Efficient photoanode with a MoS2/TiO2/Au nanoparticle heterostructure for ultraviolet-visible photoelectrocatalysis.

Green energy technology is generally becoming one of hot issues that need to be solved due to the adverse effects on the environment of fossil fuels. One of the strategies being studied and developed by theorists and experimentalists is the use of photoelectrochemical (PEC) cells, which are emerging as a candidate to produce hydrogen from water splitting. However, creating photoelectrodes that meet the requirements for PEC water splitting has emerged as the primary obstacle in bringing this technology to commercial fruition. Here, we construct a heterostructure, which consists of MoS2/TiO2/Au nanoparticles (NPs) to overcome the drawbacks of the photoanode. Owing to the dependence on charge transfer, the bandgap of MoS2/TiO2and the utilization the Au NPs as a stimulant for charges separation of TiO2by localized surface plasmon resonances effect as well as the increase of hot electron injection to cathode, leading to photocatalytic activities are improved. The results have recorded a significant increase in the photocurrent density from 2.3µAcm-2of TiO2to approximately 16.3µAcm-2of MoS2/TiO2/Au NPs. This work unveils a promising route to enhance the visible light adsorption and charge transfer in photo-electrode of the PEC cells by combining two-dimensional materials with metal NPs.

In-vivo neuronal dysfunction by Aß and tau overlaps with brain-wide inflammatory mechanisms in Alzheimer's disease.

The molecular mechanisms underlying neuronal dysfunction in Alzheimer's disease (AD) remain uncharacterized. Here, we identify genes, molecular pathways and cellular components associated with whole-brain dysregulation caused by amyloid-beta (Aß) and tau deposits in the living human brain. We obtained in-vivo resting-state functional MRI (rs-fMRI), Aß- and tau-PET for 47 cognitively unimpaired and 16 AD participants from the Translational Biomarkers in Aging and Dementia cohort. Adverse neuronal activity impacts by Aß and tau were quantified with personalized dynamical models by fitting pathology-mediated computational signals to the participant's real rs-fMRIs. Then, we detected robust brain-wide associations between the spatial profiles of Aß-tau impacts and gene expression in the neurotypical transcriptome (Allen Human Brain Atlas). Within the obtained distinctive signature of in-vivo neuronal dysfunction, several genes have prominent roles in microglial activation and in interactions with Aß and tau. Moreover, cellular vulnerability estimations revealed strong association of microglial expression patterns with Aß and tau's synergistic impact on neuronal activity (q < 0.001). These results further support the central role of the immune system and neuroinflammatory pathways in AD pathogenesis. Neuronal dysregulation by AD pathologies also associated with neurotypical synaptic and developmental processes. In addition, we identified drug candidates from the vast LINCS library to halt or reduce the observed Aß-tau effects on neuronal activity. Top-ranked pharmacological interventions target inflammatory, cancer and cardiovascular pathways, including specific medications undergoing clinical evaluation in AD. Our findings, based on the examination of molecular-pathological-functional interactions in humans, may accelerate the process of bringing effective therapies into clinical practice.

Green, facile synthesis and evaluation of unsymmetrical carbamide derivatives as antimicrobial and anticancer agents with mechanistic insights.

A very practical method for the synthesis of unsymmetrical carbamide derivatives in good to excellent yield was presented, without the need for any catalyst and at room temperature. Using a facile and robust protocol, fifteen unsymmetrical carbamide derivatives (9-23) bearing different aliphatic amine moieties were designed and synthesized by the reaction of secondary aliphatic amines with isocyanate derivatives in the presence of acetonitrile as an appropriate solvent in good to excellent yields. Trusted instruments like IR, mass spectrometry, NMR spectra, and elemental analyses were employed to validate the purity and chemical structures of the synthesized compounds. All the synthesized compounds were tested as antimicrobial agents against some clinically bacterial pathogens such as Salmonella typhimurium, Bacillus subtilis, Pseudomonas aeruginosa, Staphylococcus aureus and Candida albicans. Compounds 15, 16, 17, 19 and 22 showed potent antimicrobial activity with promising MIC values compared to the positive controls. Moreover, compounds 15 and 22 provide a potent lipid peroxidation (LPO) of the bacterial cell wall. On the other hand, we investigated the anti-proliferative activity of compounds 9-23 against selected human cancerous cell lines of breast (MCF-7), colon (HCT-116), and lung (A549) relative to healthy noncancerous control skin fibroblast cells (BJ-1). The mechanism of their cytotoxic activity has been also examined by immunoassaying the levels of key anti- and pro-apoptotic protein markers. The results of MTT assay revealed that compounds 10, 13, 21, 22 and 23 possessed highly cytotoxic effects. Out of these, three synthesized compounds 13, 21 and 22 showed cytotoxicity with IC50 values (13, IC50 = 62.4 ± 0.128 and 22, IC50 = 91.6 ± 0.112 µM, respectively, on MCF-7), (13, IC50 = 43.5 ± 0.15 and 21, IC50 = 38.5 ± 0.17 µM, respectively, on HCT-116). Cell cycle and apoptosis/necrosis assays demonstrated that compounds 13 and 22 induced S and G2/M phase cell cycle arrest in MCF-7 cells, while only compound 13 had this effect on HCT-116 cells. Furthermore, compound 13 exhibited the greatest potency in inducing apoptosis in both cell lines compared to compounds 21 and 22. Docking studies indicated that compounds 10, 13, 21 and 23 could potentially inhibit enzymes and exert promising antimicrobial effects, as evidenced by their lower binding energies and various types of interactions observed at the active sites of key enzymes such as Sterol 14-demethylase of C. albicans, Dihydropteroate synthase of S. aureus, LasR of P. aeruginosa, Glucosamine-6-phosphate synthase of K. pneumenia and Gyrase B of B. subtilis. Moreover, 13, 21, and 22 demonstrated minimal binding energy and favorable affinity towards the active pocket of anticancer receptor proteins, including CDK2, EGFR, Erα, Topoisomerase II and VEGFFR. Physicochemical properties, drug-likeness, and ADME (absorption, distribution, metabolism, excretion, and toxicity) parameters of the selected compounds were also computed.

Pharmacokinetic and molecular docking studies to pyrimidine drug using Mn3O4 nanoparticles to explore potential anti-Alzheimer activity.

Alzheimer disease (AD) is the cause of dementia and accounts for 60-80% cases. Tumor Necrosis Factor-alpha (TNF-α) is a multifunctional cytokine that provides resistance to infections, inflammation, and cancer. It developed as a prospective therapeutic target against multiple autoimmune and inflammatory disorders. Cholinergic insufficiency is linked to Alzheimer's disease, and several cholinesterase inhibitors have been created to treat it, including naturally produced inhibitors, synthetic analogs, and hybrids. In the current study, we tried to prepared compounds may also support the discovery and development of novel therapeutic and preventative drugs for Alzheimer's using manganese tetroxide nanoparticles (Mn3O4-NPs) as a catalyst to generate compounds with excellent reaction conditions. The Biginelli synthesis yields 4-(4-cyanophenyl)-6-oxo-2-thioxohexahydropyrimidine-5-carbonitrile when the 4-cyanobenzaldehyde, ethyl cyanoacetate, and thiourea were coupled with Mn3O4-NPs to produce compound 1. This multi-component method is non-toxic, safe, and environmentally friendly. The new approach reduced the amount of chemicals used and preserved time. Compound 1 underwent reactions with methyl iodide, acrylonitrile, chloroacetone, ethyl chloroacetate, and chloroacetic acid/benzaldehyde, each of the synthetized compounds was docked with TNF-α converting enzyme. These compounds may also support the discovery and development of novel therapeutic and preventative drugs for Alzheimer's disease. The majority of the produced compounds demonstrated pharmacokinetic features, making them potentially attractive therapeutic candidates for Alzheimer's disease treatment.

Phytochemical profiling, antiviral activities, molecular docking, and dynamic simulations of selected Ruellia species extracts.

The antiviral properties of the flowering aerial extracts of Ruellia tuberosa and Ruellia patula were investigated through phytochemical profiling via LC-MS/MS and HPLC techniques. Qualitative LC-MS/MS analyses identified seventy-seven metabolites from both Ruellia species. R. tuberosa had the highest phenolic content (49.3%), whereas R. patula had the highest flavonoid content (57.8%). Additionally, quantitative HPLC investigations of the compounds identified by LC-MS/MS were performed using the available standard compounds. The main constituents in the R. tuberosa extract was found to be catechin (5321.63 µg/g), gallic acid (2878.71 µg/g), and ellagic acid (2530.79 µg/g), whereas the major compounds in the R. patula extract was found to be rutin (11,074.19 µg/g) and chlorogenic acid (3157.35 µg/g). Furthermore, the antiviral activities of both Ruellia species against HAdV-40, herpes simplex type 2 and H1N1 were evaluated. These findings demonstrated that R. tuberosa was more active than R. patula against all tested viruses, except for the HSV-2 virus, against which R. patula showed greater activity than R. tuberosa, with IC50 values of 20, 65, 22.59, and 13.13 µg/ml for R. tuberosa flowering aerial parts and 32.26, 11.66, and 23.03 µg/ml for R. patula flowering aerial parts, respectively for HAdV-40, herpes simplex type 2, and H1N1. Additionally, computational docking and molecular dynamics simulations were used to assess the molecular interactions between the bioactive compounds and specific viral targets. The combined findings from the in-vitro and in-silico experiments comprehensively evaluated the antiviral activities of both Ruellia species extracts.

Verbena officinalis (VO) leaf extract as an anti-corrosion inhibitor for carbon steel in acidic environment.

In the present work, Verbena Officinalis (VO) leaf extract was used as potential corrosion inhibitor for the corrosion of carbon steel (CS) in 0.5 M H2SO4 medium. Further, the corrosion inhibiting nature of VO leaf extract towards the CS was evaluated using mass loss (ML), potentiodynamic polarization (PDP), electrical impedance spectroscopy (EIS) and surface morphological analyses using atomic force microscope (AFM) and X-ray photoelectron spectroscopy (XPS) techniques. Calculation of activation energy E a ∗ using Arrhenius equation shows the increase in activation energy when adding the VO leaf extract in 0.5 M H2SO4 medium and the maximum activation energy ( E a ∗ = 49.9 kJ mol-1) was observed for 1000 mg L-1 VO leaf extract in acid medium. The negative free energy values suggested the spontaneous and the stability of the adsorbed layer of VO leaf extract on the CS surface. Using EIS measurements, high percent inhibitory effectiveness of 91.1% for 1000 ppm solutions was achieved. With an increase in VO leaf extract dose, the double layer capacitance (Cdl) values fall while the values of charge transfer (Rct) increase. This showed that a protective layer of VO leaf extract on CS surface was formed. The polarization curves showed that the VO leaf extract acts as a mixed-type inhibitor. It is discovered that the adsorption of VO leaf extract molecules adhering to the CS surface followed the Langmuir isotherm. The anti-corrosion action of VO leaf extract is fully demonstrated by some surface techniques.

Prospective feasibility study of a novel rigidizing stabilizing overtube in the resection of complex gastrointestinal polyps.

BACKGROUND: A novel rigidizing overtube (ROT) was developed to facilitate endoscopic removal of complex gastrointestinal polyps. We aimed to prospectively evaluate the efficacy and safety of the device in the management of large gastrointestinal polyps. METHODS: A prospective, single-center study, conducted between May 2021 and April 2023, enrolled patients undergoing endoscopic resection of colon/duodenal polyps ≥25 mm. Primary outcomes were safety, technical success, and clinical success defined as the ability of ROT to facilitate endoscopic polyp removal without changing the initial resection method. RESULTS: 97 patients (98 polyps), with a mean polyp size of 33.2 mm (median 31.1), were evaluated. Technical and clinical success rates were 100% and 84%, respectively. Ileocecal valve location was the only predictor of clinical failure (P = 0.02). The mean time to reach the lesion was 7.2 minutes (95%CI 5-8), with overall resection and procedure times of 53.6 minutes (95%CI 48-61) and 88.9 minutes (95%CI 79-95), respectively. No device-related adverse events occurred. Lower technical (67%) and clinical (67%) success rates were seen for duodenal polyps (n = 6). CONCLUSION: The novel ROT was safe, with high technical and clinical success during resection of complex colon polyps. Future studies will determine timing of implementation during routine endoscopic resection.

Association of socio-demographic factors with clinical outcome among hospitalized patients in first and second waves of COVID-19 pandemic: Study from the developing world.

Background: Recent disease resurgence in China indicates that corona virus infectious disease is still a pertinent public health problem. We stand at a juncture where we are still unsure about the initial dilemmas regarding its birth, therapies, and the emerging novel strains. Medical literature has focused on the clinical, laboratory, radiological, and therapeutic aspects of disease management. There is paucity of literature on the association between socio-demographic variables on disease severity and clinical outcome. Materials and Methods: This retrospective observational study analyzing the socio-demographic variables was performed at a dedicated COVID care center in western Maharashtra, India. Electronic records of all individuals who were admitted to this hospital from July 29 2020, to June 14, 2021, and diagnosed COVID-19 positive by reverse transcriptase polymerase chain reaction (RT-PCR) were identified after due institutional ethical clearance. Patients admitted from July 29, 2020, to February 27, 2021, were categorized as patients presenting during the 'first wave of viral pandemic'. Those admitted from March 01, 2021, to June 14, 2021, have been included as patients admitted during 'second wave of viral pandemic'. The following outcome parameters were collected (presenting symptoms, duration of symptoms before the individual presented for diagnostic RT-PCR, total duration of symptoms, severity of disease at onset, duration of hospital stay, the final outcome (discharge/death) and Charlson's comorbidity index). The linear regression model was used to establish association between socio-demographic factors and disease severity at onset (mild/moderate/severe/critical). Results: A total of 37033 patients were screened, and the positivity rate with RT-PCR was 16.99% (n = 6275) during the study period. Out of which 45% (n = 2824) of the patients had mild disease requiring home isolation and the remaining 55% of patients required admission. 1590 patients from the first wave and 910 from the second wave of COVID-19 were hospitalized and included in the study after exclusion. The mean age of patients in first wave was 49 years and that in second wave was 54 years with 77.6% and 70.6% males in two waves, respectively. The burden of critical cases was higher in second wave as computed to first wave (10% vs 8%). The second wave had more outreach in the rural population as compared to second one (17.8% vs 12.2%). The mean duration from the onset of symptoms to hospitalization was 03 and 04 days, respectively, in two waves. Mortality associated in two waves was 11.9% and 24%, respectively (P < 0.05). Higher Charlson's comorbidity index was associated with higher mortality, and the cumulative survival from urban area was more as compared to the rural population (log rank - 9.148, P = 0.0002). Conclusion: The second COVID-19 wave had significantly higher case mortality. It affected elderly patients and those with rural background. The factors associated with higher mortality during COVID-19 pandemic were rural background, higher Charlson's comorbidity index and late presentation to the hospital. Ongoing vaccine campaigns, thus, should focus on rural areas and individuals with comorbidities especially in developing and least developed countries.

Iron Sulfide Microspheres Supported on Cellulose-Carbon Nanotube Conductive Flexible Film as an Electrode Material for Aqueous-Based Symmetric Supercapacitors with High Voltage.

Nanostructured iron disulfide (FeS2) was uniformly deposited on regenerated cellulose (RC) and oxidized carbon nanotube (CNT)-based composite films using a simple chemical bath deposition method to form RC/CNT/FeS2 composite films. The RC/CNT composite film served as an ideal substrate for the homogeneous deposition of FeS2 microspheres due to its unique porous architecture, large specific surface area, and high conductivity. Polypyrrole (PPy), a conductive polymer, was coated on the RC/CNT/FeS2 composite to improve its conductivity and cycling stability. Due to the synergistic effect of FeS2 with high redox activity and PPy with high stability and conductivity, the RC/CNT/FeS2/PPy composite electrode exhibited excellent electrochemical performance. The RC/CNT/0.3FeS2/PPy-60 composite electrode tested with Na2SO4 aqueous electrolyte could achieve an excellent areal capacitance of 6543.8 mF cm-2 at a current density of 1 mA cm-2. The electrode retained 91.1% of its original capacitance after 10,000 charge/discharge cycles. Scanning electron microscopy (SEM) images showed that the ion transfer channels with a pore diameter of 5-30 µm were formed in the RC/CNT/0.3FeS2/PPy-60 film after a 10,000 cycle test. A symmetrical supercapacitor device composed of two identical pieces of RC/CNT/0.3FeS2/PPy-60 composite electrodes provided a high areal capacitance of 1280 mF cm-2, a maximum energy density of 329 µWh cm-2, a maximum power density of 24.9 mW cm-2, and 86.2% of capacitance retention after 10,000 cycles at 40 mA cm-2 when tested at a wide voltage window of 1.4 V. These results demonstrate the greatest potential of RC/CNT/FeS2/PPy composite electrodes for the fabrication of high-performance symmetric supercapacitors with high operating voltages.

Middle Eastern Expert Opinion: Strategies for Successful Antifungal Stewardship Program Implementation in Invasive Fungal Infections.

In recent years, global public health efforts have increasingly emphasized the critical role of antimicrobial stewardship (AMS) in improving outcomes, reducing costs, and combating the growing threat of antimicrobial resistance. However, antifungal stewardship (AFS) has remained relatively overlooked despite the staggering impact of invasive fungal infections (IFIs). This burden is particularly pronounced in hospitals worldwide, with the Middle East facing significant unmet needs. The rising population of immunocompromised individuals vulnerable to IFI has prompted an increased reliance on antifungal agents for both prevention and treatment. Given the considerable mortality associated with IFIs and the emergence of antifungal resistance, implementing AFS programs in hospital settings is becoming increasingly urgent. In this article, we offer expert insights into the strategies that can be used for successful antifungal stewardship program implementation in IFI. Drawing upon the extensive clinical experience of a multinational and multidisciplinary panel, we present recommendations for optimizing AFS practices. We delve into the challenges and practical considerations of tailoring local AFS initiatives to the evolving landscape of fungal infections. Additionally, we provide actionable recommendations and position statements for the effective implementation of AFS programs, informed by the collective clinical experiences of panel members across their respective countries of practice.

Rs12039395 Variant Influences the Expression of hsa-miR-181a-5p and PTEN Toward Colorectal Cancer Risk.

BACKGROUND: Single nucleotide polymorphisms (SNPs) in microRNA (miRNA) genes could alter miRNA expression levels or processing and, thus, may contribute to colorectal cancer (CRC) development. Therefore, this study aimed to examine whether the MIR181A1 genomic sequence possesses SNPs that can affect the expression of hsa-miR-181a-5p and, subsequently, impact its targets and associate with CRC risk. METHODS: The NCBI dbSNP database was searched for possible SNPs associated with MIR181A1. One SNP with a minor allele frequency > 5%, rs12039395 G > T was identified. In silico analyses determined the effect of the SNP on the secondary structure of the miRNA and predicted the hsa-miR-181a-5p target genes. The SNP was genotyped using allelic discrimination assay, the relative hsa-miR-181a-5p expression level was determined using quantitative real-time PCR, and immunohistochemical staining was used to detect target genes in 192 paraffin-embedded specimens collected from 160 CRC patients and 32 healthy subjects. RESULTS: The rs6505162 SNP conferred protection against CRC, and the G-allele presence provides may provide accessibility for the transcriptional machinery. Hsa-miR-181a-5p was significantly over-expressed in the CRC group compared to controls and in samples carrying the G-allele compared to those with T-allele. PTEN, identified as the only hsa-miR-181a-5p target implicated in CRC, was significantly diminished in the CRC group compared to controls and showed an inverse relationship with hsa-miR-181a-5p expression level as well as negatively associated with the G-allele presence in CRC. CONCLUSION: This study highlights that rs12039395 G > T may protect against CRC by influencing the expression of hsa-mir-181a-5p and its target gene, PTEN.

Unmasking the ongoing challenge of equid herpesvirus- 1 (EHV-1): A comprehensive review.

Equid herpesviruses (EHVs) are a group of highly impactful viral pathogens that affect horses, presenting a substantial risk to the global equine industry. Among these, equid herpesvirus-1 (EHV-1) primarily causes respiratory infections. However, its ability to spread to distant organs can lead to severe consequences such as abortion and neurological diseases. These viruses can enter a dormant phase, with minimal activity, and later reactivate to trigger active infections at any time. Recently, there has been a notable rise in the prevalence of a particularly devastating strains of EHV-1 known as equid herpesviral myeloencephalopathy (EHM). In the light of dynamic nature of EHV-1, this review provides a thorough overview of EHV-1 and explores how advances in viral biology affect the pathophysiology of viral infection. The information presented here is crucial for understanding the dynamics of EHV-1 infections and creating practical plans to stop the virus's global spread among equid populations.

Real-Time Arabic Sign Language Recognition Using a Hybrid Deep Learning Model.

Sign language is an essential means of communication for individuals with hearing disabilities. However, there is a significant shortage of sign language interpreters in some languages, especially in Saudi Arabia. This shortage results in a large proportion of the hearing-impaired population being deprived of services, especially in public places. This paper aims to address this gap in accessibility by leveraging technology to develop systems capable of recognizing Arabic Sign Language (ArSL) using deep learning techniques. In this paper, we propose a hybrid model to capture the spatio-temporal aspects of sign language (i.e., letters and words). The hybrid model consists of a Convolutional Neural Network (CNN) classifier to extract spatial features from sign language data and a Long Short-Term Memory (LSTM) classifier to extract spatial and temporal characteristics to handle sequential data (i.e., hand movements). To demonstrate the feasibility of our proposed hybrid model, we created a dataset of 20 different words, resulting in 4000 images for ArSL: 10 static gesture words and 500 videos for 10 dynamic gesture words. Our proposed hybrid model demonstrates promising performance, with the CNN and LSTM classifiers achieving accuracy rates of 94.40% and 82.70%, respectively. These results indicate that our approach can significantly enhance communication accessibility for the hearing-impaired community in Saudi Arabia. Thus, this paper represents a major step toward promoting inclusivity and improving the quality of life for the hearing impaired.

The Inhibitors of Mucosa-Associated Lymphoid Tissue Lymphoma Translocation Protein 1 (MALT-1) Protease as Potential Treatment of ABC-DLBCL and Similar Diseases.

The invention in this patent application relates to thiazolo[5,4-b]pyridine derivatives represented generally by formula 1. These compounds are inhibitors of the activity of mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT-1) protease and may potentially be useful in the treatment of some forms of cancer, particularly ABC-DLBCL.

Somatostatin Receptor Subtype 4 Agonists for Potential Treatment of Alzheimer's Disease and Other Central Nervous System Disorders.

The invention in this patent application relates to N-(pyrrolidine-3-yl or piperidin-4-yl)acetamide derivatives represented generally by formula 1. These compounds possess activities as somatostatin receptor 4 (SSTR4) agonists and may potentially be beneficial in the treatment of diseases or disorders, associated with SSTR4 such as Alzheimer's disease (AD) and other CNS disorders such as epilepsy and depression.

Clinico-epidemiological Characteristics of the Physician Affected with Covid-19.

Coronavirus disease 2019 (Covid-19) disease have been associated with significant mortality amongst doctors globally including Bangladesh. To delineate the clinico-epidemiological characteristics of the physician affected with Covid-19 was the objective of the study. This cross-sectional 'Facebook' based survey was conducted in the period of August 2020 to September 2020. Snowball sampling methods was followed. A total of 151 physicians affected with Covid-19 participated in this survey. Self-reported perceived severity scale (zero meaning not severe at all and ten denoting the most severe) was used. Collected data were analyzed by SPSS 25.0. Among the participants, the majority were male, 98(64.9%). The most prevalent affected age groups were 24-35 years 131(86.8%). Approximately 45.0% worked in COVID dedicated hospital. Entry-level physicians (Medical Officer or Assistant Surgeon) were the most affected 117(94.4%). One-third of the physicians had at least the one co-morbidity. Bronchial asthma, obesity and diabetes were the most frequent. Predominate symptoms of the infection were fever 94(62.3%), cough 94(62.3%) and myalgia 92(60.9%). Half of the participants had sore throat, anosmia, gastro-intestinal symptoms and one-third of the patients developed dyspnea. Perceived severity of the symptoms ranged between 2 and 6. The pattern of drug use to prevent the Covid-19 showed no uniformity. However, intake of Zinc, Vitamin C, Vitamin D, antihistamine and Ivermectin was found in 74.8%, 67.5%, 41.7%, 49.0% and 37.7% respectively. As the current pandemic continues to evolve, physicians must be equipped with appropriate knowledge, skills and must be cautious on the prevention measures against Covid-19.

New insights into the anti-inflammatory and anti-melanoma mechanisms of action of azelaic acid and other Fusarium solani metabolites via in vitro and in silico studies.

Metabolites exploration of the ethyl acetate extract of Fusarium solani culture broth that was isolated from Euphorbia tirucalli root afforded five compounds; 4-hydroxybenzaldehyde (1), 4-hydroxybenzoic acid (2), tyrosol (3), azelaic acid (4), malic acid (5), and fusaric acid (6). Fungal extract as well as its metabolites were evaluated for their anti-inflammatory and anti-hyperpigmentation potential via in vitro cyclooxygenases and tyrosinase inhibition assays, respectively. Azelaic acid (4) exhibited powerful and selective COX-2 inhibition followed by fusaric acid (6) with IC50 values (2.21 ± 0.06 and 4.81 ± 0.14 µM, respectively). As well, azelaic acid (4) had the most impressive tyrosinase inhibitory effect with IC50 value of 8.75 ± 0.18 µM compared to kojic acid (IC50 = 9.27 ± 0.19 µM). Exclusive computational studies of azelaic acid and fusaric acid with COX-2 were in good accord with the in vitro results. Interestingly, this is the first time to investigate and report the potential of compounds 3-6 to inhibit cyclooxygenase enzymes. One of the most invasive forms of skin cancer is melanoma, a molecular docking study using a set of enzymes related to melanoma suggested pirin to be therapeutic target for azelaic acid and fusaric acid as a plausible mechanism for their anti-melanoma activity.

Efficacy of Lasers in Debonding Ceramic Brackets: Exploring the Rationale and Methods.

The development of ceramic brackets in orthodontics three decades ago emerged as a response to the increasing patient demand for less visible orthodontic appliances. While these brackets provide superior aesthetics, they are characterized by lower fracture toughness and higher bond strength in contrast to metal brackets. These properties present challenges during the debonding step, including the risk of enamel micro-fractures and cracks. Historically, various strategies have been developed to address challenges associated with debonding, reduce patient discomfort, and ensure that the bond failure site is confined to the bracket-adhesive interface. This included the use of specially designed debonding pliers, electrothermal debonding, ultrasonic technique, and chemical agents. Recently, there has been a shift towards utilizing different types of laser irradiation for this purpose. The burgeoning strategy, however, requires diligent scientific scrutiny to establish a standardized protocol with particular laser parameters and ultimately achieve the goal of enhancing the patient experience by reducing discomfort. This article offers a narrative review of laser-aided debonding of ceramic brackets, aimed at comparing different laser types, presenting their benefits and downsides, validating the efficiency of each method, and summarizing the published literature on this subject. It also provides insights for orthodontists on reducing patient discomfort that usually accompanies debonding ceramic brackets by delving into the science behind the use of lasers for this purpose.

Remotely monitored physical activity from older people with cardiac devices associates with physical functioning.

INTRODUCTION: Accelerometer-derived physical activity (PA) from cardiac devices are available via remote monitoring platforms yet rarely reviewed in clinical practice. We aimed to investigate the association between PA and clinical measures of frailty and physical functioning. METHODS: The PATTErn study (A study of Physical Activity paTTerns and major health Events in older people with implantable cardiac devices) enrolled participants aged 60 + undergoing remote cardiac monitoring. Frailty was measured using the Fried criteria and gait speed (m/s), and physical functioning by NYHA class and SF-36 physical functioning score. Activity was reported as mean time active/day across 30-days prior to enrolment (30-day PA). Multivariable regression methods were utilised to estimate associations between PA and frailty/functioning (OR = odds ratio, ß = beta coefficient, CI = confidence intervals). RESULTS: Data were available for 140 participants (median age 73, 70.7% male). Median 30-day PA across the analysis cohort was 134.9 min/day (IQR 60.8-195.9). PA was not significantly associated with Fried frailty status on multivariate analysis, however was associated with gait speed (ß = 0.04, 95% CI 0.01-0.07, p = 0.01) and measures of physical functioning (NYHA class: OR 0.73, 95% CI 0.57-0.92, p = 0.01, SF-36 physical functioning: ß = 4.60, 95% CI 1.38-7.83, p = 0.005). CONCLUSIONS: PA from cardiac devices was associated with physical functioning and gait speed. This highlights the importance of reviewing remote monitoring PA data to identify patients who could benefit from existing interventions. Further research should investigate how to embed this into clinical pathways.