This study investigated the inhibitory effect of Siegesbeckia orientalis ethanolic extract (SOE) on growth and metastasis of hepatic tumors in C57BL/6JNarl mice, which is the model of tumor-igenesis induced by subcutaneous injection of Hepa1-6 murine hepatoma cells on the back of mice. Feeding 25 mg SOE/kg BW daily for 14 days effectively reduced the hepatoma weight in tu-mor-bearing mice by 59.7%. SOE intervention reduced the expression of anti-apoptotic Bcl-2 gene in tumor tissue by 48.5% and down-regulated the antioxidant system, by reducing the gene ex-pression of catalase (48.0%), glutathione peroxidase (46.3%), and superoxide dismutase (32.0%). In addition, SOE intervention increased the production of ROS by 21.4%, and the gene expression of pro-inflammatory cytokines TNF-α, IL-1β, and IL-6 by 135.3%, 179.3% and 91.7%, respectively, indicating that SOE intervention promoted the acute inflammatory response. Results of H&E staining analysis showed that SOE had the ability to inhibit angiogenesis in tumor tissue. Fur-thermore, SOE treatment inhibited the expression of migration-related genes, such as MMP-2, MMP-7, MMP-9 and β-catenin, and the inhibition rates were 24.8%, 27.4%, 10.4% and 21.9%, respectively. These results imply that SOE had the ability to suppress tumor metastasis. On the other hand, SOE intervention decreased the serum contents of inflammatory cytokines, such as TNF-α, IL-1β and IL-6 by 27.4%, 30.4%, and 30.7%, respectively, indicating that SOE intervention has an anti-inflammatory effect on normal tissues of mice. Since SOE intervention had no signif-icant effect on liver and kidney weights, and no mice died throughout the experiment, it shows that it is safe to feed SOE under this experimental condition. Based on the above results, SOE has a great potential to be used in the treatment of hepatoma.

Atrial fibrillation (AF), a complex cardiac arrhythmia, necessitates a shift in management paradigms, emphasizing an integrative approach that incorporates lifestyle modifications. Investigations into the role of interleukins and inflammatory mediators are underway, exploring their potential as diagnostic markers and predictors of cardiovascular events in AF. Despite the identification of biomarkers related to cardiac remodeling, their predictive ability for post-cardioversion outcomes remains controversial. Computational models are being developed to understand proarrhythmic contributions and identify anti-AF targets. Addressing the rising global incidence of AF, linked to stroke and heart failure, presents a critical health challenge. As risk factors like obesity prevail, AF becomes a pervasive public health concern, expected to double in prevalence over the next 50 years. The impact on mortality and morbidity, especially through hospitalizations, underscores the need for early detection and effective clinical management. Identifying individuals at increased AF risk becomes crucial for screening and prevention strategies. Lifestyle modifications, including weight management and physical activity, emerge as influential factors in AF management, offering the potential to alleviate symptoms and modify disease progression. The paper concludes by emphasizing the need for safer antiarrhythmic therapies based on AF mechanisms, promising improvement in global AF management. The multifaceted nature of AF etiology requires a broader perspective beyond traditional medical interventions, acknowledging the importance of integrated care to address this significant public health challenge.

This review article focuses on the upstream pertinent pathophysiology leading to neurodegenerative disease. Specifically, the nexus appears to be blood brain barrier (BBB) leakiness resulting in a two-prong inflammatory disease spectrum damaging the microvasculature and corrupted protein synthesis and degradation with accumulating misfolded toxic proteins. The suboptimal results of removing misfolded proteins means a new approach to disease in the preclinical state is required aimed at other targets.Validated noninvasive imaging and serologic biomarkers of early preclinical disease implemented in the high-risk patient cohort along with periodic surveillance once effective treatments are developed will be required.This review discusses the physiology and pathophysiology of the BBB, new MRI imaging techniques identifying the leak and altered fluid dynamic effects in the preclinical state. The risk factors for disease development, preventative measures, and potential treatment targets are also discussed.

Inflammatory bowel diseases, comprising Crohn’s disease (CD) and ulcerative colitis (UC), are chronic, relapsing and remitting immune-mediated inflammatory diseases affecting the gastrointestinal tract. Ustekinumab (UST) is a monoclonal antibody blocking the p40 subunit of the anti-interleukin (IL) 12/23. Pivotal trials (CERTIFI and UNITI-IM for CD, UNIFI for UC) established the efficacy of UST for the induction and maintenance of remission in both CD and UC, with the most favorable results in naïve patients to biologics. In recent years, a wealth of ‘real-world’ data has emerged supporting positive clinical, endoscopic, and histological outcomes in patients treated with UST, as well as reassuring safety data. More recently, the results of the first head-to-head trials of UST and tumor necrosis factor (TNF) antagonists have been reported. Moreover, a number of studies exploring the role of UST in specific clinical settings, such as perianal CD, postoperative complications and recurrence, extraintestinal manifestations, chronic antibiotic-refractory pouchitis, and pregnancy, have been reported. This review explores results reported to date on UST, including those from pivotal trials, real-world data, and emerging studies regarding therapeutic drug monitoring and immunogenicity. The safety profile of UST was also reviewed.

Herbal cosmetics are cosmetics derived from plants. One example is bakuchiol. Bakuchiol is a meroterpene phenol from the seeds of the Psoralea corylifolia plant. Bakuchiol can be derived from Psoralea grandulosa, Pimelea drupaceae, Ulmus davidiana, Otholobium pubescens, and Piper longum. Bakuchiol has antioxidant, anti-inflammatory, and anti-aging activities such as retinol. Bakuchiol will replace retinol with much better safety. Bakuchiol and retinoids share similar cellular pathways, such as the regulation of retinoic acid, the expression of collagen, and extracellular matrix synthesis enzymes. Bakuchiol has many benefits for the skin, so cosmetics and skin therapy can use bakuchiol. This review aims to provide information about the activity of bakuchiol, which has benefits for facial skin, so that this review can be a reference in making cosmetics containing bakuchiol. Bakuchiol has many benefits for skincare such as anti-aging, anti-hyperpigmentation, anti-oxidant, anti-inflammatory, anti-acne, and anti-melanogenesis. Products containing bakuchiol on the market are cleansers, serum, nanoemulsion, and cream.

Consumer preference not only dictates what food is consumed but how that food is produced. Ingredients in livestock feed that are not antibiotics, not genetically modified, not of animal origin, and that are nutrient-like, tend to be more acceptable to consumers, retailers, and producers. Mono- and diglycerides (MDG) fit these criteria, are commonly used in food, and are generally recognized as safe. But beyond being emulsifiers and a source of energy, MDG are also known to have antimicrobial, immune and microbiome modulation, and angiogenic activity. MDG in broiler diets have been shown to impact a variety of immune-related functions such as regulation of circulating antibodies, as well as decreased gene expression or protein concentration of pro-inflammatory cytokines like TNF-α, IL-1β, IL-6, and IFN-γ. In addition, MDG can affect metabolic function and intestinal integrity. Results of this review show that MDG can serve as antimicrobial and growth-supporting alternatives for reducing poultry production losses, improving resource utilization, and meeting consumer demand for sustainably produced and safe animal protein.

In recent years, extensive research has delved into the pathophysiology of local reactions triggered by Bothrops snake venoms. Even though antivenom works well at reducing death and systemic effects, it is still not very effective in treating local reactions because the venom works so quickly, and antivenom cannot fix injuries that have already been triggered. This might be attributed to certain molecules amplifying the venom-induced innate response. While evidence suggests endogenous mediators at the venom site play a role in this envenomation, in Brazil, concurrent use of anti-inflammatories or other drugs associated with the antivenom remains uncommon. The aim of this study was to determine how various inflammatory mediators affected the leukocyte-endothelium interaction (LEI) following a B. jararaca bite. According to our findings, nitric oxide and cyclooxygenase pathway eicosanoids significantly contribute to alteration of LEI induced by B. jararaca venom. Conversely, lipoxygenase-mediated eicosanoids, histamine, or serotonin had minimal participation. Markedly, treatment with dexamethasone alongside antivenom mitigated alterations of LEI induced by the B. jararaca snake venom. The limited efficacy of the antivenom in managing Bothrops venom-induced local reactions emphasizes the critical need for supplementary treatments to enhance therapeutic outcomes.

Is it possible that the addition of wild-growing flowers with anti-inflammatory applications can improve the antioxidant properties of rapeseed and multifloral honey? The study objective was a comparative analysis of two honey varieties enriched by flowers of six plant species, based on the content of the antioxidant capacity as well as total flavonoids and phenolic content. Experiments demonstrated that at each level of enrichment there was an improvement in antioxidant properties compared to honey of both varieties without additives, especially in the case of dried flowers. Primula veris L. and Pulmonaria officinalis L. improved the antioxidant properties and phenolic content most effectively in honey at all levels of enrichment. Rapeseed-type honey produces a better matrix for the incorporation of natural plant metabolites into honey. The content of biologically active substances in honey enriched with flowers gives hope for new applications of health-promoting substances contained in wild plants.

Mild TBI (mTBI) accounts for most TBI cases, the leading cause of morbidity and mortality worldwide. Despite their high incidence, mTBI pathophysiology remains largely unknown. Recent studies have shown that the inflammatory response is activated early after mTBI and can persist for several weeks or months. However, limited evidence on the utility of inflammatory biomarkers as predictors of clinical outcomes in mTBI was previously provided. Thus, this study aims to provide an overview of the current knowledge on the role of inflammation in the pathogenesis of mTBI and the potential of some inflammatory biomolecules as biomarkers of mTBI. Thus, it was shown that the increase of IL-6, TNF-α, and IL-1β plasma levels could be implicated in the development of the early post-concussion symptoms. On the other hand, the persistence of the increased plasmatic concentrations of IL-10 and IL-8 for as long as six months following the brain injury event could suggest chronic inflammation leading to neuroinflammation and late or persistent symptoms. In this context, our findings showed that the inflammatory biomarkers could be relevant in diagnosing or predicting recovery or long-term outcomes of mTBI.

Barrett’s esophagus (BE) is a premalignant lesion for esophageal adenocarcinoma (EAC). Development of Barrett’s esophagus is caused by biliary reflux that provokes intensive mutagenesis in stem cells of epithelium in distal esophagus and gastro-esophageal junction. Other possible cell origins of Barrett’s esophagus include stem cells of mucosal esophageal glands and their ducts, of stomach, residual embryonic cells and circulating bone marrow stem cells. Classic conception of healing of caustic lesion was replaced by idea of cytokine storm that forms inflammatory microenvironment for phenotypic shift toward intestinal metaplasia of distal esophagus. The review summarizes contemporary concepts of BE and EAC pathogenesis.

(1) Background: Heavy and chronic alcohol intake causes altered gut-permeability and dysfunction; and exhibits a unique pro-inflammatory state. Thyroid-associated hormones and proteins may be dysregulated by alcohol administration; however, the impact of altered gut-derived changes on thyroid function is unclear. This study investigated the role of gut-dysfunction and pro-inflammatory activity on thyroid function in patients with alcohol use disorder (AUD). (2) Methods: Male and female AUD patients (n=44) were grouped as Gr.1 with normal thyroid stimulating hormone (TSH) levels (n=28, 0.8≤TSH≤3 mIU/L); and Gr.2 with clinically elevated TSH levels (n=16, TSH> 3 mIU/l). Demographics, drinking measures, comprehensive metabolic panel, and candidate thyroid markers (TSH, circulating triiodothyronine [T3] and free thyroxine [fT4]) were tested. Plasma-derived gut-dysfunction associated markers (lipopolysaccharide [LPS], LPS-binding protein [LBP], and LPS-induced pathogen-associated protein [CD14]), and cytokine profile (IL1-β, TNF-α, IL-6, IL-8, MCP-1, PAI-1) were analyzed and compared with the thyroid, demographic, and drinking markers. (3) Results: Both groups presented with a borderline overweight category of BMI. Gr.2 presented with numerically higher level of chronic and heavy drinking patterns vs Gr.1. fT4 levels were elevated while T3 was within normal limits in both the groups. Gut-dysfunction markers LBP and CD14 were numerically elevated in Gr.2 vs Gr.1 suggesting subtle ongoing changes; however, the difference was not statistically significant. All pro-inflammatory cytokines were significantly elevated in Gr.2 among IL1-, MCP-1, and PAI-1. Gr.2 showed a strong and statistically significant effect of gut-immune-pituitary response (r=0.896, p=0.002) on TSH levels in a multivariate regression model with LBP, CD14, and PAI-1 levels as upstream variables; this assessment was not significant in Gr.1. In addition, AUROC analysis demonstrated that many of the cytokines strongly predicted TSH in Gr.2, including IL-6 (area=0.774, p<0.001) and TNF- (area=0.708, p=0.017) among others. This was not observed in Gr.1. Gr.2 demonstrated elevated fT4 as well as TSH, which suggests that there was subclinical thyroiditis with underlying CNS dysfunction and lack of a negative feedback loop. (4) Conclusions: These findings reveal the toxic effects of heavy and chronic drinking that play a pathological role in thyroid gland dysregulation employing the gut-brain axis. These results also strongly emphasize potential directions to strongly consider thyroid dysregulation in the overall medical management of AUD.

Obesity is linked to an inflammatory process, with adipocyte release triggering insulin resistance (IR) and autonomic imbalance. A cardiovagal trainning protocol has shown favorable results in autonomic balance and decrease of inflammatory markers. The aim of this study was to analyze the autonomic behavior related to inflammatory and metabolic parameters in obese people after a cardiovagal exercise protocol. Twenty people with obesity, were distributed by their HOMA-IR value: obese without IR (n/IR) (n=8) and obese with IR (y/IR) (n=12). The cardiovagal training program was carried out in both groups for 8 weeks at a frequency of 5 times per week. A blood sample was obtained to determine insulin, leptin, TNF alpha and IL6 levels, in addition to determining the HOMA-IR index and autonomic function was measured by heart rate variability. Changes were recorded in the OB-IR group, a decrease in inflammatory markers, glycemia and a reduction of sympathetic activity after the cardiovagal training intervention. In addition, significant differences between the y/IR and n/IR groups were shown in insulin, leptin, TNFa and IL6 values. It can be concluded that after 4 weeks of intervention with a cardiovagal trainning protocol, parasympathetic modulation increased and inflammatory markers decreased in obese subjects.

In this brief communication, we propose the concept that capillary regression may represent a primary pathogenic process underlying COVID-19 infection, particularly in the serious and life-threatening manifestations of the disease. We suggest that the marked elevations of pro-inflammatory mediators that are observed in these seriously ill patients may directly induce capillary regression and endothelial cell (EC) loss. Recent autopsy studies are demonstrating EC loss leading to widespread microthrombi and associated tissue damage. Recent work has indicated that interleukin-1 beta (IL-1β), tumor necrosis factor-alpha (TNFα), and thrombin, individually and in combination, can potently cause capillary tube regression in experimental models in vitro and in vivo. Other pro-inflammatory mediators including interferon gamma (IFNγ), interleukin-4 (IL-4), and interleukin-13 (IL-13) were also shown to be pro-regressive and could be relevant mediators in COVID-19 patients. Interestingly, combinations of pharmacologic agents were identified that reduced capillary regression and protected capillary tube networks against these pro-inflammatory mediators. Such an approach might be an important therapeutic option going forward to treat key disease states where capillary regression plays a major underlying pathogenic role. Finally, if capillary regression is occurring in response to these pro-inflammatory mediators during COVID-19 infection, we suggest that combinations of blocking agents directed to these key pro-regressive mediators might be necessary to appropriately treat patients.

The human innate immune response to the pore-forming toxin of Vibrio cholerae VCC, is currently under study. Here, in vitro studies on a human macrophage cell line (THP-1), helped explore the activated pathways involved on the onset the innate immune response towards the cytotoxin. The secreted monomeric 65 KDa form interacts with mature macrophages in pg/ml concentrations, determined by dose response experiments after treatments under 1 h. Non vacuolating concentrations (pg/ml) were applied to the cells; immunoblots revealed activation of MAPKs: early overexpression of p38 and ERK. Cell lysis by release of lactate dehydrogenase (LDH) was not apparent in the first hour, nonetheless it was positive after 24 h. Finally, to discern whether the VCC stimulates transcriptional activators via MAPKs pathway, NF-κB and AP-1 were studied by real time quantitation. Increased expression of p50 (NF-κB), cJun and cFos (AP-1) was observed. Given that NF-κB is the transcription factor initiating inflammation of innate immune response and in turn, AP-1 is responsible for cell surviving response, results from this study lead us to conclude that VCC in vitro treatments, induce a pro-inflammatory and a surviving response, in less than one hour on activated macrophages.

Specific nutrients including n-3 long chain polyunsaturated fatty acids (LCPUFAs), flavonoids, vitamin A, D and E are considered to possess protective properties on human health by impacting on immunological reactions. An ‘inflammation-suppressive’ effect appears to be the common denominator of the beneficial effects of most of these dietary components which may protect against the development of chronic immune disorders such as allergy. However, the majority of these promising data are from preclinical studies such as animal disease models, as the majority of clinical studies only indicate associations. PUFAs, especially n-3 LCPUFAs, have been shown to interact with both the sensitization as well as the effector phase in food allergy. However, it should be noted and realised that PUFAs are highly susceptible to lipid oxidation. Flavonoids and fat-soluble vitamins both contain anti-inflammatory properties and are able to act as anti-oxidants as well. Here, we explore the anti-allergic properties of PUFAs, flavonoids and fat-soluble vitamins in order to create an overview and, more importantly, suggest a strategy to target food allergies using these components and combinations thereof. Dietary n-3 LCPUFAs and the above mentioned micronutrients are promising anti‐allergy agents capable of influencing the allergic immune response through multiple and different biological pathways.

We investigated the micro-threaded stem taper surface and the impact on premature failures, aseptic loosening, and infection. We have focused on the fretting, and crevice corrosion of micro-threaded tapers, as well as the characterization of microstructure and surface properties of two new and three retrieved Zweymüller stem tapers of cementless hip endoprostheses selected from a set of 45 stems. The retrievals examined were those in which the sole source of modularity with a metallic component was the head-stem taper interface between the Ti alloy taper stem and the ceramic head. To determine the surface chemistry and microstructures of both new and retrieved hip endoprostheses stem taper titanium alloy, scanning electron microscopy (SEM) was employed for morphological and microstructural analyses. At the same time, energy dispersive spectroscopy (EDS) was utilized for characterizing chemical element distribution, and electron backscattered diffraction (EBSD) was used for phase analysis. The micro-threated stem taper’s roughness for different manufacturers was investigated using an optical profilometer. Standard roughness pa-rameters Ra (average surface roughness) and Rz (mean peak to valley height of the roughness pro-file) were used in this investigation.Additionally, profile depth and peak spacing for different samples were investigated. The surface roughness results indicate no significant difference in roughness associated with varying survivorship times, ranging from 3 to 239 months, and across different manufacturers. Electrochemical studies revealed no fretting corrosion in retrieved stem tapers (ceramic head) that prematurely failed due to aseptic loosening after 239 months, infection after 3 months, and low-grade infection after a 32-month lifetime. Therefore, three retrieved ta-pers and two new ones for comparison underwent potentiodynamic measurements in Hank’s so-lution to ascertain the corrosion rate of new and retrieved stem taper surfaces. The results show a low corrosion rate for both new and retrieved samples that failed prematurely due to aseptic loosening. However, the corrosion rate of infected and low-grade infected tapers was higher. In conclusion, our study aligns with existing literature, suggesting that the use of ceramic heads de-creases the problem of taper corrosion and subsequently reduces premature failures in total hip arthroplasty.

This study advances the field of infectious disease forecasting by introducing a novel approach to micro-level contact modeling, leveraging human movement patterns to generate realistic temporal dynamic networks. Through the incorporation of human mobility models and parameter tuning, this research presents an innovative method for simulating micro-level encounters that closely mirror infection dynamics within confined spaces. Central to our methodology is the application of Bayesian optimization for parameter selection, which refines our models to emulate both the properties of real-world infection curves and the characteristics of network properties. By focusing on the distinct aspects of infection propagation within confined spaces, our approach significantly improves the realism of temporal-dynamic contact networks, offering a powerful tool for assessing the impact of specific locations on pandemic dynamics. The resulting models shed light on the role of spatial encounters in disease spread and strengthen the capability to forecast and respond to infectious disease outbreaks. This work not only contributes to the scientific understanding of micro-level transmission patterns but also offers practical insights for public health strategies and digital contact tracing efforts, aiming at more effective intervention and containment measures during pandemics.

Micro-Raman spectroscopy was carried out to evaluate the localized residual stresses in commercial Gallium Nitride-based devices, specifically AlGaN/GaN High Electron Mobility Transistors (HEMTs) in a novel packaging design provided by STMicroelectronics S.r.l. The packaging plays a key role in protecting the device core against the external environment, thus minimizing damages caused by mechanical shocks, exposure to light, and contact with chemicals, conjointly achieving an efficient heat dissipation rate. Even though the packaging is a required step for the proper functioning of ready-to-use electronic devices, its application typically may introduce mechanical stress to AlGaN/GaN HEMTs, which can result in various reliability issues. In this paper, we investigate the impact of packaging on residual stress by analyzing the frequency shift of the E2 Raman peak along GaN layers and at the GaN/Si interface. An extensive evaluation was conducted using both a packaged device and a wafer-level device. The correlation between Raman frequency shifts of the E2 mode was accurately quantified, revealing a stress mitigation of approximately 0.1 GPa. This reduction is ascribed to the compressive stress introduced by the packaging, which partially offsets the intrinsic tensile stress of the wafer-level device. The proposed methodology could, in principle, be implemented to improve the development of a packaging.

This study aimed to elucidate the similarities and differences between amyloid-forming corpora amylacea (CA) in the prostate and lung, examine the nature of CAs in cystic tumors of the atrioventricular node (CTAVN), and clarify the distinctions between amyloid-forming CA and spheroid-type amyloid deposition. We conducted proteomics analyses using liquid chromatography–tandem mass spectrometry with laser microdissection and immunohistochemistry to validate the characteristics of CAs in the lung and prostate. Our findings revealed that CAs in these organs primarily consist of common proteins (β2-microglobulin and lysozyme) and locally produced proteins. Moreover, we observed a discrepancy between the histopathological and proteomic analysis results in CTAVN-associated CAs. In addition, while the histopathological appearance of amyloid-forming CAs and spheroid-type amyloid deposits were nearly identical, the latter deposition lacked β2-microglobulin and lysozyme, and exhibited evident destruction of surrounding tissue. A literature review further supported these findings. These results suggest that amyloid-forming CAs in the lung and prostate are formed through a shared mechanism, serving as waste containers (wasteosomes) and/or storage for excess proteins (functional amyloids). In contrast, we hypothesize that while amyloid-forming CA and spheroid-type amyloid deposits are formed, in part, through common mechanisms, the latter are pathological.

Cancer is a disease caused by the abnormal growth of cells in different parts of body is one of the top causes of death globally. Microarray gene expression data plays a critical role in the identification and classification of cancer tissues. Due to recent advancements in Machine Learning (ML) techniques, researchers are analyzing gene expression data using a variety of such techniques to model the progression rate & treatment of cancer patients with great effect. But high dimensionality alongside the presence of highly correlated columns in gene expression datasets leads to computational difficulties. This paper aims to propose the use of ML classification techniques- Linear Discriminant Analysis (LDA) & Random Forest (RF) for classifying five types of cancer (breast cancer, kidney cancer, colon cancer, lung cancer and prostate cancer) based on high dimensional microarray gene expression data. Principal component analysis (PCA) was used for dimensionality reduction, and principal component scores of the raw data for classification. Six distinct categorization performance measures were used to evaluate these approaches; RF method provided us with higher accuracy than LDA method. The method and results of this article should be helpful to researchers who are dealing with many genes in microarray data.

The optical reflection characteristics of asphalt pavement are an important influencing factor in road lighting design, and the macro and micro textures of asphalt pavement significantly affect its reflection characteristics. To investigate the impact of texture parameters on the retroreflection coefficient of asphalt pavement, this study obtained the macroscopic and microscopic texture properties of rutting board specimens and on-site asphalt pavement using a pavement texture tester. The macro- and microtexture parameters, such as macroscopic texture distribution density (D1), microscopic texture distribution density (D2), profile height root-mean-square (Rq), profile slope root-mean-square (Δq), skewness Rsk and kurtosis Rku, were measured, and the corresponding retroreflection coefficient RL was measured using a retro-reflectometer. In the laboratory ex-periments, rutting specimens of AC-13, SMA-13, and OGFC-13 asphalt mixtures were formed. The changes in texture parameters and retroreflection coefficient of different rutting specimens before and after crushing were studied, and a factor influence model between macro- and microtexture parameters and RL was established. And the correlation models of texture index and RL of asphalt pavement are further established. The results showed that in the single factor model, the param-eters can be used to characterize RL with high prediction accuracy, whereas for the on-site meas-urements, the three parameters of Δq, Rsk, and Rku can characterize the RL well. The nonlinear model established on the basis of the B-P neural network algorithm improves its prediction ac-curacy. This research can provide ideas for optimizing the reflection characteristics of asphalt pavement and further provide a decision-making basis for road lighting design.

Micro-nanoparticles' characteristics in geothermal fluids can be applied to detect of deep hidden geothermal resources. Observations using a nanoparticle tracking analyzer (NTA) indicated that the karst geothermal water collected in the central area of Shandong Province (Jinan and Zibo) contains many natural micro-nanoparticles with sizes primarily ranging between 100 nm and 5 μm. The micro-nanoparticles’ type, shape, crystal form, and chemical composition in the samples were analyzed using transmission electron microscopy (TEM). TEM images and energy dispersive spectroscopy showed that the micro-nanoparticles in geothermal water samples were mostly amorphous, irregular, or nearly spherical, with rough edges. The micro-nanoparticles were mainly carbonates, sulfates, and chlorine-containing Fe, Ca, Na, and Mg. The characteristics of the particles can reveal the properties of the deep, hot reservoirs and aquifers from where they originate. Therefore, we believe that natural micro-nanoparticles can be essential to detecting and studying deep, hidden geothermal resources, which is a novel approach to exploring deep, hidden geothermal resources.

The performance and lifespan of cutting tools are significantly influenced by their surface quality. The present report highlights recent advances in enhancing the surface characteristics of tungsten carbide and high-speed steel cutting tools using a novel micro-machining technique for polishing and edge-honing. Notably, the main aim is to reduce the surface roughness while maintaining the hardness of the materials at an optimal level. By conducting a thorough analysis, of surfaces obtained with different techniques. It was that micro-machining method effectively decreased the surface roughness of the cutting tools, most effectively of the techniques investigated. Significantly, the surface roughness is reduced from an initial measurement of 400 nm to an impressive value of 60 nm. No significant change in hardness was observed, which guarantees the maintenance of the mechanical properties of the cutting tools. This analysis enhances the comprehension of surface enhancement methodologies for cutting tools through the presentation of these findings. The observed decrease in surface roughness, along with the consistent hardness, exhibits potential for improving tool performance. These enhancements possess the capacity to optimise manufacturing processes, increase tool reliability, and minimise waste generation.

The integration of Wireless Sensor Networks (WSNs) into agricultural areas has had a significant impact and has provided new, more complex, efficient, and structured solutions for enhancing crop production. This research reviews the role of Wireless Sensor Networks (WSNs) in monitoring the macro-nutrient content of plants. The review study focuses on identifying the types of sensors used to measure macro-nutrients, determining sensor placement within agricultural areas, implementing wireless technology for sensor communication, and selecting device transmission intervals and ratings. The study of NPK (Nitrogen, Phosphorus, Potassium) monitoring using sensor technology in precision agriculture is of high significance in efforts to improve agricultural productivity and efficiency. In addition to fostering technological innovations and precision farming solutions, in future this research aims to increase agricultural yields, particularly by enabling the cultivation of certain crops in locations different from their original ones.

Near-infrared (NIR) photodetectors (PDs) have attracted much attention in noninvasive medical diagnosis and treatment. Especially, the self-filtered NIR PDs are highly demandable for tremendous biomedical application due to their strong ability in wavelength discrimination. In this work, we designed and then fabricated a Si micro-holes array/Graphene (Si MHA/Gr) van der Waals (vdW) Schottky NIR photodiode by using PbS quantum dots (QDs) coating. The device exhibits a unique self-filtered NIR response with a responsivity of 0.7 A/W at -1 V and a response time of 61 μs, which are higher than that without PbS QDs coating and even most of previous Si/Gr Schottky photodiodes. The light trapping of the Si MHA and the PbS QDs coating can be attributed to the high responsivity of the vdW photodiode. Furthermore, the presented NIR photodiode can also be integrated in photoplethysmography (PPG) for real-time heart-rate (HR) monitoring. The extracted HR is in great accord with the value measured with the patient monitor by analyzing the Fourier transform of the stable and reliable fingertip PPG waveform, suggesting its potential for practical applications.

Background: Micro-RNAs (miRNA) are emerging as biomarkers in the detection and prognosis of cancers due to their inherent stability and resilience. Methods: To summarize evidence regarding urinary miRNA (umiRNAs) role in the detection, prognosis and therapeutic management of urological cancers, we performed a systematic review of the most important scientific databases using the following keywords: (urinary mir-na)AND(prostate cancer); (urinary mirna)AND(bladder cancer); (urinary mirna)AND(renal cancer); (urinary mirna)AND(testicular cancer); (urinary mirna)AND(urothelial cancer). Results: Of all, 1364 articles were initially selected. Only original studies in the English language on human specimens were considered for inclusion in our systematic review. Thus, a convenient sample of 60 original articles was identified. Urinary miRNA (UmiRNAs) are downregulated in prostate cancers and may serve as potential non-invasive molecular biomarkers. Several umiR-NAs have been identified as diagnostic biomarkers of urothelial carcinoma and bladder cancer (BCa), allowing to discriminate malignant from non-malignant forms of haematuria. UmiRNAs could serve as therapeutic targets or recurrence markers of non-muscle invasive BCa and could predict the aggressivity and prognosis of muscle-invasive BCa. In renal cell carcinoma, miRNAs have been identified as predictors of tumour detection, aggressiveness, and progression to metastasis. Conclusion: umiRNAs could play an important role in the diagnosis, prognosis, and therapy of urological cancers.

To study the feasibility and effect of compounding lignin and its derivatives to improve expansive soil, the physical properties, mechanical properties, and microstructure of the improved soil mixed with calcium lignosulfonate alone, calcium lignosulfonate and lignin fibers were investigated through indoor experiments and electron microscope scanning. Select samples with better performance for water stability tests, and discuss the improvement mechanism of expansive soil by combining macroscopic mechanical changes with microstructural characteristics. The research results show that the addition of calcium lignosulfonate can reduce the water content of the soil and enhance its strength of the soil. The overall performance is the best when the calcium lignosulfonate content is 3%. 3% calcium lignosulfonate compounded with 1.5% lignin fiber has the best all-around performance; the composite improved soil has a better pore-filling effect, the whole is more compact, and the connection between particles significantly enhances the strength, which greatly inhibits the development of cracks good water stability. Lignin and its derivatives compound improved expansive soil have better effect than traditional improvement methods, and have no pollution to the environment, which can provide a particular reference for engineering practice

To study the feasibility and effect of compounding lignin and its derivatives to improve expansive soil, the physical properties, mechanical properties, and microstructure of the improved soil mixed with calcium lignosulfonate alone, calcium lignosulfonate and lignin fibers were investigated through indoor experiments and electron microscope scanning. Select samples with better performance for water stability tests, and discuss the improvement mechanism of expansive soil by combining macroscopic mechanical changes with microstructural characteristics. The research results show that the addition of calcium lignosulfonate can reduce the water content of the soil and enhance its strength of the soil. The overall performance is the best when the calcium lignosulfonate content is 3%. 3% calcium lignosulfonate compounded with 1.5% lignin fiber has the best all-around performance; the composite improved soil has a better pore-filling effect, the whole is more compact, and the connection between particles significantly enhances the strength, which greatly inhibits the development of cracks good water stability. Lignin and its derivatives compound improved expansive soil have better effect than traditional improvement methods, and have no pollution to the environment, which can provide a particular reference for engineering practice.

In this work the close relation between vorticity and micro-rotation in micropolar flows in Rn (n = 2 or 3) is identified and used to explain the faster decay by t^(-1/2) of the angular velocity of the micro-rotation of fluid particles, as well as establishing its optimality. For this purpose important upper and lower bounds for Leray solutions in homogeneous Sobolev spaces are derived, using the monotonicity approach recently introduced by the authors for dissipative systems in general. Several related results of interest are also given along the discussion.

Since the 21st century, China's urbanization process has been rapid development, the concept and function of urban public space in the city has been gradually paid attention to. In order to guarantee life and water, most urban construction relies on rivers, and Bridges are the most important way to communicate between urban areas. The main functional part of the bridge is the span structure, that is, the bearing structure of the bridge, and the lower part of the "gray" space formed by the bridge structure. Considering the social level, with the economic growth and urbanization development, people have brought a better living environment and quality of life, and also improved the requirements for urban public environment. In the increasingly tense urban space, how to use and transform the space under the bridge is a problem that needs to be considered and solved. In view of this problem, in this study, we try to solve the micro-transformation of space under Bridges in cities through public art from the perspective of "regional culture" and "art for all". This paper analyzes the micro-transformation of space art under Bridges in two large cities of Shanghai and Foshan, namely, the space under Bridges under Songhong Road in Shanghai, the space under Bridges under Central Of Suzhou River and the space under Bridges under Pingsheng Bridge in Foshan. This paper discusses the cultural intervention of "regional culture" in the micro-transformation of the space under the bridge, and the influence and effect of "art for all" on the public art space under the bridge after the transformation to the community and the public.

Background: Shared value creation in Base of the Pyramid (BoP) communities is a crucial process towards building sustainable societies. BoP communities in developing countries represent more than four billion people who live on low incomes with limited access to basic products and services. Current or emerging technologies offer promising solutions for organisations pursuing manufacturing opportunities in BoP communities. This study seeks to explore the literature on how BoP communities may become active participants in sustainably manufacturing products using micro-manufacturing factories. The research question posed is: What are the core concepts that need to be taken into consideration for creating shared value through micro-manufacturing factories in BoP communities? Method: A Systematised Literature review (SLR) was completed following the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) method for data selection criteria and analysis. The SLR is used to explore the state of literature with regards to creating manufacturing shared value in BoP communities with the objective to identify study gaps and to explore shared value creation concepts. Results: Literature indicates BoP initiatives that have pursued to engage BoP communities through various innovation strategies. The findings of the review is organised under three strategic pillars: Capability building strategy, Implementation process, and Growth strategy. The capability building strategy defines the users’ intention to create shared value in BoP communities with Micro-manufacturing factories (MMF). It is followed by the implementation process which guides the users to create manufacturing shared value in BoP communities. This is followed by a growth strategy to scale for impact.

In Acropora, the complex canals in a coral colony connect all polyps into a holistic network to collaborate in performing biological processes. There are various types of canals, including calice, axial canals, and other internal canals, with structures that are dynamically altered during different coral growth states due to internal calcium transport. However, few studies have considered the regulation of calcium transport in Acropora. In this study, we investigated the morphological changes of the axial canal in six Acropora muricata samples by high resolution micro-computed tomography, observing the patterns of the axial canal during the processes of new branch formation and truncated branch rebuilding. We visualized the formation of a new branch from a calice and deposition of the iconic hexactin skeletons in the axial canal. Furthermore, the diameter and volume changes of the axial canal in truncated branches during rebuilding processes were calculated, revealing that the volume ratio of calcareous deposits in the axial canal exhibit significant increases within the first three weeks, returning to levels in the initial state in the following week. This work indicates that the axial canal can transport calcium to form hexactin skeletons in a new branch and rebuild the tip of a truncated branch. The calcium transport along canal network regulates various growth processes, including budding, branching, skeleton forming, and self-rebuilding of an Acropora colony. Understanding the changes in canal function under normal and extreme conditions will provide theoretical guidance for restoration and protection of coral reefs.

The study of pain requires a balance between subjective methods that rely on self-reports and complementary objective biometrics that ascertain physical signals associated with subjective accounts. There are at present no objective scales that enable the personalized assessment of pain, as most work involving electrophysiology rely on summary statistics from a priori theoretical population assumptions. Along these lines, recent work has provided evidence of differences in pain sensations between participants with Sensory Over Responsivity (SOR) and controls. While these analyses are useful to understand pain across groups, there remains a need to quantify individual differences more precisely in a personalized manner. Here we offer new methods to characterize pain using the moment-by-moment standardized fluctuations in EEG brain activity centrally reflecting the person’s experiencing temperature-based stimulation at the periphery. This type of gross data is often disregarded as noise, yet here we show its utility to characterize the lingering sensation of discomfort raising to the level of pain, individually, for each participant. We show fundamental differences between the SOR group in relation to controls and provide an objective account of pain congruent with the subjective self-reported data. This offers the potential to build a standardized scale useful to profile pain levels in a personalized manner across the general population.

Extracellular vesicles (EV) such as exosomes, are newly recognized fundamental, natural and physiologic particles of life that seemingly are involved all biologic processes and clinical diseases. Due to their universal involvements, understanding the nature and the potential therapeutic uses of these nano-vesicles requires innovative experimental approaches, in virtually every field. Of the EV group, exosome nano-vesicles and larger companion extracellular micro vesicles (MV) can mediate completely new phenomena dependent on intercellular transfer of proteins and selected RNAs; particularly miRNAs, between donor and targeted cells to elicit epigenetic alterations inducing functional cellular changes. These recipient acceptor cells are nearby (paracrine transfers) or far away after distribution via the circulation (endocrine transfers). The major properties of such vesicles seem to have been conserved over eons, suggesting that they may have ancient evolutionary origins arising perhaps even before cells in the primordial soup from which life evolved. Their potential ancient evolutionary attributes may be responsible for the ability of some modern day exosomes to withstand unusually harsh conditions; perhaps due to unusual membrane lipid compositions. This is exemplified by maternal milk exosome survival of the neonatal acid/enzyme rich stomach. It is postulated that this also applies to their durable presence in phagolysosomes; suggesting unique intracellular release of contents. A major issue discussed is the generally poorly realized superiority of these naturally evolved nano vesicles to therapies compared human engineered artificial nanoparticles; say for treatment of cancers.

Background: The Micro Hand S robot is the first domestically produced surgical robot that has entered clinical use in China, and this is the first report of its application in colon cancer. Objective: This study aimed to validate the safety and efficacy of the domestically produced Chinese minimally invasive Micro Hand S surgical robot system in complex surgery, such as robotic complete mesocolic excision (R-CME). Methods: From March 2018 to December 2018, 30 patients with right hemicolon cancer underwent R-CME with the Micro Hand S robot system. The operative findings, morbidities, oncological findings and unique characteristics were summarizedwere analyzed. Result: 12 patients with right hemicolon cancer and 18 patients with sigmoid colon cancer underwent RCME with the Micro Hand S robot system. During the study period, the median operative duration was 209 (range, 180-255) min, and the median estimated blood loss volume was 35 (range, 25-75) ml. The median number of lymph nodes harvested was 42 (21-77), and the median postoperative hospital stay was 5 (range, 4-7) days. According to the Clavien-Dindo classification, there were no severe complications except for 7 cases of grade I complications and 5 cases of grade II complications. The conversion rate for all operations was 0%. There were no cases of 30-day readmission or 30-day mortality. Conclusion: Clinical application of domestically produced Chinese minimally invasive surgical robot system “Micro Hand S ” in selected colon cancer patients is technically feasible and safe.

Background: The Micro Hand S robot is the first domestically produced surgical robot that has entered clinical use in China, and this is the first report of its application in colon cancer.Objective: This study aimed to validate the safety and efficacy of the domestically produced Chinese minimally invasive Micro Hand S surgical robot system in complex surgery, such as robotic complete mesocolic excision (R-CME).Methods: From March 2018 to December 2018, 30 patients with right hemicolon cancer underwent R-CME with the Micro Hand S robot system. The operative findings, morbidities, oncological findings and unique characteristics were summarizedwere analyzed.Result: 12 patients with right hemicolon cancer and 18 patients with sigmoid colon cancer underwent RCME with the Micro Hand S robot system. During the study period, the median operative duration was 209 (range, 180-255) min, and the median estimated blood loss volume was 35 (range, 25-75) ml. The median number of lymph nodes harvested was 42 (21-77), and the median postoperative hospital stay was 5 (range, 4-7) days. According to the Clavien-Dindo classification, there were no severe complications except for 7 cases of grade I complications and 5 cases of grade II complications. The conversion rate for all operations was 0%. There were no cases of 30-day readmission or 30-day mortality. Conclusion: Clinical application of domestically produced Chinese minimally invasive surgical robot system “Micro Hand S ” in selected colon cancer patients is technically feasible and safe.

Manipulation of micro- and nano-sized objects with optical tweezers is a well established, albeit still evolving technique. While many objects can be trapped directly with focused laser beam(s), for some applications indirect manipulation with tweezers-operated tools is preferred. We introduce a simple, versatile micro-tool operated with holographic optical tweezers. The 40 µm long dumbbell-shaped tool, fabricated with two-photon laser 3D photolithography has two beads for efficient optical trapping and a probing spike on one end. We demonstrate fluids viscosity measurements and vibration detection as examples of possible applications.

: Rasmussen’s encephalitis (RE) stands as a rare neurological disorder marked by progressive cerebral hemiatrophy and epilepsy resistant to medical treatment. Despite extensive study, the primary cause of RE remains elusive, while its histopathological features encompass cortical inflammation, neuronal degeneration, and gliosis. The underlying molecular mechanisms driving disease progression remain largely unexplored. In this case study, we present a patient with RE who underwent hemispherectomy and has remained seizure-free for over six months, experiencing gradual motor improvement. Further-more, we conducted molecular analysis on the excised brain tissue, unveiling a decrease in the expres-sion of cell cycle-associated genes coupled with elevated levels of BDNF and TNF-α proteins. These findings suggest potential involvement of cell cycle regulators in the progression of RE.

Studying models of healthy aging and exceptional longevity is crucial to understand a possible longevity signature as most of them show resistance to age-related diseases. In particular, semi- and supercentenarians are a highly selected group, having survived significant adversities, including the Spanish Flu and COVID-19 pandemics, indicating distinctive immune system characteristics. This paper analyse the inflammatory scores (INFLA-score, Systemic Inflammation Response Index (SIRI)) and Aging-Related Immune Phenotype (ARIP) indicators calculated from the dataset of the DESIGN project, including 249 participants aged 19-111 years, trying to understand the immune-inflammatory (IMFLAM) role to achieve longevity. Statistical analyses, including linear regression and one-way ANOVA, were performed to explore the correlations between these parameters and age. Both INFLA-score and SIRI showed a significant increase with age. However, no statistical difference is observed when analysing the values for semi- and supercentenarians with those for other age groups, whose values are similar to that of adults and less than younger centenariansRegarding ARIP values, it is noteworthy that when comparing the CD8 Naive/Effector scores between groups, no significant differences were observed between the semi- and supercentenarian group and the other groups. These results support the idea that the control of IMFLAM response can promote extreme longevity.

The gut has been a focus of chronic disease research. The gut microbiota produces metabolites that act as signaling molecules and substrates, closely influencing host health. Indigestible oli-gosaccharides (NDOs), as a common dietary fiber, play an important role in regulating the structure and function of gut microbiota. Their mechanism of action is mainly attributed to their carbon source as specific probiotics, producing related metabolites, and regulating the gut mi-crobial community. However, due to the selective utilization of oligosaccharides, some factors such as the types and structures of oligosaccharides have different impacts on the composition of microbial populations and the production of metabolites in the colon ecosystem. This review systematically describes the key factors influencing the selective utilization of oligosaccharides in microorganisms and elaborates how oligosaccharides affect the host's immune system, inflam-mation levels and energy metabolism by regulating microbial diversity and metabolic function, which in turn will affect the onset and progress of chronic diseases, especially diabetes, obesity, depression and intestinal inflammatory diseases, constipation. In this review, we re-examine the interaction mechanisms between gut microbiota and its associated metabolites and diseases, and explore new strategies for promoting human health and combating chronic diseases through di-etary interventions.

Despite past efforts towards therapeutical innovation, cancer remains a highly incident and lethal disease, with current treatments many times lacking efficiency and leading to severe side-effects. Hence, it is imperative to develop new, more efficient, and safer therapies. Bee venom has proven to have multiple and synergistic bioactivities, including antitumor effects. Nevertheless, some toxic effects have been associated with its administration. To tackle these issues, in this work, bee venom-loaded niosomes were developed, for cancer treatment. The vesicles had a small (150.4 ± 3.7 nm) and homogeneous (PDI of 0.162 ± 0.008) particle size, and revealed good therapeutic efficacy in in vitro gastric, colorectal, breast, lung, and cervical cancer models, with GI50 values between 12.37 ng/mL and 14.72 ng/mL. Additionally, they also revealed substantial anti-inflammatory activity, with an IC50 of 28.98 ng/mL, effects that have been reported to be complementary to direct antitumor activity. Finally, the niosomes' safety was assessed, both in vitro, on skin, liver and kidney cells, and ex vivo, in a HET-CAM assay, and results showed that compound encapsulation increased its safety. Hence, small and homogeneous bee venom-loaded niosomes were successfully developed, with substantial anticancer and anti-inflammatory effects, making them potentially promising primary or adjuvant cancer therapies.

(1) The present study investigated the effect of orally administered Limosilactobacillus fermentum HY7302 (HY7302) on the relationship between ocular tissue and the microbiome in the corneal injured dry eye mice model. (2) 0.1% benzalkonium chloride (BAC) was applied to the ocular surface for 14 days to induce corneal injury in male Balb/c mice. During the BAC treatment period, HY7302 (1 × 108 CFU/kg/day or 1 × 109 CFU/kg/day) or omega-3 positive control (200 mg/kg/day) were administered orally (n = 8/group). To examine signaling pathways affected by HY7302 treatment, the in vitro effects of HY7302 on tight junctions and the inflammatory response were investigated in a mouse colon epithelial cell line, CMT-93. (3) BAC exposure decreased tear production, induced ocular inflammation and corneal epithelial detachment, and altered gut microbiota. However, oral administration of HY7302 restored tear secretion and decreased corneal epithelial detachment in BAC-treated corneal injury mice. Further, HY7302 alleviated corneal inflammation via modulation of matrix metalloproteinase-9 (MMP-9) expression and alterations in gut microbiota composition. (4) These findings suggest that the gut–eye axis interaction between gut microbiota and eye tissue affects disease severity in corneal injury, and that alteration of the microbiota by HY7302 could improve eye health by regulating the inflammatory response.

A three-arm, randomized, placebo controlled clinical study has been performed to evaluate the effects of a lyophilized pineapple extract titrated in bromelain (Brome-Inf®), and purified bro-melain on pain, swelling, trismus and quality of life (QoL) after the surgical removal of the lower third molars. Moreover, the need for non-steroidal anti-inflammatory drugs (NSAIDs) has also been evaluated and compared with a placebo group. The study included 42 people that required the extraction of a single mandibular third molar under local anesthesia. The patients were ran-domized and distributed to receive Brome-Inf®, purified bromelain or placebo and started the treatment the day of surgery and continued it for the next 7 days. The primary outcome was the requirement of NSAIDs in the three groups. The outcome variables were pain, swelling and trismus, which were measured postoperatively at 1, 3, and 7 days. The differences in the efficacy of the freeze-dried pineapple extract and single-component bromelain were also evaluated. At the end of the study, the assumption of ibuprofen (from days 1-7) was statistically higher in the placebo group (p

The gold(I) N-heterocyclic carbene (NHC) complexes, containing a combination of 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene (iPr) and the corresponding 7-azaindole derivative (HL1-4), were prepared and structurally characterized. The complexes of the composition of [Au(iPr)(HLn)], where n = 1–4 for 5-fluoro-7-azaindole (1), 5-bromo-7-azaindole (2), 3-chloro-7-azaindole (3) and 3-iodo-7-azaindole (4), were further evaluated for their in vitro anti-cancer and anti-inflammatory activities. The results showed that complexes (1–4) behave as considerably cytotoxic against human ovarian cancer cell line A2780 (with IC50 = 4–9 mircoM) and cisplatin-resistant cell line A2780R (with IC50 = 5–8 microM, except for 2 with IC50 > 25 microM), providing significantly higher cytotoxicity than anticancer drug cisplatin. Moreover, they also revealed a relatively good selectivity over normal cells (MRC-5), with the values of selectivity index, SI > 2.5. The complex 4 was further studied for its cellular effects in A2780 cells by cell cycle analysis, induction of apoptosis, intracellular ROS production, activation of caspases 3/7 and disruption of mitochondrial membrane potential. The ability of complexes (1–4) to influence the activity of pro-inflammatory transcription factor NF-κB and secretion of TNF-α were evaluated, showing that complex 4 reveals comparable effects as the inflammatory drug Auranofin.

The interplay between Diffuse Idiopathic Skeletal Hyperostosis (DISH) and the gut microbiota represents a compelling area of research, offering insights into the relationship between spinal degenerative diseases and the gut's microbial inhabitants. This comprehensive review seeks to unravel the complex connection, shedding light on its implications for human health and potential therapeutic avenues. A crucial section dives into the world of gut microbiota (GM), exploring its impact on human health, featuring its defining characteristics, and highlighting its role in metabolism, immunomodulation, host interaction, and how its composition changes over time. The subsequent portion delves into the relationship between microbiome composition and pathological bone development, including the link between Intervertebral Disc Degeneration (IDD) and gut inflammation, emphasizing how gut inflammation and GM dysbiosis play pivotal roles. Further dissecting the interconnections, various axes of influence, including the gut-spine axis, gut-bone axis, gut-joint axis, gut-disc axis (specific to DISH), gut-ligament axis, and gut-muscle axis, are discussed. Of particular interest is the section on the impact of GM on DISH-derived pain, addressing a critical aspect of the condition's manifestation. The review discusses the potential of GM modulation as a treatment for DISH, providing hope for therapeutic advancements. Additionally, it highlights the positive impact of lifestyle interventions, such as dietary modifications, sleep optimization, and exercise regimens, in mitigating GM dysbiosis and potentially improving DISH outcomes. Lastly, the intriguing prospect of fecal microbiome transplant and its implications for DISH management is examined, opening new avenues for research and therapeutic interventions. In conclusion, this comprehensive review underscores the intricate interplay between DISH and the gut microbiota, offering a fresh perspective on the impact of GM on spinal degenerative diseases. It emphasizes the potential for innovative treatments, such as GM modulation and lifestyle interventions, and presents fecal microbiome transplant as an exciting area for future exploration.

Objectives: Studies on the association between non-steroidal anti-inflammatory drugs (NSAIDs) and major adverse cardiovascular events (MACE) in the Arabian Gulf are scarce. The aim of this study was to evaluate the association between NSAIDs use and MACE in acute coronary syndrome (ACS) patients in the Arabian Gulf region. Methods: Data was analyzed from 3,007 consecutive patients diagnosed with ACS admitted to 29 hospitals in four Arabian Gulf countries from January 2012 to January 2013 as well as being on prior NSAIDs use during the index admission. MACE included stroke/transient ischemic attacks (TIAs), myocardial infarction (MI), all-cause mortality and readmissions for cardiac reasons. Results: The overall mean age of the cohort was 62 ± 12 years and 9.6% (n = 290) of the patients were on prior NSAID use during the index admission. At 12-months follow-up, after adjusting for confounding factors, those on NSAIDs were significantly more likely to have had MACE (adjusted OR (aOR), 1.89; 95% confidence interval (CI): 1.44-2.48; p < 0.001). Specifically, the higher event rates observed were stroke/TIA (aOR, 2.50; 95% CI: 1.51-4.14; p < 0.001) and readmissions for cardiac reasons (aOR, 2.09; 95% CI: 1.59-2.74; p < 0.001) but not MI (aOR, 1.26; 95% CI: 0.80-1.99; p = 0.320) and all-cause mortality (aOR, 0.79; 95% CI: 0.46-1.34; p = 0.383). Conclusions: NSAIDs use was associated with significant stroke/TIA events as well as readmissions for cardiac reasons. However, NSAIDs were not associated with increased MI or all-cause mortality rates in ACS patients in the Arabian Gulf.

(1) Background: This case presents a rare and challenging clinical scenario involving a 50-year-old female patient diagnosed with Inflammatory Carcinoma, a particularly aggressive and rapidly growing form of breast cancer. The disease is characterized by heat, redness, swelling and noticeable changes in the breast's skin texture, resembling the skin of an orange (peau d'orange). This case is important because it contributes to the limited clinical literature on such aggressive forms of breast cancer.; (2) Methods: The multidisciplinary approach was employed. Diagnostic procedures such as imaging tests, biopsy, and histopathological examination were performed to confirm the diagnosis of Inflammatory Carcinoma and assess the extent of the disease. The presence of the HER2 protein on the tumor cells supported the selection of a combination therapy involving systemic chemotherapy and targeted biological therapy.; (3) Results: The patient responded positively to the combination therapy consisting of systemic chemotherapy and targeted biological therapy. The aggressive nature of Inflammatory Carcinoma, characterized by rapid growth and distinct skin changes, was effectively addressed. The presence of the HER2 protein on the tumor cells indicated the potential efficacy of the combination therapy in aggressive forms of breast cancer.; (4) Conclusions: This case highlights the critical importance of a multidisciplinary approach in managing complex cases of breast cancer, especially rare and aggressive subtypes like Inflammatory Carcinoma. The positive response of the patient to the combination therapy involving systemic chemotherapy and targeted biological therapy demonstrates the potential for favorable outcomes in aggressive disease presentations.

Obesity is a troubling public health problem worldwide as it increases risks of respiratory complications, systemic arterial hypertension, type 2 diabetes mellitus, sleep disorders, cardiovascular diseases, and metabolic syndrome (MetS). As a measure to counteract comorbidities associated with severe obesity, bariatric surgery stands out. This study aimed to investigate the adiponectin/leptin ratio in women with severe obesity with and without MetS undergone Roux-en-Y Gastric Bypass (RYGB) and to characterize the biochemical, glucose, and inflammatory parameters of blood in women with severe obesity before and after RYGB. Were enrolled female with severe obesity undergoing RYGP with MetS (n=11) and without (n=39). Anthropometric data and blood samples were obtained before and 6 months after RYGB to analyze total cholesterol, low-density lipoprotein (LDL), high- density lipoprotein (HDL), non-HDL total cholesterol, and glucose; and circulating levels of adiponectin and leptin. Significant reductions in weight, body mass index, and glucose, total cholesterol, LDL, and leptin were observed after surgery, with higher levels of HDL, adiponectin, and adiponectin/leptin ratio observed after surgery compared to preoperative values. This study demonstrated that weight loss induced by RYGB in patients with severe obesity with or without MetS improved biochemical and systemic inflammatory parameters, particularly the adiponectin/leptin ratio.

According to the eminent scholar, philosopher, and physician Avicenna, "the doctor has three tools: the word, the plant, the knife." The plant kingdom is recognized as humanity's earliest and most ancient healing source, employed for the management and prevention of illnesses. Tracing back through history, the most ancient documented proof of plants' utilization in medicine dates back to a Sumerian clay slab discovered in Nagpur roughly 5000 years ago. This artifact included a compilation of twelve medicinal recipes that involved over 250 diverse plant species. Sumerian healers extracted powders and infusions from plant roots and stems, while also crediting healing properties to pears and figs. Additionally, they utilized dried and ground young shoots of willow and plum trees, pine and fir needles as a component in compresses and poultices. Often, powders from animal and mineral sources were blended with those extracted from dried and crushed plants. Notably, in addition to water, wine and beer served as solvents. Thus, at least 80 centuries ago, people utilized the most uncomplicated medicinal plant-based preparations for treatment [1]. The "Pen T'Sao," an ancient Chinese text on roots and herbs, authored by Emperor Shen Nung approximately 2500 BC, contains descriptions of 900 medicaments (comprising dried components of medicinal plants). Several of these substances are still in use today, including Rhei rhisoma, camphor, Theae folium, Podophyllum, great yellow gentian, ginseng, datura, cinnamon bark, and ephedra [2]. Regarding Kazakh folk medicine, an area that has yet to be fully explicated and substantiated, it can be stated that the traditional medicinal knowledge of the Kazakh people transcends the mere treatment of ailments and rests on robust theoretical underpinnings. Oteiboydak Tleukabyluly (1388-1478), an astute healer and prominent figure in Kazakh folk medicine during the 15th century, comprehensively explicated the secrets of the healing art in his medical and ethnographic work "Medical Narrative," which he composed between 1466 and 1473 at the behest of az-Zhanibek Khan, who held him in high esteem as a great healer. This medical encyclopedia delineates the functions of various organs of the human body and provides a catalogue of the primary diseases associated with them. Furthermore, it includes a meticulous description of the methods used in traditional medicine at present, such as setting bones, listening to the pulse, and incantations. Through practical experimentation and experimentation conducted in the steppe laboratory, the healer formulated a total of 1,108 different medicinal compounds, of which 858 were derived from medicinal plants, 318 were extracted from animal organs, and roughly 60 were sourced from metals. The moniker "Teacher without a teacher" was bestowed on Oteiboydak Tleukabylov, who discovered methods for treating 1,050 different diseases [3]. At present, the employment of phytotherapy has gained widespread acceptance on a global scale. According to the World Health Organization's (WHO) global review of national policies concerning traditional, complementary, and alternative medicine, as well as the regulation of herbal medicines, there is an evident growth in the European and Asian market for herbal medicines [4]. Kazakhstan boasts a natural flora of over 6,000 plant species [5]. The exact number of medicinal plant species present in Kazakhstan remains uncertain, as the list continues to expand annually. More than 150 plant species have been employed in both official and folk medicine for various ailments. This review focuses on a selection of medicinal plants growing within the territory of the Republic of Kazakhstan that have traditionally been used to alleviate skin diseases. In conducting this study (2010-2023), emphasis was placed on the plants' phytochemical composition, with a particular focus on the principal components responsible for their therapeutic effects against inflammatory skin conditions such as dermatitis, atopic dermatitis, and eczema.

Intestinal commensal microbes, called the gut microbiota, play a critical role in host immune homeostasis through active microbial metabolites and innate and adaptive immune responses. Dysbiosis or imbalance of the gut microbiota composition is associated with inflammatory bowel disease (IBD) which includes Crohn’s disease and ulcerative colitis. The incidence and prevalence rates of IBD have been increasing worldwide. It is well recognized that butyrate, a microbial metabolite of diet fibers, is a major energy source for colonocytes and plays a crucial role in regulating immune function and maintaining epithelial barrier function and intestinal homeostasis. Emerging evidence suggests that butyrate might be a potential therapeutic agent to treat IBD. In this review, we discuss about gut microbial metabolites, particularly butyrate, the synthesis and metabolism of butyrate, mechanisms of butyrate in immune and epithelial barrier function. Furthermore, we review the current research on various therapeutic implications of butyrate in IBD.

Age-related macular degeneration is a progressive retinal disease that is associated with factors such as oxidative stress, decreased phagocytic activity, and inflammation. In this study, we evaluated the protective effects of SIG-1451, a non-steroidal anti-inflammatory drug developed for treating atopic dermatitis and known to inhibit toll-like receptor 4, on light-induced photoreceptor degeneration. SIG-1451 was intraperitoneally injected into rats once a day before exposure to 1000 lx light for 24 h; one day later, optical coherence tomography showed a decrease in retinal thickness, and electroretinogram (ERG) amplitude was also found to have decreased 3 d after light exposure. Moreover, SIG-1451 protected against this decrease in retinal thickness and increase in ERG am-plitude. One day after light exposure, upregulation of inflammatory response-related genes was observed, and SIG-1451 was found to inhibit this upregulation. Iba-1, a microglial marker, was suppressed in SIG-1451-injected rats. To investigate the molecular mechanism underlying these effects, we used lipopolysaccharide (LPS)-stimulated rat immortalised Müller cells. The upregu-lation of C-C motif chemokine 2　by LPS stimulation was significantly inhibited by SIG-1451 treatment, and western blot analysis revealed a decrease in phosphorylated I-κB levels. These results indicate that SIG-1451 protects photoreceptor cells by attenuating light damage progression through inhibiting inflammatory responses.

Chikungunya virus is a re-emerging mosquito-borne alphavirus. Outbreaks are unpredictable and explosive in nature. Fever, arthralgia, and rash are common symptoms during the acute phase. Diagnostic tests are required to differentiate chikungunya virus from other co-circulating arboviruses, as symptoms can overlap, causing a dilemma for clinicians. Arthritis is observed during the sub-acute and chronic phases, which can flare up, resulting in increased morbidity that adversely affects activities of daily living. During the 2019 chikungunya epidemic in Thailand, cases surged in Bangkok in the last quarter of the year. Here, we demonstrate the chronic sequelae of post-chikungunya arthritis in one of our patients 1 year after the initial infection. An inflammatory process involving edema, erythema, and tenderness to palpation of her fingers' flexor surfaces was observed, with positive chikungunya IgG and negative IgM tests and antigen. The condition produced stiffness in the patient’s fingers and limited their range of motion, adversely affecting daily living activities. Resolution of symptoms was observed with a short course of an anti-inflammatory agent. More research is required to determine whether sanctuaries enable chikungunya virus to evade the host immune response and remain latent, flaring up months later and triggering an inflammatory response that causes post-chikungunya arthritis.

The study explores antibacterial, antiinflammatory and cytoprotective capacity of Pelargonium sidoides DC root extract (PSRE) and proanthocyanidin fraction from PSRE (PACN) under conditions characteristic for periodontal disease. Following previous finding that PACN exerts stronger suppression of Porphyromonas gingivalis compared to the effect on commensal Streptococcus salivarius, the current work continues antibacterial investigation on Staphylococcus aureus, Staphylococcus epidermidis, Aggregatibacter actinomycetemcomitans and Escherichia coli. PSRE and PACN are also studied for their ability to prevent gingival fibroblast cell death in the presence of bacteria or bacterial lipopolysaccharide (LPS), to block LPS- or LPS+IFNγ-induced release of inflammatory mediators, gene expression and surface antigen presentation. Both PSRE and PACN were more efficient in suppressing Staphylococcus and Aggregatibacter compared to Escherichia, prevented A. actinomycetemcomitans- and LPS induced death of fibroblasts, decreased LPS-induced release of interleukin 8 and prostaglandin E2 from fibroblasts and IL-6 from leukocytes, blocked expression of IL-1β, iNOS, and surface presentation of CD80 and CD86 in LPS+IFNγ-treated macrophages, and IL-1β and COX-2 expression in LPS-treated leukocytes. None of the investigated substances affected either the level of secretion or expression of TNFα. In conclusion, PSRE, and especially PACN, possess strong antibacterial, antiinflammatory and gingival tissue protecting properties under periodontitis mimicking conditions and are suggestable candidates for treatment of the disease.

Torenia Concolor Lindley var. formosama Yamazaki ethanolic extract (TCEE) is reported to have anti-inflammatory and anti-obesity properties. However, the effects of TCEE and its underlying mechanisms in the activation of endothelial nitric oxide synthase (eNOS) have not yet been investigated. Increasing the endothelium-derived nitric oxide (NO) production has been known to be beneficial against the development of cardiovascular diseases. In this study, we investigated the effect of TCEE on eNOS activation and NO-related endothelial function and inflammation by using in vitro system. In endothelial cells (ECs), TCEE increased NO production in a concentration-dependent a manner without affecting the expression of eNOS. In addition, TCEE increased the phosphorylation of eNOS at serine 635 residue (Ser635) and Ser1179, Akt at Ser473, calmodulin kinase II (CaMKII) at threonine residue 286 (Thr286) and AMP-activated protein kinase (AMPK) at Thr172. Moreover, TCEE-induced NO production, and EC proliferation, migration and tube formation were diminished by pretreatment with LY294002 (an Akt inhibitor), KN62 (a CaMKII inhibitor) and compound C (an AMPK inhibitor). Additionally, TCEE attenuated the tumor necrosis factor-α-induced inflammatory response as evidenced by the expression of adhesion molecules in ECs and monocyte adhesion onto ECs. These inflammatory effects of TCEE were abolished by L-NG-nitroarginine methyl ester (a NOS inhibitor). Collectively, our findings suggest that TCEE confers protection from endothelial dysfunction by activating the Akt/CaMKII/AMPK/eNOS/NO signaling pathway.

The West-African variety of Sorghum bicolor leaf sheath (SBLS) Jobelyn® is a natural remedy, which has gained international recognition for its anti-anemic effect and energy boosting qualities in debilitating diseases. The widespread use of traditional medicine in the region usually confirms its safety, but not its efficacy or deep assessment of their pharmacological properties. The other major issue for herbal-based treatments is the lack of definite and complete information about the composition of the extracts. Despite limitations, efforts have been made in isolation and characterisation of active compounds in this specie of sorghum showing various subclasses of flavonoids including apigeninidin, a stable 3-deoxyanthocyanidin and potential fungal growth inhibitor, which accounts for 84% of the total extract. Non-clinical in vitro and in vivo studies support previous indications that this variety of Sorghum bicolor possesses several biologically active compounds with potent antioxidant, anti-inflammatory, anti-aging and neuro-protective properties. Clinical studies show that SBLS has the ability to boost hemoglobin concentrations in anemic conditions and most remarkably to increase CD4 count in HIV-positive patients. The multiple effects and high safety profiles of this extract may encourage its development as a therapeutic agent for the treatment of anemia, chronic inflammatory conditions or in the symptomatic management of HIV infections. This review describes the potential therapeutic aspects of SBLS extract and its potential benefits.

The peroxiredoxin (PRDX) family, a new family of proteins with a pivotal antioxidative function, is ubiquitously synthesized and abundantly identified in various organisms. In contrast to the intracellular localization of other family members (PRDX1/2/3/5/6), PRDX4 is the only known secretory form and protects against oxidative damage by scavenging reactive oxygen species in both the intracellular (especially the endoplasmic reticulum) compartments and the extracellular space. Recently, we generated unique human PRDX4 (hPRDX4) transgenic (Tg) mice on a C57BL/6J background and investigated the critical and diverse protective roles of PRDX4 against diabetes mellitus, atherosclerosis, insulin resistance, and nonalcoholic fatty liver disease (NAFLD) as well as evaluated its role in the intestinal function in various animal models. Our published data have shown that PRDX4 helps prevent the progression of metabolic syndrome by reducing local and systemic oxidative stress and synergistically suppressing steatosis, inflammatory reactions, and/or apoptotic activity. These observations suggest that Tg mice may be a useful animal model for studying the relevance of oxidative stress on inflammation and the dysregulation of lipid/bile acid/glucose metabolism upon the progression of human metabolic syndrome, and that specific accelerators of PRDX4 may be useful as therapeutic agents for ameliorating various chronic inflammatory diseases.

The objective of this study was to analyze the epidemiological links of HIV, HCV and HIV-HCV coinfections to less studied types of transmission in certain populations. We performed an observational, prospective study on 903 patients aged between 15-87 years who took part in the Open Test Project. They were divided into two subgroups: general population and individuals from prisons, and questioned about multiple risk factors. Chi-Square Independence Test was used to establish correlations between the risk factors and the results of the screening tests. Logistic regression was used to calculate the probability of a reactive screening test based on each independent risk factor and age. HIV was very strongly associated with unprotected sexual intercourse with HIV-positive partners (the strongest association), unprotected sexual intercourse with sex workers, newly diagnosed sexually transmitted diseases (STDs), intravenous drug use (IDUs) and sharing injecting materials. In the case of HCV reactive tests, very strong associations have been established with injecting drug use (the strongest association), unprotected sexual intercourse with IDUs and sharing injecting materials. Our study indicates the need for implementing targeted public health programs, tailored to the local epidemiology that can ultimately lead to micro-elimination of hepatitis and HIV infections in this area.

The amorphous Fe77Cu1Si13B9 ribbons were treated with pulsed laser interference heating (PLIH). It was confirmed here that the use of the laser heating process allowed for obtaining two-dimensional crystallised micro-areas, periodically distributed (at a distance of 17µm) on the surface of the amorphous ribbons. The correlation between structural changes (SEM, TEM, HRTEM) and the distribution of magnetic field lines of heated amorphous Fe77Cu1Si13B9 (FeCuSiB) ribbons is presented. Particular attention is paid to structure changes in micro-areas where, by controlling the laser interference heating process, partial crystallisation of amorphous alloys and the formation of clusters or single nanocrystallites (α-Fe(Si)) embedded in an amorphous matrix are given. The addition of copper to the FeSiB alloy promoted inhibition of grain growth. Electron holography of micro-areas confirmed shifts of the magnetic field lines in the areas of nanocrystallites, the presence of which in the structure caused magnetisation of the surrounding amorphous matrix.

Energy transition is one of the greatest challenges facing humanity today. All micro, small, medium and large enterprises in operation will have to face it, and some can al-ready boast the first successes in this regard. This paper focuses on the involvement of these smallest players in energy transition. Micro and small entities are the largest part of the economy, having a great influence on its development. Looking at the wide scale of their activities, these entities are distinguished by a specific owner-manager relationship. This means that the final decision-making is influenced by business goals, but also by the manager's approach, their awareness of changes, and personal and other factors. Based on a structured and standardized survey questionnaire, the research was carried out using the Computer-Assisted Telephone Interviewing technique between April and May 2022 among owners of micro and small enterprises operating in Poland. The survey showed that active engagement of micro and small enterprises in energy efficiency initiatives is related to their market success and financial health.

In the paper the experimental methodology for the single-crystal circular plate deformation measurement and subsequent procedure for mechanical properties quantitation are developed. The procedure is based on a new numerical-analytical solution of nonlinear boundary-value problem for finite deformations of a circular anisotropic plate. Using the developed method, a study of the deformation of single-crystal circular plates formed on the basis of a silicon-on-insulator structure was carried out. The values of residual stresses are determined and it is shown that the presence of these stresses increases the flexural rigidity of the plate in several times.

Patients with COVID-19 have coagulation and platelet disorders, with platelet’s alterations and thrombocytopenia representing negative prognostic parameters, being associated with severe forms of the disease, and increase lethality. Methods: Aim of this study was to study expression of platelet glycoprotein IIIa (CD61), playing a critical role in platelet aggregation, together with TRL-2 as a marker of innate immune activation Results: a total of 25 patients were investigated, with the majority (24/25, 96%) having co-morbidities and dying from a fatal form of SARS-CoV-2(+) infection (COVID-19 +), with 13 men and 12 females ranging in age from 45 to 80 years. When compared to a control group of SARS CoV-2 (-) negative lungs (COVID-19 -), TLR-2 expression was up-regulated in a subset of patients with deadly COVID-19 fatal lung illness. The proportion of Spike-1 (+) patients found by PCR and ISH correlates to the proportion of Spike-S1 positive cases as detected by digital pathology examination. Furthermore, CD61 expression was considerably higher in the lungs of dead patients. In conclusion, we demonstrate that innate immune prolonged hyperactivation is related to platelet/megakaryocytes over-expression in the lung. Conclusions: microthrombosis in deadly COVID-19+ lung disease is associated with an increase in the number of CD61+ platelets and megakaryocytes in the pulmonary interstitium as well as their functional activation; this phenomenon is associated with increased expression of innate immunity TLR2+ cells, which binds the SARS-CoV-2 E protein, and significantly with the persistence of the Spike-S1 viral sequence.

A micro-ring resonator structure was fabricated via two-photon polymerization (2PP) technique directly on a single-mode fiber tip and tested for refractive index sensing application. The micro-ring structure was used to excite whispering gallery modes (WGMs) and observations of the changes in resonance spectrum introduced by changes in refractive index of the environment served as the sensing principle. The proposed structure has the advantages of a very simple design, allowing for measurements in reflection mode, relatively easy and fast fabrication and integration with a single tip of a standard single-mode fiber, which allowed for quick and convenient measurements in the optical setup. The performance of structure was characterized, resonant spectrum giving high potential for refractive index sensing was measured. Future perspectives of the research are discussed.

Laser direct writing allows for the fabrication of complex structures, which is particularly advantageous in micro-optic applications. However, the increasing demand for optics quality requires the lowest optical power loss, which can occur from unwanted reflections. This research demonstrates the possibility of forming an anti-reflective coating on hybrid-polymer micro-lenses fabricated by employing laser direct writing (LDW), without changing their geometry. Such coating deposited by atomic layer deposition (ALD) decreased the reflection from 3.3 % to 0.1 % at the wavelength of 633 nm for one surface of SZ2080™.

The use of additive manufacturing in fabricating composite components has been gaining traction in the past decade. However, some issues with mechanical perfor-mance still need to be resolved. The issue of material porosity remains a pertinent one that needs more understanding to be able to determine viable solutions. Different re-searchers have examined the subject of porosity issues in AM-fabricated CFRP compo-sites. However, more research to quantitatively determine the effects of fabrication temperatures at the micro-scale is still needed. This study employed micro CT scan analysis to quantitatively compare the effects of fabrication temperatures at 230°C, 250°C, 270°C, and 290°C for CF-PA and CF-ABS composites. This followed an SEM evaluation which was used to determine the effects of the temperatures on interlayer and intralayer porosity generation. The porosity volume was related to the mechanical properties results in which it was determined how deposition temperatures affect the porosity volumes. It was also determined that semicrystalline composites are generally more affected by fabrication temperatures than amorphous composites, with the rela-tionship between porosity and mechanical properties also established. The overall po-rosity volume from the interlayer and intralayer voids was also determined, with the interlayer voids found to play a more determinant role in influencing the mechanical properties.

Transcription factors (TFs) and microRNAs (miRNAs) are co-actors in genome-scale decoding and regulatory networks, often targeting common genes. In this paper, we describe the algebraic geometry of both TFs and miRNAs thanks to group theory. In TFs, the generator of the group is a DNA-binding domain while, in miRNAs, the generator is the seed of the sequence. For such a generated (infinite) group $\pi$, we compute the $SL(2,\mathbb{C})$ character variety, where $SL(2,\mathbb{C})$ is simultaneously a \lq space-time' (a Lorentz group) and a \lq quantum' (a spin) group. A noteworthy result of our approach is to recognize that optimal regulation occurs when $\pi$ looks like a free group $F_r$ ($r =1$ to $3$) in the cardinality sequence of its subgroups, a result obtained in our previous papers. A non free group structure features a potential disease. A second noteworthy result is about the structure of the Groebner basis $\mathcal{G}$ of the variety. A surface with simple singularities (like the well known Cayley cubic) within $\mathcal{G}$ is a signature of a potential disease even when $G$ looks like a free group $F_r$ in its structure of subgroups. Our methods apply to groups with a generating sequence made of two to four distinct DNA/RNA bases in $\{A,T/U,G,C\}$. Several human TFs and miRNAs are investigated in detail thanks to our approach.

Sources are classified into two depending upon the factor of reviving. These sources, which cannot be revived into their original shape once they are consumed, are considered as nonrenewable energy resources, i.e., (coal, fuel) Moreover, those energy resources which are revivable to the original condition even after being consumed are known as renewable energy resources, i.e., (wind, solar, hydel) Renewable energy is a cost-effective way to generate clean and green electrical energy Now a day’s majority of the countries are paying heed to energy generation from RES Pakistan is mostly relying on conventional energy resources which are mostly nonrenewable in nature coal, fuel is one of the major resources, and with the advent of time their prices are increasing on the other hand RES have great potential in the country with the deployment of RES greater reliability and an effective power system can be obtained In this thesis, a similar concept is being used and a hybrid power system is proposed which is composed of intermixing of renewable and nonrenewable sources The Source side is composed of solar, wind, fuel cells which will be used in an optimal manner to serve load The goal is to provide an economical, reliable, uninterruptable power supply. This is achieved by optimal controller (PI, PD, PID, FOPID) Optimization techniques are applied to the controllers to achieve the desired results. Advanced algorithms (Particle swarm optimization, Flower Pollination Algorithm) will be used to extract the desired output from the controller Detailed comparison in the form of tables and results will be provided, which will highlight the efficiency of the proposed system.

A problem with synthetic aperture radar (SAR) is that, due to the poor penetrating action of electromagnetic waves inside solid bodies, the capability to observe inside distributed targets is precluded. Under these conditions, imaging action is provided only on the surface of distributed targets. The present work describes an imaging method based on the analysis of micro-movements on the Khnum-Khufu Pyramid, which are usually generated by background seismic waves. The results obtained prove to be very promising, as high-resolution full 3D tomographic imaging of the pyramid's interior and subsurface was achieved. Khnum-Khufu becomes transparent like a crystal when observed in the micro-movement domain. Based on this novelty, we have completely reconstructed internal objects, observing and measuring structures that have never been discovered before. The experimental results are estimated by processing series of SAR images from the second-generation Italian COSMO-SkyMed satellite system, demonstrating the effectiveness of the proposed method.

Organ-on-a-Chip (OoC) systems bring together cell biology, engineering, and material science for creating systems that recapitulate the in vivo microenvironment of tissues and organs. The versatility of OoC systems enables in vitro models for studying physiological processes, drug development, and testing in both academia and industry. This paper evaluates current platforms from the end-user perspective, elaborating on usability, complexity, and robustness. We surveyed 165 peers in over 30 countries and grouped the responses according to preliminary knowledge and the source of the OoC systems that are used. The survey clearly shows that current commercial OoC platforms provide a substantial level of robustness and usability - which is also indicated by an increasing adaptation of the pharmaceutical industry but a lack of complexity can challenge their use as a predictive platform. Self-made systems on the other hand are less robust and standardized but provide the opportunity to develop customized and more complex models which are often needed for human disease modeling. This review serves as a guide for researchers in the OoC field and encourages the development of next-generation OoCs.

In laser joining of copper (Cu) and aluminum (Al) sheets, the Al sheet is widely chosen as the top surface for laser irradiation because of increased absorption of laser beam and lower melting temperature of Al in contrast to Cu. This research focus on welding from Cu side to Al sheet. The main objective of irradiating the laser beam from the copper side (Cu on top) is to exploit higher solubility of Al in Cu. A significantly lower laser power can be used with 515 nm laser in comparison to 1030 nm. In addition to low laser power, a stable welding is obtained with 515 nm. Because of this advantage, 515 nm is selected for the current research. By fusion of Cu and Al the two sheet metals are welded, with presence of beneficial Cu solid solution phase and Al+Al2Cu in the joint with the brittle phases intermixed between the ductile phase. Therefore the mixed composition strengthens the joint. However excessive mixing leads to formation of more detrimental phases and less ductile phases. Therefore optimum mixing must be maintained. Energy dispersive X-ray spectroscopy (EDS) analysis indicate that large amount of beneficial Cu solid solution and Al rich phases is formed in the strong joint. From the tensile shear test for a strong joint, fracture is obtained on the heat-affected zone (HAZ) of Al. Therefore the key for welding from copper side is to have optimum melt with beneficial phases like Cu and Al+ Al2Cu and the detrimental phases intermixed between the ductile phases

The space gravitational wave detection and drag free control requires the micro-thruster to have very low thrust noise within 0.1mHz~100mHz, which poses a great challenge to the ground thrust test. The evaluation and decoupling of thermal noise are the difficulties in the application of torsion balance for most thrusters dissipate heat in the experiment. The research has adopted a calibration scheme of micro-Newton thrust torsion balance. On the basis of Lisa Pathfinder's former research and using ideas inspired from PID control and multi time scale (MTS) for reference, the paper proposes to expand the state space of temperature to be applied on thrust prediction based on fine tree regression (FTR), to subtract the thermal noise filtered by transfer function fitted with z-domain vector fitting (ZDVF). The results show that the thrust amplitude thrust density in diurnal temperature fluctuation is decoupled from 24μN/Hz1/2 to 4.9μN/Hz1/2 at 0.11mHz. And the 1μN square wave modulations of electrostatic fins (ESF) is extracted from the simultaneously ambiguous background of temperature for PTC's heating and cooling. The FTR method is well demonstrated in thermal noise decoupling and can guide the design of thermal control and be extended to other physical quantities for noise decoupling.

Hand and arm gesture recognition using radio frequency (RF) sensing modality proves valuable in man-machine interface and smart environment. In this paper, we use time series analysis method for accurately measuring the similarity of the micro-Doppler (MD) signatures between the training and test data, thus providing improved gesture classification. We characterize the MD signatures by the maximum instantaneous Doppler frequencies depicted in the spectrograms. In particular, we apply the dynamic time warping (DTW) method and compare its performance with that of the long short-term memory (LSTM) network. Both methods take into account the values as well as the temporal evolution and trends of time series data. It is shown that the DTW method achieves high gesture classification rates and is robust to time misalignment.

Epigenetic changes are a hallmark of short- and long-term transcriptional regulation, and hence instrumental in the control of cellular identity and plasticity. Epigenetic mechanisms leading to changes in chromatin structure, accessibility for recruitment of transcriptional complexes, and interaction of enhancers and promoters all contribute to acute and chronic adaptations of cells, tissues and organs to internal and external perturbations. Similarly, the peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) is activated by stimuli that alter the cellular energetic demand, and subsequently controls complex transcriptional networks responsible for cellular plasticity. It thus is of no surprise that PGC-1α is under the control of epigenetic mechanisms, and constitutes a mediator of epigenetic changes in various tissues and contexts. In this review, we summarize the current knowledge of the link between epigenetics and PGC-1α in health and disease.

Since their discovery in 1993, numerous microRNAs (miRNAs) have been identified in humans and other eukaryotic organisms, and their role as key regulators of gene expression is still being elucidated. It is now known that miRNAs not only play a central role in the processes that ensure normal development and physiology, but they are often dysregulated in various diseases. In this review, we present an overview of the role of miRNAs in normal renal development and physiology, in maladaptive renal repair after injury, and in the pathogenesis of renal parenchymal diseases. In addition, we describe methods used for their detection and their potential as therapeutic targets. Continued research on renal miRNAs will undoubtedly improve our understanding of diseases affecting the kidneys and may also lead to new therapeutic agents.

Social recommendation is almost as the integration of the business platform and social platform, and gradually become a top in recommendation system. Social recommendation algorithm solves the problem of cold start and data sparseness for traditional commodity, while the internal structure of the relationship graph in social relations has not been fully excavated. This paper proposes two models of Micro Relation Transfer Model and Macro Relation Transfer Model of social relations, and applies the social relations transfer models into the social recommendation system. A relationship graph is built from the relationship between customers on the Internet. Micro Relation Transfer Model establishes the transfer activation function by calculating the relationship between the two customers using the similarity of interests set. Micro Relation Transfer Model spreads the relationship of friends by calculating the proportion of common neighbors held by the customer's social relations. In order to effectively control the transmission range and effect of social relations graph, we introduce pruning algorithm based on Monte Carlo Decision Tree convergence algorithm. The experimental results show that SRRTC algorithm enhances the success rate and stability significantly.

Background. Coronary artery disease (CAD) with extensive stenosis presents significant clinical challenges. This case report details the management and outcomes of a 61-year-old male with a notable history of CAD, initially treated with coronary artery bypass grafting (CABG), followed by an innovative intravenous hydrogen and oxygen nanobubble therapy due to recurrent symptoms.Case Presentation. Mr. BH was diagnosed with significant stenosis in the left anterior descending (LAD) artery and left circumflex (LCx) artery, initially managed by CABG. Recurring symptoms led to the adoption of a novel treatment involving hydrogen and oxygen nanobubbles. Following treatment initiation, Mr. BH experienced substantial improvements in physical capacity and symptomatic relief, with an ability to climb 22 flights of stairs and resolution of previous symptoms such as dyspnea and cough. Despite these improvements, subsequent imaging revealed in-stent restenosis and progression of graft disease.Discussion. The application of hydrogen and oxygen nanobubbles as a therapy in CAD is explored, highlighting potential mechanisms such as reduction of oxidative stress and improvement in endothelial function. This case contrasts the effects of conventional surgical and pharmaceutical interventions with the novel nanobubble therapy, illustrating both the benefits and complexities of managing advanced CAD with innovative treatments.Conclusion. While Mr. BH showed clinical improvement with nanobubble therapy, the development of new severe stenosis and restenosis underscores the need for further research to understand the long-term efficacy and mechanisms of nanobubble therapy in complex CAD cases. This case suggests that while innovative therapies may provide symptomatic relief and functional improvement, they do not obviate the need for ongoing surveillance and possibly further intervention.

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

The increasing demand by consumers for popular healthy fruits, such as the watermelon (Citrullus lanatus), generate substantial bio-wastes, making it imperative to harness the value of these by-products. Watermelon has low-calorie content and several other nutritional benefits that make it suitable for weight management and heart-healthy diets. Within this article, the nutritional composition and bioactives of watermelon which are strongly linked to the prevention of cardiovascular disorders (CVD), cancer, and age-related conditions, will be thoroughly reviewed. In addition, the therapeutic potential effects of watermelon consumption, such as anti-inflammatory, cardio-protective and anti-cancer properties, are also examined, with emphasis to the importance of incorporating watermelon into regular diets for overall health improvement. Additionally, the study explores various applications of watermelon by-products in functional foods, contributing to meeting recommended daily nutrient allowances, as well as in other functional products like cosmetics, with health promoting properties. In conclusion, this comprehensive review underscores the role of watermelon and its by-products for the development of products that can contribute to the prevention of chronic diseases and promote overall well-being

Musculoskeletal infections (MIs) are among the most difficult-to-treat staphylococcal diseases. The limited availability of effective antibiotics has encouraged the development of innovative strategies such as combinatory therapy to combat MI. The aim of this study was to investigate the in vitro antistaphylococcal activity of anti-inflammatory and the antimicrobial combinatory effect of celecoxib with oxacillin. The minimum inhibitory concentrations (MICs) of 17 anti-inflammatory drugs were determined for standard strains and clinical isolates of S. aureus strains, counting methicillin-resistant strains (MRSA), by the broth microdilution method. The fractional inhibitory concentration indices (FICIs) were evaluated by the checkerboard assays. Celecoxib produced the most potent antistaphylococcal effect against all the tested strains (MIC ranging from 32 to 64 mg/mL), followed by diacerein against MRSA3 and MRSA ATCC 33592 (MIC 64 mg/mL). Several synergistic effects were observed for tested S. aureus strains, including MRSA (FICI ranging from 0.087 to 0.471). The strongest synergistic interaction (FICI 0.087) was obtained against MRSA ATCC 33592 at a celecoxib concentration of 2 mg/mL with a 19-fold oxacillin MIC reduction (from 512 to 26.888 mg/mL). This is the first report on the antistaphylococcal combinatory effect of celecoxib with oxacillin. Our findings suggest celecoxib and its combination with oxacillin as perspective agents for research focused on the development of novel therapies for MI caused by S. aureus. Thus, this study presents novel findings that celecoxib could, in some cases, resensitise MRSA strains to become susceptible to certain β-lactams (e.g., oxacillin) not previously tested.

Iron deficiency (ID) is by far the most common nutritional disorder in developing and developed countries. When left untreated, ID leads to anemia. Although the usual recommended treatment for iron deficiency anemia (IDA) is oral iron therapy with countless products, such therapy necessitates administration for &gt;3-6 months with questionable patient compliance since most oral iron products have an unpleasant metallic aftertaste and cause intestinal side effects. In addition, in certain gastrointestinal conditions, such as inflammatory bowel diseases or untreated gluten-sensitive enteropathy, oral iron therapy is contraindicated or unsuccessful. Intravenous iron is considered safe in adults, where adverse events are mild and easily managed. The experience with parenteral iron in children is much more limited and many pediatricians appear reluctant to use it because of uncorroborated fears of serious anaphylactic reactions. In the current article, we thoroughly review the available pediatric literature on the use of all commercially available parenteral iron products except ferumoxytol, which was recently removed from the market. We conclude that parenteral iron appears to be safe in children, it works faster than oral iron and the newer third-generation products allow replacement of the total iron deficit at a single setting.

A patient in her early 20s presented with constant and progressive lower abdominal and back pain, mainly on the right side of the abdomen, purulent vaginal discharge and pyrexia. Radio-logical assessment revealed a possible tuboovarian abscess and incidental diagnosis of ipsilateral renal agenesis. The patient was treated for pelvic inflammatory disease (PID), however after antibiotic administration and since the symptoms were not resolving, an abdominal MRI was requested which revealed a uterus didelphys with two cervices, an obstructed haemivagina and evidence of haematocolpos. The diagnosis of OHVIRA syndrome was confirmed and the patient underwent an excision of the vaginal septum, drainage of the haematopyocolpos and laparoscopic drainage of the tuboovarian abscess. She achieved a good recovery.

Purpose: Inflammation of various degrees is common among humans. There are associated side effects with orthodox delivery systems and anti-inflammatory agents hence the study investigated the characteristics of herbal lipospheres and the anti-inflammatory potency of the lipospheres formulated from Pentaclethra macrophylla with the view to having a drug with a better delivery system and lesser side effects.Methods: Herbal lipospheres were formulated using solidified reverse micellar solutions (SRMS) of P90H and goat fat and characterized for particle size and morphology, pH – time dependent analysis, encapsulation efficiency (EE%) and Fourier Transform infrared spectroscopy. The in vitro antinociceptive and anti-inflammatory study were carried out using membrane stabilization by hypotonicity induced haemolysis and determination of anti-platelet aggregatory activity models. The in-vivo anti-nociceptive and anti-inflammatory studies on egg albumin and formaldehyde induced arthritis models were done. Total white blood cell count and differential blood count were carried out on the rats. Results: The results showed that there was no change in pH for the PM unloaded lipospheres and 2.5g of PM-loaded lipospheres from Day 1 to Day 7, but mild variation in the rest of the formulations. The EE ranged from 35.2% to 94% increasing according to the drug concentration. The photomicrographs of the lipospheres showed that the particles were spherical in shape. The particle sizes were within the acceptable range for lipospheres. FTIR showed no interaction. In the arthritis study, PM-loaded lipospheres inhibited edema consistently throughout the duration of observation. Inhibition of membrane increased steadily with an increase in concentration of PM in the lipospheres and the standard drug. The platelet aggregatory inhibition decreased steadily with an increase in concentration of the PM in the lipospheres as well as the standard. The T50 dose of PM had the highest percentage of WBC and it decreased as the treatment doses increased from T100 to T200. There was no significant differences among the Neutrophil counts of the different groups.Conclusion: The study, therefore, showed that the methanol extract of Pentaclethra macrophylla formed efficient herbal lipospheres with antinociceptive and anti-inflammatory activities.

Psoriatic arthritis (PsA) is a persistent, inflammatory disease that affects individuals with psoriasis, arthritis, and enthesitis. Research has demonstrated that inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin-23 (IL-23), and interleukin-17 (IL-17) play a pivotal role in both the onset and progression of PsA. These cytokines are generated by activated immune cells and stimulate the attraction of inflammatory cells to the synovium and joint tissues, resulting in the deterioration of cartilage and bone. The blocking of these cytokines has become a successful treatment strategy for PsA, as biological drugs that inhibit TNF-α, IL-23, and IL-17 have demonstrated notable clinical benefits. The association between PsA and other types of inflammatory cytokines or chemokines, excluding TNF-α, IL-23, and IL-17, has been extensively investigated in numerous studies. These findings may provide a chance for the discovery of novel therapeutic agents targeting other molecules, distinct from the currently approved biologics and targeted synthetic disease-modifying antirheumatic drugs. In this review, we discuss the current understanding of the role of inflammatory cytokines in PsA pathogenesis and clinical implications of targeting these cytokines for PsA treatment.

This study evaluated the anti-inflammatory effects, protection of gut barrier integrity, and stimulation of phagocytosis in peripheral cells of a nutritional supplement based on a synergistic combination of yeast-based ingredients with a unique 1,3/1,6-glucan complex and a consortium of postbiotic Saccharomyces cerevisiae rich in selenium and zinc. The anti-inflammatory effect in Caco-2 cells in the presence and absence of a pro-inflammatory challenge (tumour necrosis factor alpha [TNF-α]/interferon gamma [IFN-ɣ]) showed statistically significant reductions of IFN-ɣ induced protein-10 (IP-10), and monocyte chemoattractant protein-1 (MCP-1) levels vs. controls (p &lt; 0.001). Disruption of the gut integrity in the presence or absence of Escherichia coli (ETEC H10407) showed transepithelial electrical resistance (TEER) values higher in the ABB C1® group after 6 hours of testing. Spontaneous build-up of the gut epithelium monolayer over 22 days was also greater in the ABB C1® condition vs. a negative control. ABB C1® showed a significantly higher capacity to stimulate phagocytosis as compared with controls of algae β-1,3-glucan and yeast β-1,3/1,6 glucan (p &lt; 0.001). This study supports the mechanism of action by which ABB C1® may improve the immune response and be useful to prevent infection and allergy in clinical practice.

Porifera, commonly referred to as marine sponges, have stood out as major producers of marine natural products (MNPs). Sponges of the genus Phorbas have attracted much attention along years. They are widespread in all continents, and several structurally unique compounds have been identified from species of this genus. Terpenes, mainly sesterterpenoids, represent the great majority of secondary metabolites isolated from Phorbas species, even though several alkaloids and steroids have also been reported. Many of these compounds have shown a variety of biological activities. Particularly, Phorbas sponges have been demonstrated to be a source of cytotoxic metabolites. In addition, MNPs exhibiting cytostatic, antimicrobial and anti-inflammatory activities, have been isolated and structurally characterized. This work brings an overview of Phorbas secondary metabolites reported since the first study published in 1993 until 2020, and their biological activities.

Citrus peel has been used in Asian traditional medicine for the treatment of cough, asthma, and bronchial disorders. However, the anti-inflammatory effect of quercetogetin (QUE), a polymethoxylated flavone isolated from the peel of citrus unshui is poorly understood. We investigated the anti-inflammatory effect and the molecular mechanisms of QUE in lipopolysaccharide (LPS)-induced RAW264.7 cells. QUE inhibited the production of NO and prostaglandin E2 by suppressing the LPS-induced expression of inducible nitric oxide synthase and cyclooxygenase-2 at both the mRNA and protein levels. QUE suppressed the production of proinflammatory cytokines, such as interleukin (IL)-1β, IL-6, and tumor necrosis factor-α. QUE also inhibited the translocation of the nuclear factor kappa B subunit, p65, into the nucleus by interrupting the phosphorylation of IκB-α in LPS-induced RAW 264.7 cells. Based on the finding that QUE significantly decreased p-ERK protein expression in LPS-induced RAW264.7 cells, we confirmed that suppression of the inflammatory process by QUE was mediated through the MAPK pathway. This is the first report on the strong anti-inflammatory effects of QUE, which is a compound that can potentially be used as a therapeutic agent for inflammatory diseases.

Probiotics have been used to ameliorate gastrointestinal symptoms since ancient times. Over the past 40 years, probiotics have been shown to exert major effects on the immune system, both in vivo and in vitro. This interaction is clearly linked to gut microbes, their polysaccharide antigens, and key metabolites produced by these bacteria. At least four metabolic pathways have been implicated in mechanistic studies of probiotics, based on carefully studied animal models. Microbial-immune system crosstalk has been linked to short chain fatty acid production and signaling, tryptophan metabolism and the activation of aryl hydrocarbon receptors, nucleoside signaling in the gut, and activation of the intestinal histamine-2 receptor. Several randomized controlled trials have now shown that microbial modification by probiotics may improve gastrointestinal symptoms and multi-organ inflammation in rheumatoid arthritis, ulcerative colitis, and multiple sclerosis. Future work will need to carefully assess safety issues, selection of optimal strains and combinations, and attempts to prolong the duration of colonization of beneficial microbes.

The aim of the study was to determine the possibility of suppression of the prostaglandin synthesis by new derivatives of N-phenylanthranilic acids; they inhibit the activity of the microsomal prostaglandin E synthase-1 (mPGES-1) enzyme using the method of a flexible molecular docking. For the docking studies the crystallographic structural models with high resolution from Protein Data Bank were used: mPGES-1 in the complex with glutathione (pdb code 4AL0). A flexible molecular docking was carried out using the Molecular Operating Environment (MOE) software package. According to the results of the docking studies four scoring functions were calculated (Affinity dG Scoring, Alpha HB Scoring, London dG Scoring, GBVI/WSA dG Scoring). The values of the scoring functions calculated indicate the thermodynamic probability and energy favorability of forming complexes between molecules of the substances under research and the specified receptor, in which arrangement of ligands in the active site of the receptor and residues of amino acids of side chains are of similar geometry and types of binding of the known inhibitors of mPGES-1 determined on the basis of the crystallographic studies.

From the aerial parts of Salvia ballotiflora, eleven diterpenoids were isolated, among them, four icetexanes, and one abietane (1–5), which are first reported. Their structures were established by spectroscopic means, mainly ¹H and ¹³C NMR, including 1D and 2D homo- and hetero-nuclear experiments. Most of the isolated diterpenoids were tested for their antiproliferative, anti-inflammatory, and radical scavenging activities using the sulforhodamine B assay on six cancer cell lines, the TPA induced ear edema test in mice, and the reduction of the DPPH assay, respectively. Some diterpenoids showed anti-proliferative activity, these being icetexanes 6 and 3, which were the most active with IC₅₀ (µM) = 0.27 ± 0.08 and 1.40 ± 0.03, respectively, for U251 (human glioblastoma) and IC₅₀ (µM) = 0.0.46 ± 0.05, and 0.82 ± 0.06 for SKLU-1 (human lung adenocarcinoma), when compared with adriamycin (IC₅₀ (µM) = 0.08 ± 0.003, and 0.05 ± 0.003, as the positive control, respectively. Compounds 3 and 10 showed significant reduction of the induced ear edema of 37.4 ± 2.8 and 25.4 ± 3.0% (at 1.0 µmol/ear), respectively. Compound 4 was the sole active diterpenoid in the antioxidant assay (IC₅₀ = 98. 4 ± 3.3), using α-tocopherol as positive control, IC₅₀ (µM) = 31.7 ± 1.04. The diterpenoid profile found is of chemotaxonomic relevance and reinforces the evolutionary link of S. ballotiflora with other members of the section Tomentellae.

High pressure crystallization technique has been successfully used to prepare an elusive form II of a non-steroidal anti-inflammatory drug, Mefenamic acid. Single crystal of form II was grown at 0.3 GPa from an 4:1 methanol/ ethanol mixture as a solvent using Diamond Anvil Cell. Comparison of crystal structures show that the efficient packing of MA molecules in Form II results from the structural flexibility of MA acid molecules. Compression studies performed on the single crystal of form I resulted in 14 % decrease of unit cell volume up to 2.5 GPa. No phase transition was observed up to this pressure. A reconstructive phase transition is required to induce conformational changes in the structure, which is confirmed by crystallization at high pressure results.

The human body contains 60-70% of water, depending on age. As a body fluid, it is not only a medium in which physical and chemical processes take place, but it is also one of the active mediators. Water is the richest substance with non-covalent hydrogen bonds. Water molecules, by themselves (in vacuum), are diamagnetic, but when organized into clusters, become diamagnetic or paramagnetic. Also, biomolecules (DNA, collagen, clathrin, and other proteins) have non-covalent hydrogen bonds in their structure. The interaction, as well as signal transmission, between water and biomolecules is achieved through the vibrations of covalent and non-covalent hydrogen bonds, which determine the state and dynamics of conformational changes of biomolecules. Disruptive conformational changes of biomolecules, cells, and tissues lead to their dysfunctionality, so they are a frequent cause of many disorders and diseases. For example, the rearrangement of hydrogen bonding due to mitochondrial disease mutation in cytochrome bc1 disturbs heme bH redox potential and spin state. In order to prevent and repair the dysfunctional conformational changes, a liquid substance was developed based on the second derivative of the C₆₀ molecule (SD-C₆₀), which has classical and quantum properties. Characterization of SD-C₆₀ by UV-VIS-NIR, FTIR, TEM, and AFM/MFM was done and it is shown that SD-C₆₀ water layers generate vibrations with near-zero phase dispersion which are transmitted through the Fibonacci’s water chains to biomolecules. In comparison to previously published SD-C₆₀ derivate (3HFWC, size until 10 nm, and 1-5 water layers), improved formulation (3HFWC-W, size 10-25 nm, and 6-9 water layers) showed multiplied cytotoxic activity against melanoma cell lines of different aggressiveness. Apart from this, the mode of action was preserved and based on induction of senescence rather than cell death. Importantly, high selectivity toward malignant phenotype was detected. Observed effects can be ascribed to a machinery of hydrogen bonds, which are generated in SD-C₆₀ and transmitted through water to biomolecules. This approach may open a new field in science and healthcare - a “water-based nanomedicine”.

Large animal experiments are important for preclinical studies of regenerative stem cell transplantation therapy. Therefore, we investigated the differentiation capacity of pig skeletal muscle-derived stem cells (Sk-MSCs) as an intermediate model between mice and humans for nerve muscle regenerative therapy. Enzymatically extracted cells were obtained from green-fluorescence transgenic micro-mini pigs (GFP-Tg MMP) and sorted as CD34+/45- (Sk-34) and CD34-/45-/29+ (Sk-DN) fractions. The ability to differentiate into skeletal muscle, peripheral nerve, and vascular cell lineages was examined by in vitro cell culture and in vivo cell transplantation into the damaged tibialis anterior muscle and sciatic nerves of nude mice and rats. Protein and mRNA levels were analyzed using RT-PCR, immunohistochemistry, and immunoelectron microscopy. The myogenic potential, which was tested by Pax7 and MyoD expression and the formation of muscle fibers, was higher in Sk-DN cells than in Sk-34 cells but remained weak in the latter. In contrast, the capacity to differentiate into peripheral nerve and vascular cell lineages was totally stronger in Sk-34 cells. In particular, Sk-DN cells did not engraft to the damaged nerve, whereas Sk-34 cells showed active engraftment and differentiation into perineurial/endoneurial cells, endothelial cells, and vascular smooth muscle cells, similar to the human case, as previously reported. Therefore, we concluded that Sk-34 and Sk-DN cells in pigs were closer to those in humans than to those in mice.

Background: Transient receptor potential cation channel subfamily A member 1 (TRPA1) is expressed in trigeminal neurons and brain regions important in migraine pathogenesis and is activated by many migraine triggers. Epigenetic regulation of TRPA1 expression is important in pain transmission and neurogenic inflammation.Findings: TRPA1 channels change noxious stimuli into pain signals with the involvement of epigenetic regulation, including DNA methylation, histone modifications, and effects of micro RNAs (miRNAs) and long non-coding RNAs. TRPA1 may change epigenetic profile of many pain-related genes as it may modify enzymes establishing the epigenetic profile and expression of non-coding RNAs. TRPA1 may induce the release of calcitonin gene related peptide (CGRP), from trigeminal neurons and dural tissue. Therefore, epigenetic regulation of TRPA1 may play a role in efficacy and safety of anti-migraine therapies targeting TRP channels and CGRP. TRPA1 is also involved in neurogenic inflammation, important in migraine. The fundamental role of TRPA1 in inflammatory pain transmission may be epigenetically regulated. Conclusions: Epigenetic connections of TRPA1 may play a role in efficacy and safety of anti-migraine therapy targeting TRP channels or CGRP and they should be further explored for efficient and safe antimigraine treatment.

A pilot study on laser 3D printing of inorganic free-form micro-optics is experimentally validated. Ultrafast laser nanolithography is employed for structuring hybrid organic-inorganic material SZ2080TM followed by high-temperature calcination post-processing. The combination allows production of 3D architectures and the heat-treatment results in converting the material to inorganic substance. The produced miniature optical elements are characterized and their optical performance demonstrated. Finally, the concept is validated for manufacturing compound optical components such as stacked lenses. This is opening for new directions and applications of laser made microoptics under harsh conditions such as high intensity radiation, temperature, acidic environment, pressure variations, which include open space, astrophotonics, and remote sensing.

Abstract: The glucocorticoid receptor (GR), including both alternative spliced isoforms (GRa and GRb), has been implicated in the development of primary open-angle glaucoma (POAG) and iatrogenic glucocorticoid-induced glaucoma (GIG). POAG is the most common form of glaucoma, which is the leading cause of irreversible vision loss and blindness in the world. Glucocorticoids (GCs) are commonly used therapeutically for ocular and numerous other diseases/conditions. One serious side effect of prolonged GC therapy is the development of iatrogenic secondary ocular hypertension (OHT) and OAG (i.e. GC-induced glaucoma (GIG)) that clinically and pathologically mimics POAG. GC-induced OHT is caused by pathogenic damage to the trabecular meshwork (TM), a tissue involved in regulating aqueous humor outflow and intraocular pressure. TM cells derived from POAG eyes (GTM cells) have lower expression of GRb, a dominant negative regulator of GC activity, compared to TM cells from age-matched control eyes. Therefore, GTM cells have a greater pathogenic response to GCs. Almost all POAG patients develop GC-OHT when treated with GCs, in contrast to a GC responder rate of 40% in the normal population. Increased expression of GRb can block GC-induced pathogenic changes in TM cells and reverse GC-OHT in mice. Endogenous expression of GRb in the TM may relate to differences in the development of GC-OHT among the normal population. A number of studies have suggested increased levels of endogenous cortisol in POAG patients as well as differences in cortisol metabolism, suggesting that GCs may be involved in the development of POAG. Additional studies are warranted to better understand the molecular mechanisms involved in POAG and GIG in order to develop new disease modifying therapies to better treat these two sight threatening forms of glaucoma.

Background and aim. The study aimed to assess the efficacy of the treatment of Kan Jang®, a fixed combination of Andrographis paniculata (Burm. F.) Wall. ex. Nees and Eleutherococcus senticosus (Rupr. & Maxim.) Maxim in patients with mild symptoms of COVID-19. Methods. One hundred forty patients received six capsules of Kan Jang® (n = 68, daily dose of andrographolides – 90 mg) or placebo (n=72) and supportive treatment (paracetamol) for 14 consecutive days in a randomized, quadruple-blinded, placebo-controlled, two-parallel-group design. The efficacy outcomes were the rate of cases turning to severe, the detection rate of SARS-CoV-2 virus over the time of treatment, the duration and the severity of symptoms (sore throat, runny nose, cough, headache, fatigue, loss of smell, taste, pain in muscles) in the acute phase of the disease. Other efficacy measures included improving cognitive and physical performance, quality of life, and the levels of inflammatory blood markers - IL-6, c-reactive protein, and D-dimer. Results. Kan Jang® significantly (p < 0.05) reduced the rate of cases turning to severe (5.36%) compared to placebo (17.86%) and decreased the detection rate of SARS-CoV-2 virus over the time of treatment. The statistical difference in the rates of patients with clinical deterioration in the Kan Jang treatment and placebo control groups was significant (p = 0.0176) both in 112 patients included per protocol (IPP) analysis and in 140 patients included per intention to treat (ITT) analysis (p = 0.0236); the absolute risk reduction of cases by Kan Jang treatment was 12.5%, and the number Needed to Treat by Kan Jang was 8. The patient's recovery time (Number of sick days at the home/clinic) was shorter in the Kan Jang group compared with the placebo group. The rate of resolution of inflammatory symptoms in the Kan Jang® group was significantly higher compared with the placebo group, and relief of the severity of cough, sore throat/pain, runny nose, and muscle soreness. Kan Jang® significantly decreased the Wisconsin Upper Respiratory Symptoms scores compared to placebo in the sample size of 140 patients. However, the relief of fatigue and headache and the decrease of IL-6 in the blood was observed only in a subset of the 86 patients infected during the second three waves of the pandemic. Kan Jang® significantly increased physical activity and workout; however, it did not affect cognitive functions (attention and memory), Quality of life Score, inflammatory markers D-dimer, and c-reactive protein compared with the placebo group. Conclusions. Overall, the results of this study suggest that Kan Jang® is effective in treating mild and moderate COVID-19 irrespective of SARS-Cov-2 variants infection.

Background: The aim of this study has been to investigate if inflammatory biomarkers such as the systemic immune-inflammation index (SII), neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) have any correlation with the recurrence of pleomorphic adenomas (PA) in patients afflicted by this disease. Methods: A retrospective multicentre study involving two Italian centres, the Maxillofacial Sur-gery at the Policlinico Federico II in Naples and the ENT and Maxillofacial Surgery at the IRCCS G. Pascale National Cancer Institute in Naples, has been performed. The study, involving 608 pa-tients who had received a diagnosis of PA, was conducted between January 2000 and January 2020. A Receiver Operating Characteristic (ROC) curve was used to calculate the optimal cut-off values for the SII, PLR and NLR. A linear regression model (LRM) and a non-linear logistic re-gression model (NLRM) were realized with respect to the NLR, PLR and SII. Results: The highest performance was achieved by the NLR (cut-off 2.960) with the AUC = 0.91, with an accuracy of 96.1%, sensitivity of 78.4% and specificity of 97.2%, PPV = 64.4% and NPV = 98.6%. The LRM and NLRM including all the haematological parameters did not increase the per-formance in terms of recurrence detection. Conclusion: The NLR is an excellent support tool in predicting the recurrence of PA with a cut-off of 2.960. It can be a good reference point for surgical decision-making and follow-up in clinical practice.

The plethora of bio-functional compounds present in fermented alcoholic beverages like wine, as well as the valorization of bioactives from their wineries/breweries by-products like grape pomace and grape seed, has gained significant interest in the functional foods sector. Wine has always accompanied humanity, for religion or for health. For example, Christians are using wine in the “Holy Communion”, following what Jesus Christ himself did and said during the Last Supper, while the benefits of the wine consumption in moderation was embedded in all Mediterranean civilizations, as it is mentioned by the wise King-Prophet David in his psalms, but also by Hip-pocrates and other wise men, in a Greek-based philosophy of “All things in Moderation” (Cleobulus of Lindos; 6th century BC). In modern times, and after the outbreak of research on wine benefits since the 90’s, when the term “French Paradox” was introduced in the US public during a CBS show, recent evidence has outlined that these benefits are derived by the synergisms of its bio-functional compounds and their digestion-derived metabolites. Within this article, the proposed health benefits of moderate wine consumption, as a functional component of a balanced diet (i.e. the Mediterra-nean Diet), against inflammation-related chronic disorders, is thoroughly reviewed. The various bio-functional compounds of both wine and wineries’ by-products, such as their bioactive phe-nolics, unsaturated fatty acids, polar lipids, and dietary fibers, and their functional antioxidant, anti-inflammatory and antithrombotic health promoting properties are also thoroughly evaluated. The mechanisms of actions and synergism, by which the health benefits are elicited, are also ex-plored. Functional properties of non-alcoholic wine products are also introduced. Emphasis is also given to applications of wineries’ by-products bioactives, as ingredients of bio-functional foods, supplements and nutraceuticals. Limitations and future perspectives for this popular functional alcoholic beverage (wine) ant its rich in bioactives by-products are also addressed. .

In the multicenter, non-randomized, exploratory C-reactive protein (CRP) Apheresis in Myocardial Infarction (CAMI-1) study, CRP apheresis after ST-Elevation Myocardial Infarction (STEMI) significantly decreased blood CRP concentrations in humans. Cardiac damage was assessed by Cardiac Magnetic Resonance (CMR1) 3-9 d after onset of STEMI symptoms and quantified by myocardial infarct size (IS; %), left ventricular ejection fraction (LVEF; %), circumferential strain (CS) and longitudinal strain (LS) Compared with the control group (n=34), cardiac damage was significantly lower in the apheresis group (n=32). These findings suggested improved wound healing due to CRP apheresis already within few days after the STEMI event. In the current supplementary data analysis of CAMI-1, we have tested by a follow-up CMR (CMR2) after an average of 88 (65-177) d whether the effect of CRP apheresis is clinically maintained. After this time period wound healing in STEMI is considered complete. Whereas patients with low CRP production and a CRP gradient cut off of &lt;0.6 mg/L/h in the hours after STEMI (9 of 32 patients in the CRP apheresis group) did not significantly benefit from CRP apheresis in CMR2, patients with high CRP production and a CRP gradient cut off of &gt;0.6 mg/L/h (23 of 32 patients in the CRP apheresis group) showed significant treatment benefit. In the latter patients, CMR2 revealed a lower IS (-5.4%; p=0.05), a better LVEF (+6.4%; p=0.03), and an improved CS (-6.1%; p=0.005). No significant improvement, however, was observed for LS (-2.9%; p=0.1). These data suggest a sustained positive effect of CRP apheresis on the heart physiology in STEMI patients with high CRP production well beyond the period of its application. The data demonstrate the sustainability of the CRP removal from plasma which is associated with less scar tissue.

The rising incidence of complex illnesses and their costs have revolutionized basic research, patient management, and societal needs. Between 70 to 90% of the risk of developing a disease is due to the air we breathe, the water we drink, and the surroundings in which we work and live. Visibly polluted, infectious or not, the fact remains that we are more than ever exposed to environmental risks. Air pollution is the fourth most prevalent deadly risk factor worldwide and by far the leading risk factor for hundreds of diseases, including respiratory infections, inflammatory illness, and cancer. Thus, an unhealthy environment can be considered as a pandemic, affecting 280 million people and claiming 12 million deaths every year. Although critical for identifying of the people at risk, the causal environment components (pollutants and/or the microbiome), and the affected physiological mechanisms are not well understood. Herein, we consider the dysregulation of macroautophagy (hereafter referred to as ‘autophagy’), as the mechanism at the heart of an immediate response to environmental stress. We discuss the missing link between the autophagy gene variations, and the exposome in the susceptibility, prognosis, and management of complex diseases when embracing personalized medicine.

Using pumps operating as turbines (PATs) offers the possibility of increasing the sustainability of water and energy systems by recovering the excess of energy that would be otherwise lost in pressure reducing valves or head loss chambers. In on-grid applications, there are many research works and implementations of PATs. However, there is still limited research for the optimization of efficiency and stability of PATs operating in off-grid systems. This work contributes to the development of stable direct current (DC) off-grid electric systems based on PATs, by optimizing and analysing the energy efficiency and stability for a wide range of operation. A self-excited induction generator (SEIG) coupled to the PAT is provided to cover the conventional type of electric ma-chines typically coupled to the hydraulic pumps. In this context, a methodology is proposed, based on the hydraulic, mechanical and electric subsystems, to define the PAT-SEIG operational area, to maximize energy conversion and the system efficiency. This will guarantee stable electric output quantities when operating in a DC off-grid system. In addition, an analytical model is proposed to estimate the PAT-SEIG operation under specific conditions. With this, water managers are suitable to design and optimize an off-grid PAT-SEIG system and to define the best hydraulic machines, electronic equipment, and all different control elements to maximize energy conversion within the target of operational limits. To develop and verify this new methodology, two micro PAT-SEIG setups were implemented in the hydraulic laboratory of IST/CERIS under typical operating conditions. The proposed solution proved to be resilient under a variable load regime. The system's maximum efficiency can be adapted using different capacitor values for the excitation of the SEIG, and the operational range is limited to the electric components. Considering the nominal efficiencies of the system’s components, the maximum p.u. efficiency obtained for each PAT-SEIG system were between 0.7 and 0.8 p.u.