Extracellular vesicles represent a large heterogeneous class of near and long-distance intercellular communication mediators, released by both prokaryotic and eukaryotic cells. Specifically, the scientific community has shown a growing interest in exosomes, which are nano-sized vesicles with an endosomal origin. Not so long ago, the physiological goal of exosome generation was largely unknown and required more investigation; at first, it was hypothesized that exosomes are able to remove excess, rejects and unnecessary constituents from cells to preserve cellular homeostasis. However, thanks to recent studies, the central role of exosomes in regulating cellular dialogue has emerged. Exosomes act as vectors on cell-cell signaling by their cargo, proteins, lipids, and nucleic acids, and influence physiological and pathological processes. The findings on exosomes are widespread in a large spectrum of biomedical applications from diagnosis and prognosis to thera-pies. In this review, we describe exosome biogenesis and the current methods for their isolation and characterization, emphasizing the role of their cargo in female reproductive processes, from gametogenesis to implantation, and the potential involvement in human female disorders.

Introduction: The balance of bioelements is crucial as it ensures the organism's homeostasis and proper execution of reactions within the body, nerve conductivity, and correct polarity of cell membranes, but it is also very important for fertility. It is known that disturbances in the balance of bioelements lead to reproductive dysfunction. In women, changes in the composition of follicular fluid can occur, which can lead to limited follicular growth and lack of oocyte activation. Objective: The main objective was to examine whether the concentration of bioelements Na, K, Ca, Mg, and Fe in follicular fluid influences the outcome of the in vitro fertilization process. Methods: The study involved 120 female patients undergoing in vitro fertilization. Follicular fluid obtained after follicle aspiration in the ovaries was used as biological material for analysis. The values of Na (selective electrode method), K (selective electrode method), Ca (arenajo method), Mg (spectrophotometric method), and Fe (colorimetric method) in follicular fluid were determined using the AU 680 apparatus, Beckman Coulter. Istanbul Consensus criteria for clinical embryologists were used to assess embryo quality. Statistical analysis was performed using the SPSS 20 software package. Results: Analysis of follicular fluid samples showed no correlation between the concentration of bioelements in follicular fluid and the quality of oocytes or the outcome of in vitro fertilization. Conclusion: Based on our results, it can be concluded that the concentration of bioelements in follicular fluid does not affect the outcome of in vitro fertilization.

Mitochondrial DNA copy number (mtDNAcn) is associated with mitochondrial function contributing various diseases. Understanding of the association between mtDNAcn and infant neurodevelopment, as well as the role of racial disparities, remains unknown. A cohort study was conducted with 55 preterm infants and a single blood sample was collected from each infant during their NICU stay to measure mtDNAcn. NICU Network Neurobehavioral Scale (NNNS) and Bayley Scale of Infant Developmental testing Edition III was assessed during NICU until 2 years of corrected age (CA). Linear regression models were performed to investigate the relationship between the clinical characteristics, neurobehavioral outcomes and mtDNAcn. Majority of our subjects were male, White, non-Hispanic, had C-section, and without preterm premature rupture of membrane (PPROM). Increased mtDNAcn was found associated with younger birth gestational age (GA), nonoptimal neurodevelopment. However, the opposite associations between mtDNAcn and neurodevelopmental outcomes were observed between Black and White infants up to 1 year of CA. Adverse early life experience, together with increased mtDNAcn in White infants, and decreased mtDNAcn in Black infants may be considered as significant positive predictors of poor early life neurodevelopmental outcomes in infants.

In this study, the microbial strain was isolated from the humus soil to ferment Sophora flavescens and Eleutherococcus sessiliflorus extracts. The isolated microbial was identified as Bacillus genus by 16S rRNA sequence analysis. The fermented plant extracts exhibited the antifungal effects against four types of the plant pathogens such as P. carotorum, B. cinerea, C. fructicola Sau-3, and C. gloeosporioides according to incubation time. Especially, the fermented plant extracts showed the most active activities for Colletotrichum genus to inhibit mycelium growth. Metabolite changes in fermented S. flavescens and E. sessiliflorus extracts were confirmed through LC-Q-TOF/MS. Flavonoid and peptide derivatives were improved in fermented S. flavescens and E. sessiliflorus extracts compared to their unfermented one, respectively. This study suggested that the isolated Bacillus microbial fermentation could be a valuable tool in improving the bioactivity of S. flavescens and E. sessiliflorus extracts to have potential with more environmentally-friendly antifungal agents.

Alzheimer’s disease (AD) poses a significant public health challenge due to its irreversible and progressive nature while lack of a cure. As a potential strategy to combat AD, its prevention becomes increasingly attractive. Mild Cognitive Impairment due to AD (MCI-AD) represents a critical transitional stage between normal age-related cognitive decline and more severe AD conditions, occurring just before dementia onset. Unfortunately, there is currently no established animal model that accurately recapitulates MCI-AD characteristics. While many laboratories have traditionally used normally aged wild-type animals as experimental models, this approach falls short in representing the inherently worse state of MCI-AD compared to normal aging. To address this gap, we introduce an animal model—a transgenic mouse line with genetic inactivation of G protein-coupled receptor kinase-5 (GRK5), commonly known as the GRK5 knockout (GRK5KO) mouse. These GRK5KO mice exhibit amnesia, cognitive deficits, increased β-amyloid levels, neurofibrillary tangle (NFT) immunopositive axonopathy, and hippocampal neurodegenerative changes. Importantly, these pathological alterations predominantly impact the entorhinal, transentorhinal, and hippocampal cortices, aligning with human MCI-AD criteria and Braak stage II of human AD progression. Notably, female GRK5KO mice show approximately 2.5 times more NFT-positive axonopathy than males, mirroring the higher prevalence of AD cases in women. Collectively, existing data strongly supports the GRK5KO mouse as a qualified animal model for studying MCI-AD.

AbstractPurpose: This study aimed to perform a psychometric evaluation of the preliminary preterm birth risk assessment scale (PBRAS-K) of 32-item. Method(s): There were 299 subjects, 167 in the exploratory factor analysis (EFA) group and 132 in the confirmatory factor analysis (CFA) group, who delivered before 37⁺⁰ weeks after having preterm symptoms and were admitted to high-risk pregnancy maternal-fetal intensive care units (MFICU). After an item reduction process in EFA, the psychometric property scales were assessed using SPSS 26, and CFA was accomplished using AMOS 27. Results: The Kaiser-Meyer-Olkin measure (KMO) and Bartlett’s χ² test of sphericity confirmed the adequacy of the sample for factor analysis (KMO = .81 (> .80), χ² = 1841.38, p < .001). The final version of the PBRAS-K was comprised of 23 items within seven dimensions. Factor analysis identified items explaining 65.9% of the total variance. The PBRAS-K had a mean score of 35.58 (±10.35) and showed a high internal consistency and satisfactory reliability with a Cronbach’s alpha of .85. The PBRAS-K had a low correlation with risk scoring of preterm delivery (RPD) for discriminant validity (r = .45, p < .001), a positive, high correlation with the Somatic Awareness Scale with Spontaneous Preterm Labor (SPL-SAS) for criterion validity (r = .65, p < .001), and with pregnant stress for convergent validity (r = .57, p < .001). RPD and SPL-SAS were moderately correlated (r = .53, p < .001). Conclusion(s): The PBRAS-23-K is a valid and reliable instrument for assessing pregnant women’s risk of preterm birth. Clinical nurses are encouraged to apply and obtain information for effective interventions in MFICU. This scale has meaningful results and reflects the voices of women who had a preterm birth. The scale should be evaluated for standardization and cut-off scores using larger subject sizes in the future.

53% of adults in the US acknowledge racial bias as a significant issue, 23% of Asian adults experience cultural and ethnic bias, and more than 60% conceal their cultural heritage after racial abuse. AI models like ChatGPT and Google Bard, trained on historically biased data, inadvertently amplify racial and ethnic bias and stereotypes. This paper addresses the issue of racial bias in AI models using scientific, evidence-based analysis and auditing processes to identify biased responses from AI models and develop a mitigation tool. The methodology involves creating a comprehensive database of racially biased questions, terms, and phrases from thousands of legal cases, Wikipedia, and surveys, and then testing them on AI Models and analyzing the responses through sentiment analysis and human evaluation, and eventually creation of an 'AI-BiasAudit,' tool having a racial-ethnic database for social science researchers and AI developers to identify and prevent racial bias in AI models.

With the goal of representing common denominators of aging in different organisms López-Otín et al. in 2013 described nine hallmarks of aging. Since then, this representation has become a major reference point for the biogerontology field. The template for the hallmarks of aging account originated from landmark papers by Hanahan and Weinberg (2000, 2011) defining first six and later ten hallmarks of cancer. Here we assess the strengths and weaknesses of the hallmarks of aging account. As a checklist of diverse major foci of current aging research, it has provided a useful shared overview for biogerontology during a time of transition in the field. It also seems useful in applied biogerontology, to identify interventions (e.g. drugs) that impact multiple symptomatic features of aging. However, while the hallmarks of cancer provide a paradigmatic account of the causes of cancer with profound explanatory power, the hallmarks of aging do not. A worry is that as a non-paradigm the hallmarks of aging have obscured the urgent need to define a genuine paradigm, one that can provide a useful basis for understanding the mechanistic causes of the diverse aging pathologies. We argue that biogerontology must look and move beyond the hallmarks to understand the process of aging.

3D-printed models with high anatomic fidelity are an increasingly viable tool in simulation-based medical education. One advantage of 3D models is they provide enhanced tactile and spatial understanding of complex anatomy to develop technical skills used in minimally invasive procedures. We propose that 3D anatomical models can improve the development of Interventional Radiology vascular access skills – first described in the 1950s as the Seldinger Technique – for pre-clerkship medical students. Early adoption of 3D-printed technology in pre-clinical medical education can lead to improved student engagement and satisfaction when learning procedural techniques. This study involved creating a 3D model of the upper extremity vasculature from an anonymized CT angiogram, using it as a medical education tool for 31 pre-clinical medical students practicing the Seldinger Technique on a prefabricated venipuncture arm, and assessing student satisfaction with this form of learning. Overall, attendees responded positively to the incorporation of the 3D model in medical education to improve their anatomic understanding and application to the Seldinger Technique. These results indicate that the use of 3D models in simulation-based medical education can provide benefits to acquiring technical skills and the potential to decrease training costs without harming a patient.

Motivation is essential in education, with highly motivated learners engaging more deeply with content and more ably transferring knowledge to new contexts. However, the validity of scales to measure motivation has been underexplored in pre-clerkship medical education. This study evaluates the validity of the Situational Motivation Scale (SIMS) for measuring motivation among pre-clerkship medical students in post-situational and short-term contexts. Using a sample of n = 156 students from the Frank H. Netter MD School of Medicine at Quinnipiac University, SIMS was tested for construct validity with attention paid to content, response process, internal structure, relationships to other variables, and consequences of use evidence. Small modifications from present to past tense in English were made for clarity following focus group feedback, and content validity was ensured via expert consultation. SIMS demonstrated strong internal consistency with a satisfactory Cronbach’s alpha for all subscales and anticipated patterns of correlations. Factor analysis confirmed appropriate factor loadings, with a stronger model fit for the short-term context, and no observed adverse effects on student engagement. These findings support the robustness of SIMS in capturing intrinsic, extrinsic, and amotivation in pre-clerkship medical students, highlighting its applicability for short-term and situational motivational assessment.

Aging causes various degenerative diseases in the older adult population. Senescence, a state of permanent cell-cycle arrest accompanied by the production of various pro-inflammatory factors known as senescence-associated secretory phenotype (SASP), is considered a significant contributor to the aging process and its chronic diseases. Ample evidence showed that various stressors could induce senescence, including DNA damage, telomere shortening and damage, activation of oncogenes, and mitochondrial dysfunction. Numerous credible findings indicate that environmental agents can induce senescence, including UV radiation, a high-fat diet, heavy metal exposure, and cigarette smoke. These findings posed the possibility that many more environmental agents may induce senescence and accelerate aging but remain unidentified. Senescence also becomes more intriguing due to its promising future as a pharmacological target to blunt the detrimental effects of aging and prevent aging-related diseases, either by eliminating the senescent cells or by controlling the SASP. On the other hand, investigating senescence has become more intricate due to the need for a multi-marker approach and translation in vivo analysis. This review will discuss senescence and its biomarkers, how to identify gerontogens in vivo, and also the development of senotherapy that targets senescent cells.

For the purpose of improve the sustainability of products sold in the EU, Digital Product Passports is a mandatory solution. These passports would systematically gather information about products, such as detailing the materials involved to aid recycling and remanufacturing efforts, or recording the emissions produced throughout the manufacturing process. The overall goal is the establishment of a circular economy in the EU. Current research on Digital Product Passports is focused on collating content for sector-specific applications. However, achieving sustainability goals through Digital Product Passports will require new methods and technical solutions for digital collaboration between supply chain participants, especially in the manufacturing sector. Collaborative work on Digital Product Passports requires trust and traceability in data and access management to ensure privacy over the data contained. One way to enable this securely and confidentially is through the use of blockchain technology, in which stored data cannot be concealed, which is key to the traceability of digital product data documentation. This paper therefore presents a concept for the implementation of generically applicable cross-industry blockchain-based digital product passports. To this end, generic supply chain processes have been abstracted and condensed into the architecture of smart contracts. Great attention is paid to the establishment of traceability as well as privacy through the selection of the blockchain technology Secret Network in combination with Gaia-X functionalities. An illustrative use case for digital product passports in manufacturing is used to demonstrate the applicability of the presented concept. In this use case information about the digital nameplate and carbon footprint is exchanged securely and confidentially in a multi-tenant supply chain network based on the Industry 4.0 infomation model of the Asset Administration Shell.

This paper examines the correlation between numbers of computer cores in parallel genetic algorithms. The objective to determine the linear polynomial complementary equation in order represent the relation between number of parallel processing and optimum solutions. Model this relation as optimization function (f(x)) which able to produce many simulation results. F(x) performance is outperform genetic algorithms. Compression results between genetic algorithm and optimization function is done. Also the optimization function give model to speed up genetic algorithm. Optimization function is a complementary transformation which maps a TSP given to linear without changing the roots of the polynomials.

Telomeres, located at the ends of each chromosome play a vital role in determining cellular fate and aging. Accelerated shortening of telomeres may also result in accelerated aging and occurrence of age-related degenerative diseases. Anti-aging treatments may help in increasing the telomere length along with improving quality of life, reducing dependency for daily life activities, increasing life expectancy and reducing the risks associated with aging. In this study, we evaluated the effect of anti-aging integrative therapy in 36 individuals. The treatment included a combination of HBOT, ozone therapy, colon hydrotherapy, etc. Telomere length was used as a biomarker for objectively quantifying the outcome of the treatment. The effect of treatment was also assessed on various aging symptoms. At the end of the treatment, it was found that that 97.22% individuals showed an increase in telomere length with an average increase of 0.43 Kbp and 94.44% individuals showed reduced biological age with an average decrease of 3.8 years. These improvements were statistically significant. Improvements were also recorded in the majority of the symptoms. No major adverse events were observed. These results indicate that antiaging integrative therapy has the potential to reverse aging symptoms, cellular aging and improve quality of life.

In the world's first pig-to-human cardiac xenotransplant, the elevated levels of porcine cytomeg-alovirus (PCMV) are considered key factors contributing to patient mortality. This has renewed attention to PCMV, a virus widely prevalent in pigs. Currently, there are no effective drugs or vaccines targeting PCMV, and its high detection difficulty poses challenges for prevention and control research. In this study, antiviral small hairpin RNA (shRNA) was selected and inserted into the Rosa26 and miR-17-92 loci of pigs via a CRISPR/Cas9-mediated knock-in strategy. Further in vitro viral challenge experiments demonstrated that these genetically edited pig cells could effec-tively limit PCMV replication. Through this process, we constructed a PCMV-infected cell model, validated partial viral interference sites, enhanced gene knock-in efficiency, performed gene editing at two different gene loci, and ultimately demonstrated that RNA interference (RNAi) technology combined with CRISPR/Cas9 has the potential to generate pig cells with enhanced antiviral infec-tion capabilities. This opens up possibilities for the future production of pig populations with anti-viral functionalities.

Purpose: The objective of this paper is to explore the association between insufficient lycopene intake and risk of periodontitis among older adults. Methods: Data analysis was conducted using data from the National Health and Nutritional Examination Survey 2009-2014. Overall, 1227 adults aged 65- to 79-years-old were investigated. Results: Overall, 48.7% of older adults in this study were classified with different levels of periodontitis and 49.1% of individuals with a form of periodontitis had insufficient dietary lycopene intake. Sufficient lycopene intake was found to be associated with a lower likelihood of severe periodontitis (OR: .33; 95% CI: 0.17-.65; p=0.002). Non-Hispanic Black (NHB) older adults were more likely to develop severe forms of periodontal disease in comparison to Non-Hispanic White (NHW) older adults (OR: 2.82, 95% CI: 1.46-5.45, p=0.003). Gender was also found to play a role in periodontitis status, with women being less likely to have severe periodontitis status, compared to men (OR: 0.27; 95% CI: 0.14-0.55; p=0.0007,). However, only NHW females were less likely to have severe periodontitis compared to NHW males (OR: 0.26; 95% CI: 0.12-0.56; p= 0.001). Conclusion: Dietary intake of lycopene associated with periodontitis disease for individuals over the age of 65; those who consume a sufficient amount of lycopene are less likely to develop severe periodontitis. In general, more men suffered from periodontitis in comparison to women. Such association also has been found between NHB with severe periodontitis. In addition, reduced risk of moderate periodontitis is associated with sufficient lycopene intake is explored in NHW, future targeted interventions using lycopene in dietary intake as a preventative measure to delay or prevent the onset of periodontal disease needs to be race and gender specific.

Background: SARS-CoV-2 Omicron JN.1 has the highest number of amino acid mutations in its receptor binding domain (RBD) and has acquired a hallmark L455S mutation. The immune evasion capability of JN.1 is a subject of scientific investigation. The US CDC used RT-qPCR SGTF as the proxy indicator of JN.1 infections for evaluation of the effectiveness of updated monovalent XBB.1.5 COVID-19 vaccines against JN.1 and recommended that all persons aged ≥6 months should receive an updated COVID-19 vaccine dose. Objective: Recommend Sanger sequencing for diagnosis of JN.1 infections to generate the data based on which guidelines are made to direct vaccination policies. Methods: The RNA in nasopharyngeal swab specimens from patients with clinical respiratory infection was subjected to nested RT-PCR, targeting a 398-base segment of the N-gene and a 445-base segment of the RBD of SARS-CoV-2 for amplification. The DNA sequences were analyzed for amino acid mutations. Results: The N-gene sequence showed Q229K, usually associated with Omicron BA.2.86 (+JN.1). The RBD sequence showed 24 amino acid mutations, including the hallmark L455S mutation for JN.1 and the V483del for BA.2.86 lineage. Conclusions: The CDC should consider Sanger sequencing of the RBD to diagnose JN.1 infections for statistical analysis in making vaccination policies.

Background: Retinal hemorrhages are an important ophthalmic diagnostic sign of underlying systemic vascular disorder. Capsaicin is a bioactive component of chili peppers used in most countries. Capsaicin crosses the blood–brain barrier in an efficient manner. Human exposure to capsaicinoids through diet is frequent and often substantial. Presumed lack of capsaicin toxicity in diet does not preclude rare adverse effects related to actions on the central neural system. Particularly on the retina, due to the reasons outlined in this case report. Methods: A case of a 34-year-old man, who reported sudden blurring of vision and micropsia in his left eye following ingestion of a considerable amount of red pepper. Results: The case study suggests that acute or chronic consumption of substantial amounts of hot red pepper in individuals with high reactivity towards TRPV1 agonists and/or higher expression of TRPV1 receptors in retinal ganglion cells causes retinal neovascularization. Conclusion: Acute consumption of red pepper may harm vision. This hypothesis can be easily evaluated retrospectively in larger sets of data.

Older adults with obesity have an increased risk for cognitive decline and subsequent Alzheimer’s disease. Previous research has focused on the impact of individual nutrients and overall dietary patterns to improve cognitive function. The Brain and Body Health (BB-Health) study aims to demonstrate the feasibility of a multicomponent nutritional supplement (MCNS) and weight loss (WL) intervention for individuals with overweight and obesity who are not consuming a healthy diet. BB-Health is a parallel-group randomized placebo-controlled 2x2 factorial pilot trial comparing the MCNS, WL, and MCNS+WL with a Control group. Eligible participants are 55 to 85 years of age with a body mass index 27.0 to 39.9 kg/m2. Major exclusion criteria include type 2 diabetes, moderate or severe cognitive impairment, and self-reported healthy dietary pattern. The BB-Health feasibility trial is registered as NCT05542199 at clinicaltrials.gov. The BB-Health objectives are to report: 1) recruitment and enrollment, including pace and descriptive statistics of the study sample; 2) adherence to the administered interventions; 3) successful data collection and performance of outcome assessments, including evaluation of change in key outcomes over time that are powered for this pilot study; and 4) summary statistics on outcomes for use in planning a subsequent, larger trial. The outcomes of interest are age-sensitive cognitive assessments, cerebral hemodynamics, and related health parameters. All measurements are collected at baseline, 3-, 6-, and 12-month visits. If the BB-Health protocol demonstrates feasibility, the novel MCNS with and without a parallel WL intervention has potential to be administered in a confirmatory randomized trial to evaluate ability to prevent age-related cognitive decline and improve brain health. The BB-Health Feasibility Study could significantly contribute to our understanding of the influence of diet and weight management on cognitive health

A sintered wick was formed in a heat pipe through the process of sintering a mixture of copper powder with particle sizes of 100㎛ and 200㎛, mixed with a pore-forming agent. On application to the heat pipes. The thermal resistance of heat pipes containing a sintered wick was calculated for different tilting angles (0°, 45°, and 90°) according to the type of powder, thickness of the sintered wick, and the filling ratio of the working fluid. The heat transfer efficiencies were evaluated through temperature tests. The capillary force, which is closely related to heat transfer efficiency, is determined by the effective pore radius resulting from the sintering of the copper powder. Furthermore, it was observed that the heat transfer performance of the heat pipe was at its best when the working fluid filling ratio was 30%. Additionally, the width of the wick was found to have a direct correlation with the heat transfer performance.

Weight-bearing computed tomography (WBCT) enables acquisition of three dimensional bony structure images in a physiological weight-bearing position, which is fundamental in under-standing the pathologic lesions and deformities of the ankle joint. Over the past decade, re-searchers focused on validating and developing WBCT measurements, which has significantly enhanced our knowledge of common foot and ankle disease. Consequently, understanding the application of WBCT in clinical practice is becoming more important to produce improved out-comes in the treatment of disease around the ankle joint. This review will describe an overview of what is currently being evaluated in the foot and ankle surgery using WBCT and where the course of research will be heading in the future.

Organic electrophoretic coatings have gained significant attention due to their ability to provide a uniform and controlled coating thickness, high coating adhesion, and excellent corrosion protection properties. In this work, to investigate the aging behaviors of an organic electrophoretic coating for magnesium alloys, water absorption kinetics curves of the coatings after immersion in 3.5 wt.% NaCl at 20℃ and 40℃ were measured, and parameters such as the saturated water absorption and saturation time of the free film coatings were fitted to determine the densification evolution of the organic coatings. A tensile test was used to test the tensile strength of the organic coating during service to determine the evolution of the strength and toughness of the organic coating. The evolution of wet adhesion of organic coatings with service time was tested by ASTM D4541-02. The impedance spectra of the organic coatings under the above conditions were detected by EIS, and finally, the failure behavior of the organic coatings under immersion was analyzed.

Acquired immunodeficiency syndrome (AIDS) has transitioned from a progressive, fatal disease to a chronic, manageable disease thanks to better defining of antiretroviral therapy, hence contributing to increased life expectancy. In parallel, a growing number of subjects without overt clinical signs of disease but living with chronic HIV infection (people living with HIV, PLWH) are experiencing early cardiovascular disease worldwide. However, a progressive increase in the prevalence of multiple comorbid diseases has been reported as these patients age, including cardiovascular disease (CVD). Cardiovascular mortality can be either directly related to the viral infection, a progressive reduction of response to the antiretroviral therapy, chronic inflammation or lifestyle-related. Cardiovascular ageing represents a relevant issue in the management of HIV-infected patients. Although the exact pathophysiological mechanism that leads PLWH to develop cardiovascular disease is not entirely understood, there is substantial evidence that they accumulate age-related conditions earlier than the general population. Furthermore, since the proportion of PLWH growing older than 50 years has progressively increased, this results in a complex interaction between disease-related pathophysiology and the exposition of a growing burden of cardiovascular risk factors. For this reason, we performed a systematic review of the genes most frequently associated with ageing in HIV-infected subjects, followed by a bioinformatic analysis to explore the biological impact of the genes related to ageing.

Background: Colorectal adenoma undergoes neoplastic progression via the normal epithelium-adenoma-adenocarcinoma sequence as reported in the Vogelgram. The risk of developing cancer is strongly associated with the number and size of adenoma and with the subtype. Currently, adenomatous polyps can be distinguished on the basis of histology: the prevalence are tubular, 5-15% are villous and tubular/villous. Considering the increased risk for malignant transformation described for tubular/villous adenomas, patients diagnosed with adenomatous polyposis are at increased risk of developing CRC. The Wnt/β-catenin pathway plays a key role in the onset of colorectal adenoma, in particular intestinal cells first acquire loss-of-function mutations in APC gene that induce the formation of adenomas. Methods: Wnt/β-catenin pathway APC, Wnt3a, Wnt5a, LEF1, BCL9 genes and protein expression analyses were conducted by qRT-PCR and western blot in 68 colonic samples (polyps and adjacent mucosa) from 41 patients, of which 17 affected by FAP. Ten normal colonic mucosal samples were collected from 10 healthy donors. Results: In this study both APC gene and protein resulted less expressed in colon tumor compared to the adjacent colonic mucosa. Conversely, activated β-catenin was more expressed in polyps than in the adjacent mucosa. All results confirmed literature data on carcinomas. A statistically significant correlation between Wnt3a and BCL9 both in polyps and in the adjacent mucosa underlies that the canonical Wnt pathway is activated in early colon carcinogenesis and that the adjacent mucosa is already altered. Conclusion: This is the first study analyzing the difference in expression of Wnt/β-catenin pathway in human colorectal adenomas. Understanding the progression from adenomas to colorectal carcinomas is essential for the development of new therapeutic strategies and improving clinical outcomes.

Introduction Blunt carotid injuries (BCI) in pediatric trauma are quite rare. Due to the low number of cases, only a few reports and studies have been conducted on this topic. This review will discuss how frequent BCI/ BCVI on pediatric patients after blunt trauma is, what routine diagnostics look like, if a CT/ CTA scan on pediatric patients after blunt trauma is always necessary and if there are any negative health effects? Methods This literature review includes reviews, systematic reviews, case reports and original studies in english language between 1999 and 2020 that have dealt with pediatric blunt trauma and the diagnostics of BCI and BCVI. Furthermore, publications on the risk of radiation exposure on children were included in the study. For literature research, Medline (PubMed) and the Cochrane library were used. Results Pediatric BCI/ BCVI, shows an overall incidence between 0.03 – 0.5% of confirmed BCI/ BCVI cases due to pediatric blunt trauma. 1.1 – 3.5% of pediatric blunt trauma patients underwent CTA to detect BCI. Only 0.17 – 1.2% of all CTA scans shows a positive diagnosis for BCI. In children, the median volume CT dose index on a non-contrast head CT is 33 milligray, a computed tomography angiography needs at least 138 mGy. A cumulative doses of about 50 mGy almost triples the risk of leukemia, and doses of about 60 mGy triples the risk of brain cancer. Discussion Knowing that a BCI could have extensive neurologic consequences for children, it is necessary to evaluate routine pediatric diagnostics after blunt trauma. Computed tomography scans (CT) and computed tomography angiography (CTA) are mostly used in routine BCI diagnostics. However, since radiation exposure in children should be as low as reasonably achievable, it should be asked if other diagnostic methods could be used to identify risk groups. Trauma guidelines and clinical scores like the McGovern score are reflect established BCI screening options, as well as using duplex ultrasound.

Lung involvement in rheumatic diseases is a major determinant of patient morbidity and mortality; however, its diagnosis depends on the detection methods used. We compared the incidence of pulmonary involvement in newly diagnosed treatment-naive patients with rheumatic diseases, as assessed by pulmonary function tests (PFTs) and chest high-resolution computed tomography (HRCT). This retrospective study reviewed the symptoms, spirometry results, and HRCT scans of 22 newly diagnosed, treatment-naïve patients and age-matched controls from the University General Hospital “Attikon”, Athens, Greece, between January 2021 and December 2023. Correlations between clinical findings and spirometry parameters were tested. HRCT scans revealed lung abnormalities in all patients, including peribronchial wall thickening (61.5%), ground glass opacities (59.1%), parenchymal bands (54.5%), air-trapping (50%), reticular patterns (45.5%), bronchiectatic changes (40.9%), and parenchymal opacities (31.8%). PFTs, performed in 17/22 (77.3%) patients, revealed definite pathology in 5 patients (restrictive: N=4; obstructive: N=1). No association was found between spirometric indices and clinical parameters. The results indicate a higher prevalence of abnormal chest CT than of PFT abnormalities, suggesting that HRCT is more sensitive in detecting early lung involvement in pediatric patients with rheumatic disease and should be considered in the routine evaluation of these patients.

The age-related loss of muscle mass and strength is referred to as “sarcopenia”. The combined effect of sarcopenia and osteoporosis is a devastating threat to the old adult, accounting for reduced mobility, risk for falls and subsequent fractures. In previous studies, we observed a high degree of inter-individual variability of paraspinal muscle fatty infiltration, one most relevant index of muscle wasting. This aspect solicited us to develop a computerized method to quantitatively characterize muscle fatty infiltration in aging and diseases. Magnetic resonance images of paraspinal muscles from 58 women of different age (age range 23-85 years) and physio-pathological status (healthy young, pre-menopause, post-menopause, and os-teoporosis), were used to set up the method. It is based on fractal analysis of lean muscle area (contractile muscle) to estimate muscle fatty infiltration. In particular, lacunarity was computed by parameter β from our hyperbola model function, used to fit the GBA (gliding box algorithm) curvilinear plot. Succolarity was estimated by parameter µ, for the four main directions, through an algorithm implemented on purpose. Results show that fractal lacunarity, by quantifying muscle fatty infiltration, can discriminate be-tween osteoporosis and healthy aging while succolarity can separate the other three groups showing similar lacunarity. Therefore, fractal features of contractile muscle, by measuring fatty infiltration, can represent good indices of sarcopenia in aging and disease.

The influence of playing formations and team ranking on the physical performance of professional soccer players is an open question that needs to be explored. The present study aimed to investigate the impact of these factors on the physical exertion of Serie A soccer players. We analyzed match data from 375 players, categorizing teams based on their final ranking and comparing performance across different playing formations. Krustal-Wallies test, and Dunn test with Bonferroni adjustment, revealed that high-ranking (HR) teams exhibited a higher percentage of high-intensity (HI) accelerations compared to mid-ranking teams, suggesting the critical role of HI efforts in achieving favorable match outcomes. Moreover, the 4-3-3 playing formation was associated with greater acceleration demands than other formations, particularly in HR teams. Our study also established benchmarks for various performance metrics, enabling coaches to assess player performance and identify potential signs of overtraining. These findings contribute to a deeper understanding of the physical demands in soccer and offer practical implications for coaches and players in optimizing training and performance strategies.

Penile cancer (PeCa) is a rare urological malignancy characterized by significant geographic variations in both incidence and mortality rates. Due to its rarity and the consequent lack of randomized trials, current management is based on retrospective studies and small prospective trials. In addition, the diagnostic pathways and treatment strategies exhibit substantial heterogeneity, differing significantly between less developed and well-developed countries. The prognosis of PeCa is determined by the presence and extent of regional lymph node (LN) involvement. Therefore, early detection and treatment of LN metastasis is paramount to ensure better outcomes. In recent decades, the overall survival for PeCa has increased, mainly due to advancements in imaging techniques and risk stratification. We aim to provide an overview of the current role of PET CT imaging in the management of patients with PeCa.

The objective of this study is to design and synthesize substituted η6-chromium tricarbonyl metal complexes carrying o-carborane units as potential boron neutron capture therapy (BNCT) agents. In this study, 1,2-Diphenyl-o-carborane units were used as starting materials to generate biologically active species. We investigated how the structural changes of 1,2-diphenyl-o-carborane substituted with chromium(0) tricarbonyl affect the biological properties; [(CO)3Cr]Ph2C2 (2) and [(CO)3Cr]2Ph2C2 (3) species were produced in moderate yields. The molecular structures of compounds 1–3 were identified and established by infrared (IR), 1H, 11B, and 13C nuclear magnetic resonance (NMR), and X-ray crystallography analyses. Crystal structures of o-carboranyl chromium complexes 1 [a = 10.859(1) Å, b = 24.953(3) Å, c = 13.938(2) Å, β = 111.854(2)º], 2 [a = 10.621(3) Å, b = 17.056(5) Å, c = 12.174(4) Å, β = 106.622(5)º], and 3 [a = 17.540(2) Å, b = 18.060(2) Å, c = 19.484(4) Å, α = 105.746(2)º, β = 110.226(2)º, γ = 91.256(2)º] were obtained. In vitro study using B16 and CT26 cancer cells containing the triphenyl-o-carboranyl chromium (0) complexes Ph3C2BCr2 and Ph3C2BCr3, which we have previously reported, the compounds 2 and 3 accumulated at higher levels than compounds Ph3C2BCr2 and Ph3C2BCr3. However, the phenylated o-carboranyl chromium(0) complexes have been found to be more cytotoxic than p-boronophenylalanine (BPA).

Lung cancer remains the main cause of global cancer-related deaths. Currently low-dose computed tomography (LD-CT) shows a 20% reduction of mortality. However, its clinical suitability is hindered by cost, radiation, and some false positives. Thus, the discovery non-invasive and less-expensive biomarker is urgent needed. In this scenario, proteins released in biological fluids could be considered interesting biomarkers for their role in cancer development. We conducted a pioneering case-control pilot study aimed at assessing the usefulness of Raf Kinase Inhibitory Protein (RKIP) and its phosphorylated form (pRKIP) as potential early-stage lung cancer biomarkers. Urine and Blood samples of two consecutive and independent cohorts of lung cancer patients and healthy controls were screened by means of a novel experimental ELISA assay designed to evaluate both forms of the biomarker. Although urinary levels of RKIP were not statistically different between the lung cancer group and high-risk healthy group, serum ones instead increased significantly in early stage LC patients and permitted to discriminate LC patients from both low-risk (HS) and high-risk healthy subjects (HR-HS) with an overall 93% accuracy (AUC 0.93) when LC was compared to HS and 74% (AUC 0.73) when it was compared to high-risk group. Of note, the analysis of RKIP/pRKIP ratio also showed a high accuracy (90% - AUC 0.95) in discriminating LC patients from HS and more importantly, it allowed to identify LC patients compared to HR-HS, with a higher accuracy (79% - AUC 0.79) than RKIP alone. We hypothesize that serum RKIP levels may be correlated to the activation of the immune systems against the tumor during the first phases of its development. Our study identified a preliminary, non-invasive, RKIP and pRKIP profile able to discriminate with high specificity and sensitivity the early-stage lung cancer patients from high-risk Healthy Subjects. These results, although preliminary, suggest the utility of measuring RKIP/pRKIP as potential new screening test for lung cancer and provide the basis for future validation studies.

Machine learning has gained significant recognition within healthcare organizations as a potent technology for medical image analytics. Among various medical image modalities, Contrast-Enhanced CT (CECT) is widely utilized to acquire additional diagnostic information that can help to better visualize and evaluate certain structures or abnormalities in the human body. Accordingly, there is an increasing demand for machine learning systems for disease analytics using CECT. However, developing such systems presents two significant challenges: high technical complexity and high development effort. This paper presents a software platform that can effectively remedy these challenges. This platform embodies a unified software process for CECT-specific disease diagnosis including oncological diseases, cardiovascular diseases, and gastrointestinal diseases. It integrates multiple types of machine learning models into the disease diagnosis process, where the models can diagnose lesions, malignancies, tumors, medical features of tumors, temporal transitions with a contrast agent, and disease progress. The platform has been implemented in Python using Scikit-learn and TensorFlow libraries. To validate its applicability and reusability, a Hepatocellular Carcinoma (HCC) diagnosis system has been implemented.

The work is devoted to the development of methods for constructing asymptotic formulas as x→∞ of a fundamental system of solutions of linear differential equations generated by a symmetric two-term differential expression of odd order. The coefficients of the differential expression belong to classes of functions that allow oscillation (for example, those that do not satisfy the classical Titchmarsh-Levitan regularity conditions). As a model equation, the 5th order equation i2p(x)y′′′′′+p(x)y′′′′′+q(x)y=λy, for which various cases of behavior of the coefficients p(x),q(x), is investigated. New asymptotic formulas are obtained for the case when the function h(x)=−1+p−1/2(x)∉L1[1,∞) significantly influences the asymptotics of solutions to the equation. The case when the equation contains a nontrivial bifurcation parameter is studied.

Brain aging causes a wide variety of changes at molecular and cellular levels, leading to the decline of cognitive functions and increased vulnerability to neurodegenerative disorders. The research aimed at understanding the aging of the brain has made much progress in recent decades. Technological innovations such as single-cell RNA-sequencing (scRNA-seq), proteomic analyses, and spatial transcriptomic analyses have facilitated the research on the dynamic changes occurring within neurons, glia, and other cells along with their impacts on intercellular communication during aging. In this review, we introduce recent trends of how neurons and glia change during aging and discuss the impact of the brain microenvironment such as the blood-brain barrier (BBB).

Computed tomography (CT) is a widely employed imaging modality with diverse clinical applications in pediatric and adult populations, offering numerous advantages. Despite several alternatives to imaging modalities with ionising radiation, CT scans have demonstrated persistent global popularity, contributing to a substantial amount of effective radiation doses for patients. This exposure results in hazards, including stochastic effects that amplify the radiation-induced cancer risk proportionally to the radiation dose received. CT-related radiation comprises a substantial portion of cumulative effective doses within diagnostic radiology, specifically impacting younger patient cohorts undergoing repeated investigations for chronic diseases over time. Scientific literature over recent decades has explored various methods to mitigate radiation doses during medical imaging. One notable strategy involves implementing low-dose and ultralow-dose CT protocols, maintaining diagnostic efficacy in acute and non-acute medical and surgical conditions. Utilising innovative image reconstruction algorithms, such as iterative reconstruction and emerging deep-learning algorithms based on artificial intelligence, plays a pivotal role in achieving an approximately 80% reduction in patient radiation compared to standard doses. This review article discusses the significance of low-dose protocols across a spectrum of acute and chronic medical conditions affecting different body systems.

We investigated the response of the Manila clam Venerupis philippinarum to possible temperature and salinity changes in a holding facility. First, clams were exposed to four temperatures for 15 days. Valve closure and survival of clams exposed to seawater at 18℃ were higher than that of those exposed to seawater at 24℃. Second, clams were exposed to six salinities for 15 days. Survival of clams exposed to two salinity fluctuation conditions (24–30 and 27–24 psu) was lower than that of clams exposed to constant 30 psu conditions. Valve closures of clams exposed to constant low salinity conditions (24 psu) and two salinity fluctuation conditions (24–30 and 27–24 psu) were higher than of those exposed to constant 30 psu conditions. Lastly, clams were exposed to two different temperatures and three different salinities conditions for 8 days. Valve closure and survival decreased significantly under the combination of 24℃ and 18 psu. These results suggest that an increase in temperature or a wider range of salinity fluctuations are detrimental to the survival of the Manila clam. The synergistic effect of temperature and salinity stressors may decrease the survival period of clams compared to the effect of a single stressor.

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

The biological aging, characterized by changing in metabolism and physicochemical properties of cells, has an impact on public health. Environment and lifestyle including factors like diet and physical activity seems to play a key role in healthy ageing. Several studies have shown that regular physical activity can enhance antioxidant defence mechanisms, including the activity of enzymes such as superoxide dismutase (SOD), catalase, and glutathione peroxidase. However, intense or prolonged exercise can also lead to an increase in ROS production temporarily, re-sulting in oxidative stress. This phenomenon is referred as "exercise-induced oxidative stress". The relationship between physical activity and oxidative stress in aging is complex and depends on various factors such as the type, intensity, duration, and frequency of exercise, as well as in-dividual differences in antioxidant capacity and adaptation to exercise. In this review, we ana-lyzed what is reported from several authors regarding the role of physical activity on oxidative stress in aging process as well as the role of hormesis and physical exercise as tools for preven-tion and treatment of sarcopenia, an aging related disease. Finally we reported what has recently been studied in relation to the effect of physical activity and sport on aging in women

The magnetic navigation system (MNS) with gradient and uniform saddle coils is one of the effective systems to manipulate various medical magnetic robot due to its compact structure and uniformity of the magnetic field and field gradient. However, it has limited operating time and large inductance effect due to the high current density and numerous turns of coils, respectively. In this paper, we propose an optimization methodology of the MNS considering the current density and inductance of the coils. We introduce objective functions, constraints, and design variables of the MNS. Then, the MNS was designed by an optimization algorithm. The constructed MNS was compared with the conventional MNS, and it could generate 22 % stronger magnetic field or field gradient while the maximum three-dimensional rotating magnetic field was improved by 42 %. We also demonstrated an unclogging performance of a helical robot was improved by 54 % with the constructed MNS.

Polysaccharide from Ficus carica L. (FCP) exert multiple biological activities, as a biological macromolecule, the available knowledge about the specific structures and mechanisms of biological activity of purified 'Brunswick' fig polysaccharide is currently limited. In the present study, by chemical purification and characteristics identified via specific instruments, and then the impact of FCP on the immunomodulation activity in vitro and in vivo was examined. Structural char-acteristics showed that the molecular weight of the FCP was determined to be 127.5 kDa, the primary monosaccharides present in the FCP were galacturonic acid (GalA), arabinose (Ara), galactose (Gal), rhamnose (Rha), glucose (Glc), and xylose (Xyl) at a ratio of 0.321:0.287:0.269:0.091:0.013:0.011. Based on the investigation of in vitro immunomodulatory ac-tivity, FCP was found to stimulate the production of NO, TNF-α, and IL-6 and increased the pi-nocytic activity of macrophages. Further analysis revealed that FCP activated macrophages by interacting with toll-like receptor 4 (TLR4). Moreover, the in vivo test results indicate that FCP showed significant increase serum pro-inflammatory factors in immunosuppressed mice. Overall, this study suggests that FCP has the potential to be utilized as a novel immunomodulator in the pharmaceutical and functional food industries.

The quest for youthful, healthy skin and full, vibrant hair has long been a driving force in the dermocosmetics field. However, traditional approaches often struggle to address the underlying causes of aging, damage, and hair loss. Regenerative cosmetics, powered by skin tissue engineering, offer a transformative alternative. This review explores the emerging field of using engineered skin tissues for cosmetic purposes, focusing specifically on their potential for anti-aging, repair, and hair restoration applications. We discuss how these technologies aim to rejuvenate aging skin by promoting collagen production, reducing wrinkles, and improving overall skin function. Additionally, the use of engineered skin for wound healing and scar reduction is examined, highlighting their potential to improve the appearance and functionality of damaged skin. Finally, we advance the exciting prospects of utilizing skin tissue engineering techniques to regenerate hair follicles, potentially offering solutions for hair loss and promoting denser hair growth.

Pragmatic trials aim to assess intervention efficacy in usual patient care settings, contrasting with explanatory trials conducted under controlled conditions. In aging research, pragmatic trials are important designs for obtaining real-world evidence in elderly populations, which are often underrepresented in trials. In this review, we discuss statistical considerations from a frequentist approach for the design and analysis of pragmatic trials. When choosing the dependent variable, it is essential to use an outcome that is highly relevant to usual medical care while also providing sufficient statistical power. Besides traditionally used binary outcomes, ordinal outcomes can provide pragmatic answers with gains in statistical power. Cluster randomization requires careful consideration of sample size calculation and analysis methods, especially regarding missing data and outcome variables. Mixed effects models and generalized estimating equations (GEEs) are recommended for analysis to account for center effects, with tools available for sample size estimation. Multi-arm studies pose challenges in sample size calculation, requiring adjustment for design effects and consideration of multiple comparison correction methods. Secondary analyses are common but require caution due to the risk of reduced statistical power and false-discovery rates. Safety data collection methods should balance pragmatism and data quality. Overall, understanding statistical considerations is crucial for designing rigorous pragmatic trials that evaluate interventions in elderly populations under real-world conditions. In conclusion, this review focuses on various statistical topics of interest to those designing a pragmatic clinical trial, with consideration of aspects of relevance in the aging research field.

Oxidative stress and chronic inflammation, both at the systemic and central level, are critical early events in atherosclerosis and Alzheimer’s disease (AD). Purpose. To investigate the oxidative stress, inflammatory, and Tau-phosphorylation lowering effects of pomegranate polyphenols (PP) (punicalagin, ellagic acid, peels, and arils extracts). Methods. We used flow cytometry to quantify protein expression of proinflammatory cytokines (IL-1β) and anti-inflammatory mediators (IL-10) in THP-1 macrophages, as well as M1/M2 cell-specific markers (CD86 and CD163) expression in human microglia HMC3 cells. IL-10 protein expression was also quantified in U373-MG human astrocytes. The effect of PP on human amyloid beta 1-42 (Aβ1-42)-induced oxidative stress was assessed in microglia by measuring ROS generation and lipid peroxidation, using respectively two ′,7′-dichlorofluorescein diacetate (DCFH-DA) and thiobarbituric acid reactive substances (TBARS) tests. Neuronal viability and cell apoptotic response to Aβ1-42 toxicity were assayed using the MTT (3-(4, 5-dimethyl thiazolyl-2)-2, 5-diphenyltetrazolium bromide) assay and the annexinV-FITC apoptosis detection kit; respectively. Finally, flow cytometry analysis was also performed to evaluate the ability of PP to modulate Aβ1-42-induced Tau-181 phosphorylation (pTau-181). Results. Our data indicate that PP was significantly (p<0.05) effective in countering Aβ1-42-induced inflammation through increasing the anti-inflammatory cytokines (IL-10) (in U373-MG astrocytes and THP1 macrophages) and decreasing proinflammatory markers (IL-1β) expression in THP1 macrophages. PP was also significantly (p<0.05) effective in inducing the phenotypic transition of THP-1 macrophages and microglial cells from M1 to M2 by decreasing CD86 and increasing CD163 surface receptor expression. Moreover, our treatments have a significant (p<0.05) beneficial impact on oxidative stress, illustrated in the reduction of TBARS and ROS generation. Our treatments have significant (p<0.05) cell viability improvement capacities and anti-apoptotic effects on human H4 neurons. Furthermore, our results suggest that Aβ1-42 significantly (p<0.05) increases pTau-181. This effect was significantly (p<0.05) attenuated by arils, peels, and punicalagin and drastically reduced by ellagic acid treatments. Conclusion. Our results are attributed to PP's anti-inflammatory, antioxidant, anti-apoptotic, and anti-Tau pathology potential. Future studies should aim to extend our knowledge of the potential role of PP on A1-42-induced neurodegeneration, mainly its association with the tauopathy involved in AD.

Aging-related disorders pose significant challenges due to their complex interplay of physiological and metabolic factors, including inflammation, oxidative stress, and mitochondrial dysfunction. Curcumin, a natural compound with potent antioxidant and anti-inflammatory properties, has emerged as a promising candidate for mitigating these age-related processes. However, gaps in understanding the precise mechanisms of curcumin's effects and the optimal dosages for different conditions necessitate further investigation. This systematic review synthesizes current evidence on curcumin's potential in addressing age-related disorders, emphasizing its impact on cognitive function, neurodegeneration, and muscle health in older adults. By evaluating the safety, efficacy, and mechanisms of action of curcumin supplementation, this review aims to provide insights into its therapeutic potential for promoting healthy aging. A systematic search across three databases using specific keywords yielded 2,256 documents, leading to the selection of 15 clinical trials for synthesis. Here we highlight the promising potential of curcumin as a multifaceted therapeutic agent in combating age-related disorders. The findings of this review suggest that curcumin could offer a natural and effective approach to enhancing the quality of life of aging individuals. Further research and well-designed clinical trials are essential to validate these findings and optimize the use of curcumin in personalized medicine approaches for age-related conditions.

Every individual at some point encounters the progressive biological process of aging which is considered one of the major risk factors for common diseases. The main drivers of aging are oxi-dative stress, senescence, and Reactive oxygen species (ROS). The renin-angiotensin-aldosterone system (RAAS) includes several systematic processes for the regulation of blood pressure which is caused by an imbalance of electrolytes. During activation of RAAS, binding of angiotensin II (ANG II) to angiotensin II type I receptor (AGTR1) activates intracellular NADPH oxidase to generate superoxide anions and promote uncoupling of endothelial NO synthase, which in turn decreases NO availability and increases ROS production. Promoting oxidative stress and DNA damage mediated by ANG II is tightly regulated. Individuals with sodium deficiency-associated diseases such as Gitelman syndrome (GS) and Bartter syndrome (BS) show down-regulation of inflammation-related processes and have reduced oxidative stress and ROS. Additionally, the histone deacetylase-Sirtuin-1(SIRT1) has a significant impact on the aging process with reduced activity with age. However, GS/BS patients generally sustain higher levels of SIRT1 activity than aged-matched healthy individuals. In this review, we highlight the importance of the hallmarks of aging, inflammation, and the RAAS system in GS/BS patients and how this might impact healthy aging. We further propose fu-ture research directions for studying the etiology of GS/BS at the molecular level using pa-tient-derived renal stem cells and induced pluripotent stem cells.

A number of accidents at sea are primarily caused by low visibility due to sea fog therefore, it is important to estimate sea fog intensity and visibility in real-time in the ocean environment. However, the existing estimation systems have significant costs so that it is not viable to install them at various locations, such as small vessels, minor ports, and a number of buoys. Therefore, this paper proposes an algorithm called RDCP (Reduced Dark Channel Prior) which provides the estimation at a low complexity and a low cost. For the estimation, the RDCP algorithm firstly acquires dark channels from an ocean image, then applies an optimized threshold value to the dark channels, and crops out the sky region in the ocean image. For the estimation performance evaluation, 320 raw images captured from cameras at four different ports in South Korea are used rather than artificially composed images. Considering facilities in oceans which are usually operated in the power limited environment, the processing time performance of PDCP are also examined. The experiments demonstrate that the RDCP algorithm provides reliable estimation performance in real-time.

The last decade has seen remarkable progress in the characterization of methylation clocks that track biological age in humans and many other mammalian species. While the biological processes of aging that underlie these clocks have remained unclear, several clues have pointed to a link to developmental mechanisms. These include the presence in the vicinity of clock CpG sites of genes that specify development, including those of the Hox (homeobox) and polycomb classes. Here we discuss how recent advances in programmatic theories of aging provide a framework within which methylation clocks can be understood as part of a developmental process of aging. This includes how such clocks evolve, how developmental mechanisms cause aging, and how they give rise to late-life disease. The combination of ideas from evolutionary biology, biogerontology and developmental biology open a path to a new discipline, that of developmental gerontology (devo-gero). Drawing on the properties of methylation clocks, we offer several new hypotheses that exemplify devo-gero thinking. We suggest that polycomb controls a trade-off between earlier developmental fidelity and later developmental plasticity. We also propose the existence of an evolutionarily-conserved developmental sequence spanning ontogenesis, adult development and aging, that both constrains and determines the evolution of aging.

Background: Aging is commonly accepted as a time period of declining heath. Aims: This review aimed to examine the research base concerning the use of term ‘successful aging’, a process and outcome deemed desirable, but challenging to attain. A second was to provide related information to demonstrate how health professionals as well as individuals can aim for a ‘successful aging’ process and outcome, despite the presence of disabling osteoarthritis. Methods: Information specifically focusing on ‘successful aging’ and the concept of improving opportunities for advancing ‘successful aging’ despite osteoarthritis was sought. Results: Among the many articles on ‘successful aging’, several authors highlight the need to include, a broader array of older adults into the conceptual framework. Moreover, conditions such as osteoarthritis should not necessarily preclude the individual from attaining a personally valued successful aging outcome. Conclusion: Pursuing more inclusive research and research designs, and not neglecting to include people with chronic osteoarthritis can potentially heighten the life quality of all aging individuals, while reducing pain and depression, among other adverse aging and disability correlates among those with osteoarthritis

A novel simplifying Volterra structure algorithm is proposed for intensity modulation direct detection (IM-DD) optical fiber short distance communication system by using the decision feedback equalization algorithm (DFE). Based on this algorithm, the signal damage for four-level pulse amplitude modulation signal (PAM-4) is compensated, which is caused by device bandwidth limitation and dispersion during transmission. Experiments have been carried out using a 25GHz Electro-absorption Modulated Laser (EML), showing that PAM-4 signals can transmit over 10km in standard single-mode fiber (SSMF). The 112Gbps and 128Gbps signals can reach the error rate threshold of KP4-FEC (BER=2*10-4) and HD-FEC (BER=3.8*10-3), respectively. The simplified principle and process of proposed Volterra-based equalization algorithm are presented. Experimental results show that the algorithm complexity is greatly reduced by 75%, which provides an effective theoretical support for the commercial application of this algorithm.

Background: This study investigated how the expression of heat shock protein 27 (HSP27), cellular FLICE-like inhibitory protein (cFLIP) and clusterin (CLU) affects the progression of cancer cells and their susceptibility to doxazosin-induced apoptosis. By silencing each of these genes individually, their effect on prostate cancer cell viability after doxazosin treatment was investigated. Methods: PC-3 prostate cancer cells were cultured and then subjected to gene silencing using siRNA targeting HSP27, cFLIP, and CLU, either individually, in pairs, or all together. Cells were then treated with doxazosin at various concentrations and their viability was assessed by MTT assay. Results: The study found that silencing the CLU gene in PC-3 cells significantly reduced cell viability after treatment with 25 µM doxazosin. In addition, dual silencing of cFLIP and CLU decreased cell viability at 10 µM doxazosin. Notably, silencing all three genes of HSP27, cFLIP, CLU was most effective and reduced cell viability even at a lower doxazosin concentration of 1 µM. Conclusions: Taken together, these findings suggest that simultaneous silencing of HSP27, cFLIP, and CLU genes may be a potential strategy to promote apoptosis in prostate cancer cells, which could inform future research on treatments for malignant prostate cancer.

Glioblastoma (GBM) is the most aggressive brain cancer. To model GBM in research, orthotopic brain tumor models, including syngeneic models like GL261 and genetically engineered mouse models like TRP, are used. In longitudinal studies, tumor growth and treatment response are typ-ically tracked with in vivo imaging, including bioluminescence imaging (BLI), which is quick, cost-effective, and easily quantifiable. However, BLI requires luciferase-tagged cells, and recent studies indicate that the luciferase gene can elicit an immune response, leading to tumor rejection and experimental variation. We sought to optimize the engraftment of two luciferase-expressing GBM models, GL261 Red-FLuc and TRP-mCherry-FLuc, showing differences in tumor take, with GL261 Red-FLuc cells requiring immunocompromised mice for 100% engraftment. Immuno-histochemistry and MRI revealed distinct tumor characteristics: GL261 Red-FLuc tumors were well-demarcated with densely packed cells, high mitotic activity, and vascularization. In con-trast, TRP-mCherry-FLuc tumors were large, invasive, and necrotic, with perivascular invasion. Quantifying tumor volume using the HALO® AI analysis platform yielded results comparable to manual measurements, providing a standardized and efficient approach for reliable high-throughput analysis of luciferase-expressing tumors. Our study highlights the importance of considering tumor engraftment when using luciferase-expressing GBM models, providing in-sights for preclinical research design.

Abstract: Giant Cell Arteritis (GCA) is an autoimmune/autoinflammatory disease affecting large vessels in patients over 50 years old. The disease presents as an acute inflammatory response with two phenotypes, cranial-GCA and Large Vessel Vasculitis (LV)-GCA, involving the thoracic aor-ta and its branches. 18F-fluorodeoxyglucose positron emission tomography-computed tomogra-phy (18F-FDG PET-CT) is among the imaging techniques contributing to diagnosis of patients with systemic disease. However, its association with soluble inflammatory markers is still elu-sive. This proof-of-concept study aims to identify novel soluble serum biomarkers in PET/CT pos-itive patients with LV-GCA and associate them with active (0 months) and inactive disease (6 months following treatment), in sequential samples. The Most-Disease-Segment Target-to-Background Ratio (TBRMDS) was calculated for 9 LV-GCA patients, while 12 cranial-GCA and 7 Polymyalgia Rheumatica patients with negative initial PET/CT served as disease controls. Serum macrophage-related cytokines were evaluated by Cytometric Bead Array (CBA). Finally, previously published NMR-metabolomics data acquired at the same blood sampling were associated with PET/CT findings. TBRMDS was significantly increased in active versus inactive disease (3.45 vs. 2.55, p=0.008). The analysis identified 6 serum metabolites, as more sensitive to change from the active to inactive state. Among them, choline levels were exclusively altered in the LV-GCA group, but not the disease controls. Cytokine levels were not associated with PET/CT activity. Combining with CRP, ESR, and TBRMDS a composite index was generated to depict well the differences between active and inactive systemic LV-GCA (25.45 vs 11.45, p=0.0039). These preliminary results could pave the way for more extensive studies integrating serum metabolomic parameters with PET/CT imaging data to extract sensitive composite disease indexes useful for the everyday clinical practice.

Background: This study investigated the prevalence of worsening problems using Post Stroke Checklist (PSC) at 3, 6, and 12 months post-stroke and their associations with health-related quality of life. Methods: In stroke patients admitted between June 2014 and December 2015, PSC and EuroQol-5Dthree level (EQ-5D-3L) were assessed at post-stroke 3 (n=181), 6 (n=175), and 12months (n=89). The prevalence of worsening problems and its association withEQ-5D-3L at post-stroke 3 and 6months were analyzed. Results: An average of 0.59 (range 0–12), 1.47 (range 0–12), and 1.00 (range 0–10) worsening problems per patient was identified at 3, 6, and 12months after stroke, respectively. The most frequently and continuously identified worsening problems were mood disturbances (reported by 8.8%, 16.0% and13.5% of patients at 3, 6, and 12 months post-stroke, respectively). Worsening mobility was significantly associated with worse EQ-5D index at post-stroke 3 months (β,-0.583; 95% CI, -1.045 to -0.120). The worsening of mobility and communication was significantly associated with worse EQ-5D index at post-stroke 6 months (mobility: β,-0.170; 95% CI, -0.305 to -0.034, communication: β,-0.164; 95% CI, -0.309 to -0.020). Conclusions: PSC may be useful for the detection of various subjective worsening problems during serial clinical follow-up after stroke. Appropriate rehabilitation and management strategy to solve the identified problems could improve the quality of life in stroke survivors.

D-dimer testing in combination with clinical assessment is commonly used to diagnose suspected DVT and pulmonary embolism. However, as D-dimer levels are physiologically higher in elderly patients, this test loses clinical specificity in the setting of geriatric patients. The aim of our study was to investigate the changes in D-dimer levels with age and the specificity of the D-dimer test in the diagnosis of pulmonary embolism. 1617 elderly patients consecutively admitted to the Geriatric Emergency Care Department of the INRCA-IRCCS hospital between January 2013 and February 2014 and for whom D-dimer results were available were included. The D-dimer immunoturbidimetric assay was performed on a cs-2100i Sysmex Siemens using a conventional cut-off level of 500 µg/L. The median D-dimer level was 1200 [550-2990] µg/L FEU, and the percentage of patients with D-dimer levels below the conventional cut-off was only 22.1%. As expected, there was a significant age-related increase in D-dimer, even when sex was considered, and a significant decrease in the specificity of D-dimer assay with age. The most established use of D-dimer testing is in the diagnosis of deep vein thrombosis or pulmonary embolism. Our study confirms the need for an age-adjusted cut-off for D-dimer testing in geriatric patients.

Titanium (Ti) and Ti-based alloys are commonly used in dental implants, and surface modifications of dental implants are important for achieving osseointegration (i.e., direct connection between the implant surface and bone). This study investigated the effect of an eco-friendly etching solution—a hydrogen peroxide–sodium bicarbonate mixture—on the surface properties and contact angles of and osteoblast adhesion and proliferation on Ti surfaces. Disk-shaped Ti specimens were prepared using different surface treatments (machining, sandblasting, and sandblasting/acid-etching), and they were immersed in the etching solution and then ultrasonically cleaned. Surface characterization was performed using scanning electron microscopy, digital microscopy, contact angle analysis, and X-ray photoelectron spectroscopy. MG-63 osteoblasts were cultured on the specimens, and their adhesion to the specimen surface and their proliferation were examined using staining and the MTT assay, respectively. Additional etching with the etching solution caused the formation of nano/micro hierarchical structures, increased the surface roughness, and enhanced the hydrophilicity. Osteoblast adhesion and proliferation were found to improve on the modified surfaces. The eco-friendly etching method has the potential to enhance the biological properties of Ti implant surfaces and to thereby improve the dental implant performance.

Pipelines extend thousands of kilometers to transport and distribute oil and gas. Given the challenges often faced with corrosion, fatigue, and other issues on steel pipes, the demand for glass fiber reinforced plastics (GFRP) pipes is increasing in the oil and gas gathering and transmission systems. However, the medium transported through these pipelines contains multiple acid gases such as CO2 and H2S, as well as ions including Cl-、Ca2+、Mg2+、SO42-、CO32- and HCO3-. These substances can cause a series of problems, such as aging, debonding, delamination, and fracture. In this study, a series of aging damage experiments were conducted on V-shaped GFRP pipes with depths of 2mm and 5mm. The aging and failure of GFRP were studied under the combined effects of external force and acidic solution using acoustic emission (AE) techniques. It was found that the acidic aging solution promoted matrix damage, fiber/matrix desorption, and delamination damage in GFRP pipes over a short period. However, the overall aging effect was relatively weak. Based on the experimental data, the SSA-LSSVM algorithm was proposed and applied to the damage pattern recognition of GFRP. An average recognition rate of up to 90% was achieved, indicating that this method is highly suitable for analyzing AE signals related to GFRP damage.

Toll-like receptor 4 (TLR4) is a member of the TLR family. Members of the TLR family play an important role in innate immune responses and are induced by recognition of pathogen-associated molecular patterns. They are also involved in cell proliferation and apoptosis in cancer. We investigated the role of TLR4 in apoptotic cell death in gynecological cancer cells; gynecological cancer is associated with infertility and spontaneous abortion. To examine the effect of TLR4 activation on apoptotic signaling in cancer cells, cultured primary cancer cells were treated with the TLR4 agonist lipopolysaccharide (LPS). The morphology of cancer cells was compared with normal myometrial cells. Enhanced growth rate and loss of contact inhibition with cellular overlap was observed in the cancer cells. The molecular mechanism analysis revealed differential expression of tumor suppressor genes in LPS-treated cancer cells. The expression of apoptosis-related caspase-3 was increased significantly in cancer cells with TLR4 activation after exposure to LPS. Taken together, these results suggest the pro-apoptotic activity of TLR4 as a potential therapeutic target for the treatment of gynecological cancers.

Age-related diseases place an intense and growing stress on healthcare systems. Numerous theories of ageing exist. Yet prediction, prevention and treatment limitations of age-related disease persist because we lack a complete aetiological understanding of their origins. Here we propose a new theory that aims to provide a blueprint-type understanding of ageing and disease aetiology, working across multiple scientific disciplines. Supported by specific examples, we demonstrate that the primary driver of much of age-related diseases is the futile triggering of specific molecular pathways in a pathological manner, which we term patho-pathways. Patho-pathways induce pathological cell, tissue and system changes in the form of hyperactivity (undesirable increased and new biological activities that are typical of age related disease). As part of patho-pathways, all wild-type (normal) genes have the potential to contribute to age-related diseases (though specific risk varies and can be formularised). In a domino-style effect, one patho-pathway typically triggers others, resulting in complex, but traceable, cascades. Utility, in terms of changing clinical and scientific practice, is derived from mapping these cascades to create Blueprint Maps that allow identification of biomarkers and therapeutic targets far upstream in the causal chain of events. Finally, our theory provides testable hypotheses concerning predictions of links between otherwise seemingly disparate diseases as well as new interventions into ageing.

From the formalism of the thermodynamics of irreversible processes and the theory of complex systems, characterization of longevity and aging and its relationship with the emergence and evolution of cancer was carried out. It was found that: 1. The rate of entropy production can be used as an index of robustness, plasticity, the aggressiveness of cancer, and as a measure of biological age; 2. The aging process, as well as the evolution of cancer, goes through what we have called “biological phase transition”; 3. The process of metastasis, which occurs through epithelial-mesenchymal transition (EMT), appears as a phase transition far from thermodynamic equilibrium and exhibits Shilnikov chaos-like dynamic behavior. This dynamic guarantees the robustness of the process and, in turn, its unpredictability; 4. It was shown that as the ferroptosis process is strengthened, the complexity of the dynamics associated with the emergence and evolution of cancer decreases. The theoretical framework developed contributes to a better understanding of the biophysical-chemical phenomena of longevity and aging and their relationship with cancer.

Accurate forecasting and efficient management of commodities are crucial for stakeholders in the industry, given the volatile nature of these markets. This study addresses these needs by leveraging advanced forecasting techniques and machine learning models to predict prices and enhance supply chain efficiency. TThe focus is on utilizing ARIMA, SARIMAX, and LSTM models to analyze historical trading data for commodities such as cocoa, coffee, and sugar sourced from Kaggle’s comprehensive dataset. The research applies ARIMA and SARIMAX models to forecast price trends, overcoming initial challenges related to data index frequency and seasonality. LSTM models are employed for more nuanced demand forecasting, particularly for random-length lumber, demonstrating the model's capability to predict future market trends accurately. The study highlights significant improvements in prediction accuracy and supply chain management through meticulous feature engineering and model optimization, offering valuable insights for strategic decision-making in the supply chain sector.

Achievement of solid fusion of the lumbosacral junction (L5-S1 level) is an important factor in adult spinal deformity (ASD) surgery. The purpose of this study is to explore the effectiveness and feasibility of injectable rhBMP-2 (a combination of Eschericia coli-derived rhBMP-2 and hydrogel type β-TCP carrier; NOVOSIS Inject) as a bone substitute for the fusion of lumbosacral junction. 20 patients (average age 69.1 years) diagnosed with ASD with sagittal imbalance who underwent surgical treatment including anterior lumbar interbody fusion (ALIF) in the L5-S1 level were evaluated. Injectable rhBMP-2 was applied in L5-S1 ALIF and followed-up for 1-year. Solid fusion rates and changes of clinical outcomes (Oswestry Disability Index [ODI], Visual Analog Scale [VAS] of back and leg) were measured and analyzed at 6 and 12 months after surgery. All postoperative adverse events were evaluated about the association with injectable rhBMP-2. Fusion rates were 68.4% and 100% at 6 and 12 months after surgery. Compared to baseline, ODI were improved to 45.8% and 63.7%, VAS(back) were improved to 69.2% and 72.8%, and VAS(leg) were improved to 49.2% and 64.8% at 6 and 12 months after surgery (p&lt;0.001, respectively). There were no adverse events associated with injectable rhBMP-2. Thus, injectable rhBMP-2 may be a suitable choice of a bone graft substitute when achieving solid interbody fusion in the lumbosacral junction.

Accumulation of damage is generally considered the cause of aging. Interventions that delay aging mobilize mechanisms that protect and repair cellular components. Consequently, research has been focused on studying the protective and homeostatic mechanisms within cells. However, in humans and other multicellular organisms, cells are surrounded by extracellular matrices (ECM), which are important for tissue structure, function and intercellular communication. During aging, components of the ECM become damaged through fragmentation, glycation, crosslinking, and accumulation of protein aggregation, all of which contribute to age-related pathologies. Interestingly, placing senescent cells into a young ECM rejuvenates them and we found that many longevity-assurances pathways re-activate de-novosynthesis of ECM proteins during aging. This raises the question of what constitutes a young ECM to reverse aging or maintain health? In order to make inroads to answering this question, I suggest a systems-level approach of quantifying the matrisome or ECM compositions reflecting health, pathology, or phenotype and propose a novel term, the “matreotype”, to describe this. The matreotype is defined as the composition and modification of ECM or matrisome proteins associated with or caused by a phenotype, such as longevity, or a distinct and acute physiological state, as observed during aging or disease. Every cell type produces its unique ECM. Interestingly, cancer-cell types can even be identified based on their unique ECM composition. Thus, the matreotype reflects cellular identity and physiological status. Defined matreotypes could be used as biomarkers or prognostic factors for disease or health status during aging with potential relevance for personalized medicine. Treatment with biologics that alter ECM-to-cell mechanotransduction might be a strategy to reverse age-associated pathologies. An understanding of how to reverse from an old to a young matreotype might point towards novel strategies to rejuvenate cells and help maintain tissue homeostasis to promote health during aging.

The extraocular muscles (EOMs) possess unique characteristics that set them apart from other skeletal muscles. These muscles, responsible for eye movements, exhibit remarkable resistance to various muscular dystrophies and aging, presenting a significant contrast to the vulnerability of skeletal muscles to these conditions. In this review, we delve into the cellular and molecular underpinnings of the distinct properties of EOMs. We explore their structural complexity, highlighting differences in fiber types, innervation patterns, and developmental origins. Notably, EOM fibers express a diverse array of myosin heavy chain isoforms, retaining embryonic forms into adulthood. Moreover, their motor innervation is characterized by a high ratio of nerve fibers to muscle fibers and the presence of unique neuromuscular junctions. These features contribute to the specialized functions of EOMs, including rapid and precise eye movements. Understanding the mechanisms behind the resilience of EOMs to disease and aging may offer insights into potential therapeutic strategies for treating muscular dystrophies and myopathies affecting other skeletal muscles.

Fragile X syndrome (FXS) is the most frequent monogenic form of autism spectrum disorder (ASD). Autistic FXS is caused by loss of the fmr1 gene product, the fragile X mental retardation protein (FMRP), triggering physiological and behavioral abnormalities. It is correlated with clock components for behavioral circadian rhythm. Mutation of this gene causes the disturbances in sleep patterns and circadian behavior commonly observed in patients with autistic FXS, accompanied by frequent dysregulation of melatonin synthesis and melatonin-dependent signaling. These changes impair vigilance, learning and memory, and are also linked to autistic behavior including the abnormal anxiety response. However, although several possible causes, symptoms, and clinical features of ASD have been investigated, the correlation between an altered circadian rhythm and autistic FXS has not been extensively studied. Recent works have highlighted the impact of melatonin on the nervous, immune, and metabolic systems. Even though utilization of melatonin for sleep disorder in ASD has been considered in clinical research, further studies should be aimed at its neuroprotective role in ASD during developmental period. In this review, we focus on the regulatory circuits involved in melatonin dysregulation and circadian system disruption in those with autistic FXS. Additionally, we discuss the neuroprotective effect of melatonin intervention. This may improve neuroplasticity and physical capability. We also review the underlying molecular mechanisms, and suggest that melatonin may be a useful novel treatment for autistic FXS, countering the adverse effects of circadian variation.

Physical activity (PA) benefits are well-established, yet many US adults fail to meet PA guidelines. This is especially true for minorities facing social inequities. This study explored barriers and facilitators to PA among urban Midwestern minorities using a mixed-methods approach framed on the socio-ecological model. A cross-sectional survey was conducted among community-dwelling minorities. Participants were grouped as completing low (LLPA) or high (HLPA) weekly leisure-time PA for comparison. Quantitative analysis included MANOVA, follow-up ANOVAs, and calculation of effect sizes. Qualitative data were assessed using inductive thematic analysis. Twenty-nine adults (44.83% Black, 41.37% Latino) participated in the study. The HLPA group (n = 18) reported higher leisure-time PA (p = 0.001, d = 2.21) and total PA (p = 0.02, d = 1.00) compared to the LLPA group (n = 11). LLPA participants faced more personal barriers to PA (p = 0.02, d = -0.92). Common barriers identified in the interviews included a lack of time and financial costs. Facilitators included social support and available PA facilities. Both groups achieved USPA guidelines through different PA domains. Increasing social support and lowering PA-related costs could enhance participation. Addressing barriers and leveraging existing facilitators are crucial to increasing PA among minorities.

This study explores the role of inflammation and oxidative stress, hallmarks of COVID-19, in accelerating cellular biological aging. We investigated early molecular markers—DNA methylation age (DNAmAge) and telomere length (TL)—in blood leukocytes, nasal cells (NC), and induced sputum (IS) one-year post-infection in pauci- and asymptomatic healthcare workers (HCWs) infected during the first pandemic wave (February-May 2020), compared to COPD patients, model for "aged lung". Data by questionnaires, Work Ability Index (WAI), blood analyses, autonomic cardiac balance assessments, heart rate variability (HRV), and pulmonary function tests were collected. Elevated leukocyte DNAmAge significantly correlated with advancing age, male gender, daytime work, and an aged phenotype characterized by chronic diseases, elevated LDL and glycemia levels, medications affecting HRV, and declines in lung function, WAI, lymphocyte count, hemoglobin levels, and HRV (p&lt;0.05). Increasing age, LDL levels, job positions involving intensive patient contact, and higher leukocyte counts collectively contributed to shortened leukocyte TL (p&lt;0.05). Notably, HCWs exhibited accelerated biological aging in IS cells compared to both blood leukocytes (p≤0.05) and NC (p&lt;0.001), and were biologically older than COPD patients (p&lt;0.05). These findings suggest the need for monitoring aging in pauci- and asymptomatic COVID-19 survivors, who represent the majority of the general population.

Pancreatic cancer (PC) has a poor prognosis and displays resistance to immunotherapy. A better understanding of tumor-derived extracellular vesicles (EVs) effects on immune responses might contribute to improved immunotherapy. EVs derived from Capan-2 and BxPC-3 PC cells isolated by ultracentrifugation were characterized by atomic force microscopy, western blot (WB), nanoparticle tracking analysis and label-free proteomics. Fresh PBMCs from healthy donors were treated with PC- or control-derived heterologous EVs followed by flow cytometry analysis of CD8+ and CD4+ lymphocytes. Proteomics of lymphocytes sorted from EV-treated, or -untreated PBMCs was performed and IFN-γ concentration was measured by ELISA. Notably, most of the proteins identified in Capan-2 and BxPC-3 EVs by proteomic analysis were connected in a single functional network (p=1x10-16) and were involved in “Immune System” (FDR: 1.10x10-24 and 3.69x10-19, respectively). Interestingly, treatment of healthy donor-derived PBMCs with Capan-2 EVs, but not with BxPC-3 EVs or heterologous control EVs induced early activation of CD8+ and CD4+ lymphocytes. Proteomics of lymphocytes sorted from EV-treated PBMCs was consistent with their activation by Capan-2 EVs, indicating IFN-γ among major upstream regulators, as confirmed by ELISA. Proteomic and functional analyses indicate that PC-EVs have pleiotropic effects, and some may activate early immune response, which might be relevant for the development of highly needed immunotherapeutic strategies in this immune-cold tumor.

There is scientific consensus that organismal aging did not evolve by natural selection (NS) because it lacks individual benefit. Nonetheless it exists, leading to much speculation about its origins, and when the diminishing force of selection begins. Both concepts are based upon two misconceptions; that aging occurs in and of itself and is caused by the declining strength of NS during the reproductive lifespan. Although lacking individual benefit, aging evolved by NS as a tradeoff of survival for reproduction. Based upon regulatory dynamics that participate in this tradeoff, aging begins once reproductive success has been achieved through offspring nurturing. Thereafter, the strength of NS wanes to exponentially accelerate aging, leading to death. Assumptions of the theory are that: (1) a life-long, “holistic” regulatory mechanism whose genic expression is modified epigenetically, originates in ontogenesis; (2) the regulatory mechanism of the last developmental stage becomes redundantly expressed during “morphostasis”, a non-aging, life interval of peak vitality to ensure completion of reproduction through nurturing, and (3) thereafter, loss of regulatory redundancy causes aging which reduces the strength of natural selection and allows accumulation of randomly occurring somatic damage.

As the world's population ages and the resulting health problems become more serious, medical and health policies in developed countries are focused on how to prevent and treat the diseases of the aging population and how to maintain their quality of life. Typical age-related diseases include deafness, cataracts, osteoarthritis, chronic obstructive pulmonary disease, diabetes mellitus, and dementia. Although the mechanisms by which these diseases develop differ, they are all caused by the accumulation of molecular and cellular damage over time. In addition, age-related diseases can cause a decline in physical and mental functions and the ability to perform activities of daily living, as well as the loss of roles in society and a sense of fulfillment in life. Therefore, there is a need for treatment and measures to accurately grasp and maintain their quality of life.

Abstract: Since ancient times aging has also been regarded as a disease, and humankind has always strived to extend the natural lifespan. Analyzing the genes involved in aging and disease allows for finding important indicators and biological markers for pathologies and possible therapeutic targets. An example of the use of omics technologies is the research regarding aging and the rare and fatal premature aging syndrome progeria (Hutchinson-Gilford progeria syndrome, HGPS). In our study, we focused on the in silico analysis of differentially expressed genes (DEGs) in progeria and aging, using a publicly available RNA Seq dataset (GEO dataset GSE113957) and a variety of bioinformatics tools. We identified several genes that appear to be involved both in natural aging and progeria (KRT8, KRT18, ACKR4, CCL2, UCP2, ADAMTS15, ACTN4P1, WNT16, IGFBP2). Further analyzing these genes and the pathways involved confirmed their possible roles in aging, suggesting the need for further in vitro and in vivo research. The graphical abstract illustrates the analysis workflow we used and will introduce in the following as an example to demonstrate the power of omics and bioinformatics.

This review summarizes current understanding of the interaction between circadian rhythms of gene expression and epigenetic clocks characterized by the specific profile of DNA methylation in CpG-islands which mirror the chronological age of individual cells and the entire organism. Basic mechanisms of regulation for circadian genes CLOCK- BMAL1 as well as downstream clock-controlled genes (ССG) are also discussed here. It has been shown that circadian rhythms operate by finely tuned regulation of transcription and rely on various epigenetic mechanisms including activation of enhancers / suppressors, acetylation / deacetylation of histones and other proteins as well as DNA methylation. Overall, up to 20% of all genes expressed by the cell are subject to expression oscillations associated with circadian rhythms. Also included in the review is a brief list of genes involved in the regulation of circadian rhythms, along with genes important for metabolic control, aging, and oncogenesis. Knocking out some of them (for example, Sirt1) accelerates the aging process, while overexpression of Sirt1, on the contrary, protects against age-related changes. Circadian regulators control a number of genes that activate the cell cycle (Wee1, c-Myc, p20, p21, and Cyclin D1) and regulate histone modification and DNA methylation. Approaches for determining the epigenetic age from methylation profiles across CpG islands in individual cells are described. DNA methylation, which characterizes the function of the epigenetic clock, appears to link together such key biological processes as regeneration and functioning of stem cells, aging and malignant transformation. Finally, main features of adult stem cell aging in stem cell niches and current possibilities for modulating the epigenetic clock as part of antiaging therapy are discussed.

For the past few decades, researchers have been intrigued with glassy polymers, which have applications ranging from gas separations to corrosion protection to drug delivery systems. The techniques employed to examine the sorption and diffusion of small molecules in glassy polymers are the subject of this review. Diffusion models in glassy polymers are regulated by Fickian and non-Fickian diffusion, with non-Fickian diffusion being more prevalent. The characteristics of glassy polymers are determined by sorption isotherms, and different models have been proposed in the literature to explain sorption in glassy polymers during the last few years. This review also includes the applications of glassy polymer. Despite having so many applications, current researchers still have difficulty in implementing coating challenges due to issues like as physical ageing, which is briefly discussed in the review.

Synchrotron radiation computed tomography (SRCT) allows more accurate calcified plaque and coronary stenosis assessment as a result of its superior spatial resolution, however, typical micro-computed tomography (micro-CT) systems have even higher resolution. The purpose of this study was to compare performance of high-resolution micro-CT with SRCT in the assessment of calcified plaques and a previously published dataset of coronary stenosis assessment. This experimental study involved micro-CT scanning of three-dimensional printed coronary artery models with calcification in situ used in our previously published SRCT study on coronary stenosis assessment. Measurements of coronary stenosis utilizing both modalities were compared using a paired sample t-test. The degrees of stenosis measured on all but one micro-CT dataset were statistically significantly lower than the corresponding SRCT measurements reported in our previous paper (p&lt;0.0005-0.05). This indicates that the superior spatial resolution of micro-CT was able to further reduce over-estimation of stenosis caused by extensive calcification of coronary arteries and hence false positive results. This study shows that high-resolution micro-CT outperforms SRCT in both calcified plaque and coronary stenosis assessment. This finding will become clinically important for cardiovascular event prediction and enable reclassification of individuals with low and intermediate risk into appropriate risk categories when the technical challenges of micro-CT in clinical practice such as the small field of view and demanding on image processing power are addressed.

Bone is a dynamic organ maintained by tightly regulated mechanisms. With old age, bone homeostasis which is maintained by an intricate balance between bone formation and bone resorption, undergoes deregulation. Oxidative stress-induced DNA damage, cellular apoptosis, and cellular senescence are all responsible for this tissue dysfunction and the imbalance in bone homeostasis. These cellular mechanisms have become a target for therapeutics to treat age-related osteoporosis. Pharmacological and genetic mouse models have shown the importance of senescent cell clearance in alleviating age-related osteoporosis. Senescent cells have an altered secretome, which may have an autocrine, paracrine, or endocrine function. The current review discusses the current and potential pathways which lead to a senescence profile in an aged skeleton. The review was written following an extensive literature survey of published studies, mostly excluding articles published on pre-print servers. The review discusses potential therapeutics targeting cellular senescence and the senescent secretome as underlying pathogenesis of an aging bone.

From grape cultivation to ripening and harvest timing to processing, each step can be a critical point when it comes to wine quality and phenolic composition. In this study, the influence of winemaking technology on resveratrol and quercetin content, as well as other polyphenolic compounds, was investigated. Resveratrol is a non-flavonoid polyphenolic stilbene synthesized by grape skin when damaged by infectious diseases or ionizing radiation. Quercetin is a phenol found in grape skins and stems and is produced to protect grapes from UV light damage. Trans-resveratrol and quercetin are known to act as antioxidants, reduce the risk of atherosclerosis and type 2 diabetes, inhibit the growth of cancer cells, and prevent the release of allergic and inflammatory molecules. However, the question was whether red wine could be enriched with these phenols using an innovative winemaking technology. The innovative idea was to completely replace the cold maceration process with maceration with the addition of wild yeast (Torulaspora delbrueckii, Td). Maceration with the addition of wild yeast (Td) offers the following advantages over traditional cold maceration: (1) higher concentrations of trans-resveratrol (>35-40%) and quercetin (>35-40%) in the final wine, (2) the new wine has a higher potential for human health, (3) the wine has a better aroma and stability due to the higher mannoprotein content, and (4) the better energy efficiency in the production process. The study of stability during storage and aging also included derivatives of benzoic acid and hydroxycinnamic acid, piceid, catechin, naringenin, rutin, kaempherol, hesperetin, and anthocyanins. The study found that younger wines had higher phenolic content, while storage of the wine resulted in a decrease in total phenolic content, especially monomeric stilbenes and quercetin.

The treatment of acute myeloid leukemia (AML) with adverse genetics remains unsatisfactory, with very low response rates to standard chemotherapy and shorter durations of remission commonly observed in these patients. The complex biology of AML with adverse genetics is continuously evolving. Herein, we discuss recent advances which have investigated the contribution of cell intrinsic mechanisms as well as of the immune system to myeloid leukemogenesis in this specific subset of AML. We focus on the biological rationales for combining targeted therapy and immunotherapy, which are currently being investigated in ongoing trials, and could hopefully ameliorate the poor outcomes for these patients

For a subject suffering from complex post-traumatic stress disorder, a psychological intervention program was designed, monitored in real-time during psychotherapy, and evaluated quantitatively and qualitatively after psychotherapy. One male subject participated in this program under consent. The proposed intervention program was designed using cognitive behavioral therapy and stabilization treatments for body-based sensory processes in four sessions of 90 min each. During psychotherapy, a wearable heart sensor and a communication application were utilized to determine the subject’s current psychological state. After the intervention, the effect of the proposed program was analyzed qualitatively and quantitatively using the Impact of Event Scale–Revised (IES-R-K), Athens insomnia scale (AIS), and heart rate variability (HRV). After the intervention program was conducted, the subject reconstructed his traumatic events and trained himself with certain psychological techniques to decrease his negative thoughts and emotions induced by his previous traumatic events. The IES-R-K and AIS ten months after the last session were changed positively by approximately 25% compared with the subject’s state before the first session. During psychotherapy, the HRV exhibited a significant correlation with the subject’s emotional state. The proposed intervention program induced a positive change in the subject. Although the HRV was well utilized in this investigation, more sophisticated statistical analysis will be required for clinical trials.

This study aims to evaluate the patient’s dose exposure from Computed Tomography Pulmonary Angiography (CTPA) examination and to estimates the cancer risk induced from the examinations based on the patient’s size. One hundred patients were recruited, and data information was collected retrospectively. A multi-detector (MDCT) (Philips Brilliance 128, USA) scanner were utilized for the CTPA examination, and dose data were obtained from the system. The effective diameter of each subjects’ image was measured for the Size-specific dose estimates (SSDEs). All subjects divided into Group 1 (19 – 25 cm), Group 2 (25-28 cm) and Group 3 (28-38 cm), where the association between gender were analysed. Effective dose (E), SSDE, organ dose and cancer risk of each group were evaluated and compared statistically using independent t-test and one-way ANOVA. The range of mean CTDI_vol, DLP and E values were (6.44 – 17.42 mGy), (239 – 631 mGy), (5.19 – 13.90 mSv), respectively. In respective with the patient’s effective diameter, the mean SSDE value for Group 1, Group 2 and Group 3 were 9.93 ± 3.89 mGy, 13.70 ± 9.04 mGy and 22.29 ± 7.35 mGy. The organ dose and cancer risk attained for breast, lung and liver were 17.05 ± 10.40 mGy (194 per one million procedure), 17.55 ± 10.86 mGy (192 per one million procedure) and 15.04 ± 9.75 mGy (53 per one million procedure), respectively. Lung and breast with more massive patient’s effective diameter received the highest dose exposure which increases the probability of the cancer risk. CTDI_vol was found to be underestimated, and SSDE provides more accurate in describing the radiation dose and cancer risk. Body effective diameter found to be significant on the estimation except for gender. Therefore, it is essential to apply optimised protocols in order to reduce patient’s exposure during CTPA examination.

The occurrence and intensity of the detonation phenomenon at spark-ignition (SI) engine conditions is investigated, with the objective to successfully predict super-knock and to elucidate the effect of kinetics and transport at the ignition front. The computational singular perturbation (CSP) framework is employed in order to investigate the chemical and transport mechanisms of deflagration and detonation cases in the context of 2D high-fidelity numerical simulations. The analysis revealed that the detonation development is characterized by: (i) stronger explosive dynamics and (ii) enhanced role of convection. The role of chemistry was also found to be pivotal to the detonation development which explained the stronger explosive character of the system, the latter being an indication of the system's reactivity. The role of convection was found to be enhanced at the edge of the detonating front, thereby suggesting that it is the result and not the cause of the detonation onset. Moreover, the increased contribution of convection was found to be related mainly to heat convection. Remarkably, the detonation front was mainly characterized by dissipative and not explosive dynamics. Finally, diffusion was found to have negligible role to both examined cases.

Near-infrared spectroscopy (NIRS) was implemented to monitor the moisture content of broadleaf litters. Partial least-squares regression (PLSR) models, incorporating optimal wavelength selection techniques, have been proposed to better predict the litter moisture of forest floor. Three broadleaf litters were used to sample the reflection spectra corresponding the different degrees of litter moisture. Maximum normalization preprocessing technique was successfully applied to remove unwanted noise from the reflectance spectra of litters. Four variable selection methods were also employed to extract the optimal subset of measured spectra for establishing the best prediction model. The results showed that the PLSR model with the peak of beta coefficients method was the best predictor among all candidate models. The proposed NIRS procedure is thought to be a suitable technique for on-the-spot evaluation of litter moisture.

Photon-counting Computed Tomography (PCCT) is a promising cardiovascular-imaging technique. Using detectors that count the number and energy of photons in multiple bins, PCCT offers several advantages over conventional CT, including a higher image quality, reduced contrast agent volume, radiation doses, and artifacts. Although PCCT is well established for cardiac imaging in assessing coronary artery disease, its application in vascular imaging remains limited. This review summarizes the available literature and provides an overview of the current use of PCCT for the diagnosis of vascular conditions. Of the 13 records selected in the initial search, 7 articles were included in the present review: 6 cohort studies and 1 case report. This review synthesized the available literature on PCCT in vascular imaging, focusing mainly on endoleaks detection and characterization after endovascular aneurysm repair (EVAR), contrast dose volume, and radiation exposure reduction, particularly in patients with chronic kidney disease and in those requiring follow-up CT.

The objective of this study is to preliminarily evaluate a new CT-biopsy guidance device, an origami needle guide. The device is created by laser cutting the structure from a sheet of cardboard, 3D printing two radiocontrast agent grids on to the surface and folding the structure into a rectangular prism with a viewing window. An abdominal imaging phantom was used to evaluate the device through CT imaging and the targeting of lesions for needle insertion. The lesion targeting trials resulted in a mean targeting error of 1.88 mm with a standard deviation of 0.73 mm. The device attaches to the patient and is rigid enough to adequately support standard biopsy needles, reducing the effect of gravity and the risk of laceration by the needles, making it potentially advantageous for biopsy of superficial lesions and lesions approached from a horizontal orientation. The device supports insertion of multiple needles at once, making it particularly suitable for composite ablation using multiple needles. Another advantage of the device is that it can guide off-axial needle insertion. The low-cost and disposability of the device make it well-suited for the minimally invasive image guided therapy environment.

Preventing the occurrence of secondary caries serves as one of the significant issues in dental clinic, thus make it indispensable to improving the properties of conventional composite resin (CR) by developing a novel CR. In present study, two groups of experimental CRs loaded with different contents of fluoride-doped nano-zirconia fillers (25 wt% and 50 wt%) were fabricated. The surface topography, mechanical performance, fluoride release, antibacterial effect, aging property and cytotoxicity of the experimental CRs were evaluated subsequently. A uniform distribution of the F-zirconia fillers over the whole surface of resin matrix could be observed. The experimental CRs showed continuous fluoride release within 28 days, which was positively correlated with the content of F-zirconia fillers. Moreover, the amount of fluoride release increased in the acidic buffer. Addition of F-zirconia fillers could improve the color stability, wear resistance and microhardness of the experimental CRs, without reducing the flexure strength. Furtherly, the fluoride ions released continuously from the experimental CRs resulted in effective contact and antibacterial properties, while they showed no cytotoxicity. As a consequence, considerations can be made to employ this new kind of composite resin loaded with fluoride-doped nano-zirconia fillers to meet clinical requirements when the antimicrobial benefits are desired.

The aging ability of dry white wines has been increasingly recognised. The present work aimed to understand which sensory factors drive their quality evaluation by experienced tasters. Individuals assessed several aesthetic, synthetic, and analytic flavour attributes, using dark tasting glasses. Wines originated from the grape varieties Alvarinho, Arinto, Sauvignon Blanc and Pinot Bianco with a wide range of ages. Basic physical-chemical analysis, browning (Abs 420 nm), elemental composition and a partial volatile fraction were also determined. The overall quality scores were a function of complexity and balance and were negatively influenced by the perception of faultiness. The different ages could be associated with a continuous sensory space characterised by a decreasing perception of freshness and an increase in the mellowed flavours. All wines shared an austere in-mouth perception elicited by their acidity, saltiness, bitterness, smoothness and dryness. Nevertheless, quality scores were similar from the youngest to the oldest-tasted wines (17 years old). The exception was a Sauvignon Blanc wine from a recent vintage that was judged as faulty due to the perception of earthiness. Overall, the tasted wines displayed an unexpected aging ability as demonstrated by the difference between the predicted and real wine ages. To improve the recognition of old wines, the metaphor “mellowed by age” is proposed to describe flavours resulting from beneficial aging instead of “oxidised by age”.

Pain is a major problem in sick newborn infants, especially for those needing intensive care. Pharmacological pain relief is the most commonly used but may be ineffective, have side effects, including long-term neurodevelopmental sequelae. The effectiveness and safety of alternative analgesic methods are ambiguous. The objective is to review the effectiveness and safety of non-pharmacological methods of pain relief in newborn infants and to identify those that are the most effective. PubMed and Google Scholar were searched using the terms: ‘infant’, ‘premature’, ‘pain’, ‘acupuncture’, ‘skin to skin contact’, ‘sucrose’ ‘massage’, ‘musical therapy’ and ‘breastfeeding’. We included 24 studies assessing different methods of non-pharmacological analgesic techniques. Most resulted in some degree of analgesia but many were ineffective and some were even detrimental. Sucrose, for example, was often ineffective but more effective than music therapy, massage, breast milk (for extremely premature infants) or non-invasive electrical stimulation acupuncture. There were also conflicting results for acupuncture, skin to skin care and musical therapy. Most non-pharmacological methods of analgesia provide some modicum of relief for preterm infants but none are completely effective and there is no clearly superior method. Study is also required to assess potential long-term consequences of any of these methods.

Despite increasing research efforts, there is a lack of consensus on defining aging or health. To understand the underlying processes, and to foster the development of targeted interventions towards increasing one’s health, there is an urgent need: (1) to find a broadly acceptable and useful definition of health, based on a list of features (which may or may not be molecular); (2) to operationalize features of health so that it can be measured; (3) to identify predictive biomarkers and (molecular) pathways of health, and (4) to suggest interventions, such as nutrition and exercise, targeted at putative causal pathways and processes. Based on a survey of the literature, we propose to define health as a state of an individual characterized by the core features of (a) physiological function, (b) cognitive function and (c) physical function, amended, specifically in case of humans, by (d) lack of disease, and by (e) reproductive function. Often used concepts such as lack of frailty, allostatic load, or self-reported health (in case of human), and indices such as the Healthy Aging Index can be viewed as projections or surrogates of our definition. We further define aging as the set of all processes in an individual that reduce its “wellbeing”, that is, its health or survival or both. We define biomarkers of health by their attribute of predicting future health better than chronological age. We define healthspan pathways as molecular features of health that relate to each other, specifically by belonging to the same molecular pathway. Our conceptual framework may integrate diverse operationalizations of health and guide precision prevention efforts that are a key to reducing the need for medical and nursing care.

In the last decade, the role of Computed Tomography Pulmonary Angiography (CTPA) in diagnosing and managing pulmonary embolism (PE) has significantly evolved. Once a purely diagnostic tool, CTPA now plays a crucial role in initial emergency department assessments and treatment planning tailored to the patient’s condition. Advances in CTPA technology, including image quality enhancements and artificial intelligence (AI) applications, necessitate a reassessment of its current utility. This narrative review updates on new CTPA tools and techniques and focuses on data extraction challenges in emergency settings. CTPA studies, often conducted with multidetector scanners, provide essential information for risk stratification and treatment planning. The quantification of thrombotic burden using CTPA is vital for predicting mortality and determining appropriate treatments. Classical scoring systems, such as those developed by Qanadli, Mastora, and Ghanima, convert CTPA findings into quantifiable data to assist clinical decision-making. Despite CTPA not being a standard mortality predictor, significant research suggests including CTPA data, especially RV dysfunction indicators, for prognostic purposes. Recent studies highlight automated techniques for quantifying pulmonary perfusion and thrombus composition, enhancing the accuracy of PE severity assessment. The integration of AI in CTPA, particularly through deep learning algorithms, shows promise in automating thrombus load assessment and improving risk stratification. The continuous development of imaging techniques positions CTPA as a potential tool for comprehensive PE management, aiding in diagnosis, prognosis, and treatment decisions.

The popular appreciation of dry white wines is most frequently directed to young wines. However, present consumption trends comprise the valorisation of aged dry white wines. Therefore, the present work was aimed at the sensory analysis of these wines with different ages to define their sensory space and to understand which factors drive their quality evaluation by experienced tasters (critics, oenologists and students). Individuals were asked to evaluate several synthetic and aesthetic attributes and to characterise the analytic sensory profile through a Check-All-That-Apply (CATA) methodology. The quality evaluations were differently correlated with wine synthetic parameters according to the taster group. For both critics and oenologists, overall quality scores were driven by persistence and complexity. Moreover, quality was also highly correlated with power for critics and with balance for oenologists. Quality scores were highly correlated with wine browning (absorbance at 420 nm) for critics. The tasting panel showed a homogeneous analytic description of aroma, taste and mouthfeel consistent with wine age. The different ages could be associated to a continuous sensory space characterised by a decreasing perception of freshness and increase in mature and mellowed descriptors. All wines shared an austere in-mouth perception elicited by their acidity, saltiness, bitterness, smoothness and dryness. The age prediction showed that most tasters failed to guess the age wines with more than roughly 13 years old, indicating that tasters were not familiar with the sensory features of white wines with 17 to 46 years old. In conclusion, experienced tasters consistently described the sensory space and recognised the high quality of aged dry white wines. Education programs may use the defined sensory spaces according to aging and to expand the range of quality perception by consumers.

The leading cause of illness in aging is a group known as Noncommunicable Diseases. There should be some meeting points that modify the cells homeostasis and impaired the cell physiology developing different diseases. Quantum physics studied the atomic and subatomic particles and revolutionized the reality perception with paradoxical and weird concepts. Heisenberg's uncertainty principle established that it is not possible to determine the two characteristic properties of particles with accuracy. Subatomic particles have a wave-particle duality. Two subatomic particles are entangled, something happening over here can have an instantaneous effect over there, no matter how far away there are. All these concepts have tried to apply to biology and life sciences, quantum biology is behind photosynthesis, mitochondrial respiration, enzyme activity, the sense of smell, animal migration, heredity's fidelity, and consciousness. We can apply all these concepts to diseases pathogeny. So, we describe quantum phenomena in oxidative stress, calcification, signal transduction, vitamin D production and cancer mutations. Aging diseases also could be explained by applying quantum physics concepts. It is a new, hard to believe, and an incredible path to be built, but we need to open the treatment options to our patients with new perspectives.

Application of toxic antibacterial agents is considered necessary to control prevalent fresh water microorganisms in evaporative cooling water systems, but these agents can adversely affect the environment and human health. Alternatively, natural antibacterial water chemistry has been applied in industrial cooling water systems for over 10 years with excellent results. The tower water chemistry method concentrates natural salts in highly-softened water to produce elevated pH and dissolved solids, with low calcium and magnesium. This practice conserves water while generating only a small volume of non-toxic natural salt concentrate for cost efficient separation and disposal if required. This review presents a novel perspective of natural antimicrobial chemistry for inhibiting parasitic microbiome functional relationships within the bio-triad of Legionella outbreaks, "Trojan Protozoans" and biofilms. The review further examines practical application and function of polyvalent metal ions in the inhibition of biofilms. Reducing global dependence on toxic antibacterial agents discharged to the environment is an emerging concern due to their impact on the natural microbiome, plants, animals and humans. Discharge of antibacterial agents also contributes to development of pathogen resistance. Use of natural antibacterial chemistry can play a key role in managing the cooling water environment in a more ecologically sustainable manner.

Orogenic antimony-gold deposits contribute significantly to the global antimony resource base. China's orogenic antimony-gold deposits are primarily in southern Tibet. Investigations indicate that antimony combines and migrates with sulfur hydroxides in ore-forming fluids. Previous research on fluid inclusions in orogenic antimony-gold ores with sedimentary rock accommodation revealed the presence of organic inclusions, including liquid hydrocarbons, alongside common components such as CO2, H2O, CH4, and NaCl. However, the impact of liquid hydrocarbons on antimony migration and mineralization is still de-batable. To investigate the transportability of antimony by liquid hydrocarbons in orogenic antimony ores, we selected n-dodecanethiol and n-dodecane as the subjects. We measured the solubility and occurrence form of antimony in these compounds at various temperatures and durations. The results indicate that after 5 and 10 days of reaction at 100 °C, the antimony concentrations in the n-dodecanethiol and n-dodecane groups were 67.44±7.62 ppm, 75.15±16.74 ppm, 1.40±1.02 ppm, and 3.02±3.09 ppm, respectively. At 150 °C for 5 and 10 days, the respective concentrations were 50.58±5.39 ppm, 77.26±45.20 ppm, 2.66±3.08 ppm, and 2.41±2.03 ppm. At 200 °C for 5 and 10 days, the corresponding concentrations were 339.76±71.94 ppm, 218.97±25.03 ppm and 6.53±7.17 ppm, 2.27±0.82 ppm (n=3). The measured solubility of antimony in the n-dodecanethiol group increased gradually with rising temperature. The solubility of antimony in the n-dodecane group was low and notably inferior to that observed in the n-dodecanethiol group. X-ray photoelectron spectroscopy (XPS) analysis demonstrated a distinct thiol (R-SH) peak at 163.31 eV and compound peaks of antimony reacting with thiols at 162.06 and 160.87 eV. This suggests that antimony predominantly forms complexes with thiols for migration. Our findings suggest that specific liquid hy-drocarbon components, predominantly thiols, can interact with antimony at metallogenic temperatures and persist in ore-forming fluids, facilitating migration and mineral enrichment. Earlier experimental studies on gold and crude oil have indicated that liquid hydrocarbons also play an essential role in the transportation and enrichment of gold during the formation of gold deposits, thus indicating that liquid hydrocarbons possess the considerable potential to act as an ore-forming fluid during orogenic antimony-gold deposit formation in southern Tibet.

Background The acknowledgment of computed tomography (CT) defined diagnosis in high prevalence northern Italy may identify more patients with Coronavirus Disease-2019 (COVID 19) infection, than RT-PCR alone. Methods We retrospectively reviewed 148 chest CT scans of oncological patients who were referred to the Radiological Unit of Policlinico S. Marco from 1st of February 2020 to 30th of April 2020, during the Covid-19 outbreak in Bergamo area. Therefore, we analyzed RT-PCR tests of these 148 patients. Results Among 32 patients with diagnosis of COVID-19 infection: 17 patients were asymptomatic or had mild symptoms (53.1%), while 15 developed severe disease (46.8%). The incidence of COVID-19 infection is 22.9%, the mortality rate is 18.8%. Severe COVID-19 disease is associated with higher median age. We did not find any correlation between disease severity and sex, smoke or cardiovascular comorbidities. Remarkably, patients who were on treatment developed milder disease than cancer patients who were not on treatment. Conclusions The acceptance of CT-defined diagnosis in high prevalence area like Bergamo highlighted a larger number of COVID-19 oncological population than RT-PCR alone, in particular asymptomatic and mild symptomatic patients. We observed that actively treated patients had milder disease, according to previous studies that suggested a protective role of immunosuppression.

In this research, the concept of the instability of tension in Microgrid still becomes the focus of study and purpose. Scrutinously, First-Swing Instability occurs in the system in noted changes with properties of making the system unstable or restore to a state of stability. The latter calls itself as a phenomenon of re-synchronization. Allied to aspects of system instability, it is evident that by connecting fast electric chargers for battery-electric vehicles to the distribution system from microgrids, they increase the necessary basic electrical charges and reduce the stability of the electrical energy system. Transient electrical currents have the characteristic of severely impacting microgrids not prepared in connected states or island of the main system. The occurrences of the electromagnetic incompatibility of the inrush current, due to their unpredictability and intermittent characteristic, have complex identification studies. With the elevation of electricity demand by battery-electric vehicle chargers, concerns about the effects of the integration of the electricity grid increase proportionally. The research described in this article emphasizes the influence of fast chargers’ initialization on the power variation related to the re-synchronization phenomenon and its mitigation of the stability of electricity microgrid. An optimization algorithm based on particle swarm optimization (PSO) implements the development of virtual impedances. The PSO optimization algorithm analyzes all possible operating points and aims to maximize the stability index of microgrid, maintaining reactive energy incompatibilities at the minimum level supported. The fractional objective function facilitates the service to these goals simultaneously. The optimization algorithm is implemented in a case study and the corresponding virtual impedance is incorporated into the microgrid. Voltage levels are verified as a condition in the optimization process, comparing system effectiveness.

Glioblastoma (GBM) presents a significant public health challenge as the deadliest and most common malignant brain tumor in adults. Despite standard-of-care treatment, which includes surgery, radiation, and chemotherapy, mortality rates are high, underscoring the critical need for advancing GBM therapy. Over the past two decades, numerous clinical trials have been performed, yet only a small fraction demonstrated benefit, raising concerns about the predictability of current preclinical models. Traditionally, preclinical studies utilize treatment-naïve tumors, failing to model the clinical scenario where patients undergo standard-of-care treatment prior to recurrence. Recurrent GBM generally exhibits distinct molecular alterations influenced by treatment selection pressures. In this review, we discuss the impact of treatment - surgery, radiation, and chemotherapy - on GBM. We also provide a summary of treatments used in preclinical models, advocating for their integration to enhance the translation of novel strategies to improve therapeutic outcomes in GBM.

Background: Aging impacts semantic abilities, therefore semantic exercises might be a valuable tool for cognitive stimulation in healthy older adults. However, programs in this area are limited. Methods: In the current paper, we adapted the BOX linguistic semantic program for online use via the CerUp platform. Our goal was to prepare the optimization future experience of CerUp users, including potential changes in task structure, level of difficulty and instructions, and participants’ adherence, engagement, performance accuracy, perceived difficulty, and adequacy ratings assigned to the instructions we provided that might guide future changes. Additionally, we created a map of hypothesized task-specific features that may guide tailor-made uses of the program. Results: To that end, we present preliminary results on the usability of CerUp. By analyzing task-specific usability data alongside the hypothesized map of task-specific features, we also tested the validity of the latter. Conclusions: These preliminary results on the usability of the CerUp platform highlight the potential of programs for semantic stimulation. Such findings can inform future optimizations of the program, tailored to users’ needs and effectively supporting overall language skills and general cognition.

Emotion detection holds significant importance in facilitating human-computer interaction, enhancing the depth of engagement. By integrating this capability, we pave the way for forthcoming AI technologies to possess a blend of cognitive and emotional understanding, bridging the divide between machine functionality and human emotional complexity. This progress has the potential to reshape how machines perceive and respond to human emotions, ushering in an era of empathetic and intuitive artificial systems. This paper introduces a novel approach to multimodal emotion recognition, seamlessly integrating speech and text modalities to accurately infer emotional states. Employing CNNs, we meticulously analyze speech using Mel spectrograms, while a BERT-based model processes the textual component, leveraging its bidirectional layers for profound semantic comprehension. The outputs from both modalities are combined using an attention-based fusion mechanism that optimally weighs their contributions. The proposed method undergoes meticulous testing on two distinct datasets: Carnegie Mellon University’s Multimodal Opinion Sentiment and Emotion Intensity (CMU-MOSEI) dataset and the Multimodal Emotion Lines Dataset (MELD). The results demonstrate superior efficacy compared to existing frameworks, achieving an accuracy of 88.4% and an F1-score of 87.9% on the CMU-MOSEI dataset, and a notable weighted accuracy (WA) of 67.81% and a weighted F1 (WF1) score of 66.32% on the MELD dataset. This comprehensive system offers precise emotion detection and introduces several significant advancements in the field.

We prepared poly(3,4-ethylenedioxythiophene) (PEDOT)-coated sulfonated polystyrene copolymer particles as efficient heat-shielding agents, which showed strong near-infrared (NIR) absorption, with high solid contents and good solution stability. The poly(styrene sulfonate -co-styrene) (P(SS-co-St)) copolymers were successfully synthesized via radical solution polymerization, and PEDOT-coated P(SS-co-St) (PEDOT:P(SS-co-St)) was synthesized via Fe⁺-catalyzed oxidative polymerization. PEDOT:P(SS-co-St) was characterized by nuclear magnetic resonance and Fourier transform infrared spectroscopies. The particle size and morphology of PEDOT:P(SS-co-St) were examined using transmission electron microscopy, dynamic light scattering, and zeta potential measurements. The maximum NIR-shielding efficiency of the film was 92.0% with 40% transmittance. The high solution stability of PEDOT:P(SS-co-St) make it an ideal candidate for heat-insulating materials that find application in semi-transparent heat-insulator-coated windows.

In large-capacity energy storage systems, instructions are decomposed typically using an equalized power distribution strategy, where clusters/modules operate at the same power and durations. When dispatching shifts from stable single conditions to intricate coupled conditions, this distribution strategy inevitably results in increased inconsistency and hastened system aging. This paper presents a novel differentiated power distribution strategy comprising three control variables: the rotation status, the operating boundaries for both Depth of Discharge (DOD) and C-rates (C) within a control period. The proposed strategy integrates an aging cost prediction model developed to express the mapping relationship between these control variables and aging costs. Additionally, it incorporates the multi-colony particle swarm optimization (Mc-PSO) algorithm into the optimization model to minimize aging costs. The aging cost prediction model consists of three functions: predicting health features (HFs) based on the cumulative charge/discharge throughput quantity and operating boundaries, characterizing HFs as comprehensive scores, and calculating aging costs using both comprehensive scores and residual equipment value. Further, we elaborated on the engineering application process for the proposed control strategy. In the simulation scenarios, this strategy prolonged the service life by 14.62%, reduced the overall aging cost by 6.61%, and improved module consistency by 21.98%, compared with the traditional equalized distribution strategy. In summary, the proposed strategy proves effective in elongating service life, reducing overall aging costs, and increasing the benefit of energy storage systems in particular application scenarios.

Brain aging in mammals is characterized by morphological and functional changes of neural cells. Macroscopically, this process leading to progressive cerebral volume loss and functional decline, includes memory and motor neuron defiance and behavioral disorders as well. Morphologically, brain aging is associated with aged neurons and astrocytes, appearing enlarged and flattened, and expressing an enhanced pH-dependent β-galactosidase activity. Multiple mechanisms are considered hallmarks of cellular senescence in vitro. Among them, cell cycle arrest, increased lysosomal activity, telo-mere shortening, oxidative stress and DNA damage. The most common markers for senescence identification were identified in: i) proteins implicated in cell cycle arrest, such as p16, p21, p53 ii) increased lysosomal mass iii) increased reactive oxygen species (ROS) and senescence associated secretory phenotype (SASP) expression. Finally, dys-functional autophagy, a process occurring during aging, contributes to alter brain homeostasis. The aim of this review is to summarize and update the most recent knowledge about brain aging with a comparative approach, where similarities and differences in some mammalian species are considered.

We investigate the impact of aging on exchangeable inter-arrival times in mixed renewal processes, exploring its implications for reliability and survival analysis. In this study, first, we revisit the definition of renewal point processes, where inter-event time intervals are considered as exchangeable non-negative random variables. Then, we define the concept of statistical aging as latency in the observational process of event counting. Latency affects event detection but preserves exchangeability. However, it may alter the statistical properties of inter-event time intervals. Our analytical and numerical assessments highlight the significance of aging in exchangeable lifetimes, offering insights into key metrics such as the failure survival function, renewal function, and hazard rate function. Through archetypal examples and empirical findings, we illustrate the implications of aging on renewal processes. In particular, employing a Bayesian perspective, we analyze high-frequency currency exchange rate data to assess the impact of aging on volatility risk evaluation. This study contributes novel insights to the literature of renewal theory and survival analysis, emphasizing the role of latency aging in stochastic point processes under exchangeability assumption.