Maternal type 2 diabetes mellitus (T2DM) has been shown to result in fetal programming of the hypothalamus-pituitary-adrenal (HPA) axis, leading to adverse fetal outcomes. T2DM is preceded by prediabetes and shares similar pathophysiological complications. However, no studies have investigated the effects of maternal prediabetes on fetal HPA axis function and postnatal offspring development, hence this study. Pre-diabetic (PD) and non-pre-diabetic (NPD) female Sprague Dawley rats were mated with non-prediabetic males. After gestation, male pups born from the PD and NPD groups were collected. Markers of HPA axis function, adrenocorticotropin hormone (ACTH) and corticosterone were measured in all dams and pups. Glucose tolerance and expression of mineralocorticoid (MR) and glucocorticoid (GR) receptors were further measured in all pups at birth and their developmental milestones. The results demonstrated increased basal concentrations of ACTH and corticosterone in the dams from the PD group by comparison to NPD. Furthermore, the results show an increase in pups ACTH and corticosterone concentrations, impaired glucose tolerance and dysregulated MR and GR expression in the PD group at all developmental milestones. These observations reveal that pregestational prediabetes is associated with maternal dysregulation of the HPA axis, impacting offspring HPA axis development along with impaired glucose handling.

A growing body of research has identified fetal risk factors associated with adult diseases that form the basis for the Developmental Origins of Health and Disease (DOHaD) hypothesis. This theory proposes a critical developmental period during which the fetus is highly susceptible to specific environmental influences that significantly impact health from short to long term. Maternal stress and T2DM during pregnancy are among these influences, likely leading to fetal overexposure to glucocorticoids and suggesting a shared pathway between maternal dysregulated HPA axis and fetal environmental insults. Studies demonstrate that prenatal glucocorticoid exposure alters fetal HPA axis function, affecting brain function, tissue glucocorticoid availability, and fetal growth in utero. These programmed changes, such as altered HPA axis function and reduced fetal growth, contribute to metabolic disorders persisting into adulthood. T2DM is preceded by a prediabetic state, often asymptomatic, which shares similar pathophysiological complications with T2DM, including HPA axis dysregulation observed in animals. Therefore, investigating prediabetes during pregnancy alongside maternal HPA axis function and its effects on fetal outcomes is crucial, as these areas remain understudied. This review aims to synthesize existing literature on pre-existing T2DM during pregnancy, its links to fetal programming via HPA axis changes, and possible links to pregestational prediabetes.

Apart from their established role in embryonic development Nerve Growth Factors (NGFs) have diverse functions in the nervous system. Their role in integration of physiological functioning of the nervous system is now attracting attention. In the present analysis, we propose a novel paradigm about a novel role of NGFs: NGFs play imperative role in maintaining psychological integrity of an individual as a biological system. This function may be mediated through HPA-axis- operated homeostatic mechanisms; stress induced disruption of which may lead to psychiatric disorders. Current literature suggests existence of constitutive homeostatic regulatory mechanisms for NGFs disruption which may lead to pertinent and imperative behavioural effects. NGFs are known to play crucial role in endocrine regulation. This is especially true with the prototype ‘NGF’ and Brain Derived Neurotrophic Factor (BDNF). These moieties have been observed to play important function in maintaining neuro-endocrine homeostasis thereby having a profound impact on the psychological health of an individual. Role of NGFs and HPA-axis activation (in separate studies) in developing psychiatric disorders - especially those born of stress - have been reported. Literature suggests their unique interplay for producing a common effect which might be implicated in stress induced genesis of psychiatric disorders. This aspect, therefore, needs to be elucidated further as a disease etiogenesis model. This model may yield important insights into the biology of psychiatric disorders and may open ways for new therapeutic approaches.

Abstract A multiple number of studies provide evidence that vasopressin (AVP) and steroid hormones are frequently secreted together and closely cooperate in the regulation of blood pressure, metabolism, water-electrolyte balance, and behavior, securing thereby survival and comfort of life. Vasopressin interacts with hormones of the hypothalamo-pituitary-adrenal axis (HPA) at several levels through regulation of release of corticotropin-releasing hormone (CRH), adrenocorticotropic hormone ACTH, and multiple steroid hormones, as well as through interactions with steroids in the target organs. The interactions are facilitated by positive and negative feedbacks occurring between specific components of the HPA axis with engagement of other regulatory molecules. Altogether AVP and HPA cooperate closely as a coordinated functional AVP-HPA system. It has been shown that cooperation between AVP and steroid hormones may be affected by the cellular stress combined with hypoxia, and by metabolic, cardiovascular and respiratory disorders, neurogenic stress and inflammation. Growing evidence indicates that central and peripheral interactions of AVP and steroid hormones are reprogrammed in cardiovascular diseases and that the rearrangements play either beneficial or harmful effects. The present review highlights specific mechanisms of interactions of AVP and steroids at cellular and systemic levels and analyses consequences of inappropriate cooperation between various components of the AVP-HPA system for the regulation of the cardiovascular system and energy balance in cardiovascular and metabolic diseases.

Consumption of poultry meat is higher than red meat due to easy availability, good taste, low cost and palatability. Significant improvement in meat yield and growth rate of broiler chicken has been brought about with the help of genetic selection of desirable traits. The present study was conducted to comparatively evaluate the chronic effect of domestic and broiler chicken meat consumption on male hypothalamic pituitary gonadal axis, lipid profile and oxidative stress on postnatal male rats. Rats were divided into five groups: control, B1, B2, D1 and D2 groups and were fed with 0.17g and 0.34g of broiler and domestic chicken meat from postnatal day 21 to PND90.The significant elevated body weight and weight gain in B2 group (P<0.01), minor change in B1 and D40 group (P<0.05) were detected. In gonadosomatic index absolute and relative epididymis weight, weight of seminal vesical and Prostate weight was significantly augmented in B2 compared to control and D2. Kidney and liver weight in B1, B2 was markedly elevated and minor change in D2 groups. ROS level in B2 was significantly higher than other experimental groups. Serum level of FSH, LH, testosterone, estradiol and low density lipoprotein was significantly elevated in B2 compared to control and D2. In B2 rats fed with 0.34g broiler meat exhibited a marked decreased seminiferous tubule diameter, epithelial height and increased lumen diameter changes that were more prominent compared to rats fed with 0.34g domestic chicken meat. Conclusively chronic administration of broiler meat induces marked alteration in reproductive system, testicular morphology, sexual hormones and oxidative stress in postnatal Sprague Dawley male rats compared to domestic chicken meat.

Thyroid hormones are essential for regulating the metabolic rate, growth, development, and maintenance of many physiological processes in vertebrates. They are synthesized by the thyroid gland, which is an ancient organ that evolved early in vertebrate evolution. This study aims to characterize the evolutionary path of polymorphic variants associated with the hypothalamus-pituitary-thyroid (HPT) axis by comparing ancient DNA (aDNA) sequences of Late Pleistocene-Holocene hominin populations with those of modern humans. We evaluated the genetic sequences of several populations, including Neanderthals, Denisovans, Palaeolithic hunter-gatherers from European Russia and Sunghir, and Neolithic hunter-gatherers/farmers from Anatolia focusing on genes involved in the development of the thyroid gland and thyroid hormone (TH) biosynthesis, secretion, and transport. Results showed interesting variants in the DIO2 (rs225014), TPO (rs4927611), and TG (rs2069556 and rs1133076) genes. All SNPs seemed to confirm that Neanderthals, and in part Denisovas, were physiologically hypothyroidic. Probably they had lower T3 levels due to defective production or peripheral conversion. From the moment that the most favourable alleles in terms of T3 production appear during the Paleolithic, we are inclined to assume that their selection was linked to environmental pressure.Our study supports insight into the evolutionary history of the endocrine system and can help in providing understanding into the evolution of physiological systems and their adaptation to changing environments. Understanding the evolution of thyroid hormones can also shed light on the mechanisms underlying thyroid disorders in humans.

External stressors strongly increase cardiovascular activity and induce metabolic changes that ensure the availability of glucose and oxygen as part of a co-ordinated stress response. Exposure to stress during early life appears to have an exaggerated long-term effect on this response, leading to an increased risk or cardiometabolic disorders. Here we demonstrate that acute stress induced glucose release is impacted by the early life environment in rodent maternal deprivation and early-life infection models and this was validated in our EpiPath human early-life adversity cohort. In all three models differences in baseline blood glucose levels after ELA exposure were sex dependent. The human ELA model showed higher levels of basal glucose in females, similar to the mouse infection and rat maternal deprivation models. We anticipated that the stress induced glucose rise would be a GC dependent process. However, the kinetics of stress-induced glucose release, peaking 15-28 minutes before cortisol suggest that it is a GC-independent process. We confirmed this by administering an escalating dose of cortisol to a health human cohort, and the inability of an intravenous GC bolus induce a glucose rise in man confirms that it is a rapid, GC independent, process.In conclusion, we provide a novel perspective on the mechanisms behind stress related metabolic changes and highlights the importance of collecting early life data as a measure to understand an individual’s metabolic status in a better light.

Using analytic approach we study the effect of HPA axis secretions to the emotional variation of bipolar II disorder patient. Modified Duffing – Van der Pol oscillator was used to model the emotional variation, that was solved analytically using multiple scale perturbation to obtain an asymptotic solution. The solution was graphed to understand the effect of the variation of the cortisol to the oscillator. It was observed that the increase or decrease of the HPA hormone from the basal level in the body system, affects the mood variation of bipolar II disorder patients.

Text mining is a technological trend often highlighted in the continuous exchange of information through interconnected media. Its applicability goes beyond private organizations, as the public sector also requires it to treat textual information regarding services offered. Within this scenario, public security emerges as a prominent user of text mining that seeks to ensure the construction of data and knowledgebases to support decision-making about law enforcement actions to ensure citizen welfare. The primary objectives of this article are: (i) to develop a survey to identify text mining applications, techniques, opportunities, and challenges in public security, and (ii) to outline research directions concerning these topics and provide insights so that interested researchers can develop new studies. The literature was searched within four databases: Scopus, IEEE Xplore, ACM Digital Library, and Web of Science. A filtering process was applied to extract the works most aligned with the target theme, resulting in the selection of 194 of the most relevant works for a literature review. There were identified nineteen key applications of text mining related to public security and the most recurrent techniques and technologies reported between 2014 to 2021, supporting outlining three axes for future directions: one with possible expansion of objectives for new research; another on changes and adaptations in scopes for the methodological context; and the last one on expansions and changes in application scenarios based on the literature.

The epithelial cell tight junction structure is the site of the transepithelial movement of solutes and water between epithelial cells (paracellular permeability). Paracellular permeability can be divided into two distinct pathways, the Pore Pathway mediating the movement of small ions and solutes and the Leak Pathway mediating the movement of large solutes. Claudin proteins form the basic paracellular permeability barrier and mediate the movement of small ions and solutes via the Pore Pathway. The Leak Pathway remains less understood. Several proteins have been implicated in mediating the Leak Pathway, including occludin, ZO proteins, tricellulin, and actin filaments, but the proteins comprising the Leak Pathway remain unresolved. The properties of the Leak Pathway, such as its molecular mechanism, its regulation, and whether or not it has a size limit, remain controversial. This review will trace the evolution of the Leak Pathway concept from its origins, will discuss the current information about the properties of the Leak Pathway, and will discuss recent research suggesting a possible molecular basis for the Leak Pathway. Based on these findings, we propose a model for the molecular mechanism underlying the Leak Pathway and its regulation.

The hypothalamus is the site of synthesis and secretion of a number of endocrine peptides that are involved in the regulation of hormonal activity of the pituitary and other endocrine targets. Tumors of the hypothalamus have been recognized to have both structural and functional effects including hormone hypersecretion. The classification of these tumors had advanced over the last few years and biomarkers are now available to classify these tumors and provide accurate structure-function correlations. This review provides an overview of tumors in this region that is critical to metabolic homeostasis with a focus on advances in the diagnosis of gangliocytomas, neurocytomas and pituicytomas that are unique to this region.

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.

Cardiovascular morbidities are the main cause of mortality in pituitary disorders accruing either from hormonal excess or deficiency. Cushing disease is associated with various cardiovascular abnormalities;visceral obesity, insulin resistance, atherosclerosis, arterial hypertension, dyslipidaemia and hypercoagulability, structural and functional changes in heart, which do not seem to reverse completely even after remission. Acromegaly is related with insulin resistance, but also with structural and functional heart changes which consist acromegalic cardiomyopathy. Patients with prolactinomas demonstrate an aggravation of metabolic parameters, obesity, dysregulation of glucose and lipid metabolism and endothelial dysfunction. On the other hand, hypopituitarism and conventional hormonal replacement which is far from ideal contribute to an unhealthy metabolic status which leads to atherosclerosis and premature mortality. This review aims to update literature on cardiovascular risk and relevant morbidities in pituitary disorders.

Immunostaining of transcription factors allows a more exact classification of pituitary neuroendocrine tumours (PitNETs), but not a better prediction of their clinical behaviour. This retrospective, single-centre study aims to classify a series of PitNETs using Trouillas et al.’s clinicopathological classification from 2013. We analysed 166 patients undergoing PitNET surgery in 2013–2023. Tumours were identified according to the gene and immunohistochemical expression of PitNET transcription factors plus adenohypophyseal hormones. Tumours were classified according to a grading system based on MRI invasion and Ki-67 index. Eighty-one (48.8%) patients had grade 2a tumours; 71 (42.8%), grade 1a; 8 (4.8%), 2b; and 6 (3.6%), 1b. At a mean follow-up of 57.8 (standard deviation 30) months, 13.9% (n=23) showed recurrence/progression; independent predictors of recurrence were tumour volume (p=0.031) and T2 signal intensity ratio (SIR) (p&lt;0.001). This risk was 18.6-fold higher for a T2 SIR of 2 or more. Grade 2a and 2b tumours, T2 SIR, and silent corticotroph adenomas (SCAs) were associated with lower progression-free survival. Our results add more evidence to the prognostic value of the five-grade PitNET classification and suggest higher clinical surveillance of patients with SCAs is warranted. The MRI findings highlight the increasing value of radiological evaluation for managing PitNETs.

The detection of subtle changes in the pituitary dimensions has relevant implications since this gland is crucial for the endocrine system. In cats, few studies established the cut-offs values of the pituitary gland’s dimensions, but using small and inhomogeneous samples. The aims of this study were: to determine by computed tomography (CT) the pituitary linear dimensions and the pituitary-to-brain (P:B) ratio in a sample of domestic short-haired (DSH) cats; to assess the effects of sex, age and weight on pituitary dimensions; to evaluate the inter- and intra-observer agreement for such measurements. Exclusion criteria were: clinical, laboratory or CT alterations of pituitary gland or brain diseases, fractures of the neurocranium, or diabetes mellitus. Pituitary dimensions and brain area were assessed by two different observers using multiplanar reconstructions and automated segmentation tools. Fifty-one cats were included in the final sample. The intraclass correlation coefficient for intra- and inter-observer reliability showed good/excellent and moderate/good reliability, respectively. No differences between sexes were detected, and negligible correlations were found with age and weight. Findings from the current study provided normal reference values for pituitary height (1.88 – 4.01 mm) and P:B ratio (0.25 – 0.49), useful for assessing abnormally enlarged pituitary gland in DSH cats.

We are in amidst of COVID-19 pandemic. Since Dec 2019, severe acute respiratory corona virus (SAR-CoV-2) has infected more than half a billion people killing nearly 7 million people worldwide. Now the BA.5 variant of SARS-CoV-2 is causing mayhem and driving the global surge. Epidemiologist are aware of the fact that this virus is capable of escaping immunity and likely to infect the same person multiple times despite adequate vaccination status. Elderly people of age more than 60 years and those with underlying health conditions are considered as high-risk who are likely to suffer complications and death. While it is tempting to frame complications and mortality from COVID-19 as a simple matter of too much of a virulent virus in too weak of a host, much more is at play here. Framing the pathophysiology of COVID-19 in the context of the Chrousos and Gold model of the central stress response system can shed insight into its complex pathogenesis. Understanding the mechanisms by which pharmacologic modulation of the central stress response system via administration of clonidine and/or dexamethasone may offer an explanation as to why a viral pathogen can be well tolerated and cleared by one host while inflaming and killing another.

Background: Very low-calorie ketogenic diet (VLCKD) is associated with improvement of metabolic and cardiovascular disorders. We aimed to evaluate the effects of VLCKD in patients with Cushing’s disease (CD) as adjunctive therapy to treatment for primary disease. Methods: We evaluated clinical, hormonal and metabolic parameters in 15 patients with CD and 15 controls at baseline and after 1 week and 3 weeks of VLCKD and further 2 weeks of low-carbohydrate ketogenic diet (LCKD). Results: After 5 weeks of diet a significant decrease in BMI (p=0.002), waist circumference (WC) (p=0.024), systolic (p=0.015) and diastolic blood pressure (p=0.005), ACTH (p=0.026), cortisone (p=0.025), total (p=0.006) and LDL cholesterol (p=0.017), triglycerides (p=0.016), alkaline phosphatase (p=0.008) and a significant increase in HDL cholesterol (p=0.017), vitamin D (p=0.015) and oral disposition index (Dio)(p=0.004) was observed in CD. A significant decrease in BMI (p=0.003), WC (p=0.002), systolic (p=0.025) and diastolic (p=0.007) blood pressure and total cholesterol (p=0.026) and increase in HDL cholesterol (p=0.001) and DIo (p&lt;0.001) was observed in controls. Conclusions: The current study confirms that ketogenic diet is effective in improving metabolic disorders and shows that a nutritional approach may be combined with conventional CD therapy in order to improve metabolic and cardiovascular comorbidities.

Context: CYP21A2 deficiency represents 95% of congenital adrenal hyperplasia cases (CAH), a group of genetic disorders that affect steroid biosynthesis. The genetic and functional analysis provides critical tools to elucidate complex CAH cases. One of the most accessible tools to infer the pathogenicity of new variants is in silico prediction. Objective: Analyze the performance of in silico prediction tools to categorize missense single nucleotide variants (SNVs) of the CYP21A2. Methods: SNVs of the CYP21A2 characterized in vitro by functional assays were selected to assess the performance of online single and meta predictors. SNVs were tested separately or in combination with the related phenotype (severe or mild CAH form). In total, 103 SNVs of the CYP21A2 (90 pathogenic and 13 neutral) were used to test the performance of 13 single-predictors and four meta-predictors. Results: SNVs associated with the severe phenotypes were well categorized by all tools, with an accuracy between 0.69 (PredictSNP2) and 0.97 (CADD), and Matthews' correlation coefficient (MCC) between 0.49 (PoredicSNP2) and 0.90 (CADD). However, SNVs related to the mild phenotype had more variation, with the accuracy between 0.47 (S3Ds&GO and MAPP) and 0.88 (CADD), and MCC between 0.18 (MAPP) and 0.71 (CADD). Conclusion: From our analysis, we identified four predictors of CYP21A2 pathogenicity with good performance. These results can be used for future analysis to infer the impact of uncharacterized SNVs' in CYP21A2.

Prediction of tumor consistency is valuable for planning transsphenoidal surgery for pituitary adenoma. A prospective study was conducted involving 49 participants with pituitary adenoma to determine whether quantitative pharmacokinetic analysis of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is useful for predicting consistency of adenoma. Pharmacokinetic parameters in the adenomas including volume of extravascular extracellular space (EES) per unit volume of tissue (ve), blood plasma volume per unit volume of tissue (vp), volume transfer constant between blood plasma and EES (Ktrans), and rate constant between EES and blood plasma (kep) were obtained. The pharmacokinetic parameters and the histologic percentage of collagen content (PCC) were compared between soft and hard adenomas using Mann–Whitney U test. Pearson’s correla-tion coefficient was used to correlate pharmacokinetic parameters with PCC. Hard adenomas showed significantly higher PCC (44.08 ± 15.14% vs. 6.62 ± 3.47%, p < 0.01), ve (0.332 ± 0.124% vs. 0.221 ± 0.104%, p = 0.02), and Ktrans (0.775 ± 0.401/min vs. 0.601 ± 0.612/min, p = 0.02) than soft adenomas. Moreover, a significant positive correlation was found between ve and PCC (r = 0.601, p < 0.01). The ve derived using DCE-MRI may have predictive value for consistency of pituitary adenoma.

New research points to a possible link between Autism Spectrum Disorder and the gut microbiota as many autistic children have co-occurring gastrointestinal problems. This review focuses on specific alterations of gut microbiota mostly observed in autistic patients. Particularly, the mechanisms through which such alterations may trigger the production of the bacterial metabolites or leaky gut in autistic people are described. Various altered metabolite levels were observed in autistic children, many of those were of bacterial origin such as short chain fatty acids (SCFAs), indoles and lipopolysaccharides. A less integrative gut-blood-barrier is abundant in autistic individuals. This explains the leakage of bacterial metabolites into the patients triggering new body responses or altered metabolism. Some other co-occurring symptoms such as mitochondrial dysfunction, oxidative stress in the cells, altered tight junctions in the blood brain barrier and structural changes in cortex, hippocampus, amygdala and cerebellum were detected. Moreover, this paper suggests that autism is associated with an unbalanced gut microbiota (dysbiosis). Although the cause-effect relationship between autism and gut microbiota is not yet well established, consumption of specific probiotics may represent a powerful tool to re-establish gut homeostasis and promote gut health. Diagnostic and therapeutic value of new biomarkers leading to the perturbation in the phenylalanine metabolism will be discussed.

Pituitary adenomas are benign brain tumors that pose a heavy burden on patients worldwide. However, the local burden of disease is yet to be established due to scarcity of data. In line with this, this study aims to present the challenges and gaps in the treatment of pituitary adenomas in the Philippines. A scoping review of available relevant literature on epidemiology, clinical experience with treatment, health financing, and healthcare delivery system based on the Preferred Reporting Items for Systematic reviews and Meta-analysis guidelines extension for Scoping Reviews was conducted. The scarcity of updated local clinical data, inequity of distribution of resources, inadequate government support, and lack of affordable diagnostic testing, medications and neurosurgical procedures are the factors that hinder provision of adequate care of pituitary adenomas in the Philippines. There are notable treatment gaps in the management of pituitary adenomas in the Philippines, which may be addressed by strengthening universal healthcare. Strategies to address these gaps were proposed, including improving public-private insurance coverage, increasing manpower, enhancing accessibility to resources, and spreading more awareness.

Animals in human care are affected by stressors that can ultimately reduce fitness. When reproduction is affected, endangered species’ conservation programmes can be severely compromised. Thus, understanding factors related to stress and reproduction, and measures of related hormones, are important to ensure captive breeding success. Red pandas are endangered and populations in the wild are threatened with extinction. A global captive breeding programme has been launched to conserve the species with the goal of reintroduction. However there is little informaiton on how stressors impact reproductive aspects of the species. This study measured fecal glucocorticoid (fGCM), fecal progestagen (fPM) and fecal androgen (fAM) metabolite concentrations in 12 female and 8 male red pandas (Ailurus fulgens fulgens) at three zoos in northeastern India to determine predictors of adrenal and gonadal steroid activity and the influence of fGCM on reproduction. Results indicated that fGCM concentrations were higher in males than females, and positively correlated with number of visitors, while negatively related to frequency of feedings and enclosure area. Sex, visitor number, frequency of feeding, and enclosure area explained 67% of the variations in fGCM concentrations in the study population. Concentrations of fPM were positively associated with tree density in the enclosure, explaining 47% of the variation among females. For fAM, positive associations were found with frequency of feeding, but concentrations were negatively related to age and number of visitors; these three covariates explained 45% of the variation in fAM concentration among males. Comparison of fGCM with fPM showed a negative trend, indicating increasing adrenal hormones may decrease reproductive function among female red pandas. The study thus suggests that zoo management should consider increasing feeding frequency, providing larger enclosures with more trees, and regulating visitor numbers to reduce stress and increase reproductive fitness among red pandas.

Hip joint surgeries, including total hip replacement or resurfacing, have increased tremendously in the last decades. Number of patients of all ages, replace their hip, due to severe injuries or trauma problems, so as to have a better life. According to these factors, new material and processes in implants manufacturing are imported to medicine, through research programs, every year. In the scope of one of these programs, that has to do with ceramic coatings on metallic resurfacing implants, a new 3axis Hip simulator was designed and manufactured in the Laboratory of Manufacturing Technology of the National Technical University of Athens. The scope of this paper is to present the main parts, materials and process used to manufacture the simulator as well as the way the simulator is working and how its movement in 3axis is accomplished. Furthermore, the evaluation of the machine and its use to examine resurfacing implants is presented.

From oxidative eustress and distress, to bioenergetic metabolism, and cell death, the reactive species interactome (RSI) and mitochondria are two connected metabolisms that require further investigation improving redox medicine. The step before, finding new clues needs a comprehensive discussion of the two metabolisms, and their relationship. Here, the review focuses on the RSI-mitochondria axis, from mitochondrial roles to crosstalk between mitochondria and other organelles, and the major implication of the RSI in mitochondrial roles. Specifically, the review discussed the apoptosis-necroptosis-ferroptosis death traingle, mitochondrial protein quality control system, calcium homeostasis, and mitochondrial metabolome. Through mitochondrial diseases, and mitochondrial dysfunction associated with diseases, the RSI-mitochondria axis is proposed as a brand-new perspective, including with the involvement of bacterial microbiota, on redox signaling, and redox medicine.

The PI3K-AKT-mTOR signal transduction pathway regulates a variety of biological processes including cell growth, cell cycle progression and proliferation, cellular metabolism and cytoskeleton reorganization. Fine-tuning of the PI3K pathway signaling output is essential for the maintenance of tissue homeostasis and uncontrolled activation of this cascade leads to a number of human pathologies including cancer. Inactivation of the tumour suppressor phosphatase PTEN and/or activating mutations in the proto-typical lipid kinase PI3K have emerged as some of the most frequent events associated with human cancer and as a result the PI3K pathway has become a highly sought-after target for cancer therapies. In this review we summarize the essential role of the PTEN-PI3K axis in controlling cellular behaviors by modulating activation of key proto-oncogenic molecular nodes and functional targets. Further, we highlight important functional redundancies and peculiarities of these two critical enzymes that over the last few decades have become a central part of the cancer research field and have instructed hundreds of pre-clinical and clinical trials to better cancer treatments.

Saturated fatty acids are implicated in the development of metabolic diseases, including obesity and type 2 diabetes. There is evidence, however, that polyunsaturated fatty acids can counteract the pathogenic effects of saturated fatty acids. To gain insight into the early molecular mechanisms by which fatty acids influence hypothalamic inflammation and insulin resistance, we performed time-course experiments in a hypothalamic cell line, using different durations of treatment with the saturated fatty acid palmitate, and the omega-3 polyunsaturated fatty acid, docosahexaenoic acid (DHA). Western blot analysis revealed that palmitate elevated the protein levels of phospho(p)AKT in a time-dependent manner. This effect seems involved in the pathogenicity of palmitate, as temporary inhibition of the PI3K/AKT pathway by selective PI3K inhibitors prevented palmitate-induced insulin resistance. Similarly to palmitate, DHA also increased levels of pAKT, but to a weaker extent. Co-administration of DHA with palmitate decreased pAKT close to the basal level after 8 h, and prevented palmitate-induced insulin resistance after 12 h. Measurement of the inflammatory markers pJNK and pNFκB-p65 revealed tonic elevation of both markers in the presence of palmitate alone. DHA alone transiently induced elevation of pJNK, returning to basal levels by 12 h treatment. Co-administration of DHA with palmitate prevented palmitate-induced inflammation after 12 h, but not at earlier time points.

Trio-based exome sequencing and high-resolution HLA typing were employed to analyze three patients with autoimmune adrenal insufficiency (AAI), including those with autoimmune polyglandular syndrome (APS) type 2, as well as their parents. Benign or likely benign variants of the AIRE gene were identified in all participants of the study. These variants, coupled with clinical data and the results of antibody studies to type I interferons, helped to exclude APS-1. Patients with APS-2, in contrast to patient with AAI, inherited distinct variants of unknown significance in the CLEC16A gene, which is associated with autoimmune diseases including AAI. Various risk alleles in other genes associated with autoimmunity were identified in all patients. HLA typing of second class loci revealed alleles related to APS types 2, 3, and 4. Nevertheless, the frequencies of the haplotypes identified are substantial in the healthy Russian population, precluding from regarding these alleles as genetic determinants linked to APS development. Immunological examination can detect antibody carriers and predict the risk of autoimmune disease development. In the future, to identify genetic predictors of autoimmune endocrinopathies, it is recommended to analyze the whole genome of patients and their relatives, examining clinically relevant variants in non-coding regions.

Patients with degenerative diseases refer to feeling more pain during the night. However, it is unknown whether spinal nociception can be circadian and how is it controlled. We investigated whether the paw withdrawal threshold (PWT) could exhibit physiological circadian behavior as well as the contribution of the dopaminergic A11 nucleus and the spinal dopamine (DA) receptors (DRs) on the circadian PWT and the spinal clock gene transcription. Results revealed that control rats present a circadian PWT. Injecting 6-hydroxidopamine (6-OHDA) into the dopaminergic A11 nucleus reduced DA tissue content in the lumbar spinal cord, abolished the circadian PWT, induced allodynia, and reduced Period 1 and 2 (Per1 and 2), retinoid-related orphan receptor α (Rorα), Cryptochrome 1 (Cry1), and brain and muscle aryl-hydrocarbon receptor nuclear translocator-like protein (Bmal) mRNA. Likewise, administration of D1-like and D2-like DR antagonists blunted circadian PWT, producing allodynia, and altered the clock genes mRNA. In contrast, administration of D1-like or D2-like DR agonists blocked 6-OHDA-induced allodynia. This study shows that the spinal cord has physiological circadian PWT, which is modulated by the descending dopaminergic A11 through differential activation of the spinal DRs. Also, A11 nuclei and spinal DRs can regulate the clock gene transcription, which can likely modulate the circadian PWT.

Background: To assess effectiveness, safety of computed tomography (CT)-guided cryoablation for treating adrenal metastases (AMs). Materials and Methods: This study involved 12 patients treated with 13 CT-guided cryoablation procedures for AMs between 2016 and 2020. Patients’ ineligible for surgery, with tumors ≤5 cm, and no significant health risks were included. The procedures, conducted by expert radiologists, included initial non-contrast CT scans to determine lesion morphology, followed by cryoablation with monitoring for complications. Post-treatment, patients underwent regular physical and laboratory checks, including hormonal analysis, and CT scans at specified intervals to assess the treatment's effectiveness and detect disease recurrence or progression. Results: In this study, 12 patients with AMs successfully underwent cryoablation, achieving a primary technical success rate of 91.7% and a secondary rate of 100% after a repeat procedure for one patient. All cryoablation sessions were completed without major complications, with ice ball formations extending 1 cm beyond tumor margins to ensure safety. Over an 8–24-month follow-up (average 16.3 months), six patients required further systemic therapy, with three developing extra-adrenal tumors. Local progression was noted in two patients (16.7%), one of whom underwent a repeat cryoablation. Systemic progression was observed in five patients, involving renal and NSCLC cancer recurrences and bone metastasis. The study reported five deaths due to tumor progression and heart failure, with an average overall survival duration of 32.4 ± 7.6 months.

Recurrent hypoglycaemia, a common side-effect of insulin therapy in the treatment of type 1 diabetes, induces impaired glucose-sensing. Better understanding of how astrocytes, important non-neuronal cells in the brain, function in low glucose environments may improve our understanding of recurrent hypoglycaemia-induced defective counterregulation. Astrocytes contribute to glutamatergic signalling, which is required for hypoglycaemia counterregulation and is impaired by recurrent insulin-induced hypoglcyaemia. This study examined the glutamate response of astrocytes when challenged with acute and recurrent low glucose (RLG) exposure. The metabolic responses of cortical (CRTAS) and hypothalamic (HTAS) primary rat astrocytes were measured in acute and recurrent low glucose using extracellular flux analyses. RLG caused mitochondrial adaptations in both HTAS and CRTAS, many of which were attenuated by glutamate exposure during low glucose treatments. We observed an increase in capacity of HTAS to metabolise glutamine after RLG exposure. Demonstrating astrocytic heterogeneity in the response to LG, CRTAS increased cellular acidification, a marker of glycolysis in LG, whereas this decreased in HTAS. The directional change in intracellular Ca2+ levels of each cell type, correlated with the change in extracellular acidification rate (ECAR) during LG. Further examination of glutamate-induced Ca2+ responses in low glucose treated CRTAS and HTAS identified sub-populations of glucose-excited- and glucose-inhibited-like cells with differing responses to glutamate. Lastly, release of the gliotransmitter ATP by HTAS was elevated by RLG, both with and without concurrent glutamate exposure. Therefore, hypothalamic astrocytes adapt to RLG by increasing glutamate uptake and oxidation in a manner that attenuates RLG-induced mitochondrial adaptations.

Cirrhosis is a chronic disease with multiple etiologies, multiple manifestations, and multi-organ involvement. Affects about 200 million people worldwide. Its main complication is Portal hypertension (PHT). Cirrhotic cardiomyopathy is a consequence of PHT, with heart failure (HF) being the main manifestation. On the other hand, for people with cardiopathy due to other reasons beyond cirrhosis, the presence of the last could act as a trigger to acute HF. Finally, when HF and cirrhosis coexist, the renal system suffers the most, originating from type-5 cardio-renal syndrome, a complex entity with many challenges in diagnosis and treatment. This entity was recently defined and there is a lack of data on the epidemiology of this syndrome. A 77-year-old woman, with cardiovascular risk factors; heart failure with reduced ejection fraction (HFrEF), secondary ischemic and valvular cardiopathy, chronic Kidney disease (CKD), and stable decompensated cirrhosis, went to the emergency department after progressive abdominal perimeter augmentation, legs’ edema and hematochezia. It was assumed acute decompensated cirrhosis and acute decompensated chronic kidney disease, had triggered digestive bleeding and the patient stayed hospitalized. Intravenous diuretic therapy was started but, the ascites and kidney function got worse, the Nt pro-BNP grew until 1125000 pg/ml, and a transthoracic echocardiography showed important signs of congestion, isolated right ventricular dysfunction, with normal cardiac output. After teamwork’s discussion, a type-5 cardio-renal syndrome was assumed deciding not to act on tricuspid regurgitation due to the maladaptive RV remodeling. Hepatorenal syndrome treatment was begun (oral terlipressin and intravenous albumin), followed by decongestion therapy, resulting in a marked improvement in clinical presentation. The kidney, heart, and liver recovered to these basal states. With this clinical case, the authors want to show how multidisciplinary management is important to face tricuspid regurgitation and right ventricular dysfunction.

21-hydroxylase deficiency (21OHD), the most common form of congenital adrenal hyperplasia (CAH), is associated with pathogenic variants in CYP21A2 gene. The clinical form of the disease ranges from classic or severe to non-classic (NC) or mild late onset. The CYP21A2 gene is located on the long arm of chromosome 6, within the RCCX region, one of the most complex loci in the human genome. The 3’untranslated sequence of CYP21A2 exon 10 overlap the last exon of TNXB gene (these genes lie on the opposite strands of DNA and have the opposite transcriptional direction) that encodes an extracellular matrix glycoprotein tenascin-X (TNX). A recombination event between TNXB and its pseudogene TNXA causes a 30-kb deletion producing a chimeric TNXA/TNXB gene (CAH-X chimera) where both CYP21A2 and TNXB genes are impaired. This genetic condition characterizes a subset of patients with 21OHD who display the hypermobility phenotype of Ehlers Danlos Syndrome (hEDS) (CAH-X Syndrome). The aim of this study was to assess the prevalence of CAH-X syndrome in an Italian cohort of patients with 21OHD. At this purpose, 196 probands were recruited. Multiplex ligation-dependent probe amplification (MLPA) and Sanger sequencing were used to identify the CAH-X genotype. Twenty-one individuals showed the heterozygous continuous deletion involving the CYP21A2 and part of the TNXB gene. EDS-related clinical manifestations were identified in most patients carrying the CAH-X chimera. A CAH-X prevalence of 10.7% was estimated in our population.

Micro-electro-mechanical systems (MEMS) are once proposed in 1970s and evolving rapidly. The current researchers are seeking for better designs and better applications of MEMS actuators. This work presents an electrostatic driven dual-axis scanning micromirror, i.e., two-dimensional (2D) scanning micromirror with a mirror size of 500 μm × 500 μm. The scanning mirror is implemented by using bulk micromachining process on silicon on insulator (SOI) substrate, which is compatible with present complementary metal oxide semiconductor (CMOS) manufacturing technology. The scanning frequencies of the slow and the fast axis are 4.87 kHz and 31.15 kHz, respectively. The impact factors of the dimensions of comb fingers and torsional beams are analyzed and discussed in this study. Under the driving voltage difference of 100 volts and 70 volts, the deviation angle is 4.57° × 13.08°. Therefore, a simple design of a dual-axis MEMS scanning micromirror is proposed, which can be precisely controlled without additional complex sensors or circuits.

The cytoskeleton is a master organizer of cell cortex, organelles positioning and membrane trafficking. Therefore, playing a decisive role in establishment of apico-basal polarity. Septins are critical cytoskeleton components which function in apico-basal polarity remain weakly investigated. Here, using 3D culture system, we demonstrate that septin9 localizes at basolateral membrane (BM). Its depletion induces an inverted polarity phenotype, decreasing -catenin at BM and increasing the expression of the transforming growth factor (TGF) and the epithelial-to-mesenchymal transition (EMT) markers. Similar effects were observed upon deleting its two polybasic domains, and the mutant become cytoplasmic and apical. The cysts with an inverted polarity phenotype display an invasive phenotype, with src and cortactin accumulating at the peripheric membrane. Inhibition of TGF-receptor and RhoA rescues the polarized phenotype. Although the cysts from overexpressed-septin 9, overgrowth and present a filled lumen. Both phenotypes correspond to tumor features. This suggests that septin 9 expression and assembly through the two PB domains are essential for establishing and maintaining apico-basal polarity against tumor development through a mechanism involving TGF-dependent EMT and RhoA activity.

Parabens are classified as endocrine disrupting compounds (EDCs), capable of interfering with the normal functioning of the thyroid, affecting the proper regulation of the biosynthesis of thyroid hormones (TH) which is controlled by hypothalamic-pituitary-thyroid axis (HPT). Given the crucial role of these hormones in health and the growing evidence of diseases related to thyroid dysfunction, this review looks at the effects of paraben exposure on the thyroid. In this study, we considered research carried out in vitro, in vivo, and epidemiological studies published between 1951 and 2023, which demonstrated an association between exposure to parabens and dysfunctions of the HPT axis. In humans, exposure to parabens appears to increase thyroid-stimulating hormone (TSH) levels, while in rodents, exposure decreases TSH levels. The effects on HT levels are also poorly described, as well as peripheral metabolism. Regardless, recent studies have shown different actions between different subtypes of parabens on the HPT axis, which allows us to speculate that the mechanism of action of these parabens is different. Furthermore, studies of exposure to parabens are more evident in women than in men. Therefore, future studies are needed to clarify the effects of exposure to parabens and their mechanisms of action on this axis.

For gravitational wave (GW) detected neutron star mergers, one of the leading candidates for electromagnetic (EM) counterparts is the afterglow from an ultra-relativistic jet. Where this afterglow is observed, it will likely be viewed off-axis, such as the afterglow following GW170817/GRB 170817A. The temporal behaviour of an off-axis observed GRB afterglow can be used to reveal the lateral jet structure, and statistical model fits can put constraints on the various model free-parameters. Amongst these parameters is the inclination of the system to the line of sight. Along with the GW detection, the afterglow modelling provides the best constraint on the inclination to the line-of-sight and can improve the estimates of cosmological parameters e.g. the Hubble constant, from GW-EM events. However, modelling of the afterglow depends on the assumed jet structure and, often overlooked, the effects of lateral spreading. Here we show how the inclusion of lateral spreading in the afterglow models can affect the estimated inclination of GW-EM events.

The described data set contains features from the machine control of a five-axis milling machine. The features were recorded during thirteen series productions. Each series production includes a changeover process in which the machine was set up for the production of a different product. In addition to the timestamps and the twenty recorded features derived from Numerical Control (NC) control variables, the data set also contains labels for the different production phases. For this purpose, up to 23 phases were assigned, which are based on a generalized milling process. The data set consists of thirteen .csv files, each representing a series production. The data set was recorded in a production company in the contract manufacturing sector for components with real series orders in ongoing industrial production.

Although first described in the final decade of the 19th century, the axis responsible for atrioventricular conduction has long been the source of multiple controversies. Some of these continue to reverberate. When first described by His, for example, many doubted the existence of the bundle we now name in his honour, while Kent suggested that multiple pathways crossed the atrioventricular junctions in the normal heart. It was Tawara who clarified the situation, although many of his key definitions have not universally been accepted. In key studies in the third decade of the 20th century, Mahaim then suggested the presence of ubiquitous connections that provided "paraspecific" pathways for atrioventricular conduction. In this review, we show the validity of these original investigations, based on our own experience with a large number of datasets from human hearts prepared by serial histological sectioning. Using our own reconstructions, we show how the atrioventricular conduction axis can be placed back within the heart. We emphasise that newly emerging techniques will be key in providing the resolution to map cellular detail to the gross evidence provided by the serial sections

BACKGROUND: It has been known for decades that breastfeeding leads to a lower risk of asthma, respiratory infections, or metabolic syndrome at school age. In addition, evidence is now accumulating on the influence of breast milk on the shape, volume, or function of the heart and lungs. Within this field of research into the effects of breast milk on the structure of the heart and lungs, we have set out to analyze the differential electrocardiographic characteristics of schoolchildren who were once breastfed. METHOD: Observational cross-sectional study including 138 children aged 6 or 12 consecutively presenting to a well-child clinic between May and December 2022. Inclusion criteria: the ability to perform reproducible ECG records, the feasibility of weighing and measuring patient, and breastfeeding data collected from birth. RESULTS: Using the 40º cut-off value for the mean P-wave axis among schoolchildren, 76% of never breastfed children in our sample have a P-wave axis in a more vertical position than the mean as compared to 58% of ever-breastfed children (OR:2.25;95%CI:3.13-1.36); there was no other significant difference between infant feeding groups in somatometric characteristics or ECG parameters, CONCLUSION: We found a significant difference of the mean values of the P-wave axis between never and ever breastfed children. Although this report should be approached cautiously, these findings add to the renewed interest in discerning developmental interventions to improve cardiovascular health.

Probability is an open question in the ontological interpretation of quantum mechanics. It has been discussed in some trajectory interpretations such as Bohmian mechanics and stochastic mechanics. New questions arise when the domain of probability extends to the complex space, including the generation of complex trajectories, the definition of the complex probability, the relation of the complex probability to the real quantum probability, and so on. The complex treatment proposed here applies the optimal quantum guidance law to derive the stochastic differential (SD) equation governing the particle’s random motions in the complex plane. The ensemble of the complex quantum random trajectories (CQRTs) solved from the complex SD equation is used to construct the probability distribution ρc(t,x,y) of the particle’s position over the complex plane z=x+iy. The correctness of the obtained complex probability is confirmed by the solution of the complex Fokker-Planck equation. The significant contribution of the complex probability is that it can be used to reconstruct both quantum probability and classical probability, and to clarify their relationship. Although quantum probability and classical probability are both defined on the real axis, they are obtained by projecting complex probability onto the real axis in different ways. This difference explains why the quantum probability cannot exactly converge to the classical probability when the quantum number is large.

This paper presents a new optical, multi-functional, high-resolution 3-axis sensor which serves to navigate and can, for example, replace standard joysticks in medical devices such as electric wheelchairs, surgical robots or medical diagnosis devices. A light source, e.g. a laser diode is affixed to a movable axis and projects a random geometric shape on an image sensor (CMOS or CCD). The software in the downstream microcontroller identifies the geometric shape’s center, distortion and size, then calculates X, Y, and Z coordinates. These coordinates can then be processed in attached devices. The 3-axis sensor is characterized by its very high resolution, precise reproducibility and plausibility of the coordinates produced. In addition, optical processing of the signal provides a high level of safety against electromagnetic and radio frequency interference. The sensor presented here is adaptive and can be adjusted to fit a user’s range of motion (stroke and force). This recommendation aims to optimize sensor systems such as joysticks in medical devices in terms of safety, ease of use, and adaptability.

The gut-brain axis (GBA) represents a complex, bidirectional communication network that intri-cately connects the gastrointestinal tract with the central nervous system (CNS). Understanding and intervening in this axis opens a pathway for therapeutic advancements. In light of this, the current review assesses the effectiveness of neuromodulation techniques in treating neurological and gastrointestinal disorders by modulating the GBA, involving key elements such as gut micro-biota, neurotrophic factors, and proinflammatory cytokines. Through a comprehensive literature review encompassing PubMed, Google Scholar, Web of Science, and the Cochrane Library, and analyzing 182 relevant articles, this research highlights how neuromodulation can positively impact the management of functional gastrointestinal disorders (FGIDs), chronic pain, inflammation, and a range of GI disorders like Crohn's disease and ulcerative colitis. Despite existing challenges, the ability of neuromodulation to adjust disrupted neural pathways, alleviate pain, and mitigate in-flammation is significant in improving the quality of life for patients, thereby offering exciting prospects for future advancements in patient care.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can cause potentially life-threatening coronavirus disease (COVID-19). COVID-19 is a multisystem disease and is associated with significant respiratory distress, systemic hyper inflammation, vasculitis and multi-organ failures. SARS-CoV-2 causes deterioration of numerous systems with increasing evidence implying that COVID-19 affects endothelium and vascular function. The endothelium is important for preserving vascular tone and homeostasis. The overactivation and dysfunction of endothelial cells are significant outcomes of severity in patients with COVID-19. The Angiopoietin 1/Tie 2 pathway plays an important role in endothelium quiescence and vessel stability. The disruption of Angiopoietins/Tie balance affects vessel contact barrier and leads to vessel leakage, and this in turn causes endothelial dysfunction. Although vascular instability through SARS-CoV-2 is associated with endothelial dysfunction, it is still not understood if the virus affects Angiopoietin/Tie axis directly or via other mechanisms such as cytokine storm and/or immune response associated with the infection. This review provides an overview of the impact SARS-CoV-2 has on endothelial function and more specifically the Angiopoietin/Tie pathway.

Lung cancer accounts for the highest number of deaths among men and women worldwide. Although extensive therapies, either alone or in conjunction with some specific drugs, continue to be the principal regimen for evolving lung cancer, significant improvements are still needed to understand the inherent biology behind progressive inflammation and its detection. Unfortunately, despite every advancement in its treatment, lung cancer patients display different growth mechanisms and continue to die at significant rates. Autophagy, which is a physiological defense mechanism, serves to meet the energy demands of nutrient-deprived cancer cells and sustain the tumor cells under stressed conditions. In contrast, autophagy is believed to play a dual role during different stages of tumorigenesis. During early stages, it acts as a tumor suppressor, degrading oncogenic proteins; however, during later stages, autophagy supports tumor cell survival by minimizing stress in the tumor microenvironment. The pivotal role of the IL6-IL17-IL23 signaling axis has been observed to trigger autophagic events in lung cancer patients. Since the obvious roles of autophagy are a result of different immune signaling cascades, systems biology can be an effective tool to understand these interconnections and enhance cancer treatment and immunotherapy. In this review, we focus on how systems biology can be exploited to target autophagic processes that resolve inflammatory responses and contribute to better treatment for carcinogenesis.

The flow field around a straight chain of multiple slip spherical particles rotating steadily in an incompressible Newtonian fluid about their line of centers is analyzed at low Reynolds numbers. The particles may vary in radius, slip coefficient, and angular velocity, and they are permitted to be unevenly spaced. Through the use of a boundary collocation method, the Stokes equation governing the fluid flow is solved semi-analytically. The interaction effects among the particles are found to be noteworthy under appropriate conditions. For the rotation of two spheres, our collocation results for their hydrodynamic torques are in good agreement with the analytical asymptotic solution in the literature obtained by using a method of twin multipole expansions. For the rotation of three spheres, the particle interaction effect indicates that the existence of the third particle can influence the torques exerted on the other two particles noticeably. The interaction effect is stronger on the smaller or less slippery particles than on the larger or more slippery ones. Torque results for the rotation of chains of many particles visibly show the shielding effect among the particles.

‘Dysbiosis’ of the adult gut microbiota, in response to challenges such as infection, altered diet, stress, and antibiotics treatment has been recently linked to pathological alteration of brain func-tion and behavior. Moreover, gut microbiota composition constantly controls microglia matura-tion as revealed by morphological observations and gene expression analysis. However, it is un-clear whether gut microbiota influences microglia functional properties and crosstalk with neu-rons, known to shape and modulate synaptic development and function. Here, we investigated how antibiotic mediated alteration of the gut microbiota influences microglial and neuronal functions in adult mice hippocampus. Hippocampal microglia from adult mice treated with oral antibiotics exhibited increased microglia density, altered basal patrolling activity, and impaired process rearrangement in response to damage. Patch clamp recordings at CA3-CA1 synapses revealed that antibiotics treatment alters neuronal functions, reducing spontaneous postsynaptic glutamatergic currents and decreasing synaptic connectivity, without reducing dendritic spines density. The effect of dysbiosis on neuronal functions are mediated by microglia-neuron cross-talk through the CX3CL1-CX3CR1 axis, as antibiotics treatment of CX3CR1 deficient mice, mod-ulates microglia density and processes rearrangement leaving unaltered synaptic function. To-gether, our findings show that the antibiotics alteration of gut microbiota impairs synaptic effi-cacy, probably through CX3CL1-CX3CR1 signaling supporting microglia as a major player in in the gut-brain axis, and in particular in the gut microbiota-to-neuron communication pathway.

There is robust evidence that major depression (MDD) is accompanied by a low-grade activation of the immune-inflammatory response system, which is involved in the pathophysiology of this disorder. It is also becoming apparent that glia cells are in reciprocal communication with neurons and orchestrate various neuromodulatory, homeostatic, metabolic, and immune mechanisms and have a crucial role in neuroinflammatory mechanisms in MDD. Those cells mediate the central nervous system (CNS) response to systemic inflammation and psychological stress, but at the same time, they may be an origin of the inflammatory response in the CNS. The sources of activation of the inflammatory response in MDD are immense, however, in recent years, it is becoming increasingly evident that the gastrointestinal tract with gut-associated lymphoid tissue (GALT) and increased intestinal permeability to bacterial LPS and food-derived antigens contribute to activation of low-grade inflammatory response with subsequent psychiatric manifestations. Furthermore, an excessive permeability to gut-derived antigenic material may lead to subsequent autoimmunities which are also known to be comorbid with MDD. In this chapter, we discuss fascinating interactions between the gastrointestinal tract, increased intestinal permeability, intestinal microbiota, and glia-neuron crosstalk, and their roles in the pathogenesis of the inflammatory hypothesis of MDD. To emphasize those crucial intercommunications for the brain functions, we propose the term of microbiota-gut-immune-glia (MGIG) axis.

Physical-law based models are widely utilized in the aerospace industry. One such use is to provide flight dynamics models for use in flight simulators. For human-in-the-loop use, such simulators must run in real-time. Due to the complex physics of rotorcraft flight, to meet this real-time requirement, simplifications to the underlying physics sometimes have to be applied to the model, leading to model response errors in the predictions compared to the real vehicle. This study investigated whether a machine-learning technique could be employed to provide rotorcraft dynamic response predictions, with the ultimate aim of this model taking over when the physics-based model's accuracy degrades. In the current work, a machine-learning technique was employed to train a model to predict the dynamic response of a rotorcraft. Machine learning was facilitated using a Gaussian Process (GP) non-linear autoregressive model, which predicted the on-axis pitch rate, roll rate, yaw rate and heave responses of a Bo105 rotorcraft. A variational sparse GP model was then developed to reduce the computational cost of implementing the approach on large data sets. It was found that both of the GP models were able to provide accurate on-axis response predictions, particularly when the input contained all four control inceptors and one lagged on-axis response term. The predictions made showed improvement compared to a corresponding physics-based model. The reduction of training data to one-third (rotational axes) or one-half (heave axis) resulted in only minor degradation of the GP model predictions.

The application of numerical simulation methods for studying vertical-axis wind turbines offers significant advantages over conventional horizontal-axis wind turbines regarding wind energy utilisation, start-up wind speed, and environmental impact. This paper aims to investigate and establish the aerodynamic design performance of asymmetrical (NACA 4412) airfoils used in the application of vertical-axis wind turbines. The computational fluid dynamics (CFD) simulation uses Ansys software based on the Reynolds Averaged Navier-Stokes (RANS) equations. The aerodynamic parameters (pressure and velocity) are evaluated and compared within a range of angles of attack (AoA) 5-12 degrees at a fixed Reynolds number, as is a usual condition for wind turbine application. The lift coefficient (Cl), drag coefficient (Cd), and Cl/Cd ratio are obtained within the range AoA for the asymmetrical airfoils, and the performances have been predicted using the potential flow panel and CFD methods. This study suggests that while Xfoil may not be as precise as computational fluid dynamics (CFD), its predicted lift and drag coefficients generally align with experimental results. These help us to understand the best air-foil selection in a wind turbine application and predict its optimum AoA at which it performs at its best.

Prototypical functions of the chemokine receptor CCR6 include immune regulation by manoeuvring cell chemotaxis and selective delimiting of the pro-inflammatory TH17 and regulatory Treg subsets during chronic or acute systemic inflammation. Inhibition of CCR6 is proposed to attenuate disease symptoms and promote recuperation of multiple inflammatory and autoimmune disorders. Prescription medicines with pharmacodynamics involving the inhibition of the chemokine axis CCR6-CCL20 is very limited. Developing such therapeutics is still at an early experimental stage which has mostly utilized pre-clinical models and neutralizing mono or polyclonal antibodies against either partner, CCR6 or CCL20. Other methods have been constitutive use of small molecules as peptide inhibitors or small interfering ribonucleic acid (siRNA) to interfere with transcription at the nuclear level. We in our review aim at introducing the wide array of potential CCR6-CCL20 inhibitors that have been tried to date in the research field with accent on attendant immune-modulator capacity and which are immensely promising compounds as forerunners of future curatives. 16 different tractable inhibitors of the CCR6-CCL20 duo have been identified to possess high medicinal potential to the drug developers worldwide to treat autoimmune and inflammatory diseases. A multitude of antibody preparations are already available in the current pharmaceutical market as patented treatment for diseases in which the CCR6-CCL20 axis is operative, yet must be used only as supplements with existing routinely prescribed medication as they collectively produce adverse side effects. Novel inhibitors are needed to evaluate this invaluable therapeutic target which holds much promise in the research and development of complaisant remedies for inflammatory diseases.

Long Covid is a heterogeneous clinical condition in which Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and brain fog stand out among the different clinical symptoms and syndromes. The cerebral metabolic alterations and neuroendocrine disorders seem to constitute an important part of Long Covid. Given the substantial lack of drugs and effective therapeutic strategies, hypothalamic phospholipid liposomes which have been on the market for several years as adjuvant therapy of cerebral metabolic alterations resulting from neuroendocrine disorders, can be taken into consideration in an overall therapeutic strategy that aims to control the Long Covid associated symptoms and syndromes. Their pharmacological mechanisms and clinical effects strongly support their usefulness in Long Covid. Our initial clinical experience corroborates this rationale. Further research is imperative in order to obtain robust clinical evidence.

A method was developed to perform shape optimization of a tidal stream turbine hydrofoil using a multi-objective genetic algorithm. A bezier curve parameterized the refrence hydrofoil profoil NACA 63815. Shape optimization of this hydrofoil maximized its lift-to-darg ratio and minimized its pressure coefficient, thereby increasing the turbines power output power and improving its cavitation characteristics. The Elitist Non-dominated Sorting Genetic Algorithm (NSGA-II) was employed to perform the shape optimization. A comparative study of two-and three-dimensional optimizations was carried out. The effect of varing the angle of attack on the quality of optimized results was also studied. predictions based on two-dimensional panel method results was also studied. Preditions based on a two-dimensional panel method and on a computational fluid dynamics code were compared to experimental measurments.

The size of the home is considered the most critical issue affecting the quality of life. This can be measured by the quality of the house and its environment. This paper highlights the housing quality index at the urban axis level in Bistrita-Nasaud county and the impact of socioeconomic activities on the index. The Household Quality of Life Index (HQLI) was calculated based on 11 variables. Household quality of life comprises two distinctive indices: the Housing Conditions Index (HCI) and the Asset Possession Index (API). The study found a variation in the housing condition variables across the urban focus areas. The impact of the socioeconomic environments is disproportionately dependent on the social-economic profile of the urban environments that make up the Urban Axis and the related economic activities that take place in the area of influence in the administrative-territorial units and the variability of the Housing Conditions Index This can be measured by the quality of the house and its environment. This paper highlights the housing quality index at the urban axis level in Bistrita-Nasaud county and the impact of socioeconomic activities on this index. The study area comprises territories in the municipality of Bistrita. The socio-economic context of the area has been the basis for understanding the patterns of evolution identified in the urban landscape, and being a driver in ongoing urban transformations and processes. The impact of the socio-economic is disproportionate to the socioeconomic profile of the urban environments that make up the Urban Axis and the economic activities related to the economic activities taking place in the catchment area in the administrative-territorial units, hence the variability of the Housing Conditions Index which is a system Housing Quality Indicator (HQI) is a tool for measuring and evaluating housing systems based on quality and not just cost.

Health-Related Quality of Life (HRQoL) encompasses the comprehensive evaluation of an indi-vidual's health and well-being across multiple dimensions. Mindfulness, recognized as a scientifi-cally supported strategy for anxiety management, plays a role in enhancing both physical and mental health. The Gut-Brain Axis (GBA) serves as the bidirectional communication link between the gastrointestinal system and the central nervous system. This study aims to explore the associa-tion between Mindfulness and factors influencing the GBA in both healthy individuals and those with Inflammatory Bowel Diseases (IBD). A cross-sectional investigation involved 338 adults, in-cluding 50 IBD patients, utilizing validated Greek scales for Mindfulness (MAAS-15), Mediterra-nean Diet (14-MEDAS), and HRQoL (EQ-5D-5L). The questionnaire gathered demographic, an-thropometric, and lifestyle data. Among healthy participants, EQ-5D-5L showed a moderate cor-relation with the MAAS-15 scale (r=0.389, p

This review investigates the multifaceted role of the p66Shc adaptor protein and the gut microbiota in regulating mitochondrial function and oxidative stress, and their collective impact on the pathogenesis of chronic diseases. The study delves into molecular mechanisms by which p66Shc influences cellular stress responses through Rac1 activation, Forkhead-type transcription factors inactivation, and mitochondria-mediated apoptosis, alongside modulatory effects of gut microbiota-derived metabolites and endotoxins. Employing an integrative approach, the review synthesizes findings from a broad array of studies, including molecular biology techniques and analyses of microbial metabolites' impacts on host cellular pathways. The results underscore a complex interplay between microbial metabolites, p66Shc activation, and mitochondrial dysfunction, highlighting the significance of the gut microbiome in influencing disease outcomes through oxidative stress pathways. Conclusively, the review posits that targeting the gut microbiota-p66Shc-mitochondrial axis could offer novel therapeutic strategies for mitigating the development and progression of metabolic diseases. This underscores the potential of dietary interventions and microbiota modulation in managing oxidative stress and inflammation, pivotal factors in chronic disease etiology.

Terahertz tomography is a promising method among non-destructive inspection techniques to detect faults and defects in dielectric samples. Image quality recently significantly improved through the incorporation of a priori information and off-axis data. However, this improvement has come at the cost of increased measurement time. To aim toward industrial applications, it is therefore necessary to speed up the measurement by parallelizing the data acquisition employing multi-channel setups. In this work, we present two tomographic frequency-modulated continuous wave (FMCW) systems working at a bandwidth of 230-320 GHz, equipped with an eight-channel detector array, and compare their imaging results with a single-pixel setup. While in the first system, the additional channels are used exclusively to detect radiation refracted by the sample, the second system features an f-θ lens, focusing the beam at different positions on its flat focal plane, and thus utilizing the whole detector array directly. The usage of the f-θ lens in combination with a scanning mirror eliminates the necessity of the formerly used slow translation of a single-pixel transmitter. This opens up the potential for a significant increase in acquisition speed, in our case by a factor of four to five, respectively.

The “Gut-Liver Axis” refers to physiological bidirectional interplay between the gut and its microbiota and the liver which, in health, occurs thanks to a condition of immune tolerance. In recent years, several studies have shown that, in case of modifications of gut bacterial homeostasis or impairment of intestinal barrier functions, cholangiocytes, which are the epithelial cells lining the bile ducts, activate innate immune responses against gut-derived microorganisms or bacterial products that reach the liver via enterohepatic circulation. Intestinal dysbiosis or impaired intestinal barrier functions expose cholangiocytes to an increasing amount of microorganisms and may exacerbate inflammatory responses thus leading to fibrotic remodeling of the organ. The present review focuses on the role of the gut liver axis in the pathogenesis of cholangiopathies.

Blisks subjected to rough machining for channel creation must undergo finishing processes, and such processes must achieve the required tolerance limits. A high-quality surface finish and predictable long tool life are critical for the finish milling of blisks. Accordingly, the aim of this study was to optimize parameters for the finish machining of an Inconel 718 alloy monolithic blisk. Ball-cone mills were used to machine the blade surface at a constant depth. A sensory tool holder was used to collect cutting force signals during machining, and a digital microscope was used to examine tool wear. The surface texture measuring instrument was used to measure blisk blade surface roughness to evaluate processing quality. This study manipulated two cutting parameters, namely cutting speed and feed per tooth, and investigated their effects. The relationship between cutting conditions and machining efficiency was analyzed. According to the experimental results, we identified a set of optimal parameters for marginal tool wear and fast cutting speeds and then estimated the corresponding tool life by using the derived parameters.

The three-axis stabilization geostationary remote sensing satellite features high time resolution and plays a significant role in weather forecasting and environmental monitoring. With the future development of satellite technology, we propose a rapid geolocation algorithm for three-axis stabilization geostationary remote sensing satellites from the perspective of software algorithms. The method assesses conventional remote sensing data geolocation methods and the coordination group for meteorological satellites (CGMS, Coordination Group for Meteorological Satellites) nominal grid publishing format. First, the initial incident viewing vector of each detector on the sensor was constructed. Then, by reflecting the satellite platform's east-west and north-south mirrors, the outgoing vector of the payload coordinate system was obtained. This vector was converted to the satellite body coordinate system and, subsequently, to the satellite orbit coordinate system. The conversion of the earth-fixed coordinate system and the mirror rotation angle under ideal CGMS grid conditions were obtained, and the mirror rotation angle was converted to the corresponding CGMS nominal grid position to complete data positioning. The algorithm omits the complex process of calculating the intersection point between the viewing vector and the geodetic ellipsoid sphere from the earth-fixed coordinate system, resulting in an 83.3% improvement in computational efficiency without compromising positioning accuracy compared with conventional geolocation methods. This algorithm greatly improves the processing efficiency of geostationary meteorological satellite positioning, but its limitation is that the data processing results must be released in the CGMS nominal grid format.

Gut microbiota affects progression of rheumatoid arthritis (RA). The present study aims at investigating the protective potential of Bifidobacterium longum cell wall lipoproteins (Lpps) shown to modulate the intestinal microbiome and prevent osteoarthritis. Arthritis was induced by collagen (CIA) or anti-collagen antibodies (CAIA) injection. Intake of 0.5 mg Lpps /L, but not 0.25 and 1mg Lpps/L significantly alleviated RA symptoms in CIA DBA/1OOaHsd mice. Arthritis index (AI) was also reduced in CAIA mice. In CIA protected group, colon Ligilactobacillus murinus, caecal Lactobacillus johnsonii and spleen weight correlated with AI, whereas the reverse was observed with splenic CD11c+ dendritic cells (cDCs). The unprotected CIA Lpps group harbored higher caecal and colon E. coli and lower caecal L.murinus. Lpps administration to CAIA mice after arthritis induction led to lower colon E. plexicaudatum counts. Splenocytes from CIA protected mice triggered by LPS secreted higher Il-10 than control ones. However, higher IL-10 response was not elicited in gnotobiotic RA mice splenocytes with lower cDCs recruitment. Labeled bacteria with Lpps signal were detected in CIA mice bone marrow (BM) cDCs 5 and 16h post-gavage but not in Peyer’s patches and spleen. In vitro uptake of Lpps by primary BM and thymus cells was observed within 24h. FACS analysis detected the Lpps signal in the plasmacytoid cell compartment but not in cDCs. In conclusion, Lpps dosing is critical for preventing arthritis progression and appropriately modulating the microbiome. Our results also highlight the possible triggering of the immune system by Lpps.

Serine/threonine kinase (AKT) signaling regulates diverse cellular processes and is one of the most important aberrant cell survival mechanisms associated with tumorigenesis, metastasis, and chemoresistance. Targeting AKT has become an effective therapeutic strategy for the treatment of many cancers. AKT3 (PKBγ), the least studied isoform of the AKT family, has emerged as a major contributor to malignancy. AKT3 is frequently overexpressed in human cancers, and many regulatory oncogenic or tumor suppressor small non-coding RNAs (ncRNAs), including microRNAs (miRNAs), have recently been identified to be involved in regulating AKT3 expression. Therefore, a better understanding of regulatory miRNA/AKT3 networks may reveal novel biomarkers for diagnosis of patients with cancer and provide invaluable information for developing more effective therapeutic strategies. The aim of this review is to summarize current research progress in the isoform-specific functions of AKT3 in human cancers and the roles of dysregulated miRNA/AKT3 in specific types of human cancers.

The liver is not only a digestive gland, but also an immune tissue that receives a double infusion from the hepatic artery and the hepatic portal vein. Receiving 80% of its blood supply from the intestine through the hepatic portal vein system, the liver is enriched with a large number of innate immune cells, which carry out the process of immune response by detecting pathogens entering the organism through the intestine. The intestine and liver communicate extensively through the bile ducts, portal vein and the somatic circulation, a bidirectional communication known as the intestinal-liver axis. The mammalian gut is considered an important microbial ecosystem. The interplay between the natural immune system and microbes coordinates the physiology of the whole organism, and in specific mammalian lineages, there is a dependency between the host and its associated microbes. To this end, we explored the regulatory mechanisms of natural immunity genes at the genome-wide level. Based on comparative genomics, 1473 bovine natural immunity genes were obtained by collecting the latest reports of human natural immunity genes and updated bovine genomic data for comparison, and a bovine natural immunity gene database was initially constructed to screen and match calf liver natural immunity differential genes mainly affected by the phylum Mimosoidea and the phylum Thick-walled Bacteria, and 16 differentially expressed natural immunity genes were obtained. In addition, the results of IPA analysis indicated that the upstream factor IL-2 initiated the PI3K/AKt/mTOR, mitogen-activated protein kinase (MAPK) pathway and JAK/STAT5 pathway, leading to the liver's involvement in gut microbial immune regulation.

The dynamics of a low-energy charged particle in an axis-symmetric magnetic field is known to be a regular superposition of periodic–although possibly incommensurate–motions. The projection of the particle orbit along the two non-ignorable coordinates (x,y) may be expressed in terms of each other: y=y(x), yet–to our knowledge–such a functional relation has never been directly produced in literature, but only by way of a detour: first, equations of motion are solved, yielding x=x(t),y=y(t), and then one of the two relations is inverted, x(t)→t(x). In this paper we present a closed-form functional relation which allows to express coordinates of the particle’ orbit without the need to pass through the hourly law of motion.

The basic equation for estimating the aerodynamic power captured by an Anderson Vertical Axis Wind Turbine (AVAWT) is a solution of the Navier-Stokes(N-S) equations for a baroclinic, inviscid flow. In a nutshell, the pressure difference across the AVAWT is derived from Bernoulli’s equation; an upshot of the integration of the N-S momentum equation for a baroclinic inviscid flow, Euler’s momentum equation. The resulting expression for the pressure difference across the AVAWT rotor is plotted as a function of freestream speed. Experimentally determined airstream speeds at the AVAWT inlet and outlet, coupled with corresponding freestream speeds are used in estimating the aerodynamic power captured. The aerodynamic power is subsequently used in calculating the aerodynamic power coefficient of the AVAWT. The actual power coefficient is calculated from the power generated by the AVAWT at various free stream speeds and plotted as a function of the latter. Experimental results show that, at all free stream speeds and tip speed ratios, the aerodynamic power coefficient is higher than the actual power coefficient of the AVAWT. Consequently, the power generated by the AVAWT prototype is lower than the aerodynamic power captured, given the same inflow wind condition.

A modified free-wake vortex ring model is proposed to compute the dynamics of a floating horizontal-axis wind turbine. The model is divided into two parts. The near wake model uses a blade bound vortex model and trailed vortex model, which is developed based on vortex filament method. By contrast, the far wake model is based on the vortex ring method. The proposed model is a good compromise between accuracy and computational cost, for example when compared with more complex vortex methods. The present model is used to assess the influence of floating platform motions on the performance of a horizontal-axis wind turbine rotor. The results are validated on the 5MW NREL rotor and compared with other aerodynamic models for the same rotor subjected to different platform motions. It was found that the results from the proposed method are more reliable than the results from BEM theory especially at small angles of attack in the region of low wind speeds, on the one hand, and high wind speeds with blade pitch motions, on the other hand. And also the proposed method is less time consuming and has similar accuracy when comparing with more advanced vortex based methods.

In this paper, we define Ulisse Dini-type helicoidal hypersurface with spacelike axis in Minkowski 4-space ${\mathbb{E}}_1^4$ . We compute the Gaussian and the mean curvature of the hypersurface. Moreover, we obtain some special symmetry to the curvatures when they are flat and maximal.

Vertical-axis wind turbines (VAWTs) are receiving more and more attention as they involve simple design, cope better with turbulence and are insensitive to wind direction which has a huge impact on the cost since the yaw mechanism is not needed. However, VAWTs still suffer from low conversion efficiency. As a results tremendous efforts are exerted to improve its efficiency which mainly focus on two methods regardless of whether the study is a CFD simulation or a field test or lab test experiment. An active approach which involves the modification of the rotor itself such as the blade design, angle, trailing and leading edges, inner blades, chord thickness, contra-rotating rotor, etc. While the second approach involves passive techniques where the flow is directed to optimally face the downwind rotor by mounting a guiding vane such as a diffuser or other shapes at the upwind position of the rotor. Among all techniques undertaken, the CRWT rotor technique seems to be the most effective with an output even comparable to that of Horizontal Axis Wind Turbines (HAWT), while the Savonius rotor received more attention compared to other designs of VAWTs. Apart from technological issues, it was also suggested that geographical issues such as proper site siting of the wind turbine rotor at a particular location where a uniform flow could be guaranteed is of paramount importance to ensure an effective conversion capacity of wind turbines.

FacioScapuloHumeral Dystrophy (FSHD) is one of the most prevalent inherited muscle disorders, and is linked to the inappropriate expression of the DUX4 transcription factor in adult muscles. The deregulated molecular network causing FSHD skeletal muscle dysfunction and pathology is still not well understood. It has been shown that the hypoxia response factor HIF1α is critically disturbed in FSHD and has a major role in DUX4 induced cell death. In this study, we further explore the relationship between DUX4 and HIF1α. We found that the DUX4 and HIF1α link differed according to the stage of myogenic differentiation and was conserved between human and mouse muscle. Furthermore, we found that HIF1α knock-down in a mouse model of DUX4 local expression exacerbated DUX4-mediated muscle fibrosis. Our data indicate that the suggested role of HIF1α in DUX4 toxicity is complex and that targeting HIF1α might be challenging in the context of FSHD therapeutic approaches.

The central nervous system (CNS) and the human gastrointestinal (GI) tract communicate through the gut-brain axis (GBA). Such communication is bi-directional and involves neuronal, endocrine and immunological mechanisms. The scientific data are mounting that gut microbiota is a source of a number of neuroactive and immunocompetent substances, which shape the structure and function of brain regions involved in control of emotions, physical activity and cognition. Most of GI maladies are associated with altered transmission within the GBA and influenced both by genetic and environmental factors. Current treatment protocols widely advocated for the treatment of GI disorders may positively or adversely affect the composition of intestinal microbiota with diverse impact on therapeutic outcome. The alterations of gut microbiota have been associated with mood and depressive disorders. and mental health is frequently altered in the course of many GI and non-GI ailments. Deregulation of the GBA may constitute a grip point for the development of diagnostic tools and personalized microbiota-based therapy. For example next generation sequencing (NGS) offers detailed analysis of microbiome footprints in patients with mental and GI disorders. Psychobiotics are new class of beneficial bacteria, with documented efficacy in the treatment of gut-brain axis disorders.

Optimizing the NACA0015 airfoil which is widely applied in small-scale vertical axis wind turbine to make it has a better aerodynamic performance. In the optimization process, using CST parameterization method to perturb the airfoil geometry, the thickness and camber of the airfoil are selected as the constraint, and the value of the maximum tangential force coefficient is chosen as the objective function, the genetic algorithm based on non-dominated sorting (NSGA-II)is selected as an optimization method, calculates the aerodynamic performance of the airfoil by applying the approach of combining XFOIL program and Viterna-Corrigan post-stall mode ,and establishes the optimizing process by the optimization software modefrontier for NACA0015 airfoil’s muti-point optimization, validate the airfoil’s performance with CFD finally. The result illustrates that, by comparing with the NACA0015 airfoil, the optimized airfoil’s lift to drag ratio is improved over a wide range of attack angles, the stall performance is more gentle. The maximum lift coefficient, the maximum lift-drag ratio and the maximum tangential force coefficient are increased by 7.5%,9 and 8.87%, respectively. The optimized airfoil has a wide variable condition performance, more suitable for the operating conditions of a vertical axis wind turbine. Finally, predict the rotor efficiency with optimized airfoil and NACA0015 airfoil for different tip speed ratios and different solidities with multiple streamtube model, the result shows the rotor with optimized airfoil has a higher efficiency.

Understanding the pathophysiology of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is critical for advancing treatment options. This review explores the novel hypothesis that herpesviruses' infection of endothelial cells (ECs) may underlie ME/CFS symptomatology. We review evidence linking herpesviruses to persistent EC infection and the implications for endothelial dysfunction, encompassing blood flow regulation, coagulation, and cognitive impairment – symptoms consistent with ME/CFS and Long COVID. The paper provides a synthesis of current research on herpesvirus latency and reactivation, detailing the impact on ECs and subsequent systemic complications, including latent modulation and long-term maladaptation. We suggest that the chronicity of ME/CFS symptoms and the multisystemic nature of the disease may be partly attributable to herpesvirus-induced endothelial maladaptation. Our conclusions underscore the necessity for further investigation into the prevalence and load of herpesvirus infection within ECs of ME/CFS patients. This review offers a conceptual advance by proposing an endothelial infection model as a systemic mechanism contributing to ME/CFS, steering future research towards potentially unexplored avenues in understanding and treating this complex syndrome.

To investigate the optimum layouts of small vertical axis wind turbines, a two-dimensional analysis of dynamic fluid body interaction is performed via computational fluid dynamics for a rotor pair in various configurations. The rotational speed of each turbine rotor (diameter: D = 50 mm) varies based on the equation of motion. First, the dependence of rotor performance on the gap distance (gap) between two rotors is investigated. For parallel layouts, counter-down (CD) layouts with blades moving downwind in the gap region yield a higher mean power than counter-up (CU) layouts with blades moving upwind in the gap region. CD layouts with gap/D = 0.5–1.0 yield a maximum average power that is 23% higher than that of an isolated single rotor. Assuming isotropic bidirectional wind speed, co-rotating (CO) layouts with the same rotational direction are superior to the combination of CD and CU layouts regardless of the gap distance. For tandem layouts, the inverse-rotating configuration (IR) shows an earlier wake recovery than the CO configuration. For 16-wind-direction layouts, both the IR and CO configurations indicate similar power distribution at gap/D = 2.0. For the first time, this study demonstrates the phase synchronization of two rotors via numerical simulation.

The global energy crisis has lead researchers explore other sources of energy like wind, resulting in a wide acceptance of wind turbines. Vertical axis wind turbines (VAWT) more suitable for small scale application in urban conditions than their horizontal-axis counterparts. A Helical bladed VAWT would reduce the ripple effect when compared to Straight bladed VAWT. The effect of the blade helix angle on the aerodynamic performance of VAWT using 3D numerical simulations is studied. Turbulence modelled using 4-Equation transition SST k-w model. Three different helix angles of 60, 90 and 120 of a 3 bladed VAWT operating across different tip speed ratios were studied. The 60 helical bladed VAWT was found to perform better than all other helical bladed and straight bladed VAWT. Standard deviation of the moment coefficient generated by a blade plotted against 360 of azimuth rotation revealed that the ripple effect on the shaft produced by cyclic loading of the straight blade is considerably reduced upon introduction of helix angle, with 120 helical blade giving lowest standard deviation. The analysis has been done for the percentage of power generated by each quartile of flow and the contribution of each section of the blade. A comparative study was also conducted between different helical bladed VAWT and straight bladed VAWT. Flow feature analysis also revealed the reasons behind secondary peaks and the performance improvement when tip speed ratio increases. Wake structure analysis and flow contours were also studied for a better understanding of the flow field.

In present study, the effect of Inonotus Obliquus extracts used in traditional medicine was investigated on the expression of matrix metalloproteinases-1 (MMP-1) in the normal human dermal fibroblasts. As shown our results, extracts of Inonotus Obliquus decreased MMP1 expression in oxidative stress-exposed normal human dermal fibroblasts. Additionally, Inonotus Obliquus extracts decreased AP-1 transcriptional activity and phospho-JNK in oxidative stress exposed normal human dermal fibroblasts. The results suggest that Inonotus Obliquus extracts decreased MMP1 expression using decreasing AP-1 transcriptional activity and phospho-JNK. Therefore, Inonotus Obliquus extracts has potential to reduce formation of wrinkle and to use as a cosmetic ingredient.

In the Korean construction industry, legal and institutional safety management improvements are continually being pursued. However, there was a 4.5% increase in the number of workers’ deaths at construction sites in 2017 compared to the previous year. Failure to wear safety helmets seems to be one of the major causes of the increase in accidents, and so it is necessary to develop technology to monitor whether or not safety helmets are being used. However, the approaches employed in existing technical studies on this issue have mainly involved the use of chinstrap sensors and have been limited to the problem of whether or not safety helmets are being worn. Meanwhile, improper wearing, such as when the chinstrap and harness fixing of the safety helmet are not properly tightened, has not been monitored. To remedy this shortcoming, a sensing safety helmet with a three-axis accelerometer sensor attached was developed in this study. Experiments were performed in which the sensing data were classified whether the safety helmet was being worn properly, not worn, or worn improperly during construction workers’ activities. The results verified that it is possible to differentiate among wearing status of the proposed safety helmet with a high accuracy of 97.0%

Nearly Zero Energy Buildings (NZEBs) play a key role in the world energy transition and this is motivating the scientific community to develop innovative electrical and thermal systems, characterized by very high efficiency to specifically address the energy needs of modern buildings. Naturally, the integration on buildings of latest generation PV-systems helps to satisfy this need and, having in mind this objective, an innovative and highly efficient BIPV-system is presented and discussed in this paper. First, the proposed PV-system is purpose-built to be fully integrated into a variety of buildings and, preferably, into their rooftop. It is based on a certain number of innovative rotating and bifacial PV-modules which are specifically made to be installed “under-glass”, within a likewise custom-made transparent casing. Each of the aforementioned PV-module has the form of single row of bifacial PV-cells and is equipped with two special terminations; the PV-modules are then installed inside their transparent casing, side by side and suitably spaced from each other. Thanks to the aforementioned properties, the PV-modules can rotate around their central longitudinal axis, by using a very low-power, reliable and efficient mono-axial solar tracking system. Finally, by the aforementioned way, the proposed PV-system assumes – de facto - the form of a transparent BIPV-generator (PV-skylight), equipped with an innovative “under-glass” single axis solar tracking system. Once the proposed PV-generator is fully integrated into a building, it generates electricity and, additionally, helps to improve both the whole energy performances and the aesthetic appearance of the building. The electricity generation and illuminance performances of the proposed BIPV-generator are experimentally tested by using a low-power home-made prototype driven by different solar tracking logics and under different operating conditions; the most relevant results are summarized and extensively discussed.

The goal of this study was to analyze the instability during stepping of young and older adults at fast and spontaneous speed. To this aim, the anteroposterior and the mediolateral distances between the body center of mass (COM) and the minimum moment axis (MMA) were computed. A total of 15 young adults (25y.o. [19-29]) and 15 older adults 68.7y.o. [63-77] volunteered for this study. For the computation of the distances, a complete biomechanical protocol combining two force platforms and a 3D motion capture analysis system was setup. The subjects were equipped with 47 reflective markers and were modeled as a frictionless multibody with 19 segments, 18 joints and 42 degrees of freedom and were asked to perform a stepping at both speeds. The stepping was divided in 5 phases with successive swing and double stance phases. The greater instability was observed during the swing phases. The distances indicate a significant higher instability at fast speed for both groups (p &lt; 0.001) for all the phases. The anteroposterior distance also increases significantly for older adults highlighting greater instability while no differences were observed for the mediolateral distance all along the 5 phases suggesting higher risks of backward of forward falls during stepping.

The aim of this study was to create a novel machine learning (ML) algorithm for predicting the post-pubertal mandibular length and Y-axis in females. Cephalometric data from 176 females with Angle Class I occlusion were used to train and test 7 ML algorithms. For all ML methods tested, the mean absolute errors (MAEs) for the 2-year prediction ranged from 2.78-5.40 mm and 0.88-1.48 degrees, respectively. For the 4-year prediction, MAEs of mandibular length and Y-axis ranged from 3.21-4.00 mm and 1.19-5.12 degrees, respectively. The most predictive factors for post-pubertal mandibular length were mandibular length at previous timepoints, age, sagittal positions of the maxillary and mandibular skeletal bases, mandibular plane angle, and anterior and posterior face heights. The most predictive factors for post-pubertal Y-axis were Y-axis at previous timepoints, mandibular plane angle, and sagittal positions of the maxillary and mandibular skeletal bases. ML methods were identified as capable of predicting mandibular length within 3 mm, and Y-axis within 1 degree. Compared to each other, all of the ML algorithms were similarly accurate, with the exception of MLP regressor.

The increasing enhancement in the modulation accuracy of spatial light modulators has garnered significant attention towards real-time control technology for light fields based on these modulators. It has been empirically demonstrated that this technology possesses a remarkable capability to generate vector beams with arbitrary complex amplitude distributions. Nevertheless, past studies indicate that the generation of only one vector beam at a time has been observed. The simultaneous generation of numerous vector light fields can give rise to several challenges, including compromised picture quality, limited single mode operation, and intricate optical path configurations. In pursuit of this objective, we present a novel methodology that integrates the coding methodology of modified off-axis interferometric holography with the idea of optical superposition. This technique facilitates the concurrent generation of several vector beams. In this study, we present a demonstration of the simultaneous creation of twelve vector beams using a single spatial light modulator (SLM) as a proof of concept. Significantly, this technology has the ability to generate an unlimited quantity of vector light fields concurrently, under the assumption that the resolution of the SLM does not impose any limitations. The findings indicate that the imaging quality achieved by this technology is of a high standard. Furthermore, it is possible to separately control the beam waist radius, topological charge, polarization order, and extra phase of each beam.

Research conducted on individuals with depression reveals that major depressive disorders (MDDs) coincide with diminished levels of the inhibitory neurotransmitter γ-aminobutyric acid (GABA) in the brain, as well as modifications in the subunit composition of the primary receptors (GABAA receptors) responsible for mediating GABAergic inhibition. Furthermore, there is substantial evidence supporting the significant role of GABA in regulating stress within the brain, which is a pivotal vulnerability factor in mood disorders. Although there is substantial evidence indicating that GABA may be affecting GABA receptors in peripheral tissues, there is comparatively less evidence supporting its direct action within the brain. Emerging evidence highlights that GABA may exert beneficial effects on the brain and psyche through the gut-brain axis. GABA is readily available and approved as a food supplement in many countries. While GABA enjoys wide consumer acceptance in Eastern Asian markets, with many consumers reporting favorable effects on stress regulation, mood, and sleep, rigorous independent research is still largely lacking. Basic research, coupled with initial clinical findings, makes GABA an intriguing neuro-nutritional compound deserving of clinical studies in individuals with depression and other psychological problems.

Exposure to psychosocial stress is a risk factor for cardiovascular disease, including vascular aging, angiogenesis, and atherosclerosis-based cardiovascular disease (ACVD). Dipeptidyl peptidase-4 (DPP-4) is a complex enzyme (also called CD26) that acts as a membrane-anchored cell surface exopeptidase. DPP4 is upregulated in metabolic and inflammatory cardiovascular disorders. The widespread expression of DPP4 macrophages and immune cells and the noncatalytic function of DPP4 (also called CD26) as a signaling and binding protein across a wide range of species suggest a teleological role for DPP4 in inflammation and immune response. DPP-4 exhibits many physiological and pharmacological functions by regulating its extremely abundant substrates [e.g., stromal cell-derived factor-1α/ C-X-C chemokine receptor type-4, glucagon-like peptide-1 (GLP-1), etc.]. Over last ten year, emerging data demonstrated unexpected roles for GLP-1 and DPP-4 in extracellular and intracellular signaling, immune activation, inflammation, oxidative stress production, cell apoptosis, insulin resistance, and lipid metabolism,. This mini review has focuses on recent novel findings in this field, highlighting an imbalance between GLP-1 and DPP4 as a potential therapeutic molecular target in treatments of chronic psychological stress-related atherosclerotic cardiovascular disease in humans and animals.

Identifying appropriate animal models is critical in developing translatable in vitro and in vivo systems for therapeutic development and investigating disease pathophysiology. These animal models should have direct biological and translational relevance to the underlying disease they are supposed to mimic. Aging dogs naturally develop a cognitive decline in many aspects including learning and memory, but also exhibit human-like individual variability in the aging process. Neurodegenerative processes that can be observed in both human and canine brains include the progressive accumulation of β-amyloid (Aβ) found as diffuse plaques in the prefrontal cortex, including the gyrus proreus, the hippocampus, and in the cerebral vasculature. A growing body of epidemiological data shows that human patients with neurodegenerative diseases have concurrent intestinal lesions, and histopathological changes in the gastrointestinal (GI) tract occurs decades that evolve before neurodegenerative changes. Gut microbiome alterations also have been observed in many neurodegenerative diseases including Alzheimer’s and Parkinson’s diseases, and inflammatory CNS diseases. Interestingly, only recently has the dog gut microbiome been recognized to more closely resemble in composition and in functional overlap with the human gut microbiome as compared to rodent models. This article aims to review the physiology of the gut-brain axis (GBA), and its involvement with neurodegenerative diseases in dogs and humans. Additionally, we outline the advantages and disadvantages of traditional in vitro and in vivo models and discuss future research directions investigating major human neurodegenerative diseases such as Alzheimer’s and Parkinson’s diseases using dogs.

The gut microbiota (GM) communicates with the brain via biochemical signaling constituting the gut-brain axis, which significantly regulates the body's physiological processes. The GM dysbiosis can impact the digestive system and the functioning of the central nervous system (CNS) linked to the onset of neurodegenerative diseases. In this review, the scientific data compiled from diverse sources primarily emphasizes the neuropathological characteristics linked to the accumulation of modified insoluble proteins (such as β-Amyloid peptides and hyperphosphorylated tau proteins) in Alzheimer’s Disease (AD) and the potential impact of gut microbiota (GM) on AD susceptibility or resilience. The specific GM profile of human beings may serve as an essential tool for preventing or progressing neurodegenerative diseases like AD. This review focuses mainly on the effect of gut microfauna on the gut-brain axis in the onset and progression of AD. The GM produces various bioactive molecules that may serve as proinflammatory or anti-inflammatory signaling, contributing directly or indirectly to the repression or progression of neurodegenerative disorders by modulating the response of the brain axis. Human studies must focus on further understanding the gut-brain axis and venture to clarify microbiota-based therapeutic strategies for AD.

In order to enhance the comfort of cycling, it is imperative to investigate the effects of vibration on non-motorized bicycle riding from the perspectives of road characteristics and traffic features. Through an analysis of the mechanisms by which road and traffic conditions influence cycling vibrations, 13 influencing factors were identified. Subsequently, the non-motorized bicycle lanes in Wuhan city were selected as the subject of empirical research, where three-axis accelerometers attached to the rider's torso were employed to measure and categorize vibration comfort levels. The experimental road segments were found to exhibit comfort levels falling between slightly uncomfortable and relatively uncomfortable. Further analysis of the influencing factors was conducted using the Random Forest algorithm and Logistic Regression. The results revealed that six factors significantly impact the comfort of cycling: the presence of dedicated non-motorized bicycle lanes, the absence of physical separation between non-motorized and motorized traffic, cycling speed, the number of road surface irregularities, the presence of parking areas within the non-motorized bicycle lane, and the type of non-motorized bicycle. This study provides valuable insights into the factors affecting non-motorized bicycle lane usage and contributes to the refined design of urban non-motorized bicycle infrastructure, thereby facilitating better support for sustainable urban transportation.

The cost effective design of tidal turbines requires a good estimation of the loading cycles and their extrema that are related to the unsteady fluctuations of the current velocity. Apart from the ambient turbulence, the main source of velocity fluctuations is the presence of surface waves. In the present study, we analyse the effect of waves propagating against the current on the performance and the loads of a twin vertical axis tidal turbine by an experimental approach at a 1/20 scale. Overall, the results show little or no effect of the waves on the average power and loads compared to the condition with current only, but a significant impact on their standard deviation that rises linearly with the waves amplitude. The drag, lift and pitching moment show extended ranges up to 7.5 times higher and extreme values exceedance by 60 to 100 % with irregular waves compared to the condition without waves. Those load and power fluctuation increase are fully due to the presence of waves as the coherence function between the rotor torque or the loads and the velocity spectra exceed 0.5 on the whole wave frequency bandwidth. The results also reveal a rotational sampling of the waves by the rotors that had also been observed on horizontal axis turbines. From a structural design point of view, the authors recommand to conduct tests in irregular wave conditions as the loads range and extreme values are 1.5 to 2 times higher than those encountered with regular waves of the same significant height and period.

The human ankle is a complex joint, most commonly represented as talocrural and subtalar axes. It is difficult to locate and take in vivo measurements of the ankle joint. There are no instruments for patients lying on a bed or the floor; that can be used in outdoor or remote sites. We have developed a "Turmell-meter" to address these issues. We started with the study of ankle anatomy and anthropometry, then we used the product of exponentials’ formula to visualize the movements. Furthermore, we built a prototype using human proportions and statistics. For pose estimation, we used a trilateration method by applying tetrahedral geometry. Additionally, we computed the axis direction by fitting 3D circles, plotting the manifold and chart as an ankle joint model. We presented the results of simulations, a prototype comprising 45 parts, specifically designed draw-wire sensors, and electronics. Finally, we tested the device by capturing positions and fitting them into the bi-axial ankle model as a Riemannian manifold. The Turmell-meter is intended to be a hardware platform for human ankle joint axis estimation, it is adjustable and has an easy setup. The proposed model has the properties of a chart in a geometric manifold, we provided the details

Direct cardiac reprogramming of fibroblasts into induced cardiomyocytes (iCMs) is a promising approach but remains a challenging technology of regenerative medicine for damaged myocardium. Efforts have been focused on improving the efficiency by understanding fundamental mechanisms. One of the major challenges is that the plasticity of cultured fibroblast varies batch to batch with unknown mechanisms. Here, we noticed that a portion of in vitro cultured fibroblasts have been activated to differentiate into myofibroblasts, marked by the expression of αSMA, even in the primary cell culture of tissues. Both forskolin, which activates adenylyl cyclase and increases cAMP concentration, and TGFbeta inhibitor SB431542 can efficiently suppress myofibroblast differentiation of cultured fibroblasts. However, SB431542 improved but forskolin blocked iCM reprogramming of fibroblasts that were infected with retroviruses of Gata4, Mef2c and Tbx5 (GMT). Moreover, inhibitors of cAMP downstream signaling pathways, PKA or CREB-CBP, significantly improved the efficiency of iCM reprogramming. Consistently, inhibition of p38/MAPK, another upstream regulator of CREB-CBP, also improved reprogramming efficiency. We then investigated if inhibition of these signaling pathways in primary cultured fibroblast could improve their plasticity for reprogramming, and found that preconditioning of cultured fibroblasts with CREB-CBP inhibitor significantly improved the cellular plasticity of fibroblasts to be reprogrammed, yielding ~2-fold amount of reprogrammed iCMs compared to that of untreated control cells. In conclusion, suppression of cAMP/PKA/CREB signaling axis improves fibroblast plasticity for direct cardiac reprogramming.

Endothelial autocrine signaling is essential to maintain vascular hemostasis. There is limited in-formation about the role of endothelial autocrine signaling in regulating severe pulmonary vas-cular remodeling during the onset of pulmonary arterial hypertension (PAH). In this study, we employed the first severe PAH mouse model, Egln1Tie2Cre (Tie2Cre-mediated disruption of Egln1) mice, to identify the novel autocrine signaling mediating the pulmonary vascular endothelial cells (PVECs) hyperproliferation and the pathogenesis of PAH. PVECs isolated from Egln1Tie2Cre lung expressed upregulation of many growth factors or angiocrine factors such as CXCL12, and exhib-ited hyperproliferative phenotype in coincident with upregulation of proliferation specific tran-scriptional factor FoxM1. Treatment of CXCL12 on PVECs increased FoxM1 expression, which was blocked by CXCL12 receptor CXCR4 antagonist AMD3100 in culture human PVECs. Endo-thelial specific deletion of Cxcl12 (Egln1/Cxcl12Tie2 Cre) or AMD3100 treatment in Egln1Tie2Cre mice downregulated FoxM1 expression in vivo. We then generated and characterized a novel mouse model with endothelial specific FoxM1 deletion in Egln1Tie2Cre mice (Egln1/Foxm1Tie2Cre), and found that endothelial FoxM1 deletion reduced pulmonary vascular remodeling and right ventricular systolic pressure. Together, our study identified a novel mechanism of endothelial autocrine sig-naling in regulating PVECs hyperproliferation and pulmonary vascular remodeling in PAH.

We present a compact optical head design for wide-range and low noise displacement sensing using deep frequency modulation interferometry. The on-axis beam topology is realised in a quasi-monolithic component and relies on cube beamsplitters and beam transmission through perpendicular surfaces to keep angular alignment constant when operating in air or vacuum, which leads to the generation of ghost beams that can limit the phase readout linearity. We investigate the coupling of these beams into the non-linear phase readout scheme of DFMI and demonstrate adjustments of the phase estimation algorithm to reduce this effect. This is done through a combination of balanced detection and the inherent orthogonality of beat signals with different relative time-delays in deep frequency modulation interferometry that is a unique feature not available for heterodyne, quadrature or homodyne interferometry.

The prevalence of type-2 diabetes mellitus (T2D) is increasing worldwide and there are no long-term preventive strategies to stop this growth. Emerging research shows that perturbations in the gut microbiome significantly contribute to the development of T2D, while microbiome modulators may be beneficial for T2D prevention. However, microbiome modulators that are effective, safe, affordable, and able to be integrated daily in the diet are not yet available. Based on our previous pro- and prebiotic studies, we developed a novel synbiotic yogurt comprised of human-origin probiotics and plant-based prebiotics and investigated its impact on diet- and streptozotocin-induced T2D in mice. We compared the effects of our synbiotic yogurt to those of a commercially-available yogurt (control yogurt). Interestingly, we found that feeding of this synbiotic yogurt significantly reduced the development of hyperglycemia (diabetes) in response to high-fat diet feeding and streptozotocin compared to milk-fed controls. Surprisingly, the control yogurt exacerbated diabetes progression. Synbiotic yogurt beneficially modulated the composition of gut microbiota compared to milk; conversely, the control yogurt negatively modulated the gut microbiota by significantly increasing the abundance of detrimental bacteria like Proteobacteria and Enterobacteriaceae. In addition, the synbiotic yogurt protected intact pancreatic islet morphology compared to the milk control, while the commercial yogurt demonstrated worse effects on pancreatic physiology. These results suggest that our newly developed synbiotic yogurt protects against diabetes in mice and can be used as a modality to prevent diabetes progression.

Inflammatory bowel disease (IBD) is a CC chemokine receptor 6 (CCR6) - associated immune mediated disorder which has attracted an extensive superfluity of experimental analyses. IBD has come to the fore of varied scrutinizing owing to its complexity by nature for comprising of two synergistic sub phenotypes; Crohn’s disease (CD) and Ulcerative colitis (UC). Both these disease entities cause potent immune dysregulation followed by intense tissue damage within the gut mucosal system, initiating symptoms which are severely debilitating. Multiple causative factors are said to be responsible for IBD but direct immune dysfunction is kindled by overplay of innate and adaptive immune responses produced against a pathogenic microbial attack through the weakened or leaky gut epithelial barrier. Once immune homeostasis is not achieved by tolerating agents, the self-assertive adaptive immunity mobilize its various T and B cell cohorts initializing their allied immune mechanisms by vigorously deploying them towards the site of infection. CCR6 and its unique solitary ligand CC-chemokine ligand 20 (CCL20) are small protein molecules which are abundantly expressed by T and B lymphocytes and act as chemotactic immune-modulatory envoys that help in the deployment of the effector lymphocyte arm of the immune system, producing two directly opposing outcomes in IBD. This dichotomous immunity consists of either immune tolerance or inflammation which then develops into a chronic state, remaining catatonic to inherent immunity or targeted clinical therapy. In this review, we have chronologically identified a plethora of experimental studies radiating into 14 different compartments highlighted in the visual depiction which have employed both mouse models and clinical subjects spanning a period of nearly two decades. In doing so, we expect the research community would further benefit by tracing through the history, thereby understanding the CCR6 –CCL20 axis in IBD and identifying the gaps in literature which can be fortuitously filled in the future.

Real-time multi-axis distributed tactile sensing is a critical capability if robots are to perform stable gripping and dexterous manipulation, as it provides crucial information about the sensor-object interface. In this paper, we present an optical-based 6-axis tactile sensor designed in a fingertip shape for robotic dexterous manipulation. The distributed sensor can precisely estimate local XYZ force and displacement at ten distinct locations, and provide global XYZ force and torque measurements. Its compact size, comparable to that of a human thumb, and minimal thickness allow seamless integration onto existing robotic fingers, eliminating the need for complex modifications to the gripper. The proposed sensor design uses a simple, low-cost fabrication method. Moreover, the optical transduction approach uses light angle and intensity sensing to infer force and displacement from deformations of individual sensing units that form the overall sensor, providing distributed 6-axis sensing. The local force precision at each sensing unit in the X, Y, and Z axes is 20.89 mN, 19.19 mN, and 43.22 mN, respectively, over an local force range of approximately ±1.5 N in X and Y and 0 to -2 N in Z. The local displacement precision in the X, Y and Z axes is 56.70 μm, 50.18 μm and 13.83 μm, respectively, over a local displacement range of ±2 mm in the XY directions and 0 to -1.5mm in Z (i.e., compression). Additionally, the sensor can measure global torques, Tx, Ty and Tz, with a precision of of 1.90 N-mm, 1.54 N-mm and 1.26 N-mm, respectively. The fabricated design is showcased by integrating it with an OnRobot RG2 gripper and illustrating real-time measurements during in simple demonstration task which generate changing global forces and torques.

Adrenarche is a developmental phase that occurs only in humans and chimpanzees. It is characterized by the maturation of the adrenal zona reticularis, culminating in the synthesis and secretion of enormous amounts of dehydroepiandro-sterone sulfate (DHEAS) into the blood stream. The purpose of adrenarche, and the flooding of the circulation with DHEAS in the period preceding the onset of adult human body size, has been described as “enigmatic.” This laboratory has uncovered a previously unknown, human-specific “kill-switch” tumor suppression mechanism in which circulating DHEAS is pumped into cells that have undergone tumorigenic mutation(s)— primarily in the TP53 tumor suppressor gene. We refer to such tumorigenic single cells as singularities. The advantage of eliminating tumorigenic cells while they are still in their single cell state, before they have evolved into the heterogeneous tumor cell populations that have proven refractory to chemotherapeutic sterilization, is obvious. This is accomplished by activation of the kill-switch in singularities by de-sulfating imported DHEAS to dehydroepiandrosterone (DHEA), a potent uncompetitive inhibitor of the enzyme Glucose-6-phosphate Dehydrogenase (G6PD). G6PD is responsible for the production of most of the NADPH required for the synthesis and maintenance of activity of anti-oxidant selenoproteins, and for the ubiquinol that prevents ferroptosis. In singularities, uncompetitive inhibition of G6PD by DHEA rapidly becomes irreversible, leading to ROS/ferroptosis-mediated cell death.

Background In this study we investigated in detail the role of cannabidiol (CBD), Beta-caryophyllene (BC), or their combinations in diabetic peripheral neuropathy (DN). The key factors that contribute to DN include mitochondrial dysfunction, inflammation, and oxidative stress. Methods Briefly, Streptozotocin (STZ) (55 mg/kg) was injected intraperitoneally to induce DN in Sprague Dawley rats and performed procedures including Randall Sellito Calipers, Von Frey Aesthesiometer, hot plate, and cold plate methods to determine mechanical and thermal hyperalgesia in vivo. The blood flow to the nerves was assessed by using the Laser Doppler device. Schwann cells were exposed to high glucose (HG) at a dose of 30 mM to induce hyperglycemia and DCFDA, JC1 & Mitosox staining were done to determine mitochondrial membrane potential, reactive oxygen species and mitochondrial superoxides in-vitro. The rats were administered i.p with BC (30mg/kg), CBD (15mg/kg), or combination while Schwann cells were treated with 3.65 µM CBD, 75 µM BC, or combination to assess their role in DN amelioration. Results Our results revealed that exposure to BC and CBD diminished HG-induced hyperglycemia in Schwann cells, in part, through reducing mitochondrial membrane potential, reactive oxygen species and mitochondrial superoxides. Further, BC and CBD combination treatment in-vivo could prevent the deterioration of mitochondrial quality control system by promoting autophagy and mitochondrial biogenesis while improving blood flow. CBD and BC treatments also reduced pain hypersensitivity to hyperalgesia and allodynia with increased antioxidant and anti-inflammatory action in diabetic rats. These in vivo effects were attributed to significant upregulation of AMPK, SIRT3, Nrf2, PINK1, PARKIN, LC3B, Beclin1 and TFAM functions while downregulation of NLRP3 inflammasome, NFκB, COX2 and p62 activity was noted as determined by western blotting. Conclusion the present studies demonstrated that STZ & HG induced oxidative and nitrosative stress play a crucial role in the pathogenesis of diabetic neuropathy. We find, for the first time, that CBD and BC combination ameliorate DN via modulating the mitochondrial quality control system.

Gut microbiota plays a critical role in physiological regulation throughout life and is specifically modified to meet the demands of individual life stages and during pregnancy. Maternal gut microbiota is uniquely adapted to the pregnancy demands of the mother and the developing fetus. Both animal studies in pregnant germ-free rodents and human studies have supported a critical association between the composition of maternal microbiota during pregnancy and fetal development. Gut microbiota may also contribute to the development of the fetal gut-brain axis (GBA), which is increasingly recognized for its critical role in health and disease. Most studies consider birth as the time of GBA activation and focus on postnatal GBA development. This review focuses on GBA development during the prenatal period and the impact of maternal gut microbiota on fetal GBA development. It is hypothesized that adaptation of maternal gut microbiota to pregnancy is critical for the GBA prenatal development and maturation of GBA postnatally. Consequently, factors affecting maternal gut microbiota during pregnancy, such as maternal obesity, diet, stress and depression, infection, and medication, also affect fetal GBA development and are critical for GBA activity postnatally. Altered maternal gut microbiota during gestation has been shown to have long-term impact postnatally and multigenerational effects. Thus, understanding the impact of maternal gut microbiota during pregnancy on fetal GBA development is crucial for managing fetal, neonatal, and adult health, and should be included among public health priorities.

In tumour cells of more than 20 different cancer types, the CXCR4-CXCL12-axis is involved in multiple key processes including proliferation, survival, migration, invasion, and metastasis. Since data on this axis in diffuse large B cell lymphoma (DLBCL) are inconsistent and limited, we comprehensively studied the CXCR4-CXCL12-axis in our DLBCL cohort as well as the effects of CXCR4 antagonists on lymphoma cell lines in vitro. In DLBCL, we observed a 140-fold higher CXCR4 expression compared to non-neoplastic controls. Interestingly, high expression of CXCR4 was associated with poor clinical outcome. Furthermore, in corresponding bone marrow biopsies, we observed a correlation of CXCL12 expression and lymphoma infiltration rate as well as a reduction of CXCR4 expression in remission of bone marrow involvement after treatment. Furthermore, the niacin derivate of the CXCR4 antagonist AMD070, which was synthesized by us, demonstrated stronger pro-apoptotic effects than AMD070 in vitro and induced expression of certain pro-apoptotic genes in CXCR4 positive lymphoma cell lines. Finally, WK1 treatment resulted in reduced expression of JNK-, ERK1/2- and NFκB/BCR-target genes. These data indicate that the CXCR4-CXCL12-axis impacts the pathogenesis of DLBCL and represents a potential therapeutic target in aggressive lymphomas.

The rapid development of multicopters has led to many security problems. In order to prevent multicopters from invading restricted areas or famous buildings, an Anti-UAV Defense System (AUDS) has been developed and become a research topic of interest. Topics under research in relation to this include electromagnetic interference guns for unmanned aerial vehicles (UAVs), high-energy laser guns, US military net warheads, and AUDSs with net guns. However, these AUDSs use either manual aiming or expensive radar to track UAVs. This paper proposes a dual-axis rotary platform with UAV automatic tracking. The tracking platform uses visual image processing technology to track and lock the dynamic displacement of a UAV. When a target UAV is locked, the system uses a nine-axis attitude meter and laser rangefinders to measure its flight altitude and calculates its longitude and latitude coordinates through sphere coordinates to provide UAV monitoring for further defense or attack missions. Tracking tests of UAV flights in the air were carried out using a DJI MAVIC UAV at a height of 30 meters to 100 meters. It was set up for UAV image capture and visual recognition for tracking under various weather conditions by a thermal imager and a full-color camera respectively. When there was no cloud during the daytime, the images captured by the thermal imager and full-color camera provide a high-quality image recognition result. However, under dark weather, black clouds will emit radiant energy and seriously affect the capture of images by a thermal imager. When there is no cloud at night, the thermal imager performs well in UAV image capture. When the UAV is tracked and locked, the system can effectively obtain the flight altitude and longitude and latitude coordinate values.

Wind turbines are a solution for sustainable energy, significantly reducing carbon emissions and fostering a circular economy for more cost-effective and cleaner power generation, in line with worldwide environmental aspirations. In this context, this research aims to explore a novel Two-Stage Twisted Blade micro-Vertical Axis Wind Turbine ($\mu$-VAWT) alternative inspired by the Savonius Rotor (SR). This investigation utilizes the $\kappa-\omega$ SST turbulence model to explore the power coefficient ($C_P$) and torque coefficient ($C_T$), finding $C_P$ values ranging from 0.02 to 0.04 across the turbine by altering the free stream velocity ($V$). $C_T$ analysis further delves into four specific sections, highlighting areas of particular interest. These results are validated by examining velocity contours, pressure contours, and streamlines in four horizontal sections, demonstrating that the proposed turbine model exhibits minimal torque fluctuation. Moreover, the analysis of vertical wind streamlines illustrates very low interference with various wind turbine proposals, underscoring the turbine's efficiency and potential for integration into diverse wind energy projects.

This paper numerically investigates a 3D mesh independency study of a straight blade horizontal axis tidal turbine modelled using Computational Fluid Dynamics (CFD). The solution was produced by employing two turbulence models, the standard k-ε model and Shear Stress Transport (SST) in ANSYS CFX. Three parameters were investigated: mesh resolution, turbulence model, and power coefficient in the initial CFD, analysis. It was found that the mesh resolution and the turbulence model affect the power coefficient results. The power coefficients obtained from the standard k-ε model are 15% to 20% lower than the accuracy of the SST model. It can also be demonstrated that the torque coefficient increases with the increasing Tip Speed Ratio (TSR), but drops drastically after TSR = 5 and k-ε model failing to capture the non-linearity in the torque coefficient with the increasing TSR.

Magnetic nanoparticles (MNPs) have attracted a great interest in nanomedical research. MNPs exhibit many important properties, particularly, magnetic hyperthermia for selective killing of cancer cells is one of them. In hyperthermia treatment, MNPs act as nano-heaters when they are under the influence of an alternating magnetic field (AMF). In this work, micromagnetic simulations have been used to investigate the magnetization dynamics of a single-domain nanoparticle of magnetite in an external AMF. Special attention is paid to the circumstances dealing with a dynamic phase transition (DPT). Besides, we focus on the influence of the orientation of the magnetic easy-axis of the MNP on the dynamic magnetic properties. For amplitudes of the external AMF above certain critical value, the system is not able to follow the magnetic field and it is found in a dynamically ordered phase; whereas for larger amplitudes, the state corresponds to a dynamically disordered phase and the magnetization follows the external AMF. Our results suggest that the way how the order-disorder DPT takes place, and both the metastable lifetime as well as the specific loss power (SLP), are strongly dependent on the interplay between the orientation of the magnetic easy-axis and the amplitude of the external AMF.