using different covariate sets and landslide inventories, the latter containing the slope failures triggered by an extreme rainfall event of November 2009 and those induced by the earthquakes of 2001. Moreover, two validation scenarios were employed, including the 25% and 95% of the mapped landslides, respectively. The results of our experiment revealed that: (i) MARS algorithm provides reliable predictions of coesismic landslides; (ii) models calibrated with rainfall-induced landslides predict with acceptable accuracy landslides caused by deep earthquakes and distributed over vast areas; (iii) the best accuracy is achieved by models trained with both preparatory and trigger variables; (iv) a small portion of the landslides produced by an earthquake can be used to calibrate MARS predictive models that help to identify slopes where yet unreported landslides may have occurred.

The NF-κB (nuclear factor K-light-chain-enhancer of activated B cells) transcription factor family is critical for modulating the immune proinflammatory response throughout the body. During the resting state, inactive NF-κB is sequestered by IκB in the cytoplasm. Proteasomal degradation of IκB activates NF-κB, mediating its translocation into the nucleus to act as a nuclear transcription factor in the upregulation of proinflammatory genes. Stimuli that initiate NF-κB activation are diverse, but are canonically attributed to proinflammatory cytokines and chemokines. Downstream effects of NF-κB are cell type specific and, in the majority of cases, result in activation of pro-inflammatory cascades. Acting as the primary immune responders of the central nervous system, microglia exhibit upregulation of NF-κB upon activation in response to pathological conditions. Under such circumstances, microglial crosstalk with other cell types in the central nervous system can induce cell death, further exacerbating the disease pathology. In this review, we will emphasize the role of NF-κB in triggering neuroinflammation mediated by microglia.

Inflammation is an underlying problem for many disease states and has been implicated in iron deficiency (ID). This study aimed to determine whether iron status is improved by epigallocate-chin-3-gallate (EGCG) through reducing inflammation. Thirty-two male Sprague-Dawley rats were randomly divided into four groups (n = 8 each): positive controls, negative controls, lipo-polysaccharide (LPS, 0.5 mg/kg body weight), and LPS + EGCG (LPS plus 600 mg EGCG/kg diet). Iron status, hepcidin, C - reactive protein (CRP), serum amyloid A (SAA), and interleukin-6 (IL-6) were measured. There were no differences in treatment groups compared with control in CRP, hepcidin, and liver iron concentrations. Serum iron concentrations were significantly lower in the LPS (p=0.02) and the LPS+EGCG (p=0.01) than in the positive control group. Compared to the positive control group, spleen iron concentrations were significantly lower in the negative con-trol (p<0.001) but not with both LPS groups. SAA concentrations were significantly lower in LPS + EGCG group compared to LPS alone group. IL-6 concentrations were significantly higher in LPS+EGCG (p= 0.004) than in any of the three groups. EGCG reduced SAA concentrations but did not affect hepcidin or improve serum iron concentration or other iron markers.

Periodontitis is a progressive and inflammatory oral disease and results in the damage of the supporting tissues of teeth. Peroxiredoxin6 (PRDX6) is an antioxidant enzyme and has been identified as a regulator in redox balance. This study aimed to investigate whether PRDX6 could protect human gingival fibroblasts (HGFs) from lipopolysaccharide (LPS) induced inflammation and its mechanisms. Here, both inflamed and non-inflamed human gingival tissues were collected to assess the expression of PRDX6 and NRF2 by Immunohistochemistry and Western blotting. Furthermore, HGFs were stimulated with LPS, MJ33 (PRDX6 phospholipase A2 inhibitor), or ML385 (NRF2 inhibitor). The expression levels of inflammatory cytokines were measured by RT-qPCR and ELISA, and reactive oxygen species (ROS) was detected using DCFH-DA. PRDX6 was downregulated in inflamed gingival tissues. In HGFs, LPS induced inflammatory cytokines and ROS was upregulated in PRDX6 knockdown cells. Furthermore, co-treatment with MJ33 alleviated LPS-induced inflammatory cytokines and ROS, while inhibiting NRF2 upregulated those in HGFs. Therefore, this study provided a new mechanistic insight that PRDX6, regulated by the NRF2 signaling, alleviates LPS- induced periodontitis in human gingival fibroblasts.

Severe COVID-19 disease is characterised by an exaggerated inflammatory response, called cytokine storm, accompanied by a condition of immune depression. Even sepsis is characterised by an exaggerated inflammatory response, called SIRS (Systemic Inflammatory Response Syndrome), accompanied by a condition of immune depression called CARS (compensatory anti-inflammatory response syndrome). Clinical studies reveal that most sepsis patients who did not die during the hyper inflammatory response (SIRS) subsequently succumbed to the condition of immune depression (CARS). Severe acute pancreatitis begins with local inflammation that induces systemic inflammatory response syndrome (SIRS), accompanied and followed by a compensatory anti-inflammatory response (CARS). In COVID-19 disease, the male response to SARS CoV-2 virus is typically characterised by a robust inflammatory response. Instead, a cell-mediated immune response is dominant in women. This means that the male sex tends to have a more robust hyper inflammatory response than the female one. Furthermore, in women the condition of immune depression is less represented, therefore they are more protected. Sepsis, severe acute pancreatitis and COVID-19 disease evolve between two fundamental aspects: hyper inflammation and immunodepression. The experience gained over years of studies of sepsis and severe acute pancreatitis suggests that therapies should be differentiated according to the evolutionary stage of the disease. The goal is to save the lives of most patients with COVID-19 disease. The identification of critical points, suitable for designing the windows of therapeutic opportunity, may allow the use of therapeutic interventions, in the COVID-19 disease, which are effective (there are no approved drugs yet), safe (without significant side effects), targeted (based on the evolutionary phase of the disease) personalized, (based on sex, co-morbidities, age, etc.) and timely (based on signs, symptoms, laboratory parameters and instrumental investigations).

Micronutrient homeostasis is a key factor in maintaining a healthy immune system. Zinc is an essential micronutrient that is involved in the regulation of the innate and adaptive immune responses. The main cause of zinc deficiency is malnutrition. Zinc deficiency leads to cell-mediated immune dysfunctions among other manifestations. Consequently, such dysfunctions lead to a worse outcome in the response towards bacterial infection and sepsis. For instance, zinc is an essential component of the pathogen-eliminating signal transduction pathways leading to neutrophil extracellular traps formation, as well as inducing cell-mediated immunity over humoral immunity by regulating specific factors or differentiation. Additionally, zinc deficiency plays a role in inflammation, mainly elevating inflammatory response as well as damage to host tissue. Zinc is involved in the modulation of the proinflammatory response by targeting Nuclear Factor Kappa B, a transcription factor that is the master regulator of proinflammatory responses. It is also involved in controlling oxidative stress and regulating inflammatory cytokines. Zinc plays an intricate function during an immune response and its homeostasis is critical for sustaining proper immune function. This review will summarize the latest findings concerning the role of this micronutrient during the course of infections and inflammatory response and how the immune system modulates zinc depending on different stimuli.

Drug-induced liver disease represents one of the main problems in the therapeutic field. As with most pathologies, also in this case various risk factors can be recognised, such as age, sex, but also the gut microbiota. Therefore all drugs on the market can, in fact, cause hepatotoxicity of varying degrees. Drugs used in the treatment of IBD can also cause these adverse effects and even lead to DILI. In this review, the various classes of drugs used in the treatment of IBD were taken into consideration and the various adverse effects on the liver were illustrated. In particular, a major role has emerged regarding hepatotoxicity of immunosuppressants. Biological drugs, however, seem to be responsible for these complications to a much lesser extent.

Within the spectra of lanthanide atoms quite often overlapping spectral lines (blends) are observed. On the example of complicated blend situations within Pr I and La I it is shown that in such cases a combination of optogalvanic and laser-induced fluorescence detection is necessary to find all transitions contributing to the observed spectral signature.

Peptidylarginine deiminases (PADs) have an important role in the pathogenesis of generating citrullinated proteins which is one type of protein posttranslation modifications (PTMs). Additionally, peptidylarginine deiminases 4 (PAD4) is a component of neutrophil extracellular traps (NET) that leads to autoimmune disease during NETosis. Our aim was to check the PAD4 enzyme expression at level of gene and protein expression in streptozotocin (STZ) induced diabetic rat pancreas and checking the link between PAD4 and inflammatory cytokines. Wistar rats were divided into two groups: control group and diabetic STZ group. STZ was administered by intraperitoneally (60 mg/kg/ body weight). Rats were caged for six weeks and then terminated. Pancreatic tissue was harvested for measurement of PAD4 protein expression, PAD4 mRNA, citrulli-nated histone-3 protein (CITH3), cytokines and Ca2+ content. All measurements in diabetic rats were significantly in-creased compared to non-diabetic rats (p

Tongue mobility is an obstructive sleep apnoea (OSA) marker and myofunctional therapy (MFT) target. For this reason, all patients with sleep-disordered breathing should require a combined functional assessment from an ear, nose, and throat (ENT) specialist and a phonoaudiologist to confirm or rule out the presence of tongue-tie. To our knowledge, this is the first case of a 13-year-old girl diagnosed with severe OSA and a significant decrease of 94% in her apnoea index (AI), requiring frenotomy with immediate postoperative change in the tongue position. A drug-induced sleep en-doscopy (DISE) was performed before and immediately post-frenotomy, and the anatomical changes provoked by this surgery during sleep were confirmed for the first time.

Induced pluripotent stem cells (iPSC) are derived from reprogrammed adult somatic cells. These adult cells are manipulated in vitro to express genes and factors essential for acquiring and maintaining embryonic stem cell (ESC) properties. This technology is widely applied in many fields, and there has been much attention to developing iPSC-based disease models to validate drug discovery platforms and study pathophysiological molecular processes underlying disease onset. Especially in neurological diseases, there is a great need for iPSC-based technological research, as these cells can be obtained from each patient and carry the individual’s bulk of genetic mutations and properties. Moreover, iPSC can differentiate into multiple cell types. These are essential characteristics since the study of neurological diseases is affected by limited access to injured sites, in vitro models composed of various cell types, the complexity of reproducing the brain’s anatomy, ethical issues, and the fact that post-mortem cell culture is challenging. Neurodegenerative diseases enormously impact global health due to their high incidence, symptoms severity, and usually lack of effective therapies. Recently, analyses using disease-specific iPSC-based models confirmed their efficacy for testing multiple drugs. This review summarizes the advances in iPSC technology used in disease modeling and drug testing with a primary focus on neurodegenerative diseases, including Parkinson’s and Alzheimer’s diseases.

Idiosyncratic drug induced liver injury (DILI) is an unpredictable reaction of exposed individual on a certain drug, and the drug-induced autoimmune hepatitis (DIAIH) presents a DILI phenotype that mimics idiopathic autoimmune hepatitis (AIH) when considering the clinical, biochemical, serological and histological parameters. We present a case of a 48-year-old male that was hospitalized due to severe hepatocellular liver injury two months after the self-treatment with the muscle-building dietary supplement based on arginine-alpha-ketoglutarate, L-citrulline, L tyrosine, creatine malate and beet extract. His immunology panel was positive with increased IgG levels, and the radiologic methods showed no signs of chronic liver disease. He underwent corticosteroid treatment with adequate response. After the therapy withdrawal, a clinical relapse occurred. Seven months after the initial presentation liver MR suggested the initial cirrhotic changes of the right liver lobe. Liver biopsy revealed abundant lymphoplasmacytic infiltrate with piecemeal necrosis and grade 2 fibrosis. He responded well on the corticosteroid treatment again, and was further treated with low dose prednisone without additional relapses. Several years later, further management confirmed presence of liver cirrhosis with no histological or biochemical signs of the disease activity. DIAIH is a DILI phenotype difficult to distinguish from idiopathic AIH despite a wide armamentarium of diagnostic methods. Regular patient monitoring and clinical open-mindedness with the adjustment of therapeutic approaches according to the disease course are more important than strict labelling of the disease.

Background: Pteropodine (PT) is a component of some plants with potentially useful pharmaco-logical activities for humans. This compound has biomedical properties related to the modulation of the immune system, nervous system, and inflammatory processes. This study addresses the an-ti-inflammatory and antioxidant capacity of pteropodin in a murine model of arthritis and induced edema of the mouse ear. Methods: To evaluate the anti-inflammatory activity, we used the reversed passive Arthus reaction (RPAR), which includes the rat paw edema test, the rat pleurisy test, and a mouse ear edema model. The antioxidant effect was evaluated by determining the myeloperoxidase enzyme activity. Results: PT showed an anti-inflammatory effect in the different specific and non-specific tests. We found a 52 to 74% of inhibitory effect of PT in the rat paw edema test, 52% of reduction of the pleural exudate volume, and low neutrophil count (28%), when compared to the control group. We also found a 81% of inflammatory inhibition of the ear edema, and a significant myeloperoxidase enzyme inhibition by the three doses of PT. Conclusions: PT exerted a potent an-ti-inflammatory effect in the acute inflammation model in rodents.

The soil-borne pathogens, particularly Fusarium oxysporum f. sp. niveum (FON) and southern root-knot nematode (RKN, Meloidogyne incognita) are the major threat to watermelon production in the south-eastern United States. The role of soil micronutrients on induced resistance (IR) to plant diseases is well-documented in soil-based mediums. However, soil-based mediums limit the determination of the role(s) of individual micronutrients in IR. In this manuscript, we utilized hydroponics to assess the effect of controlled application of micronutrient, including iron (Fe), manganese (Mn), and zinc (Zn) on the expression of some IR genes (PR1, PR5, and NPR1 from salicylic acid (SA) pathway, and VSP, PDF, and LOX genes from jasmonic acid (JA) pathway) in watermelon seedlings upon inoculation with either FON or RKN or both. Plants were treated with higher (3X) or lower (0.5X) concentrations of micronutrients in Steiner solution (X= standard dose of micronutrient) for 7 days in a hydroponics system under greenhouse conditions. A subset of micronutrient-treated plants was inoculated (on the 8th day of micronutrient application) with FON and RKN (single and mixed). The expression of the IR genes in treated and control samples were evaluated using qRT-PCR. Although, significant phenotypic differences were not observed with respect to the severity of wilt symptoms or RKN galling with any of the micro-nutrient treatments within the 30 day-experimental-period, differences in the induction of IR genes were observed. However, the level of gene expression varied with sampling period, type and concentration of micro-nutrients ap-plied, and pathogen-inoculation. In the absence of pathogens, no significant changes were observed in the expression level of IR genes on 7th day of micronutrient treatment. However, pathogen inoculation affected the expression levels of the IR genes at 3-day post-inoculation. In FON inoculated plants, PDF was upregulated in high Fe treatment, whereas in RKN inoculated plants, low Mn treatment resulted in up-regulation of VSP. In the case of mixed inoculation with FON and RKN, the plants with low Zn treatment resulted in the upregulation of PR1. These observations suggest that the type and concentration of micronutrients in watermelon may potentially induce systemic resistance against FON and RKN through SA and JA pathways.

MiRNAs are 20-22 nucleotide long single-stranded non-coding RNA sequences, which can regulate post transcriptional activity of mRNA by binding with it at 3’UTR region (untranslated region). Thus deregulation of miRNA expression is responsible for dysregulating mRNA function which contributes in developing various diseases as well as cancerous phenotypes. Alteration of single nucleotide in miRNA sequence is one of the reasons behind deregulation of miRNA expression. The most frequent carcinoma in current day is breast cancer which causes a high mortality among women around the world as well as India. Despite of the advancement of diagnostic tools, strategies and treatment, the cases of breast cancer is increasing every year. There are plenty of biomarkers like ER, PR, Her2, Ki-67, etc available which are frequently used in diagnosis and treatment of breast cancer. After the discovery of MiRNA in 1993 in Caenorhabiditis elegans, it is attracting all the limelight in diagnosis and treatment of different carcinomas as well as breast cancer. In this review we will discuss on involvement of different types of MiRNAs and miR SNPs in breast cancer occurrence and susceptibility in a detailed manner.

The color changes corresponding to chromophore structures in lignin caused by exposure of Eucalyptus（Eucalyptus grandis and E. urophylla）to heat were investigated. Eucalyptus wood samples were heated in saturated steam atmospheres for 10 h at 110℃, 130℃, and 150℃. The lignin was isolated before and after heat treatment. The physicochemical properties of the lignin and changes in chromophore structures during heat treatment was evaluated through wet chemical analysis, FTIR, UV-Vis, GPC, XPSand 13C-NMR. The color of the wood became darker and redder with the increase in pressure and temperature. Depolymerization and dehydration reactions occurred via demethoxylation with heat treatment in saturated steam at 110℃ or 130℃. Lignin condensed to form insoluble compounds after heat treatment in saturated steam at 150℃. G units increased and S units decreased through demethylation during heat treatment, as revealed by FTIR and 13C-NMR analysis.

In the present study, field observation wind data from the time of the wind turbine blade damage accident on Shiratakiyama Wind Farm were analyzed in detail. In parallel, high-resolution LES turbulence simulations were performed in order to examine the model’s ability to numerically reproduce terrain-induced turbulence. The comparison of the observed and simulated time series (1 second average values) from a 10 minute period from the time of the accident led to the conclusion that the settings of the horizontal grid resolution and time increment are important to numerically reproduce the terrain-induced turbulence that caused the wind turbine blade damage accident on Shiratakiyama Wind Farm. A spectral analysis of the same set of observed and simulated data revealed that the simulated data reproduced the energy cascade of the actual terrain-induced turbulence well.

At the Atsumi Wind Farm in Aichi Prefecture, Japan, damage to wind turbines occurred frequently due to terrain-induced turbulence. In the present study, numerical analyses of terrain-induced turbulence were conducted by reproducing the topography in the vicinity of the wind turbine sites in high resolution and using RIAM-COMPACT natural terrain version, which is based on large eddy simulation (LES). The results of the diagnoses indicated that, in the case of south-easterly wind, terrain-induced turbulence is generated at a small terrain feature located upstream of Wind Turbine (WT) #2, which serves as the origin of the turbulence. At the Atsumi Wind Farm, a combination of the series of wind diagnoses and on-site operation experience led to a decision to adopt an "automatic shutdown program" for WTs #1 and #2. Here, "automatic shutdown program" refers to the automatic suspension of wind turbine operation upon the wind speed and direction meeting the conditions associated with significant effects of terrain-induced turbulence at a wind turbine site. The adoption of the "automatic shutdown program" has successfully resulted in a large reduction in the number of occurrences of wind turbine damage, thus, creating major positive economic effects. 1) a reduction in the repair costs by 9.322 million yen per year per wind turbine, 2) an increase in the availability factor by 8.05%, and 3) an increase in the capacity factor by 1.7%.

We use earthquake ground motion modelling via Ground Motion Prediction Equations (GMPEs) and numerical simulation of seismic waves to consider the effects of site amplification and basin resonance in Jakarta, the capital city of Indonesia. While spectral accelerations at short periods are sensitive to near-surface conditions (i.e., Vs30), our results suggest that, for basins as deep as Jakarta’s, available GMPEs cannot be relied upon to accurately estimate the effect of basin depth on ground motions at long periods (>1 s). Amplitudes at such long periods are influenced by entrapment of seismic waves in the basin, resulting in longer duration of strong ground motion, and interference between incoming and reflected waves as well as focusing at basin edges may amplify seismic waves. In order to simulate such phenomena in detail, a basin model derived from a previous study is used as a computational domain for deterministic earthquake scenario modeling in a 2-dimensional cross-section. A M_w 9.0 megathrust, a M_w 6.5 crustal thrust and a M_w 7.0 instraslab earthquake are chosen as scenario events that pose credible threats to Jakarta, and the interactions with the basin of seismic waves generated by these events were simulated. The highest PGV amplifications are recorded at sites near the middle of the basin and near its southern edge, with maximum amplifications of PGV in the horizontal component of 200% for the crustal, 600% for the megathrust and 335% for the deep intraslab earthquake scenario, respectively. We find that the levels of ground motion response spectral acceleration fall below those of the 2012 Indonesian building Codes's design response spectrum for short periods (< 1 s), but closely approach or may even exceed these levels for longer periods.

A metastable β-Ti alloy, Ti–10V–3Fe–3Al (wt.%), was subjected to thermos-mechanical processing including the compression test at 725°C, which is below the β transus temperature (780°C), and at strain rate of 10-3s-1. The presence of phases was determined using transmission electron microscopy and X-ray diffraction. Although the dynamic recovery took place together with slip, both deformation-induced α˝ martensite and ω were detected as other operating mechanisms for the first time in metastable-β Ti alloys deformed in α+β region. The volume fraction of stress-induced α˝ was higher than that of the same alloy deformed at room temperature due to higher strain applied. Stress-induced twinning was not operational, which could be related to the priority of slip mechanism at high temperature resulted from thermally-assisted nucleation and lateral migration of kink-pairs.

The first detection of gypsum (CaSO4.2H2O) by the Mars Science Laboratory (MSL) rover Curiosity in the Gale Crater, Mars created a profound impact on planetary science and exploration. The unique capability of plasma spectroscopy involving in situ elemental analysis in extraterrestrial environments, suggesting the presence of water in the red planet based on phase characterization and providing a clue to Martian paleoclimate. The key to gypsum as an ideal paleoclimate proxy lies in its textural variants, and in this study terrestrial gypsum samples from varied locations and textural types have been analyzed by Laser Induced Breakdown Spectroscopy (LIBS) technique. Petrographic, sub-microscopic and powder X-ray diffraction characterizations confirm the presence of gypsum (hydrated calcium sulphate; CaSO4.2H2O), bassanite (semi-hydrated calcium sulphate; CaSO4.1/2H2O) and anhydrite (anhydrous calcium sulphate; CaSO4) along with accessory phases (quartz and jarosite). The principal component analysis of LIBS spectra from texturally varied gypsums can be differentiated from one another because of the chemical variability in their elemental concentrations. The concentration of gypsum is determined from the partial least-square regressions model. Rapid characterization of gypsum samples with LIBS is expected to work well in extraterrestrial environments.

The concept of vulnerable carotid plaques is pivotal in understanding the pathophysiology of is-chemic stroke secondary to large-artery atherosclerosis. At the macroscopic evaluation, vulnera-ble plaques are characterized by one or more of the following features: microcalcification, neo-vascularization, lipid-rich necrotic core (LRNC), intraplaque hemorrhage (IPH), thin fibrous caps, plaque surface ulceration, huge dimension determining stenosis, and plaque rupture. Recognizing these macroscopic characteristics is crucial to estimating the risk of cerebrovascular events, also in case of non-significant (less than 50%) stenosis. Inflammatory biomarkers, such as cytokines and adhesion molecules, lipid-related markers like oxidized low-density lipoprotein (LDL), and proteolytic enzymes capable of degrading extracellular matrix components are among the key molecules that will be scrutinized for their associative roles in plaque instability. Through their quantification and evaluation, these biomarkers reveal intricate molecular cross-talking govern-ing plaque inflammation, rupture potential, and thrombogenicity. Current evidence demonstrates that plaque vulnerability phenotypes are multiple and heterogeneous and are associated with as many highly complex molecular pathways that determine the activation of an immune-mediated cascade that culminates in thromboinflammation. This narrative review provides a comprehen-sive analysis of current knowledge on molecular biomarkers expressed by symptomatic carotid plaques. It explores the association of these biomarkers with the structural and compositional at-tributes that characterize vulnerable plaques

Background: The UK dairy sheep industry is relatively small but growing, particularly for cheese and yogurt products. Anecdotally, sheep milk (SM) is better tolerated by humans than cows’ milk and could have environmental as well as health benefits. All milk contains sub-micron particles called extracellular vesicles (EV) which are mainly derived from the mammary epithelium. Physiologically, milk derived EV are thought to aid development of infant immunity and the microbiome but may also have health benefits to adult humans. Methods: Using sequential ultracentrifugation vesicles of &lt;1µm (LEV) followed by &lt;200nm (sEV) were isolated from six individual sheep during mid lactation. RNA was extracted and microRNA analysed by RTqPCR for sequences previously identified in cows’ milk. Human THP-1 monocytes were differentiated into macrophages and incubated with SM-derived LEV and sEV in the presence of pro-inflammatory LPS to measure effects on secretion of the chemokine CCL-2 or in the presence of DMNQ and fluorescent dihydrorhodamine-1,2,3 to measure reactive oxygen species. Results: LEV induced an increase in ROS in both monocytes and macrophages, whilst sEV decreased DMNQ-mediated ROS in macrophages but not monocytes. Interestingly, the LEV did not induce CCL2 release, however they increased LPS-induced CCL2 secretion in monocytes but not macrophages. miR26a, miR92a, miR125b, miR155, miR223, were identified in both sEV and LEV by RT-qPCR and could be responsible for modulation of ROS and CCL2 expression. Conclusions: These findings suggest that sheep milk can influence human monocyte/macrophage responses and so is worthy of further investigation for its potential human and non-human animal health benefits.

Systemic inflammation plays a central role in many diseases and is, therefore, an important therapeutic target. In a scoping review, we assessed the evidence base for anti-inflammatory effects of pre-, pro- and synbiotics in children. Of 1254 clinical trials published in English in Ovid Medline and Cochrane Library PubMed from January 2003 through September 2022, 29 were included in the review. In 6 studies of healthy children (n=1552), one reported that fructo-oligosaccharides added to infant formula significantly reduced pro-inflammatory biomarkers and one study of a single strain probiotic reported both anti- and pro-inflammatory effects. No effects were seen in the remaining two single-strain and one multi-strain probiotic and one synbiotic study. In 23 studies of children with diseases (n=1550), prebiotics were tested in 3, single-strain in 16 and multi-strain probiotics in 6 and synbiotics in 2 studies. Significantly reduced inflammatory biomarkers were reported in 7/10 studies of atopic/allergic conditions, 3/5 studies of auto-immune diseases, 1/2 studies of preterm infants, 1 study of overweight/obesity, 2/2 studies of severe illness and 2/3 studies of other diseases. However, often only one or two of several biomarkers were improved, increased pro-inflammatory biomarkers occurred in 5 of these studies and a probiotic increased inflammatory biomarkers in a study of newborns with congenital heart disease. The evidence base for the effects of pre-, pro- and synbiotics on systemic inflammation in children is weak. Further research is needed to determine if anti-inflammatory effects depend on the specific pre-, pro- and synbiotic preparations, health status and biomarkers studied.

Doxorubicin (DOX) is an incessantly used chemotherapeutic drug that can cause detrimental dose-dependent effects such as cardiotoxicity and congestive heart failure. Hence, there is a need to discover innovative therapeutic approaches to counteract DOX-induced cardiotoxicity (DIC). MSC-Exos have shown to reduce apoptosis and cardiac fibrosis and promote cardiomyocyte proliferation in myocardial infracted mice. However, the effect of MSC-Exos on ameliorating DOX-induced pyroptosis has not been investigated. In this current study H9c2 were first exposed to DOX to stimulate pyroptosis, followed by subsequent treatment with MSC-Exos, with further analysis performed through immunocytochemistry, western blotting, and RT-PCR. Our data depicted that post-treatment with MSC-Exos significantly (p&lt;0.05) reduced the HMGB1/TLR4 axis, inflammasome formation (NLRP3), pyroptotic markers (caspase-1, IL-1β, and IL-18), and the pyroptotic executioner (GSDMD) in DOX-treated H9c2 cells. In conclusion, our data shows that MSC-Exos attenuates inflammation-induced pyroptosis in our in vitro DIC model. Our findings indicate that MSC-Exos may serve as a promising therapeutic intervention for mitigating DIC, as they maintain the therapeutic capabilities of MSCs while circumventing the drawbacks associated with traditional stem cell therapy.

Mangoes have a unique nutrient profile (carotenoids, polyphenols, sugars, vitamins) that we hypothesized would mitigate post-exercise inflammation. This study examined the effects of mango ingestion in moderating exercise-induced inflammation in a randomized crossover trial with 22 cyclists. In random order with trials separated by a 2-week washout period, the cyclists ingested 330 g/day mangoes with 0.5 liters water or 0.5 liters water alone for 2 weeks, followed by a 2.25-h cycling bout challenge. Blood and urine samples were collected pre- and post-2 weeks supplementation, with additional blood samples collected immediately post-exercise, and then 1.5-h, 3-h, and 24-h post-exercise. Urine samples were analyzed for targeted mango-related metabolites. The blood samples were analyzed for 67 oxylipins that are upstream regulators of inflammation and other physiological processes. After 2-weeks mango ingestion, three targeted urine mango-related phenolic metabolites were significantly elevated compared to water alone (interaction effects, p≤0.003). Significant post-exercise increases were measured for 49 oxylipins, but various subgroup analyses showed no differences in the pattern of change between trials (all interaction effects, p&gt;0.150). The 2.25-h cycling bouts induced significant inflammation but no countermeasure effect was found after 2-weeks mango ingestion despite the elevation of mango gut-derived phenolic metabolites.

Increased insulin levels may support the development of neural circuits involved in cognition, while chronic mild inflammation may also result in cognitive impairment. This study aimed to gain more insight into whether cognition is impacted already during adolescence in a genetic rat model for obesity and type 2 diabetes. Cognitive functioning throughout adolescence and early adulthood was investigated in Zucker Diabetic Fatty (ZDF), ZDF lean and healthy outbred Long Evans rats using operant touchscreens. Blood glucose, insulin and lipids were longitudinally analyzed. Histological analyses were performed in the liver, white adipose tissues and the prefrontal cortex. Adolescent ZDF obese rats outperformed lean rats on visual discrimination performance. During the longitudinal cognitive testing period, insulin levels sharply increased over weeks in ZDF obese rats and were significantly enhanced from 6 weeks of age onwards. Early signs of liver steatosis and enlarged adipocytes in white adipose tissue were observed in ZDF early adult obese rats. Histological analyses at early adulthood showed no group differences in the number of prefrontal cortex neurons and microglia, nor PSD95 and SIRT1 mRNA expression levels. Together, our data show that adolescent obese ZDF rats even display enhanced cognition despite their early diabetic profile.

Thimerosal (TmHg) has been used in thimerosal-containing vaccines (TCV) and various med-icines, although to our knowledge, there are no studies evaluating its effects on microglia. Microglia are a crucial glial component that have important functions in inflammatory diseases, particularly in the Central Nervous System (CNS). They are also considered a key player in neurotoxicity. Furthermore, microglia are responsible for the activation of immune responses and plays an essential role for the maintenance of brain homeostasis. Microglial response is important for the maintenance of CNS immune regulation. Moreover, microglia cells partici-pate in the removal of cellular debris and pathogens, playing an important role as neuroprotectants in several CNS diseases, including neurodegeneration. The objective of this study was to evaluate the effects of TmHg and its metabolite ethylmercury (EtHg) on microglial cells. Our novel findings demonstrated that microglia are more sensitive to TmHg than to EtHg with EC50 1.4 ± 0.4 μM and 2.3± 0.9 μM for 24h, respectively. The mercury compounds also induced the transcription of pro-inflammatory markers s such as IL-1β; iNOS, and to a lesser extent TNF-α expression. Likewise, the increase in Beclin-1 expression - a protein associated to autophagy - and the number of senescent cells indicate that microglia are activated by TmHg and EtHg. The effects of thimerosal may have different consequences depending on the health status and susceptibility of the populations.

Interleukin (IL)-23 is a central proinflammatory cytokine with a broad range of effects on immune responses. The pathological consequences of excessive IL-23 signaling have been linked to its ability to promote the production of inflammatory mediators such as IL-17, IL-22 by stimulating the differentiation and proliferation of T helper type 17 (Th17 cells). Emerging evidence suggests a potential pro-fibrotic role for IL-23 in the development of chronic inflammatory autoimmune diseases characterized by intense fibrosis. In this review, we summarized the biological features of IL-23 and gathered recent research on the role of IL-23 in fibrotic autoimmune conditions, which could provide a theoretical basis for clinical targeting and drug development.

Anastomotic leakage (AL) after the creation of a gastrointestinal (GI) anastomosis remains an important complication in GI surgery. From its introduction more than 60 years ago, Cyanoacrylate (CA) has gained popularity in colorectal surgery to provide “prophylaxis” against AL. However although in surgical practice it is increasingly used, evidences on humans are still lacking. The aim of this study is to evaluate in humans the safety of CA to seal colorectal anastomosis. All consecutive patients from Jannuary 2022 through December 2022 who underwent minimally invasive colorectal surgery were retrospectively analysed from a prospectively maintained database. Inclusion criteria were histological diagnosis of cancer, totally minimally invasive procedure and absence of intraoperative complications. 103 patients were included in the study, N-butyl cyanoacrylate with metacryloxisulfolane (Glubran 2 ®) was used to seal colorectal anastomosis, no adverse reactions to CA or postoperative complications related to inflammation and adhesions occurred, only one case of AL (0.9%) was recorded. We can consider this study an important proof of concept on safety of CA to seal colorectal anastomosis. It opens the possibility to start performing prospective and comparative studies in humans to evaluate effectiveness of CA in preventing colorectal AL.

Kidney disease is a significant health problem worldwide, affecting an estimated 10% of the global population. Kidney disease encompasses a diverse group of disorders that vary in their underlying pathophysiology, clinical presentation, and outcomes. These disorders include acute kidney injury (AKI), chronic kidney disease (CKD), glomerulonephritis, nephrotic syndrome, polycystic kidney disease, diabetic kidney disease, and many others. Despite their distinct etiologies, these disorders share a common feature of immune system dysregulation and metabolic disturbances. The immune system and metabolic pathways are intimately connected and interact to modulate the pathogenesis of kidney diseases. The dysregulation of immune responses in kidney diseases includes a complex interplay between various immune cell types, including resident and infiltrating immune cells, cytokines, chemokines, and complement factors. These immune factors can trigger and perpetuate kidney inflammation, causing renal tissue injury and progressive fibrosis. In addition, metabolic pathways play critical roles in the pathogenesis of kidney diseases, including glucose and lipid metabolism, oxidative stress, mitochondrial dysfunction, and altered nutrient sensing. Dysregulation of these metabolic pathways contributes to the progression of kidney disease by inducing renal tubular injury, apoptosis, and fibrosis. Recent studies have provided insights into the intricate interplay between immune and metabolic pathways in kidney diseases, revealing novel therapeutic targets for the prevention and treatment of kidney diseases. Potential therapeutic strategies include modulating immune responses through targeting key immune factors or inhibiting pro-inflammatory signaling pathways, improving mitochondrial function, and targeting nutrient-sensing pathways such as mTOR, AMPK, and SIRT1. This review highlights the importance of the interplay between immune and metabolic pathways in kidney diseases and the potential therapeutic implications of targeting these pathways.

The lethal combination involving TB and HIV, known as 'syndemic’ diseases synergistically act upon one another to magnify the disease burden. Individuals on ART are at risk of developing TB-associated immune reconstitution inflammatory syndrome (TB-IRIS). The underlying inflammatory complication includes the rapid restoration of immune responses following ART eventually leading to exaggerated inflammatory responses to MTB antigens. TB-IRIS continues to be a cause of morbidity and mortality among HIV/TB coinfected patients initiating ART, and although significant quantum of knowledge has been acquired on the pathogenesis of IRIS, the underlying pathomechanisms and identification of a sensitive and specific diagnostic markers still remain a grey area of investigation. Here, we reviewed the latest research developments in IRIS immunopathogenesis, and outlined the modalities to prevent and manage strategies for better clinical and diagnostic outcomes for IRIS.

Ranolazine (Rn) is a drug used to treat persistent chronic coronary ischemia. It has also been shown to have therapeutic benefits on the central nervous system and an anti-diabetic effect by lowering blood glucose levels and however, no effects of Rn on cellular sensitivity to insulin (Ins) have been demonstrated yet. The present study aimed to investigate the permissive effects of Rn on the actions of Ins in astrocytes in primary culture. Ins at 10-8 M, Rn (10-6 M) and Ins+Rn (10-8 M and 10−6 M respectively) were added to astrocytes during 24 h. In comparison to control cells, Rn and/or Ins caused modifications in cell viability and proliferation. p-AKT, p-ERK, p-eNOS, Mn-SOD, COX-2, and the anti-inflammatory protein COX-2 were all upregulated by ins. On the contrary, no significant changes were found in the protein expression of Cu/Zn-SOD, NF-κB and IκB. The presence of Rn produced an increase in p-ERK protein and a significant decrease in COX-2 protein expression. Furthermore, Rn significantly increased the effects of Ins on the expression of p-AKT, p-eNOS, p-ERK, Mn-SOD, and PPAR-γ. On the other hand, Rn+Ins produced a significant decrease in COX-2 expression. In conclusion, Rn facilitated the effects of insulin on the p-AKT, p-eNOS, p-ERK, Mn-SOD and PPAR-γ, signaling pathways, as well as on the anti-inflammatory and antioxidant effects of the hormone.

HIV-associated neurocognitive disorders (HAND) persist despite the advent of antiretroviral therapy (ART), suggesting underlying systemic and central nervous system (CNS) inflammatory mechanisms. The endogenous cannabinoid receptors 1 and 2 (CB1 and CB2) modulate inflammatory gene expression and play an important role in maintaining neuronal homeostasis. Cannabis use is disproportionately high among people with HIV (PWH) and may provide a neuroprotective effect for those on ART due to its anti-inflammatory properties. However, expression profiles of CB1 and CB2 in the brains of PWH on ART with HAND have not been reported. In this study, biochemical and immunohistochemical analyses were performed to determine CB1 and CB2 expression in brain specimens of HAND donors. Immunoblot revealed CB1 and CB2 were differentially expressed in frontal cortices from HAND brains compared to neurocognitively unimpaired (NUI) brains from PWH. CB1 expression levels negatively correlated with memory and information processing speed. CB1 was primarily localized to neuronal soma in HAND brains versus a more punctate distribution on neuronal processes of NUI brains. CB1 expression was increased in cells with glial morphology and showed increased colocalization with an astroglial marker. These results suggest that targeting the endocannabinoid system may be a potential therapeutic strategy for HAND.

Inflammation is considered an important target for stroke therapy because it induces secondary brain damage after the initial ischemic insult. Peripheral monocytes migrate to the brain parenchyma after a central insult. They then differentiate to macrophages in a positive feedback fashion contributing to damage instead of ischemic resolution and inflammation control. A cyclic diterpenoid, (1S,2E,4R,6R,7E,11E)-cembra-2,7,11-triene-4,6-diol (4R), decreases neurodegeneration after ischemia with central anti-inflammatory activity. This study aims to determine whether the central anti-inflammatory effect of 4R is effective against peripheral inflammation triggered by brain ischemia. To investigate the anti-inflammatory effect of 4R, we treated macrophages with lipopolysaccharide (LPS) as an inflammatory model, followed by treatment with 4R. Microarray transcriptome analysis of over 30,000 genes identified the differential expression of 393 genes. Genes related to inflammation, cell adhesion, and transcription were validated with qPCR, and reduced expression was determined. Quantification of NF-kB phosphorylation served as a marker for the modulation of inflammation through gene transcription. Our results show that 4R was associated with a reduction in NFKB1 and ITGB5 gene expression, increased phosphorylation of NF-kB, and a decrease in macrophage adhesion in a blood-brain barrier model. These results indicate that 4R can partially modulate the peripheral immune response, making 4R a potential drug against post-ischemic inflammation.

Toll-like receptor 5 ligand, flagellin, and Vascular Adhesion Protein-1 (VAP-1) are involved in non-alcoholic fatty liver disease (NAFLD). This study aimed to determine whether VAP-1 mediates flagellin-induced hepatic fat accumulation. The effects of flagellin on adipocyte VAP-1 expression were first studied in vitro. Then, flagellin (100 ng/mouse) or saline was intraperitoneally injected to C57BL/6J WT and C57BL/6-Aoc3^-/- (VAP-1 KO) mice on high-fat diet twice a week every two weeks for 10-weeks. After that, the effects on inflammation, insulin signaling, and metabolism were studied in liver and adipose tissues. Hepatic fat was quantified histologically and biochemically. Because flagellin challenge increased VAP-1 expression in human adipocytes, we used VAP-1 KO mice to determine whether VAP-1 regulates the inflammatory and metabolic effects of flagellin in vivo. In mice, VAP-1 mediated flagellin-induced inflammation, leukocyte infiltration and lipolysis in visceral adipose tissue. Consequently, increased release of glycerol led to hepatic steatosis in WT but not KO mice. Flagellin-induced hepatic fibrosis was not mediated by VAP-1. VAP-1 KO mice harbored more inflammation-related microbes than WT, while flagellin did not affect the gut microbiota. Our results suggest that by acting on visceral adipose tissue, flagellin increased leukocyte infiltration that induced lipolysis. Further, the released glycerol participated in hepatic fat accumulation. In conclusion, the results describe that gut microbial flagellin through VAP-1 induced hepatic steatosis.

Ulcerative colitis (UC) is a relatively frequent, chronic disease that impacts significantly the patient’s quality of life. Although many therapeutic options are available, additional approaches are needed because many patients either do not respond to current therapies or show significant side effects. Cardiotrophin-1 (CT-1) is a cytokine with potent cytoprotective, anti-inflammatory, and antiapoptotic properties. The purpose of this study was to assess if the administration of CT-1 could reduce colon damage in mice with experimental UC. UC was induced with 5% dextran sulfate sodium (DSS) in the drinking water. Some mice received i.v. dose of CT-1 (200 µg/kg) 2 hours before and 2 and 4 days after DSS administration. Animals were followed during 7 days after DSS. The severity of UC was measured by standard scores. Colon damage was assessed by histology and immunohistochemistry. Inflammatory mediators were measured by Western blot and PCR. CT-1 administration to DSS-treated mice ameliorated both the clinical course (disease activity index), histological damage, inflammation (colon expression of TNF-α, IL-17, IL-10, INF-γ, and iNOS), and apoptosis. Our results suggest that CT-1 administration before UC induction improves the clinical course, tissue damage and inflammation degree in DSS-induced UC in mice.

Atherosclerosis is a chronic inflammatory disease which results in thickening of the vessel wall and narrowing of the lumen. It is a leading cause of death worldwide. Preventive treatment is taken into prioritized consideration since currently no effective approaches to cure atherosclerosis are available. These treatments mainly focus on lowering blood cholesterol levels, especially LDL-C, by statins. Even so, lowering lipid levels is not sufficient to reduce the risk of cardiovascular events in all patients. Recently, atherosclerosis has increasingly been recognized as a chronic inflammatory disease involving the immune system, initiating new therapeutic approaches which could alleviate or prevent atherosclerosis by modulating inflammation. Mesenchymal stem cells (MSCs) have emerged as a promising option to relieve inflammation and balance immune responses in inflammatory diseases. Several studies including our group also reported that MSCs may be a new therapeutic option for atherosclerosis. This review summarizes the updated state of our knowledge in the administration of MSCs to alleviate atherosclerosis and discusses some of the key unresolved challenges that need to be solved in future studies.

While over half of all spinal cord injuries (SCIs) occur in the cervical region, the majority of preclinical studies have focused on models of thoracic injury. However, these two levels are anatomically distinct—with the cervical region possessing a greater vascular supply, grey-white matter ratio and sympathetic outflow relative to the thoracic region. As such, there exists a significant knowledge gap in the secondary pathology at these levels following SCI. In this study, we characterized the systemic plasma markers of inflammation over time (1, 3, 7, 14, 56 days post-SCI) after moderate-severe, clip-compression cervical and thoracic SCI in the rat. Using high-throughput ELISA panels, we observed a clear level-specific difference in plasma levels of VEGF, leptin, IP10, IL18, GCSF, and fractalkine. Overall, cervical SCI had reduced expressions of both pro- and anti-inflammatory proteins relative to thoracic SCI, likely due to sympathetic dysregulation associated with higher level SCIs. However, contrary to the literature, we did not observe level-dependent splenic atrophy with our incomplete SCI model. This is the first study to compare the systemic plasma-level changes following cervical and thoracic SCI using level-matched and time-matched controls. The results of this study provide the first evidence in support of level-targeted intervention and also challenge the phenomenon of high SCI-induced splenic atrophy in incomplete SCI models.

Inflammation is known to be risk factors for metabolic diseases. The purpose of this study was to develop a Food-based Index of Dietary Inflammatory Potential (FBDI) and conduct its validation assessment. This study analyzed raw data from Korean Genome and Epidemiology Study 2012–2014 data of 17,771 people. We carried out the correlation analysis between 51 food groups and hs-CRP. The FBDI was developed by multiple regression method with hs-CRP and selected 17 food group. For the validation of FBDI, 7795 people in the 6th Korea National Health and Nutrition Examination Survey (KNHAES) was used. Binary logistic regression analysis was used for risk analysis of metabolic syndrome and FBDI. The FBDI model included that 7 were composed of anti-inflammatory food groups and 3 of inflammatory food groups. The FBDI was calculated by multiplying the intake of food group by β coefficients. KNHAES were included in the validation of FBDI. The risk of metabolic syndrome was found to be 2.152 times higher in the group with the highest FBDI than in the group with the lowest one (95% Cl:1.458–3.178, p for trend = 0.000). This study developed FBDI reflecting food intake for Koreans, which showed a significant relationship with the risk of metabolic syndrome.

1) Background: Keloids occur after the failure during the wound-healing process, persist the inflammation and are refractory to various treatments. The pathogenesis of keloids is still unclear. We previously analyzed the gene expression profiles in keloid tissue using microarray and Northern blot analysis and found that HtrA1 was markedly upregulated in the keloid lesions. HtrA1 is a member of the HtrA family of serine protease, has been suggested to play a role in the pathogenesis of various diseases including age-related macular degeneration and osteoarthritis by modulating proteins in extracellular matrix or cell surface. We focused on HtrA1, analyzed the localization and the role in keloid pathogenesis. 2) Methods: Twenty seven keloid patients and seven unrelated patients were enrolled in this study. We performed in situ hybridization analysis, immunohistochemical analysis, western blot analysis and cell proliferation assay. 3) Results: First, the fibroblast-like cells expressed HtrA1 higher in the active keloid lesions than in the surrounding lesions in situ hybridization. Second, the proportion of HtrA1-positive cells in keloid was higher than that of in normal skin significantly in immunohistochemical analysis. Third, HtrA1 protein was up-regulated, relative to normal skin tissue samples in western blot analysis. Finally, silencing of HtrA1 gene expression suppressed the cell proliferation significantly. 4) Conclusion: HtrA1 was highly expressed in keloid tissues and the suppression of HtrA1 gene inhibited the proliferation of keloid-derived fibroblasts. HtrA1 may promote keloid development through accelerating cell proliferation and remodeling keloid-specific extracellular matrix or cell surface molecules. HtrA1 is suggested to have an important role in keloid pathogenesis.

Introduction the outbreak of the Israel-Gaza conflict, initiated by a major attack on the civilian population in Israel provided a tragic opportunity to study the community wide association between severe emotional stressors related to acts of war and the incidence and clinical characteristics of Takotsubo cardiomyopathy (TCM) in this scenario. Methods Eight consecutive cases of TCM diagnosed during the first 50 days of the Israel-Gaza conflict were retrospectively collected from two southern medical centers who provided care to most of the war victims throughout the period of monitoring. The medical records were thoroughly reviewed and analyzed. Results During the monitoring period, the incidence of TCM increased substantially compared to the control period. Eight patients were included in the analysis. All patients were female and 100% of patients presented within the first 3 weeks of conflict whereas after this initial phase, despite the continuing war, the incidence of TCM reverted to pre-conflict levels. Two patients (25%) were under 50 years of age. All patients had hazardous clinical characteristics including severe left ventricular (LV) dysfunction (≤35%) and prolonged QTc interval (>500 ms). Five patients (62.5%) experienced complications. Nevertheless, no in-hospital mortality was reported. Conclusions Repeated exposure to severe emotional stress, on both personal and national level, due to mass crisis such as war is associated with an increased incidence of TCM potentially with high-risk phenotype in comparison to TCM following other, less potent, psychological insults.

Familial Alzheimer’s disease (FAD) can be caused by mutations in PSEN1 that encodes presenilin-1, a component of the gamma-secretase complex that cleaves amyloid precursor protein. Alterations in calcium (Ca2+) homeostasis and glutamate signaling are implicated in the pathogenesis of FAD, however it has been difficult to assess in humans whether or not these phenotypes are the result of amyloid or tau pathology. This study aimed to assess early calcium and glutamate phenotypes of FAD by measuring the Ca2+ response of induced pluripotent stem cell (iPSC)-derived neurons bearing PSEN1 mutations to glutamate and the ionotropic glutamate receptor agonists NMDA, AMPA and kainate compared to isogenic control and healthy lines. The data shows that in early neurons, even in the absence of amyloid and tau phenotypes, FAD neurons exhibit increased Ca2+ responses to glutamate and AMPA, but not NMDA or kainate. Together this suggests that PSEN1 mutations alter Ca2+ and glutamate signaling as an early phenotype of FAD.

In contemporary construction, the prevalence of vibration serviceability issues in lightweight and slender structures has become increasingly common, owing to advancements in building materials and construction methods. While these structures often meet the criteria for ultimate limit states, they can still elicit complaints due to excessive vibrations induced by human activity. To address this challenge, the Integral Resonant Control (IRC) technique has emerged as a favored approach for actively damping vibrations in various systems. This study introduces a fresh perspective on implementing a multi-input multi-output (MIMO) IRC scheme for active vibration control (AVC) specifically tailored for pedestrian structures utilizing inertial mass actuators. Building upon a common framework and design methodology outlined in previous research, this work presents a novel application of MIMO IRC for AVC. The designed controller is rigorously tested and implemented on a laboratory floor structure to validate its efficacy.

Hiccups can significantly reduce the quality of life of patients and can occur as a drug side effect. Previous report using the Drug Adverse Event Database revealed sex-specific differences in the incidence of drug-induced hiccups. However, the pathogenesis of drug-induced hiccups remains unknown, and there is limited evidence on its treatment or prevention. This study examined molecular initiating events (MIEs), which are the starting point of adverse events, to investigate the drug-induced pathways of hiccups. We extracted drugs suspected to cause hiccups using FDA Adverse Event Reporting System, a large database on adverse drug reactions. Information on drugs suspected to be associated with hiccups were extracted from the overall population and sex-specific subgroups divided. In each data table, the predicted activity values of nuclear receptors (NRs) and stress response pathways (SPs) for each drug were calculated using the toxicity predictor, a machine-learning model. Univariate analysis extracted NRs and SPs associated with hiccups, and a multivariate analysis was performed to evaluate independent factors. Transforming growth factor-beta and antioxidant response element were considered an independent factor for hiccups in the male and female subgroups, respectively. This report first examined one of the mechanisms of drug-induced hiccups and identified MIEs associated with drug-induced hiccups.

Contrast-Induced Acute Kidney Injury (CI-AKI) remains a frequent iatrogenic condition since radiological procedures using intra-vascular iodinated contrast media (CM) are being widely administered for diagnostic and therapeutic purposes. Despite the improvement of the medical healthcare system worldwide, CI-AKI is still associated with direct short-term and indirect long-term outcomes including increased morbidity and mortality, specially, in patients under-lying pre-existing renal function impairment, cardiovascular disease or diabetes that could rap-idly progress into Chronic Kidney Disease. Although the RIFLE (Risk, Injury, Failure, Loss, End-Stage Kidney Disease), AKIN (Acute Kidney Injury Network) and KDIGO (Kidney Disease Improving Global Outcomes) clinical criteria and recommendation guidelines are based on tra-ditional “gold standard” biomarkers known as serum creatinine, glomerular filtration rate and urinary output, new reliable serum and urinary biomarkers are still needed for an effective uni-fied diagnostic strategy for AKI. Starting from previous and recent publications on the benefits and limitations of validated biomarkers responding to kidney injury, glomerular filtration and inflammation among others, this review unravels the role of new emerging biomarkers used alone or in combination, as reliable tools for early diagnosis and prognosis of CI-AKI, taking into account patients and procedures-risk factors towards a new clinical perspective.

Lichens are unique extremophilic organisms due to their phenomenal resistance to adverse environmental factors, including ultraviolet (UV) irradiation. Melanization plays a special role in the protection of lichens from UV-B stress. In present study, we analyzed the binding of melanins with the components of cell walls of mycobiont of upper cortex in the melanized lichen thalli Lobaria pulmonaria. Using scanning electron and atomic force microscopy, the morphological and nanomechanical characteristics of melanized layer of mycobiont cells were visualized. Melanization of lichen thalli led to the smoothing the surface relief and thickening mycobiont cell walls and resulted in the increase of deformation values and reduction of adhesion properties of lichen thallus. Treatment of thalli with hydrolytic enzymes, especially chitinase and lichenase, enhanced the yield of melanin from melanized thalli and release of carbohydrates, while treatment with pectinase increased the release of carbohydrates and phenols. Our results suggest that melanin by firmly binding with hyphal cell wall carbohydrates, particularly chitin and 1,4-β-glucans, can form associations, strengthen the melanized upper cortex of lichen thalli, and thereby can contribute to lichen survival under UV stress.

Controlled deposition of CoCrFeNiMo0.2 high entropy alloy (HEA) micro-particles was achieved using laser induced forward transfer (LIFT). Ultra-short laser pulses, 230 fs of 515 nm wavelength, were tightly focused into ∼ 2.4 μm focal spots on the ∼50 nm thick plasma-sputtered films of CoCrFeNiMo0.2. The HTA films were transferred onto glass substrates by magnetron sputtering in vacuum (10−8 atm) from the thermal spray coated substrates. The absorption coefficient of CoCrFeNiMo0.2 α ≈ 6 × 105 cm−1 was determined at 600 nm wavelength. The real and imaginary parts of refractive index (n + iκ) of HEA were determined from reflectance and transmittance using nano-films.

Granular superconductivity at high temperatures in graphite can emerge at certain two-dimensional (2D) stacking faults (SFs) between regions with twisted (around the c-axis) or untwisted crystalline regions with Bernal (ABA...) and/or rhombohedral (ABCABCA...) stacking order. One way to observe experimentally such 2D superconductivity is to measure the frozen magnetic flux produced by a permanent current loop that remains after removing an external magnetic field applied normal to the SFs. Magnetic force microscopy was used to localize and characterize such a permanent current path found in one natural graphite sample out of ∼50 measured graphite samples of different origins. The position of the current path drifts with time and roughly follows a logarithmic time dependence similar to the one for flux creep in type II superconductors. We demonstrate that a ≃10nm deep scratch on the sample surface at the position of the current path causes a change in its location. A further scratch was enough to irreversibly destroy the remanent state of the sample at room temperature. Our studies clarify some of the reasons for the difficulties of finding a trapped flux in remanent state at room temperature in graphite samples with SFs.

Since the discovery of the aggregation-induced emission effect in 2001, diaminodicyanoquinone derivatives (DADQs) have presented interesting fluorescence properties, allowing them to be considered fluorescent dyes capable of showing quantum yields above 90%. Besides, the diaminodiacyanoquinone core represents a versatile building block propense either to modification or integration into different systems to obtain and provide them unique photophysical features. Herein, we carried out a theoretical study on the fluorescence properties of three different diaminodicyanoquinodimethane systems. Therefore, time-dependent density functional theory (TD-DFT) was used to obtain the values associated with the dipole moments, oscillator strengths, and the conformational energies between the ground and the first excited states of each molecule. The results suggest that only two of the three studied systems possess significant luminescent properties. In a further stage, the theoretical insights were confirmed by means of experimental measurements, which not only retrieved the luminescence of the DADQs, but also suggest a preliminary and promising antibacterial activity of these systems.

China historically exhibits spatial differentiation from population distribution to ecological or economic development, and the forest pest control work is an epitome of this tendency. In recent times, global warming, man-made monoculture tree plantations, increasing human population density and intensified international trade aggravate forest pest outbreaks. Although Chinese government has complied with the internationally recommended practices, few stones remain unturned due to existing differential regional imbalance of forest pest distribution and control abilities. Evidence shows that the high-income provinces in the south have taken advantage of economic and technological superiority, resulting in the adoption of more efficient pest-control measures. To the contrary, in economically underdeveloped provinces of the northwest, a paucity of financial support has led to serious threats of pest damage that almost mirrored the demarcations of the Hu Huanyong Line. In this paper, we propose introducing public-private partnership (PPP) model into forest pest control and combining the national strategies to enact regional prevention measures in order to break the current spatially differentiated trends in China.

To gain insight into riser motions and associated fatigue damage due to vortex-induced vibration (VIV), data loggers such as strain sensors and/or accelerometers are sometimes deployed on risers to monitor their motion in different current velocity conditions. Accurate reconstruction of the riser response and empirical estimation of fatigue damage rates over the entire riser length using measurements from a limited number of sensors can help in efficient utilization of the costly measurements recorded. Several different empirical procedures are described here for analysis of the VIV response of a long flexible cylinder subjected to uniform and sheared current profiles. The methods include weighted waveform analysis (WWA), proper orthogonal decomposition (POD), modal phase reconstruction (MPR), a modified WWA procedure, and a hybrid method which combines MPR and the modified WWA method. Fatigue damage rates estimated using these different empirical methods are compared and cross-validated against measurements. Detailed formulations for each method are presented and discussed with examples. Results suggest that all the empirical methods, despite different underlying assumptions in each of them, can be employed to estimate fatigue damage rates quite well from limited strain measurements.

Ionizing radiation-induced bystander effects (RIBE) encompass a number of effects with potential for a plethora of damages in adjacent non-irradiated tissue. The cascade of molecular events is initiated in response to the exposure to ionizing radiation (IR), something that may occur during diagnostic or therapeutic medical applications. In order to better investigate these complex response mechanisms, we employed a unified framework integrating statistical microarray analysis, signal normalization and translational bioinformatics functional analysis techniques. This approach was applied to several microarray datasets from Gene Expression Omnibus (GEO) related to RIBE. The analysis produced lists of differentially expressed genes, contrasting bystander and irradiated samples versus sham-irradiated controls. Furthermore, comparative molecular analysis through BioInfoMiner, which integrates advanced statistical enrichment and prioritization methodologies, revealed discrete biological processes, at the cellular level. For example, negative regulation of growth, cellular response to Zn2+- Cd2+, Wnt and NIK/NF-kappaB signalling, which refine the description of the phenotypic landscape of RIBE. Our results provide a more solid understanding of RIBE cell-specific response patterns, especially in the case of high-LET radiations like α-particles and carbon-ions.

This study aimed to evaluate a cantilever beam-type piezoelectric energy harvester operating on train-induced vibrations for powering Wireless Sensor Networks (WSNs) used in railway track monitoring systems. The harvester's behaviors under different conditions are simulated in MATLAB using the analytical model. Natural frequency, maximum deflection, and stress were calculated with greater precision using eigenfrequency and stationary analysis using COMSOL Multiphysics. At a base excitation of 2 g and a resonant frequency of 4.38 Hz, the simulated results showed that the developed energy harvester prototype could generate up to 14 V of AC output voltage and 550 mW of output power. These findings highlight the promising potential of the proposed energy harvester for transforming train mechanical energy into electrical power. This energy harvester's viability and dependability for real-world applications in monitoring railway tracks are supported by developed analytical and simulation models.

Drugs are known to cause substantial liver injury, with hepatotoxicity ranging from asymptomatic increase of liver enzymes to hepatic failure. HIV/AIDS patients, with compromised immune systems, are especially vulnerable to opportunistic infections such as tuberculosis (TB). Patients with co-infection frequently get combined antiretroviral (ART) and antitubercular (ATD) regimens, which can cause hepatotoxicity. Hepatotoxicity has been linked to commonly administered antiretroviral drug regimens as well as first-line antitubercular agents such isoniazid, rifampin, and pyrazinamide, which are required for the treatment of both drug-sensitive and drug-resistant tuberculosis. As a result, there is an urgent need to investigate treatments based from traditional herbs known for their hepatoprotective abilities against ART and ATD-induced liver injury. Many researchers have investigated the effectiveness of medicinal plants in treating chemically caused hepatotoxicity. Medicinal plants are high in phytochemicals and secondary metabolites, both of which have a variety of medicinal benefits. Currently, there is a lack of specific therapeutic regimens to address this adverse effect, and management often relies on symptomatic treatment or therapy withdrawal. Traditional medicinal plants may have the potential to restore normal liver function, enzyme activity, and cellular structure in response to ART and ATD-induced hepatotoxicity. This review aims to examine the scientific evidence supporting the use of medicinal plants as hepatoprotective agents against liver damage induced by ART and ATDs.

Inflammation is a cause of number of disorders. Many anti-inflammatory drugs are available to cure and prevent inflammation and its related disorders. Some of the drugs are from plant and animal origin. Among animals snake venom is also utilized as treatment option of certain disorders. In the current study the venom of N. oxiana from Northern areas of Pakistan is assayed to determine its anti-inflammatory activity. The Naja oxiana is also called central Asian cobra is endemic to Central Asia. Naja oxiana belong to family Elapidae and it is highly venomous snake. The venom has many enzymatic proteins as well as nonenzymatic proteins that is neurotoxins. The venom is lethal having very high mortality rate and the death may occur due to respiratory failure in 45 minutes to 24 hrs depending upon the nature and amount of venom. As the venom is highly toxic so initially after venom milking its protein estimation was done and toxicity profile and LD50 was determined to find out its therapeutic dose at which anti-inflammatory activity was observed. The toxicity and anti-inflammatory activity was determined on mice model. Inflammation was induced by carrageenan induced peritonitis method. The inflammatory markers ROS, TNF-α and IL-β were determined by ELIZA in peritoneal fluid. The LD50 of crude venom, fraction 1 and fraction 2 was found as 34 µg/kg, 7.4 µg/kg and 416 µg/kg respectively. Anti-inflammatory activity crude venom, fraction 1 and fraction 2 was found at dose 19 µg/kg, 1.8 µg/kg and 267 µg/kg respectively. The levels of inflammatory markers reduced after therapeutic dose administration of venom and its fractions that indicates that it can be utilized as anti-inflammatory agent and so can be effective in various disorders.

This paper presents a comprehensive analysis of the SEIRS COVID-19 pandemic model with saturated incidence rate. By modifying the existing model and proposing a new simplified version, we investigate the dynamics of disease transmission, including the impact of saturation terms on disease spread. Through stability analysis at disease-free and endemic equilibria, we aim to enhance understanding of the spread of COVID-19 and inform effective control strategies. Drawing on mathematical models and epidemiological insights, this study contributes to the ongoing efforts to combat the global pandemic.

To investigate the associated mechanisms concerning collagen and the expression of apoptosis-related proteins in porcine skin injuries induced by laser exposure, pig skin was treated with a 1064 nm laser. The healing process of the laser-treated areas, alterations in collagen structure, and changes in apoptosis were continuously observed and analyzed from 6 hours to 28 days post-irradiation. On the 28th day following exposure, wound contraction and recovery were notably sluggish in the medium-high dose groups, displaying more premature and delicate type III collagen within the newly regenerated tissues. The collagen density in these groups was roughly 37-58% of that in the normal group. Between days 14 and 28 after irradiation, there was a substantial rise in apoptotic cell count in the forming epidermis and granulation tissue of the medium-high dose group, in contrast to the normal group. Notably, the expression of proapoptotic proteins bax, caspase-3, and caspase-9 surged significantly 14 days after irradiation in the medium-high dose groups and persisted at elevated levels on the 28th day. During the later stage of wound healing, the augmented apoptotic cell population and insufficient collagen generation in the newborn skin tissue of the medium-high dose groups were closely associated with delayed wound recovery.

Circadian rhythm disruption is increasingly considered an environmental risk factor for the development and exacerbation of inflammatory bowel disease. We have reported in a previous study that nychthemeral dysregulation is associated with an increase in intestinal barrier permeability and inflammation in mice with dextran sulfate sodium (DSS)-induced colitis. To investigate the effect of circadian rhythm disruption on the composition and diversity of the gut microbiota (GM). Sixty male C57BL/6J mice were divided initially to two groups, the shifted group (n=30) exposed to circadian shifts for three months and the non-shifted group (n=30) under a normal light-dark cycle. The mice of the shifted group were cyclically housed for five days under the normal 12:12 hour light-dark cycle followed by another five days under reversed light-dark cycle. At the end of the three months a colitis was induced by 2 % DSS given in the drinking water of 30 mice. Animals were then divided into four groups (n=15 per group), sham group non-shifted (Sham-NS), sham group shifted (Sham-S) and DSS non-shifted (DSS-NS) and DSS shifted (DSS-S). Fecal samples were collected from rectal content to investigate changes in GM composition by DNA extraction followed by high-throughput sequencing of the bacterial 16S rRNA gene. The mouse GM was dominated by three phyla: Firmicutes, Bacteroidetes and Actinobacteria. The Firmicutes/Bacteroidetes ratio decreased in mice with induced colitis. The richness and diversity of the GM were reduced in the colitis group, especially in the group with inverted circadian rhythm. Moreover, GM composition was also modified in the inverted circadian rhythm group, with an increase in Alloprevotella, Turicibacter, Bacteroides and Streptococcus genera. Circadian rhythm inversion exacerbates GM dysbiosis to a less rich and diversified extent in a DSS-induced colitis model. These findings shows a possible interplay between circadian rhythm disruption, GM dynamics, and colitis pathogenesis.

Silkworm ovary-derived BmN4 cells rely on chromatin-induced spindle assembly to form microtubule-based square mitotic spindles that ensure accurate segregation of holocentric chromosomes during cell division. The chromosome passenger protein Aurora B regulates chromosomal condensation and segregation, spindle assembly checkpoint, and cytokinesis; however, its role in holocentric organisms needs further clarification. This study examined the architecture and dynamics of spindle microtubules during prophase and metaphase in BmN4 cells and those with siRNA-mediated BmAurora B knockdown using immunofluorescence labelling. Anti-α-tubulin and anti-γ-tubulin antibodies revealed faint γ-tubulin signals co-localized with α-tubulin in early prophase during nuclear membrane rupture, which intensified as prophase progressed. At this stage, bright regions of α-tubulin around and on the nuclear membrane surrounding the chromatin suggested the start of microtubule assembling in the microtubule organizing centers (MTOCs). In metaphase, the number and size of γ-tubulin foci increased and were detected on both sides of the chromosomes. This resulted in a distinctive multipolar square spindle with holocentric chromosomes aligned at the metaphase plate. siRNA-mediated BmAurora B knockdown significantly reduced the γ-tubulin foci during prophase, impacting microtubule nucleation and spindle structure in metaphase. Spatiotemporal BmAurora B expression analysis provided new insights into the regulation of this mitotic kinase in silkworm larval gonads during gametogenesis. Our results suggest that BmAurora B is crucial for the formation of multipolar square spindles in holocentric insects, possibly through the activation of γ-tubulin ring complexes in multiple centrosome-like MTOCs.

(1) Background: National health system databases represent one of the most obvious sources of information about epidemiology of adverse drug reactions including drug-induced allergy and anaphylaxis. (2) Methods: Retrospective analysis of data from national database of pharmacovigilance in the Russian Federation (analyzed period 02.04.2019 - 21.06.2023) was performed. The prevalence of anaphylactic reactions (ARs) was determined, the structure of drugs involved was estimated together with patients’ characteristics. (3) Results: ARs were reported in 8.3% of drug-induced allergic reactions (2304/27,727), mean age of patients was 48.2 ± 15.8 years, 53.2% were females. Main causative groups of drugs were antibiotics, ABs (44.62%), local anesthetics, (19.97%), and cyclooxygenase (COX)-inhibitors (10.07%). Fatal ARs was reported in 9.5% (218/2304), mean age 48.0 ± 16.7 years, 56.2% females. Pediatric population accounted for 5.8% (133/2304), mean age 11.8± 4.5 years, 51.9% females. Elderly population accounted for 2.8% (65/2304), mean age 73.0±5.3 years, 43.5% (27/65) females. ABs were the leading causative groups of ARs in the elderly (40%), children (42.86%), and among fatal cases (50%). (4) Conclusions: ARs accounted for 8.3% of all drug-induced allergic reactions, and ABs were the most common causative agents. Females predominated in all groups except elderly patients.

The oscillation of an elastically mounted rigid cylinder excited by steady fluid flow is investigated. Regarding the nonlinearity of real practical structures like marine risers and the stay cable of a long-span bridge, the dynamic behavior of the circular cylinder is described by double Duffing equations and the aerodynamic force performance of the wake flow is expressed by wake oscillator equation. Unlike previous studies, in the present investigation, attention is focused on coupling the wake oscillator equations, taking into account quadratic terms. Following this approach, the cylinder's combined cross-flow and in-line Vortex-Induced Vibrations (VIV) are modeled more accurately. Empirical coefficients are adjusted through comparison with previous credible experimental studies and the effects of changing coefficients of the quadratic terms on major VIV parameters are investigated. The oscillating amplitude calculated by the present model is close to that of the experiment. The relative error of results obtained by the present coupled model is lower than the previous model. Moreover, the present model successfully predicts the moving trajectories of a circular cylinder under VIV in a figure-of-eight shape.

Legumes play a significant role in the alleviation of food insecurity, maintaining soil fertility and achieving sustainable crop production under adverse environmental conditions. The increased demand in legume production contemplates that attention on the genetic improvement of these crops through various means such as genetic engineering and mutation breeding should take a centre stage in global agriculture. Therefore, this paper provides succinct analysis of currently available literature on morphological and physiological traits in polyploidised leguminous plants to counter the adverse effects of drought stress. The effects of colchicine on various morphological and physiological traits of polyploidised legumes compared to their diploid counterparts were examined. Numerous reports revealed variations in these traits such as improved root and shoot growth, plant biomass, chloroplastidic content, protein, RNA and DNA. The differences observed were also associated with the strong relationship between plant ploidy-induction and colchicine application. Furthermore, the analysis indicated that polyploidisation remains dose-dependent, and may be achievable at a shorter space of time as this antimitotic chemical interferes with chromosome separations in somatic plant cells. The efficiency of this process also depends on the advancement of treatment conditions (in vitro, in vivo or ex vitro) and successful regeneration of polyploidised plants for adaptation under drought stress conditions. As such, the improvement in metabolite profile and other essential growth characteristics serves as a clear indication that induced polyploidy needs to be further explored to confer resilience to environmental stress, and improve crop yield under drought stress conditions in leguminous plants.

Background: Muscle wasting is a common phenomenon in oncology and appears to be alleviated by exercise training. This study aims to determine the degree of aggressiveness of cancer-induced muscle wasting in two different phenotypic muscles, and whether exercise training can attenuate this muscle dysfunction. Methods: Fifty Sprague-Dawley rats were randomly assigned to four experimental groups, two control groups (sedentary and exercised) and two breast cancer model groups (sedentary and exercised) induced by 1-methyl-1-nitrosoureia (MNU). After 35 weeks of endurance training the animals were sacrificed and the gastrocnemius and soleus muscles were harvested for morphometric analysis. Results: A significant reduction in cross-sectional area (P < 0.05) was found in both muscles of sedentary tumor-bearing animals. Interstitial fibrosis was significantly higher in the gastrocnemius of sedentary tumor-bearing animals (P < 0.05), but not in the soleus. A shift from large to small fibers was observed in the gastrocnemius of sedentary tumor-bearing animals. Long-term exercise training was able to prevent this cancer-related mus-cle dysfunction. Conclusions: The Gastrocnemius muscle showed a very pronounced reduction in cross-sectional area and marked interstitial fibrosis in sedentary animals with tumors. The soleus muscle showed a less pronounced but significant reduction in cross-sectional area, and collagen deposition did not differ between tumor groups. These contrasting results confirm that can-cer-induced muscle wasting can affect specific fiber types, and specific muscles, namely fast glycolytic muscles, and that exercise training can act to improve it.

Epithelial cells can undergo apoptosis by manipulating the balance between pro-survival and apoptotic signals. In this work, we show that TRAIL-induced apoptosis can be differentially regulated by the expression of α(1,6)fucosyltransferase (FucT-8), the only enzyme in mammals that transfers the (1,6)fucose residue to the pentasaccharide core of complex N-glycans. Specifically, in the cellular model of colorectal cancer (CRC) progression formed using the human syngeneic lines SW480 and SW620, knockdown of the FucT-8-encoding FUT8 gene significantly enhanced TRAIL-induced apoptosis in SW480 cells. However, FUT8 repression did not affect SW620 cells, which suggests that core fucosylation differentiates TRAIL-sensitive premetastatic SW480 cells from TRAIL-resistant metastatic SW620 cells. In this regard, we provide evidence that phosphorylation of ERK1/2 kinases can dynamically regulate TRAIL-dependent apoptosis and that core fucosylation can control the ERK/MAPK pro-survival pathway in which SW480 and SW620 cells participate. Moreover, the depletion of core fucosylation sensitises primary tumour SW480 cells to the combination of TRAIL and low doses of 5-FU, oxaliplatin, irinotecan or mitomycin C. In contrast, combination of TRAIL and oxaliplatin, irinotecan or bevacizumab reinforces resistance of FUT8-knockdown metastatic SW620 cells to apoptosis. Consequently, FucT-8 could be a plausible target for increasing apoptosis and drug response in early CRC.

When there are multiple key strata in the overburden of deep coal seam and the surface subsid-ence coefficient after mining is small, it indicates that the overlying key strata fail to break com-pletely after mining. On this occasion, the stress concentration on the working face occurs easily, which in turn leads to the occurrence of dynamic disasters such as rock burst. This study adopted a comprehensive analysis method of field monitoring and numerical simulation to explore the in-fluence of key stratum on the evolution law of mining-induced stress in the working face. Dis-tributed optical fiber sensor (DOFS) and surface subsidence GNSS monitoring system were re-spectively arranged inside and at the mouth of the ground observation borehole. According to the monitoring results of strain obtained from DOFS, the height of broken stratum inside the overlying strata was obtained; according to the monitoring results of surface subsidence, the sur-face subsidence coefficient was proved to be less than 0.1, indicating that the high key stratum does not break completely, but enters a state of bending subsidence instead. In order to reveal the influence of key stratum on the mining-induced stress of working face, two 3DEC numerical models with and without key stratum were established for comparative analysis. As the numeri-cal simulation results show, when there are multiple key strata in the overburden, the stress in-fluence range and stress concentration coefficient of coal seam after mining are relatively large. The study revealed the working mechanism of rock burst accidents after large-scale mining and predicted the potential area of rock burst risk after the mining of the working face, which has been verified by field investigation. The research results are of great guiding significance for the revelation of the working mechanism of rock burst in deep mining condition and its prevention and control.

Potato tubers are susceptible to wounding during post-harvest processes, leading to quality decline, perishability and large economic losses. In this study, the potato cultivar, ‘Longshu No.7’, was foliar-sprayed with 3% chitosan (w/v) three times during the pre-harvest period after flowering to evaluate the effect of foliar spraying with chitosan on suberization processing at wounds of harvested potato tubers. Our results demonstrate that foliar-sprayed with chitosan significantly reduced wound-induced fresh weight loss and dry rot disease index by 37.34% and 41.60% on the 28 day after wounding, respectively. Foliar-sprayed with chitosan accelerated the deposition of suberin polyphenolics and lignin at the wound sites of potato tubers with the formation of thicker cell layers. This occurred with increased localized activities of key enzymes in the suberin polyphenolics and lignin pathways, including phenylalanine ammonia lyase, 4-coumaryl-coenzyme A ligase, cinnamyl alcohol dehydrogenase and peroxidase (33.90–64.32%), as well as the contents of cinnamic acid, sinapic acid, flavonoids, lignins and total phenolics (19.70–23.46%) at wound sites of potato tubers on the 7 day after wounding. Our results indicated that foliar application of chitosan accelerated wound-induced suberization of potato tubers and could mitigate post-harvest product damages.

Here we investigated the acute effects of an exhaustive intermittent exercise session on immunological parameters of the elderly and the subsequent incidence of upper respiratory tract infections and compare with the moderate-intensity. To do so, ixty-three old subjects were divided into three groups HIIT (n=21) submitted at one High-intensity interval training, SCG (n=21) kept in a sedentary state, and MICT (n=21) submitted at moderate intensity walking. Blood were collected at 5 time points, before, immediately after, 2h, 24h, and 48h after the intervention. In result the IL-6 and TNF-α were overexpressed immediately after the IL-10 stood overexpressed and correlated with IL-17, denoting an inflammatory process, and evidencing an immunologic competence without enhancement of the prevalence of upper respiratory infection tract (URTIs). So a modulation in the balance of Th1/Th2/Th17 cytokines and leukocytes, these modifications did not cause the effect characterized as an immunological window. Perhaps, the typical inflammation process, with IL-10 and IL-17 participation could also produce benefits to combat infections, a pertinent discussion during a post-pandemic time; we consider it a safe exercise program for older adults.