Mild traumatic brain injuries (mTBIs) are highly prevalent and can lead to chronic behavioral and cognitive deficits, often associated with the development of neurodegenerative diseases. The formation of reactive oxygen species (ROS) and oxidative stress have been implicated in mTBI-mediated axonal injury and pathogenesis. However, the underlying mechanisms and contributing factors are not completely understood. In this study, utilizing a murine model of repetitive mTBI (r-mTBI) involving five closed-skull concussions in young adult C57BL/6J mice, we observed a significant elevation of Na+/H+ exchanger protein (NHE1) expression in GFAP+ reactive astrocytes, IBA1+ microglia, and OLIG2+ oligodendrocytes across various brain regions (including the cerebral cortex, corpus callosum, and hippocampus). This elevation was accompanied by astrogliosis, microgliosis and the accumulation of amyloid precursor protein (APP). Concurrently, r-mTBI mice displayed impaired motor learning and spatial memory deficits. However, post-r-mTBI administration of a potent NHE1 inhibitor, HOE642, attenuated locomotor and cognitive functional deficits as well as gliosis, oxidative stress, axonal damage, and white matter damage. These findings underscore the role of NHE1 upregulation in r-mTBI-induced oxidative stress, axonal damage, and gliosis, suggesting NHE1 as a promising therapeutic target to alleviate mTBI-induced injuries and restore neurological function.

Based on the traditional Chinese cultural belief of "male breadwinner, female homemaker," as well as the systemic and interactive characteristics of families, this study aims to explore the influence of maternal gatekeeping behavior on the quality and quantity of paternal parenting, as well as adolescent aggressive behavior. A total of 483 seventh-grade students completed questionnaires on maternal gatekeeping behavior, paternal involvement, parenting styles and aggressive behavior. Latent profile analysis identified four parenting combinations: positive, negative, mixed, and neglectful. Adolescents under negative parenting exhibited the highest aggression, while those under positive and neglectful parenting showed the least aggression. Maternal gatekeeping behavior correlated with paternal negative parenting and adolescent aggression. Paternal negative parenting mediated the relationship between maternal gatekeeping and aggression, while paternal involvement moderated this relationship. These findings highlight the role of parental interaction in adolescent behavior and support family-based interventions.

The COVID-19 pandemic remains a serious public health problem globally. During winter flu seasons, more aggressive SARS-CoV-2 infections with fatalities have been documented, indicating that influenza co-infections may significantly impact the disease outcome of COVID-19. Both influenza and SARS-CoV-2 viruses share many similarities in their transmission and cellular tropism for their replication in the human respiratory tract. However, it is still unclear how the two pathogens interplay to ensure their survival in the same lung microenvironment. In addition, clinical studies on influenza co-infections in COVID-19 patients do not provide conclusive evidence on how influenza co-infection mechanistically modifies the disease outcome in COVID-19. This mini-review discusses various viral as well as host factors that potentially influence the survival or synergism of these two respiratory pathogens in the infected lung microenvironment.

Under the background that the international technological innovation environment VUCA has been intensifying and the innovation situation of Chinese manufacturing enterprises has been impacted, the innovation dilemma faced by enterprises has attracted increasing attention, while the innovation dilemma is also one of the important factors affecting the operation efficiency of enterprises. Based on the micro-data of China’s A-share manufacturing listed enterprises, this paper empirically analyzes the impact of innovation dilemmas faced by enterprises on operational efficiency (innovation dilemmas are measured by the difference when actual innovation performance is lower than expected innovation performance). The results show that the innovation dilemma of manufacturing enterprises significantly inhibits the operational efficiency of manufacturing enterprises by reducing their risk tolerance, development ability expectation and profitability. After using a series of tests, such as instrumental variable method, propensity score matching method, DID (Differences-in-Differences) and changing variable measure method, the conclusion is still robust. In addition, the inhibitory effect of innovation dilemma on enterprise operation efficiency is more obvious for private enterprises, small and medium-sized enterprises, enterprises in the ascend or decline phase, high-tech enterprises and enterprises in the eastern region. Therefore, the government should strengthen the policy support for the manufacturing enterprises in the innovation dilemma, help the enterprises to overcome the innovation bottleneck. Manufacturing enterprises themselves should enhance their innovation capabilities and strive to get rid of the innovation dilemma in order to maintain a stable footing in the fierce market competition and improve the high-quality development of China’s manufacturing industry.

The tailoring of the surface properties of cellulose nanocrystals (CNCs) to meet various requirements in environmental, food, and material areas has always been of great interest. In this study, the surface chemistry of CNCs was noncovalently modified by cetyltrimethylammonium bromide (CTAB), followed by characterizations and an application as a coating material for interfacial interaction investigation over various substrates. Due to the CTAB modification, the surface charge of the CNCs was neutralized, resulting in an increased size of each nanocrystal at the aqueous status and the aggregated microfibers when dried up. The CTAB modification not only decreased the crystallinity of the samples from 48.57% to 9.12% but also hydrophobized the CNCs and decreased their total surface energy. Finally, the adsorption behavior of the CNCs and CTAB-CNCs over nonionic, anionic, and cationic polymers was investigated by ellipsometry. Based on the thickness of the CNC and CTAB-CNC layers over 2-Hydroxyethyl cellulose (HEC), carboxymethyl cellulose (CMC), and polyethyleneimine (PEI), we proposed that the adsorption behavior was overall influenced by electrostatic interaction, hydrogen bonding, and van der Waals forces and the thickness of the adsorbed layers could be impacted by both the surface charge and the size of the crystals.

Background: Progression of metabolic dysfunction associated steatotic liver disease (MASLD) to steatohepatitis (MASH) is driven by stress-inducing lipids that promote liver inflammation and fibrosis. MASH can lead to cirrhosis and hepatocellular carcinoma. We showed coordinated defenses regulated by transcription factors, nuclear factor erythroid 2 related factor-1 (Nrf1) and -2 (Nrf2), protect against hepatic lipid stress. Here, we investigated protective effects of hepatocyte Nrf1 and Nrf2 against MASLD-induced liver fibrosis and tumorigenesis. Methods: Using mice fed MASH diet for 24-52 weeks, we examined MASLD in mice with hepatocyte specific Nrf1, Nrf2, or combined deletion, and compared this to control. In a separate study, mice received weekly injections of carbon tetrachloride to induce liver fibrosis. From week 16-24, mice were treated with Nrf2 activating drug bardoxolone, hepatocyte overexpression of human NRF1 (hNRF1), or both, and groups were compared to control. Results: Hepatocyte Nrf2 deficiency had no effect. Hepatocyte Nrf1 and combined deficiency caused MASH but only hepatocyte Nrf1 deficiency in male mice increased tumor number. Bardoxolone reduced liver steatosis, fibrosis, inflammation, and proliferation, and this effect when combined with hNRF1 was greater than bardoxolone alone. Conclusion: Physiologic Nrf1 delays MASLD progression, Nrf2-induction alleviates MASH, and combined enhancement synergistically protects against steatosis.

Background/Objectives: Population aging is rapidly increasing, and the importance of preventive medicine has been stressed. Health checkup, diet, and exercise are of paramount importance. This study aimed to evaluate the effectiveness of a personalized dual-task intervention that combined exercise with cognitive tasks in improving physical and cognitive functions among independently living elderly individuals. Methods: Participants were aged >65 years who were mostly independent in their activities of daily living, divided into 2 groups. The group receiving the 20-min robot-assisted session was compared to the group receiving traditional functional restoration training. This randomized trial assessed the impact of this intervention on the 30-s chair stand test score and Montreal Cognitive Assessment-Japanese version score of the participants. Results: Both scores significantly improved in the intervention group, indicating enhanced lower-limb function and cognitive capabilities. Conclusions: These findings suggest that integrating cognitive tasks with physical exercise can be a potent strategy to improve overall well-being in the elderly, offering valuable insights for designing comprehensive preventive health programs tailored to this demographic.

Raman spectra of [TeX6](Y2) (X, Y - Cl, Br, I) were recorded in the temperature range 5-300 K. The vibration frequency of molecular halogens as function on temperature and the type of halogen X- in the [TeX6]2- complex was obtained. The vibration frequency of the molecular halogen Y2 depends on the type of halogen X- complex [TeX6]2- The temperature dependence of the Y2 frequency is anomalous compared to what was expected for a conventional anharmonic oscillator. It is shown that the interpretation of the experimental results based on the concept of traditional chemical bonding is quite satisfactory in all cases. The study was motivated by the need to consider the mechanism of interaction in the X-Y2 contacts.

Intense rainfall events frequently occur in Brazil, often leading to rapid flooding. Despite their recurrence, there is a notable lack of sub-daily studies in the country. This research aims to assess patterns related to the structure and microphysics of clouds driving intense rainfall in Brazil, resulting in high accumulations within 1 hour. Employing a 40 mm/h threshold and validation criteria, 83 events were selected for study, observed by both single and dual-polarization radars. Contoured Frequency by Altitude Diagrams (CFADs) of reflectivity, Vertical Integrated Liquid (VIL), and Vertical Integrated Ice (VII) are employed to scrutinize the vertical cloud characteristics in each region. To address limitations arising from the absence of polarimetric coverage in some events, three case studies focusing on polarimetric variables are included. A fourth case study enhances the overall understanding of these events, emphasizing the underexplored nature of short-term intense rainfall studies in Brazil. Results reveal that the generating system significantly influences the rainfall pattern, especially in the Southern, Southeastern, and Central-Western regions. Regional CFADs unveil primary convective columns with 40-50 dBZ reflectivity, extending to approximately 6 km. The microphysical analysis highlights the rapid structural intensification, challenging the event predictability and the issuance of timely specific warnings.

Intellecta dataset emerges as an innovative synthetic dataset, engineered to enhance the cognitive processing capabilities of contemporary language models. With a composition of 11.53 billion tokens, integrating 8.01 billion tokens of synthetic data with 3.52 billion tokens of rich textbook data, Intellecta is crafted to foster advanced reasoning and comprehensive educational narrative generation. Leveraging the Mixtral-8x7B-Instruct-v0.1 model, the dataset facilitates the generation of complex thought processes and detailed, textbook-style explanations, thus enabling language models to engage in both critical thinking and profound educational discourse. This hybrid dataset stands as a testament to the potential of synthetic data in pushing the boundaries of AI, offering a repository that is not only vast and varied but also refined to align with ethical standards and intellectual rigor.

This manuscript presents a novel approach to estimating the potential within Schrödinger equations, with a particular focus on applications to the Navier-Stokes problem in fluid dynamics. By establishing new theoretical estimates, we delve into the intricate dynamics of fluid flow, aiming to unveil previously obscured aspects of the Navier-Stokes equations. Through a rigorous mathematical framework, we explore how these new potential estimates can provide a fresh perspective on fluid mechanics, contributing to the ongoing quest to solve some of its most persistent challenges.

Brain-Computer Interface (BCI) systems can assist physically challenged people to interact with their surroundings and improve the quality of their lives. Decoding human thoughts is a powerful technique that can assist paralyzed people who have lost their speech production ability. Speaking is a combined process involving synchronizing the brain and the oral articulators. This paper proposed a high-accuracy brain wave pattern recognition based on inner speech using a novel feature extraction method. Only eight EEG electrodes were used in this study, and they were set on selected spots on the scalp. Support Vector Machine (SVM) was employed to decode the recorded EEG dataset into four internally spoken words which are: Up, Down, Left, and Right. The proposed approach achieved overall classification accuracy that ranges between 96.20% to 97.5%. In addition, more performance evaluation metrics were estimated to test the reliability of classifying the EEG-based inner speech data, and we obtained 97.61%, 97.50%, and 97.73% for F1-score, recall, and precision respectively. Furthermore, the Area Under Curve of the Receiver Operating Characteristic (AUC-ROC) proved the strength of the proposed approach for classifying the specified inner speech commands by achieving a macro-average amount of 99.32%. The inner speech classification method using electroencephalography proposed in this work can clinically help improve communication for patients with problems including speech disorder, mutism, cognitive development, executive function, and psychopathology.

1,3,5-Tris-(α-naphthyl)benzene is an organic non-electrolyte with notable stability of an amorphous phase. Its glassy and supercooled liquid states were previously studied by spectroscopic and calorimetric methods. However, the thermodynamic parameters of phase transitions available from the literature are inconsistent. In this work, the heat capacities of crystalline and liquid phases, the temperature dependence of the saturated vapor pressures, fusion and vaporization enthalpies were determined using differential and fast scanning calorimetry and verified using the estimates based on solution calorimetry. The structural features of 1,3,5-tris-(α-naphthyl)benzene are discussed based on the computations performed and the data on the molecular refractivity. The consistency between the values obtained by independent techniques was demonstrated. The deviations in the previously published data were attributed to possible polymorphism.

Aiming to improve medical diagnosis and treatment, artificial intelligence (AI) has emerged as a transformational force in the healthcare industry. In this article, we examine how AI is increasingly being used to improve healthcare, with an emphasis on how it is changing medical diagnosis and treatment. We explore the opportunities, threats, and ethical concerns of incorporating AI into healthcare practice. In addition, we feature important AI applications in radiology, pathology, cardiology, and cancer. AI has great potential to improve patient outcomes, diagnostic accuracy, and the ability to provide individualized treatment plans in the future if it is used and refined with care.

The brown pelican (Pelecanus occidentalis) is a species often affected by natural and man-made disasters such as hurricanes and oil spills as well as general human activities; that subsequently receives medical care and rehabilitation. During rehabilitation, blood may be collected for various testing to help with diagnosis, treatment, and monitoring. Reference intervals for this species are limited, dated, and typically from small sample sizes. Seventy one presumed healthy brown pelicans were sampled as a part of their pre-release examination from rehabilitation at the Wildlife Center of Texas after a large volume stranding in December 2014 to January 2015, and various venous analytes were measured to establish updated reference intervals for Brown Pelicans. Fibrinogen was measured via heat precipitation and the Abaxis VSPro equine Fibrinogen cartridge to determine reference intervals, and in an attempt to validate the VSPro for use in avian species. Abaxis VS2 Avian/Reptile Chemistry panel, iSTAT CG4+, and iSTAT Chem8+ results in addition to body condition score, spun PCV, cloacal temperature and fibrinogen were measured. Proposed reference intervals for brown pelicans are presented. Fibrinogen results were not comparable between the gold standard method and the VSPro, indicating that the VSPro is not appropriate for use in brown pelicans.

Adamantinomatous Craniopharyngioma (ACP) is a rare epithelial tumor located in the craniopharyngeal duct, often associated with high morbidity and a high long-term recurrence rate. ACP is predominantly diagnosed in children below the age of 15 and accounts for a majority of Craniopharyngioma cases in the United States. It is most commonly caused by a mutation in exon 3 of the CTNNB1 gene, which promotes overaccumulation of β-Catenin in the WNT pathway. As β-Catenin accumulates, it over-activates the transcription factor, causing an over-transcription of WNT proteins and uncontrolled cell growth. Current methods of treatment for ACP are centered around surgical intervention and radiotherapy, including gross-total resection (GTR), subtotal resection (STR), and a combination of subtotal resection and adjuvant radiotherapy (STR+XTR). These methods of treatment are associated with high risk due to the proximity of ACP to critical structures near the craniopharyngeal duct. High recurrence rates and morbidity are closely associated with current methods of treatment and other methods have yet to be attempted in craniopharyngioma. This review will explore two possible methods of non-surgical and non-radiological therapeutic interventions. The use of RNAi therapy and CRISPR may provide insight and be a potential way to treat ACP with increased quality of life and decreased recurrence rates.

This study delves into the Schrödinger equation's new invariants, shedding light on their crucial implications for theoretical physics and beyond. Specifically, it explores the behavior of scattering amplitudes and bound states concerning the choice of coordinate systems. The research unveils that while the energy of bound states remains invariant under coordinate transformations, the phase of scattering amplitudes undergoes variations, underscoring its pivotal role in theories reliant on phase normalization. Moreover, these findings have played a pivotal role in constructing estimates for three-dimensional Navier-Stokes equations, enhancing our ability to model complex fluid dynamics with greater precision and reliability. Additionally, in seismic exploration, tomography, and ultrasound imaging, these properties allow researchers to optimize phase selection, facilitating the most effective interpretation of measurement results. This strategic phase manipulation ensures clearer insights into subsurface structures, tissue composition, and fluid dynamics, with the flexibility to seamlessly transition back to the original coordinate system post-interpretation. This interdisciplinary synergy underscores the profound impact of fundamental theoretical research on advancing practical applications across diverse scientific domains.

In recent years, thanks to continuous technological development, temperature data loggers have been used to collect data from the breeding progress of birds, which can be used, e.g. to obtain information on the length of incubation breaks, to detect the start of incubation or to record unsuccessful breeding. Temperature data loggers have been used in various types of bird nests, but not in a „closed“ nests such as a burrow or cavity. The study presents the results of using a temperature data loggers in natural nest holes of the common kingfisher (Alcedo atthis). Their nests, which lack substantial insulating structures, are primarily influenced by the relatively stable soil temperature. The temperature of the space inside a nest chamber was measured on a continuous basis with an interval of 1 minute between measurements. The measurement was carried out from egg laying/incubation to a successful leave of the nest chamber/death of chicks (5 nests on 3 different streams in 3 breeding seasons). The temperature curves showed the laying of the eggs, the start of incubation, the successful flight out of the nest chamber or the death of the chicks in the nest chamber. It was not always possible to determine exactly when the chicks hatched from the temperature data.

With the emergence of autonomous functions in road vehicles, there has been an increased use of Advanced Driver Assistance Systems comprising various sensors to perform automated tasks. Light Detection and Ranging (LiDAR) is one of the most important types of optical sensor that detects the positions of obstacles, representing them as clusters of points in 3-dimensional space. LiDAR performance degrades significantly when driving in rain as raindrops adhere to the outer surface of the sensor assembly. The performance degradation behaviors include missing points and reduced reflectivity of the points. It was found that the extent of degradations is highly dependent on the interface material properties, which subsequently affects the shapes of the adherent droplets, causing different perturbations to the optical rays. A fundamental investigation is performed on the protective polycarbonate cover of the LiDAR assembly coated with four classes of materials – hydrophilic, almost-hydrophobic, hydrophobic, and superhydrophobic. Water droplets are controllably dispensed onto the cover to quantify the signal alteration due to each droplet of various sizes and shapes. To further understand the effects of droplet motion on LiDAR signals, sliding droplet conditions are simulated using numerical analysis and validated with physical optical tests using a 905 nm laser source and receiver to mimic the LiDAR detection mechanism. Comprehensive explanations are presented on LiDAR performance degradation in rain from both material and optical perspectives. These can aid component selection and the development of signal enhancing strategies for integrating LiDARs in vehicle designs to minimize the impact of rain.

The etiology of Autism Spectrum Disorder (ASD) has been linked to both genetic and epigenetic factors. Among the epigenetic factors, exposure to valproic acid (VPA), an antiepileptic and mood-modulating drug, has been shown to induce characteristic traits of ASD when exposed during embryogenesis. Conversely, in animal models, Enriched Environment (EE) has demonstrated positive behavioral and neural effects, suggesting its potential as a complementary treatment to pharmacological approaches in central nervous system disorders. In this study, we utilized zebrafish to model ASD characteristics induced by VPA and hypothesized that sensory stimulation through EE could ameliorate the behavioral and neuroanatomical features associated with ASD. To test this hypothesis, we assessed social behavior, cerebellar volume, and Purkinje cell populations via histology and immunohistochemistry after exposing the fish to EE. The results revealed that zebrafish exposed to VPA exhibited social deficits, reduced cerebellar cortex volume, and a decrease in c-Fos-positive cells in the Purkinje layer. In contrast, VPA-exposed fish treated with EE showed increased socialization, augmented cerebellar cortex volume, and an elevation in c-Fos-positive Purkinje cells. These findings suggest that alterations induced by VPA may be ameliorated through EE treatment, highlighting the potential therapeutic impact of sensory stimulation in conditions related to ASD.

This paper introduces a low-tech capacitive micromachined ultrasonic transducer (CMUT) designed with low environmental footprint materials. The fabrication process involves a copper plate as the fixed bottom electrode, a polymer-based adhesive as a dielectric material, and an aluminum foil as the top electrode.Finite element simulations include studies of displacement, mechanical stresses, and eigenfrequency. Experimental measurements validate the device's electromechanical behavior, showing an eigenfrequency of 88.6 kHz and a displacement of 22 pm. The low-tech CMUT demonstrates potential for applications such as ultrasonic actuation and energy harvesting, offering simplicity, biocompatibility, and low environmental impact. While not directly ready for applications, these transducers provide hands-on experience with technology similar to high-performance silicon-based implementations. These low-tech MUTs are perfect practical case studies for teaching purposes, combining simulation and experimental validation.

This review paper delves into the multifaceted aspects of pineapple cultivation, focusing on morphology studies, harvesting challenges, and mechanization efforts. Pineapple, renowned for its commercial value and unique flavor, holds a prominent position in global agriculture, with India alone producing 19.64 lakh tonnes annually. However, the hilly terrains of regions like northeastern India pose significant hurdles to traditional harvesting methods, necessitating innovative solutions. Understanding the morphology of pineapple plants is crucial for optimizing cultivation practices and designing efficient harvesting equipment. Insights from various studies shed light on leaf structure, fruit maturity, and growth patterns, providing valuable information for engineering tailored solutions. Mechanization endeavors, including semi-mechanized harvesting machines and semi-manual harvesters, demonstrate promising results in improving efficiency and reducing labor-intensive practices. Despite challenges such as increased crop losses and operational costs, continued research and development in mechanization hold the key to sustainable pineapple cultivation. This paper underscores the importance of integrating morphology studies and mechanization efforts to address the unique challenges faced by pineapple farmers, particularly in hilly terrains, and highlights the need for ongoing innovation to ensure the long-term sustainability of pineapple cultivation.

Background: Fibonacci patterns and tubular forms both arose early in the phylogeny of multicellular organisms. Tubular forms offer the advantage of a regulated internal milieu, and Fibonacci forms may offer packing efficiencies. The underlying mechanisms behind the cellular genesis of Fibonacci and tubular forms remain unknown.

With much more challenging scenarios encountered in engineering, traditional quadrotors couldn’t accomplish all desired missions perfectly. Task-driven based reconfigurable quadrotors have more latent capacity in environment with dense obstacles and narrow corridors. The translational reconfigurable quadrotors and rotational reconfigurable quadrotors are proposed in this presentation, assumptions, mathematical models and related motion control laws are given subsequently, in order to cope with hazard missions, model reference adaptive control laws are proposed, sufficient numerical simulations demonstrate the validity of the proposed control laws.

Cervical cancer is caused by a persistent and high-grade infection, caused by the Human Papilloma Virus (HPV), which, when entering cervical cells, alters their physiology and generates serious lesions. HPV 18 - is among those most involved in carcinogenesis in this region, but there are still no drug treatments that cause cure or total remission of lesions caused by HPV. Knowing that L-Asparaginase is an amidohydrolase, which plays a significant role in the pharmaceutical industry, particularly in the treatment of specific cancers, due to its antitumor properties, some studies have demonstrated its cytotoxic effect against cervical cancer cells. However, the commercial version of this enzyme has side effects, such as hypersensitivity, allergic reactions and silent inactivation due to the formation of antibodies. To mitigate these adverse effects, several alternatives have been explored, including the use of L-asparaginase from other microbiological sources, which is the case with the use of the fungus Aspergillus niger, a high producer of L-asparaginase. The study investigated the influence of the type of fermentation, precipitant, purification, characterization and in vitro cytotoxicity of L-asparaginase. The results revealed that semisolid fermentation produced higher enzymatic activity and protein concentration of A. niger. The characterized enzyme showed excellent stability at pH 9.0, temperature of 50ºC, resistance to surfactants and metallic ions, and an increase in enzymatic activity was also noted with the organic solvent ethanol. Furthermore, it exhibited low cytotoxicity in GM and RAW cells, and significant cytotoxicity in HeLa cells. These findings indicate that L-asparaginase derived from Aspergillus niger may be a promising alternative for pharmaceutical production. Its attributes, including stability, activity and low toxicity in healthy cells, suggest that this modified enzyme could overcome challenges associated with antitumor therapy.

In light of the prevalent pest and disease issues faced by greenhouse cucumbers, a staple vegetable during winter, this study introduces a detection method based on the enhanced YOLOv8s model. This method aims to provide technical support for detecting and classifying pests and diseases in cucumber agricultural production. The model integrates the 'MultiCat' module for multiscale feature fusion and employs the 'C2fe' and 'ADC2f'modules to strengthen spatial and channel attention. The 'Block2d' function also facilitates the choice between average pooling and attention-based spatial pooling. Channel fusion is achieved through additive and multiplicative operations, allowing the model to delve deeper into feature learning. Experimental results confirm that our approach outperforms the original YOLOv8s model in pest detection, particularly excelling in the identification of small-scale and overlapping afflictions.

The right heart catheterisation constitutes the gold standard for pulmonary hypertension (PH) diagnosis. However, echocardiography remains a reliable, non-invasive, inexpensive, convenient, and easily reproducible modality not only for the preliminary screening of PH but also for PH prognosis. The aim of this review is to describe a cluster of echocardiographic parameters for the detection and prognosis of PH and analyse the challenges of echocardiography implementation in patients with suspected or established PH. The most important echocardiographic index is the calculation of pulmonary arterial systolic pressure (PASP) through the tricuspid regurgitation (TR). It has shown high correlation with invasive measurement of pulmonary pressure, but several drawbacks have questioned its accuracy. Besides this, the right ventricular outflow track acceleration time (RVOT-AT) has been proposed for PH diagnosis. A plethora of echocardiographic indices: right atrial area, pericardial effusion, the tricuspid annular plane systolic excursion (TAPSE), the TAPSE/PASP ratio, tricuspid annular systolic velocity (s′) and recently, can reflect the severity and prognosis of PH. Recent advances in echocardiography with 3-dimensional right ventricular (RV) ejection fraction, RV free wall strain and right atrial strain may further assist the prognostication of PH.

Pycnodont fishes were a successful clade of neopterygian fishes that are predominantly found from shallow marine deposits. However, throughout their long 180 million years reign (Late Triassic - end Eocene), they have made multiple incursions into both brackish and freshwater environments. This fossil record mostly consists of fragmentary dental material but articulated specimens are known from Early Cretaceous lacustrine localities in Spain. This review article aims to document all non-marine occurrences of Pycnodontiformes throughout most of the Mesozoic and early Palaeogene. This review highlights two interesting trends in the history of non-marine habitat colonization by pycnodonts: (1) a huge spike in non-marine occurrences during the Cretaceous, (2) the most occurrences in non-marine localities occurred at the latest Cretaceous, the Maastrichtian. The high number of colonization events within the Cretaceous lines up with extreme climatic events such as high temperatures resulting in high sea levels which regularly flooded continental masses, allowing pycnodonts easier access to non-marine habitats. The increased presence of pycnodonts in brackish and freshwater habitats during the Maastrichtian might have played a role in their survival through the K/Pg extinction event. Freshwater habitats are not as vulnerable as marine ecosystems to environmental disturbance as the base of their food chain relies on detritus. Pycnodonts might have used such environments as a refuge and began to occupy marine waters after the K/Pg extinction event.

Solventogenic Clostridium species are important for establishing sustainable industrial bioproduction of fuels and important chemicals. The inherent versatility of these species in substrate utilization and the range of solvents produced during acetone butanol-ethanol (ABE) fermentation make solventogenic Clostridium an attractive choice for biotechnological applications such as production of fuels and chemicals. The functional qualities of these microbes have thus been identified to be due to complex regulatory networks that play essential roles in modulating the metabolism of this group of bacteria. Genomes of solventogenic Clostridium species have relatively greater prevalence of genes that are intricately controlled by various regulatory molecules than most other species. Consequently, the use of genetic or metabolic engineering strategies that do not consider the underlying regulatory mechanisms will not be effective. Several regulatory factors involved in substrate uptake/utilization, sporulation, solvent production, and stress responses (Carbon Catabolite Protein A, Spo0A, AbrB, Rex, CsrA) have been identified and characterized. In this review, the focus is on newly identified regulatory factors in solventogenic Clostridium species, the interaction of these factors with previously identified molecules, and potential implications on substrate utilization, solvent production, and resistance/tolerance to lignocellulose-derived microbial inhibitory compounds.

Background: Since cytokine receptor like factor 1 (CRLF1) has been implicated in tissue regeneration, we hypothesized that CRLF1 released by mesenchymal stem cells can promote the repair of osteochondral defects. Methods: The degree of a femoral osteochondral defect repair in rabbits after intra-articular injections of bone marrow derived mesenchymal stem cells (BMSCs) that were transduced with empty adeno associated virus (AAV) or AAV containing CRLF1 was determined by morpholog-ical, histological and microCT analyses. The effects of CRLF1 on chondrogenic differentiation of BMSCs or catabolic events of interleukin-1beta-treated chondrocyte cell line TC28a2 were deter-mined by alcian blue staining, gene expression levels of cartilage and catabolic marker genes us-ing real time PCR analysis, and immunoblot analysis of Smad2/3 and STAT3 signaling. Results: Intra-articular injections of BMSCs overexpressing CRLF1 markedly improved repair of a rabbit femoral osteochondral defect. Overexpression of CRLF1 in BMSCs resulted in the release of a homodimeric CRLF1 complex that stimulated chondrogenic differentiation of BMSCs via enhancing Smad2/3 signaling, whereas the suppression of CRLF1 expression inhibited chondro-genic differentiation. In addition, CRLF1 inhibited catabolic events in TC28a2 cells cultured in an inflammatory environment, while a heterodimeric complex of CRLF1 and Cardiotrophin like Cytokine (CLC) stimulated catabolic events via STAT3 activation. Conclusion: A homodimeric CRLF1 complex released by BMSCs enhanced the repair of osteochondral defects via the inhibition of catabolic events in chondrocytes and the stimulation of chondrogenic differentiation of precursor cells.

Vimentin has been reported to play diverse roles in cell processes such as spreading, migration, and cell-matrix adhesion. Here, we use vimentin knock out cells (Vim KO) to assess how vimentin impacts cell spreading, morphology, and myofibroblast transformation of human corneal fibro-blasts. Overall, loss of vimentin did not significantly impact corneal fibroblast spreading, as indicated by Vim KO morphology and mechanical activity (traction force). However, we found that Vim KO cells had reduced elongation in response to PDGF as compared to controls. Furthermore, absence of vimentin did not completely block TGFβ induced myofibroblast transformation, since αSMA protein expression was detected in Vim KO cells. Nonetheless, the degree of transformation and amount of αSMA protein was reduced as compared to control cells. Proteomics showed that Vim KO cells cultured in TGFβ had a similar pattern of protein expression as controls. One exception included periostin, an ECM protein associated with wound healing and fibrosis in other cell types, which was highly expressed only in Vim KO cells. We also demonstrate for the first time that LRRC15, a protein previously associated with myofibroblast transformation of cancer-associated fibroblasts, is also expressed by corneal myofibroblasts. Overall, our data shows that vimentin has a limited, yet measurable impact on corneal fibroblast spreading and myofibroblast transformation. We also identified novel proteins that may regulate corneal myofibroblast transformation in the presence and/or absence of vimentin.

DNA damage causes the mutations that are the principal source of genetic variation. DNA damage detection and repair mechanisms therefore play a determining role in generating the genetic diversity on which natural selection acts. Speciation, it is commonly assumed, occurs at a rate set by the level of standing allelic diversity in a population. The process of speciation is driven by a combination of two evolutionary forces: genetic drift and ecological selection. Genetic drift takes place under conditions of relaxed selection, and results in a balance between rates of mutation and rates of genetic substitution. These two processes, drift and selection, are necessarily mediated by a variety of mechanisms guaranteeing genome stability in any given species. One of the outstanding questions in evolutionary biology concerns the origin of the widely varying phylogenetic distribution of biodiversity across the tree of life, and how the forces of drift and selection contribute to shaping that distribution. The following examines some of the molecular mechanisms underlying genome stability and the adaptive radiations that are associated with biodiversity and the widely varying species richness and evenness in the different eukaryotic lineages.

The increasing growth in road users who are unfamiliar with traffic rules and regulations provides a serious safety problem for Pakistani traffic conditions. This study has two main objectives. First, it seeks to validate the reliability and applicability of the Dula Dangerous Driving Index (DDDI) in Pakistan. Second, it intends to investigate the effects of DDDI, sociodemographic characteristics, seat belt use, and driving training on the occurrence of traffic accidents. A total of 623 Pakistani individuals completed a questionnaire as part of this study. The questionnaire consists of items related to dangerous driving behaviors, sociodemographic characteristics, seat belt use, driving instruction, and accident involvement. The DDDI's accuracy was evaluated by comparing it to self-reported traffic incidents and seat belt compliance. To discover predictors within the DDDI dimensions, generalized linear models were used. A binary logistic regression analysis was also performed to evaluate the factors that influence traffic accidents. DDDI dimensions, demographic characteristics, seat belt usage, and driving training were all considered in this study. The use of seat belts while driving reduced the likelihood of an accident by 25%. On the other hand, aggressive driving and risky driving increased the chances of getting involved in traffic accidents by 36%% and 20%. Furthermore, the chances of being involved in a traffic accident decreased by 21% as the drivers age increased. The results also illustrate that Pakistani drivers are more aggressive and risk taker compared to Chinese drivers who are more disciplined. This study suggests that lack of comprehensive and standardized driving training and education programs, in consistent enforcement of traffic laws, the quality of road infrastructure and lack of public awareness campaigns can be attributed to adverse road safety situations in country.

The human-readable simplicity with which the CSV format was devised, together with the absence of a standard that strictly defines this format, has allowed the proliferation of several variants in the dialects with which these files are written. The latter has meant that the exchange of information between data management systems, or between countries and regions, requires human intervention during the data mining and cleansing process. This has led to the development of various computational tools that aim to accurately determine the dialects of CSV files, in order to avoid data loss at data loading stage in a given system. However, the dialect detection is a complex problem and current systems have limitations or make assumptions that need to be improved and/or extended. This paper proposes a method for determining CSV file dialects through table uniformity, a statistical approach based on table consistency and records dispersion measurement along with the detection of data type over each field. The new method has a 100\% accuracy on a dataset with 148 CSV files composed of samples coming from a data load testing framework and some others added as verification of the parsing routines. In tests on truly messy data, the proposed solution outperforms the state-of-the-art tool by achieving an improvement of about 10\% in the accuracy with which dialects are detected. Furthermore, the proposed method is accurate enough to determine dialects by reading only ten records, requiring more data to disambiguate those cases where the first records do not contain the necessary information to conclude with a dialect determination.

VE is a powerful technique for analyzing a design with a focus on functionality, reducing costs, and increasing value. However, in order to proceed with the design of VE, the theoretical basis for the VE target selection process, which must be preceded in the preparation stage, is lacking, and as a result, it is difficult to verify the most effective target selection. Thus, a theoretical basis is needed. In this study, we intend to quantify the WORTH value of the COST TO WORTH technique and present an objective model of the target selection method using the derived Value Index (VI). For this purpose, cost worth (WORTHC) was calculated based on the performance data of 1,008 cases of 15 building types provided by the Domestic Public Procurement Service and the share of 83 detailed processes in 7 fields. Then, a survey was conducted targeting the ordering companies, and the final worth (WORTHF) was calculated by multiplying the derived customer value (WORTHV ) weight for each detailed work type. We calculated the Value Index (VI) by comparing COST and WORTHF for each detailed construction type of the VE project and developed a model to select construction types that exceed the VI standard value derived using the standard error of the population. Both cost experts and non-cost experts can use the developed model to specify the VE target selection criteria in order to easily select the key target, objectively sort the values that serve as the basis for calculating the value index and make it possible to more easily select the VE target selection criteria based on theoretical evidence. Also, the model can be used to obtain effective detailed design VE results.

This paper provides a study on the development of solar energy, its prospects, and its impacts in Africa. Although the main focus is on technologies adopted for different uses (solar farms, mini-grids, off-grid, solar houses, irrigation, lighting, etc.), we also consider some aspects that increase the adoption of solar energy, such as legislation and business models. Finally, we will examine current and future solar projects managed by NGOs and international companies and how they benefit to leveraging social and economic standards, quality of life as well as capacity building in Africa. This study shows the plethoric interest of institutions outside Africa in the market of solar energy in the continent and that there is no African strategy to increase its independency toward a sustainable development particularly through energy transition.

Bovine whey cheese (WC) is a product from southern European countries that presents some challenges: their elaboration process involves high energy inputs, the yield is low and WC has a short shelf-life. The application of ultrafiltration to bovine whey before its manufacture and the employment of protective cultures can reduce these disadvantages. The aim of this work was to manufacture whey cheeses using ultrafiltrated (UF) concentrated bovine cheese whey with added probiotics or probiotics plus protective cultures. Three types of WC were produced: control, without any addition (C); with the addition of the probiotic Lactobacillus acidophilus (LA5); with the addition of Lactobacillus acidophilus plus a protective culture containing Lactobacillus paracasei and Lactobacillus rhamnosus (LA5FQ4). The WCs were stored under refrigerated conditions for 28 days. The products with added cultures presented a lower pH and a higher titratable acidity when compared to the control. Sample LA5 presented the lowest pH and the highest titratable acidity while LA5FQ4 presented intermediate values. Slight differences were observed between products regarding color parameters, chiefly as a result of storage time. The samples with added cultures were firmer when compared to the control, showing LA5 cheeses the highest values at the end of the storage. Lactobacilli and lactococci counts were of the order of log 8-9 CFU/g for the products with added cultures. Lower levels of yeasts and moulds were detected on the sample with the protective culture (LA5FQ4), that by the end of storage presented counts one log cycle lower than C and LA5. Hence, it is evident the beneficial impact of the protective culture on the shelf life of the product. In what concerns to sensory evaluation, LA5FQ4 cheeses obtained the highest scores regarding all parameters evaluated. It could be concluded that the use of UF associated to the addition of protective cultures can be very useful to reduce the energy consumption of the process, prolong the shelf life of WC, and to improve its sensory properties.

This paper addresses challenges and solutions in urban development and infrastructure resilience, particularly in the context of Japan's rapidly urbanizing landscape. It explores the integration of smart city concepts to combat land subsidence and liquefaction, phenomena highlighted by the 2011 Great East Japan Earthquake. Using advanced technologies such as smart sensing and predictive analytics through kriging and ensemble learning, the study aims to improve the accuracy of geotechnical investigations and urban planning. By analyzing data from 433 geotechnical surveys in Setagaya, Tokyo, it develops predictive models to accurately determine the depth of bearing layers critical to urban infrastructure. The results demonstrate the superiority of ensemble learning in predicting the depth of bearing layers, with significant implications for smart city development and the sustainability of urban environments. This interdisciplinary approach not only seeks to mitigate risks associated with geological disturbances, but also promotes sustainable urban growth that prioritizes safety and prosperity. Through advanced technology and comprehensive research, the study underscores the potential of smart cities to address urban complexities and ensure a resilient, sustainable future.

Cancer diagnosis stands at the cusp of a profound transformation, driven by the burgeoning capabilities of Artificial Intelligence (AI) and Machine Learning (ML). This comprehensive review illuminates the extraordinary impact of AI and ML in the field, unraveling their multifaceted roles in the realm of oncology. In the arena of cancer diagnosis, AI and ML serve as invaluable allies, empowering healthcare professionals with unparalleled tools for precision and efficiency. Notably, AI's prowess in analyzing medical images, including radiological scans and pathology slides, elevates the early detection of malignancies to new heights. Coupled with its ability to dissect genomic data, AI tailors therapeutic strategies to the individual, promising optimized treatment outcomes. However, the incorporation of AI and ML into clinical practice necessitates a careful navigation of ethical considerations, data privacy, and regulatory landscapes. Safeguarding patient data, ensuring transparency, and addressing algorithmic biases emerge as pivotal challenges that require vigilant attention. Yet, the future of AI and ML in cancer diagnosis is brimming with promise. The integration of multi-modal data, real-time monitoring, and Explainable AI (XAI) methods holds the potential to enrich diagnostic capabilities and engender patient trust. Global collaboration and data sharing initiatives are fostering the development of robust AI models. Furthermore, AI's role in cancer prevention, identifying high-risk individuals and enabling targeted preventive strategies, is poised to revolutionize healthcare. AI and ML are forging a path toward an era of unparalleled accuracy, efficiency, and personalization in cancer diagnosis. Challenges notwithstanding, these technologies bear the promise of fundamentally reshaping patient care, elevating outcomes, and advancing the fight against cancer. The ongoing exploration and responsible implementation of AI and ML in oncology will be pivotal in harnessing their full potential and paving the way for a brighter future for cancer patients.

Advancements in genomics and molecular biology have propelled our understanding of genetic information far beyond the iconic double helix structure of DNA. This comprehensive review delves into the intricate world of DNA and RNA networks, exploring the complexities that extend beyond the classical model. We investigate the dynamic interactions, regulatory mechanisms, and functional implications of the broader genetic landscape, encompassing both coding and non-coding elements. From chromatin architecture to the diverse array of non-coding RNAs, this exploration seeks to provide a holistic perspective on the multifaceted roles played by DNA and RNA in cellular processes. The three-dimensional organization of genetic material within the cell has emerged as a crucial determinant of cellular function. Chromatin architecture, comprising DNA, histones, and other associated proteins, plays a dynamic role in regulating gene expression. We delve into the intricate choreography of chromatin remodeling, deciphering the interplay between transcription factors, epigenetic modifications, and higher-order structures that modulate gene activity. The exploration of chromatin dynamics unveils a nuanced understanding of how the genome responds to environmental cues, cellular signals, and developmental processes. Moreover, the once-dismissed non-coding portion of the genome has emerged as a key regulator of cellular function. Various classes of non-coding RNAs, such as microRNAs, long non-coding RNAs, and circular RNAs, have been implicated in diverse cellular processes, ranging from fine-tuning gene expression to modulating chromatin structure. The review critically examines the functional roles of these non-coding RNAs, shedding light on their involvement in cellular homeostasis, development, and disease. As I traverse this landscape beyond the double helix, our review synthesizes current knowledge on the intricacies of DNA and RNA networks. By exploring the regulatory mechanisms, functional implications, and emerging paradigms, we aim to inspire a deeper appreciation for the molecular choreography that underlies the cellular symphony of life. Furthermore, we discuss the implications of these findings in the context of disease, highlighting potential diagnostic and therapeutic avenues that arise from a comprehensive understanding of DNA and RNA networks. In doing so, this exploration not only broadens our theoretical understanding but also opens new frontiers for translational research in genetics and molecular medicine.

PVC items are environmentally friendly as, unlike polyolefins, they are mainly based on chlorine, one of the most abundant elements on earth. However, in the eco-design context, articles' durability plays the crucial role, contributing to the enhancement of their sustainability. In this framework the research on additives capable of increasing the weatherability of outdoor articles is essential. The theory section of the paper reviews the mechanisms of weathering leading to PVC degradation that undermine the durability of items such as window frames or roller shutters. The weathering of PVC items is a complex phenomenon involving photo-chemical and secondary chemical reactions, that yields the formation of conjugated polyene sequences underskin in absence of oxygen and carbonyls in the surface. Here the chain scission of the polymer backbone occurs, bringing the disintegration of the surface of the item and causing the typical discoloration called chalking, especially evident in dark-colored articles. In the experimental section of the paper the effect of different acid scavengers on the item weathering has been studied with natural outdoor and two accelerated exposures, xenon-arc and Q-UV testing devices. Results confirm that some acid scavengers are efficient in preventing chalking, but some are ineffective or even detrimental. Thus, the PVC formulations of durable articles upon weathering still depend on a complex choice of the appropriate ingredients, and several outdoor and indoor accelerated weathering tests are needed to predict the articles' lifetime.

This study presents a dynamic modeling approach to investigate the impact of saturation dynamics on HIV/AIDS transmission in the presence of vertical transmission and treatment strategies. The proposed model incorporates disease-free and endemic equilibria, with a focus on analyzing the basic reproduction number and conducting stability analysis. Results indicate that the disease-free equilibrium is locally asymptotically stable under certain conditions. The findings suggest that a combination of treatment interventions and awareness campaigns, along with other control measures, may play a crucial role in curbing the spread of the HIV/AIDS virus. This research contributes to understanding the complex dynamics of HIV/AIDS epidemics and highlights the importance of considering saturation effects in epidemic modeling.

Some global difficulties in the modern period include energy storage conversion. Researchers have looked to renewable energy resources to discover long-term answers to this dilemma. Fuel cells are one example of prospective energy producing technology. Although these technologies appear to be very enticing, they are known to be expensive due to high expenses. Catalyst costs, as well as concerns concerning energy density. Pt based Electrocatalysts have traditionally been used to drive ORR and offer efficient power outputs. However, cost constraints have limited the use of these electrocatalysts, rendering them inefficient. Apart from the high price, Pt-based Electrodes are prone to time-dependent drift and CO deactivation, both of which occur gradually. Electrocatalysts deteriorate over time, reducing the efficiency of fuel cells. This is why alternative electrocatalysts are in high demand for future energy applications. This review covers the comparative study of Platinium and Non-Platinium based electrocatalyst in fuel cells, their shortcomings and recent advancement for efficient and optimized electrocatalyst.

The mechanism of sex determination and differentiation in animals remains a central focus of reproductive and developmental biology research, and the regulation of sex differentiation in amphioxus remains poorly understood. Cytochrome P450 Family 19 Subfamily A member 1 (CYP19A1) is a crucial sex differentiation gene that catalyzes the conversion of androgens into estrogens. In this study, we identified two aromatase-like genes in amphioxus: cyp19-like1 and cyp19-like2. Cyp19-like1 is more primitive and may represent the ancestral form of cyp19 in zebrafish and other vertebrates. Cyp19-like2, on the other hand, is likely the result of gene duplication within am-phioxus suggesting its potential role as a key gene in sex differentiation. To gain further insights into the expression patterns of these two aromatase-like, we examined their expression in different gonad tissues and during different stages of gonad development. While the expression patterns of the two genes differ in gonad tissues, both are highly expressed in the gonad primordium and are primarily localized to microsomal membrane systems. However, as development proceeds, their expression levels decrease significantly. This study enhances our understanding of sex dif-ferentiation mechanisms in amphioxus and provides valuable insights into the formation and evolution of sex determination mechanisms in vertebrates.

This Paper delves into the critical role played by fossil fuel-based polymers in promoting United Nations Sustainable Development Goals (SDGs) in the face of challenges brought about by swift population growth, suburbanization, and mechanization. It sheds light on the environmental and energy security recompences of converting plastic waste into biofuels and other valuable energy resources through state-of-the-art processes such as thermochemical conversion and pyrolysis. Besides, the research investigates the utilization of polymers in solar energy, energy storage, and low carbon transportation, emphasizing the inevitability of a dual approach that combines advancements in bio-based polymers and recycling technologies. It highlights the significance of collaborative endeavors involving governments, industries, and communities to overcome the technical, economic, and regulatory complications in transitioning towards a sustainable and circular plastic economy. Eventually, it showcases the potential of fossil fuel-based polymers in fostering a sustainable energy landscape, conducive to decarbonization efforts, and endorsing environmental sustainability.

An easy and short-time TLC-densitometric method was developed for the separation of metronidazole, secnidazole, ornidazole, tinidazole, and 2-methyl-5-nitroimidazole and for the determination of metronidazole and tinidazole in Metronidazole Polpharma and Tinidazolum Polpharma tablets. Analyzes were performed on chromatographic plates precoated with silica gel 60F254 using the optimal mobile phase: chloroform + methanol + diethylamine in a volume ratio of 9:1:1. The method has been validated. The intraday and interday precision values for the three different concentrations ranged from 0.99% to 1.48% and 0.89% to 1.76%, and the precision values ranged from 1.13% to 2.48% and 0.95% to 2.49% for metronidazole and tinidazole, respectively. The limit of quantification (LOQ) was 0.036 and 0.066 µg/spot for metronidazole and tinidazole, respectively. The mean recovery was 103.1% and 100.6% for metronidazole and tinidazole, respectively. The content of metronidazole and tinidazole in tablets in relation to the content declared by the manufacturer was 101.3% and 99.8%, respectively. The obtained results were verified using the pharmacopoeial method. The presented method is fast, sensitive, precise, selective, accurate and robust. It allows for the analysis of several samples on one chromatography plate at the same time.

The tribology behavior, tribofilm formation and structure evolution of polytetrafluoroethylene (PTFE) filled with α-Al2O3 and SiO2 nanoparticles during sliding against steel counterparts under different loads were studied. It is found that both composites exhibit good wear resistance across the pressure of 1 MPa to 10 MPa, with the α-Al2O3/PTFE composite demonstrates better performance stability compared to the SiO2/PTFE composite. The high wear resistance is attributed to the formation of tribofilms at the friction interface. For the α-Al2O3/PTFE, an island-like tribofilm is formed with a thickness ranging from 100 to 200 nm, while the tribofilm of the SiO2/PTFE composite is thinner, measuring approximately 50 to 100 nm, and manifest a striped pattern. The chemical composition, both at the surface and subsurface levels, as well as the morphology of the tribofilms were studied using FTIR spectrometry, X-Ray photoelectron spectroscopy (XPS), and FIB-TEM. It is found that the difference in thickness and microstructure of the tribofilms for the two composites is mainly due to the tribochemistry of the nanoparticles. The α-Al2O3 nanoparticle plays a "cohesion" role during the formation of the tribofilm, which facilitates the formation of a thicker, more uniform, and stronger adhered tribofilm on the metallic counterpart, making it more robust against higher shear stress.

DNA polymerases replicate cell genomes and/or participate in the maintenance of genome integrity. DNA polymerases sharing high sequence homology with E. coli DNA polymerase I (pol I), have been grouped in Family A. Pol I participates in Okazaki fragment maturation and in bacterial genome repair. Since its discovery in 1956, pol I has been extensively studied, primarily to get deeper insights into the mechanism of DNA replication. As research on DNA polymerases advances, many novel functions of this group of polymerases are uncovered. For example, human DNA polymerase θ (a Family A DNA pol) has been shown to synthesize DNA using RNA as a template, a function typically attributed to retroviral reverse transcriptase. A heightened interest in drug discovery against pol θ has emerged due to its roles in cancer. Likewise, Pol I family enzymes also appear attractive drug-development targets against microbial infections. Development of antimalarial compounds targeting apicoplast apPOL, an ortholog of Pol I, further extends the druggability of this family of enzymes. Here, we summarize reported drug-development efforts against Family A polymerases, and future perspective regarding these enzymes as antibiotic targets. Current techniques such artificial intelligence can be used to facilitate the goal of new drugs.

Now day; the interest for the synthesis of heterocyclic compounds containing hydroquinoline fragments has increased tremendously due to their wide variety of pharmaceutical and industrial applications. This work details the synthesis of linear and fused heterocyclic systems containing hydroquinoline fragments and the pharmacological activity spectra of the synthesized compounds was predicted by in silico method using Prediction of Activity Spectra of Substances (PASS) program. 1,2,2,4-tetramethyl-1,2-dihydroquinoline-6-carbaldehyde 5a was reacted for three hours with a system of hydroxylammonium chloride/pyridinium chloride/toluene to produce 1,2,2,4-tetramethyl-1,2-dihydroquinoline-6-nitrile 7. N-benzyl-2,2,4-trimethyl-1,2,3,4-tetrahydroquinoline-6-carbaldehyde 6b and iodine reacted at room temperature in aqueous ammonia water, followed by aq. treatment with Na2S2O3 and produced N-benzyl-2,2,4-trimethyl-1,2,3,4-tetrahydroquinoline-6-nitrile 8. 30-60% 2-phenyl-1,3-oxazol-5(4H)-ones 9a,b; 10a,b were synthesized via the condensation reaction of N-alkylhydroquinoline-6-carbaldehydes 5a,b; 6a,b with hippuric acid in acetic acid. When activated 7-methylazolopyrimidines 11a,b were reacted with N-alkyl-2,2,4-trimethyl-1,2,3,4-tetrahydroquinoline-6-carbaldehydes 6a,b, the reaction produced 60–70% yield of 7-[(E)-2,2,4-trimethylhydroquinolin-6-ylidenemethyl]azolo[1,5-a]pyrimidin-6-yl carboxylic acids 12a,b. The condensation reaction of 7-hydroxy-1,2,2,4-tetramethyl-1,2-dihydroquinoline 3h with dimethylacetylenedicarboxylate (DMAD) and ethylacetoacetate afforded methyl (Z)-2-(5,7,7,8-tetramethyl-2-oxo-7,8-dihydrofuro[3,2-g]quinolin-3(2H)-ylidene)acetate 16 and 4,6,8,8,9-pentamethyl-8,9-dihydro-2H-pyrano[3,2-g]quinolin-2-one 17, respectively. The condensation reaction of 6-formyl-7-hydroxy-1,2,2,4-tetramethyl-1,2-dihydroquinoline 5e with methylene active compounds ethylcyanoacetate/dimethyl-3-oxopentanedioate/ ethylacetoacetate/diethylmalonate/Meldrum’s acid afforded 3-substituted dihydroquinoline containg coumarins 19 & 21. A pentacyclic coumarin 22 was obtained via the random condensation reaction of malononitrile with 5e in the presence of catalytic amount of piperidine in ethanol. The potential biological activities of the synthesized compounds were evaluated using PASS computer program. According to the prognosis, (E)-4-(N-alkylhydroquinolin-6-yl)-3-buten-2-ones, 13a, b & 14 showed high probability of being active (Pa) as the Gluconate 2-dehydrogenase inhibitor, Anti-allergic, Anti-asthmatic, and Anti-arthritic with the Pa value of 0.849-0.870. It was also found out that hydroquinolinecarbonitrile compounds 7 & 8 have a propensity to act as a good progesterone antagonists, anti-allergic, anti-asthmatic, and anti-arthritic (Pa = 0.276-0.827). Among the coumarin moieties containing hydroquinolines, compounds 17, 19a, and 19c were predicted to be good progesterone antagonists with the Pa values of 0.710, 0.630 and 0.615; respectively.

INTRODUCTION: With an increase in the aging population, the application of evidence-based practice in geriatric education can strengthen knowledge, skills, and clinical experience for healthcare students caring for older adults. Age Friendly Health Systems (AFHS) is one of the frameworks founded on providing evidence-based and low-risk care centered on what matters most to older adults, their families, and caregivers. Virtual Reality (VR) platforms are gaining popularity due to their ability to provide an immersive, hands-on learning experience resembling an actual medical practice or care setting. Immersive learning enhances students’ sensory perceptions, promoting an innovative and engaging way of acquiring concepts that are difficult to teach in real life. This study aimed to design, develop, implement, and evaluate a case-based training module highlighting AFHS and educating medical students on the 4Ms approach in geriatric care (What Matters, Medication, Mentation, and Mobility). METHODOLOGY: The project was a feasibility study completed in two phases. Phase one included planning and development of a case-based scenario incorporating 4Ms of AFHS. Phase two included implementing and evaluating the VR training module into the geriatric curriculum for medical students. RESULTS: The final VR case displays a hospital and post-acute setting where an elderly patient is admitted for a hip fracture. Students learn how to triage and treat patients from admission to discharge while demonstrating their knowledge of AFHS. Approximately 10% of students completed the evaluation survey, and preliminary results indicate significant knowledge change in pre-post scenario-based training on AFHS. CONCLUSION: The VR education platform and embedded scenario promise an innovative adaptation of technology in learning the concepts of the 4Ms of AFHS. However, future studies should explore VR education with clinical assessment evaluation to ensure competence in providing Age-Friendly care.

This paper presents the results of quantitative research examining the impacts of demographic and socioeconomic factors on community resilience to disasters. The survey was carried out utilising a questionnaire distributed and subsequently collected online from 321 participants during January 2024. The study employed an adapted version of the '5S' social resilience framework, encompassing five sub-dimensions – social structure (10 variables), social capital (9 variables), social mechanisms (17 variables), social equity and diversity (13 variables), and social belief (13 variables). This customized framework includes 62 indicators, providing a thorough assessment of community (social) disaster resilience in the research context. To explore the relationship between predictors and community (social) disaster resilience in Serbia, their attitudes towards the mentioned five sub-dimensions, as well as their engagement in preventive measures and their perception of resilience to various disasters with a particular focus on demographic and socio-economic impacts, statistical methods including t-tests, one-way ANOVA, Pearson’s correlation, and multivariate linear regression were employed. The results of the multivariate regressions across various community disaster resilience subscales indicate that age emerged as the most significant predictor for the social structure subscale. At the same time, education stood out as the primary predictor for the social capital subscale. Additionally, employment status proved to be the most influential predictor for both social mechanisms and social equity-diversity subscales, with property ownership being the key predictor for the social beliefs sub-scale. Despite being considered in the analyses, gender, marital status, income level, and number of household members did not emerge as the most significant predictors across the investigated community (social) disaster resilience subscales. The determined mean value of the community (social) disaster resilience index is M = 2.62, and the findings reveal that participants assigned the highest ratings to the social beliefs subscale (M = 2.76), while the lowest values were observed in the social structure subscale (M = 2.46). Findings can be used to create strategies and interventions aimed at enhancing the resilience of communities in Serbia by addressing the intricate interplay between demographic characteristics, socio-economic factors, and their ability to withstand, adapt to, and recover from different disasters.

In this paper we investigate some properties of square-free numbers. In particular, we study a function that counts the number of square-free numbers no larger than the given number n. We show that this function has asymptotics consistent with the predictions of the Riemann hypothesis and use this to obtain new and better estimates of the density of square-free numbers. Finally, we present a well-known generalization of the concept of a square-free number to monoids and research on square-free factorizations.

This paper offers a theoretical and experimental examination of the concurrent production of electricity and heat using photovoltaic thermal (PV/T) technology. The efficiency performance of the PV/T system is meticulously analyzed using MATLAB/Simulink software environments. Notably, the proposed PV/T system shows reliable performance, and its validity is confirmed through experimental validation on a test stand with a single PV/T panel positioned at a 45-degree angle to the horizontal and a 0-degree azimuth angle.

Many studies have addressed sex differences in patients with psoriatic arthritis, although these are aimed more at describing the phenotype than at investigating the causes underlying the differences. Cross-sectional study of 203 patients. The clinical and demographic variables included age, years of education, time since onset, smoking, type of treatment, clinical presentation, number of entheses affected, dactylitis, fatigue, and cutaneous involvement. Disease activity,functioning and disease was measured. The comorbid conditions evaluated included obesity (and leptin as an associated parameter), anxiety and depression, and sleep quality. Mean age was 54.6, and 46.8% of patients were women. Women less frequently presented axial involvement and more frequently presented enthesitis. They also presented greater disease activity, greater disease impact, and poorer functioning, as well as greater fatigue. As for comorbid conditions, women presented a higher leptin/BMI ratio, higher levels of anxiety and depression, and poorer sleep quality. By sex, pain affecting women was associated with the leptin/BMI ratio and sleep quality. The leptin/BMI ratio was not associated with any component of disease activity in men. Sex was associated with several clinical manifestations, disease activity, functioning, and disease impact. Leptin was associated with intensity of pain in women.

Chromosomal instability (CIN), defined by variations in the number or structure of chromosomes from cell to cell, is recognized as a distinctive characteristic of cancer, associated with the ability of tumors to adapt to challenging environments. CIN has been recognized as a source of genetic variation that leads to clonal heterogeneity (CH). Recent findings suggest a potential association between CIN and CH with the prognosis of BC patients, particularly in tumors expressing the epidermal growth factor receptor 2 (HER2+). In fact, information on the role of CIN in other BC subtypes, including luminal B BC, is limited. Additionally, it remains unknown whether CIN in luminal B BC tumors, above a specific threshold, could have a detrimental effect on the growth of human tumors, or if low or intermediate CIN levels could be linked to a more favorable BC patient prognosis when contrasted with elevated levels. Clarifying these relationships could have a substantial impact on risk stratification and the development of future therapeutic strategies aimed at targeting CIN in BC. This study aimed to assess CIN and CH in tumor tissue samples from ten patients with luminal B BC, and compared them with established clinicopathological parameters. The results of our study show that luminal B BC patients exhibit intermediate CIN and stable aneuploidy, both of which correlated with lymphovascular invasion. These findings suggest that evaluating CIN, CH and aneuploidy could improve risk stratification, the prediction of clinical outcomes and future therapeutic approaches in luminal B BC patients.

Proteolysis Targeting Chimeras (PROTACs) describe compounds that bind to and induce degradation of a target by simultaneously binding to a ubiquitin ligase. More generally referred to as bifunctional degraders, PROTACs have led the way in the field of targeted protein degradation (TPD) with several compounds currently undergoing clinical testing. Alongside bifunctional degraders, single-moiety compounds, or molecular glue degraders (MGDs), are increasingly being considered as a viable approach for development of therapeutics, driven by advances in rational discovery approaches. This review focusses on drug discovery with respect to bifunctional and molecular glue degraders within the ubiquitin proteasome system, including analysis of mechanistic concepts and discovery approaches, with an overview of current clinical and pre-clinical degrader status in oncology, neurodegenerative and inflammatory disease.

Drug repurposing, rebranding an existing drug for a new therapeutic indication, is deemed a beneficial approach for a quick and cost-effective drug discovery process by skipping preclinical, Phase 1 trials and pharmacokinetic studies. Several psychotropic drugs including selective serotonin reuptake inhibitors (SSRIs) and tricyclic antide-pressants (TCAs) were studied for their potential application in different diseases es-pecially in cancer therapy. Fluoxetine (FLX) is one of the most prescribed psychotropic agents from SSRIs class for the treatment of several neuropsychiatric disorders with a favourable safety profile. FLX exhibited different oncolytic effects via mechanisms dis-tinct from its main serotonergic activity. Taking advantage of its ability to rapidly pen-etrate the blood-brain barrier, FLX could be particularly useful in brain tumors. This was proved by different in vitro and in vivo experiments using FLX as a monotherapy or combination with temozolomide (TMZ) or radiotherapy. In this review of literature, we summarize the potential pleiotropic oncolytic roles of FLX against different cancers highlighting the multifaceted activities of FLX and its ability to interrupt cancer prolif-eration via several molecular mechanisms and even surmount multidrug resistance (MDR). We elaborated on the successful synergistic combinations such as FXR/temozolomide and FXR/raloxifene for the treatment of glioblastoma and breast cancer, respectively. We showcased beneficial pharmaceutical trials to load FLX on car-riers to enhance its safety and efficacy on cancer cells. This is the first review article ex-tensively summarizing all previous FLX repurposing studies for the management of cancer.

Chronic kidney disease (CKD) affects approximately 12% of the global population posing a significant health threat. Inflammation plays a crucial role in the uremic phenotype of CKD contributing to elevated cardiovascular and overall mortality in affected individuals. This study aimed to explore novel metabolic pathways in non-dialysis dependent stage 5 CKD patients using semitargeted metabolomics. In a prospective observational design involving 50 patients, blood samples collected before the initial hemodialysis session underwent liquid chromatography and high resolution mass spectrometer analysis. Univariate (Mann-Whitney test) and multivariate (logistic regression with LASSO regularization) methods identified metabolomic variables associated with inflammation. Notably, adenosine-5’-phosphosulfate (APS), dimethylglycine, pyruvate, lactate, and 2-ketobutyric acid exhibited significant differences in the presence of inflammation. Cholic acid, homogentisic acid, and 2-phenylpropionic acid displayed opposing patterns. Multivariate analysis indicated increased inflammation risk with certain metabolites (N-Butyrylglycine, dimethylglycine, 2-Oxoisopentanoic acid, and pyruvate), while others (homogentisic acid, 2-Phenylpropionic acid, and 2-Methylglutaric acid) suggested decreased probability. These findings unveil potential inflammation-associated biomarkers related to defective mitochondrial fatty acid beta oxidation and branched-chain amino acid breakdown in CKD, shedding light on cellular energy production and offering insights for further clinical validation.

Plant viral nanoparticles (VNPs) are attractive to researchers in nanomedicine due to their safety, easy production, resistance, and straightforward functionalization. In this paper, we developed and successfully purified a VNP derived from turnip mosaic virus (TuMV), a well-known plant pathogen, that exhibits high affinity for immunoglobulins G (IgG) thanks to its functionalization with the Z domain from staphylococcal protein A via gene fusion. We selected cetuximab as a model IgG to prove the versatility of this novel TuMV VNP by developing a fluorescent nanoplatform to mark tumoral cells of the line Cal33, from tongue squamous cell carcinoma. We observed that the fluorescent VNP-cetuximab bound selectively to Cal33 and were internalized by confocal microscopy, revealing the potential of this nanotool in cancer research.

Phosphatase and tensin homolog (PTEN) is a negative regulator of the phosphoinositide 3-kinases/protein kinase B (PI3K/AKT) signaling pathway. Notably, its active site harbors a cysteine residue that is susceptible to oxidation by hydrogen peroxide (H2O2). This oxidation inhibits the phosphatase function of PTEN, critically contributing to the activation of the PI3K/AKT pathway. Upon stimulation of cell surface receptors, the activity of NADPH oxidase 2 (NOX2) generates a transient amount of H2O2, serving as a mediator in this pathway by oxidizing PTEN. The mechanism underlying this oxidation, occurring despite the presence of highly efficient and abundant cellular oxidant-protecting and reducing systems, continues to pose a perplexing conundrum. Here, we demonstrate that the presence of bicarbonate (HCO3-) promoted the rate of H2O2-mediated PTEN oxidation, probably through the formation of peroxymonocarbonate (HCO4-), consequently potentiated the phosphorylation of AKT. In essence, our findings consolidate the crucial role of HCO3- in the redox regulation of PTEN by H2O2, lead to the presumption regarding HCO4- as a signaling molecule during cellular physiological processes.

Caring for dolphins is a delicate process that requires experienced caretakers to pay close attention to their behavioral characteristics. However, caretakers may sometimes lack experience or not be able to give their full attention, which can lead to misjudgment or oversight. To address these issues, a dolphin behavior analysis system has been designed to assist caretakers in making accurate assessments. The study utilized image preprocessing techniques to reduce sunlight reflection in the pool and enhance the outline of dolphins, making it easier to analyze their movements. The dolphins were divided into 11 keypoints using an open-source tool called DeepLabCut, which helped accurately mark various body parts for skeletal detection. The AquaAI Dolphin Decoder (ADD) was then used to analyze six dolphin behaviors. To improve behavior recognition accuracy, the Long Short-Term Memory (LSTM) neural network was introduced. The ADD and LSTM models were integrated to form the ADD-LSTM system. Several classification models, including unidirectional and bidirectional LSTM, GRU, and SVM, were compared. The results showed that the ADD module combined with a double-layer bidirectional LSTM method achieved high accuracy in dolphin behavior analysis. The accuracy rates for each behavior were over 90%.

The space shuttle, a revolutionary spacecraft that has played a significant role in human space exploration, was composed of various advanced materials that were carefully selected to meet the extreme demands of spaceflight. This review paper provides a comprehensive examination of the materials historically employed in the construction of space shuttles and explores the latest trends shaping the field. The evolution of space shuttle materials is traced from the inception of the space program to contemporary missions, highlighting key milestones, challenges, and breakthroughs. Emphasis is placed on the critical role that materials play in the overall performance, safety, and sustainability of space shuttles. The paper begins by elucidating the diverse requirements that materials must fulfill in the harsh and complex environment of space, encompassing extreme temperatures, radiation exposure, and mechanical stresses. A detailed analysis of the materials utilized in the fabrication of various shuttle components, such as thermal protection systems, structural elements, and propulsion systems, is presented. Special attention is given to the challenges posed by re-entry and the strategies employed to mitigate heat-related issues. Furthermore, the review explores recent innovations and emerging materials that are reshaping the landscape of space shuttle design. Advancements in nanotechnology, composite materials, and additive manufacturing are discussed in the context of their potential applications for enhancing shuttle performance and reducing mission costs. The paper also addresses the importance of sustainability in space exploration, exploring materials with lower environmental impact and improved recyclability. The review concludes with a forward-looking perspective on the future of materials, considering ongoing research, development, and the potential incorporation of cutting-edge technologies. Insights are provided into how the evolving landscape of materials science may influence the design and manufacturing processes of the next generation of space vehicles. This paper provides an overview of the materials used in the construction of the space shuttle, including their properties, applications, and challenges. The materials used in the space shuttle are critical in ensuring the safety, performance, and longevity of the spacecraft, and understanding their characteristics and performance in space is crucial for the advancement of aerospace engineering.

Introductions- Liveable housing environments face the menace of global climate change. In-frastructure (including buildings and houses) continuously experiences significant impacts ex-acerbated by natural variability in climate. The study addressed how climate change impacts the resilience of residential buildings, increased maintenance frequency, and the wellbeing and comfort of residents in UK residential buildings. Design/Methodology/Approach: This study used deductive reasoning and an empirical epis-temological methodology as a data-collecting basis to evaluate primary information obtained via a questionnaire. Regression analysis was ultimately employed to analyse the collected da-ta. Result/Discussions: The findings show a significant relationship between climate change and the wellbeing of the occupants of UK residential buildings. Also, the results show that social wellbeing is more important to the occupants than mental and physical wellbeing. It reveals that residential buildings in the UK suffer the cost of maintenance due to continuous reduc-tion in the building fabric's resilience to the impacts of climate change; for instance, a recent increase in rainfall/storms results in unprecedented flooding, which continues to damage the UK residential building fabrics.

Synthetic cathinones, derived from cathinone found in the plant Catha edulis, represent the second-largest and most frequently seized group of new psychoactive substances. They are considered as β-keto analogs of amphetamine, sharing pharmacological effects with amphetamine and cocaine. This review describes the neurotoxic properties of synthetic cathinones, encompassing their capacity to induce neuroinflammation, dysregulate neurotransmitter systems, and alter in monoamine transporters and receptors. Additionally, it discusses the rewarding and abuse potential of synthetic cathinones drawing from findings obtained through various preclinical animal models, contextualized with other classical psychostimulants. The review also offers an overview of current abuse trends of synthetic cathinones on the illicit drug market, specifying the aspects covered, and underscores the risks they pose to public health.

Background. Implementing mammogram screening means that clinicians are seeing many breast cancers that will never develop metastases. The purpose of this study was to identify subgroups of breast cancer patients who did not present events related to long-term breast cancer mortality, taking into account diagnosis at breast screening, absence of palpability and axillary involvement, and genomic analysis with PAM50. Patients and Methods. To identify them, a retrospective observational study was carried out selecting patients without palpable tumour, without axillary involvement, and a genomic analysis was performed with PAM50. Results. The probability of distant metastasis-free interval (DMFI) of 337 patients was 0.92 (95% CI, 0.90-0.93) at 20 years and 0.96 (95% CI, 0.92-1.00) in 95 patients (28%) with available PAM50 tests. In 22 (23.15%) luminal A tumours and in 9 (9.47%) luminal B tumours smaller than 1 cm and in HER2 and basal type tumours there were no metastatic events (20-year DMFI of 1.00). Conclusion. Patients with nonpalpable breast cancer found at screening with negative nodes are at very low risk. It is possible to identify subgroups without metastatic events by determining the intrinsic subtype and tumour size less than 1 cm. De-escalation of treatment should be considered.

Fibroblast activation protein (FAP) is a serine protease characterized by its high expression in cancer-associated fibroblasts (CAFs) and near absence in adult normal tissues and benign lesions. This unique expression pattern positions FAP as a prospective biomarker for targeted tumor radiodiagnosis and therapy. The advent of FAP-based radiotheranostics is anticipated to revolu-tionize cancer management. Among various types of FAP ligands, peptides and antibodies, have shown advantages over small molecules, exemplifying prolonged tumor retention in human volunteers. Within its scope, this review summarizes the recent research progress of the FAP radiopharmaceuticals based on antibodies and peptides, on tumor imaging and therapy. Additionally, it incorporates insights from recent studies, providing valuable perspectives on the clinical utility of FAP-targeted radiopharmaceuticals.

Environmental DNA (eDNA) sampling has emerged as a powerful approach for monitoring biodiversity in the context of diverse terrestrial and aquatic ecosystems, and has broad potential for both environmental surveys and species management. eDNA studies focusing on plant and animal species have capitalized on analytical methodologies developed originally for metagenomic studies of microorganisms, and on technological improvements in sample collection. However, while eDNA studies have proliferated rapidly, efforts to standardize sampling and analytical methods are still nascent. Critically, fundamental data concerning the distribution and persistence of eDNA in different ecological contexts are lacking, complicating both confidence in species detection and comparability between studies. We propose that key deficits could be addressed by using well-designed synthetic DNA standards or tracers, which are widely used in fields ranging from medical diagnostics to hydrology. In-field application of a standardized mixture of barcoded synthetic DNA fragments of varying lengths and concentrations that are recovered concommitantly with eDNA sampling should provide critical yet missing data on environmental DNA distribution and turnover, as well as an internal molecular standard to enhance both species detection and comparability between eDNA studies.

Infrared small target detection (ISTD) plays a crucial role in both civilian and military applications. The detection of small targets against dense cluttered backgrounds remains a challenging task, requiring the collaboration of false alarm source elimination and target detection. Existing approaches primarily focus on modeling targets while often neglecting false alarm sources. To address this limitation, we propose a Target and False Alarm Collaborative Detection Network to leverage the information provided by false alarm sources and the background. Firstly, we introduce a False Alarm Source Estimation Block (FEB) that estimates potential interferences present in the background by extracting features on multiple scales and employing stepwise upsampling for feature fusion. Subsequently, we propose a framework that employs multiple FEBs to eliminate false alarm sources across multiple scales. Finally, a Target Segmentation Block (TSB) is introduced to accurately segment the targets to produce the final detection result. Experiments on public datasets demonstrate that, compared to other methods, our model achieves high accuracy in segmenting targets while being able to extract false alarm sources which can be used for further studies.

The Casimir effect can either work over very short distances or at very low temperatures. At the cosmic scale, we naturally deal with long distances, but at the same time, we encounter extraordinarily low temperatures, namely the CMB (Cosmic Microwave Background) tem- perature. Recently, there has been increased interest in the Casimir effect and its implications in cosmology. Here, we briefly demonstrate that the luminosity and radiation pressure of the CMB is mathematical identical to a theoretical Casimir effect within the Hubble sphere, or actually our solution seems to be valid for any Schwarzschild black hole. The Casimir effect forevery Schwarzschild black hole is identical. This also include the Hubble sphere if we treat it as a Schwarzschild black hole that is related to increased interest in black hole cosmology.

Tumor immunotherapy represented by immune target blocking and chimeric antigen receptor cell therapy has developed rapidly. Among them, Natural Killer Cell (NK) is gradually becoming another preferred immunotherapy method after T cell immunotherapy because of its unique killing effect in innate immunity and adaptive immunity. Although NK cell therapy has achieved promising results in clinical trials, there are still some problems, such as low efficacy in solid tumors, insufficient penetration of NK cells and high cost of treatment. Nanomaterials are expected to be an excellent tool to improve the anti-tumor immune response of NK cells due to their advantages such as chemical specificity, biocompatibility and simple synthesis. Nanomaterials can enhance the cytotoxicity of NK cells, participate in the modification and noninvasive cell-tracking patterns of NK cells，and mediate their homing and infiltration, and thus significantly improve the efficiency of NK cell immunotherapy. In this review, we will briefly introduce the methods and mechanisms of tumor immunotherapy, emphasize the research progress of NK cell-based immunotherapy and imaging, and finally summarize the direction and research progress of nanomaterials in NK cell-based immunotherapy.

AbstractThe emergence of AI-powered deepfakes, manipulatively realistic synthetic media, raises unprecedented challenges for human information processing and decision-making. This paper explores the cognitive and emotional consequences of exposure to deepfakes, delving into how these digitally fabricated experiences can reshape perception, trust, and social interactions. By reviewing existing research and outlining potential methodological approaches, this paper aims to establish a framework for investigating the multifaceted impact of deepfakes on the human brain.BackgroundThe digital age has ushered in an era of unprecedented information abundance and accessibility. Yet, this abundance breeds vulnerability, particularly with the emergence of AI-powered deepfakes. These hyper-realistic synthetic media creations present a potent threat to the fundamental trust and integrity of information sources. Deepfakes have infiltrated various domains, from entertainment and social media to politics and journalism, blurring the lines between truth and fabrication. Consequently, understanding the cognitive and emotional consequences of encountering deepfakes becomes crucial for navigating this increasingly deceptive landscape.ObjectivesThis research aims to: Investigate how exposure to deepfakes impacts various cognitive functions, including perception, attention, memory, and decision-making. Elucidate the emotional responses elicited by deepfakes and their underlying neural mechanisms. Evaluate the role of individual differences, such as susceptibility to deception and emotional sensitivity, in mediating the impact of deepfakes. Develop a comprehensive framework for understanding the multifaceted influence of deepfakes on the human brain. Results (anticipated)This research is expected to yield insights into: The specific cognitive and emotional processes altered by deepfakes, providing evidence for potential mechanisms of deception and manipulation. The neural circuitry involved in detecting and responding to deepfakes, leading to the development of more effective detection methods. The influence of individual differences (e.g., age, cognitive style) on susceptibility to deepfakes, informing targeted interventions and educational efforts.ConclusionBy deciphering the impact of deepfakes on the human brain, this research will offer valuable tools for mitigating the harmful consequences of misinformation and promoting responsible use of this powerful technology. Ultimately, understanding how deepfakes manipulate our cognitive and emotional landscape is not merely a scientific pursuit, but a critical step towards ensuring a future where truth prevails in the digital world.

Abstract Background Context Pelvic ring fractures are becoming more common in the aging population and can prove to be fatal, having mortality rates between 10% and 16%. Stabilization of these fractures is challenging and often require immediate internal fixation. Therefore, it is necessary to have a biomechanical understanding of the different fixation techniques for pelvic ring fractures. Methods A previously validated three-dimensional finite element model of the lumbar spine, pelvis, and femur was used for this study. A unilateral pelvic ring fracture was simulated by resecting the left side of the sacrum and pelvis. Five different fixation techniques were used to stabilize the fracture. A compressive follower load and pure moment was applied to compare different biomechanical parameters including range of motion (contralateral sacroiliac joint, L1-S1 segment, L5-S1 segment), and stresses (L5-S1 nucleus stresses, instrument stresses) between different fixation techniques. Results Transiliac -trans sacral screw fixation at S1 and S2 showed the highest stabilization for horizontal and vertical displacement at the sacral fracture site and reduction of contralateral sacroiliac joint for bending and flexion range of motion by 165% and 121%, respectively. DTSF (Double transiliac rod and screw fixation) model showed highest stabilization in horizontal displacement at the pubic rami fracture site, while the L5_PF_W_CC (L5-Ilium posterior screw fixation with cross connectors) and L5_PF_WO_CC ( L5-Ilium posterior screw fixation without cross connectors) showed higher rod stresses, reduced L1-S1 (approximately 28%), and L5-S1 (approximately 90%) range of motion. Conclusions Longer sacral screw fixations were superior in stabilizing sacral and contralateral sacroiliac joint range of motion. Lumbopelvic fixations displayed a higher degree of stabilization in the horizontal displacement compared to vertical displacement of pubic rami fracture, while also indicating the highest rod stresses. When determining the surgical approach for pelvic ring fractures, patient-specific factors should be accounted for to weigh the advantages and disadvantages for each technique.

This study focused on the investigation of myeloperoxidase through a Molecular Docking approach with various natural compounds to identify potential substances for cardiovascular research. Recent research has linked elevated myeloperoxidase levels to the severity of coronary artery disease. The results of the docking analysis revealed Polydatin, Daidzin, Astringin, Ginkgetin, and Amentoflavone as promising compounds with excellent binding capacity. To complement this, toxicity prediction studies were conducted using pkCSM. Overall, all four investigated molecules (Amentoflavone, Daidzin, Ginkgetin, and Astringin) were found to be non-toxic, exhibiting high maximum tolerated doses (human) and favorable values for Oral Rat Acute Toxicity and Oral Rat Chronic Toxicity. Moreover, they showed non-AMES toxicity and non-hepatotoxicity. Astringin, in particular, stood out with the highest positive effects, including a high maximum tolerated dose (human) and favorable values for Oral Rat Chronic Toxicity, along with dual inhibition of hERG II and hERG I. These findings suggest the potential utility of these compounds in cardiovascular research with minimized unwanted effects.

Glypicans are a family of heparan sulfate proteoglycans that are attached to the outer plasma membrane leaflet of the producing cell by a glycosylphosphatidylinositol anchor. Glypicans are involved in the regulation of many signalling pathways, including those that regulate the activities of Wnts, Hedgehog (Hh), Fibroblast Growth Factors (FGFs) and Bone Morphogenetic Proteins (BMPs), among others. In the Hh signalling pathway, glypicans have been shown to be essential for ligand transport and the formation of Hh gradients over long distances, for the maintenance of Hh levels in the extracellular matrix and for its unimpaired reception in distant recipient cells. Recently, two mechanistic models have been proposed to explain how Hh can form the signalling gradient and how glypicans may contribute to it. In this review, we describe the structure, biochemistry and metabolism of glypicans and their interactions with different components of the Hh signalling pathway that are important for the release, transport and reception of Hh.

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

Glycosylation, a prevalent post-translational modification, plays a pivotal role in regulating intricate cellular processes by covalently attaching glycans to macromolecules. Dysregulated glycosylation is linked to a spectrum of diseases, encompassing cancer, neurodegenerative disorders, congenital disorders, infections, and inflammation. This review delves into the intricate interplay between glycosylation and protein conformation, with a specific focus on the profound impact of N-glycans on the selection of distinct protein conformations, characterized by distinct interactomes – namely protein assemblies - under normal and pathological conditions across various diseases. We begin by examining the spike protein of the SARS virus, illustrating how N-glycans regulate the infectivity of pathogenic agents. Subsequently, we utilize the prion protein and the chaperone glucose-regulated protein 94 as examples, exploring instances where N-glycosylation transforms physiological protein structures into disease-associated forms. Unraveling these connections provides valuable insights into potential therapeutic avenues and a deeper comprehension of the molecular intricacies that underlie disease conditions. This exploration of glycosylation's influence on protein conformation effectively bridges the gap between the glycome and disease, offering a comprehensive perspective on the therapeutic implications of targeting conformational mutants and their pathologic assemblies in various diseases. The goal is to unravel the nuances of these post-translational modifications, shedding light on how they contribute to the intricate interplay between protein conformation, assembly and disease.

In this study, a new structure is proposed based on the body-centered cubic (BCC) lattice structure: adding a cubic truss in the center of the BCC structure, which is denoted by TLC (Truss-lattice-cube). The different dimensions of the central cube can affect the mechanical properties of the lattice structure notably. With a fixed length (15mm) of a unit cell, the optimal size for the central cube is determined to be 5 mm. Quasi-static compressive tests are performed on specimens made of Polylactic Acid (PLA) using additive manufacturing technology. The deformation characteristics of the new structure is analyzed in detail by experiments and numerical simulations. Compared to the BCC structure, the mechanical properties of the TLC structure are significantly improved. The initial flow stress of the TLC has been increased by 122% at a strain of 0.1; the specific strength has been enhanced by 293% at a strain of 0.5; and the specific energy absorption has been improved by 312% at the strain of 0.6. Printing defects in the lattice structure could deteriorate the mechanical property remarkably. In this work, incorporation of microcracks into the finite element model makes the simulation capture the influence of printing defects and improve the predictive accuracy of simulation significantly.

Numerous researchers acknowledge that occupational pension protects employees. However, the total occupational pension is shared by employees and employers in China, which is a cost. This study aimed to explore the occupational pension on corporate social responsibility (CSR) and organizational resilience. We drew upon insights from cost-stickiness and resource-based theories to develop a model that illuminates how occupational pension affected firms’ stance toward CSR in the context of the COVID-19 pandemic and how this, in turn, has result organizational resilience. This study categorized CSR into strategic and responsive activities based on cost stickiness. We selected a total of 34,145 observations of Chinese listed companies over the period 2010-2023 as a sample to investigate whether occupational pension changes CSR strategies. The results showed that the cost pressure to contribute to occupational pension drove firms to reduce their responsive CSR and boost their strategic CSR. Moreover, strategic CSR improved organizational resilience, but responsive CSR did not. This relationship between occupational pension and CSR was significantly and negatively moderated by the minimum wage and population aging. Whereas, the relationship between CSR and organizational resilience was significantly and positively moderated by digital transformation and marketing capabilities. This study has implications for decision-making regarding high-quality firm development.

In "genome editing," a type of genetic engineering, DNA is added, taken away, or changed in an organism's genome. Biomedicine, biotechnology, and synthetic biology, just to name a few, have all gained a lot from how often this method is used. Before the editing process can start, a Double-Strand Breaks (DSB) must be made in the DNA at a specific gene. Researchers have made nucleases, which are sometimes called "molecular scissors," to fix this DSB. Transcription activator-like effector nucleases (TALENs), Zinc-finger nucleases (ZFNs), and homing endonucleases are all examples of protein targets that have been studied and changed. The last part gave an overview of these study projects and explained how to make Cas12a for specific uses. The applications of Cas12a have been extensively studied in recent years, but the protein still holds a lot of promise as a treatment and screening tool. In order to give a quick review of CRISPR-Cas12a and its uses, we will briefly talk about the structure and function of the different parts of the reaction pathway that lead up to the catalysis of the target DNA. Cas12a uses a multistep process to make sure that it is selecting the right DNA. This is a good trait for a device that changes the DNA because it makes it less likely that something bad will happen. Even though data shows that a new CRISPR RNAs (crRNA) molecule can stop Cas12a from randomly destroying ssDNA, it may still hurt the host cell while trying to change the genome. The action of Cas12a catalysis, which is a powerful tool for changing the genome, needs to be changed so that it can be more easily controlled and managed. Using what we know about how Cas12a works, we have made mutants that are less active on ssDNA and more active on dsDNA. So far, only Cas9 and Cas12a, which are both part of the CRISPR family, have been used to change the genome. Because of how similar and different these two endonucleases are, CRISPR can now be used for multiple scientific purposes. Cas12a is better than Cas9 because it makes double-strand breaks (DSBs) that favor Homology-Directed Repair (HDR) over Non-homologous end joining (NHEJ) and can change more than one copy of the genome at the same time. Both Cas9 and Cas12a are being changed to make them better at detecting Protospacer Adjacent Motif (PAM) than they are in their natural state. This will make it possible to start focusing on more genes.

This research delves into the intricate challenges confronting the agricultural sector, with a specialized focus on mitigating infections in tomato crops, particularly powdery mildew induced by the Leveillula Taurica pathogen. Tomatoes, renowned for their nutritional richness, are vital to global food security. However, conventional methodologies for disease detection exhibit both laborious processes and limited accuracy. In response to these challenges, this study advocates for an innovative fusion of hyperspectral imaging and deep learning methodologies to detect crop disease and its severity. The systematic workflow commenced with the curation of a dataset, involving the acquisition of live images through OpenCV, followed by conversion to RGB format and subsequent feature extraction utilizing a pre-trained visual geometry group (VGG-16) model for enhanced analysis. Sequentially, RGB images were transformed into simulated hyperspectral images (SHSI) leveraging a Neural Network generator model, offering a distinctive viewpoint on spectral information. This novel approach transcends conventional constraints by delivering a three-dimensional perspective, seamlessly integrating spatial and spectral dimensions for holistic data acquisition. The SHSI is further transmuted into a 3D visualization cube comprehensive grasp of spatial and spectral aspects encompassing spectral, spatial, and Haralick features. The research concludes with severity detection, categorized as low, moderate, or high, employing a Gaussian Mixture Model (GMM) and K-means for visualization.

Muscle-enriched A-type lamin-interacting protein (MLIP) is an emerging protein involved in cellular homeostasis and stress adaptation. Eukaryotic cells regulate various cellular processes, including metabolism, DNA repair, and cell cycle progression, to maintain cellular homeostasis. Disruptions in this homeostasis can lead to diseases such as cancer, characterized by uncontrolled cell growth and division. This review aims to explore for the first time the unique role MLIP may play in cancer development and progression, given its interactions with the PI3K/Akt/mTOR pathway, p53, and FOXO transcription factors, all critical regulators of cellular homeostasis and tumor suppression. We discuss the current understanding of MLIP's involvement in pro-survival pathways and its potential implications in cancer cells' metabolic remodeling and dysregulated homeostasis. Additionally, we examine the potential of MLIP as a novel therapeutic target for cancer treatment. This review aims to shed light on MLIP's potential impact on cancer biology and contribute to developing innovative therapeutic strategies.

Introduction: Within primary ARDS, SARS-CoV-2-associated ARDS (C-ARDS) emerged in late 2019, reaching its peak during the subsequent two years. Recent efforts in ARDS research have concentrated on phenotyping this heterogeneous syndrome to enhance comprehension of its pathophysiology. Methods and Results: A retrospective study was conducted on C-ARDS patients from April 2020 to February 2021, encompassing 110 participants with a mean age of 63.2±11.92 (26-83 years). Of these, 61.2% (68) were male, and 25% (17) experienced severe ARDS, resulting in a mortality rate of 47.3% (52). Ventilation settings, arterial blood gases, and chest X-ray (CXR) were evaluated on the first day of invasive mechanical ventilation and between days two and three. CXR images were scrutinized using a convolutional neural network (CNN). A binary logistic regression model for predicting C-ARDS mortality was developed based on the most influential variables: age, PaO2/FiO2 ratio (P/F) on days one and three, CNN-extracted CXR features, and age. Initial performance assessment on test data (23 patients out of the 110) revealed an area under the receiver operating characteristic (ROC) curve of 0.862 CI (0.654-0.969). Conclusion: Integrating data available in all intensive care units enables the prediction of C-ARDS mortality by utilizing evolving P/F ratios and CXR. This approach can assist in tailoring treatment plans and initiating early discussions to escalate care and extracorporeal life support. Machine learning algorithms for imaging classification can uncover otherwise inaccessible patterns, potentially evolving into another form of ARDS phenotyping. The combined features of these algorithms and clinical variables demonstrate superior performance compared to either element alone.

This study analyzes the relationship between economic policy uncertainty (hereinafter EPU) and corporate value, and verifies the differential effects of EPU on corporate value according to corporate social responsibility (hereinafter CSR) activities. The study period was from 2010 to 2020, and the EPU indexes measured by Baker et al. (2016)'s method and Hexun's CSR scores for companies listed on the Chinese stock market were used. Hexun is one of the three major evaluation agencies in China, and the CSR scores evaluated by this agency have been widely used in previous studies as a representative indicator of Chinese companies' CSR performance. The results of this study are as follows. First, EPU and corporate value were found to have a negative (-) relationship. Second, active CSR activities relieved the negative (-) relationship between EPU and corporate value. Finally, companies were divided into groups according to CSR activity scores to analyze the relationship and according to the result, the negative (-) relationship between EPU and corporate value was greater in the groups with low CSR activity scores than in the groups with high CSR activity scores. A lag model was applied to control endogeneity, and the results were consistent with the main results above. Previous studies have mainly focused on microscopic factors to investigate factors affecting corporate value. This study focused on macroeconomic policies and paid attention to the effects of changes in the macroenvironment caused by economic policy uncertainty on corporate value. In addition, this study is meaningful in that it expanded previous studies related to CSR activities by confirming that active CSR activities can be an advantageous tool for overcoming EPU.

Punica granatum L., commonly known as pomegranate, is a typical fruit of Asia, Mediterranean countries, Middle East and USA areas. While in the ancient time pomegranate was considered an ornamental plant, nowadays numerous scientific studies have highlighted its antioxidant and anti-radical activities, up to consider pomegranate as a “superfood”. Pomegranate presents a high content of natural bioactive compounds (NBCs) and its consumption appears to exert numerous healthy beneficial effects, in particular, in several pathological conditions, namely in patients affected by metabolic syndrome, cancer, nephrolithiasis, urinary tract infections and neurodegenerative diseases. Moreover, recent studies pointed out the possible beneficial action of pomegranate on oral health. For these reasons, the utility of pomegranate in internal medicine and in dentistry represents a promising field, as it could permit the development of innovative natural adjuvant therapies, able to empower the standard pharmaceutical therapies.

The currently available anti-cancer therapies, such as gamma-radiation and chemotherapeutic agents, induce cell death and cellular senescence not only in cancer cells but also in the adjacent normal tissue. New anti-tumor approaches focus on limiting the side effects on normal cells. In this frame, the potential anti-tumor properties of Pulsed Electromagnetic Fields (PEMFs) through irradiation of breast cancer epithelial cells (MCF-7 and MDA-MB-231) and normal fibroblasts (FF95) were investigated. PEMFs had a frequency of 8 Hz, full-square wave type, magnetic flux density of 0.011 T and applied twice daily for 5 days. Data collected showcases that PEMF application decreases the proliferation rate and viability of breast cancer cells while having the opposite effect on normal fibroblasts. Moreover, PEMF irradiation induced cell death and cellular senescence only in breast cancer cells without any effect in the non-cancerous cells. These findings suggest PEMF irradiation as a novel, non-invasive anti-cancer strategy in combination with senolytic drugs, to eliminate both cancer and the remaining senescent cells while simultaneously avoiding the side effects of the current treatments.

Violence against paramedics is widely recognized as a serious, but underreported, problem. While injurious physical attacks on paramedics are generally reported, non-physical violence is less likely to be documented. Verbal abuse can be very distressing, particularly if the harassment targets personal or cultural identities, such as race, ethnicity, gender, or sexual orientation. Leveraging a novel, point-of-event reporting process, our objective was to estimate the prevalence of harassment on identity grounds against paramedics in a single paramedic service in Ontario, Canada, and assess its potentially differential impact on emotional distress. In an analysis of 502 reports filed between February 1, 2021, through February 28, 2022, two paramedic-supervisors independently coded the free-text narrative descriptions of violent encounters for themes suggestive of sexism, racism, and homophobia. We achieved high interrater agreement across the dimensions (k=0.73-0.83), and after resolving discrepant cases, we found that 1 in 4 violent reports documented abuse on at least one of the identity grounds. In these cases, paramedics were 60% more likely to indicate being emotionally distressed than for other forms of violence. Our findings offer unique insight into the type of vitriol paramedics experience in the course of their work and its potential for psychological harm.

Corrugated board, widely used in the packing industry, is a recyclable and durable material. Its strength and cushioning, influenced by geometry, environmental conditions like humidity and temperature, and paper quality, make it versatile. Double-walled (or five-ply) corrugated board, comprising two flutes and three liners, enhances these properties. This study introduces a novel approach to analyze 5-layered corrugated board, extending a previously published algorithm for single-walled boards. Our method focuses on measuring layer and overall board thickness, flute height, and center lines of each layer. Integrating image processing and genetic algorithms, the research successfully developed an algorithm for precise geometric feature identification of double-walled boards. Images were recorded using a special device with a sophisticated camera and image sensor for detailed corrugated board cross-sections. Demonstrating high accuracy, the method faced limitations only with very deformed or damaged samples. This research contributes significantly to quality control in the packaging industry and paves the way for further automated material analysis using advanced machine learning and image sensors. It emphasizes the importance of sample quality and suggests areas for algorithm refinement to enhance robustness and accuracy.

Urinary tract infections (UTIs) caused by Uropathogenic Escherichia coli (UPEC) are a serious healthcare concern that must be treated with appropriate antibiotic therapy. However, antibiotic resistance among UPEC strains is increasing, particularly among individuals with recurrent illness. The proliferation of Extended-Spectrum Beta-Lactamase (ESBL) generating UPEC, as well as the increase of UPEC strains that display resistance to several antimicrobial drugs, adds to the difficulty of managing UTIs. UPEC strain genetic variants have a significant influence in their capacity to resist antimicrobial agents and adapt to changing environments. Understanding the genomic landscape of developing UPEC strains is critical for understanding the genetic basis of their resistance. Furthermore, tracking these genetic strains is critical for identifying patterns of resistance spread, directing infection control efforts, and educating.

Chronic Fatigue Syndrome (CFS) can be triggered by different factors and create a complex health situation. In the last decades incidence has been increasing. This situation is a clear example of how humans, viruses, and the environment are all connected. In the 90s cases related to CFS, com-plaints about a feeling of chronic fatigue, inability for everyday tasks, dull pain, cephalalgia, de-pression, anxiety, poor concentration. Clinical tests for EBV, HHV, CMV, IgG, IgM, T4 and T8 subsets were tested, along with hormones and hemogram tests. Most of the cases were women. The timeline of the medical history showed also myomas, breast lumps, premenstrual syndrome previously to CFS development. The nature of these conditions promoted the idea of a possible common link among them and CFS. Some cases also suffered from allergies, food intolerances, candidiasis, intestinal impairment, thyroid implications, endometriosis. As an initial working hypothesis, The Liver Link (TLL) was proposed in order to understand those different conditions affecting body, mind and emotional wellbeing. Considering liver implication can make a differ-ence in treatment and recovery. Low grade inflammatory conditions are related to Th2 predom-inance and liver functions. Functional disharmonies are very important because they usually still do not appear in any conventional tests. In 2002, TLL was presented as a framework to explain the concomitance of CFS and other conditions and the relationship with some viruses such as EBV, HHV, CMV, as a lecture in a congress at the University of Westminster (London). When SARS-CoV-2 outbroke, TLL helped to warn about the post-covid syndrome more likely to occur in specific individuals.

Rectenna is the key component in radio-frequency circuits for receiving and converting electromagnetic waves into direct current. However, it is very challenging for the conventional semiconductor diode switches to rectify high-frequency signals for 6G telecommunication (>100 GHz), medical detection (>THz) and rectenna solar cells (optical frequencies). Such a major challenge can be resolved by replacing the conventional semiconductor diodes with tunneling diodes as the rectenna switches. In this work, metal-insulator-metal (MIM) tunneling diodes based on 2D insulating materials were designed, and their performance was evaluated using a comprehensive simulation approach which includes density-function-theory simulation of 2D insulator materials, modeling of the electrical characteristics of tunneling diodes, and circuit simulation for rectifiers. It is found that novel 2D insulators such as monolayer TiO2 can be obtained by oxidizing sulfur-metal layered materials. The MIM diodes based on such insulators exhibit fast tunneling and excellent current rectifying properties. Such tunneling diodes effectively convert the received high-frequency electromagnetic waves into direct current.

Human language and social cognition are two key disciplines that have traditionally been studied as separate domains. However, emerging research from detailed studies of comparative animal behavior, human social behavior, language acquisition in children, social cognitive neuroscience, and the cognitive neuroscience of language suggest that language and social cognition are two deeply interrelated capacities of the human species. For instance, recent developmental studies on the acquisition of language in infants and young children, draw attention to the important crucial benefits associated with several different aspects of social stimulation for youngsters, including the quantity and quality of linguistic input, dyadic infant/child-to-parent verbal and non-verbal social interactions, and other important social cues integral for facilitating language learning and social bonding. Studies of the adult human brain further suggest a high degree of specialization for sociolinguistic information processing, memory retrieval, and comprehension, suggesting the function of these regions may link language with social cognition and social bonding. In effect, the social brain and social complexity hypotheses may jointly help to explain how neurotypical children and adults learn language, why autistic adults and children exhibit simultaneous deficits in language and social cognition, and why nonhuman primates and other animals with significant computational abilities do not acquire the capacity for language. But perhaps most critically, the following article argues that this and related research will allow scientists to generate a holistic profile and deeper understanding of the healthy adult social brain, while developing more innovative and effective diagnoses, prognoses, and treatments for maladies and deficits also associated with the social brain.

The potentiality of cv. Malbec grape pomace (GP) as a functional ingredient in the formulation of bakery foods (muffins, biscuits and cereal bars) was studied. The effect of GP addition on the phenolic compounds (PCs) composition, nutritional and sensory properties were evaluated. The addition of GP increased the content of dietary fiber, proteins, ash, total phenolic content (TPC), antioxidant activity (AA), anthocyanins and non-anthocyanins PCs while decreasing the carbohydrates content. The main PCs given by the GP to supplemented foods were (-)-gallocatechin, quercetin-3-O-glucoside, rutin, caffeic acid, syringic acid and (+)-catechin. For anthocyanins, the acylated derivatives were more stable to heat treatment (baking) in food processing which was evidenced by a higher proportion of these PCs compounds when compared to the same derivatives quantified in GP. In general, when the TPC or individual concentrations of PCs were analyzed in a nutritional or functional context, one portion of the supplemented foods showed levels high enough to satisfy the recommended dose per day of these bioactive compounds. Additionally, the foods were well received by consumers during the sensory evaluation and supplemented biscuits got the highest acceptability. This study demonstrated that GP could be a viable functional ingredient in bakery foods to give nutritionally enhanced properties like TPC, PCs, AA and dietary fiber in consumer’s diets.

Streptomyces sp. HNS054, which was previously isolated from a marine sponge, demonstrates vigorous growth and facile genetic modification. This study explores its potential as a marine ac-tinomycete chassis through complete genome sequencing and genetic engineering. With a 7.5 Mb genome containing 6678 predicted genes, 21 secondary metabolic biosynthetic gene clusters (BGCs), and 8 common site-specific recombination (SSR) system attB loci, HNS054 shows a close phylogenetic relation to S. griseoincarnatus strain RB7AG. Utilizing multiplexed site-specific ge-nome engineering (MSGE) and the CRISPR/Cas9 method, engineered strains derived from HNS054 (with three copies of the target BGCs) produce higher amounts of aborycin and ac-tinorhodin than S. coelicolor M1346 (containing three copies of the same BGCs). HNS054 stands out for its remarkable characteristics, including salt tolerance, rapid growth, and compatibility with synthetic biology tools, and positions it as a promising candidate for developing marine ac-tinomycete hosts to enhance secondary metabolite production.

Gliomas are central nervous system (CNS) derived tumors that originate from glial cells and affect six per 100,000 people in the United States. They are the most common form of CNS neoplasm and are highly diffusely infiltrative to surrounding brain tissue. Gliomas of diffusive nature are classified into different subcategories: astrocytomas, oligodendrogliomas, and ependymomas. Computed tomography (CT) and Magnetic Resonance Imaging (MRI) are used to determine tumor category and spread which may dictate treatment options. This paper focuses on emerging treatments of chemotherapy management with temozolomide and Avastin as well as emerging immune modulation treatment with vaccinations, manipulation of cellular checkpoints CTLA-4 and PD-1, co-receptor modulation of neuropilin-1, CAR-T cell therapy, and CRISPR-Cas9 gene editing. The employment of TMZ and BEV has been supported in the literature, however, more research is necessitated to fully optimize regimens and to avoid immune- and toxicity-related effects of these drugs. Moreover, an even closer consideration is warranted for current immunotherapies as they are in their infancy compared to TMZ and BEV. Thus, although promising emerging treatment options, therapies involving cancer vaccines, ICIs, immune modulation of neuropilin-1, CAR-T, and CRISPR-Cas9 technology require further investigation into their long-term efficacy and utility in treating gliomas.

Radiotherapy is a crucial treatment for head and neck malignancies, but it usually leads to sensorineural hearing loss (SNHL). Changes in the immune microenvironment and sensorial neuroepithelium of the inner ear after radiation exposure remain poorly understood. This study investigated cochlear morphology and macrophages in the inner ear after high-dose irradiation. The heads of 8-week-old Cx3cr1GFP/+ heterozygous male mice were irradiated with 30Gy X-rays and biological samples were taken on the 1st, 7th, and 10th days after irradiation. Auditory brainstem responses were used to assess auditory function in mice. The changes of basal membrane hair cells, spiral ganglion (SGN), and inner ear macrophages were observed using hematoxylin-eosin (HE) staining and immunofluorescence staining. The expression of inflammatory mediators in the inner ear was detected by reverse transcription-polymerase chain reaction (RT-PCR) in cochlear tissue. As a result, there was no significant hair cell loss after high doses of radiation, but the mice developed full-frequency hearing loss on day 10 when HE staining revealed SGN atrophy and immunofluorescence revealed decreased neurofilament expression. The number of macrophages in the inner ear decreased over time. RT-PCR showed that cochlear inflammatory factors and chemokines were briefly up-regulated on the first day after irradiation and then decreased over time. In summary, high-dose irradiation causes acute SNHL that does not involve hair cell loss and may be associated with SGN changes. Radiation-induced SNHL is accompanied by a reduction in cochlear macrophages and changes in the immune microenvironment, but the relationship between the two has yet to be explored.

Cenobamate is approved by the European Medicine Agency for the treatment of adult patients with epilepsy (PWEs) who suffer from ongoing focal-onset seizures despite appropriate treatment with at least two established antiseizure medications. Pivotal trials and post-marketing real-world observational studies have suggested a high efficacy with unusually high seizure-free rates. We sought to investigate the serum trough levels of cenobamate under steady-state conditions in seizure-free versus non-responding PWEs, and in PWEs who experienced adverse events versus those who did not. We analyzed samples from 101 PWEs treated with adjunct cenobamate under steady-state conditions. In all, 36 PWEs were seizure-free and 65 were non-responders. In 31 PWEs, adverse events were apparent, whereas in the remaining 70, no tolerability issues were reported. We found a linear correlation between the daily doses (range: 100 mg – 400 mg) and the plasma levels (3.8 mg/l – 54.6 mg/l). Neither the daily doses nor the plasma levels differed significantly between seizure-free and non-responding PWEs or between PWEs with a satisfactory tolerability and those who experienced adverse events. The main reason for this result was that the individual therapeutic ranges varied widely: seizure freedom and adverse effects were observed alongside low doses and plasma levels in some PWEs. Conversely, there were examples of PWEs who did not respond or who reported no tolerability issues at high doses or plasma levels. Still, to evaluate the individual therapeutic range and to better understand the influence of other drugs in cases where concomitant medications are used, the therapeutic drug monitoring of cenobamate may be useful.

Obesity is associated with serious comorbidities and economic implications. Bariatric surgery, most commonly Roux-en-Y gastric bypass and sleeve gastrectomy, are effective options for weight loss and improvement of obesity-related comorbidities. With the growing obesity epidemic, there has been a concomitant rise in bariatric surgeries, particularly in sleeve gastrectomy, which has been the most widely performed bariatric surgery since 2013. Gastroesophageal reflux disease (GERD) is highly prevalent in obese individuals, can significantly impact quality of life and may lead to serious complications. Obesity and GERD both improve with weight loss. However, as the incidence of sleeve gastrectomy rises, recent data has revealed a risk of exacerbation of pre-existing GERD or the development of de novo GERD following sleeve gastrectomy. We performed a detailed review of GERD post-sleeve gastrectomy, including its overall incidence, pathophysiology and current treatment paradigms.

Rural women constitute one of the most marginalized and vulnerable groups in the world. Despite playing a critical role in sustainable development and food security, they face systemic inequalities and structural constraints that limit their access to resources, services and opportunities. The purpose of this research is to identify advances and setbacks in the formulation of 17 SDG indicators for rural women. Systematic Review Registered in PROSPERO: CRD42023420583. Sixteen articles were included. Three indicators were identified: entrepreneurship, empowerment and gender equality. Due to its relevance in rural areas where women have an active role in family income through cooperatives, associations and companies to improve quality of life and that of their community, however, aspects of discrimination are still evident in gender and inequality in participation in economic spheres and decision making.

We are currently witnessing a strong global transition towards new, more sustainable models of development and consumption. This transition is both activating and highlighting a series of discrepancies between the various actors in agri-food marketing systems, including the institutions that govern regulatory and trade aspects. These discrepancies highlight how, on a global level, the agri-marketing system is unable to provide adequate responses to the new principles of sustainability that are increasingly expected by civil society. This inability is often linked to the phenomena of opportunism, information asymmetries and lock-in effects (resulting from the slowness or inability of some sectors or actors to evolve technologically and culturally). The control of all these factors is often ineffective and often involves high transaction costs . These conditions lead the global market into an ongoing state of failure, creating structural holes, in which new forms of exchange are born, in response to the principles mentioned above. We identify these as nested markets: hybrid market forms that, thanks to new information technologies, create a new form of proximity that transcends the classical concept of physical proximity. This new proximity directly links producers and consumers in relationships based mainly on two substantial values: reciprocity and reputation. Both of these values significantly reduce transaction costs which today play an increasing role in determining the form and repetition of exchanges. This condition is difficult to interpret from classical and neo-classical economic theories. To do so it is necessary to use a multidisciplinary approach. In this article we combine neo-institutional theory and network analysis to interpret phenomena that are increasingly emerging in all areas of the world. Using these two theories, and case studies from Brasil, North America, China and Europe, we try to highlight how the market is not only the place where the price of products and of their quantities are formed. Market is a complex social spaces, where more-or-less stable relationships are formed, based on the values of reciprocity and reputation that determine behaviour and codes of conduct aimed at containing opportunism and encouraging sustainable, autonomous, forms of self-regulation. These relationships are also the driving forces that ensure the ongoing continuation of the exchanges and the diffusion and preservation of knowledge over time and space. These relationships represent the beating heart of nested markets and their dynamic ability to adapt to the continuous changes that occur in the socio-economic and environmental context in which they are rooted. In this way sustainability is built as an expression of the co-production between different actors (producers, consumers, institutions) and natural resources.

IP Multimedia Subsystem (IMS) supports high-speed transmission of multi-media like data, audio, and video between mobiles and other wireless devices. IMS is the most suitable for multimedia communication across multiple networks using the Internet of Things (IoT) and cloud computing. IoT-IMS can efficiently manage the huge amount of data generated by smart devices for audio-video during live streaming applications. During these services, the main problem is that an intruder can launch a Session Initialization Protocol (SIP) messages flooding attack on IMS that does not have the functionality to prevent itself from these types of attacks. In this paper, an intrusion detecting and preventing system (IDPS) is proposed that effectively detects the register flooding and spoofing attacks using SIP messages. We proposed a watermark embedding algorithm on the user side and an extraction algorithm on receiving side. A test-bed is set up for IMS where we have considered four different scenarios to evaluate the IDPS approach as compared to counterparts. Results illustrate the dominance of our scheme in terms of response time, register flooding attack detection ratios, CPU load utilization, fault detection ratio, and memory utilization. The fault detection ratio averagely 98.18