Beneficial Effects Research Articles

Gene-edited cells: novel allogeneic gene/cell therapy for epidermolysis bullosa.

Epidermolysis bullosa (EB) is a group of rare genetic skin fragility disorders, which are hereditary. These disorders are associated with mutations in at least 16 genes that encode components of the epidermal adhesion complex. Currently, there are no effective treatments for this disorder. All current treatment approaches focus on topical treatments to prevent complications and infections. In recent years, significant progress has been achieved in the treatment of the severe genetic skin blistering condition known as EB through preclinical and clinical advancements. Promising developments have emerged in the areas of protein and cell therapies, such as allogeneic stem cell transplantation; in addition, RNA-based therapies and gene therapy approaches have also become a reality. Stem cells obtained from embryonic or adult tissues, including the skin, are undifferentiated cells with the ability to generate, maintain, and replace fully developed cells and tissues. Recent advancements in preclinical and clinical research have significantly enhanced stem cell therapy, presenting a promising treatment option for various diseases that are not effectively addressed by current medical treatments. Different types of stem cells such as primarily hematopoietic and mesenchymal, obtained from the patient or from a donor, have been utilized to treat severe forms of diseases, each with some beneficial effects. In addition, extensive research has shown that gene transfer methods targeting allogeneic and autologous epidermal stem cells to replace or correct the defective gene are promising. These methods can regenerate and restore the adhesion of primary keratinocytes in EB patients. The long-term treatment of skin lesions in a small number of patients has shown promising results through the transplantation of skin grafts produced from gene-corrected autologous epidermal stem cells. This article attempts to summarize the current situation, potential development prospects, and some of the challenges related to the cell therapy approach for EB treatment.

Sports Activities in Children with Cerebral Palsy: A Narrative Review.

Physical exercise is known to have beneficial effects on psychosocial well-being and cognitive performance. Children with cerebral palsy (CP) showed lower levels of physical activity (PA) than healthy children; this fact, in addition to the basic clinical condition, increased the sedentary habit with a psychological impact and motor impairment of these children. Furthermore, children and adolescents with CP are less committed to sports activities than typically developing children of the same age. The aim of the present narrative review was to increase the amount of knowledge regarding the effectiveness and importance of specific and individualized sports in children with CP. A comprehensive search of MED-LINE and EMBASE databases was performed, including specific search terms such as "cerebral palsy" combined with "sport", "physical activity", and the names of different sports. No publication date limits were set. We included studies with an age range of 0-18 years. The main results pointed out that most of the sports improved motor function, quality of life, and coordination in children and adolescents with CP. Physicians, therapists, and parents should become aware of the benefits of sports activities for this population of patients. Specific sports activities could be included as a usual indication in clinical practice in addition to rehabilitation treatment.

Protective effects of docosahexaenoic acid supplementation on cognitive dysfunction and hippocampal synaptic plasticity impairment induced by early postnatal PM2.5 exposure in young rats.

PM2.5 exposure is a challenging environmental issue that is closely related to cognitive development impairment; however, currently, relevant means for prevention and treatment remain lacking. Herein, we determined the preventive effect of docosahexaenoic acid (DHA) supplementation on the neurodevelopmental toxicity induced by PM2.5 exposure. Neonatal rats were divided randomly into three groups: control, PM2.5, and DHA + PM2.5 groups. DHA could ameliorate PM2.5-induced learning and memory dysfunction, as well as reverse the impairment of hippocampal synaptic plasticity, evidenced by enhanced long-term potentiation, recovered synaptic ultrastructure, and increased expression of synaptic proteins. Moreover, DHA increased CREB phosphorylation and BDNF levels and attenuated neuroinflammation and oxidative stress, reflected by lower levels of IBA-1, IL-1β, and IL-6 and increased levels of SOD1 and Nrf2. In summary, our findings demonstrated that supplementation of DHA effectively mitigated the cognitive dysfunction and synaptic plasticity impairment induced by early postnatal exposure to PM2.5. These beneficial effects may be attributed to the upregulation of the CREB/BDNF signaling pathway, as well as the reduction of neuroinflammation and oxidative stress.

Effect of Vermicompost and Nitrogen Fertilizer on the Growth and Production of Aloe Vera

Purpose: The effect of vermicompost and nitrogen fertilizers on the growth and production of Aloe vera were conducted using factorial based on Randomized Complete Block Design (RCBD).
 Background: Vermicompost can be used in sustainable agriculture to support growing populations by increasing water holding capacity, nutrient supply, high porosity, adequate ventilation and drainage, and production of plant hormones that have beneficial effects on seed germination.
 Methods: According to the RCBD method, treatments were included: four levels of vermicompost (V0: Control, V1: 75, V2: 150 and V3: 200 g per pot) and four levels of nitrogen fertilizer (N0: control, N1: 500, N2: 1000, and N3: 1500 mg per pot) using urea.
 Results: The results showed that application of 150 g of vermicompost and 1000 mg of nitrogen had the highest effect on growth traits, and application of 200 g of vermicompost and 1500 mg of nitrogen had the greatest effect on sucker characteristics, so that the highest number of suckers was obtained by using 200 g of vermicompost and 1000 and 1500 mg of nitrogen. However, simultaneous application of 150 g of vermicompost and 1000 mg of nitrogen had the greatest effect on plant height, number of leaves, and leaf diameter, and treatment with 200 g of vermicompost and 1500 mg of nitrogen had the greatest effect on the number of suckers, stem weight, number of leaves, sucker height, total biomass and Aloin content.
 Conclusions: Therefore, simultaneous use of vermicompost and nitrogen fertilizer in Aloe vera cultivation plays an important role in the production and enhancement of sucker and plant yield.

Evaluating Strategies to Enhance Li Transference in Salt-in-Ionic Liquid Electrolytes: Mixed Anions, Coordinating Cations, and High Salt Concentration.

The increased safety of salt-in-ionic liquid electrolytes compared with established carbonate-based systems has promoted intense research in this field, but low conductivities, slow lithium transport, and unfavorable lithium anion correlations still prevent a mass market application. In particular, strong Li-anion correlations lead to dominant vehicular Li transport with the same drift direction for anions and lithium in the electric field. Here, three different strategies and their mutual interplay are evaluated, which could reduce Li-anion coordination, i.e., high salt concentration, a mixed-anion composition, as well as an ether functionalization of the organic cation. To this end, two series of highly concentrated IL-based electrolytes, based on either ethylmethylimidazolium (EMIM) or the ether-functionalized 1-methoxyethyl-1-methylpyrrolidinium (Pyr12O1) organic cation, and employing mixed bis(fluorosulfonyl)imide/bis(trifluoromethylsulfonyl)imide (FSI/TFSI) anions are investigated. Measurements of conductivities, diffusion coefficients, and electrophoretic mobilities reveal no beneficial effect due to the increased heterogeneity of the FSI/TFSI-based electrolyte matrix, generally showing improved transport properties with increasing FSI share. However, a combination of both the ether-functionalized cation and high FSI content is proven successful, as lithium mobilities are positive, and vehicular transport is overcome by structural Li transport. Our study demonstrates the decisive role of synergy of the different approaches: While the single effect of a high salt concentration, weakly lithium-coordinating anions, or organic cations with lithium-affine functional groups is too weak to prevent vehicular transport, their joint effect can overcome vehicular Li transport, leading to improved Li conduction in ionic liquids.

Physical exercise: a polypill against chronic kidney disease.

We are currently facing a pandemic of physical inactivity that might contribute to the growing prevalence of chronic kidney disease (CKD). Here, we summarize currently available evidence on the association between physical activity and CKD, and also review the effects of exercise intervention in affected patients. Physical activity/exercise might act as a polypill against CKD, preventing its development or even exerting beneficial effects once it is established (i.e. improvements in patients' physical fitness and cardiovascular risk, as well as in kidney function). Exercise benefits are also found at advanced CKD stages or in patients under hemodialysis. The biological mechanisms behind the clinical evidence are also discussed. An active lifestyle appears as a cornerstone in CKD prevention and management.

Effect of high-dose vitamin C on renal ischemia-reperfusion injury

Acute kidney injury frequently occurs after cardiac surgery, and is primarily attributed to renal ischemia-reperfusion (I/R) injury and inflammation from surgery and cardiopulmonary bypass. Vitamin C, an antioxidant that is often depleted in critically ill patients, could potentially mitigate I/R-induced oxidative stress at high doses. We investigated the effectiveness of high-dose vitamin C in preventing I/R-induced renal injury. The ideal time and optimal dosage for administration were determined in a two-phase experiment on Sprague–Dawley rats. The rats were assigned to four groups: sham, IRC (I/R + saline), and pre- and post-vitC (vitamin C before and after I/R, respectively), with vitamin C administered at 200 mg/kg. Additional groups were examined for dose modification based on the optimal timing determined: V100, V200, and V300 (100, 200, and 300 mg/kg, respectively). Renal I/R was achieved through 45 min of ischemia followed by 24 h of reperfusion. Vitamin C administration during reperfusion significantly reduced renal dysfunction and tubular damage, more than pre-ischemic administration. Doses of 100 and 200 mg/kg during reperfusion reduced oxidative stress markers, including myeloperoxidase and inflammatory responses by decreasing high mobility group box 1 release and nucleotide-binding and oligomerization domain-like receptor 3 inflammasome. Overall beneficial effect was most prominent with 200 mg/kg. The 300 mg/kg dose, however, showed no additional benefits over the IRC group regarding serum blood urea nitrogen and creatinine levels and histological evaluation. During reperfusion, high-dose vitamin C administration (200 mg/kg) significantly decreased renal I/R injury by effectively attenuating the major triggers of oxidative stress and inflammation.

Engineered MgO nanoparticles for cartilage-bone synergistic therapy.

The emerging therapeutic strategies for osteoarthritis (OA) are shifting toward comprehensive approaches that target periarticular tissues, involving both cartilage and subchondral bone. This shift drives the development of single-component therapeutics capable of acting on multiple tissues and cells. Magnesium, an element essential for maintaining skeletal health, shows promise in treating OA. However, the precise effects of magnesium on cartilage and subchondral bone are not yet clear. Here, we investigated the therapeutic effect of Mg2+ on OA, unveiling its protective effects on both cartilage and bone at the cellular and animal levels. The beneficial effect on the cartilage-bone interaction is primarily mediated by the PI3K/AKT pathway. In addition, we developed poly(lactic-co-glycolic acid) (PLGA) microspheres loaded with nano-magnesium oxide modified with stearic acid (SA), MgO&SA@PLGA, for intra-articular injection. These microspheres demonstrated remarkable efficacy in alleviating OA in rat models, highlighting their translational potential in clinical applications.

SGLT2 inhibitors: from glucose-lowering to cardiovascular benefits.

An increasing number of individuals are at high risk of type 2 diabetes (T2D) and its cardiovascular complications, including heart failure (HF), chronic kidney disease (CKD), and eventually premature death. The sodium-glucose co-transporter-2 (SGLT2) protein sits in the proximal tubule of human nephrons to regulate glucose reabsorption and its inhibition by gliflozins represents the cornerstone of contemporary T2D and HF management. Herein, we aim to provide an updated overview of the pleiotropy of gliflozins, provide mechanistic insights and delineate related cardiovascular (CV) benefits. By discussing contemporary evidence obtained in preclinical models and landmark randomized controlled trials, we move from bench to bedside across the broad spectrum of cardio- and cerebrovascular diseases. With landmark randomized controlled trials confirming a reduction in major adverse CV events (MACE; composite endpoint of CV death, non-fatal myocardial infarction, and non-fatal stroke), SGLT2 inhibitors strongly mitigate the risk for heart failure hospitalization in diabetics and non-diabetics alike while conferring renoprotection in specific patient populations. Along four major pathophysiological axes (i.e. at systemic, vascular, cardiac, and renal levels), we provide insights into the key mechanisms that may underlie their beneficial effects, including gliflozins' role in the modulation of inflammation, oxidative stress, cellular energy metabolism, and housekeeping mechanisms. We also discuss how this drug class controls hyperglycaemia, ketogenesis, natriuresis, and hyperuricaemia, collectively contributing to their pleiotropic effects. Finally, evolving data in the setting of cerebrovascular diseases and arrhythmias are presented and potential implications for future research and clinical practice are comprehensively reviewed.

Schizophrenia and Nicotine - A Bittersweet Psychiatric Story

Abstract Background: Schizophrenia is a chronic mental disorder affecting mood, perception, and most importantly cognition. This severely interferes with the functioning of such patients. On the other hand, nicotine use (both smoke and smokeless tobacco) is very much prevalent in schizophrenic patients, much more than normal population. This study aims to find the relation between nicotine use and cognition in schizophrenic patients. Methodology: Fifty-six new patients diagnosed with schizophrenia of both sexes between ages 18 and 60 years, giving valid and informed consent, were selected for the study. Fagerstrom test for nicotine dependence was done and the patients were divided into two groups: scores 4 or less (low-to-moderate dependence) and scores 5 or more (severe dependence). The Cognitive Assessment Interview was performed. Then, an independent sample t-test was used to compare the scores on various cognitive domains between the two groups. Results: The cognitive scores were better in the group with severe tobacco dependence, both globally and across individual domains. These associations were statistically significant (P = 0.001). The mean difference was highest in the social cognition group. Among all the domains, the t-value was highest for the speed of processing domain, indicating that this particular cognitive domain has the best discriminative value when compared between two groups of nicotine users. Conclusions: Hence, to conclude, whether nicotine has indeed a beneficial effect on cognition in schizophrenia has to be investigated longitudinally so that a possible treatment option to address cognitive impairment in schizophrenia is obtained. Extensive longitudinal studies needs to be conducted to better understand the long-term effect of tobacco use and cognition in schizophrenia patients.

Therapeutic Potential of Diosgenin in Amelioration of Carbon Tetrachloride-Induced Murine Liver Injury.

Diosgenin is a sapogenin with antidiabetic, antioxidant, and anti-inflammatory properties. The current study investigated whether diosgenin could ameliorate carbon tetrachloride (CCL4)-induced liver injury. To cause liver injury, CCL4 was injected intraperitoneally twice a week for 8 weeks. Daily oral administration of diosgenin at doses of 20, 40, and 80 mg/kg was started one day before CCL4 injection and continued for 8 weeks. Finally, serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and also albumin were assessed. Catalase and superoxide dismutase (SOD) activities in addition to glutathione (GSH) and malondialdehyde (MDA) levels were also quantified in the liver homogenate and routine histological evaluation was also conducted. Elevated serum levels of liver enzymes and decreased serum level of albumin caused by CCL4 were significantly restored following diosgenin administration at doses of 40 and 80 mg/kg. Long-term administration of CCL4 increased inflammatory and apoptotic factors such as IL-1β, caspase 3, TNF-α, and IL-6 and decreased SOD and catalase activities as well as GSH level in liver homogenates; while MDA level was increased. Treatment with diosgenin increased SOD and catalase activities and GSH levels in the liver of injured animals. In addition, liver MDA, IL-1β, caspase 3, TNF-α, and IL-6 level or activity decreased by diosgenin treatment. Additionally, diosgenin aptly prevented aberrant liver histological changes. According to obtained results, diosgenin can dose-dependently diminish CCl4-induced liver functional deficits and histological changes in a dose-dependent manner, possibly due to its antioxidant and anti-inflammation properties, and its beneficial effect is comparable to known hepatoprotective agent silymarin.

Long-term analysis of a psychoeducational course on university students’ mental well-being

AbstractAlthough many higher educational institute (HEI) psychoeducational courses teaching positive psychology interventions report benefits to mental well-being upon completion, they have not typically addressed whether such beneficial effects are sustained long-term beyond the period of the courses. Here, we report a pre-registered follow-up of 228 undergraduate students, from a variety of disciplines, who took a positive psychology course 1 or 2 years previously. Overall, group analysis revealed that students who had taken the course did not continue to show the originally reported benefits at follow-up. Students who had taken the course scored higher on mental well-being than other students tested using a university-wide survey, but they were also higher at baseline 1–2 years earlier indicating a sampling bias. An exploratory analysis, however, revealed that 115 students (51% of the group) who had continued to practice the recommended activities taught during the course maintained their increased mental well-being over the period of follow-up. We therefore suggest that continued engagement is a key factor in sustaining the long-term benefits of positive psychology courses. Implementation of such courses should therefore include provision and mechanisms for maintaining future student engagement.

Blockade of sympathetic ganglia improves vascular dysfunction in septic shock.

Sepsis/septic shock activates the sympathetic nervous system (SNS) to deal with the infection stress. However, an imbalanced or maladaptive response due to excessive or uncontrolled activation characterizes autonomic dysfunction. Our hypothesis was that reducing this excessive activation of the autonomic nervous system would impact positively in sepsis. Using ganglionic blockers as a pharmacological approach, the main aim of the present report was to assess the role of ganglionic transmission in the vascular dysfunction associated with sepsis.Sepsis was induced in rats by cecal ligation and puncture (CLP). One hour after CLP surgery, rats were treated subcutaneously with hexamethonium (15 mg/kg; ganglionic blocker), pentolinium (5 mg/kg; a blocker with a higher selectivity for sympathetic ganglia compared to hexamethonium), or vehicle (PBS). Basal blood pressure and the response to adrenergic agonists were evaluated at 6 and 24 h after CLP surgery. Reactivity to vasoconstrictors, nitric oxide (NO) synthase 2 (NOS-2) expression, IL-1 and TNF plasma levels, and density of α1 adrenergic receptors were evaluated in the aorta 24 h after CLP.Septic shock resulted in hypotension and hyporesponsiveness to norepinephrine and phenylephrine, increased plasma cytokine levels and NOS-2 expression in the aorta, and decreased α1 receptor density in the same vessel. Pentolinium but not hexamethonium recovered responsiveness and α1 adrenergic receptor density in the aorta. Both blockers normalized the in vivo response to vasoconstrictors, and reduced plasma IL-1 and NOx levels and NOS-2 expression in the aorta.Blockade of ganglionic sympathetic transmission reduced the vascular dysfunction in experimental sepsis. This beneficial effect seems to be, at least in part, due to the preservation of α1 adrenergic receptor density and to reduced NOS-2 expression and may lead to adjuvant ways to treat human sepsis.

Exposure to Canadian French Cued Speech Improves Consonant Articulation in Children With Cochlear Implants: Acoustic and Articulatory Data.

One of the strategies that can be used to support speech communication in deaf children is cued speech, a visual code in which manual gestures are used as additional phonological information to supplement the acoustic and labial speech information. Cued speech has been shown to improve speech perception and phonological skills. This exploratory study aims to assess whether and how cued speech reading proficiency may also have a beneficial effect on the acoustic and articulatory correlates of consonant production in children. Eight children with cochlear implants (from 5 to 11 years of age) and with different receptive proficiency in Canadian French Cued Speech (three children with low receptive proficiency vs. five children with high receptive proficiency) are compared to 10 children with typical hearing (from 4 to 11 years of age) on their production of stop and fricative consonants. Articulation was assessed with ultrasound measurements. The preliminary results reveal that cued speech proficiency seems to sustain the development of speech production in children with cochlear implants and to improve their articulatory gestures, particularly for the place contrast in stops as well as fricatives. This work highlights the importance of studying objective data and comparing acoustic and articulatory measurements to better characterize speech production in children.

Purinergic Astrocyte Signaling Driven by TNF-α After Cannabidiol Administration Restores Normal Synaptic Remodeling Following Traumatic Brain Injury

Traumatic brain injury (TBI) is a prevalent form of cranial trauma that results in neural conduction disruptions and damage to synaptic structures and functions. Cannabidiol (CBD), a primary derivative from plant-based cannabinoids, exhibits a range of beneficial effects, including analgesic, sedative, anti-inflammatory, anticonvulsant, anti-anxiety, anti-apoptotic, and neuroprotective properties. Nevertheless, the effects of synaptic reconstruction and the mechanisms underlying these effects remain poorly understood. TBI is characterized by increased levels of tumor necrosis factor-alpha (TNF-α), a cytokine integral for the modulation of glutamate release by astrocytes. In the present study, the potential of CBD in regulating aberrant glutamate signal transmission in astrocytes following brain injury, as well as the underlying mechanisms involved, were investigated using immunofluorescence double staining, enzyme-linked immunosorbent assay (ELISA), western blot analysis, hematoxylin and eosin (H&E) staining, Nissl staining, transmission electron microscopy, and RT-qPCR. In this study, we examined the impact of CBD on neuronal synapses, focusing on the TNF-α-driven purinergic signaling pathway. Specifically, our research revealed that CBD pretreatment effectively reduced the secretion of TNF-α induced by astrocyte activation following TBI. This reduction inhibited the interaction between TNF-α and P2Y1 receptors, leading to a decrease in the release of neurotransmitters, including Ca2+ and glutamate, thereby initiating synaptic remodeling. Our study showed that CBD exhibits significant therapeutic potential for TBI-related synaptic dysfunction, offering valuable insights for future research and more effective TBI treatments. Further exploration of the potential applications of CBD in neuroprotection is required to develop innovative clinical strategies.

Morin loaded mesoporous molecular sieves as novel devices to the potential treatment of tumor pathologies.

Morin is an antioxidant and anticancer flavonoid, extracted from natural sources, that may exert beneficial effects for several pathologies. Despite this, the administration of morin represents a challenge due to its low aqueous solubility. Mesoporous silica materials have emerged as biocompatible tools for drug delivery, as their pore size can be modulated for maximum surface area to volume ratio. In this contribution, we evaluate the ability of iron-modified mesoporous materials, for morin loading and controlled delivery. The SBA-15 and MCM-41 sieves were synthesized and modified with iron (metal content 4.02 and 6.27 % wt, respectivily). Characterization by transmission electron microscopy, XRD and UV-Vis revealed adequate pore size and agglomerates of very small metallic nanospecies (nanoclusters), without larger iron oxide nanoparticles. FT-IR spectra confirmed the presence of silanol groups in the solid hosts, which can interact with different groups present in morin molecules. SBA-15 materials were more efficient in terms of morin loading capacity (LC) due to their larger pore diameter. LC was more than 35% for SBA-15 materials when adsorptions studies were carried out with 9mg of drug. Antioxidant activity were assayed by using DPPH test. Free iron materials presented a significate improvement as antioxidants after morin incorporation, reaching a scavenging activity of almost a 90%. On the other hand, in iron modified mesoporous materials, the presence of morin did not affect the scavenging activity. The results could be related with the formation of a complex between the flavonoid and the iron. Finally, biosafety studies using normal epithelial cells revealed that neither the loaded nor the unloaded materials exerted toxicity, even at doses of 1mg/ml. These findings expand knowledge about mesoporous materials as suitable carriers of flavonoids with the aim of improving therapies for a wide range of pathologies.

Beneficial effects of resistance training on both mild and severe mouse dystrophic muscle function as a preclinical option for Duchenne muscular dystrophy.

Mechanical overloading (OVL) resulting from the ablation of muscle agonists, a supra-physiological model of resistance training, reduces skeletal muscle fragility, i.e. the immediate maximal force drop following lengthening contractions, and increases maximal force production, in mdx mice, a murine model of Duchene muscular dystrophy (DMD). Here, we further analyzed these beneficial effects of OVL by determining whether they were blocked by cyclosporin, an inhibitor of the calcineurin pathway, and whether there were also observed in the D2-mdx mice, a more severe murine DMD model. We found that cyclosporin did not block the beneficial effect of 1-month OVL on plantaris muscle fragility in mdx mice, nor did it limit the increases in maximal force and muscle weight (an index of hypertrophy). Fragility and maximal force were also ameliorated by OVL in the plantaris muscle of D2-mdx mice. In addition, OVL increased the expression of utrophin, cytoplamic γ-actin, MyoD, and p-Akt in the D2-mdx mice, proteins playing an important role in fragility, maximal force gain and muscle growth. In conclusion, OVL reduced fragility and increased maximal force in the more frequently used mild mdx model but also in D2-mdx mice, a severe model of DMD, closer to human physiopathology. Moreover, these beneficial effects of OVL did not seem to be related to the activation of the calcineurin pathway. Thus, this preclinical study suggests that resistance training could have a potential benefit in the improvement of the quality of life of DMD patients.

The REV-ERB antagonist SR8278 modulates keratinocyte viability in response to UVA and UVB radiation.

The nucleotide excision repair (NER) system removes UV photoproducts from genomic DNA and is controlled by the circadian clock. Given that small-molecule compounds have been developed to target various clock proteins, we examined whether the cryptochrome inhibitor KS15 and REV-ERB antagonist SR8278 could modulate keratinocyte responses to UV radiation invitro. We observed that though SR8278 promoted cell viability in UVB-irradiated cells, it had little effect on NER or on the expression of the clock-regulated NER factor XPA. Rather, we found that both KS15 and SR8278 absorb light within the UV spectrum to limit initial UV photoproduct formation in DNA. Moreover, SR8278 promoted UVB viability even in cells in which the core circadian clock protein BMAL1 was disrupted, which indicates that SR8278 is likely acting via other REV-ERB transcriptional targets. We further observed that SR8278 sensitized keratinocytes to light sources containing primarily UVA wavelengths of light likely due to the generation of toxic reactive oxygen species. Though other studies have demonstrated beneficial effects of SR8278 in other model systems, our results here suggest that SR8278 has limited utility for UV photoprotection in the skin and will likely cause phototoxicity in humans or mammals exposed to solar radiation.

Effect of high-intensity interval training on self-care and anxiety-like behaviors in naive rats.

Self-care behavior covers individual's health, life and well-being to maintain the necessary activities. The aim of this study is to examine the self-care and possible anxiolytic effects of high-intensity interval exercise (HIIT). Eight-week-old Wistar Albino male rats were divided into Control (n = 8), and Exercise (n = 8). Rat exercised for 38min a day, 5days a week, for 8weeks The animals were then subjected to open field test and splash test, and the behaviors were video recorded. Student t test and Shapiro-Wilk test were used as statistical tests. In the exercise group, spray-induced grooming behavior increased significantly in terms of duration and frequency (p < 0.05), but no significant difference was observed in the latency of grooming (p > 0.05). In the open-field test, the total distance traveled, which is a locomotor activity parameter, did not change between the groups. Anxiolytic-like behaviors such as total rearing behavior, unsupported rearing, central time, and central region entries increased remarkably in the exercise group vs. control (p < 0.0001). Freezing as an anxiogenic behavior decreased in the exercise group positively (p < 0.0001). Intermittent high-intensity exercise improved and increased self-care behaviors. Further, the present study shows that HIIT has beneficial effects on different aspects of behaviors such as exploratory behaviors, increasing anxiolytic behaviors, and reducing anxiogenic behavior. The present study is a preclinical study that will pave the way for new studies.

In-Situ Formed Electron Inhibitor Enabling Dendrite-free Garnet Electrolytes: A Case Study of Fumed Silica.

Ta-doped Li7 La3 Zr2 O12 (LLZTO) solid-state electrolytes (SEs) show great promise for solid-state batteries due to its high conductivity and safety. However, one of the challenges it faces is lithium dendrite propagation upon long-term cycling. To address this issue, we propose the incorporation of fumed silica (FS) at the grain boundaries of LLZTO to modify the properties of the garnet pellet, which effectively inhibits the dendrite growth. The introduction of FS has demonstrated several beneficial effects. Firstly, it reduces the migration barrier of lithium ions, which helps prevent dendrite formation and propagation. Additionally, FS reduces the electronic conductivity of the SEs pellet, suppressing the dendrite formation. Moreover, the formed lithium silicates from FS might also be acted as electron inhibitor, thus inhibiting the lithium dendrite growth upon cycling. By investigating the use of FS as a modifier in LLZTO-based electrolytes, our study contributes to advancing dendrite-free solid-state electrolytes and thus the development of high-performance all-solid-state batteries.