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The gut microbiota, a complex ecosystem, is vital to host health as it aids digestion, modulates the immune system, influences metabolism, and interacts with the brain-gut axis. Various factors influence the composition of this microbiota. Enzymes, as essential catalysts, actively participate in biochemical reactions that have an impact on the gut microbial community, affecting both the microorganisms and the gut environment. Enzymes play an important role in the regulation of the intestinal microbiota, but the interactions between enzymes and microbial communities, as well as the precise mechanisms of enzymes, remain a challenge in scientific research. Enzymes serve both traditional nutritional functions, such as the breakdown of complex substrates into absorbable small molecules, and non-nutritional roles, which encompass antibacterial function, immunomodulation, intestinal health maintenance, and stress reduction, among others. This study categorizes enzymes according to their source and explores the mechanistic principles by which enzymes drive gut microbial activity, including the promotion of microbial proliferation, the direct elimination of harmful microbes, the modulation of bacterial interaction networks, and the reduction in immune stress. A systematic understanding of enzymes in regulating the gut microbiota and the study of their associated molecular mechanisms will facilitate the application of enzymes to precisely regulate the gut microbiota in the future and suggest new therapeutic strategies and dietary recommendations. In conclusion, this review provides a comprehensive overview of the role of enzymes in modulating the gut microbiota. It explores the underlying molecular and cellular mechanisms and discusses the potential applications of enzyme-mediated microbiota regulation for host gut health. Full article

Maintaining the physiological function of the vascular endothelium and endothelial glycocalyx is crucial for the prevention of cardiovascular disease, which is one of the leading causes of morbidity and mortality worldwide. Damage to these structures can lead to atherosclerosis, hypertension, and other cardiovascular problems, especially in individuals with risk factors such as diabetes and obesity. Endothelial dysfunction is associated with ischemic disease and has a negative impact on overall cardiovascular health. The aim of this review was to comprehensively summarize the crucial role of the vascular endothelium and glycocalyx in cardiovascular health and associated thrombo-inflammatory conditions. It highlights how endothelial dysfunction, influenced by factors such as diabetes, chronic kidney disease, and obesity, leads to adverse cardiovascular outcomes, including heart failure. Recent evidence suggests that hyperbaric oxygen therapy (HBOT) may offer therapeutic benefits in the treatment of cardiovascular risk factors and disease. This review presents the current evidence on the mechanisms by which HBOT promotes angiogenesis, shows antimicrobial and immunomodulatory effects, enhances antioxidant defenses, and stimulates stem cell activity. The latest findings on important topics will be presented, including the effects of HBOT on endothelial dysfunction, cardiac function, atherosclerosis, plaque stability, and endothelial integrity. In addition, the role of HBOT in alleviating cardiovascular risk factors such as hypertension, aging, obesity, and glucose metabolism regulation is discussed, along with its impact on inflammation in cardiovascular disease and its potential benefit in ischemia–reperfusion injury. While HBOT demonstrates significant therapeutic potential, the review also addresses potential risks associated with excessive oxidative stress and oxygen toxicity. By combining information on the molecular mechanisms of HBOT and its effects on the maintenance of vascular homeostasis, this review provides valuable insights into the development of innovative therapeutic strategies aimed at protecting and restoring endothelial function to prevent and treat cardiovascular diseases. Full article

Ebola virus (EBOV) causes severe disease in humans, with mortality as high as 90%. The small-molecule antiviral drug remdesivir (RDV) has demonstrated a survival benefit in EBOV-exposed rhesus macaques. Here, we characterize the efficacy of multiple intravenous RDV dosing regimens on survival of rhesus macaques 42 days after intramuscular EBOV exposure. Thirty rhesus macaques underwent surgical implantation of telemetry devices for the fine-scale monitoring of body temperature and activity, as well as central venous catheters, to enable treatment administration and blood collection. Treatment, consisting of a loading dose of RDV followed by once-daily maintenance doses for 11 days, was initiated 4 days after virus exposure when all animals were exhibiting disease signs consistent with incipient EBOV disease as well as quantifiable levels of EBOV RNA in plasma. In the RDV treatment groups receiving loading/maintenance doses of 5/2.5 mg/kg, 10/5 mg/kg, and 20/10 mg/kg, a total of 6 of 8 (75%), 7 of 8 (87.5%), and 5 of 7 (71.4%) animals survived, respectively. In the vehicle control group, one of seven animals (14.3%) survived. The improved survival rate compared to the control group was statistically significant only for the 10/5 mg/kg RDV treatment group. This treatment regimen also resulted in a significantly lower systemic viral load compared to the vehicle control after a single RDV treatment. All three RDV regimens produced a significantly lower systemic viral load after two treatments. For most animals, RDV treatment, regardless of dose, resulted in the amelioration of many of the clinical–pathological changes associated with EBOV disease in this model. Full article

Placental serotonin is recognized as a key component of feto-placental physiology and can be influenced by environmental factors such as maternal diet, drugs, stress, and immune activation. In this study, we compared the contribution of placental and fetal sources to the maintenance of serotonin levels required for normal fetal development during ontogenetic dynamics. Our results demonstrated the leading role of the placenta at almost all stages of development. We investigated the modulatory effect of inflammation on placental serotonin levels. The data obtained showed that the susceptibility to prenatal inflammation depends on its severity and varies considerably at different stages of development. According to our results, inflammation-induced modulation of placental serotonin levels can be prevented by immunoglobulin administration at both early and late stages of development. Disturbances in placental serotonin signaling during critical developmental periods may have long-lasting consequences for the health and behavior of the offspring. Therefore, the ability to prevent environmental modulation of placental serotonin, and hence negative effects on the developing fetus, is of great importance. Full article

Background/Objectives: People with multiple sclerosis (MS) often experience sensory, psychomotor, and cognitive impairment, sphincter disturbances, and fatigue, which can affect their ability to perform work-related tasks, self-care, and daily activities. This study aimed to analyze the lifestyle changes, cognitive function, and disability outcomes over a seven-year follow-up period, exploring potential associations with predictive markers. Methods: At the end of the seven-year follow-up period, 32 participants returned for cognitive and clinical reassessment with the Twenty-Five-Foot Walk Test, Nine-Hole Peg Test, and Brief Repeatable Neuropsychological Battery. Lifestyle data were acquired via interviews regarding sleep quality, reading habits, technology use, physical activity levels, household responsibilities, and participation in leisure and cultural activities. Results: The occupational profile did not demonstrate significant changes, but 11 (34%) participants showed disability accumulation, and the number of relapses increased (p = 0.001). Over time, improvement was observed in verbal episodic memory and worsening in psychomotor speed. Better cognitive performance in mental agility was associated with higher levels of physical activity (p = 0.021) and technology use (p = 0.039). In addition, better cognition (verbal memory p = 0.038 and processing speed 0.015) and psychomotor speed (upper limbs p = 0.017 and lower limbs p = 0.003) and lower functional disability (p = 0.022) were associated with maintenance of household activities. Conclusions: The changes in verbal memory and psychomotor speed were more prominent over time, and verbal memory, psychomotor and processing speed, and mental agility were associated with good lifestyle habits, mainly household activities. The treatment strategies should include lifestyle changes and pharmacological interventions. Full article

Background/Objectives: Standard chemotherapy is generally considered the best approach to treat many solid cancers, even accounting for severe side effects. Therefore, the development of a drug delivery system for chemotherapeutic administration could significantly improve standard chemotherapy by maintaining the cytotoxic effects of the drugs while decreasing the inherent side effects of the treatment. The aim of our study is the optimization of a loading strategy that conjugates the use of extracellular vesicles (EVs) as drug delivery carriers, by preserving their integrity, with the loading efficiency and activity maintenance of chemotherapeutics. Methods: We compared the EV loading of the chemotherapeutics epirubicin, mitomycin, methotrexate and mitoxantrone by co-incubation. Once loaded, the activity of drug-carrying EVs was tested on cancer cells and compared to that of free chemotherapeutics. Results: We defined a linear correlation between chemotherapeutics’ concentration and their absorbance at the drug-specific wavelength, which allowed the definition of a highly sensitive absorbance-based spectrophotometric quantification system, enabling the assessment of drug loading efficiency. Co-incubation of EVs and chemotherapeutics was sufficient to obtain quantifiable drug loading, and the efficacy of EV loading was drug-dependent. Epirubicin-loaded vesicles showed increased toxicity to bladder cancer cells with respect to the free chemotherapeutic. The cytotoxicity was maintained even upon 6-month storage at −80 °C of loaded EVs. Conclusion: We established an absorbance-based spectrophotometric quantification system that enables a straightforward measure of drug loading efficiency into EVs, and we demonstrated that chemotherapeutic-carrying EVs can be obtained by co-incubation, preserving and increasing drug cytotoxicity. Full article

With the Fourth Industrial Revolution unfolding worldwide, technologies including the Internet of Things, sensors, and artificial intelligence are undergoing rapid development. These technological advancements have played a significant role in the dramatic growth of the predictive maintenance market for mechanical equipment, prompting active research on noise removal techniques and classification algorithms for the accurate determination of the causes of equipment failure. In this study, time series data were preprocessed using the denoising autoencoder technique, a deep learning-based noise removal method, to improve the accuracy of failure classification from mechanical equipment data. To convert the preprocessed time series data into frequency components, the short-time Fourier transform technique was employed. The fault types of mechanical equipment were classified using the vision transformer (ViT) technique, a deep learning technique that has been actively used in recent image analysis research. Additionally, the classification performance of the ViT-based technique for vibration time series data was comparatively validated against existing classification algorithms. The accuracy of failure classification was the highest when the data, preprocessed using a Denoising Autoencoder (DAE), were classified by a Vision Transformer (ViT). Full article

Cisplatin-based platinum compounds are important clinical chemotherapeutic agents that participate in most tumor chemotherapy regimens. Through density-functional theory calculations, the formation and stability of the inorganic oxide carrier, the mechanisms of the hydrolysis reaction of the activated platinum compound, and its binding mechanism with DNA bases can be studied. The higher the oxidation state of Pt (II to IV), the more electrons transfer from the magnesia–gold composite material to the platinum compound. After adsorption on the composite carrier, 5d←2p coordination bonds of Pt-N are strengthened. For flat and oblique adsorption modes of cisplatin, there is no significant difference in the density of states of the gold and magnesium oxide film, indicating the maintenance of the heterojunction structural framework. However, there are significant changes in the electronic states of cisplatin itself with different adsorption configurations. In the flat configuration, the band gap width of cisplatin is larger than that of the oblique configuration. The Cl-Pt bond range in the Pt(III) compound shows a clear charge reduction on the magnesia film, indicating the Cl-Pt bond is an active site with the potential for decomposition and hydrolysis. The substitution of chloride ions by water can lead to hydrolysis products, enhancing the polarization of the composite and showing strong charge separation. The hydrolysis of the free platinum compound is endothermic by 0.309 eV, exceeding the small activation energy barrier of 0.399 eV, indicating that hydrolysis of this platinum compound is easily achievable. ADME (absorption, distribution, metabolism, and excretion) prediction parameters indicate that hydrolysis products have good ESOL (Estimated SOLubility) solubility and high gastrointestinal absorption, consistent with Lipinski’s rule. During the coordination reaction process, there are significant changes in the distribution of frontier molecular orbitals, with the HOMO (highest occupied molecular orbital) of the initial state primarily located on the purine base, providing the possibility for electron transfer to the empty orbitals of the platinum compound in the LUMO (lowest unoccupied molecular orbital). The HOMO and HOMO-1 of the transition state and product are mainly distributed on the platinum compound, indicating clear electron transfer and orbital rearrangement. The activation energy barrier for the purine coordination reaction with the hydrolysis products is reduced to 0.61 eV, and the dipole moment gradually decreases to 6.77 Debye during the reaction, indicating a reduction in the system’s charge separation and polarization. This contribution is anticipated to provide a new theoretical clue for developing inorganic oxide carriers of platinum compounds. Full article

The Wilms’ tumor suppressor WT1 is essential for the development of the heart, among other organs such as the kidneys and gonads. The Wt1 gene encodes a zinc finger transcription factor that regulates proliferation, cellular differentiation processes, and apoptosis. WT1 is also involved in cardiac homeostasis and repair. In adulthood, WT1-expression levels are lower compared to those observed through development, and WT1 expression is restricted to a few cell types. However, its systemic deletion in adult mice is lethal, demonstrating that its presence is also key for organ maintenance. In response to injury, the epicardium re-activates the expression of WT1, but little is known about the roles it plays in cardiomyocytes, which are the main cell type affected after myocardial infarction. The fact that cardiomyocytes exhibit a low proliferation rate in the adult heart in mammals highlights the need to explore new approaches for cardiac regeneration. The aim of this review is to emphasize the functions carried out by WT1 in cardiomyocytes in cardiac homeostasis and heart regeneration. Full article

Epstein–Barr virus is highly associated with nasopharyngeal carcinoma (NPC) with genes expressed for tumor transformation or maintenance of viral latency, but there are certain genes that can modulate immune molecules. Butyrophilin 2A1 (BTN2A1) is an important activating protein for presenting phosphoantigens for recognition by Vγ9Vδ2 T cells to achieve antitumor activities. We have previously shown that Vγ9Vδ2 T cells achieve efficacy against NPC when BTN2A1 and BTN3A1 are upregulated by stimulating EBV gene expression, particularly LMP1. While BTN3A1 can be induced by the LMP1-mediated IFN-γ/JNK/NLRC5 pathway, the viral gene that can regulate BTN2A1 remains elusive. We showed that BTN2A1 expression is directly mediated by EBV BRRF1, which can trigger the BTN2A1 promoter and downstream JAK3-STAT3 pathway in NPC43 cells, as shown by RNA-seq data and verified via inhibitor experiments. Furthermore, BRRF1 downregulated IL-22 binding protein (IL-22RA2) to complement the EBNA1-targeting probe (P₄)-induced IL-22 expression. Therefore, this study elucidated a new mechanism of stimulating BTN2A1 expression in NPC cells via the EBV gene BRRF1. The JAK3-STAT3 pathway could act in concordance with IL-22 to enhance the expression of BTN2A1, which likely leads to increased tumor cell killing by Vγ9Vδ2 T cells for enhanced potential as immunotherapy against the cancer. Full article

The expansion of urban areas and unsustainable land use associated with human activities have brought about a decline in habitat quality (HQ), especially in arid regions with fragile ecosystems. A precise prediction of land use and habitat quality changes across different scenarios is crucial for the sustainable maintenance of ecological diversity. In this article, the InVEST model was employed to assess both the quality and degradation levels of habitats in the Turpan–Hami Basin (THB) spanning 1990~2020. Additionally, the InVEST-PLUS coupling model was employed to forecast habitat conditions under three different scenarios in 2050. Specifically, it involved the comparison of land use changes and spatial distribution of HQ across natural development (ND) scenarios, town development (UD) scenarios, and ecological protection (EP) scenarios, along with the analysis of hot spots of HQ spanning 1990~2050. The outcomes revealed the following: (1) The primary land use in the THB was categorized as unused land, alongside notable expansions in cultivated land, grassland, and built-up land. Conversely, there was a considerable decline observed in forests, water bodies, and unused land spanning 1990~2020. (2) The HQ within the THB exhibited evident spatial clustering characteristics. Between 1990 and 2020, areas with low HQ accounted for over 85%, areas with unchanged HQ constituted 88.19%, areas experiencing deteriorated HQ comprised approximately 5.02%, and areas displaying improved HQ encompassed around 6.79%. (3) Through the comparison of HQ for the ND, UD, and EP scenarios in 2050, it was observed that the average HQ under the EP scenario ranked highest, exhibiting the lowest degree of degradation on average. This indicates that the EP scenario is most advantageous for preserving HQ. Conclusively, this research provides valuable viewpoints for making decisions aimed at enhancing HQ in ecologically fragile arid regions. Full article

Different life histories result in different strategies to allocate energy in biosynthesis, including growth and reproduction, and somatic maintenance. One of the most notable life history differences between Lepidoptera and Blattodea species is that the former grow much faster than the latter, and during metamorphosis, a large amount of tissue in Lepidoptera species disintegrates. In this review, using Lepidoptera caterpillars and cockroach nymphs as examples, we show that, due to these differences in growth processes, cockroach nymphs spend 20 times more energy on synthesizing one unit of biomass (indirect cost of growth) than butterfly caterpillars. Because of the low indirect cost of growth in caterpillars, the fraction of metabolic energy allocated to growth is six times lower, and that for maintenance is seven times higher in caterpillars, compared to cockroach nymphs, despite caterpillar’s higher growth rates. Moreover, due to the higher biosynthetic energy cost in cockroach nymphs, they have better cellular qualities, including higher proteasomal activity for protein quality control and higher resistance to oxidative stress. We also show that under food restriction conditions, the fraction of assimilated energy allocated to growth was reduced by 120% in cockroach nymphs, as they lost body weight under food restriction, while this reduction was only 14% in hornworms, and the body mass increased at a lower rate. Finaly, we discuss future research, especially the difference in adult lifespans associated with the energetic differences. Full article

Background/Objectives: The aim of this study is to shed light on activity-based prospective memory upon the awakening and its association with motor sleep inertia in different phenotypes of insomnia disorder. Methods: To this end, 67 patients with insomnia and 51 healthy controls took part in the study. After enrollment, previously proposed actigraphic quantitative criteria were adopted, and the following phenotypes of insomnia disorder were observed in the patient sample: sleep onset (n = 12), maintenance (n = 19), mixed (n = 17), and negative misperception (n = 19). Each participant had used the Micro Motionlogger Watch (Ambulatory Monitoring, Inc., Ardsley, NY, USA) actigraph for one week. Actigraphic recording allowed for a description of both the activity-based prospective memory performance upon the awakening—by computing the time interval between sleep end and the time participants actually remembered to push the event-marker button of the actigraph—and the motor sleep inertia, i.e., the mean motor activity, minute-by-minute, in the first 60 min after sleep end in the morning. Results: Compared to healthy controls, a longer time interval was observed between sleep end and activity-based prospective memory performance in patients with mixed and maintenance insomnia. Moreover, a significant association was highlighted between motor sleep inertia and the activity-based prospective memory performance: higher levels of motor activity in those who remembered to perform the memory task early after sleep end, that spread over a longer time interval in maintenance and mixed insomnia. Conclusions: Overall, the present results seem to highlight a more marked cognitive inertia in patients with mixed and maintenance insomnia as well as a significant association between motor and cognitive inertia that spreads over a different time interval according to the phenotype of insomnia. Full article

Acne, a commonly treated skin disease, requires control of one’s daily routine for an optimal outcome. As skincare products continue to advance, and with the introduction of dermocosmetics (active cosmetics, functional cosmetics, cosmeceuticals), it is necessary for clinicians to stay updated and give professional guidance. Following a literature review, a panel discussed and, using an online review process, explored the available acne dermocosmetics and convened to develop consensus statements on acne skincare incorporating patient- and treatment-related factors. Recommendations tailored to several distinct patient subgroups, namely, preadolescent acne, adolescent/adult acne, acne with comorbid atopic dermatitis, acne in pregnancy, drug-induced acne, and acne cosmetica, were generated to maximize the use of dermocosmetics in acne management. In adolescent and adult acne, products with active ingredients that mark key aspects of acne pathophysiology are called for; in atopics, agents which protect and restore the skin barrier are primarily considered; and in the preadolescent age group and pregnant and lactating women, the use of acne dermocosmetics should be prioritized as there are limited treatment options. While skincare alone is often sufficient for mild acne and for maintenance, adjunctive skincare can enhance treatment efficacy as well as patient adherence in various settings. This guideline seeks to offer insights into acne dermocosmetics and provide skincare recommendation tailored to Asian patient subgroups. Full article

The progressive development of resistance in Neisseria gonorrhoeae to almost all available antibiotics has made it crucial to develop novel approaches to tackling multi-drug resistance (MDR). One of the primary causes of antibiotic resistance is the over-expression of the MtrCDE efflux pump protein, making this protein a vital target for fighting against antimicrobial resistance (AMR) in N. gonorrhoeae. This study was aimed at evaluating the potential MtrCDE efflux pump inhibitors (EPIs) and their stability in treating gonorrhoea infection. This is significant because finding novel EPIs would allow for the longer maintenance of antibiotics at therapeutic levels, thereby prolonging the susceptibility of currently available antibiotics. A virtual screening of the selected Helichrysum populifolium compounds (4,5-dicaffeoylquinic acid, apigeninin-7-glucoside, and carvacrol) was conducted to evaluate their potential EPI activity. An integrated computational framework consisting of molecular docking (MD), molecular mechanics generalized born, and surface area solvation (MMGBSA) analysis, molecular dynamics simulations (MDS), and absorption, distribution, metabolism, and excretion (ADME) properties calculations were conducted. Of the tested compounds, 4,5-dicaffeoylquinic acid revealed the highest molecular docking binding energies (−8.8 kcal/mol), equivalent MMGBSA binding free energy (−54.82 kcal/mol), indicative of consistent binding affinity with the MtrD protein, reduced deviations and flexibility (root mean square deviation (RMSD) of 5.65 Å) and, given by root mean square fluctuation (RMSF) of 1.877 Å. Carvacrol revealed a docking score of −6.0 kcal/mol and a MMGBSA computed BFE of −16.69 kcal/mol, demonstrating the lowest binding affinity to the MtrD efflux pump compared to the remaining test compounds. However, the average RMSD (4.45 Å) and RMSF (1.638 Å) of carvacrol-bound MtrD protein showed no significant difference from the unbound MtrD protein, except for the reference compounds, implying consistent MtrD conformation throughout simulations and indicates a desirable feature during drug design. Additionally, carvacrol obeyed the Lipinski rule of five which confirmed the compound’s drug-likeness properties making it the most promising EPI candidate based on its combined attributes of a reasonable binding affinity, sustained stability during MDS, its obedience to the Lipinski rule of five and compliance with drug-likeness criteria. An in vitro validation of the potential EPI activities of H. populifolium compounds confirmed that 4,5-dicaffeoylquinic acid reduced the expulsion of the bis-benzimide dye by MtrCDE pump, while carvacrol showed low accumulation compared to other compounds. While 4,5-dicaffeoylquinic acid demonstrated the highest binding affinity in computational analysis and an EPI activity in vitro, it showed lower stability compared to the other compounds, as indicated in MDS. This leaves carvacrol, as a better EPI candidate for the management of gonorrhoea infection. Full article