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Background: Hyperuricemia is associated with several disease conditions, such as atherosclerosis, arthritis, kidney stones, and many others. Xanthine oxidase (XO) is an enzyme that catalyzes the conversion of xanthine to uric acid. Hence, XO is a major therapeutic drug target in the treatment of hyperuricemia and associated disorders. Objectives: The current study aimed to identify XO inhibitors based on quinazoline derivatives, with the potential to be used against gout and other hyperuricemia-associated diseases. Methods: In the current study, eighteen quinazoline derivatives 2-19 were synthesized and assessed for their in vitro xanthine Oxidase (XO) inhibitory activity. Furthermore, the most active compounds, 5 and 17, were subjected to kinetics studies, followed by computational docking. Human BJ fibroblast cells were used to measure the cytotoxicity of active compounds. Results: Compounds 4-6, 8, 10, 13, 15-17, and 19 were found active against XO, with an IC50 values between 33.688 to 362.173μM. The obtained results showed that compounds 5 and 17 possess a significant xanthine oxidase inhibitory activity. The kinetics and molecular docking studies suggested that compounds 5 (IC50 = 39.904 ± 0.21 μM) and 17 (IC50 = 33.688 ± 0.30 μM) bind in the allosteric site of XO and exhibit a non-competitive type of inhibition. The molecular docking studies also predicted that the NH group of the pyrimidine ring binds with Ser344 residues of XO. Furthermore, all active compounds were non-cytotoxic on the human BJ fibroblasts cell line. Conclusion: This study identifies a series of quinazoline compounds as xanthine oxidase inhibitors, with the potential to be further investigated.

Background: In medicinal chemistry, searching for new therapeutic entities to treat diabetes mellitus is of great concern. The piperidinyl-substituted chalcone scaffold has piqued our interest as a potential antidiabetic agent. Methods: A variety of piperidinyl-substituted chalcones 2–28 were synthesized and tested for α-amylase inhibitory and 2,2-diphenyl-1-picrylhydrazyl and 2,2′-azino- bis(3-ethylbenzothiazoline-6-sulfonic acid) radical-scavenging activities. Results: Compared with the standard acarbose, all compounds inhibited α-amylase, with IC50 values of 9.86–35.98 μM. Docking studies revealed an important binding interaction with the enzyme’s catalytic site. The compounds also demonstrated promising radical-scavenging potential against 2,2-diphenyl-1-picrylhydrazyl and 2,2′-azino- bis(3-ethylbenzothiazoline-6-sulfonic acid) radicals. Conclusion: This study has identified potential lead candidates for further advanced research searching for antidiabetic agents.

Aim: To synthesize pyrrolopyridine-based thiazolotriazoles as a novel class of α-amylase and α-glucosidase inhibitors and to determine their enzymatic kinetics. Methodology: Pyrrolopyridine-based thiazolotriazole analogs (1–24) were synthesized and characterized through proton nuclear magnetic resonance, carbon-13 nuclear magnetic resonance and high-resolution electron ionization mass spectrometry. Results: All synthesized analogs displayed good inhibitory potential of α-amylase and α-glucosidase ranging 17.65–70.7 μM and 18.15–71.97 μM, respectively, compared with the reference drug, acarbose (11.98 μM and 12.79 μM). Analog 3 was the most potent among the synthesized analogs, having α-amylase and α-glucosidase inhibitory activity at 17.65 and 18.15 μM, respectively. The structure–activity relationship and binding modes of interactions between selected analogs were confirmed via docking and enzymatic kinetics studies. The compounds (1–24) were tested for cytotoxicity against the 3T3 mouse fibroblast cell line and were observed to be nontoxic.

The 7-quinolinyl bearing 1,3,4-thiadiazole-2-amine analogues were synthesized (1–17) and based on the literature these analog were screened in vitro for their α-amylase and α-glucosidase inhibitory profile. All analogues showed moderate to good inhibitory potentials ranging between 0.80 ± 0.05 µM to 40.20 ± 0.70 µM and 1.20 ± 0.10 µM to 43.30 ± 0.80 µM against α-amylase and α-glucosidase. Among the series, analogues 2 (IC50 = 2.10 ± 0.10 µM), (IC50 = 2.40 ± 0.10 µM), 3 (IC50 = 0.80 ± 0.05 µM), (IC50 = 1.20 ± 0.10 µM) and 4 (IC50 = 1.50 ± 0.10 µM), (IC50 = 1.90 ± 0.10 µM) with flouro substitution at phenyl ring of the 1,3,4-thiadiazole ring were identified to be the most potent inhibitors against α-amylase and α-glucosidase enzymes. The structure of all the newly synthetics analogues were confirmed by using different types of spectroscopic techniques such as HREI-MS, 1H- and 13C-NMR spectroscopy. To find structure-activity relationship, molecular docking studies were carry out to understand the binding mode of active inhibitors with active site of enzymes and results supported the experimental data. Due to the most potent inhibitory activity of analogue 4 among all the synthesized compound, it was screened against streptozotocin induced diabetic animal model.

Locally advanced breast cancer (LABC) is a subset of breast cancer with locoregional progression without distant metastasis. The multimodality treatment (surgery, chemotherapy, radiotherapy, hormonal and targeted therapy if required) could significantly improve results in this specific group of patients. The complex and multiple options of treatment with similar mortality rates but different outcomes depending on the patient’s desires, preferences and social environment require aid to facilitate the individual patient’s decisions (e.g. Decision Aids (DAs) targeting patients considering primary or adjuvant treatment in LABC). In this context, DAs have been proven fundamental to help patients and clinicians share and agree on the best value option. The current systematic review aimed to evaluate the existing DAs related to these patients with LABC and identify current status and possible improvement areas (possible scarcity and heterogeneity of instruments, the status of their development, explanation of their purpose,…). No previous systematic reviews have been published on this topic. Following Prospero registration no: CRD42021286173, studies about LABC DAs were identified, without data or language restrictions, through a systematic search of bibliographic databases in December 2021. Quality was assessed using Qualsyst criteria (range 0.0–1.0). The quality of the 17 selected studies ranged from 0.46 to 0.95. Of them, 14/17 (82%) were DAs about treatment, only one (6%) about diagnosis, and 2/17 (12%) about the employment of DAs. No screening or follow-up DAs were retrieved. Twelve (70.6%) DAs were online tools. They varied broadly regarding their characteristics and purposes. Most of the studies focused on developing and testing different DAs (5/17; 29.4%) and their impact (7/17; 41.2%). Only 4/17 (23.5%) analysed their implementation and cost. These instruments have proven to improve patient’s knowledge and decision-making, decrease patient anxiety, and patients tend to undergo treatment. However, nowadays, there is still a need for further research and consensus on methodology to develop practical DAs.

Aims: The synthesis of bioactive compounds has antioxidant potential. Background: All aerobic bodies including human beings, have antioxidant defense systems that protect them from oxidative damage, and many enzymes to remove or heal damaged molecules. However, this normal antioxidant mechanism can be incompetent, and hence dietary intakes of antioxidant compounds are important. Objective: Synthesis of isophthalate Schiff base derivatives 1-14 and screened for their antioxidant activities (DPPH, ferrous ion Fe2+ chelating and ferric Fe3+ reducing activities) Method: This study aimed to synthesize isophthalate Schiff base derivatives 1-14 and screen them for their antioxidant activities (DPPH, ferrous ion Fe2+ chelating, and ferric Fe3+ reducing activities). Result: Compounds were screened for their antioxidant activities (DPPH, ferrous ion Fe2+ chelating, and ferric Fe3+ reducing activities). Most of the compounds showed significant antioxidant activities. A structure- activity relationship has also been discussed. Conclusion: Most of the synthetic isophthalate Schiff bases were found to be moderately active when screened for their antioxidant activities by three assays such as DPPH radical scavenging, ferrous ionchelating, and ferric reducing activities. These moderately active compounds can serve as lead molecules to further modify the structure and identify more powerful antioxidant agents.

Background: Diabetes mellitus is a serious global health concern, and this is expected to impact more than 300 million people by 2025. The current study focuses on identifying substituted indolin-2-one-based inhibitors for two indispensable drug targets, α-amylase and α-glucosidase. Methods: The structures of synthetic compounds were confirmed by spectroscopic techniques and evaluated for enzyme inhibition activities. Kinetic and in silico studies were also performed. Results: All compounds exhibited good-to-moderate inhibitory potential. Most importantly, compounds 1, 2, 6, 16 and 17 were identified as potent α-glucosidase inhibitors (IC50 = 9.15 ± 0.12–13.74 ± 0.12 μM). Conclusion: This study identified that these synthetic compounds might serve as potential lead molecules for antidiabetic agents.

Background: Identification of molecules having dual capabilities to reduce postprandial hyperglycemia and oxidative stress is one of the therapeutic approaches to treat diabetes mellitus. In this connection, a library of benzofuran-linked chalcone derivatives were evaluated for their dual action. Methods: A series of substituted benzofuran-linked chalcones (2–33) were synthesized and tested for α-amylase inhibitory as well as 2,2-diphenylpicrylhydrazyl (DPPH) and 2,2′-azino- bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging activities. Results: All compounds showed α-amylase inhibitory activity ranging from IC50 = 12.81 ± 0.03 to 87.17 ± 0.15 μM, compared with the standard acarbose (IC50 = 13.98 ± 0.03 μM). Compounds also demonstrated radical scavenging potential against DPPH and ABTS radicals. Conclusion: The identified compounds may serve as potential leads for further advanced research.

Background and Objective: Acid–base status is mandatory for clinical assessment of patients with septic shock and severe sepsis. Generally, venous blood gas sample collection is easier, however, the data regarding this approach are lesser defined in our population as a substitute for arterial blood gas (ABG) sample. The present study aimed to determine and compare the pH, pCO2, and bicarbonate levels in VBG and ABG samples in patients with sepsis and septic shock. Method: A cross sectional comparative study was conducted on 350 patients with sepsis and/or septic shock admitted to the medical emergency of Jinnah Hospital, Lahore, Pakistan. Both ABG and VBG samples were collected and pH, pCO2, and bicarbonate levels were determined by standard methods. Data were analyzed using Pearson correlation and the Bland–Altman method for bias. Results: An interclass correlation (r = 0.995, r = 0.929 and r = 0.946) was found for pH, pCO2, and bicarbonate between ABG and VBG samples, respectively. The Bland–Altman method showed a high degree of agreement for two sets of measurements; pH (bias ± SD, 0.089 ± 0.00472) and pCO2 (bias ± SD, -1.1096 ± 1.0089) with a clinically acceptable difference whereas the difference in bicarbonate measurement was found slightly higher (bias ± SD, 1.124 ± 0.674) revealing, however, a good degree of agreement with clinically acceptable bias. Conclusion: Use of a venous blood sample in patients with sepsis or septic shock is a clinically acceptable substituent for ABG measurement in evaluating acid-base status of these patients for further management.

Trichoderma, a major fungal genus attaining importance due to its diverse application in biological control programs and is considered a substitute for chemical pesticides. This research was conducted to characterize various Trichoderma species isolated from rhizospheric soil samples morphologically followed by its confirmation using molecular tools. A systematic survey of Trichoderma populations associated with soils of different vegetable hosts would enable a clear picture of the distribution of species in the region. Samples were collected from the rhizospheres of a variety of vegetable hosts and obtained numerous Trichoderma isolates (T. harzianum, T. viride, T. hamatum, T. longibrachiatum, T. asperellum, T. koningii and T. longipile). Morphological characteristics revealed that T. harzianum resembles T. viride but is more pigmented with confined rings than T. viride and other associated species. T. viride sporulation was more rapid than other species, producing a soft mat on PDA media. T. viride produces a sweet smell of coconut; T. asperellum produces a misty odour while T. longibrachiatum produces a yellow pigmentation in the media. Fifty out of 200 morphologically identified species were genetically characterized using universal primers (ITS-1 and ITS-4). ITS-based sequencing resulted in a product of 650 bp in all the isolates. The sequencing of these isolates showed five different species. As per rDNA, the species identified are: T. harzianum, T. hamatum, T. longibrachiatum, T. asperellum and T. viride with 98-100% sequence similarities to other related Trichoderma isolates reported from China, India, Mexico, USA, Portugal, Germany, Spain and Brazil. Bioinformatics analysis was conducted using maximum parsimony (MP) that supports the resemblance of the present study Trichoderma species with species reported from other countries. It is concluded that Trichoderma strains with biocontrol activity are genetically different compared to the pathogenic ones. The findings of this study help in providing an opportunity to test these isolates against different plant pathogens and ultimately leads to the development of bio-pesticides that could be eco-friendly and cost-effective with no chance of resistance development

This study was designed to screen novel thiourea derivatives against different enzymes, such as α-amylase, α-glucosidase, protein tyrosine phosphatase 1 B, and advanced glycated end product (AGEs). A cytotoxicity analysis was performed using rat L6 myotubes and molecular docking analysis was performed to map the binding interactions between the active compounds and α-amylase and α-glucosidase. The data revealed the potency of five compounds, including E (1-(2,4-difluorophenyl)-3-(3,4-dimethyl phenyl) thiourea), AG (1-(2-methoxy-5-(trifluoromethyl) phenyl)-3-(3-methoxy phenyl) thiourea), AF (1-(2,4-dichlorophenyl)-3-(4-ethylphenyl) thiourea), AD (1-(2,4-dichlorophenyl)-3-(4-ethylphenyl) thiourea), and AH (1-(2,4-difluorophenyl)-3-(2-iodophenyl) thiourea), showed activity against α-amylase. The corresponding percentage inhibitions were found to be 85 ± 1.9, 82 ± 0.7, 75 ± 1.2, 72 ± 0.4, and 65 ± 1.1%, respectively. These compounds were then screened using in vitro assays. Among them, AH showed the highest activity against α-glucosidase, AGEs, and PTP1B, with percentage inhibitions of 86 ± 0.4% (IC

Conductive textiles have found notable applications as electrodes and sensors capable of detecting biosignals like the electrocardiogram (ECG), electrogastrogram (EGG), electroencephalogram (EEG), and electromyogram (EMG), etc; other applications include electromagnetic shielding, supercapacitors, and soft robotics. There are several classes of materials that impart conductivity, including polymers, metals, and non-metals. The most significant materials are Polypyrrole (PPy), Polyaniline (PANI), Poly(3,4-ethylenedioxythiophene) (PEDOT), carbon, and metallic nanoparticles. The processes of making conductive textiles include various deposition methods, polymerization, coating, and printing. The parameters, such as conductivity and electromagnetic shielding, are prerequisites that set the benchmark for the performance of conductive textile materials. This review paper focuses on the raw materials that are used for conductive textiles, various approaches that impart conductivity, the fabrication of conductive materials, testing methods of electrical parameters, and key technical applications, challenges, and future potential.

Anticipation of the key reversal points in trading markets is of key interest to the portfolio managers, investors, researchers, technical Analysts. These points trigger investment or divestment for investors’ holdings within the financial markets. Many techniques are used to anticipate these points. Use of Fibonacci numbers has gained significant importance in this context. The tools like ‘Fibonacci Retracements’ are available to investors; however, another important determinant in the value of an investment is the ‘timings’ within a certain time frame. This study aims to understand whether such a predictive relationship exists between the Fibonacci time horizons and the modern-day financial markets. For this purpose, two renowned indices i.e., Dow Jones Industrial Average (DJIA) and Dow Jones Transport Average (DJTA) have been taken as the population. Data of these averages, since their inception in 1896, till 2020, has been taken in to account, in order to remove any speculative sentiments, in the long run. The observation periods of data have been classified into daily, monthly and yearly time frames. Charting package, ‘meta stocks’ version 8.0 has been used to map the Fibonacci sequence against the actual reversal points placed on the data from the first day of trading on DJIA and DJTA. The results reveal striking similarity between the reversal points inferred from Fibonacci sequence, and the actual reversal points. The study concludes with a recommendation to trace this similarity against the technical analysis and charting for further investigation by the future studies. These findings are of significant importance for the portfolio managers, technical analysists, and researchers interested in forecasting the movement of the market index.