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Guoqiang Yang,1– 3 Jiraporn Kantapan,3 Maryam Mazhar,4,5 Qiongdan Hu,1,5,6 Xue Bai,5,7 Yuanxia Zou,1,3 Honglian Wang,1 Sijin Yang,4,5 Li Wang,1,5 Nathupakorn Dechsupa3 1Research Center for Integrated Chinese and Western Medicine, the Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, People’s Republic of China; 2Acupuncture and Rehabilitation Department, the Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, People’s Republic of China; 3Molecular Imaging and Therapy Research Unit, Department of Radiologic Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand; 4National Traditional Chinese Medicine Clinical Research Base and Drug Research Center of the Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, People’s Republic of China; 5Institute of Integrated Chinese and Western Medicine, Southwest Medical University, Luzhou, People’s Republic of China; 6Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand; 7Department of Neurology and National Traditional Chinese Medicine Clinical Research Base, the Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, People’s Republic of ChinaCorrespondence: Li Wang; Nathupakorn Dechsupa, Email wangli120@swmu.edu.cn; nathupakorn.d@cmu.ac.thBackground: Intracerebral hemorrhage (ICH), a devastating form of stroke, is characterized by elevated morbidity and mortality rates. Neuroinflammation is a common occurrence following ICH. Mesenchymal stem cells (MSCs) have exhibited potential in treating brain diseases due to their anti-inflammatory properties. However, the therapeutic efficacy of MSCs is limited by the intense inflammatory response at the transplantation site in ICH. Hence, enhancing the function of transplanted MSCs holds considerable promise as a therapeutic strategy for ICH. Notably, the iron-quercetin complex (IronQ), a metal-quercetin complex synthesized through coordination chemistry, has garnered significant attention for its biomedical applications. In our previous studies, we have observed that IronQ exerts stimulatory effects on cell growth, notably enhancing the survival and viability of peripheral blood mononuclear cells (PBMCs) and MSCs. This study aimed to evaluate the effects of pretreated MSCs with IronQ on neuroinflammation and elucidate its underlying mechanisms.Methods: The ICH mice were induced by injecting the collagenase I solution into the right brain caudate nucleus. After 24 hours, the ICH mice were randomly divided into four subgroups, the model group (Model), quercetin group (Quercetin), MSCs group (MSCs), and pretreated MSCs with IronQ group (MSCs+IronQ). Neurological deficits were re-evaluated on day 3, and brain samples were collected for further analysis. TUNEL staining was performed to assess cell DNA damage, and the protein expression levels of inflammatory factors and the cGAS-STING signaling pathway were investigated and analyzed.Results: Pretreated MSCs with IronQ effectively mitigate neurological deficits and reduce neuronal inflammation by modulating the microglial polarization. Moreover, the pretreated MSCs with IronQ suppress the protein expression levels of the cGAS-STING signaling pathway.Conclusion: These findings suggest that pretreated MSCs with IronQ demonstrate a synergistic effect in alleviating neuroinflammation, thereby improving neurological function, which is achieved through the inhibition of the cGAS-STING signaling pathway.Keywords: mesenchymal stem cells, IronQ, intracerebral hemorrhage, cGAS/STING/NFκB, inflammatory response

Umer Ejaz,1 Muhammad Afzal,1 Modasrah Mazhar,1 Muhammad Riaz,1 Naveed Ahmed,2 Waleed Y Rizg,3,4 Amerh Aiad Alahmadi,4 Moutaz Y Badr,5 Rayan Y Mushtaq,6 Chan Yean Yean2 1Department of Basic and Applied Chemistry, Faculty of Science and Technology, University of Central Punjab, Lahore, 54000, Pakistan; 2Department of Medical Microbiology and Parasitology, School of Medical Sciences, Health Campus, Universiti Sains Malaysia, Kubang Kerian, Kelantan, 16150, Malaysia; 3Center of Innovation in Personalized Medicine (CIPM), 3D Bioprinting Unit, King Abdulaziz University, Jeddah, 21589, Saudi Arabia; 4Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah, 21589, Saudi Arabia; 5Department of Pharmaceutical Sciences, College of Pharmacy, Umm Al-Qura University, Makkah, 24381, Saudi Arabia; 6Department of Pharmaceutics, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, Dammam, 31441, Saudi ArabiaCorrespondence: Chan Yean Yean, Department of Medical Microbiology and Parasitology, School of Medical Sciences, Health Campus, Universiti Sains Malaysia, Kubang Kerian, Kelantan, 16150, Malaysia, Email yeancyn@yahoo.com Muhammad Afzal, Department of Basic and Applied Chemistry, Faculty of Science and Technology, University of Central Punjab, Lahore, 54000, Pakistan, Email dr.afzal@ucp.edu.pkIntroduction: Silver nanoparticles (AgNPs) have been found to exhibit unique properties which show their potential to be used in various therapies. Green synthesis of AgNPs has been progressively gaining acceptance due to its cost-effectiveness and energy-efficient nature.Objective: In the current study, aqueous extract of Thymus vulgaris (T. vulgaris) was used to synthesize the AgNPs using green synthesis techniques followed by checking the effectiveness and various biological activities of these AgNPs.Methods: At first, the plant samples were proceeded for extraction of aqueous extracts followed by chromatography studies to measure the phenolics and flavonoids. The synthesis and characterization of AgNPs were done using green synthesis techniques and were confirmed using Fourier transform infra-red (FT-IR) spectroscopy, UV–visible spectroscopy, scanning electron microscope (SEM), zeta potential, zeta sizer and X-Ray diffraction (XRD) analysis. After confirmation of synthesized AgNPs, various biological activities were checked.Results: The chromatography analysis detected nine compounds accounting for 100% of the total amount of plant constituents. The FT-IR, UV–vis spectra, SEM, zeta potential, zeta sizer and XRD analysis confirmed the synthesis of AgNPs and the variety of chemical components present on the surface of synthesized AgNPs in the plant extract. The antioxidant activity of AgNPs showed 92% inhibition at the concentration of at 1000 μg/mL. A greater inhibitory effect in anti-diabetic analysis was observed with synthesized AgNPs as compared to the standard AgNPs. The hemolytic activity was low, but despite low concentrations of hemolysis activity, AgNPs proved not to be toxic or biocompatible. The anti-inflammatory activity of AgNPs was observed by in-vitro and in-vivo approaches in range at various concentrations, while maximum inhibition occurs at 1000 μg (77.31%).Conclusion: Our data showed that the potential biological activities of the bioactive constituents of T. vulgaris can be enhanced through green synthesis of AgNPs from T. vulgaris aqueous extracts. In addition, the current study depicted that AgNPs have good potential to cure different ailments as biogenic nano-medicine.Keywords: nanotechnology, medicinal plants, antioxidant, anti-inflammatory, antidiabetic

Olabola Awosika,1 Lori Kim,2 Momina Mazhar,2 Monica Rengifo-Pardo,1,2 Alison Ehrlich1,2 1Department of Dermatology, The George Washington Medical Faculty Associates, Washington, DC, USA; 2George Washington University School of Medicine & Health Sciences, Washington, DC, USA Abstract: Atopic dermatitis (AD) is a common inflammatory skin disorder that manifests as eczematous lesions, often associated with allergic rhinitis and asthma. Historically, moderate-to-severe disease has been managed with systemic immunosuppression, such as oral corticosteroids, which result in relapse and limiting side effects. Due to recent advancements in the identification of interleukin (IL)-4 and IL-13 as key mediators in AD, new biological agents have been developed for treatment. Dupilumab is a recently approved monoclonal antibody that targets the alpha subunit of the IL-4 receptor and, thus, downregulates activity of IL-4 and IL-13. This review discusses the profile of dupilumab and its potential for efficacy and safety in treating moderate-to-severe AD by reviewing data from Phase I–III clinical trials. Results suggest that dupilumab shows great therapeutic promise for AD. Further studies investigating extended use of dupilumab and dupilumab in comparison to other agents are needed to establish long-term efficacy and safety. Keywords: atopic dermatitis, dupilumab, IL-4, IL-13, biologics

Tariq Munshi, Mir Mazhar, Tariq HassanDepartment of Psychiatry, Kingston General Hospital, Kingston, ON, CanadaAbstract: We describe a case of a patient whose clozapine was discontinued after a "red result" following R-CHOP (rituximab with cyclophosphamide, hydroxydaunorubicin, Oncovin, and prednisolone) chemotherapy for large B-cell lymphoma. In some cases, manufacturers grant permission, on compassionate grounds, for clozapine to be continued or reinitiated following assessment by their consultant hematologist. Other than a recent case report, there is not much literature surrounding this medical issue. However, since the two leading causes of mortality in schizophrenia are cancer and cardiac disease, this is not an uncommon occurrence. Clinicians are reluctant to prescribe clozapine in view of its side-effect profile, despite its proven efficacy for managing treatment-resistant schizophrenia. The alternative is to prescribe two antipsychotics to manage symptoms. This approach may be associated with increased side effects, and evidence for actual benefits is scant. The consequences were disastrous in this case, as the individual not only relapsed following clozapine discontinuation, but the therapy for this treatable form of lymphoma had to be delayed. He was eventually admitted to an inpatient unit after having been stable for 15 years. We managed to stabilize him with olanzapine and aripiprazole which enabled the heme-oncology group to resume R-CHOP therapy with filgrastim (granulocyte colony-stimulating factor). Even so, he continued to exhibit severe psychotic symptoms, with religious delusions and auditory hallucinations. We therefore applied for permission to rechallenge him on clozapine. Permission was granted when protocol conditions were met, and reinitiation went without any adverse events. The patient's symptoms showed improvement within a few weeks, and the other antipsychotics were discontinued once clozapine was titrated up to 300 mg. The decision to reinitiate clozapine following a red result is not to be taken lightly, but needs to be considered in terms of the risks versus benefits. More literature surrounding this issue would be of great benefit to clinicians, patients, and their families.Keywords: clozapine agranulocytosis, clozapine discontinuation, red result, clozapine rechallenge, R-CHOP chemotherapy

The -application of nanoparticles for accurate diagnosis and ample treatment to various human diseases. Despite the use of diverse polymers in nanoparticle synthesis, biosynthesis of these particles in viable, metal-tolerant microorganisms is preferred over all other prevalent procedures including chemical methods, because of its cost-effectiveness, and eco-friendliness. Diabetes is the most fifth growing trend prevalent diseases worldwide due to the lifestyle changes, physical inactivity, aging, nutrition and lack of diet nutrition. The disease spread is influenced by numerous hereditary facts, environmental causes, temporal and additional behaviour. The study purpose by using in-silico approach identify inhibitors binding with a-glucosidase against DM. The a-glucosidase protein sequence from Saccharomycescerevisiae was retrieved using NCBI and utilizing software molecular docking and AdmetSAR were perormed. AdmetSAR utilized for the identification of properties of (ligand) MgONPs associate brain blood 0.9827% barrier and human intestinal 0.9848% absorption. MgONPs biodegradation 0.77% percentage was calculated with acute oral toxicity 0.589%. Total positive and negative charged residues Arg + Lys:73, Asp + Glu: 87 were also calculated. MgONPs exhibited super hydrogen bond formation interaction with polar amino acids, including ASP 37, SER 30, and LYS 39 residues of a-glucosidase.64.28 aliphatic index with -0.670 (GRAVY) grand average hydropathicity. The 100 µg/mL specimen cytotoxic concentration would be safe to ship. The a-glucosidase amino acids (ASP 46, VAL 325 and GLU 286) have a strong binding infinity with MgONPs. The amino acids of a-glucosidase (ASP 46, GLU 286 and VAL 325) have a strong binding interaction with MgONPs. [ABSTRACT FROM AUTHOR]

Phosphate is the second most essential nutrient for plant growth and development. Although the soil contains abundant phosphorus, only 0.1% is used by plant roots due to the significant amount of calcium carbonate (CaCO3) present in the calcareous soil, which limits the availability of P by reacting calcium ions with phosphate ions. It leads to alkaline reactions by generating insoluble phosphate compounds such as tricalcium phosphate. Here we study to boost phosphate solubilization in PSMs as an alternate strategy. Twenty-one bacterial isolates were selected from two different crops and investigated in vitro for their plant growth potential. All bacteria show capacity for phosphate solubility by producing a clear halo zone beneath and much more around bacterial colonies on Pikovskaya agar. In contrast, on modified Pikovskaya and only seven isolates with 60% reduction in zone formation were revealed to be positive for phosphate solubilization in which SWC5 was the best phosphate solubilizers with 1.25 phosphate solubilization index, respectively. All phosphate solubilizing bacteria showed irregular pattern in lowering the pH ranging from 4.1-6.27, where maximum decreased in pH was shown by SWS10.All bacteria showed phosphate solubilization ability in Pikovskaya broth phosphomolybdate assay ranging from 6.31 to 20.9 µg ml-1 in which the highest efficiency was demonstrated by SWS10. Phosphate solubilization efficiency in the potential isolates was confirmed by the presence of PqqE gene. The presence of the pqqE gene which is involved in phosphate solubilization was found in SWC4, SWC5, SWS10, and SW14 and it was absent in SWS9, SW18, and SW21. All the bacterial isolates were phylogenetically identified by sequencing and analyzing the 16S rRNA gene. The potential isolates Pseudomonas Koreensis, Pantoea dispersa, Pseudomonas sp., Agrobacterium sp. and consortia were selected for controlled condition experiment on Triticum aestivum. The highest plant dry weight was achieved by application of consortia and Pseudomonas Koreensis by increasing 65% and 59%, respectively, compared to control. [ABSTRACT FROM AUTHOR]

Background: There is a global shortage of health workforce. Females do not continue their careers due to a number of reasons. This study aims to find out the career pursuits of female doctors & their associated hurdles. Methods: After approval from IRB, this analytical cross-sectional study was conducted on 255 female doctors who graduated from a private medical college in Lahore from July to December 2022. Simple random sampling was done after getting lists of graduated female doctors from the medical college. The selfstructured questionnaire consisted of sociodemographic data, hurdles of career pursuits, and harassment at the workplace. Data were entered and analyzed by SPSS version 23, and the chi-square test was applied to find an association between the hurdles in practicing and non-practicing female graduates. A p-value of <0.05 was considered statistically significant. Results: Two hundred and fifty five participants were included in the study. Out of which 222 were practicing. 36(14%) experienced harassment at the workplace. The most frequently faced hurdles for career pursuits were less pay, increased workload, difficulty to take time off, and difficulty to give time to family. Conclusion: In this study 81.7% of the female graduates of the private medical college were working but are facing hurdles during their careers. Harassment in the workplace is common even in the medical profession. There is a lack of support from the family or in-laws, the expectation from women to be the homemaker, and women feeling guilty about prioritizing their careers over their children and family life. [ABSTRACT FROM AUTHOR]

Globally, industrial hemp offers consumers over 25,000 value-added products that are valued at approximately US$4.2 billion of current market value and likely to surpass US$26.6 billion by 2025. In Northern Australia, the industrial hemp sector is at infancy stages of development. Given the suitability of certain Northern Australia's geographical zones in terms of soil, water, and climate, a study was conducted to identify potential industrial hemp value chains. Probable value chains were developed by characterizing the production to market segments of the supply chains to determine the return on investment and analyzing the capacity of the stakeholders in terms of communication and relationships. Consequently, the strengths, weaknesses, opportunities, and threats (SWOT) of the developed value chains were analyzed. This study collected data from three complementary sources that included review of the literature, results of variety trials evaluation conducted in Northern Australia, and survey of hemp industry stakeholders. Results suggested that Northern Australia offers conducive growing conditions for hemp that allows for the development of three value chains including seed, fiber, and silage. The research recommended ongoing investment in the industry through engagement of public and private sector while focusing on further establishment of the industry. [ABSTRACT FROM AUTHOR]

Abstract In this article, some concepts of locally ( δ , ϕ ) $(\delta ,\phi )$ -dominated mappings, locally ( δ , ϕ ) $(\delta ,\phi )$ -continuous mappings and L R − ( δ , ϕ ) $LR-(\delta ,\phi )$ complete dislocated quasi-metric spaces have been introduced. Fixed point results for such mappings under new contractive conditions in these spaces have been established. As an application, fixed point results endowed with order and graph in such spaces have been examined. Furthermore, the results are substantiated with specific examples. Our empirically validated results represent a novel contribution to the existing body of literature.

Sadia Qazi,1 Muhammad Atif Mazhar,1 Abdul Ahad Shaikh,2 Abdul Jabar Rasool,2 Kanza Atif,3 Akef Obeidat1 1Anatomy Department, College of Medicine, Alfaisal University, Riyadh, Saudi Arabia; 2Physiology Department, College of Medicine, Alfaisal University, Riyadh, Saudi Arabia; 3College of Medicine, Alfaisal University, Riyadh, Saudi ArabiaCorrespondence: Sadia Qazi, Anatomy Department, College of Medicine, Alfaisal University, Riyadh, Saudi Arabia, Email sqazi@alfaisal.eduAbstract: This study explores the implementation of Team-Based Learning (TBL) at Alfaisal University’s College of Medicine through the lens of Complex Adaptive Systems (CAS) theory. The research question investigates how the application of CAS principles can enhance the implementation and effectiveness of TBL in medical education. The study employed a convergent parallel mixed methods longitudinal design, integrating quantitative performance metrics and qualitative themes. Quantitative analysis revealed modest improvements in individual and team-based learning scores, with a promising trend of students moving from the lower to the higher quartiles over time. Qualitative insights aligned with CAS principles, highlighting the adaptive implementation, emergent outcomes, self-organization, positive feedback loops, and depth of learning facilitated by TBL. The findings demonstrate the value of a CAS-informed approach in navigating the complexities of educational change and fostering a more resilient and adaptive educational model. The study contributes to the understanding of how CAS theory can guide the successful implementation of innovative pedagogies like TBL in medical education.Keywords: educational change, adaptive implementation, emergent behaviors, feedback loops, self-organization

OBJECTIVE: It is suggested that hidradenitis suppurativa (HS) is more prevalent and causes greater morbidity in Black patients than in White. Clinical data are however lacking. PATIENTS AND METHODS: We therefore describe HS risk factors, disease severity and clinical phenotypes in the Blacks and Whites. Patients referred for HS between 1984 and 2019 at the Johns Hopkins Hospital were identified using the Pathology Data System (PDS). Clinical and sociodemographic characteristics were extracted and the van der Zee & Jemec HS clinical phenotypes were recovered. RESULTS: A total of 278 patients were identified. Ethnically, 108 (38.8%) were White, and 170 (61.2%) Black. The following HS phenotypes were found: Regular (n=193, 69.4%), scarring folliculitis (n=40, 1.4%), frictional furuncle (11.2%), conglobata (n=9, 3.2%), syndromic (n=3, 1.1%) and ectopic (n=2, 0.7%). No statistically significant ethnic differences in clinical presentation were found. Blacks however had more severe diseases than Whites (p= 0.024 for trend). With multivariate logistic regression analysis, we found that male sex, disease duration, and smoking were independent predictors of regular HS phenotype. Major limitations are the limited number of cases studied and the lack of data regarding response to therapies. CONCLUSIONS: Demographics and phenotypical presentation of HS patients do not seem to be associated with Black ethnicity. However, there is a significant trend for Blacks to present with more Hurley stage 2 and 3 disease compared to White patients. It is speculated that ethnic differences are epiphenomena to social factors, highlighting the broader importance of ethnicity. [ABSTRACT FROM AUTHOR]

Climate change, dramatic fluctuations in the cost of fuel can cause an increase in the prices of basic food items. Pakistan is undergoing a serious energy crisis. Fortunately, this degrading situation is countered with the help of biomass energy (bioethanol) invention. However, the selection of the best strains with efficient enzymes for the production of bioethanol is in a continuous process of improvement. The objective of this work is to compare and analyze the structure of extremophilic strains with currently used organisms. Protein sequences of two different strains both zinc- and iron-dependent alcohol dehydrogenases (ADHs) were retrieved from Uniprot. Sequence analysis using protein sequence was conducted separately for both Zn- and Fe strains with Saccharomycescervisae and Zymomonasmobilis respectively with the help of T-coffee and Aliview. 3D protein structure modelswere built using the swiss model. The accuracy of predicted models was confirmed through online servers molprobity, ERRAT score VERIFY 3D values, and VADAR. Upon acquiring complete structural information of target strains, mutations were carried out in Fe and Zn-based organisms to check the best conformation of the enzyme for maximum bioethanol yield. The study demonstrated that the ability to withstand high-temperature ADH of thermophilic bacteria is considered a key enzyme for bioethanol production. Metal-binding residue sites His-62, Cys-38, Glu-63, and Cys-154 in Zn strains and Asp-204, His-208, His-271, and His-285 in Fe strains was conserved. Ligand interaction with residues in Fe and Zn strains was found similar in Saccharomycescervisae and Zymomonasmobilis strains. Structural and mutational analyses were performed to interpret the significance of mutated residues (A62, A38, Q63, A154 in Sulfolobus acidoculdarius and E204, R208, R271, R285 in Archaeglobus fulgidus) at the active binding site of ADH. Mutations at the active binding site in both Fe and Zn dependent ADH will impair structural stability, disturbance in catalytic pockets and bonds hence subordinating the overall enzyme-substrate complex and decreased efficiency in binding lignocellulosic biomass as substrate. [ABSTRACT FROM AUTHOR]

The publisher would like to point out that the heading of Table 2, Table 3 and Figure 1 were incorrectly printed. The following headings are correct. Table 2. Thyroid profile of control (n=100) and case (n=288) groups. Table 3. Antioxidative and hormonal profile of control (n=100) and case (n=288) groups. Figure 1. CTSS levels of control (n=100) and case (n=288) groups. A significant difference between groups is indicated by *p