Effect of Mn2+ Doping on the Photoluminescence of Hybrid One-Dimensional Lead Halide Post-Perovskites.

Although organic-inorganic hybrid one-dimensional (1D) lead halide postperovskites (LHPPs) have been reported to show white luminescence and tunable photoluminescence quantum yield (PLQY), their structure-property relationships are not fully understood. Here, we used Mn2+ to test the doping effect on the luminescence of two 1D-LHPPs compounds, namely, {TETA[Pb2Br6]}n 1 and {TETA[Pb2Cl6]}n 2, where TETA = triethylenetetrammonium. We found the pristine compounds show yellowish (551 nm) and bluish (447 nm) emission for 1 and 2, respectively, nanosecond excitation lifetimes (4.17 ns for 1 and 2.29 ns for 2) and low PLQYs (4.65 and 3.57% for 1 and 2, respectively). By fine-doping the Mn2+ ions to ca. 8% the PLQYs for 1 and 2 are maximized to 24 and 25% for 1 and 2, respectively. Upon the increasing Mn2+ dopant, the emission wavelengths can also vary gradually from 551 to 615 nm and from 447 to 660 nm for 1 and 2, respectively, covering almost the whole visible-light range, and the excitation lifetimes are enhanced to microseconds (0.77 µs for 1 and 0.39 µs for 2), owing to the more spin-forbidden d-d transition (4T1-6A1) component from the Mn2+ ions present in the photoluminescence spectra. Moreover, these Mn2+-doped 1D-LHPPs demonstrate high structural and optical stability in humid and high-temperature environments. Hence, such doped materials can be fabricated into a UV-pumped white light-emitting diode, rendering the potential application for solid-state lighting and display systems.

Applying a Random Encounter Model to Estimate the Asiatic Black Bear (Ursus thibetanus) Density from Camera Traps in the Hindu Raj Mountains, Pakistan.

Estimating the population density of vulnerable species, such as the elusive and nocturnal Asiatic black bear (Ursus thibetanus), is essential for wildlife conservation and management. We used camera traps and a Random Encounter Model (REM) to estimate the population density of U. thibetanus during the autumn and winter seasons in the Hindu Raj Mountains. We installed 23 camera traps from October to December 2020 and acquired 66 independent pictures of Asiatic black bears over 428 trap nights. Our results showed that the bears preferred lowland areas with the presence of Quercus spp. We estimated, using the REM, a population density of U. thibetanus of 1.875 (standard error = 0.185) per square kilometer, which is significantly higher than that in other habitats. Our results showed that during autumn and winter, the bear population density tends to concentrate at lower elevations. Forest cover showed a positive correlation with the rates of bear encounters unlike the Euclidean distance to human settlements, altitude, and aspect variables. The approaches used here are cost-effective for estimating the population density of rare and vulnerable species such as U. thibetanus, and can be used to estimate their population density in Pakistan. Population density estimation can identify areas where the bears live and human-bear conflicts occurred and use this information in future wildlife management plans.

Oil recovery from microwave co-pyrolysis of polystyrene and polypropylene plastic particles for pollution mitigation.

Addressing the mounting environmental challenge of non-degradable polymeric waste, the world grapples with escalating production driven by population growth, modernization, and industrialization. Pyrolysis has emerged as a promising and strategic solution for transforming non-degradable polymeric waste into valuable fuels and other chemical products. This study detailed the high-quality oil recovery from microwave co-pyrolysis of polystyrene (PS) and polypropylene (PP) mixtures. The effects of PS/PP ratio (30:0, 10:20, 15:15, 20:10, and 30:0 g), microwave power (400, 500, 600, 700, and 800 W), and pyrolysis temperature (450, 500, 550, 600, and 650 °C) on oil yield and components were studied, and the synergistic effect, higher heating value (HHV) and thermal efficiency were also detailed. The results revealed that the highest oil yield was 93.84 wt% when PS/PP ratio, microwave power, and pyrolysis temperature were adjusted at 20:10 g, 600 W, and 550 °C, respectively. And the maximum higher heating value and thermal efficiency were 45.67 MJ/kg and 56.53%, respectively. The contents of aromatic hydrocarbons, cyclic hydrocarbons, and oxygenated hydrocarbons varied in the ranges of 1.92-58.88 area%, 10.47-41.76 area%, and 5.06-24.36 area%, respectively. The contents of the major carbon numbers were C8 and C9, and they varied in 2.51-43.66 area% and 7.31-20.09 area%, respectively. The results presented in this study showed that high-quality oil can be recovered from polystyrene and polypropylene plastics by using microwave irradiation, contributing to cleaner ways for plastics recycling.

Staphylococcus haemolyticus: An updated review on nosocomial infections, antimicrobial resistance, virulence, genetic traits, and strategies for combating this emerging opportunistic pathogen.

Staphylococcus haemolyticus, a key species of the Staphylococcus genus, holds significant importance in healthcare-associated infections, due to its notable resistance to antimicrobials, like methicillin, and proficient biofilms-forming capabilities. This coagulase-negative bacterium poses a substantial challenge in the battle against nosocomial infections. Recent research has shed light on Staph. haemolyticus genomic plasticity, unveiling genetic elements responsible for antibiotic resistance and their widespread dissemination within the genus. This review presents an updated and comprehensive overview of the clinical significance and prevalence of Staph. haemolyticus, underscores its zoonotic potential and relevance in the one health framework, explores crucial virulence factors, and examines genetics features contributing to its success in causing emergent and challenging infections. Additionally, we scrutinize ongoing studies aimed at controlling spread and alternative approaches for combating it.

Preparation and characterization of biodegradable food packaging films using lemon peel pectin and chitosan incorporated with neem leaf extract and its application on apricot fruit.

The present study aims to develop and characterize biodegradable packaging films from lemon peel-derived pectin and chitosan incorporated with a bioactive extract from neem leaves. The films (PCNE) contained varying concentrations of neem leaf extract and were comprehensively assessed for their physical, optical, mechanical, and antimicrobial attributes. The thickness, moisture content, water solubility, and water vapor permeability of the biodegradable packaging films increased with the increasing concentration of neem leaf extract. Comparatively, the tensile strength of the films decreased by 42.05 % compared to the control film. The Scanning Electron Microscopy (SEM) confirmed that the resultant blended pectin-chitosan films showed a uniform structure without cracks. Furthermore, the analysis targeting Staphylococcus aureus and Aspergillus niger indicated that the films had potent antimicrobial activity. Based on these results, the optimum films were selected and subsequently applied on apricot fruits to increase their shelf life at ambient temperature. The findings, after examining factors such as colour, firmness, total soluble solids, shrinkage, weight loss, and appearance, concluded that the apricots coated by PCNE-5 had the most delayed signs of spoilage and increased their shelf life by 50 %. The results showed the potential applicability of lemon peel pectin-chitosan-neem leaf extract blend films in biodegradable food packaging.

Alternative splicing generates a novel ferroportin isoform with a shorter C-terminal and an intact iron- and hepcidin-binding property.

Ferroportin (FPN) is a transmembrane protein and is the only known iron exporter that helps in maintaining iron homeostasis in vertebrates. To maintain stable iron equilibrium in the body, ferroportin works in conjunction with a peptide called hepcidin. In this study, we have identified an alternatively spliced novel isoform of the human SLC40A1 gene, which encodes for the FPN protein and is found to be expressed in different tissues. The novel transcript has an alternate last exon and encodes 31-amino acid long peptide sequence that replaces 104 amino acids at C-terminal in the novel transcript. Molecular modelling and molecular dynamics (MD) simulation studies revealed key structural features of the novel isoform (FPN-N). FPN-N was predicted to have 12 transmembrane domains similar to the reported isoform (FPN), despite being much smaller in size. FPN-N was found to interact with hepcidin, a key regulator of ferroportin activity. Also, the iron-binding sites were retained in the novel isoform as revealed by the MD simulation of FPN-N in bilipid membrane. The novel isoform identified in this study may play important role in iron homeostasis. However, further studies are required to characterize the FPN-N isoform and decipher its role inside the cell.

Evolving therapeutic interventions for the management and treatment of Alzheimer's disease.

Alzheimer's Disease (AD) patients experience diverse symptoms, including memory loss, cognitive impairment, behavioral abnormalities, mood changes, and mental issues. The fundamental objective of this review is to discuss novel therapeutic approaches, with special emphasis on recently approved marketed formulations for the treatment of AD, especially Aducanumab, the first FDA approved moiety that surpasses the blood-brain barrier (BBB) and reduces amyloid plaques in the brain, thereby reducing associated cognitive decline. However, it is still in the phase IV trial and is to be completed by 2030. Other drugs such as lecanemab are also under clinical trial and has recently been approved by the FDA and is also discussed here. In this review, we also focus on active and passive immunotherapy for AD as well as several vaccines, such as amyloid-beta epitope-based vaccines, amyloid-beta DNA vaccines, and stem cell therapy for AD, which are in clinical trials. Furthermore, ongoing pre-clinical trials associated with AD and other novel strategies such as curcumin-loaded nanoparticles, Crispr/ cas9, precision medicine, as well as some emerging therapies like anti-sense therapy are also highlighted. Additionally, we discuss some off-labeled drugs like non-steroidal anti-inflammatory drugs (NSAID), anti-diabetic drugs, and lithium, which can manage symptoms of AD and different non-pharmacological approaches are also covered which can help to manage AD. In summary, we have tried to cover all the therapeutic interventions which are available for the treatment and management of AD under sections approved, clinical phase, pre-clinical phase or futuristic interventions, off-labelled drugs, and non-pharmacological interventions for AD, offering positive findings and well as challenges that remain.

Aberrant photoelectric effect in the topological insulator/n-GaN heterojunction (Bi2Te3/n-GaN) under unpolarized illumination.

A topological insulator has a unique graphene-like Dirac cone conducting surface state, which is excellent for broadband absorption and photodetector applications. Experimental investigations on the Bi2Te3/n-GaN heterojunction exhibited an aberrant photoelectric effect under the influence of unpolarized light. Transport measurements of the Bi2Te3/n-GaN heterojunction revealed a negative photoconductance, with a sudden increase in resistance. This was consistent with the applied range of wavelength and power used for incident light while it was contrary to the usual gap-state transition model, which states that a negative conductance is due to the trapping of charge carriers. The observed aberrant photoelectric effect seen in Bi2Te3/n-GaN heterojunction devices was due to the polycrystalline nature of the Bi2Te3 topological insulator film, where the incident photon-induced bandgap in the Dirac cone surface state resulted in a negative photoelectric effect. This phenomenon opens the possibility for applications in highly sensitive photodetectors and non-volatile memories, along with employing the bandgap-opening concept in retinomorphic devices.

Nanocoating and its application as antimicrobials in the food industry: A review.

Nanocoatings are ultra-thin layers on the nanoscale (<100 nm) that are deposited on the substrate to improve their properties and functionality. These nanocoatings provide significant advantages compared to traditional coating, including stain resistance, antimicrobial and antioxidant activities, odor control and delivery of active agents, and liquid repellence properties. In the food industry, nanocoating is widely used in the food packaging sector. In this regard, nanocoating offers antimicrobials and antioxidant properties to active food packaging by incorporating active bioactive compounds into materials used in already existing packaging. The application of nanocoating is applied to these kinds of food packaging with nano coating to improve shelf life, safety, and quality of food packaging. In smart/intelligent packaging, the active packaging coating is promising food packaging, which is designed by releasing preservatives and nanocoating as an antimicrobial, antifungal, antioxidant, barrier coating, and self-cleaning food contact surfaces. In addition, nanocoating can be used for food contact surfaces, kitchen utensils, and food processing equipment to create antimicrobial, antireflective, and dirt-repellent properties. These are critical properties for food processing, especially for meat and dairy processing facilities, which can reduce biofilm formation and prevent cross-contamination. Recently, appreciable growth in the development of the application of nanocoating as edible films for coating food products has emerged to improve food safety issues. In this regard, much scientific research in the area of nanocoating fruits and vegetables, and other food products was performed to address food safety issues. Hence, this promising technology can be a great addition to the agricultural and food industries. Thus, this review addresses the most relevant information about this technology and the applications of nanocoating in the food industry.

Stabilization challenges and aggregation in protein-based therapeutics in the pharmaceutical industry.

Protein-based therapeutics have revolutionized the pharmaceutical industry and become vital components in the development of future therapeutics. They offer several advantages over traditional small molecule drugs, including high affinity, potency and specificity, while demonstrating low toxicity and minimal adverse effects. However, the development and manufacturing processes of protein-based therapeutics presents challenges related to protein folding, purification, stability and immunogenicity that should be addressed. These proteins, like other biological molecules, are prone to chemical and physical instabilities. The stability of protein-based drugs throughout the entire manufacturing, storage and delivery process is essential. The occurrence of structural instability resulting from misfolding, unfolding, and modifications, as well as aggregation, poses a significant risk to the efficacy of these drugs, overshadowing their promising attributes. Gaining insight into structural alterations caused by aggregation and their impact on immunogenicity is vital for the advancement and refinement of protein therapeutics. Hence, in this review, we have discussed some features of protein aggregation during production, formulation and storage as well as stabilization strategies in protein engineering and computational methods to prevent aggregation.

Ketamine as a therapeutic agent in major depressive disorder and posttraumatic stress disorder: Potential medicinal and deleterious effects.

Major depressive disorder (MDD) and posttraumatic stress disorder (PTSD) are the most common causes of emotional distress that impair an individual's quality of life. MDD is a chronic mental illness that affects 300 million people across the world. Clinical manifestations of MDD include fatigue, loss of interest in routine tasks, psychomotor agitation, impaired ability to focus, suicidal ideation, hypersomnolence, altered psychosocial functioning, and appetite loss. Individuals with depression also demonstrate a reduced behavioral response while experiencing pleasure, a symptom known as anhedonia. Like MDD, PTSD is a prevalent and debilitating psychiatric disorder resulting from a traumatic incident such as sexual assault, war, severe accident, or natural disaster. Symptoms such as recalling event phases, hypervigilance, irritability, and anhedonia are common in PTSD. Both MDD and PTSD pose enormous socioeconomic burdens across the globe. The search for effective treatment with minimal side effects is still ongoing. Ketamine is known for its anesthetic and analgesic properties. Psychedelic and psychotropic effects of ketamine have been found on the nervous system, which highlights its toxicity. In this article, the effectiveness of ketamine as a potential therapeutic for PTSD and MDD along with its mechanisms of action, clinical trials, and possible side effects have been discussed.

Quantifying the microstructural and biomechanical changes in the porcine ventricles during growth and remodelling.

Cardiac tissue growth and remodelling (G & R) occur in response to the changing physiological demands of the heart after birth. The early shift to pulmonary circulation produces an immediate increase in ventricular workload, causing microstructural and biomechanical changes that serve to maintain overall physiological homoeostasis. Such cardiac G & R continues throughout life. Quantifying the tissue's mechanical and microstructural changes because of G & R is of increasing interest, dovetailing with the emerging fields of personalised and precision solutions. This study aimed to determine equibiaxial, and non-equibiaxial extension, stress-relaxation, and the underlying microstructure of the passive porcine ventricles tissue at four time points spanning from neonatal to adulthood. The three-dimensional microstructure was investigated via two-photon excited fluorescence and second-harmonic generation microscopy on optically cleared tissues, describing the 3D orientation, rotation and dispersion of the cardiomyocytes and collagen fibrils. The results revealed that during biomechanical testing, myocardial ventricular tissue possessed non-linear, anisotropic, and viscoelastic behaviour. An increase in stiffness and viscoelasticity was noted for the left and right ventricular free walls from neonatal to adulthood. Microstructural analyses revealed concomitant increases in cardiomyocyte rotation and dispersion. This study provides baseline data, describing the biomechanical and microstructural changes in the left and right ventricular myocardial tissue during G & R, which should prove valuable to researchers in developing age-specific, constitutive models for more accurate computational simulations. STATEMENT OF SIGNIFICANCE: There is a dearth of experimental data describing the growth and remodelling of left and right ventricular tissue. The published literature is fragmented, with data reported via different experimental techniques using tissues harvested from a variety of animals, with different gender and ages. This prevents developing a continuum of data spanning birth to death, so limiting the potential that can be leveraged to aid computational modelling and simulations. In this study, equibiaxial, non-equibiaxial, and stress-relaxation data are presented, describing directional-dependent material responses. The biomechanical data is consolidated with equivalent microstructural data, an important element for the development of future material models. Combined, these data describe microstructural and biomechanical changes in the ventricles, spanning G &R from neonatal to adulthood.

ViSHWaS: Violence Study of Healthcare Workers and Systems-a global survey.

OBJECTIVE: To provide insights into the nature, risk factors, impact and existing measures for reporting and preventing violence in the healthcare system. The under-reporting of violence against healthcare workers (HCWs) globally highlights the need for increased public awareness and education. METHODS: The Violence Study of Healthcare Workers and Systems study used a survey questionnaire created using Research Electronic Data Capture (REDCap) forms and distributed from 6 June to 9 August 2022. Logistic regression analysis evaluated violence predictors, including gender, age, years of experience, institution type, respondent profession and night shift frequency. A χ2 test was performed to determine the association between gender and different violence forms. RESULTS: A total of 5405 responses from 79 countries were analysed. India, the USA and Venezuela were the top three contributors. Female respondents comprised 53%. The majority (45%) fell within the 26-35 age group. Medical students (21%), consultants (20%), residents/fellows (15%) and nurses (10%) constituted highest responders. Nearly 55% HCWs reported firsthand violence experience, and 16% reported violence against their colleagues. Perpetrators were identified as patients or family members in over 50% of cases, while supervisor-incited violence accounted for 16%. Around 80% stated that violence incidence either remained constant or increased during the COVID-19 pandemic. Among HCWs who experienced violence, 55% felt less motivated or more dissatisfied with their jobs afterward, and 25% expressed willingness to quit. Univariate analysis revealed that HCWs aged 26-65 years, nurses, physicians, ancillary staff, those working in public settings, with >1 year of experience, and frequent night shift workers were at significantly higher risk of experiencing violence. These results remained significant in multivariate analysis, except for the 55-65 age group, which lost statistical significance. CONCLUSION: This global cross-sectional study highlights that a majority of HCWs have experienced violence, and the incidence either increased or remained the same during the COVID-19 pandemic. This has resulted in decreased job satisfaction.

Ganoderic Acid A targeting leucine-rich repeat kinase 2 involved in Parkinson's disease-A computational study.

Objective: This study aims to find the most promising Ganoderma lucidium targeting LRRK2 involved in PD. Methods: First ADMET analysis was performed for five compounds followed by molecular docking of each compound. Then, we perform molecular dynamics simulation of all five compounds and finally MMGBSA of all five compounds. Results: Based on molecular dynamics and MMGBSA result we reach the conclusion that Ganoderic Acid A (GAA) is the most promising compound targeting LRRK2. Therefore, GAA needs further validation through in vitro and in vivo studies. Conclusion: Ganoderma lucidum exhibits cytotoxic, hepatoprotective, antioxidative, anticancer, and antinociceptive activities. This study predicted that Ganoderma lucidum could even be used to treat neurological disorders like PD. This study suggest that the best-identified molecule against LRRK2 is GAA and it needs rigorous in vitro and in vivo validations.

Identification of a novel Sorcin isoform with a different C-terminal but intact dimerization property.

Sorcin (Sri), a member of penta EF-hand protein family plays a diverse role in maintaining calcium homeostasis, cell cycle and vesicular trafficking. Sri is highly conserved amongst mammals and consists of N-terminal glycine rich domain and C-terminal calcium binding domain that mediates its dimerization and interacts with different compounds. In the present study, with the help of combination of computational and molecular biology techniques, we have identified a novel isoform (Sri-N) in mouse which differs only in the C-terminal domain with that of Sri reported earlier. The novel isoform contains a new last exon that is different from the one present in the reported transcript (Sri). The presence of the novel isoform was further validated in different tissues by RT-PCR and DNA sequencing. The transcript was conceptually translated and subjected to in-silico analysis using different bioinformatics tools. The novel transcript variant encodes for a longer protein isoform without any change in the sub-cellular localization as predicted by PSORT-II online tool. Molecular modelling was performed to compare the structural changes in Sri-N and Sri isoforms. The structural characterization of the novel isoform using MD simulation depicted its overall stability under the physiological conditions. The molecular docking of proteins with various chemotherapeutic drugs revealed that their binding affinity is more for Sri-N as compared to that for the previously reported transcript Sri.

A Spectrum of Solutions: Unveiling Non-Pharmacological Approaches to Manage Autism Spectrum Disorder.

Autism spectrum disorder (ASD) is a developmental disorder that causes difficulty while socializing and communicating and the performance of stereotyped behavior. ASD is thought to have a variety of causes when accompanied by genetic disorders and environmental variables together, resulting in abnormalities in the brain. A steep rise in ASD has been seen regardless of the numerous behavioral and pharmaceutical therapeutic techniques. Therefore, using complementary and alternative therapies to treat autism could be very significant. Thus, this review is completely focused on non-pharmacological therapeutic interventions which include different diets, supplements, antioxidants, hormones, vitamins and minerals to manage ASD. Additionally, we also focus on complementary and alternative medicine (CAM) therapies, herbal remedies, camel milk and cannabiodiol. Additionally, we concentrate on how palatable phytonutrients provide a fresh glimmer of hope in this situation. Moreover, in addition to phytochemicals/nutraceuticals, it also focuses on various microbiomes, i.e., gut, oral, and vaginal. Therefore, the current comprehensive review opens a new avenue for managing autistic patients through non-pharmacological intervention.

Hydroxyapatite and ionic liquid coupled with hybrid membranes for toxic pollutant removal and remediation.

Access to clean water is the mandatory requirement for every living being to sustain life. So, membrane-based integrated approach of adsorption and separation technology has recently been preferred by scientists over other conventional techniques, for wastewater treatment. Current research focused on the synthesis of novel imidazolium (A1) based IL, which was further functionalized with hydroxyapatite (HAp; extracted from Labeo rohita scales), to create possible solutions towards environmental remediation. Cellulose acetate (CA) was used for the fabrication of three different ionic liquid membranes. All the synthesized products were characterized by FTIR, XRD and TGA. Two dyes of different nature, i.e., congo red (anionic) and crystal violet (cationic) were selected because of their highly toxic and carcinogenic effects, for batch adsorption experiments. Antibacterial activity of the synthesized membranes was also evaluated against S. aureus. Results of the study revealed that CA-HA1 1:2 acted as the best adsorbent towards the removal of crystal violet, exhibiting removal efficiency of 98% with the contact time of 24 h while in case of congo red adsorption, CA-HA1 (1:2) proved as prime adsorbent with the removal efficiency of 96% for the same preceding contact time. Considering the antibacterial character of the synthesized membranes, CA-A1 (1:1) emerged as very efficient antibacterial agent with the inhibition zone of 50 mm after 48 h. The overall behavior of monolayer and multilayer adsorption was witnessed for both dyes while kinetic studies favored the pseudo-second order reaction for all adsorbents.

Crimean-Congo Hemorrhagic Fever Presented in Dengue Epidemic: A Case Report.

In Pakistan, hemorrhagic diseases, including dengue and Crimean-Congo hemorrhagic fever (CCHF), are common. Therefore, an accurate diagnosis is challenging in the early stages of sickness owing to geographic overlap and early clinical similarities between the two disorders. A 35-year-old man who had previously experienced hematemesis and high-grade fever presented to our hospital. Despite receiving supportive care for a preliminary diagnosis of dengue hemorrhagic fever, the patient's condition worsened. The results of the dengue IgM antibody test were negative. On the fourth day of admission, a qualitative polymerase chain reaction test for CCHF virus RNA was performed, and the result returned positive. All medical personnel and attendants who had contact with the patient had to receive ribavirin prophylaxis, which required significant investment in resources. Because CCHF can have long-term financial and health repercussions for contacts, including healthcare personnel in developing nations, it is essential to identify and treat it as soon as possible. It is necessary to keep track of dengue and CCHF cases more closely to develop predictors of disease diagnosis that are reasonably trustworthy, affordable, and quick. These predictors can aid in directing future choices regarding the care of similar situations. Ultimately, such an approach might result in improved cost control in environments with limited resources. Consideration should also be given to patients who receive ribavirin prophylaxis.

Identification of potential neuroprotective compound from Ganoderma lucidum extract targeting microtubule affinity regulation kinase 4 involved in Alzheimer's disease through molecular dynamics simulation and MMGBSA.

Objective: Alzheimer's disease (AD) is one of the most prevalent neurological ailments, affecting around 50 million individuals globally. The condition is characterized by nerve cell damage due to the formation of amyloid-beta plaques and neurofibrillary tangles. Only a few US Food and Drug Administration (FDA)-approved medications are available in the market which are devoid of side effects, thus, making it imperative to investigate new alternatives for countering this disease. According to a recent study, microtubule affinity regulation kinase 4 (MARK4) is attributed as one of the most promising drug targets for AD, thus, being selected for this study. Compounds from Ganoderma lucidum (Reishi mushroom) extracts were selected to be used as ligands for this study. Methods: In this study, the five most potent compounds from Ganoderma lucidum were selected and their absorption, distribution, metabolism, excretion, and toxicity (ADMET) analysis was performed, followed by molecular docking, and molecular dynamics simulation of each compound with MARK4 and supported by molecular mechanics generalized born surface area (MMGBSA) binding free energy calculations. Results: The promising compounds were selected based on their ADMET profile and interactions with the active site residues of MARK4. Based on docking scores of -9.1 and -10.3 kcal/ mol, respectively, stability assessment by molecular dynamics simulation, and MMGBSA calculations, ganoderic acid A and ganoderenic acid B were found to be the most promising compounds against MARK4 which will require further in vitro and in vivo validations. Conclusion: Through this study, it is suggested that ganoderic acid A and ganoderenic acid B might be a class of promising compounds against AD, based on computational research, and can be further studied for preclinical and clinical studies.

Circadian dysfunction and Alzheimer's disease - An updated review.

Alzheimer's disease (AD) is considered to be the most typical form of dementia that provokes irreversible cognitive impairment. Along with cognitive impairment, circadian rhythm dysfunction is a fundamental factor in aggravating AD. A link among circadian rhythms, sleep, and AD has been well-documented. The etiopathogenesis of circadian system disruptions and AD serves some general characteristics that also open up the possibility of viewing them as a mutually reliant path. In this review, we have focused on different factors that are related to circadian rhythm dysfunction. The various pathogenic factors, such as amyloid-beta, neurofibrillary tangles, oxidative stress, neuroinflammation, and circadian rhythm dysfunction may all contribute to AD. In this review, we also tried to focus on melatonin which is produced from the pineal gland and can be used to treat circadian dysfunction in AD. Aside from amyloid beta, tau pathology may have a notable influence on sleep. Conclusively, the center of this review is primarily based on the principal mechanistic complexities associated with circadian rhythm disruption, sleep deprivation, and AD, and it also emphasizes the potential therapeutic strategies to treat and prevent the progression of AD.