Search

Ali Attiq,1 Sheryar Afzal,2 Habibah A Wahab,1 Waqas Ahmad,1 Mahmoud Kandeel,2,3 Yassir A Almofti,2,4 Ahmed O Alameen,2,5 Yuan Seng Wu6,7 1School of Pharmaceutical Sciences, Universiti Sains Malaysia, Gelugor, Penang, 11800, Malaysia; 2Department of Biomedical Sciences, College of Veterinary Medicine, King Faisal University, Al Ahsa, 31982, Saudi Arabia; 3Department of Pharmacology, Faculty of Veterinary Medicine, Kafrelsheikh University, Kafrel Sheikh, 6860404, Egypt; 4Department of Biochemistry, Molecular Biology and Bioinformatics, College of Veterinary Medicine, University of Bahri, Khartoum, 12217, Sudan; 5Department of Physiology, Faculty of Veterinary Medicine, University of Khartoum, Shambat, 13314, Sudan; 6Sunway Microbiome Centre, School of Medical and Life Sciences, Sunway University, Subang Jaya, Selangor, 47500, Malaysia; 7Department of Biological Sciences, School of Medical and Life Sciences, Sunway University, Subang Jaya, Selangor, 47500, MalaysiaCorrespondence: Sheryar Afzal, Department of Biomedical Sciences, College of Veterinary Medicine, King Faisal University, Al Ahsa, 31982, Saudi Arabia, Email safzal@kfu.edu.sa Ali Attiq, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Gelugor, 11800, Penang, Malaysia, Email aliattiq@usm.myAbstract: Angiotensin-converting enzyme 2 receptors (ACE2R) are requisite to enter the host cells for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). ACE2R is constitutive and functions as a type I transmembrane metallo-carboxypeptidase in the renin-angiotensin system (RAS). On thyroid follicular cells, ACE2R allows SARS-CoV-2 to invade the thyroid gland, impose cytopathic effects and produce endocrine abnormalities, including stiff back, neck pain, muscle ache, lethargy, and enlarged, inflamed thyroid gland in COVID-19 patients. Further damage is perpetuated by the sudden bursts of pro-inflammatory cytokines, which is suggestive of a life-threatening syndrome known as a “cytokine storm”. IL-1β, IL-6, IFN-γ, and TNF-α are identified as the key orchestrators of the cytokine storm. These inflammatory mediators upregulate transcriptional turnover of nuclear factor-kappa B (NF-κB), Janus kinase/signal transducer and activator of transcription (JAK/STAT), and mitogen-activated protein kinase (MAPK), paving the pathway for cytokine storm-induced thyroid dysfunctions including euthyroid sick syndrome, autoimmune thyroid diseases, and thyrotoxicosis in COVID-19 patients. Targeted therapies with corticosteroids (dexamethasone), JAK inhibitor (baricitinib), nucleotide analogue (remdesivir) and N-acetyl-cysteine have demonstrated effectiveness in terms of attenuating the severity and frequency of cytokine storm-induced thyroid dysfunctions, morbidity and mortality in severe COVID-19 patients. Here, we review the pathogenesis of cytokine storms and the mechanisms and pathways that establish the connection between thyroid disorder and COVID-19. Moreover, cross-talk interactions of signalling pathways and therapeutic strategies to address COVID-19-associated thyroid diseases are also discussed herein.Keywords: COVID-19, cytokine storm, signalling pathways, inflammation, thyroid disorders, cross talks

Studying the flow of ternary nanofluids [Ag, Cu, MoS2] holds significant importance in both science and engineering. Ternary nanofluids are vital in advancing thermal management systems, heat exchangers, aerospace, and materials processing applications.

This study explores factors impacting the effectiveness of forest protection policies in Indonesia, focusing on legal regulatory norms. Field findings reveal that community members continue cutting down trees due to economic need and limited awareness of forest protection policies, contributing significantly to forest degradation. To examine these factors, data were gathered through purposive sampling, targeting respondents— primarily farmers and cultivators—engaged in wood harvesting. Questionnaire results highlight economic motives and lack of policy knowledge as main drivers of logging, with many respondents indicating limited familiarity with policy specifics regarding forest conservation.The study also reviews the enforcement of existing sanctions, such as administrative penalties, fines, and imprisonment, and their effect within societal norms. The findings suggest that current sanctions have yet to effectively curb violations. Based on these observations and a policy review, this study proposes incorporating local wisdom into forest protection strategies and introducing more impactful social sanctions to strengthen policy effectiveness. This research contributes to understanding regulatory challenges in forest conservation and suggests pathways to enhance policy enforcement through culturally sensitive approaches and tailored sanctions.

This paper presents numerical analysis of double slanted central cracks in square plates under mode I tension stress. ANSYS finite element program is used to model and solve the problem of slanted cracks where the stress intensity factor is determined according to J-integral approach. Three relative crack length, a/W = 0.1, 0.2 and 0.3 is used while relative spacing between the cracks, s/2a are ranged between 0.1 to 0.6. In order to study the roles of slanted cracks on the stress intensity factor, several slanted angles are used such as 0°, 15°, 30°, 45°, 60° and 75°. According to the numerical analysis, all parameters above played an important role in determining the stress intensity factors. As expected, longer crack produced higher stress intensity factor. For the cracks with a/W ≤ 0.2, insignificant crack interaction is observed however when crack reached a/W=0.3, the interaction is gradually increased. Increasing the slanted angles slightly increased the interaction factor however the effect of relative crack spacing became insignificant.

Abstract Background Previously, the hypothetical protein, KPN00728 from Klebsiella pneumoniae MGH78578 was the Succinate dehydrogenase (SDH) chain C subunit via structural prediction and molecular docking simulation studies. However, due to limitation in docking simulation, an in-depth understanding of how SDH interaction occurs across the transmembrane of mitochondria could not be provided. Results In this present study, molecular dynamics (MD) simulation of KPN00728 and SDH chain D in a membrane was performed in order to gain a deeper insight into its molecular role as SDH. Structural stability was successfully obtained in the calculation for area per lipid, tail order parameter, thickness of lipid and secondary structural properties. Interestingly, water molecules were found to be highly possible in mediating the interaction between Ubiquinone (UQ) and SDH chain C via interaction with Ser27 and Arg31 residues as compared with earlier docking study. Polar residues such as Asp95 and Glu101 (KPN00728), Asp15 and Glu78 (SDH chain D) might have contributed in the creation of a polar environment which is essential for electron transport chain in Krebs cycle. Conclusions As a conclusion, a part from the structural stability comparability, the dynamic of the interacting residues and hydrogen bonding analysis had further proved that the interaction of KPN00728 as SDH is preserved and well agreed with our postulation earlier.

Dengue is one of the most prevalent viruses transmitted by the Aedes aegypti mosquitoes. Currently, no specific medication is available to treat dengue diseases. The NS2B-NS3 protease is vital during post-translational processing, which is a key target in this study. Due to methoxy group substitution, methoxyflavones are more bioavailable and metabolically stable than hydroxylated flavones. To date, research on the anti-dengue activity of methoxyflavones is limited. Hence, this work aims to determine the inhibitory activity of methoxyflavones against the dengue NS2B-NS3. Methoxyflavones derivatives were screened using molecular docking. The result showed a strong binding interaction of compound 1 and compound 2 with NS2B-NS3 protease. Both compounds exhibited comparable binding energy as the reference compound, quercetin, with values lower than - 8.1 kcal/mol. Molecular dynamics simulation using GROMACS revealed the stability and stiffness of the complexes over a 100 ns time scale. In addition, an in vitro assay for NS2B-NS3 protease inhibition revealed inhibitory effects of compounds 1 and 2 with IC 50 values of 316.80 µM and 463.30 µM, respectively. The ADMET analyses showed favorable pharmacokinetics profiles that comply with Lipinski's Rule of Five. Collectively, our findings suggest that compounds 1 and 2 inhibit dengue NS2B-NS3 activity. These findings hold promise of methoxyflavones as starting compounds for potential dengue treatment, highlighting the need for further investigation., Competing Interests: Declarations. Conflict of interest: The authors report no competing interests to disclose., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

This study aims to examine the accessibility of Community-Based Rehabilitation trainees to public health services in Malaysia. Quantitative data were collected from 290 parents and guardians across 14 CBR locations using multi-stage simple random sampling. Accessibility to health services and facilities was measured in terms of service availability, suitability, convenience, and adequacy. A four-level Likert scale was employed to assess the condition of the health services and facilities. A questionnaire was employed, and data were analyzed using SPSS. Findings revealed high satisfaction with health campaigns (79.0%), preventive services (74.8%), healthy food programs (74.5%), medical treatment (73.8%), equipment/assistive services (74.1%), and rehabilitation/therapy (67.2%). Results demonstrated significant correlations between trainees' self-change and satisfaction with health services. Improved accessibility to health services was shown to positively impact trainees' ability to perform daily activities, highlighting the importance of tailored, accessible health programs in supporting the development and independence of individuals with disabilities.

Background: Melioidosis is difficult to diagnose due to its wide range of clinical symptoms. The culture method is time-consuming and less sensitive, emphasizing the importance of rapid and accurate diagnostic tests for melioidosis. Burkholderia invasion protein D (BipD) of Burkholderia pseudomallei is a potential diagnostic biomarker. This study aimed to isolate and characterize single-stranded DNA aptamers that specifically target BipD., Methods: The recombinant BipD protein was produced, followed by isolation of BipD-specific aptamers using Systematic Evolution of Ligands by EXponential enrichment. The binding affinity and specificity of the selected aptamers were evaluated using Enzyme-Linked Oligonucleotide Assay., Results: The fifth SELEX cycle showed a notable enrichment of recombinant BipD protein-specific aptamers. Sequencing analysis identified two clusters with a total of seventeen distinct aptamers. AptBipD1, AptBipD13, and AptBipD50 were chosen based on their frequency. Among them, AptBipD1 exhibited the highest binding affinity with a K d value of 1.0 μM for the recombinant BipD protein. Furthermore, AptBipD1 showed significant specificity for B. pseudomallei compared to other tested bacteria., Conclusion: AptBipD1 is a promising candidate for further development of reliable, affordable, and efficient point-of-care diagnostic tests for melioidosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The focus of the current work is the study of the effect of the photo-catalytic activity of ZnO nanoparticles. The photocatalytic destruction of methylene blue dye, a common water contaminant, was used to assess the photocatalytic efficiency of the ZnO nanoparticles from its aqueous solution by using ZnO nanoparticles thin film under UV light and laser irradiation. Sol-gel methods prepared ZnO nanoparticle thin films. X-ray diffraction and a field-emitted scanning electron microscope were utilized to examine the structure of the produced ZnO nanoparticles. An extended characterization by laser-based fluorescence and UV-visible spectroscopic techniques. The effects of operational parameters such as photo-catalyst load and contact time on photocatalytic degradation of methylene blue were investigated. The recent study's findings showed that irradiation with a UV laser increases with power density 25 µW/cm 2 , the photo-catalytic rate. The UV spectra show decay for the band at 664nm decreased and the concentration of M.B. in monomer form decayed to 26% of the original concentration in 24 h, while the band at 612 which is related to the dimer M.B. molecules was not affected. The laser irradiation did the same for monomer M.B. molecules in only 3 h, while the dimer decreased to 28% of its original concentration. The reaction mechanism has been discussed by molecular modelling. Quantum mechanical calculations at B3LYP/6-311g(d,p) level indicated that methylene blue changed from dimers to monomers in the existence of ZnO. The current results present a method for degrading M.B. not only in wastewater but also in the industrial waste scale., (© 2024. The Author(s).)

The primary goal was to enhance the stability and bioavailability of chloramphenicol for ophthalmic use without compromising patient comfort, such as causing blurry vision. This study employed a 2-level full factorial design to optimize the formulation, exploring different concentrations of poloxamer 407 and HPMC to achieve this objective., (© 2024. The Author(s).)

This study focuses on the synthesis of zinc and copper oxide nanoparticles using green methods by plant extracts. The resulting metal oxides were analyzed using FT-IR spectroscopy, TGA, TEM, zeta potential and assessed for their efficacy as pigments based on properties such as Hydrogen Ion Concentration, Oil absorption, Moisture Content, Fineness of grinding, Bleeding, and loss on ignition. The results confirmed that the prepared ZnO and CuO nanoparticles exhibited the formation of nanoparticles in the range of 10-40 nm with potential as pigments. Two paint formulations incorporating these nanoparticles and silicon resins as binders were tested for physico-mechanical attributes, chemical resistance, heat resistance, and corrosion resistance of the dry paint films. The study found that the films containing the prepared oxides demonstrated excellent performance, with no damage or color alteration observed after exposure to temperatures up to 500 °C. Moreover, the paint films containing ZnO nanoparticles showed superior efficiency after a 500 h salt spray test compared to those with CuO nanoparticles. These findings suggest that the synthesized mixed oxide nanoparticles are promising candidates for heat-resistant pigment applications., (© 2024. The Author(s).)

This work focused on the preparation of novel antifouling paint based on Ca 2 Cr 2 O 5 and CaMnO 3 NPs as a safe protective pigment which were replaced with cuprous oxide. Three paint formulations were prepared for comparison, a blank formula without an antifouling agent (F1), a commercial antifouling formula based on 100% cuprous oxide as an antifouling agent (F2), and AF formula based on 75% Ca 2 Cr 2 O 5 and CaMnO 3 NPs and 25% Cu 2 O. The high performance and durability of the paints based on the prepared pigments were evident from their impact resistance, adhesion, pending, hardness, and chemical resistance, which were compared to the blank formula (F1). The corrosion resistance of the painted films was also investigated using the salt spray test method, and the results were promising compared to the blank and standard formulations. All painted steel plates were exposed to seawater through field tests in the Suez Canal at Port Said for up to 6 months. The results showed that the paints based on F2 and F3a, b enhanced the antifouling activity through six months of exposure. The obtained results demonstrated greater efficiency of the painted steel-based F3a than F1 and F3b, and being comparable to the standard formula (F2)., (© 2024. The Author(s).)

Objective: This study aims to develop and validate bioanalytical method for quantifying warfarin in VAMS samples using liquid chromatography tandem mass spectrometry (LC-MS/MS), directly implementing the method to patients receiving warfarin therapy., Methods: The UPLC-MS/MS method was developed and optimized, with quercetin as the internal standard. Sample preparation was carried out using protein precipitation with methanol-acetonitrile (1:3 v/v)., Results: Chromatographic separation was achieved using Acquity® UPLC BEH C18 column with 0.1 % formic acid-acetonitrile-methanol (30:69:1 v/v) as mobile phase, in isocratic elution. Multiple Reaction Monitoring (MRM) detection was done using m / z values of 307.10 → 161.06 for warfarin and 301.03 → 150.98 for quercetin as internal standard, using Electrospray Ionization (ESI) negative ion source. The clinical application of the bioanalytical method was carried out on 25 patients receiving warfarin therapy at Universitas Indonesia Hospital and warfarin levels were well within the calibration range from 6.05 to 431.39 ng/mL., Conclusion: A novel method has been developed to analyze warfarin in VAMS samples. This method has been fully validated according to guideline from FDA 2022 and is linear in the range of 5-500 ng/mL and the value of r ≥ 0.9977, and successfully applied for the analysis of warfarin in VAMS samples of clinical patients., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier Ltd.)

The development of flame-retardant materials has become an important research direction. For the past dozen years, researchers have been exploring flame retardants with high flame-retardant efficiency, low toxicity, less smoke, or other excellent performance flame retardants. Therefore, this work aimed to synthesize new cyclodiphosph(V)azane derivatives and their Cu(II) and Cd(II) metal complexes and investigated their potential applications as high flame-retardant efficiency. Various techniques were used to characterize the prepared ligand H 2 L and its metal complexes, including elemental analyses, mass spectra, conductivity measurements, electronic spectral data UV-vis, FT-IR, 1 H, 13 C-NMR, TGA, XRD, and molecular docking experiments studies were M. tuberculosis receptors (PDB ID: 5UHF) and the crystal structure of human topoisomerase II alpha (PDB ID: 4FM9). Wood-based paint was physically mixed with the ligand H 2 L and its metal complexes. The obtained results of mechanical characteristics of the dried paint layers were noticed to improve, such as gloss value, which ranged from 85 to 95, hardness 1.5-2.5 kg, adhesion 4B to 5B, and impact resistance, which improved from 1.3 to 2.5 J. Moreover, the obtained results of flame-retardant properties showed a significant retardant impact compared to the blank sample, such as ignitability, which includes the heat flux which increased from 10 to 25 kW/m 2 , and ignition time, ranging from 550 to 1200 s, respectively, and limiting oxygen index (LOI) (%) which has been increased from 21 to 130 compared with the plywood sample and sample blank. The ordering activity of the observed results was noticed that coated sample based on Cd(II) metal complexes > coated sample based on Cu(II) metal complexes of Cyclophosphazene ligand > coated sample based on phosphazene ligand H 2 L > coated sample without additives > uncoated sample. This efficiency may be attributed to (1) the H 2 L is an organophosphorus compound, which contains P, N, Cl, and aromatic six- and five-member ring, (2) Cu(II) and Cd(II) metal complexes characterized by high thermal stability, good stability, excellent performance flame retardants, and wide application., (© 2024. The Author(s).)

The Zingiber zerumbet rhizomes are traditionally used to treat fever, and the in vitro inhibitory effect of ethyl acetate extract from Zingiber zerumbet rhizomes (EAEZZR) against DENV2 NS2B/NS3 (two non-structural proteins, NS2 and NS3 of dengue virus type 2) has been reported earlier. This study was carried out to establish an acute toxicity profile and evaluate the anti-fever (anti-pyretic) activities of EAEZZR in yeast-induced fever in rats. The major compound of EAEZZR, zerumbone, was isolated using chromatographic methods including column chromatography (CC) and preparative thin-layer chromatography (PTLC). Additionally, the structure of zerumbone was elucidated using nuclear magnetic resonance (NMR), liquid chromatography mass spectrometer-ion trap-time of flight (LCMS-IT-TOF), infrared (IR), and ultraviolet (UV) spectroscopy. The toxicity of EAEZZR was evaluated using Organization for Economic Cooperation and Development Test Guideline 425 (OECD tg-425) with minor modifications at concentrations EAEZZR of 2000 mg/kg, 3000 mg/kg, and 5000 mg/kg. Anti-fever effect was determined by yeast-induced fever (pyrexia) in rats. The acute toxicity study showed that EAEZZR is safe at the highest 5000 mg/kg body weight dose in Sprague Dawley rats. Rats treated with EAEZZR at doses of 125, 250, and 500 mg/kg exhibited a significant reduction in rectal temperature (T R ) in the first 1 h. EAEZZR at the lower dose of 125 mg/kg showed substantial potency against yeast-induced fever for up to 2 h compared to 0 h in controls. A significant reduction of T R was observed in rats treated with standard drug aspirin in the third through fourth hours. Based on the present findings, ethyl acetate extract of Zingiber zerumbet rhizomes could be considered safe up to the dose of 5000 mg/kg, and the identification of active ingredients of Zingiber zerumbet rhizomes may allow their use in the treatment of fever with dengue virus infection., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: This study aimed to develop, optimize and evaluate glyceryl monooleate (GMO) based cubosomes as a drug delivery system containing cisplatin for treatment of human lung carcinoma., Significance: The significance of this research was to successfully incorporate slightly water soluble and potent anticancer drug (cisplatin) into cubosomes, which provide slow and sustained release of drug for longer period of time., Methods: The delivery system was developed through top-down approach by melting GMO and poloxamer 407 (P407) at 70 °C and then drop-wise addition of warm deionized water (70 °C) containing cisplatin. The formulation then exposed to probe sonicator for about 2 min. A randomized regular two level full factorial design with help of Design Expert was used for optimization of blank cubosomal formulations. Cisplatin loaded cubosomes were then subjected to physico-chemical characterization., Results: The characterization of the formulation revealed that it had a sufficient surface charge of -9.56 ± 1.33 mV, 168.25 ± 5.73 nm particle size, and 60.64 ± 0.11% encapsulation efficiency. The in vitro release of cisplatin from the cubosomes at pH 7.4 was observed to be sustained, with 94.5% of the drug being released in 30 h. In contrast, 99% of cisplatin was released from the drug solution in just 1.5 h. In vitro cytotoxicity assay was conducted on the human lung carcinoma NCI-H226 cell line, the cytotoxicity of cisplatin-loaded cubosomes was relative to that of pure cisplatin solution, while blank (without cisplatin) cubosomes were nontoxic., Conclusions: The obtained results demonstrated the successful development of cubosomes for sustained delivery of cisplatin.

New phenylisoxazole quinoxalin-2-amine hybrids 5a-i were successfully synthesised with yields of 53-85% and characterised with various spectroscopy methods. The synthesised hybrids underwent in vitro α-amylase and α-glucosidase inhibitory assays, with acarbose as the positive control. Through the biological study, compound 5h exhibits the highest α-amylase inhibitory activity with IC 50 = 16.4 ± 0.1 μM while compounds 5a-c, 5e and 5h exhibit great potential as α-glucosidase inhibitors, with 5c being the most potent (IC 50 = 15.2 ± 0.3 μM). Among the compounds, 5h exhibits potential as a dual inhibitor for both α-amylase (IC 50 = 16.4 ± 0.1 μM) and α-glucosidase (IC 50 = 31.6 ± 0.4 μM) enzymes. Through the molecular docking studies, the inhibition potential of the selected compounds is supported. Compound 5h showed important interactions with α-amylase enzyme active sites and exhibited the highest binding energy of -8.9 ± 0.10 kcal mol -1 , while compound 5c exhibited the highest binding energy of -9.0 ± 0.20 kcal mol -1 by forming important interactions with the α-glucosidase enzyme active sites. The molecular dynamics study showed that the selected compounds exhibited relative stability when binding with α-amylase and α-glucosidase enzymes. Additionally, compound 5h demonstrated a similar pattern of motion and mechanism of action as the commercially available miglitol., Competing Interests: The authors declare no conflict of interest., (This journal is © The Royal Society of Chemistry.)

Lung cancer is the one of the most prevalent cancer in the world. It kills more people from cancer than any other cause and is especially common in underdeveloped nations. With 1.2 million instances, it is also the most prevalent cancer in men worldwide, making about 16.7% of the total cancer burden. Surgery is the main form of curative treatment for early-stage lung cancer. However, the majority of patients had incurable advanced non-small cell lung cancer (NSCLC) recurrence after curative purpose surgery, which is indicative of the aggressiveness of the illness and the dismal outlook. The gold standard of treatment for NSCLC patients includes drug targeting of specific mutated genes drive in development of lung cancer. Furthermore, patients with advanced NSCLC and those with early-stage illness needing adjuvant therapy should use cisplatin as it is the more active platinum drug. So, this review encompasses the non-small cell lung cancer microenvironment, treatment approaches, and use of cisplatin as a first-line regimen for NSCLC, its mechanism of action, cisplatin resistance in NSCLC and also the prevention strategies to revert the drug resistance., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Quassinoids are degraded triterpene compounds that can be obtained from various species of the Simaroubaceae plant family, including Eurycoma longifolia. Quassinoids are the major compounds in E. longifolia , and they are known to have various medicinal potentials, such as anticancer and antimalarial properties. Dihydrofolate reductase (DHFR) was reported to be one of the important targets for certain anticancer and antimalarial drugs. Twelve quassinoids from E. longifolia were identified to have anticancer effects based on their IC50 values. This study aimed to evaluate the interactions of these twelve quassinoids with DHFR via Autodock 4.2 software and Biovia Discovery Studio Visualiser., Methods: Twelve quassinoids from E. longifolia and their interactions with DHFR were evaluated via Autodock 4.2 software and Biovia Discovery Studio Visualiser. Their drug-likeness and pharmacokinetic properties were also assessed using the ADMETlab 2.0 program., Results: The molecular docking results showed that eleven quassinoids showed better docking scores than methotrexate, in which the binding energy (BE) of these quassinoids ranged from - 7.87 to -9.58 kcal/mol. Their inhibition constant (Ki) ranged from 0.095 to 1.71 μM. At the same time, the BE and Ki values for methotrexate were -7.80 kcal/mol and 1.64 μM, respectively., Conclusion: From the analysis, 6-dehydrolongilactone and eurycomalide B are among the twelve compounds that showed great potential as hit-to-lead compounds based on the docking score on DHFR, drug-likeness, and ADMET properties. These results suggest a great potential to pursue validation studies via in vitro and in vivo models., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Bisphenol-A (BPA) has a well-proven deleterious effect on the hypothalamicpituitary- gonadal axis., Objectives: The current study investigated the therapeutic potentials of mesenchymal stem cells (MSCs) in a murine model of BPA-induced ovarian damage., Methods: Fifty adult female rats were divided into: Group 1; control group, Group IIa, IIb: rats were given oral gavage of BPA (25 and 50 mg/Kg body weight respectively) on a daily basis for 15 days, and Group IIIa, IIIb; rats were intravenously treated with of MSCs (10 6 cells) after receiving the last dose of BPA as in group II. Plasma and ovarian tissue levels of Malondialdehyde (MDA) and gonadal axis hormones were assessed. Apoptosis was evaluated by TUNNEL assay and by apoptosis markers (FAS, FASL, Caspase 3, SLTM). A histological examination of ovarian tissue was also conducted., Results: BPA resulted in a significant elevation in plasma levels of LH, FSH, and ovarian tissue levels of MDA and a significant decrease in estradiol and progesterone. All genetic and protein markers of apoptosis were elevated in BPA treated group with decreased oestrogen receptor expression in the ovarian tissue. Increased apoptotic cells were confirmed by TUNEL assay. A high dose of BPA was able to increase the number of atretic follicles in the ovarian tissue whereas the numbers of primordial, primary, secondary and Graafian follicles were decreased. All the laboratory and histological abnormalities were ameliorated by treatment with MSCs., Conclusion: The antioxidant and anti-apoptotic effects of MSCs could possibly explain the ability of this therapeutic modality to ameliorate BPA-induced-ovarian damage., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

This study presents the numerical solutions of the fractional schistosomiasis disease model (SDM) using the supervised neural networks (SNNs) and the computational scaled conjugate gradient (SCG), i.e. SNNs-SCG. The fractional derivatives are used for the precise outcomes of the fractional SDM. The preliminary fractional SDM is categorized as: uninfected, infected with schistosomiasis, recovered through infection, expose and susceptible to this virus. The accurateness of the SNNs-SCG is performed to solve three different scenarios based on the fractional SDM with synthetic data obtained with fractional Adams scheme (FAS). The generated data of FAS is used to execute SNNs-SCG scheme with 81% for training samples, 12% for testing and 7% for validation or authorization. The correctness of SNNs-SCG approach is perceived by the comparison with reference FAS results. The performances based on the error histograms (EHs), absolute error, MSE, regression, state transitions (STs) and correlation accomplish the accuracy, competence, and finesse of the SNNs-SCG scheme.

Applications : the study of highly advanced hybrid nanofluids has aroused the interest of academics and engineers, particularly those working in the fields of chemical and applied thermal engineering. The improved properties of hybrid nanoliquids are superior to those of earlier classes of nanofluids (which are simply referred to as nanofluids). Therefore, it is essential to report on the process of analyzing nanofluids by passing them through elastic surfaces, as this is a typical practice in engineering and industrial applications. Purpose and methodology : the investigation of hybrid nanoliquids was the sole focus of this research, which was conducted using a stretched sheet. Using supporting correlations, an estimate was made of the improved thermal conductivity, density, heat capacitance, and viscosity. In addition, the distinctiveness of the model was increased by the incorporation of a variety of distinct physical limitations, such as thermal slip, radiation, micropolarity, uniform surface convection, and stretching effects. After that, a numerical analysis of the model was performed, and the physical results are presented. Core findings : the results of the model showed that it is possible to attain the desired momentum of hybrid nanofluids by keeping the fluidic system at a uniform suction, and that this momentum may be enhanced by increasing the force of the injecting fluid via a stretched sheet. Surface convection, thermal radiation, and high dissipative energy are all great physical instruments that can be used to acquire heat in hybrid nanofluids. This heat acquisition is significant from both an applied thermal engineering perspective and a chemical engineering perspective. The features of simple nano and common hybrid nanoliquids have been compared and the results indicate that hybrid nanofluids exhibit dominant behavior when measured against the percentage concentration of nanoparticles, which enables them to be used in large-scale practical applications., Competing Interests: The authors declare that there is no financial/competing interest regarding this work., (This journal is © The Royal Society of Chemistry.)

Objective: Breast cancer affects women globally, regardless of age or location. On the other hand, Tamoxifen (TXN), a class II biopharmaceutical drug is acting as a prophylactic/treating agent for women at risk of and/or with hormone receptor-positive breast cancer. However, its oral administration has life-threatening side effects, which have led researchers to investigate alternative delivery methods. One such method is transdermal drug delivery utilizing bile salts as penetration enhancers, aka Bilosomes., Methods: Bilosomes formulations were optimized statistically for the outcome of vesicle shape, size, and entrapment efficiency using two types of bile, i.e. sodium taurocholate and sodium cholate. These bilosomes were then loaded into HPMC base gel and further characterized for their morphology, drug content, pH, viscosity, spreadability and eventually ex-vivo skin penetration and deposition studies., Results: Findings showed that sodium cholate has superiority as a penetration enhancer over sodium taurocholate in terms of morphological characterizes, zeta potential, and cumulative amounts of tamoxifen permeated per unit area (15.13 ± 0.71 μg/cm 2 and 6.51 ± 0.6 μg/cm 2 respectively). In fact, bilosomes designed with sodium cholate provided around 9 folds of skin deposition compared to TXN non-bilosomal gel., Conclusion: Bilosomes gels could be a promising option for locally delivering tamoxifen to the breast through the skin, offering an encouraging transdermal solution.

In recent years, in situ gel delivery systems have received a great deal of attention among pharmacists. The in situ gelation mechanism has several advantages over ointments, the most notable being the ability to provide regular and continuous drug delivery with no impact on visual clarity. Bioavailability, penetration, duration, and maximum medication efficacy are all improved by this mechanism. Our review systematically synthesizes and discusses comparisons between three types of in situ gelling system according to their phase change performance based on the physicochemical aspect from publications indexed in the Pubmed, ResearchGate, Scopus, Elsevier, and Google Scholar databases. An optimal temperature-sensitive in situ gelling solution must have a phase change temperature greater than ambient temperature (25 °C) to be able to be readily delivered to the eye; hence, it was fabricated at 35 °C, which is the precorneal temperature. In a pH-sensitive gelling system, a gel develops immediately when the bio-stimuli come into contact with it. An in situ gelling system with ionic strength-triggered medication can also perhaps be used in optical drug-delivery mechanisms. In studies about the release behavior of drugs from in situ gels, different models have been used such as zero-order kinetics, first-order kinetics, the Higuchi model, and the Korsmeyer-Peppas, Peppas-Sahlin and Weibull models. In conclusion, the optimum triggering approach for forming gels in situ is determined by a certain therapeutic delivery application combined with the physico-chemical qualities sought.

Eurycomanone and eurycomalactone are known quassinoids present in the roots and stems of Eurycoma longifolia . These compounds had been reported to have cytotoxic effects, however, their mechanism of action in a few cancer cell lines have yet to be elucidated. This study was aimed at investigating the anticancer effects and mechanisms of action of eurycomanone and eurycomalactone in cervical (HeLa), colorectal (HT29) and ovarian (A2780) cancer cell lines via Sulforhodamine B assay. Their mechanism of cell death was evaluated based on Hoechst 33342 assay and in silico molecular docking toward DHFR and TNF-α as putative protein targets. Eurycomanone and eurycomalactone exhibited in vitro anticancer effects manifesting IC 50 values of 4.58 ± 0.090 µM and 1.60 ± 0.12 µM (HeLa), 1.22 ± 0.11 µM and 2.21 ± 0.049 µM (HT-29), and 1.37 ± 0.13 µM and 2.46 ± 0.081 µM (A2780), respectively. They induced apoptotic cancer cell death in dose- and time-dependent manners. Both eurycomanone and eurycomalactone were also predicted to have good inhibitory potential as demonstrated by the docking into TNF-α with binding affinity of -8.83 and -7.51 kcal/mol, respectively, as well as into DHFR with binding affinity results of -8.05 and -8.87 kcal/mol, respectively. These results support the evidence of eurycomanone and eurycomalactone as anticancer agents via apoptotic cell death mechanism that could be associated with TNF-α and DHFR inhibition as among possible protein targets.

The retrieval of important information from a dataset requires applying a special data mining technique known as data clustering (DC). DC classifies similar objects into a groups of similar characteristics. Clustering involves grouping the data around k-cluster centres that typically are selected randomly. Recently, the issues behind DC have called for a search for an alternative solution. Recently, a nature-based optimization algorithm named Black Hole Algorithm (BHA) was developed to address the several well-known optimization problems. The BHA is a metaheuristic (population-based) that mimics the event around the natural phenomena of black holes, whereby an individual star represents the potential solutions revolving around the solution space. The original BHA algorithm showed better performance compared to other algorithms when applied to a benchmark dataset, despite its poor exploration capability. Hence, this paper presents a multi-population version of BHA as a generalization of the BHA called MBHA wherein the performance of the algorithm is not dependent on the best-found solution but a set of generated best solutions. The method formulated was subjected to testing using a set of nine widespread and popular benchmark test functions. The ensuing experimental outcomes indicated the highly precise results generated by the method compared to BHA and comparable algorithms in the study, as well as excellent robustness. Furthermore, the proposed MBHA achieved a high rate of convergence on six real datasets (collected from the UCL machine learning lab), making it suitable for DC problems. Lastly, the evaluations conclusively indicated the appropriateness of the proposed algorithm to resolve DC issues., Competing Interests: he authors have declared that no competing interests exist., (Copyright: © 2023 Salih et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The terrible reality is that acrylamide (AA) is a common food contaminant found in a wide variety of commonly consumed foods. This research involves the advancement of a more dependable technique for the bio-fabrication of zinc oxide nanoparticles (ZNPs) through the green method using Moringa Oleifera extract (MO-ZNPs) as an efficient chelating agent for acrylamide (AA). The effects of AA on glutathione redox dynamics, liver function, lipid profile, and zinc residues in Sprague Dawley rats are investigated. Finally, the microarchitecture and immunohistochemical staining of Caspase-3 and CYP2E1 were determined in the liver tissue of rats. Four separate groups, including control, MO-ZNPs (10 mg/kg b. wt), AA (20 mg/kg b. wt), and AA + MO-ZNPs for 60 days. The results revealed a suppressed activity of glutathione redox enzymes (GSH, GPX,and GSR) on both molecular and biochemical levels. Also, AA caused elevated liver enzymes, hepatosomatic index, and immunohistochemical staining of caspase-3 and CYP2E1 expression. MO-ZNPs co-treatment, on the other hand, stabilized glutathione-related enzyme gene expression, normalized hepatocellular enzyme levels, and restored hepatic tissue microarchitectures. It could be assumed that MO-ZNPs is a promising hepatoprotective molecule for alleviating AA-induced hepatotoxicity. We witnessed changes in glutathione redox dynamics to be restorative. Glutathione and cytochrome P450 2E1 play crucial roles in AA detoxification, so maintaining a healthy glutathione redox cycle is necessary for disposing of AA toxicity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Phaleria macrocarpa (Scheff.) Boerl. is geographically distributed around Papua Island, Indonesia. Traditionally, P. macrocarpa is exercised to reduce pain, stomachache, diarrhea, tumor problems, blood glucose, cholesterol, and blood pressure. A growing interest in the medicinal values of P. macrocarpa especially in Asia reflects the usage of diverse extraction techniques, particularly modern approaches. In this review article, the extraction methods and solvents relevant to P. macrocarpa were discussed, with the extent of its pharmacological activities. Recent bibliographic databases such as Google Scholar, PubMed, and Elsevier between 2010 and 2022 were assessed. Based on the findings, the pharmacological studies of P. macrocarpa are still pertinent to its traditional uses but primarily emphasise anti-proliferative activity especially colon and breast cancer cells with low toxicity and fruit as the most studied plant part. The utilization of modern separation techniques has predominantly been aimed at extracting mangiferin and phenolic-rich compounds and evaluating their antioxidant capacity. However, the isolation of bioactive compounds remains a challenge, leading to the extensive utilization of the extracts in in vivo studies. This review endeavors to highlight modern extraction methods that could potentially be used as a point of reference in the future for exploring novel bioactive compounds and drug discovery on a multi-scale extraction level., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 Published by Elsevier B.V. on behalf of King Saud University.)

Aerogel is a high-performance thermal resistance material desired for high-temperature applications like dye-sensitized solar cells, batteries, and fuel cells. To increase the energy efficiency of batteries, an aerogel is required to reduce the energy loss arising from the exothermal reaction. This paper synthesized a different composition of inorganic-organic hybrid material by growing the silica aerogel inside a polyacrylamide (PAAm) hydrogel. The hybrid PaaS/silica aerogel was synthesized using different irradiation doses of gamma rays (10-60 kGy) and different solid contents of PAAm (6.25, 9.37, 12.5, and 30 wt %). Here, PAAm is used as an aerogel formation template and carbon precursor after the carbonization process at a temperature of (150, 350, and 1100 °C). The hybrid PAAm/silica aerogel was converted into aluminum/silicate aerogels after soaking in a solution of AlCl 3 . Then, the carbonization process takes place at a temperature of (150, 350, and 1100 °C) for 2 h to provide C/Al/Si aerogels with a density of around 0.18-0.040 gm/cm 3 and porosity of 84-95%. The hybrid C/Al/Si aerogels presented interconnected networks of porous structures with different pore sizes depending on the carbon and PAAm contents. The sample with a solid content of 30% PAAm in the C/Al/Si aerogel was composed of interconnected fibrils whose diameter was about 50 μm. The structure after carbonization at 350 and 1100 °C was a condensed opening porous 3D network structure. This sample gives the optimum thermal resistance and a very low thermal conductivity of 0.073 (w/m·k) at low carbon content (2.71% at temperature 1100 °C) and high v pore (95%) compared with carbon content 42.38% and v pore (93%) which give 0.102 (w/m·k). This is because at 1100 °C, the carbon atoms evolve to leave an area between Al/Si aerogel particles, increasing the pore size. Furthermore, the Al/Si aerogel had excellent removal ability for various oil samples., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

In our paper, we have synthesized modified PEA and alkyd resin by replacing the new source of polyol (SDEA) which was confirmed by different analyses such as IR, and 1HNMR spectra. A series of conformal, novel, low-cost, and eco-friendly hyperbranched modified alkyd and PEA resins were fabricated with bio ZnO, CuO/ZnO) NPs through an ex-situ method for mechanical and anticorrosive coatings. The synthesized biometal oxides NPs and its composite modified alkyd and PEA were confirmed by FTIR, SEM with EDEX, TEM, and TGA, and can be stably dispersed into modified alkyd and PEA resins at a low weight fraction of 1%. The nanocomposite coating was also subjected to various tests to determine their surface adhesion, which ranged from (4B-5B), physico-mechanical characteristics such as scratch hardness, which improved from < 1.5 to > 2 kg, gloss (100-135) Specific gravity (0.92-0.96) and also chemical resistance test which passed for water, acid, and solvent except alkali, was poor because of the hydrolyzable ester group in the alkyd and PEA resins. The anti-corrosive features of the nanocomposites were investigated through salt spray tests in 5 wt % NaCl. The results indicate that well-dispersed bio ZnO and CuO/ZnO) NPs (1.0%) in the interior of the hyperbranched alkyd and PEA matrix improve the durability and anticorrosive attributes of the composites, such as degree of rusting, which ranged from 5 to 9, blistering size ranged from 6 to 9, and finally, scribe failure, which ranged from 6 to 9 mm. Thus, they exhibit potential applications in eco- friendly surface coatings. The anticorrosion mechanisms of the nanocomposite alkyd and PEA coating were attributed to the synergistic effect of bio ZnO and (CuO/ZnO) NPs and the prepared modified resins are highly rich in nitrogen elements, which might be regarded as a physical barrier layer for steel substrates., (© 2023. The Author(s).)

An increase in the occurrence of viral infectious diseases is a global concern for human health. According to a WHO report, dengue virus (DENV) is one of the most common viral diseases affecting approximately 400 million people annually, with worsening symptoms in nearly 1% of cases. Both academic and industrial researchers have conducted numerous studies on viral epidemiology, virus structure and function, source and route of infection, treatment targets, vaccines, and drugs. The development of CYD-TDV or Dengvaxia ® vaccine has been a major milestone in dengue treatment. However, evidence has shown that vaccines have some drawbacks and limitations. Therefore, researchers are developing dengue antivirals to curb infections. DENV NS2B/NS3 protease is a DENV enzyme essential for replication and virus assembly, making it an interesting antiviral target. For faster hit and lead recognition of DENV targets, methods to screen large number of molecules at lower costs are essential. Similarly, an integrated and multidisciplinary approach involving in silico screening and confirmation of biological activity is required. In this review, we discuss recent strategies for searching for novel DENV NS2B/NS3 protease inhibitors from the in silico and in vitro perspectives, either by applying one of the approaches or by integrating both. Therefore, we hope that our review will encourage researchers to integrate the best strategies and encourage further developments in this area., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Norshidah, Leow, Ezleen, Wahab, Vignesh, Rasul and Lai.)

Acetylcholinesterase (AChE) inhibitors remain the primary therapeutic drug that can alleviate Alzheimer's disease's (AD) symptoms. Several Cassia species have been shown to exert significant anti-AChE activity, which can be an alternative remedy for AD. Cassia timoriensis and Cassia grandis are potential plants with anti-AChE activity, but their phytochemical investigation is yet to be further conducted. The aims of this study were to identify the phytoconstituents of C. timoriensis and C. grandis and evaluate their inhibitory activity against AChE and butyrylcholinesterase (BChE). Two compounds were isolated for the first time from C. timoriensis : arachidyl arachidate ( 1 ) and luteolin ( 2 ). Five compounds were identified from C. grandis : β-sitosterol ( 3 ), stigmasterol ( 4 ), cinnamic acid ( 5 ), 4-hydroxycinnamic acid ( 6 ), and hydroxymethylfurfural ( 7 ). Compound 2 showed significant inhibition towards AChE (IC 50 : 20.47 ± 1.10 µM) and BChE (IC 50 : 46.15 ± 2.20 µM), followed by 5 (IC 50: 40.5 ± 1.28 and 373.1 ± 16.4 µM) and 6 (IC 50 : 43.4 ± 0.61 and 409.17 ± 14.80 µM) against AChE and BChE, respectively. The other compounds exhibited poor to slightly moderate AChE inhibitory activity. Molecular docking revealed that 2 showed good binding affinity towards Tc AChE (PDB ID: 1W6R) and Hs BChE (PDB ID: 4BDS). It formed a hydrogen bond with TYR121 at the peripheral anionic site (PAS, 2.04 Å), along with hydrophobic interactions with the anionic site and PAS (TRP84 and TYR121, respectively). Additionally, 2 formed three H-bonds with the binding site residues: one bond with catalytic triad, HIS438 at distance 2.05 Å, and the other two H-bonds with GLY115 and GLU197 at distances of 2.74 Å and 2.19 Å, respectively. The evidence of molecular interactions of 2 may justify the relevance of C. timoriensis as a cholinesterase inhibitor, having more promising activity than C. grandis .

Targeting vascular endothelial growth factor receptor (VEFGR) and its co-receptor neuropilin-1 (NRP-1) is an interesting vascular strategy. tLyp-1 is a tumor-homing and penetrating peptide of 7 amino acids (CGNKRTR). It is a truncated form of Lyp-1 (CGNKRTRGC), which is known to target NRP-1 receptor, with high affinity and specificity. It is mediated by endocytosis via C-end rule (CendR) internalization pathway. The aim of this study is to evaluate the importance of each amino acid in the tLyp-1 sequence through alanine-scanning (Ala-scan) technique, during which each of the amino acid in the sequence was systematically replaced by alanine to produce 7 different analogues. In silico approach through molecular docking and molecular dynamics are employed to understand the interaction between the peptide and its analogues with the NRP-1 receptor, followed by in vitro ligand binding assay study. The C-terminal Arg is crucial in the interaction of tLyp-1 with NRP-1 receptor. Substituting this residue dramatically reduces the affinity of this peptide which is clearly seen in this study. Lys-4 is also important in the interaction, which is confirmed via the in vitro study and the MM-PBSA analysis. The finding in this study supports the CendR, in which the presence of R/K-XX-R/K motif is essential in the binding of a ligand with NRP-1 receptor. This presented work will serve as a guide in the future work pertaining the development of active targeting agent towards NRP-1 receptor., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

According to the World Health Organisation (WHO), as of week 23 of 2022, there were more than 1,311 cases of dengue in Malaysia, with 13 deaths reported. Furthermore, there was an increase of 65.7% during the same period in 2021. Despite the increase in cumulative dengue incidence, there is no effective antiviral drug available for dengue treatment. This work aimed to evaluate several nitro-benzylidene phenazine compounds, especially those that contain 4-hydroxy-3,5- bis ((2-(4-nitrophenyl)hydrazinylidene)-methyl)benzoate through pharmacophore queries selection method as potential dengue virus 2 (DENV2) NS2B-NS3 protease inhibitors. Herein, molecular docking was employed to correlate the energies of selected hits' free binding and their binding affinities. Pan assay interference compounds (PAINS) filter was also adopted to identify and assess the drug-likeness, toxicity, mutagenicity potentials, and pharmacokinetic profiles to select hit compounds that can be considered as lead DENV2 NS2B-NS3 protease inhibitors. Molecular dynamics assessment of two nitro-benzylidene phenazine derivatives bearing dinitro and hydroxy groups at the benzylidene ring showed their stability at the main binding pocket of DENV2 protease, where their MM-PBSA binding energies were between -22.53 and -17.01 kcal/mol. This work reports those two nitro-benzylidene phenazine derivatives as hits with 52-55% efficiency as antiviral candidates. Therefore, further optimisation is required to minimise the lead compounds' toxicity and mutagenicity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Salin, Hariono, Khalili, Zakaria, Saqallah, Mohamad Taib, Kamarulzaman, Wahab and Khawory.)

Fluorescent organic nanoparticles (FONs) are a large family of nanostructures constituted by organic components that emit light in different spectral regions upon excitation, due to the presence of organic fluorophores. FONs are of great interest for numerous biological and medical applications, due to their high tunability in terms of composition, morphology, surface functionalization, and optical properties. Multifunctional FONs combine several functionalities in a single nanostructure (emission of light, carriers for drug-delivery, functionalization with targeting ligands, etc.), opening the possibility of using the same nanoparticle for diagnosis and therapy. The preparation, characterization, and application of these multifunctional FONs require a multidisciplinary approach. In this review, we present FONs following a tutorial approach, with the aim of providing a general overview of the different aspects of the design, preparation, and characterization of FONs. The review encompasses the most common FONs developed to date, the description of the most important features of fluorophores that determine the optical properties of FONs, an overview of the preparation methods and of the optical characterization techniques, and the description of the theoretical approaches that are currently adopted for modeling FONs. The last part of the review is devoted to a non-exhaustive selection of some recent biomedical applications of FONs.

Salinity and water stress are serious environmental issues that reduced crop production worldwide. The current research was initiated (2012) in the wirehouse of the Institute of Soil and Environmental Sciences, University of Agriculture, Faisalabad, Pakistan to investigate the growth, stress tolerance, and physiological responses of guava to salinity and water shortage. Guava was grown for one year in pots containing soil with Eight treatments (control, 10 dS m -1 , 20 dS m -1 , 40 dS m -1 , control + water stress (WS), 10 dS m -1  + WS, 20 dS m -1  + WS, 40 dS m -1  + WS) in a completely randomized design. The results indicated that plant growth, stress tolerance, and physiological parameters declined at higher salinity and water stress and could not survive at 40 dS m -1 . The 20 dS m -1  + WS caused a > 70% decline in dry weights of shoot and root regarding control. Similarly, the highest decrease in stress tolerance was noticed in 20 dS m -1  + WS followed by the 20 dS m -1 treatment than control. Our findings validated that guava can be cultivated on soils having salinity ≤ 10 dS m -1 but it could not be cultivated on soils having salinity ≥ 20 dS m -1 with limited water supply., (© 2022. The Author(s).)

Dengue virus (DENV) is an arbovirus widespread through tropical and subtropical areas. It is transmitted to humans through Aedes mosquitoes. Infections with DENV can lead to a series of complications, including dengue fever, dengue haemorrhagic fever, or dengue shock syndrome, which might manifest through secondary infections because of a vulnerable immune system. To date, only one tetravalent DENV vaccine is approved to be administered to children whom have been previously DENV-infected and between 9 and 16 years of age. One of the key targets in discovering DENV antiviral agents is the NS2b/NS3 protease. This protease is a crucial enzyme complex for the proteolytic and cleavage activities of the translated polyprotein during DENV life cycle. Several studies were conducted to discover potential antivirals from natural sources or synthetic compounds and peptides. In this review, we describe the recent studies from the past five years dealing with isolated natural products as potential inhibitors of DENV with a greater focus on inhibiting the NS2b/NS3 protease. This review describes recent discoveries in anti-DENV potential of isolated phytochemicals belonging to different groups including fatty acids, glucosides, terpenes and terpenoids, flavonoids, phenolics, chalcones, acetamides, and peptides. Curcumin, quercetin, and myricetin were found to act as non-competitive inhibitors for the NS2b/NS3 protease enzyme. In some studies, the molecular targets of some of these compounds are yet to be identified using in-silico and in-vitro approaches. So far, none of the isolated natural products was tested clinically for the management of DENV infections. The discussed studies demonstrate that natural products are a rich source of potential anti-DENV compounds. However, not all of these compounds were studied for their kinetic molecular mechanism and type of inhibition. In-silico studies provided an ample number of phytochemical hits to be tested experimentally as DENV protease inhibitors. In conclusion, derivatives of these natural products can be designed and synthesised, which could enhance their specificity and efficacy towards the protease. Other sources of natural products, such as fungi, bacterial toxins, marine organisms, and animals, should also be explored towards discovering more potential and effective DENV NS2b/NS3 protease inhibitors., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Antirrhinum majus (Snapdragon) is a perennial Mediterranean-native plant that is commonly used for mass display. Few reports acknowledged the traditional use of A. majus for its medicinal and therapeutic effects. Herein, we assess the impact of A. majus 's sample preparation and extraction methods on the plant-aerial parts' phytochemical contents and antimicrobial activity. Furthermore, the microbial targets of the extracts' secondary metabolites are inspected using molecular docking simulations., Methods: The leaves and flowers of A. majus were prepared as fresh and air-dried samples, then extracted using cold maceration and hot reflux, respectively. Extracts with the best phytochemical profiles were selected to test their antimicrobial activities against Bacillus subtilis, Staphylococcus aureus, Enterobacter aerogenes, Escherichia coli and Candida albicans . Besides, molecular docking of 66 reported isolated compounds was conducted against various microbial targets., Results: The dried-refluxed samples revealed a massive deterioration in their phytochemical profiles, whereas the macerated flowers extract exhibited the highest total phenolic content and antimicrobial activity against all tested bacterial strains. However, both flowers and leaves extracts showed similar minimum inhibitory and lethal concentrations against C. albicans . Molecular docking studies revealed that chlorogenic acid, chalcononaringenin 4'-glucoside, 3,4,2',4',6'-pentahydroxy-chalcone 4'-glucoside, apigenin-7-glucuronide, and luteolin-7-glucuronide were the lead compounds in expressing the antimicrobial activity. Yet, A. majus 's compounds could neither inhibit the 30S ribosomal subunit nor muramyl ligase E., Conclusion: Our results suggest that cold maceration of A. majus fresh aerial parts gave higher flavonoid and phenolic content contributing to its antimicrobial properties. These flavonoids and phenolic compounds are predicted to have a crucial role in inhibiting fungal sterol 14-demethylase, and bacterial dihydropteroate synthase and gyrase B subunit proteins., Competing Interests: The authors declare no conflict of interest., (© 2022 Published by Elsevier Ltd.)

Because of the extraordinary advancements in biomedical nanotechnology over the last few decades, traditional drug delivery systems have been transformed into smart drug delivery systems that respond to stimuli. These well-defined nanoplatforms can boost therapeutic targeting efficacy while reducing the side effects/toxicities of payloads, which are crucial variables for enhancing patient compliance by responding to specific internal or external triggers. Cubosomes are lipid-based nano systems that are analogous to well-known vesicular systems, such as lipo- and niosomes. They could be used as part of a unique drug delivery system that includes hydro-, lipo-, and amphiphilic drug molecules. In this review, we critically analyze the relevant literature on cubosomesregarding theories of cubosomeself-assembly, composition, and manufacturing methods, with an emphasis on tumor-targeted drug delivery applications. Due to the bioadhesive and -compatible nature of cubosome dispersion, this review also focuses on a variety of drug delivery applications, including oral, ophthalmic and transdermal.

Despite much interest and studies toward the genus Podocarpus , the anti-malarial evaluation of Podocarpus polystachyus 's phytoconstituents remains lacking. Herein, the phytoconstituents of P. polystachyus leaves and their anti-malarial effect against Plasmodium falciparum were investigated for the first time. One new natural product, 8ß,13ß-kaur-15-en-17-al ( 1 ), along with three known compounds, 8ß,13ß-kaur-15-en-17-ol ( 2 ) and 13ß-kaur-16-ene ( 3 ), and α-tocopherol hydroquinone ( 4 ) were isolated via HR-ESI-MS and NMR analyses. Compounds 1 and 2 inhibited P. falciparum growth at 12 and 52 µM of IC 50 , respectively. Their anti-malarial activity was associated with the in silico P. falciparum lactate dehydrogenase ( Pf LDH) inhibition. Molecular docking of ligands 1 and 2 with the putative target Pf LDH revealed ~-2 kcal/mol of binding energies more negative than the control. Molecular dynamic simulations (100 ns) showed equal or smaller deviation values (RMSD, RMSF, Rg) and stronger interactions of Pf LDH- 1 and Pf LDH- 2 complexes via at least one consistent H-bond than the control. Additionally, a slightly increased Pf LDH H-bond profile in their interactions improved the Pf LDH dynamic and structural stabilities. Overall, this study supports the relevance of 1 and 2 as plasmodial growth inhibitors with their putative anti- Pf LDH activity, which could be a potential scaffold for developing anti-malarial drugs.

Alzheimer's disease (AD) causes progressive memory loss and cognitive dysfunction. It is triggered by multifaceted burdens such as cholinergic toxicity, insulin resistance, neuroinflammation, and oxidative stress. Syzygium plants are ethnomedicinally used in treating inflammation, diabetes, as well as memory impairment. They are rich in antioxidant phenolic compounds, which can be multi-target neuroprotective agents against AD. This review attempts to review the pharmacological importance of the Syzygium genus in neuroprotection, focusing on anti-cholinesterase, anti-diabetic, anti-inflammatory, and antioxidant properties. Articles published in bibliographic databases within recent years relevant to neuroprotection were reviewed. About 10 species were examined for their anti-cholinesterase capacity. Most studies were conducted in the form of extracts rather than compounds. Syzygium aromaticum (particularly its essential oil and eugenol component) represents the most studied species owing to its economic significance in food and therapy. The molecular mechanisms of Syzygium species in neuroprotection include the inhibition of AChE to correct cholinergic transmission, suppression of pro-inflammatory mediators, oxidative stress markers, RIS production, enhancement of antioxidant enzymes, the restoration of brain ions homeostasis, the inhibition of microglial invasion, the modulation of ß-cell insulin release, the enhancement of lipid accumulation, glucose uptake, and adiponectin secretion via the activation of the insulin signaling pathway. Additional efforts are warranted to explore less studied species, including the Australian and Western Syzygium species. The effectiveness of the Syzygium genus in neuroprotective responses is markedly established, but further compound isolation, in silico, and clinical studies are demanded.

Macaranga tanarius (MT) and Syzygium jambos (SJ) are pharmacologically reported to have anti-oxidant, anti-inflammatory, and anti-diabetic effects, and can be neuroprotective agents. Our previous work revealed that MT and SJ exhibited 76.32% and 93.81% inhibition against acetylcholinesterase (AChE) at 50 μg/mL final concentration in their ethyl acetate and hexane fractions, respectively. This study was aimed to investigate the bioactive constituents of MT and SJ and their molecular mechanism toward AChE inhibition. Bioassay-guided isolation afforded prenylflavonoids 1 - 3 from MT and anacardic acid derivatives 4 and 5 from SJ that were confirmed by NMR and MS data. Compound 5 exerted the strongest anti-AChE potential (IC 50 : 0.54 μM), followed by 1 , 4 , 3 , and 2 (IC 50 : 1.0, 2.4, 6.8, and 33 μM, respectively). In silico molecular docking revealed 5 formed stronger molecular interactions including three H-bonds than its derivative 4 based on the saturation of their alkyl chains. The addition of a five carbon-prenyl chain in 1 increased the number of binding interactions, justifying its greater activity than derivatives 2 and 3 . This research reflects the first report of AChE inhibitors from these species, thereby adding pharmacological values to MT and SJ as potential remedies in neuroprotection.

Neuraminidase (NA) is an enzyme that prevents virions from aggregating within the host cell and promotes cell-to-cell spread by cleaving glycosidic linkages to sialic acid. The best-known neuraminidase is the viral neuraminidase, which present in the influenza virus. Thus, the development of anti-influenza drugs that inhibit NA has emerged as an important and intriguing approach in the treatment of influenza. Garcinia atroviridis L. (GA) dried fruits (GAF) are used commercially as seasoning and in beverages. The main objective of this study was to identify a new potential neuraminidase inhibitor from GA. A bioassay-guided fractionation method was applied to obtain the bioactive compounds leading to the identification of garcinia acid and naringenin. In an enzyme inhibition study, garcinia acid demonstrated the highest activity when compared to naringenin. Garcinia acid had the highest activity, with an IC 50 of 17.34-17.53 µg/mL or 91.22-92.21 µM against Clostridium perfringens -NA, and 56.71-57.85 µg/mL or 298.32-304.31 µM against H1N1-NA. Based on molecular docking results, garcinia acid interacted with the triad arginine residues (Arg118, Arg292, and Arg371) of the viral neuraminidase, implying that this compound has the potential to act as a NA enzyme inhibitor.

The present work is to solve the nonlinear singular models using the framework of the stochastic computing approaches. The purpose of these investigations is not only focused to solve the singular models, but the solution of these models will be presented to the extended form of the delayed, prediction and pantograph differential models. The Gudermannian function is designed using the neural networks optimized through the global scheme "genetic algorithms (GA)", local method "sequential quadratic programming (SQP)" and the hybridization of GA-SQP. The comparison of the singular equations will be presented with the exact solutions along with the extended form of delayed, prediction and pantograph based on these singular models. Moreover, the neuron analysis will be provided to authenticate the efficiency and complexity of the designed approach. For the correctness and effectiveness of the proposed approach, the plots of absolute error will be drawn for the singular delayed, prediction and pantograph differential models. For the reliability and stability of the proposed method, the statistical performances "Theil inequality coefficient", "variance account for" and "mean absolute deviation'' are observed for multiple executions to solve singular delayed, prediction and pantograph differential models.

Certain plant extracts (PEs) contain bioactive compounds that have antioxidant and lifespan-extending activities on organisms. These PEs play different roles in cellular processes, such as enhancing stress resistance and modulating longevity-defined signaling pathways that contribute to longevity. Here, we report the discovery of PEs that extended chronological life span (CLS) in budding yeast from a screen of 222 PEs. We identified two PEs, the leaf extracts of Manihot esculenta and Wodyetia bifurcata that extended CLS in a dose-dependent manner. The CLS-extending PEs also conferred oxidative stress tolerance, suggesting that these PEs might extend yeast CLS through the upregulation of stress response pathways.

The aim of this work is to introduce a stochastic solver based on the Levenberg-Marquardt backpropagation neural networks (LMBNNs) for the nonlinear host-vector-predator model. The nonlinear host-vector-predator model is dependent upon five classes, susceptible/infected populations of host plant, susceptible/infected vectors population, and population of predator. The numerical performances through the LMBNN solver are observed for three different types of the nonlinear host-vector-predator model using the authentication, testing, sample data, and training. The proportions of these data are chosen as a larger part, i.e., 80% for training and 10% for validation and testing, respectively. The nonlinear host-vector-predator model is numerically treated through the LMBNNs, and comparative investigations have been performed using the reference solutions. The obtained results of the model are presented using the LMBNNs to reduce the mean square error (MSE). For the competence, exactness, consistency, and efficacy of the LMBNNs, the numerical results using the proportional measures through the MSE, error histograms (EHs), and regression/correlation are performed., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Zulqurnain Sabir et al.)

Drug targeting is a progressive area of research with folate receptor alpha (FRα) receiving significant attention as a biological marker in cancer drug delivery. The binding affinity of folic acid (FA) to the FRα active site provides a basis for recognition of FRα. In this study, FA was conjugated to beta-cyclodextrin (βCD) and subjected to in silico analysis (molecular docking and molecular dynamics (MD) simulation (100 ns)) to investigate the affinity and stability for the conjugated system compared to unconjugated and apo systems (ligand free). Docking studies revealed that the conjugated FA bound into the active site of FRα with a docking score (free binding energy < -15 kcal/mol), with a similar binding pose to that of unconjugated FA. Subsequent analyses from molecular dynamics (MD) simulations, root mean square deviation (RMSD), root mean square fluctuation (RMSF), and radius of gyration (Rg) demonstrated that FA and FA-βCDs created more dynamically stable systems with FRα than the apo-FRα system. All systems reached equilibrium with stable RMSD values ranging from 1.9-2.4 Å and the average residual fluctuation values of the FRα backbone atoms for all residues (except for terminal residues ARG8, THR9, THR214, and LEU215) were less than 2.1 Å with a consistent Rg value of around 16.8 Å throughout the MD simulation time (0-100 ns). The conjugation with βCD improved the stability and decreased the mobility of all the residues (except residues 149-151) compared to FA-FRα and apo-FRα systems. Further analysis of H-bonds, binding free energy (MM-PBSA), and per residue decomposition energy revealed that besides APS81, residues HIS20, TRP102, HIS135, TRP138, TRP140, and TRP171 were shown to have more favourable energy contributions in the holo systems than in the apo-FRα system, and these residues might have a direct role in increasing the stability of holo systems.

Acetylcholinesterase (AChE) inhibitors are the most effective drugs for Alzheimer's disease treatment. However, considering the potential and failure rates of AChE inhibitors, chemical scaffolds targeting cholinesterase specifically are still very limited. Herein, we report a new class of AChE inhibitors identified by employing a virtual screening approach that combines shape similarity with molecular docking calculations. Virtual screening followed by the evaluation of AChE inhibitory activity allowed us to identify 1,2,4-triazolylthioethanones as a novel class of AChE inhibitors. Thirteen compounds with 1,2,4-triazolylthiothanone core and IC 50 values in the range of 0.15±0.07 to 3.32±0.92 μM have been reported here. Our findings shed light into a class of AChE inhibitors that could be useful starting point for the development of novel therapeutics to tackle Alzheimer's disease., (© 2021 Wiley-VCH GmbH.)