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Abstract The most serious long-term effects of diabetes is peripheral artery disease (PAD) which increases the chance of developing diabetic foot ulcers, gangrene and even lower limb amputation. The clinical manifestations of PAD which are typically not revealed until symptoms like intermittent claudication, rest pain and ischemic gangrene develop, are not present in majority of diabetes mellitus patients with PAD due to diabetic peripheral neuropathy. Therefore, current study is aimed to evaluate the inflammatory and endothelial dysfunction markers with their correlation to biomarkers that can help for in-time diagnosis and efficient prognosis of developing diabetes-associated PAD. Enzyme-linked immunosorbent assay was used to evaluate the interlukin-6, interlukin-8, intercellular adhesion molecule (ICAM) and vascular cell adhesion molecule (VCAM) in PAD with diabetes group, diabetic group and healthy individual group while biomarkers were measured by kit method. It was observed that serum IL-6, IL-8, ICAM and VCAM levels in type II diabetes mellitus (T2DM) with PAD patients were increased significantly (85.93, 597.08, 94.80 and 80.66) as compared to T2DM patients (59.52, 231.34, 56.88 and 50.19) and healthy individuals (4.81, 16.93, 5.55 and 5.16). The overall means for the parameters, IL-6, IL-8, ICAM, VCAM, urea, S/creatinine, CK-MB, AST, ALT, cholesterol, triglyceride, HDL, LDL, PT, aPTT, INR, HbA1C, and CRP within all groups were significantly (P

The author posits that the establishment of a blockchain-based health data marketplace where EHR, IoMT, and wearable-derived data can be monetized by selling it to data consumers like medical professionals, researchers, regulators, third-party (e.g., AI service providers) and policymakers can solve this data centralization problem.

The study examined the effects of jasmonic acid (100 nmol, JA) priming and foliar application of spermidine (1 mM, Spd), both individually and combined, on mitigating cadmium (100 µM, Cd) stress-induced oxidative damage in wheat. Cadmium stress reduced plant height and dry mass, but JA priming and/or Spd treatment increased resistance. Cd stress significantly decreased carotenoids, total chlorophylls, glutamate 1-semialdehyde (GSA), and δ-aminolevulinic acid (ALA), but JA and Spd treatments counteracted these reductions. Photosynthetic parameters improved under JA and Spd treatments, with combined treatment showing greater alleviation. Cd exposure increased lipid peroxidation, hydrogen peroxide, electrolyte leakage, and superoxide, but these oxidative stress indicators were significantly reduced after JA and Spd treatment. Antioxidant enzyme activity was upregulated by JA priming and Spd application, both under unstressed and Cd-stressed conditions. JA and/or Spd treatments also increased ascorbic acid, lowered glutathione concentration, and upregulated glyoxylase activity, reducing methylglyoxal accumulation. Additionally, secondary compounds (phenols and flavonoids) and osmolytes (proline and glycine betaine) levels improved. Proline oxidase activity decreased, indicating controlled proline buildup, while γ-glutamyl kinase activity increased. JA and/or Spd treatments significantly reduced Cd accumulation in seedlings. The study concluded that JA and Spd treatments enhance the plant's defensive mechanisms against oxidative stress by boosting antioxidant enzymes and secondary metabolism.

An important component of the pathogenicity of potentially pathogenic bacteria in humans is the urease enzyme. In order to avoid the detrimental impact of ureolytic bacterial infections, the inhibition of urease enzyme appears to be an appealing approach. Therefore, in the current study, morpholine-thiophene hybrid thiosemicarbazone derivatives (5a-i) were designed, synthesized and characterized through FTIR, 1H NMR, 13C NMR spectroscopy and mass spectrometry. A range of substituents including electron-rich, electron-deficient and inductively electron-withdrawing groups on the thiophene ring was successfully tolerated. The synthesized derivatives were evaluated in vitro for their potential to inhibit urease enzyme using the indophenol method. The majority of compounds were noticeably more potent than the conventional inhibitor, thiourea. The lead inhibitor, 2-(1-(5-chlorothiophen-2-yl)ethylidene)-N-(2-morpholinoethyl)hydrazinecarbothioamide (5g) inhibited the urease in an uncompetitive manner with an IC50 value of 3.80 ± 1.9 µM. The findings of the docking studies demonstrated that compound 5g has a strong affinity for the urease active site. Significant docking scores and efficient binding free energies were displayed by the lead inhibitor. Finally, the ADME properties of lead inhibitor (5g) suggested the druglikeness behavior with zero violation.

Diabetes mellitus is a multi-systematic chronic metabolic disorder and life-threatening disease resulting from impaired glucose homeostasis. The inhibition of glucosidase, particularly α-glucosidase, could serve as an effective methodology in treating diabetes. Attributed to the catalytic function of glucosidase, the present research focuses on the synthesis of sulfonamide-based acyl pyrazoles (5a-k) followed by their in vitro and in silico screening against α-glucosidase. The envisaged structures of prepared compounds were confirmed through NMR and FTIR spectroscopy and mass spectrometry. All compounds were found to be more potent against α-glucosidase than the standard drug, acarbose (IC50 = 35.1 ± 0.14 µM), with IC50 values ranging from 1.13 to 28.27 µM. However, compound 5a displayed the highest anti-diabetic activity (IC50 = 1.13 ± 0.06 µM). Furthermore, in silico studies revealed the intermolecular interactions of most potent compounds (5a and 5b), with active site residues reflecting the importance of pyrazole and sulfonamide moieties. This interaction pattern clearly manifests various structure–activity relationships, while the docking results correspond to the IC50 values of tested compounds. Hence, recent investigation reveals the medicinal significance of sulfonamide-clubbed pyrazole derivatives as prospective therapeutic candidates for treating type 2 diabetes mellitus (T2DM).

Because there are a few typos in the supersymmetry-breaking sfermion masses and trilinear soft term, regarding the current Large Hadron Collider (LHC) and dark matter searches, we revisit a three-family Pati–Salam model based on intersecting D6-branes in Type IIA string theory on a T6/(Z2×Z2) orientifold with a realistic phenomenology. We study the viable parameter space and discuss the spectrum consistent with the current LHC Supersymmetry searches and the dark matter relic density bounds from the Planck 2018 data. For the gluinos and first two generations of sfermions, we observe that the gluino mass is in the range [2, 14] TeV, the squarks mass range is [2, 13] TeV and the sleptons mass is in the range [1, 5] TeV. We achieve the cold dark matter relic density consistent with 5σ Planck 2018 bounds via A-funnel and coannihilation channels such as stop–neutralino, stau–neutralino, and chargino–neutralino. Except for a few chargino–neutralino coannihilation solutions, these solutions satisfy current nucleon-neutralino spin-independent and spin-dependent scattering cross-sections and may be probed by future dark matter searches.

Introduction: Cancer contributes to a high mortality rate worldwide spanning its diversity from genetics to resistant therapeutic response. To date emerging strategies to combat and manage cancer are particularly focused on the development of targeted therapies as conventional treatments account for the destruction of normal cells as well. In this regard, medicinal plant-based therapies are quite promising in imposing minimal side effects; however, limitations like poor bioavailability and stability of bioactive phytochemicals are associated with them. In parallel, nanotechnology provides nominal solution to deliver particular therapeutic agent without compromising its stability.Methods: In this study, Solanum nigrum, an effective medicinal plant, loaded arabinoxylan cross-linked β-cyclodextrin nanosponges (SN-AXCDNS) were designed to evaluate antitumor activity against breast cancer. Therefore, SN-AXCDNS were prepared by using cross-linker melt method and characterized by physicochemical and pharmacological parameters.Results: Hydrodynamic size, zeta potential and entrapment efficiency (EE%) were estimated as 226 ± 4 nm, −29.15 ± 5.71 mV and 93%, respectively. Surface morphology of nanocomposites showed spherical, smooth, and porous form. Antitumor pharmacological characterization showed that SN loaded nanosponge demonstrated higher cytotoxicity (22.67 ± 6.11 μg/mL), by inducing DNA damage as compared to void SN extract. Flow cytometry analysis reported that encapsulated extract promoted cell cycle arrest at sub-G1 (9.51%). Moreover, in vivo analysis demonstrates the reduction in tumor weight and 85% survival chances in nanosponge treated mice featuring its effectiveness. In addition, in silico analysis revealed that β-cyclodextrin potentially inhibits MELK in breast cancer cell lines (B.E = −10.1 Kcal/mol).Conclusion: Therefore, findings of current study elucidated the therapeutic potential of β-cyclodextrin based nanosponges to be an alternative approach regarding the delivery and solubilization of antitumor drugs.

Background: Monkeypox virus is an enveloped DNA virus that belongs to Poxviridae family. The virus is transmitted from rodents to primates via infected body fluids, skin lesions, and respiratory droplets. After being infected with virus, the patients experience fever, myalgia, maculopapular rash, and fluid-filled blisters. It is necessary to differentiate monkeypox virus from other poxviruses during diagnosis which can be appropriately envisioned via DNA analysis from swab samples. During small outbreaks, the virus is treated with therapies administered in other orthopoxviruses infections and does not have its own specific therapy and vaccine. Consequently, in this article, two potential peptides have been designed. Methods: For the purpose of designing a vaccine, protein sequences were retrieved followed by the prediction of B- and T-cell epitopes. Afterward, vaccine structures were predicted which were docked with toll-like receptors. The docked complexes were analyzed with iMODS. Moreover, vaccine constructs nucleotide sequences were optimized and expressed in silico. Results: COP-B7R vaccine construct (V1) has antigenicity score of 0.5400, instability index of 29.33, z-score of − 2.11-, and 42.11% GC content whereas COP-A44L vaccine construct (V2) has an antigenicity score of 0.7784, instability index of 23.33, z-score of − 0.61, and 48.63% GC content. It was also observed that COP-A44L can be expressed as a soluble protein in Escherichia coli as compared to COP-B7R which requires a different expression system. Conclusion: The obtained results revealed that both vaccine constructs show satisfactory outcomes after in silico investigation and have significant potential to prevent the monkeypox virus. However, COP-A44L gave better results.

Abstract The World Health Organization categorized SARS-CoV-2 as a variant of concern, having numerous mutations in spike protein, which have been found to evade the effect of antibodies stimulated by the COVID-19 vaccine. The susceptibility to omicron variant by immunization-induced antibodies are direly required for risk evaluation. To avoid the risk of arising viral illness, the construction of a specific vaccine that triggers the production of targeted antibodies to combat infection remains highly imperative. The aim of the present study is to develop a particular vaccine exploiting bioinformatics approaches which can target B- and T-cells epitopes. Through this approach, novel epitopes of the S protein-SARS-CoV-2 were predicted for the development of a multiple epitope vaccine. Multiple epitopes were selected on the basis of toxicity, immunogenicity and antigenicity, and vaccine subunit was constructed having potential immunogenic properties. The epitopes were linked with 3 types of linker EAAAK, AAY and GPGPG for vaccine construction. Subsequently, vaccine structure was docked with the receptor and cloned in a pET-28a (+) vector. The constructed vaccine was ligated in pET-28a (+) vector in E. coli using the SnapGene tool for the expression study and a good immune response was observed. Several computational tools were used to predict and analyze the vaccine constructed by using spike protein sequence of omicrons. The current study identified a Multi-Epitope Vaccine (MEV) as a significant vaccine candidate that could potentially help the global world to combat SARS-CoV-2 infections.

Phosphorus (P) availability is the major constrain in obtaining optimum crop yield in calcareous soils due to its precipitation as dicalcium and octacalcium phosphate by reacting with Ca+2 and Mg+2. Therefore, we explored the role of phosphate solubilizing bacteria (without and with PSB @ 2 kg ha−1) in optimizing maize yield and P availability from soluble and insoluble P sources applied @ of 100 kg P2O5 into calcareous soil. PSB inoculation significantly improved maize plant height (5.6%), 1,000 grain weight (11%), dry matter (7.5%), stover (10.8%) and grain yield (6.8%), plant P concentration (10.1%) and uptake (18.6%), extractable P (3.1%), agronomic (48%) and uptake (53%) P use efficiency over uninoculated plots. Phosphorus application significantly improved maize yield, soil health and agronomic P use efficiency (4.84 times over control); however, its impact was more pronounced when applied as 50% P each from farmyard manure (FYM) and single super phosphate (SSP). On the basis of overall performance, the sources were ranked as 50% FYM + 50% SSP >50% rock phosphate (RP) + 50% SSP > 100% SSP > 75% FYM + 25% SSP > 75% RP +25% SSP > 100% FYM > 100 RP > control. Interactively, a significant and maximum increased over absolute control in most of the soil and plant tested characteristics were observed when 100 kg P2O5 ha−1 was supplemented 50% each as FYM and SSP along with PSB inoculation which was followed by 50% P each as FYM and SSP demonstrating that PSB were effective in enhancing RP solubilization under calcareous soil. Maximum value cost ratio of 3.1 was observed for 50% P each as FYM and SSP + PSB which was similar to 100% P as FYM + PSB and 75% FYM+ 25% SSP + PSB. Therefore, in calcareous soil P shall be amended 50% each as organic and mineral sources with PSB for its efficient utilization and obtaining optimum yield of maize.

With the growing use of digital technologies, the vision of a predictive, preventive and personalised healthcare system, commonly termed healthcare 4.0, is becoming tangible. However, the manifestation of healthcare 4.0 relies on empowering patients as active stakeholders of the healthcare system and transforming traditionally siloed data repositories into accessible ones. Combining blockchain-like distributed technology and Airbnb-like sharing economy model, this paper proposes a digital health data marketplace (DHDM) through which patients, as the data producer, can sell their health data to data consumers like medical practitioners, researchers, policymakers and machine learning algorithm developers without compromising privacy and security. In conjunction with the Welsh Secure Anonymised Information Linkage (SAIL) Databank, a traditional centralised and siloed data repository, DHDM was evaluated in a simulated environment to understand the technical feasibility, regulation compliance and, most importantly, the impact of such marketplace on healthcare 4.0 transformation.

Fall armyworm (FAW), Spodoptera frugiperda (Lepidoptera: Noctuidae) is most destructive specie of genus Spodoptera for several agricultural crops. In Pakistan's Sindh province, the invasive fall armyworm Spodoptera frugiperda was first documented causing serious maize damage in 2019. There is need to develop management strategies against this pest in the country. The current study was conducted to check the toxicity of different insecticides against FAW in maize field. The results showed among tested insecticides, deltamethrin was recorded most toxic insecticide followed by chlorantraniliprole and emamectin benzoate. At 1d days after first spray, least number of larvae were recorded with deltamethrin (0.07 larvae/plant), chlorantraniliprole (0.11d larvae/plant) and emamectin benzoate (0.13 larvae/plant). After three days application of first spray, significantly a minimum number of larvae were recorded with deltamethrin (1.11bcd larvae/plant) chlorantraniliprole (1.13d larvae/plant) and emamectin benzoate (1.17d larvae/plant). The maximum and minimum population of larvae was recorded at 1st day of first spray and 14 days of spray, respectively. The least number of larvae were recorded at 14 days of second spray. At 14 days after 2nd spray, 0.07ab, 0.10e and 0.10de larvae per plant were recorded with deltamethrin, chlorantraniliprole and emamectin benzoate, respectively.

Weeping fig, Ficus benjamina, belongs to Moraceae family is planted alongside the roads as decorative plant and landscape purposes. Fig plants were seen infested with Trilocha varians for three years ago in University of Agriculture Faisalabad, Punjab Pakistan. The complete defoliation, even death of whole plant was observed caused by larvae. The complete metamorphosis was recorded with five larval instars. The fecundity of female was recorded very high (180-300) during its whole life period. The results showed that male was long lived than female. Further studies on current pest biology, host range, biological fauna and management associated with it are necessary to avoid future outbreak in Pakistan.

While the past 50 years have been categorized as the Information or Digital Age, the mass amounts of digitized data has been sorely underutilized. It was only recently through the COVID-19 pandemic that accelerated efforts were sought to harness this data with the use of blockchain technology in healthcare. Through the infrastructure and its tokenization applications, we can now effectively leverage healthcare data into more efficient business processes, secure better patient engagement and outcomes all while generating new revenue streams for an array of healthcare stakeholders. It is in compiling this stockpiled data into new, compliant business models and utilizing blockchain technology that we can reap the full potential of this era. Here are some predictions as to how we might set about these efforts in 2023.

Despite substantial progress achieved with shrimp production during the last three and a half decades, growth of shrimp export remains minimal in Bangladesh. In the absence of effective traceability and transparency practices, a wide range of malpractice occurs both at the production and post-harvest stages. Traditional paper-based record-keeping methods for the shrimp supply chain are disparate and, therefore, cannot provide efficient traceability capacity and holistic view of the supply chain. These limit the identification of any issues in earlier juncture to proactively ensure food safety, best practice, and good governance. Addressing this multiplexed challenge, we present here ShrimpChain, a public-private hybrid blockchain-based conceptual framework. Focusing on the export market and utilizing existing technologies, the conceptual framework addresses the traceability, transparency, and certification challenges associated with shrimp export. In this framework, from the post-larva purchasing to the final packaging stage, relevant data for every stage will be entered by the associated actors via mobile/web app or Internet of Things devices to the blockchain network. Data authentication will be achieved by a novel approach of incorporating community consensus in conjunction with the machine-derived data entry timestamping method. Instead of the traditional central and endpoint certification approach, we propose a distributed and accumulative score-based certification approach that will grade packaged shrimps according to the completeness and accuracy of the authenticated data entered during different stages. Such distributed approach of certification will enhance not only food safety but also the quality and compliance to best practices. Most importantly, engaging shrimp farmers in the safety and quality assurance as well as to the certification process will empower them to have better control over the market and incentive to produce high-quality shrimp for high-value market.

The increasing use of social media has led to the emergence of a new challenge in the form of abusive content. There are many forms of abusive content such as hate speech, cyberbullying, offensive language, and abusive language. This article will present a review of abusive content automatic detection approaches. Specifically, we are focusing on the recent contributions that were using natural language processing (NLP) technologies to detect the abusive content in social media. Accordingly, we adopt PRISMA flow chart for selecting the related papers and filtering process with some of inclusion and exclusion criteria. Therefore, we select 25 papers for meta-analysis and another 87 papers were cited in this article during the span of 2017–2021. In addition, we searched for the available datasets that are related to abusive content categories in three repositories and we highlighted some points related to the obtained results. Moreover, after a comprehensive review this article propose a new taxonomy of abusive content automatic detection by covering five different aspects and tasks. The proposed taxonomy gives insights and a holistic view of the automatic detection process. Finally, this article discusses and highlights the challenges and opportunities for the abusive content automatic detection problem.

Chickpea (Cicer arietinum L.) is a major pulse crop worldwide, renowned for its nutritional richness and adaptability. Weeds are the main biotic factor deteriorating chickpea yield and nutritional quality, especially Asphodelus tenuifolius Cav. The present study concerns a two-year (2018–19 and 2019–20) field trial aiming at evaluating the effect of weed management on chickpea grain quality. Several weed management practices have been here implemented under a factorial randomized complete block design, including the application of four herbicides [bromoxynil (C7H3Br2NO) + MCPA (Methyl-chlorophenoxyacetic acid) (C9H9ClO3), fluroxypyr + MCPA, fenoxaprop-p-ethyl (C18H16ClNO5), pendimethalin (C13H19N3O4)], the extracts from two allelopathic weeds (Sorghum halepense and Cyperus rotundus), two mulches (wheat straw and eucalyptus leaves), a combination of A. tenuifolius extract and pendimethalin, and an untreated check (control). Chickpea grain quality was measured in terms of nitrogen, crude protein, crude fat, ash, and oil content. The herbicides pendimethalin (Stomp 330 EC (emulsifiable concentrate) in pre-emergence at a rate of 2.5 L ha−1) and fenoxaprop-p-ethyl (Puma Super 7.5 EW (emulsion in water) in post-emergence at a rate of 1.0 L ha−1), thanks to A. tenuifolius control, showed outstanding performance, providing the highest dietary quality of chickpea grain. The herbicides Stomp 330 EC, Buctril Super 40 EC, Starane-M 50 EC, and Puma Super 7.5 EW provided the highest levels of nitrogen. Outstanding increases in crude protein content were observed with all management strategies, particularly with Stomp 330 EC and Puma Super 7.5 EW (+18% on average). Ash content was highly elevated by Stomp 330 EC and Puma Super 7.5 EW, along with wheat straw mulching, reaching levels of 2.96% and 2.94%. Crude fat content experienced consistent elevations across all treatments, with the highest improvements achieved by Stomp 330 EC, Puma Super 7.5 EW, and wheat straw mulching applications. While 2018–19 displayed no significant oil content variations, 2019–20 revealed the highest oil content (5.97% and 5.96%) with herbicides Stomp 330 EC and Puma Super 7.5 EW, respectively, followed by eucalyptus leaves mulching (5.82%). The results here obtained are of key importance in the agricultural and food sector for the sustainable enhancement of chickpea grain’s nutritional quality without impacting the environment.

Background: Since the SARS-CoV-2 outbreak in December 2019 in Wuhan, China, the virus has infected more than 153 million individuals across the world due to its human-to-human transmission. The USA is the most affected country having more than 32-million cases till date. Sudden high fever, pneumonia and organ failure have been observed in infected individuals. Objectives: In the current situation of emerging viral disease, there is no specific vaccine, or any therapeutics available for SARS-CoV-2, thus there is a dire need to design a potential vaccine to combat the virus by developing immunity in the population. The purpose of present study was to develop a potential vaccine by targeting B and T-cell epitopes using bioinformatics approaches. Methods: B- and T-cell epitopes are predicted from novel M protein-SARS-CoV-2 for the development of a unique multiple epitope vaccine by applying bioinformatics approaches. These epitopes were analyzed and selected for their immunogenicity, antigenicity scores, and toxicity in correspondence to their ability to trigger immune response. In combination to epitopes, best multi-epitope of potential immunogenic property was constructed. The epitopes were joined using EAAAK, AAY and GPGPG linkers. Results: The constructed vaccine showed good results of worldwide population coverage and promising immune response. This constructed vaccine was subjected to in-silico immune simulations by C-ImmSim. Chimeric protein construct was cloned into PET28a (+) vector for expression study in Escherichia coli using snapgene. Conclusion: This vaccine design proved effective in various computer-based immune response analysis as well as showed good population coverage. This study is solely dependent on developing M protein-based vaccine, and these in silico findings would be a breakthrough in the development of an effective vaccine to eradicate SARS-CoV-2 globally.

We employ the low energy Minimal Supersymmetric Standard Model (MSSM) to explore the parameter space associated with Z-pole and Higgs-pole solutions. Such parameter spaces can not only saturate the cold dark matter relic density bound within 5σ set by the Planck 2018, but also satisfy the other standard collider mass bounds and B-physics bounds. In particular, we show that the right-handed selectron can be light. Thus, we propose a search for the relatively heavier right-handed selectron at the future lepton colliders with the center-of-mass energy s=240 GeV and integrated luminosity 3000 fb−1 via the mono-photon channel: eR+eR−→χ˜10(bino)+χ˜10(bino)+γ. We show that for the Z-pole case the right-handed selectron will be excluded up to 180 GeV and 210 GeV respectively at 3σ and 2σ, while the right-handed selectron will be excluded up to 140 GeV and 180 GeV respectively at 3σ and 2σ in case of Higgs-pole.

The influence of dry leachates of Acasia saligna was tested on the seedling growth, photosynthesis, biochemical attributes, and gene expression of the economically important crops, including wheat (Triticum aestivum L.), radish (Raphanus sativus L.), barley (Hordeum vulgare L.) and arugula (Eruca sativa L.). Different concentrations (5%, 10%, 15%, 20%, and 25%) of stem extract (SE) and leaf extract (LE) of A. saligna were prepared, and seedlings were allowed to grow in Petri plates for 8 days. The results showed that all plant species exhibited reduced germination rate, plant height, and fresh and dry weight due to leachates extracts of A. saligna. Moreover, the activities of antioxidant enzymes, including superoxide dismutase (SOD), catalase (CAT), and ascorbate peroxidase (APX), exhibited differential regulation due to the extract treatment. The SOD was increased with increasing the concentration of extracts, while CAT and APX activities were decreased with increasing the extract concentrations. In addition, leachate extract treatment decrease chlorophyll content, photosynthesis, PSII activity, and water use efficiency, with evident effects at their higher concentrations. Furthermore, the content of proline, sugars, protein, total phenols, and flavonoids were reduced considerably due to leachates extract treatments. Furthermore, seedlings treated with high concentrations of LE increased the expression of genes. The present results lead to the conclusion that A. saligna contains significant allelochemicals that interfere with the growth and development of the tested crop species and reduced the crops biomass and negatively affected other related parameters. However, further studies are suggested to determine the isolation and purification of the active compounds present in A. saligna extracts.

Non-small cell lung cancer (NSCLC) is the most common form of lung cancer. Despite the existence of various therapeutic options, NSCLC is still a major health concern due to its aggressive nature and high mutation rate. Consequently, HER3 has been selected as a target protein along with EGFR because of its limited tyrosine kinase activity and ability to activate PI3/AKT pathway responsible for therapy failure. We herein used a BioSolveIT suite to identify potent inhibitors of EGFR and HER3. The schematic process involves screening of databases for constructing compound library comprising of 903 synthetic compounds (602 for EGFR and 301 for HER3) followed by pharmacophore modeling. The best docked poses of compounds with the druggable binding site of respective proteins were selected according to pharmacophore designed by SeeSAR version 12.1.0. Subsequently, preclinical analysis was performed via an online server SwissADME and potent inhibitors were selected. Compound 4k and 4m were the most potent inhibitors of EGFR while 7x effectively inhibited the binding site of HER3. The binding energies of 4k, 4m, and 7x were −7.7, −6.3 and −5.7 kcal/mol, respectively. Collectively, 4k, 4m and 7x showed favorable interactions with the most druggable binding sites of their respective proteins. Finally, in silico pre-clinical testing by SwissADME validated the non-toxic nature of compounds 4k, 4m and 7x providing a promising treatment option for chemoresistant NSCLC.

The Fermi-Lab Collaboration has announced the results for the measurement of muon anomalous magnetic moment. Combining with the previous results by the BNL experiment, we have 4.2σ deviation from the Standard Model (SM), which strongly implies the new physics around 1 TeV. To explain the muon anomalous magnetic moment naturally, we analyze the corresponding five Feynman diagrams in the supersymmetry SMs (SSMs), and show that the Electroweak Supersymmetry (EWSUSY) is definitely needed. We realize the EWSUSY in the Minimal SSM (MSSM) with Generalized Minimal Supergravity (GmSUGRA). With the Feynman diagram inspired focus scan and general scan, we find large viable parameter space, which is consistent with all the current experimental constraints. In particular, the Lightest Supersymmetric Particle (LSP) neutralino can be at least as heavy as 550 GeV. Most of the viable parameter space can be probed at the future HL-LHC, while we do need the future HE-LHC to probe some viable parameter space. However, it might still be challenge if R-parity is violated.

In this paper, novel computing paradigm by exploiting the strength of feed-forward artificial neural networks (ANNs) with Levenberg-Marquardt Method (LMM), and Bayesian Regularization Method (BRM) based backpropagation is presented to find the solutions of initial value problems (IVBs) of linear/nonlinear pantograph delay differential equations (LP/NP-DDEs). The dataset for training, testing and validation is created with reference to known standard solutions of LP/NP-DDEs. ANNs are implemented using the said dataset for approximate modeling of the system on mean squared error based merit functions, while learning of the adjustable parameters is conducted with efficacy of LMM (ANN-LMM) and BRMs (ANN-BRM). The performance of the designed algorithms ANN-LMM and ANN-BRM on IVPs of first, second and third order NP-FDEs are verified by attaining a good agreement with the available solutions having accuracy in the range from 10-5 to 10-8 and are further endorsed through error histograms and regression measures.

During the COVID-19 pandemic, we witnessed how sharing of biological and biomedical data have facilitated the researchers, medical practitioners and policymakers to tackle the pandemic at a global scale. Despite the growing use of EHR by medical practitioners and wearable digital gadgets by individuals, 80% of the health and medical data remain unused, adding little value to the researchers and medical practitioners. Legislative constraints related to health data sharing, centralised siloed design of traditional data management systems and most importantly, lack of incentivisation models are thought to be the underpinning bottlenecks for sharing health data. With the advent of the General Data Protection Regulation (GDPR) of the EU and the development of technologies like blockchain and distributed ledger technologies (DLT), it is now possible to create a new paradigm of data sharing by changing the incentivisation model from current authoritative or altruistic form to a shared economic model where financial incentivisation will be the main driver for data sharing. This can be achieved by setting up a digital health data marketplace (DHDM). Here we reviewed papers that proposed technical models or implemented frameworks that use blockchain-like technologies for health data. We seek to understand and compare different technical challenges associated with implementing and optimising the DHDM operation outlined in these papers. We also examined the legal limitations in the context of European Union and other countries such as the USA to accommodate any compliance requirement for such a marketplace. Last but not least, we reviewed papers that investigated the short, medium and long terms socioeconomic impact of such a marketplace on a wide range of stakeholders.

Alkaptonuria (AKU) is a rare genetic autosomal recessive disorder characterized by elevated serum levels of homogentisic acid (HGA). In this disease, tyrosine metabolism is interrupted because of the alterations in homogentisate dioxygenase (HGD) gene. The patient suffers from ochronosis, fractures, and tendon ruptures. To date, no medicine has been approved for the treatment of AKU. However, physiotherapy and strong painkillers are administered to help mitigate the condition. Recently, nitisinone, an FDA-approved drug for type 1 tyrosinemia, has been given to AKU patients in some countries and has shown encouraging results in reducing the disease progression. However, this drug is not the targeted treatment for AKU, and causes keratopathy. Therefore, the foremost aim of this study is the identification of potent and druggable inhibitors of AKU with no or minimal side effects by targeting 4-hydroxyphenylpyruvate dioxygenase. To achieve our goal, we have performed computational modelling using BioSolveIT suit. The library of ligands for molecular docking was acquired by fragment replacement of reference molecules by ReCore. Subsequently, the hits were screened on the basis of estimated affinities, and their pharmacokinetic properties were evaluated using SwissADME. Afterward, the interactions between target and ligands were investigated using Discovery Studio. Ultimately, compounds c and f were identified as potent inhibitors of 4-hydroxyphenylpyruvate dioxygenase.

Alzheimer’s disease (AD) is one of the progressive neurological disorders and the main cause of dementia all over the world. The multifactorial nature of Alzheimer’s disease is a reason for the lack of effective drugs as well as a basis for the development of new structural leads. In addition, the appalling side effects such as nausea, vomiting, loss of appetite, muscle cramps, and headaches associated with the marketed treatment modalities and many failed clinical trials significantly limit the use of drugs and alarm for a detailed understanding of disease heterogeneity and the development of preventive and multifaceted remedial approach desperately. With this motivation, we herein report a diverse series of piperidinyl-quinoline acylhydrazone therapeutics as selective as well as potent inhibitors of cholinesterase enzymes. Ultrasound-assisted conjugation of 6/8-methyl-2-(piperidin-1-yl)quinoline-3-carbaldehydes (4a,b) and (un)substituted aromatic acid hydrazides (7a-m) provided facile access to target compounds (8a-m and 9a-j) in 4–6 min in excellent yields. The structures were fully established using spectroscopic techniques such as FTIR, 1H- and 13C NMR, and purity was estimated using elemental analysis. The synthesized compounds were investigated for their cholinesterase inhibitory potential. In vitro enzymatic studies revealed potent and selective inhibitors of AChE and BuChE. Compound 8c showed remarkable results and emerged as a lead candidate for the inhibition of AChE with an IC50 value of 5.3 ± 0.51 µM. The inhibitory strength of the optimal compound was 3-fold higher compared to neostigmine (IC50 = 16.3 ± 1.12 µM). Compound 8g exhibited the highest potency and inhibited the BuChE selectively with an IC50 value of 1.31 ± 0.05 µM. Several compounds, such as 8a-c, also displayed dual inhibitory strength, and acquired data were superior to the standard drugs. In vitro results were further supported by molecular docking analysis, where potent compounds revealed various important interactions with the key amino acid residues in the active site of both enzymes. Molecular dynamics simulation data, as well as physicochemical properties of the lead compounds, supported the identified class of hybrid compounds as a promising avenue for the discovery and development of new molecules for multifactorial diseases, such as Alzheimer’s disease (AD).

The development of new drugs/drug candidates for medical treatment remains an exciting but challenging process as only a limited number of synthetic compounds fit well into the discovery and development process after multiple experiments and screening for their preclinical properties [...]

With the significant growth of internet usage, people increasingly share their personal information online. As a result, an enormous amount of personal information and financial transactions become vulnerable to cybercriminals. Phishing is an example of a highly effective form of cybercrime that enables criminals to deceive users and steal important data. Since the first reported phishing attack in 1990, it has been evolved into a more sophisticated attack vector. At present, phishing is considered one of the most frequent examples of fraud activity on the Internet. Phishing attacks can lead to severe losses for their victims including sensitive information, identity theft, companies, and government secrets. This article aims to evaluate these attacks by identifying the current state of phishing and reviewing existing phishing techniques. Studies have classified phishing attacks according to fundamental phishing mechanisms and countermeasures discarding the importance of the end-to-end lifecycle of phishing. This article proposes a new detailed anatomy of phishing which involves attack phases, attacker’s types, vulnerabilities, threats, targets, attack mediums, and attacking techniques. Moreover, the proposed anatomy will help readers understand the process lifecycle of a phishing attack which in turn will increase the awareness of these phishing attacks and the techniques being used; also, it helps in developing a holistic anti-phishing system. Furthermore, some precautionary countermeasures are investigated, and new strategies are suggested.

In the past few decades, there has been a sharp rise of research irreproducibility and retraction, to a point that now is deemed as a crisis. Addressing this crisis, we present a peer-to-peer (P2P) publication model that utilizes blockchain and smart contract technologies. Focusing primarily on researchers and reviewers, the conceptual P2P publication model addresses the sociocultural and incentivization aspects of the irreproducibility crisis. In the P2P publication model, instead of a complete publication, a preapproved experimental design will be published on an incremental basis (unit-by-unit) and authorship will be shared with reviewers. The concept of the P2P publication model was inspired by the transformational journey the music publishing industry has undertaken as it traverses through vinyl age (complete albums) to the Spotify age (single-by-single), where there is a growing inclination among artists toward building an incremental album, taking account of feedback from fans and utilizing automated revenue collection and sharing systems. The ability to publish incrementally through the P2P publication model will relieve researchers from the burden of publishing complete and “good results” while simultaneously incentivizing reviewers to undertake rigorous review work to gain authorship credit in the research. The proposed P2P publication model aims to transform the century-old publication model and incentivization structure in alignment with open access publication ethos of the 21st century.

Voriconazole (VRC) is a broad-spectrum antifungal agent belonging to BCS class II (biopharmaceutical classification system). Despite many efforts to enhance its solubility, this primary issue still remains challenging for formulation scientists. Transethosomes (TELs) are one of the potential innovative nano-carriers for improving the solubility and permeation of poorly soluble and permeable drugs. We herein report voriconazole-loaded transethosomes (VRCT) fabricated by the cold method and followed by their incorporation into carbopol 940 as a gel. The prepared VRCT were evaluated for % yield, % entrapment efficiency (EE), surface morphology, possible chemical interaction, particle size, zeta potential, and polydispersity index (PDI). The optimized formulation had a particle size of 228.2 nm, a zeta potential of −26.5 mV, and a PDI of 0.45 with enhanced % EE. Rheology, spreadability, extrudability, in vitro release, skin permeation, molecular docking, antifungal, and antileishmanial activity were also assessed for VRCT and VRC loaded transethosomal gel (VTEG). Ex-vivo permeation using rat skin depicted a transdermal flux of 22.8 µg/cm2/h with enhanced efficiency up to 4-fold. A two-fold reduction in inhibitory as well as fungicidal concentration was observed against various fungal strains by VRCT and VTEG besides similar results against L-donovani. The development of transethosomal formulation can serve as an efficient drug delivery system through a topical route with enhanced efficacy and better patient compliance.

Trust in corporations, governments and public services has been steadily declining over the last few decades. Lack of transparency and auditability has been a key driver for this decline. Blockchain technology has been commended as a solution that can help with disintermediation and filling the consistently increasing trust challenges faced by corporate and public sector. Public services are seeking solutions that can help establish trust and increase transparency with its citizens and businesses are undertaking extensive business analysis to determine the need and effectiveness of blockchain like platforms as the basis for transforming their existing platforms. Due to the decisive nature, most of the analysis results thus indicate that if a trusted third party is an option, then blockchain should not be used. Here we highlight the challenges and opportunities of establishing trust and how blockchain technology can help public services bridge the trust gap with its citizens. We argue that all information technology systems rely on a suite of technologies, thus blockchain should be added to the current technology stack rather than taking an “all or nothing” approach. We also argue that analysing the effectiveness of futuristic technology like blockchain with industrial age methodology and mind set may limit the realisation of its impact on society and economy. Therefore, we propose to take a heuristic approach where different properties of blockchain technology needs to be mapped against different aspects of current business process with a futuristic view in mind. Taking Companies House – a government organisation that holds over four million UK based companies records as an example, we demonstrate how certain business processes in Companies House can benefit from adapting a blockchain based solution.

Transgender community face serious socio-economic predicaments due to the discrepancy between their current gender expression and assigned gender identity at birth. Even though, a considerable amount work have been done to protect their basic human rights such as security, equality and social acceptance; trans people are still large victims of hate related crimes. With GDPR and other data protection laws and policies in place, now it is ever more important to protect the confidentiality of gender change information as well as to establish technical solutions that can prevent from inferring any sense of gender change from historical data. In this context, distributed ledger technologies such as blockchain present great opportunities for information integrity, security, privacy and access. However, at the same time provenance information extracted from immutable blockchain can be exploited to infer gender change. Addressing this paradox here we propose recommendations for managing gender change information in the blockchain environment in context of present sociopolitical, legislative and technical challenges associated with gender change.

This present work is designed to evaluate the anti-diabetic potential of 22 ginsenosides via the inhibition against rat lens aldose reductase (RLAR), and human recombinant aldose reductase (HRAR), using DL-glyceraldehyde as a substrate. Among the ginsenosides tested, ginsenoside Rh2, (20S) ginsenoside Rg3, (20R) ginsenoside Rg3, and ginsenoside Rh1 inhibited RLAR significantly, with IC50 values of 0.67, 1.25, 4.28, and 7.28 µM, respectively. Moreover, protopanaxadiol, protopanaxatriol, compound K, and ginsenoside Rh1 were potent inhibitors of HRAR, with IC50 values of 0.36, 1.43, 2.23, and 4.66 µM, respectively. The relationship of structure–activity exposed that the existence of hydroxyl groups, linkages, and their stereo-structure, as well as the sugar moieties of the ginsenoside skeleton, represented a significant role in the inhibition of HRAR and RLAR. Additional, various modes of ginsenoside inhibition and molecular docking simulation indicated negative binding energies. It was also indicated that it has a strong capacity and high affinity to bind the active sites of enzymes. Further, active ginsenosides suppressed sorbitol accumulation in rat lenses under high-glucose conditions, demonstrating their potential to prevent sorbitol accumulation ex vivo. The findings of the present study suggest the potential of ginsenoside derivatives for use in the development of therapeutic or preventive agents for diabetic complications.

Background/AimsClassical M1 macrophage activation exhibits an inflammatory phenotype while alternative M2 macrophage activation exhibits an anti-inflammatory phenotype. We aimed to determine whether there are discriminant patterns of macrophage polarization in Crohn's disease (CD) and intestinal tuberculosis (iTB).MethodsColonic mucosal biopsies from 29 patients with iTB, 50 with CD, and 19 controls were examined. Dual colored immunohistochemistry was performed for iNOS/CD68 (an M1φ marker) and CD163/CD68 (an M2φ marker), and the ratio of M1φ to M2φ was assessed. To establish the innate nature of macrophage polarization, we analyzed the extent of mitochondrial depolarization, a key marker of inflammatory responses, in monocyte-derived macrophages obtained from CD and iTB patients, following interferon-γ treatment.ResultsM1φ polarization was more prominent in CD biopsies (P=0.002) than in iTB (P=0.2) and control biopsies. In granuloma-positive biopsies, including those in CD, M1φ predominance was significant (P=0.001). In iTB, the densities of M1φ did not differ between granuloma-positive and granuloma-negative biopsies (P=0.1). Interestingly, higher M1φ polarization in CD biopsies correlated with high inflammatory response exhibited by peripheral blood-derived monocytes from these patients.ConclusionsProinflammatory M1φ polarization was more common in colonic mucosa of CD patients, especially in the presence of mucosal granulomas. Further characterization of the innate immune system could help in clarifying the pathology of iTB and CD.

Type 2 diabetes mellitus has been a major health issue with increasing morbidity and mortality due to macrovascular and microvascular complications. The urgent need for improved methods to control hyperglycemic complications reiterates the development of innovative preventive and therapeutic treatment strategies. In this perspective, xanthone compounds in the pericarp of the mangosteen fruit, especially α-mangostin (MGN), have been recognized to restore damaged pancreatic β-cells for optimal insulin release. Therefore, taking advantage of the robust use of nanotechnology for targeted drug delivery, we herein report the preparation of MGN loaded nanosponges for anti-diabetic therapeutic applications. The nanosponges were prepared by quasi-emulsion solvent evaporation method. Physico-chemical characterization of formulated nanosponges with satisfactory outcomes was performed with Fourier transform infra-red (FTIR) spectroscopy, differential scanning calorimetry (DSC), and scanning electron microscopy (SEM). Zeta potential, hydrodynamic diameter, entrapment efficiency, drug release properties, and stability studies at stress conditions were also tested. Molecular docking analysis revealed significant interactions of α-glucosidase and MGN in a protein-ligand complex. The maximum inhibition by nanosponges against α-glucosidase was observed to be 0.9352 ± 0.0856 µM, 3.11-fold higher than acarbose. In vivo studies were conducted on diabetic rats and plasma glucose levels were estimated by HPLC. Collectively, our findings suggest that MGN-loaded nanosponges may be beneficial in the treatment of diabetes since they prolong the antidiabetic response in plasma and improve patient compliance by slowly releasing MGN and requiring less frequent doses, respectively.

The rapidly growing global burden of cancer poses a major challenge to public health and demands a robust approach to access promising anticancer therapeutics. In parallel, nanotechnology approaches with various pharmacological properties offer efficacious clinical outcomes. The use of new artificial variants of nanosponges (NS) as a transporter of chemotherapeutic drugs to target cells has emerged as a very promising tool. Therefore, in this research, ethylcellulose (EC) NS were prepared using the ultrasonication assisted-emulsion solvent evaporation technique. Withaferin-A (WFA), an active ingredient in Withania somnifera, has been implanted into the nanospongic framework with enhanced anticancer properties. Inside the polymeric structure, WFA was efficiently entrapped (85 ± 11%). The drug (WFA) was found to be stable within polymeric nanosponges, as demonstrated by Fourier transform infrared (FTIR) spectroscopy and differential scanning calorimetry (DSC) studies. The WFA-NS had a diameter of 117 ± 4 nm and zeta potential of −39.02 ± 5.71 mV with a polydispersity index (PDI) of 0.419 ± 0.073. In addition, scanning electron microscopy (SEM) revealed the porous surface texture of WFA-NS. In vitro anticancer activity (SRB assay) results showed that WFA–NS exhibited almost twice the anticancer efficacy against MCF-7 cells (IC50 = 1.57 ± 0.091 µM), as quantified by flow cytometry and comet tests. Moreover, fluorescence microscopy with DAPI staining and analysis of DNA fragmentation revealed apoptosis as a mechanism of cancer cell death. The anticancer activity of WFA-NS was further determined in vivo and results were compared to cisplatin. The anticancer activity of WFA-NS was further investigated in vivo, and the data were consistent to those obtained with cisplatin. At Day 10, WFA-NS (10 mg/kg) significantly reduced tumour volume to 72 ± 6%, which was comparable to cisplatin (10 mg/kg), which reduced tumour volume to 78 ± 8%. Finally, the outcomes of molecular modeling (in silico) also suggested that WFA established a stable connection with nanosponges, generating persistent hydrophobic contacts (polar and nonpolar) and helping with the attractive delayed-release features of the formulation. Collectively, all the findings support the use of WFA in nanosponges as a prototype for cancer treatment, and opened up new avenues for increasing the efficacy of natural product-derived medications.

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder and the leading cause of dementia worldwide. The limited pharmacological approaches based on cholinesterase inhibitors only provide symptomatic relief to AD patients. Moreover, the adverse side effects such as nausea, vomiting, loss of appetite, muscle cramps, and headaches associated with these drugs and numerous clinical trial failures present substantial limitations on the use of medications and call for a detailed insight of disease heterogeneity and development of preventive and multifactorial therapeutic strategies on urgent basis. In this context, we herein report a series of quinoline-thiosemicarbazone hybrid therapeutics as selective and potent inhibitors of cholinesterases. A facile multistep synthetic approach was utilized to generate target structures bearing multiple sites for chemical modifications and establishing drug-receptor interactions. The structures of all the synthesized compounds were fully established using readily available spectroscopic techniques (FTIR, 1H- and 13C-NMR). In vitro inhibitory results revealed compound 5b as a promising and lead inhibitor with an IC50 value of 0.12 ± 0.02 μM, a 5-fold higher potency than standard drug (galantamine; IC50 = 0.62 ± 0.01 μM). The synergistic effect of electron-rich (methoxy) group and ethylmorpholine moiety in quinoline-thiosemicarbazone conjugates contributes significantly in improving the inhibition level. Molecular docking analysis revealed various vital interactions of potent compounds with amino acid residues and reinforced the in vitro results. Kinetics experiments revealed the competitive mode of inhibition while ADME properties favored the translation of identified inhibitors into safe and promising drug candidates for pre-clinical testing. Collectively, inhibitory activity data and results from key physicochemical properties merit further research to ensure the design and development of safe and high-quality drug candidates for Alzheimer’s disease.

Alzheimer’s disease (AD), a progressive neurodegenerative disorder, characterized by central cognitive dysfunction, memory loss, and intellectual decline poses a major public health problem affecting millions of people around the globe. Despite several clinically approved drugs and development of anti-Alzheimer’s heterocyclic structural leads, the treatment of AD requires safer hybrid therapeutics with characteristic structural and biochemical properties. In this endeavor, we herein report a microwave-assisted synthesis of a library of quinoline thiosemicarbazones endowed with a piperidine moiety, achieved via the condensation of 6/8-methyl-2-(piperidin-1-yl)quinoline-3-carbaldehydes and (un)substituted thiosemicarbazides. The target N-heterocyclic products were isolated in excellent yields. The structures of all the synthesized compounds were fully established using readily available spectroscopic techniques (FTIR, 1H- and 13C-NMR). Anti-Alzheimer potential of the synthesized heterocyclic compounds was evaluated using acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes. The in vitro biochemical assay results revealed several compounds as potent inhibitors of both enzymes. Among them, five compounds exhibited IC50 values less than 20 μM. N-(3-chlorophenyl)-2-((8-methyl-2-(piperidin-1-yl)quinolin-3-yl)methylene)hydrazine carbothioamide emerged as the most potent dual inhibitor of AChE and BChE with IC50 values of 9.68 and 11.59 μM, respectively. Various informative structure–activity relationship (SAR) analyses were also concluded indicating the critical role of substitution pattern on the inhibitory efficacy of the tested derivatives. In vitro results were further validated through molecular docking analysis where interactive behavior of the potent inhibitors within the active pocket of enzymes was established. Quinoline thiosemicarbazones were also tested for their cytotoxicity using MTT assay against HepG2 cells. Among the 26 novel compounds, there were five cytotoxical and 18 showed proliferative properties.

In a continuation of our previous work for the exploration of novel enzyme inhibitors, two new coumarin-thiazole 6(a–o) and coumarin-oxadiazole 11(a–h) hybrids have been designed and synthesized. All the compounds were characterized by 1H- and 13C-NMR spectroscopy and elemental analysis. New hybrid analogs were evaluated against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) in order to know their potential for the prevention of Alzheimer's disease (AD). In coumarinyl thiazole series, compound 6b was found as the most active member against AChE having IC50 value of 0.87 ± 0.09 μM, while the compound 6j revealed the same efficacy against BuChE with an IC50 value of 11.01 ± 3.37 μM. In case of coumarinyl oxadiazole series, 11a was turned out to be the lead candidate against AChE with an IC50 value of 6.07 ± 0.23 μM, whereas compound 11e was found significantly active against BuChE with an IC50 value of 0.15 ± 0.09 μM. To realize the binding interaction of these compounds with AChE and BuChE, the molecular docking studies were performed. Compounds from coumarinyl thiazole series with potent AChE activity (6b, 6h, 6i, and 6k) were found to interact with AChE in the active site with MOE score of −10.19, −9.97, −9.68, and −11.03 Kcal.mol−1, respectively. The major interactions include hydrogen bonding, π-π stacking with aromatic residues, and interaction through water bridging. The docking studies of coumarinyl oxadiazole derivatives 11(a–h) suggested that the compounds with high anti-butyrylcholinesterase activity (11e, 11a, and 11b) provided MOE score of −9.9, −7.4, and −8.2 Kcal.mol−1, respectively, with the active site of BuChE building π-π stacking with Trp82 and water bridged interaction.

2-(4-Chlorophenyl)-2-oxoethyl 3-bromobenzoate, C15H10BrClO3, was synthesized in a single-step reaction by condensation of 3-bromobenzoic acid with 2-bromo-1-(4-chlorophenyl)ethanone in dimethylformamide in the presence of triethylamine as a catalyst. The structure consists of an aryl ketone moiety linked to an aryl ester unit by a methylene group. Both units are reasonably planar (r.m.s. deviations of 0.119 and 0.010 Å for the aryl ketone and aryl ester units, respectively) and are almost orthogonal, with an angle of 88.60 (3)° between them. In the crystal, molecules form five separate sets of inversion dimers. Three of these are generated by two C—H...O interactions and a C—H...Br contact, and form chains along c and along the ab cell diagonal. In addition, two inversion-related π–π stacking interactions between like aryl rings again form chains of molecules but in this instance along the bc diagonal. These contacts generate infinite layers of molecules parallel to (011) and stack the molecules along the a-axis direction.

A facile one-pot synthesis of methyl 5-(4-chlorobenzoyloxy)-1-phenyl-1H-pyrazole-3-carboxylate (4) is described. The title compound was efficiently synthesized by the reaction of phenyl hydrazine, dimethyl acetylenedicarboxylate and 4-chlorobenzoyl chloride in dichloromethane under reflux in good yield. The structure of the target compound was deduced by modern spectroscopic and analytical techniques and unequivocally confirmed by a single crystal X-ray diffraction analysis. The crystal of the title compound belongs to orthorhombic system, space group P 21 21 21 with cell parameters a = 6.6491(3) Å, b = 7.9627(6) Å, c = 30.621(5) Å, α = β = γ = 90° and Z = 4. The crystal packing of the compound (4) is stabilized by an offset π-stacking between the planar benzoyl-substituted diazole moieties.

The acid catalyzed esterification of 2,6-dimethoxybenzoic acid (1) in the presence of absolute ethanol afforded ethyl 2, 6-dimethoxybenzoate (2). The structure of the resulting compound was supported by spectroscopic data and unambiguously confirmed by single crystal X-ray diffraction studies. The title compound crystallized in the triclinic space group P ī with unit cell parameters a = 8.5518(3) Å, b = 10.8826(8) Å, c = 11.9939(6) Å, α = 101.273(5)°, β = 98.287(3)°, γ = 94.092(4)°, V = 1077.54(10) Å3, Z = 4, Dc = 1.296 Mg/m3, F(000) = 448 and μ = 0.098 mm−1. Compound (2) crystallizes with two molecules in the asymmetric unit with similar conformations.

OBJECTIVE: To determine the degree of hypovitaminosis D in healthy medical college students. METHODS: This institution based cross-sectional study was conducted at Peshawar Medical College, Peshawar. One hundred and four healthy students were included in the study. Those who were taking vitamin D supplements, having any chronic disorder or having signs and symptoms of vitamin D deficiency were excluded from the study. A semi structured questionnaire was administered to all the participants to know about their demographic details, daily milk consumption and approximate duration of daily sunlight exposure. Five milliliter of blood was collected from the participants for determination of vitamin D levels. RESULTS: The mean age of the sample was 23.26+0.98. There were 65 (62.5%) girls and 39 (37.5%) boys. The mean vitamin D level was 11.88±0.41 ngm/mL in male and 10.02±0.42 ngm/mL in female students. Vitamin D deficiency was observed in 99 (95.19%) cases. A total of 3(2.88%) students had mild deficiency, 19 (18.26%) were having moderate deficiency, and 77(74%) were having severe deficiency. Regarding the daily milk consumption, 70 (67.30%) students didn’t consume even a single cup of milk per day & 29(27.88%) used to take 1 cup of milk per day. Sun exposure of >120 minutes was observed in 84.6% of boys and 12.3% of girls and

The molecule of the title compound, C16H13BrO3, is built of two approximately planar fragments, viz. 3-bromobenzoate [maximum deviation = 0.055 (2) Å and 2-oxo-2-p-tolylethyl [maximum deviation = 0.042 (2) Å], inclined by 46.51 (7)°. In the crystal, weak C—H...O hydrogen bonds and Br...Br contacts [3.6491 (7) Å] connect the molecules into infinite layers parallel to (-221).