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We have synthesized thiadiazole-isatin hybrid analogues (1–20), characterized through different spectroscopic techniques such as 1HNMR, 13CNMR, HREI-MS, and evaluated against α-glucosidase and α-amylase enzymes. All analogues showed potent inhibitory potentials, having an IC50 values ranged from 22.08 ± 0.09 to 54.03 ± 0.07 μM (against α-amylase) and 19.03 ± 0.04 to 50.03 ± 0.02 μM (α-glucosidase) when compared with the standard drug acarbose (IC50 = 22.07 ± 0.02 μM for α-amylase and IC50 = 18.01 ± 0.06 μM for α-glucosidase respectively). Among the series, analogues 13 (IC50 = 19.03 ± 0.04 and 22.08 ± 0.09 μM), 12 (IC50 = 21.03 ± 0.07 and 24.03 ± 0.07 μM), and 5 (IC50 = 22.02 ± 0.03 and 26.02 ± 0.04 μM) were identified as the most active inhibitors. The structure–activity relationship was carried out, mainly associated with the nature, number, position, and electron-donating and electron-withdrawing effects of the substituent (s) on the phenyl ring. With the help of molecular docking, the binding interaction of the most active analogues within the active site of enzymes was confirmed. Almost twelve compounds were also screened for antibacterial potential, and few were found to be effective against Bacillus subtilis. All compounds were verified for cytotoxicity against the 3 T3 mouse fibroblast cell line and detected non-toxic.

A series of new benzohydrazide based thiourea derivatives were synthesized, characterized through different spectroscopic techniques like 1HNMR, 13CNMR and HREI-MS and screened against Bacillus pasteurii (B.P) and Jack bean (J.B) ureases enzymes. All derivatives showed good inhibitory potential ranging from 20.05 ± 0.03 to 39.34 ± 1.05 (against J.B Urease) and 23.54 ± 0.21 to 58.65 ± 0.41 (against B.P Urease) as compared to the standard thiourea (IC50 = 14.02 ± 0.25 and 18.01 ± 0.13 µM, respectively). It was observed that the two scaffold 1 (IC50 = 23.54 ± 0.21 and 20.05 ± 0.03 µM) and 2 (IC50 = 26.20 ± 0.32 and 21.33 ± 0.17 µM) among the series showed good inhibitory potential. The binding interaction of the most potent analogues with the active site of enzyme were examined through the molecular docking study.

We have synthesized 1,2,4-triazole bearing benzenesulfonohydrazide analogues (1–21), characterized through different spectroscopic techniques such as 1HNMR, 13CNMR, HREI-MS and were evaluated against Acetylcholinesterase (AChE) and Butyrylcholinesterase (BuChE) enzymes. All the newly synthesized analogues showed excellent to good inhibition potential with IC50 values ranged from 0.30 ± 0.050 to 15.21 ± 0.50 µM (against AChE) and 0.70 ± 0.050 to 18.27 ± 0.60 µM (against BuChE) as compared to the standard drug Donepezil (IC50 = 2.16 ± 0.12 and 4.5 ± 0.11 µM, respectively). Analogues 2 and 4 which were found inactive against these enzymes. However, analogues 17 (IC50 = 0.30 ± 0.050 and 0.70 ± 0.050 µM) and 13 (IC50 = 0.70 ± 0.05 and 1.70 ± 0.050 µM) were found to have potent inhibitory potentials against the targeted enzymes. Structure-activity relationship was carried out which mainly depends upon the nature, position and numbers of the substitution present on phenyl rings that may be electron withdrawing/donating. Molecular docking study was carried out to know about the binding mode of interaction of the most active site of the synthesized analogues with the targeted enzymes.

SiGe‐SiO2‐based structures present high interest for their high photosensitivity from visible to short‐wavelength infrared. Herein, two postdeposition annealing procedures, that is, rapid thermal annealing (RTA) and rapid‐like furnace annealing (FA), are compared. Both RTA and FA are performed at 600 °C for 1 min for SiGe nanocrystals (NCs) formation in SiO2 matrix in Si/SiO2/SiGe/SiO2 structures deposited by magnetron sputtering. The FA imitates RTA resulting in enhanced spectral response. X‐ray diffraction, transmission electron microscopy, and Raman spectroscopy are carried out showing Ge‐rich SiGe NCs with 11.3 ± 1.2 nm size for RTA and 9.4 ± 0.8 nm for FA. Photocurrent spectra for both structures show several peaks that are annealing dependent. The photocurrent intensity for FA samples is ≈7 times higher than RTA samples while cutoff wavelengths are slightly different, that is, 1365 nm for FA and 1375 nm for RTA. The FA structures show (at −1.5 V) over 4 A W−1 responsivity at 730 nm, 6.4 × 107 Jones detectivity at 735 nm, and 2.2 × 107 Jones at about 1210 nm. FA structures contain small SiGe NCs with incorporated residual strain, while RTA ones are formed of columnar SiGe NCs separated by SiGeOx amorphous regions and show increased tensile strain in the SiGe.

Aim: This meta-analysis investigates the association between testosterone replacement therapy [TRT] and carotid artery atherosclerosis. Methods: 3 databases were searched for studies up to June 2023 per the PRISMA guidelines. The eligibility criteria comprised RCTs and observational studies involving hypogonadal males receiving exogenous testosterone, in which CIMT was assessed. CAA was the primary outcome, whereas secondary outcomes included HDL, LDL, CRP, total cholesterol and total testosterone. The statistical analysis was performed using Review Manager. Results: Statistical analysis revealed no association between TRT and assessed outcomes. There was a significant increase in total testosterone levels, depicting indirect anti-atherosclerotic effects of TRT. Conclusion: Meta-analysis shows no relation between TRT and CIMT or other markers, allowing its safe usage for hypogonadal males.

Esophageal cancer is extremely rare in pregnant women, accounting for only 0.07%–0.1% of all malignant neoplasms in pregnancy. It is rapidly progressive in nature and requires timely intervention. Our literature search yielded six case reports of esophageal cancers in pregnancy thus far. We herein report the case of a 30-year-old female, presenting at 32 weeks of gestation with complaints of hoarseness, dysphagia, and weight loss. The biopsy taken from within the esophagus, using an endoscope during an upper endoscopy procedure confirmed the diagnosis of squamous cell carcinoma of esophagus and Positron emission tomography-computed tomography revealed metastasis to parathyroid region. She was confirmed with metastatic squamous cell cancer positive for cytokeratin 5/6 and cytokeratin P40 immunohistochemistry. The Positron emission tomography-computed tomography of the chest showed a large hypermetabolic soft tissue mass in the mid-esophagus with significant proximal dilation. The head-and-neck computed tomography scan represented a necrotic nodal mass in the neck and circumferential mural thickening involving the mid-esophagus resulting in the proximal dilation confirming the primary tumor site. Two weeks after the delivery, the patient started a chemotherapy regimen consisting of nine cycles of Carboplatin and Paclitaxel. Postchemotherapeutic computed tomography showed remonstration of lesion in the thyroid gland and middle part of the esophagus. Thus, in pregnant patients with new onset hoarseness, dysphagia, or substantial weight loss, clinicians should keep esophageal cancer as part of their differentials. A thorough history, detailed physical examination, and imaging should be performed to determine esophageal cancer, as it can advance swiftly and has a poor prognosis if left untreated.

Diabetes and ulcer are the major health problems all over the world. The present study reports synthesis and bio-evaluation of 19 benzimidazole analogs in search of antiglycation, antioxidant and antiulcer agents. The synthetic analogs were characterized using 1H NMR, 13C NMR and HR-EIMS. All compounds were checked for their antiglycation, antiurease and antioxidant activities. The fluorophenyl benzimidazole analogs 12–14 strongly inhibited glycation with IC50 values ranging from 142 µM to 193 µM. The same fluorophenyl analogs (12–14) were also found to exhibit the highest antioxidant activity with IC50 values ranging from 1.2 µM to 6.6 µM which further highlights the significance of these bioactive analogs. The dihydroxyphenyl analogs 6–9 demonstrated the most potent enzyme inhibitory activity with IC50 values ranging from 3.10 µM to 5.90 µM. Molecular docking studies were performed on the active analogs to investigate their interactions with the urease enzyme and provide a plausible explanation for their observed urease inhibitory activity.

Abstract Accurate small vessel stent visualization using CT remains challenging. Photon-counting CT (PCD-CT) may help to overcome this issue. We systematically investigate PCD-CT impact on small vessel stent assessment compared to energy-integrating-CT (EID). 12 water-contrast agent filled stents (3.0–8 mm) were scanned with patient-equivalent phantom using clinical PCD-CT and EID-CT. Images were reconstructed using dedicated vascular kernels. Subjective image quality was evaluated by 5 radiologists independently (5-point Likert-scale; 5 = excellent). Objective image quality was evaluated by calculating multi-row intensity profiles including edge rise slope (ERS) and coefficient-of-variation (CV). Highest overall reading scores were found for PCD-CT-Bv56 (3.6[3.3–4.3]). In pairwise comparison, differences were significant for PCD-CT-Bv56 vs. EID-CT-Bv40 (p ≤ 0.04), for sharpness and blooming respectively (all p

Background and Objective: Procedural error reporting system is an effective step towards patient safety. In Pakistan adverse event reporting system is deficient. The study aimed to identify the presence of procedural error reporting system and their referral in endodontic clinics of private and public dental institutes in Punjab. Methods: This study was conducted in six private and two public dental institutes in Punjab via questionnaires developed by the authors and distributed online using Google forms. The questionnaire had 14 items targeting demographics, a procedural error reporting system, and ways to manage procedural errors. Results: The majority of the dental colleges, both private and public, did not have any procedural error reporting system or a hierarchical order (70.1%) for the management of errors in their endodontic departments (60.5%). The most frequent approach was self-management of errors (86.5%), followed by referring to a senior endodontist (45%) and asking colleagues for help (36.5%). 13% of the respondents never informed patients, while 6% never reported procedural errors to their departments. There was a statistically significant difference between house officers, postgraduate trainees and demonstrators regarding self-management of errors and putting patients on follow-up. Conclusion: Most endodontic departments lack a system for reporting procedural errors, with no significant difference between private and public institutes. Most respondents report errors to patients and departments, with self-management being the most common approach. Postgraduate trainees tend to manage errors independently. It is imperative to create a comprehensive error reporting system that could be implemented progressively

A rare but lethal central nervous system disease known as granulomatous amoebic encephalitis (GAE) and potentially blinding Acanthamoeba keratitis are diseases caused by free-living Acanthamoeba. Currently, no therapeutic agent can completely eradicate or prevent GAE. Synthetic compounds are a likely source of bioactive compounds for developing new drugs. This study synthesized seventeen 1,4-benzothiazine derivatives (I –XVII) by a base-catalyzed one-pot reaction of 2-amino thiophenol with substituted bromo acetophenones. Different spectroscopic techniques, such as EI-MS, 1H-, and 13C NMR (only for the new compounds), were used for the structural characterization and conformation of compounds. These compounds were assessed for the first time against Acanthamoeba castellanii. All compounds showed anti-amoebic potential in vitro against A. castellanii, reducing its ability to encyst and excyst at 100 μM. Compounds IX, X, and XVI showed the most potent activities among all derivatives and significantly reduced the viability to 5.3 × 104 (p

The β-carboline scaffold are very potent for encouraging molecular interactions with a wide range of Alzheimer’s target. Based on biological importance of carboline nucleus, we have designed a new series of carboline derivatives and screened them for acetyl cholinesterase and butyrylcholinesterase inhibition. The structural interpretation of the synthesized analogs was done by spectroscopic techniques such as 1H NMR, 13C NMR. Almost all analogs of the series exhibited good to moderate inhibition activities. The most potent analog among the series was analog 2 having, three hydroxyl groups on the phenyl ring. The IC50 values for this analog was 0.10 ± 0.01 for acetylcholinesterase and 0.30 ± 0.01 for butyrylcholinesterase. To understand the interactions of this analogs with the active sites of enzyme docking study was also carried out.

Alzheimer's disease (AD) is treated by targeting cholinesterase enzymes like acetylcholinesterase and butyrylcholinesterase, and these enzymes' inhibitors serve as important tools for treatment of alzheimer diseases. Hybrid analogues with a 1,3-oxazole moiety based on benzoxazole were designed, developed, and then tested for their cholinesterase inhibition. All the newly synthesized analogues showed moderate to good inhibitory potentials having IC50 values raging between 0.90 ± 0.05 µM to 35.20 ± 0.70 µM against acetylcholinesterase and 1.10 ± 0.10 µM to 37.70 ± 0.60 µM against butyrylcholinesterase enzymes. Among the series, the analogue 11 (IC50 = 0.90 ± 0.05 µM), (IC50 = 1.10 ± 0.10 µM) and 18 (IC50 = 1.20 ± 0.05 µM), (IC50 = 2.10 ± 0.10 µM) being the strongest acetylcholinesterase and butyrylcholinesterase inhibitors as compared to standard donepezil drug. Nonetheless, the remaining analogues also displayed better inhibition profile against both these targeted enzymes. Furthermore, the structures of all the synthesized analogues were confirmed by using HREI-MS, 1HNMR and 13CNMR spectroscopy. Additionally, molecular docking experiments were conducted to determine the potential mode of interaction between the majority of active analogues and the enzyme active site. The findings corroborated the experimental data.

Reduced iodine loads for computed tomography (CT)-based vascular assessment prior to transcatheter aortic valve implantation (TAVI) may be feasible in conjunction with a spectral detector CT scanner. This prospective single-center study considered 100 consecutive patients clinically referred for pre-TAVI CT. They were examined on a dual-layer detector CT scanner to obtain an ECG-gated cardiac scan and a non-ECG-gated aortoiliofemoral scan. Either a standard contrast media (SCM) protocol using 80 mL Iohexol 350 mgI/mL (iodine load: 28 gI) or a body-mass-index adjusted reduced contrast media (RCM) protocol using 40–70 mL Iohexol 350 mgI/mL (iodine load: 14–24.5 gI) were employed. Conventional images and virtual monoenergetic images at 40–80 keV were reconstructed. A threshold of 250 HU was set for sufficient attenuation along the arterial access pathway. A qualitative assessment used a five-point Likert scale. Sufficient attenuation in the thoracic aorta was observed for all patients in both groups using conventional images. In the abdominal, iliac, and femoral segments, sufficient attenuation was observed for the majority of patients when using virtual monoenergetic images (SCM: 96–100% of patients, RCM: 88–94%) without statistical difference between both groups. Segments with attenuation measurements below the threshold remained qualitatively assessable as well. Likert scores were ‘excellent’ for virtual monoenergetic images 50 keV and 55 keV in both groups (RCM: 1.2–1.4, SCM: 1.2–1.3). With diagnostic image quality maintained, it can be concluded that reduced iodine loads of 14–24.5 gI are feasible for pre-TAVI vascular assessment on a spectral detector CT scanner.

OBJECTIVES To assess the inter-rater reliability regarding the radiolucencies associated with a second molar adjacent to an impacted third molar. METHODOLOGY A cross-sectional comparative study was conducted in the College of Dentistry, Sharif Medical and Dental College, Lahore, in which dentists from four different specialities, namely; Oral Pathology, Endodontics, Prosthodontics and Oral and Maxillofacial surgery, were included as raters. 21 Orthopantomograms were assigned to each rater for assessing radiolucencies associated with a second molar adjacent to an impacted third molar. RESULTS The level of agreement regarding the radiolucencies associated with the second molar observed on the Orthopantomograms between rater 1 with rater 2 (κ=0.158., p=0.036) and rater 1 with rater 3 (κ=0.139, p=1.000) was very weak but was fair between rater1 and 4 (κ=0.271, p=0.200). CONCLUSION The only radiolucency that rater one observed was external root resorption. Rater 2 identified one case of radiolucency as dental caries and another as caries and periapical radiolucency that were identified by Rater 1 as external resorption; hence they had a weak agreement between Rater 1 and Rater 2 regarding the radiolucencies associated with second molars. Rater 3 identified radiolucencies owing to caries which were reported to be radiolucency due to external resorption by rater 1, and this agreement was weak. Most radiolucencies determined by rater 1 as external resorption were reported to be external resorption by rater 4, resulting in a fair agreement between rater 1 and 4.

Madam, Tirzepatide, also known as Mounjaro, has become increasingly popular among diabetic patients due to its potential to aid in weight loss. However, with the growing demand for this medication for its weight-loss benefits, there are apprehensions that it may soon become scarce. Tirzepatide, a dual Glucagon-like peptide (GLP-1) and Glucose-dependent insulinotropic polypeptide (GIP) receptor agonistis an injectable synthetic peptide with glucose-lowering effects.(1) It stimulates first- and second-phase insulin secretion, and reduce glucagon levels. Since its approval by the FDA in late 2021, Tirzepatide has become increasingly popular among diabetic patients as it has reported a mean decrease of 1.53% in patients' HbA1C levels in the first 40 weeks of use, which is higher than other drugs available in the market(1,2). Many patients also reported significant weight loss after starting the medication, which has led to increased demand for the drug. While this drug is yet to be approved by FDA for weight loss, it is expected that it will be approved for weight loss by mid of 2023. Despite that, some doctors already e off-label as a weight loss drug in people not suffering from Diabetes(3). This can lead to an increased demand for the drug as seen earlier in the case of Ozempic (semaglutide) in 2022 leading to an acute shortage (4). Pharmacies are already reporting low supplies of Tirzepatide, and some patients are facing trouble in getting their prescriptions filled(5). For diabetic patients who are relying on Tirzepatide to manage their blood glucose levels and promote weight loss, this shortage could have serious consequences. Patients who are unable to acquire the drug may be forced to switch to other medications or try alternative treatments, which may not be as effective. In conclusion, the recent surge in demand for Tirzepatide has led to concerns about a potential shortage of the medication. While the drug has shown promise in helping diabetic patients improve glycemic control and promote weight loss, patients need to have access to the medication when they need it. To help mitigate the shortage of Tirzepatide, some experts are calling for increased production of the drug and improved distribution channels to ensure that patients can continue to benefit from this promising treatment option.

Diabetes mellitus is a syndrome that is caused due to the imbalance of insulin production in the body. In the present study we have synthesized a class of fifteen compounds (1–15) based on thiadiazole-bearing thiourea that were assessed for in vitro alpha-amylase and alpha-glucosidase inhibitory potentials against standard drug acarbose. In this series, all the synthesized scaffolds were recognized as potentials inhibitors of both targeted enzymes, α-amylase having varied range from IC50 values = 35.70 ± 0.70 µM to 1.30 ± 0.05 µM against standard drug acarbose (10.30 ± 0.20 µM) while for α-glucosidase IC50 values = 37.60 ± 0.80 µM to 2.20 ± 0.10 µM against standard drug acarbose (9.80 ± 0.20 µM). Among the series, nine scaffolds such as 4, 6, 7, 9, 8, 11, 12, 14 and 15 showed excellent activity against a-amylase and a-glucosidase and were found many folds more potent than standard acarbose drugs due to the change in nature and number/s of substituent along the entire skeleton. A molecular docking study was conducted against active compounds to understand the binding modes of the synthetic analogs and how they show interaction with the active part of the enzymes. To confirm the structure of synthetic analogs different spectroscopic techniques will be used like NMR and HREI-MS.

The current study reports synthesis, structure establishment, anti-glycation, and anti-oxidant activities of ligand 4-[(2-hydroxynaphthalene-1-ylmethylene)-amino]-benzenesulfonamide (L) and its coordination compounds with Mn(II), Co(II), Ni(II), Cu(II), and Zn(II) metal ions. The analytical techniques used (UV-Vis, FT-IR, CHN/S) confirmed the bidentate nature of the ligand, coordinating via O and N atoms in 2:1 ligand-to-metal ratio. The TG/DTA anylsis displayed that these compounds are thermally stable. Furthermore, the synthesized compounds were evaluated for their anti-glycation and antioxidant potential and showed significant activities with IC50 values range 184.11–386.34 µM and 37.05–126.27 µM, respectively. The Mn (IC50 = 184.11 ± 2.11 µM), Ni (IC50 = 211.26 ± 1.46 µM), Cu (IC50 = 254.56 ± 1.16 µM), and Zn (IC50 = 276.43 ± 2.14 µM) metal complexes exhibited substantial anti-glycation activity and comparatively better activity than the standard rutin (IC50 = 294.4 ± 1.50 µM), whereas Zn complex (IC50 = 37.05 ± 1.53 μM) also showed better DPPH radical scavenging activity than the standard tert-butyl-4-hydroxyanisole (IC50 = 44.7 ± 1.21 µM).

The current study has afforded twelve analogs (4a-l) of pyridine-derived bis-oxadiazole containing bis-schiff base and subsequently evaluated for their potential to inhibit thymidine phosphorylase(in vitro). All the synthesized analogs were structurally elucidated using various spectroscopic tools including NMR and HREIMS. All synthesized scaffolds showed varied range of inhibitory potential with IC50values ranging from 5.19 ± 1.10 to 36.18 ± 4.60 μM in comparison to 7-deazaxanthine (IC50 = 30.28 ± 2.10 μM) as a standard drug. All analogs (except analog 4 l which displayed less potency than standard drug) showed improved potency having IC50 values of 19.73 ± 2.30, 16.14 ± 1.20, 18.93 ± 1.60, 22.78 ± 1.80, 30.47 ± 3.70, 5.19 ± 1.10, 23.13 ± 1.90, 21.56 ± 2.50, 4.88 ± 1.10, 26.63 ± 2.90 and 6.67 ± 1.10 respectively.Results obatined were compared to standard 7-deazxanthine drug with IC50 values of 30.28 ± 2.10 μM. Structure-activity relationship (SAR) studies revealed that analogs bearing –NO2, -CF3, –OH and –Cl moieties at various position of aryl part showed many folds more potency than standard 7-deazaxathine standard drug. In order to determine the potential mode of interactions with thymidine phosphorylase active sites, the most active analogs 4f (bearing 3-CF3& 5-NO2), 4i (bearing 3-OH & 5-NO2), and 4 k (bearing 2-OH &5-NO2) were further subjected to molecular docking study. The results confirmed that these active analogs adopted numerous important interactions including hyrognen bonding, pi-donor hydrogen bond, pi-pi T shaped, pi-pi stacking, pi-alkyl, pi-anion, pi-sigma, halogen (flourine) and numerous Vander Waals interactions with the amino acid of enzyme being targeted.

The clinical significance of benzimidazole-containing drugs has increased in the current study, making them more effective scaffolds. These moieties have attracted strong research interest due to their diverse biological features. To examine their various biological significances, several research synthetic methodologies have recently been established for the synthesis of benzimidazole analogs. The present study aimed to efficiently and quickly synthesize a new series of benzimidazole analogs. Numerous spectroscopic techniques, including 1H-NMR, 13C-NMR, and HREI-MS, were used to confirm the synthesized compounds. To explore the inhibitory activity of the analogs against α-amylase and α-glucosidase, all derivatives (1–17) were assessed for their biological potential. Compared to the reference drug acarbose (IC50 = 8.24 ± 0.08 µM), almost all the derivatives showed promising activity. Among the tested series, analog 2 (IC50 = 1.10 ± 0.10 & 2.10 ± 0.10 µM, respectively) displayed better inhibitory activity. Following a thorough examination of the various substitution effects on the inhibitory capacity of α-amylase and α-glucosidase, the structure-activity relationship (SAR) was determined. We looked at the potential mechanism of how active substances interact with the catalytic cavity of the targeted enzymes in response to the experimental results of the anti-glucosidase and anti-amylase. Molecular docking provided us with information on the interactions that the active substances had with the various amino acid residues of the targeted enzymes for this purpose.

Here, we discuss the synthesis of thiosemicarbazide derivatives based on benzoxazole. These compounds were obtained via sequence of reactions. The targeted products were confirmed using a number of spectroscopic methods, including NMR (1H and 13C) and EI-MS. After spectral confirmation all the synthesized compounds were evaluated for urease and β-Glucuronidase inhibitory activity in order to explore their biological significances in the presence of standard drug thiourea (IC50 = 21.86 ± 0.40) and D-saccharic acid 1,4-lactone (IC50 value 22.00 ± 1.10 µM) respectively. Among the evaluated series, compounds 14 and 15 (1.10 and 0.01 and 2.20 and 0.60) were shown to have slightly greater potential than standard drugs. Anti-nematodal activity was also employed to explore the cytotoxic nature of synthesized analogs. In order to establish the binding relationship with enzyme active sites, molecular docking experiments were done and directions for compound modification based on SAR features were addressed. In addition, ADMET prediction study also investigated to found drug like properties of the potential analogs.

Accurate and fast breath monitoring is of great importance for various healthcare applications, for example, medical diagnoses, studying sleep apnea, and early detection of physiological disorders. Devices meant for such applications tend to be uncomfortable for the subject (patient) and pricey. Therefore, there is a need for a cost-effective, lightweight, small-dimensional, and non-invasive device whose presence does not interfere with the observed signals. This paper reports on the fabrication of a highly sensitive human respiratory sensor based on silicon nanowires (SiNWs) fabricated by a top-down method of metal-assisted chemical-etching (MACE). Besides other important factors, reducing the final cost of the sensor is of paramount importance. One of the factors that increases the final price of the sensors is using gold (Au) electrodes. Herein, we investigate the sensor’s response using aluminum (Al) electrodes as a cost-effective alternative, considering the fact that the electrode’s work function is crucial in electronic device design, impacting device electronic properties and electron transport efficiency at the electrode–semiconductor interface. Therefore a comparison is made between SiNWs breath sensors made from both p-type and n-type silicon to investigate the effect of the dopant and electrode type on the SiNWs respiratory sensing functionality. A distinct directional variation was observed in the sample’s response with Au and Al electrodes. Finally, performing a qualitative study revealed that the electrical resistance across the SiNWs renders greater sensitivity to breath than to dry air pressure. No definitive research demonstrating the mechanism behind these effects exists, thus prompting our study to investigate the underlying process.

None. Applied manuscript is a letter to the editor.

Abstract Background Anthranilic acid is an active compound with diverse biological activities such as anti-inflammatory, antineoplastic, anti-malarial and α-glucosidase inhibitory properties. It can also chelate transition metals to form complexes with applications as antipathogens, photoluminescent materials, corrosion inhibitors, and catalysts. Results Anthranilic acid complexes (1–10) of Zn(II), Bi(III), Ag(I), Fe(II), Co(II), Cu(II), Mn(II), Al, Ni(II), and Cr(III) were synthesized and characterized using thermogravimetric (TGA), elemental analysis, FT-IR, UV–vis spectrometry, mass spectrometry and magnetic susceptibility. The morphology and size of metal complex (1–10) particles were determined by scanning electron microscope (SEM) and the surface area was determined by BET analysis. TGA and CHN analysis data indicated that the stoichiometries of complexes were 1:2 metal/ligand except for Ag(I), Al and Bi. Furthermore, DFT study was performed to optimize the structure of selected complexes. The complexes (1–10) were evaluated for their catalytic activity in the reduction of 4-nitrophenol (4-NP), antibacterial activity against S. aureus, P. aeroginosa and E. coli as well as their antifungal activity against F. solani and A. niger. The complexes were also tested against the second-stage juveniles (J2) root-knot nematodes. Conclusion Co(II) complex 5 and Cu(II) complex 6 showed high catalytic activity for the reduction of 4-NP to 4-aminophenol (4-AP). Ag(I) complex 3 showed the best activity against the pathogens that were tested namely clinically important bacteria S. aureus, P. aeroginosa and E. coli, commercially important fungi F. solani and A. niger and J2 root-knot nematodes M. javanica.

In the present study, the thermal conductivity of two distinct water-based nanofluids of single-walled CNTs and Al2O3, as well as their hybrid solution, was investigated experimentally. The Al2O3 and CNTs nanoparticle concentrations are taken to be 2%v/v, while the hybrid solution contained 2%v/v of both Al2O3 and CNTs nanoparticles. A PSS (Polly styrene sulphonic acid) solution was used as a surfactant to increase the suspension time of the nanoparticles to avoid sedimentation. The dispersion and breaking of the particles of CNT and Al2O3 into nano size were performed employing a probe sonicator and bath sonicator. Moreover, a hot plate magnetic stirrer was used to obtain a consistent liquid mixture. The experiments are performed on the Computer Controlled Thermal Conductivity of Liquid and Gases (TCLGC) unit available in the heat transfer lab at GIKI. The results concluded that the thermal conductivity of water-based single-walled CNT nanofluids was higher compared to Al2O3 and their hybrid solution. Therefore, Al2O3 and a hybrid solution are less desirable for thermal conduction compared to CNTs.

Abstract The present work reports the evolution and growth of GeGaAs(O) polytype nanoislands over GaAs p‐type substrate with photoemission application in mind. Several morphological transformations from NIs to simultaneously present nanopits/holes are observed as a function of annealing parameters that is, temperature (350‐800°C) and time (5‐90 minutes). Structural and elemental analyses are executed using atomic force microscopy, scanning electron microscopy and energy dispersive X‐ray spectroscopy. Photoemission current of the nanostructured surfaces, measured upon exposure from 265 nm light emitting diode, is found to depend on the nanoislands size, which in turn depends on the annealing parameters. A maximum photoelectric emission is obtained for structure annealed at 650°C for 60 minutes, upon which an increment of roughly two orders of magnitude is observed.

Microbial fuel cell (MFC) has received much attention in the last decade as a promising technology to simultaneously generate electricity and decontaminate wastewater. This study aims to quantitatively review the published literature on MFC, published in the period of 1970–2020, based on the Web of Science (WoS) database. For the first time in literature, a comprehensive quantitative review of MFC has been conducted by employing the technique of bibliometric and content analyses. A total of 11,397 publications have been retrieved from WoS, out of which 81.6% are research articles. The evaluation in the field of MFC has been mapped in various categories, such as publication history, publication distribution, subject category distribution, leading journals, leading countries and leading organizations in MFC research. Additionally, content analysis has been conducted to unearth the research trends in MFC; and some hot research topics in MFC have been spotted. Results depict that the period 2011–2020 has been the most appreciating era for MFC research, as it contributed 87% of the total publications. Among the subject categories, energy fuel and microbiology lead with contributions of 26.5% for each, butthe overall growth of the energy fuel category in the last decade has been the highest. Out of 1,147 journals publishing MFC research, Bioresource Technology is the leading one; and countries like China, USA and India are the main hub of MFC research with 26.47%, 16.95% and 7.69% contributions in publications, respectively. The hottest topics in MFC research are nanoparticles, catalysts, air electrodes, graphene electrodes, power enhancement, air cathode and nitrogen removal. Moreover, major research areas are engineering, energy fuels and biotechnology with each contribution 26.5% of the total publications.

Objective: To analyse the efficacy of preoperative intravenous injection of 120mg of methylprednisolone acetate steroid on the formation of seroma after modified radical mastectomy in breast cancer patients. Method: The case-control study was conducted at Ward 3, Surgical Unit 1, Department of General Surgery, Jinnah Postgraduate Medical Centre, Karachi, from November 2020 to April 2021, and comprised female patients with biopsy-proven carcinoma of breast who were scheduled for elective definitive breast cancer surgery. The subjects were randomised into treatment group A and control group B. Group A was given a single dose of intravenous injection methylprednisolone acetate 120mg half-an-hour before surgery, while group B underwent similar surgery without the said injection. Seroma was graded using the Common Terminology Criteria for Adverse Events v3.0. The groups were compared for age, total drainage, duration of drainage, seroma grading and wound status. Data was analysed using SPSS 25. Results: Of the 60 patients, there were 30(50%) in each of the two groups. The age difference between groups was non-significant (p=0.346). There was a significant difference in the mean total drainage volume and mean duration of drainage between the groups (p=0.001). Seroma formation, seroma grading and wound status were not significantly different between the groups (p>0.05). The efficacy in treatment was high in group A (odds ratio: 2.78; 95% confidence interval: 0.65-13.94). Conclusion: A single preoperative dose of Injection methylprednisolone acetate was effective in terms of post-mastectomy outcomes. Key Words: Modified radical mastectomy, Methylprednisolone, Formation of seroma.

The development of drugs resistance in diabetes mellitus is a growing clinical problem, creates many challenges for patient. To overcome these problems, there is a serious deficiency of anti-diabetic agents, may be synthesized that inhibit alpha amylase and alpha glucosidase activity. Here, we have design and synthesized benzoxazole based sulphonamide derivatives and evaluated for their anti-diabetic activity. Twenty-two benzoxazole based sulphonamide derivatives were synthesized by reacting 2-aminophenol with carbon disulphide in the presence of base (Et3N) to obtained 2-marcapto benzoxazole which was further dissolved in ethanol by slow addition of different substituted phenacyl bromide in the presence of triethylamine, afforded varied S-substituted benzoxazole products. These products were dissolved in ethanol and hydrazine hydrate was added an excess in the presence of acetic acid to gives Schiff base. This Schiff base products were further dissolved in THF along with different substituted benzene sulphonyl chloride followed by addition of few drops of Et3N, yielded benzoxazole based sulphonamide derivatives (1–22). Moreover, SAR was established for the synthesized compounds and molecular docking studies were conducted for the potent moieties in order to explore the binding modalities of analogs. Among the tested series few analogues were found few folds better potential than standard drug but analog 1 (IC50 = 1.10 ± 0.20 µM, 1.20 ± 0.30 µM), showed promising anti-diabetic activity against α-amylase and α-glucosidase (11.12 ± 0.15 µM and 11.29 ± 0.07 µM respectively).

We report microwave synthesis of seven unique pyrimidine anchored derivatives (1–7) incorporating multifunctional amino derivatives along with their in vitro anticancer activity and their activity against COVID-19 in silico. 1–7 were characterized by different analytical and spectroscopic techniques. Cytotoxic activity of 1–7 was tested against HCT116 and MCF7 cell lines, whereby 6 exhibited highest anticancer activity on HCT116 and MCF7 with EC50 values of 89.24 ± 1.36 µM and 89.37 ± 1.17 µM, respectively.Molecular docking was performed for derivatives (1–7) on main protease for SARS-CoV-2 (PDB ID: 6LU7). Results revealed that most of the derivatives had superior or equivalent affinity for the 3CLpro, as determined by docking and binding energy scores. 6 topped the rest with highest binding energy score of −8.12 kcal/mol with inhibition constant reported as 1.11 µM. ADME, drug-likeness, and pharmacokinetics properties of 1–7 were tested using Swiss ADME tool. Toxicity analysis was done with pkCSM online server.All derivatives showed high GI absorption. Except 1 and 3, all derivatives showed blood brain barrier permeability. Most derivatives showed negative logKp values suggesting derivatives are less skin permeable and bioavailability score of all derivatives was 0.55. The toxicity analysis demonstrated that all derivatives have no skin sensitization properties. 6 and 7 showed maximum tolerated dose (Human) values of −0.03 and −0.018, respectively and absence of AMES toxicity.

This work has described the synthesis of novel class (1–25) of benzofuran based hydrazone. The hybrid scaffolds (1–25) of benzofuran based hydrazone were evaluated in vitro, for their urease inhibition. All the newly synthesized analogues (1–25) were found to illustrate moderate to good urease inhibitory profile ranging from 0.20 ± 0.01 to 36.20 ± 0.70 µM. Among the series, compounds 22 (IC50 = 0.20 ± 0.01 µM), 5 (IC50 = 0.90 ± 0.01 µM), 23 (IC50 = 1.10 ± 0.01 µM) and 25 (IC50 = 1.60 ± 0.01 µM) were found to be the many folds more potent than thiourea as standard inhibitor (IC50 = 21.86 ± 0.40 µM). The elevated inhibitory profile of these analogues might be due to presence of dihydroxy and flouro groups at different position of phenyl ring B attached to hydrazone skeleton. These dihydroxy and fluoro groups bearing compounds have shown many folds better inhibitory profile through involvement of oxygen of dihydroxy groups in hydrogen bonding with active site of enzymes. Various types of spectroscopic techniques such as 1H-, 13C- NMR and HREI-MS spectroscopy were used to confirm the structure of all the newly developed compounds. To find SAR, molecular docking studies were performed to understand, the binding mode of potent inhibitors with active site of enzymes and results supported the experimental data.

Background: This study investigates whether the scan length adjustment of prospectively ECG-triggered coronary CT angiography (CCTA) using calcium-scoring CT (CAS-CT) images can reduce overall radiation doses. Methods: A retrospective analysis was conducted on 182 patients who underwent CAS-CT and prospectively ECG-triggered CCTA using a second-generation Dual-Source CT scanner. CCTA planning was based on CAS-CT images, for which simulated scout view planning was performed for comparison. Effective doses were compared between two scenarios: Scenario 1—CAS-CT-derived CCTA + CAS-CT and Scenario 2—scout-view-derived CCTA without CAS-CT. Dose differences were further analyzed with respect to scan mode and body mass index. Results: Planning CCTA using CAS-CT led to a shorter scan length than planning via scout view (114.3 ± 9.7 mm vs. 133.7 ± 13.2 mm, p < 0.001). The whole-examination effective dose was slightly lower for Scenario 1 (3.2 [1.8–5.3] mSv vs. 3.4 [1.5–5.9] mSv; p < 0.001, n = 182). Notably, Scenario 1 resulted in a significantly lower radiation dose for sequential scans and obese patients. Only high-pitch spiral CCTA showed dose reduction in Scenario 2. Conclusions: Using CAS-CT for planning prospectively ECG-triggered CCTA reduced the overall radiation dose administered compared to scout view planning without CAS-CT, except for high-pitch spiral CCTA, where a slightly opposite effect was observed.

BackgroundAim of this study was to report and to identify risk factors for distal aortic failure following aortic arch replacement via the frozen elephant trunk (FET) procedure.MethodsOne hundred eighty-six consecutive patients underwent the FET procedure for acute and chronic aortic dissection. Our cohort was divided into patients with and without distal aortic failure. Distal aortic failure was defined as: (I) distal aortic reintervention, (II) aortic diameter dilatation to ≥ 6 cm or > 5 mm growth within 6 months, (III) development of a distal stent-graft-induced new entry (dSINE) and/or (IV) aortic-related death. Preoperative, intraoperative, postoperative and aortic morphological data were analyzed.ResultsDistal aortic failure occurred in 88 (47.3%) patients. Forty-six (24.7%) required a distal reintervention, aortic diameter dilatation was observed in 9 (4.8%) patients, a dSINE occurred in 22 (11.8%) patients and 11 (6.4%) suffered an aortic-related death. We found no difference in the number of communications between true and false lumen (p = 0.25) but there were significantly more communications between Ishimaru zone 6–8 in the distal aortic failure group (p = 0.01). The volume of the thoracic descending aorta measured preoperatively and postoperatively within 36 months afterward was significantly larger in patients suffering distal aortic failure (p < 0.001; p = 0.011). Acute aortic dissection (SHR 2.111; p = 0.007), preoperative maximum descending aortic diameter (SHR 1.029; p = 0.018) and preoperative maximum aortic diameter at the level of the diaphragm (SHR 1.041; p = 0.012) were identified as risk factors for distal aortic failure.ConclusionThe incidence and risk of distal aortic failure following the FET procedure is high. Especially those patients with more acute and more extensive aortic dissections or larger preoperative descending aortic diameters carry a substantially higher risk of developing distal aortic failure. The prospective of the FET technique as a single-step treatment for aortic dissection seems low and follow-up in dedicated aortic centers is therefore paramount.

In the present study, twenty (20) structural variants of nitrofurazone were synthesized based on BIODS (Biology-oriented drug synthesis) approach. The structure elucidation of the synthetic molecules (1–20) was carried out using different spectroscopic techniques, and their α-glucosidase inhibitory activity was also determined. The synthetic molecules 1–20 exhibited good α-glucosidase inhibition than the parent, nitrofurazone. Four compounds 2, 4, 6, and 7 showed potential inhibition against α-glucosidase with IC50 values ranging between 0.63 ± 0.25–1.29 ± 0.46 µM as compared to the standard acarbose (IC50 = 2.05 ± 0.41 µM). Nevertheless, compounds 15 (IC50 = 0.74 ± 0.12 µM), and 19 (IC50 = 0.54 ± 0.3 µM) also displayed good α-glucosidase inhibition and compound 19 was the most active compound of the series. Kinetic study of the active compounds 7 and 19 was also carried out to confirm the mode of inhibition. The binding interactions of the most active compounds within the active site of enzyme were determined by molecular docking. Moreover, molecular dynamic simulation of compound 19 was also performed in order to determine the stability of the overall complex (α-glucosidase + c19) in an explicit watery environment. The synthetic molecules were predicted as non-cytotoxic, however, seven compounds 1, 3, 4, 9, 10, 11, and 12 were predicted as carcinogenic.

In the present study, Indole-based-oxadiazole (1A-17A) compounds were successfully synthesized. The structures of all synthesized compounds were fully characterized by different sophisticated spectroscopic techniques such 1H NMR, 13C NMR, and HREI-MS. Further, the synthesized compounds were explored to investigate their broad-spectrum antibacterial and antibiofilm potential against multidrug resistant Pseudomonas aeruginosa (MDR-PA) and methicillin resistant Staphylococcus aureus (MRSA). The compounds possessed a broad spectrum of antibacterial activity having MIC values of values 1–8 mg/ml against the tested microorganisms. Compound A6 and A7 shows maximum antibacterial activity against MDR-PA, whereas A6, A7 and A11 shows highest activity against MRSA. Furthermore, antibiofilm assay shows that A6, A7 and A11 showed maximum inhibition of biofilm formation and it was found that at 4 mg/ml; A6, A7 and A11 inhibit MRSA biofilm formation by 81.1, 77.5 and 75.9%, respectively; whereas in case of P. aeruginosa; A6 and A7 showed maximum biofilm inhibition and inhibit biofilm formation by 81.5 and 73.7%, respectively. Molecular docking study showed that compounds A6, A7, A8, A10, and A11 had high binding affinity to bacterial peptidoglycan, indicating their potential inhibitory activity against tested bacteria, whereas A6 and A11 were found to be the most effective inhibitors of SARS CoV-2 main protease (3CLpro), with a binding affinity of − 7.78 kcal/mol. Furthermore, SwissADME and pkCSM-pharmacokinetics online tools was applied to calculate the ADME/Tox profile of the synthesized compounds and the toxicity of these chemicals was found to be low. The Lipinski, Veber, Ghose, and Consensus LogP criteria were also used to predict drug-likeness levels of the compounds. Our findings imply that the synthesized compounds could be a useful for the preventing and treating biofilm-related microbial infection as well as SARS-CoV2 infections.

Objectives: The aim of the present study was to isolate and evaluate cytotoxicity and anti-inflammatory activities of new novel compounds isolated from Prismatomeris glabra. Materials and Methods: Dried root of P. glabra was extracted under reflux with methyl alcohol, fractionated through the vacuum liquid chromatography technique, and evaporated and then purified the compounds using column chromatography and preparative thin-layer chromatography. THP-1 cells were treated with amentoflavone, 5,7,4′-hydroxyflavonoid, and stigmasterol with various concentrations (0–30 µg/mL) and then incubated with MTS reagent for 2h. Treatment was done for 24, 48, and 72h. Then, effects of these compounds were also tested on PGE2, TNF-α, and IL-6 expression in human THP-1-derived macrophage cells for 24h. Results: Three new compounds such as amentoflavone, 5,7,4′-hydroxyflavonoid, and stigmasterol were isolated. After 24h of incubation, a significant decrease in cell viability was reported with IC50 values of amentoflavone, 5,7,4′- hydroxyflavonoid, and stigmasterol (21 µg/mL ≡ 38 M), (18 µg/mL ≡ 66 M) and (20 µg/mL ≡ 48.5 M), respectively. Whereas for 48 and 72h treatment showed a less decreased cell viability compared with 24h treatment. These compounds also showed a significant reduction in the production of TNF-α, IL-6, and PGE2 in a dose-dependent manner. Conclusions: The isolated new compounds showed significant cytotoxicity and anti-inflammatory effects.

The present study comprised of the synthesis of dicyanoaniline derivatives of pyridine, thiophene, furan, and substituted phenyl 1–29. All synthetic derivatives were evaluated for their potential to inhibit α-amylase and α-glucosidase enzymes. The synthesized compounds are classified into three categories A, B, and C based on variable substituents at R1 and R2, and the structure–activity relationship was discussed accordingly. Amongst twenty-nine derivatives, 1–29, five compounds 2, 9, 18, 23, and 24 displayed excellent inhibition against α-amylase and α-glucosidase enzymes with the IC50 values ranging between 20.33 ± 0.02–25.50 ± 0.06 µM and 21.01 ± 0.12–27.75 ± 0.17 µM, respectively, while other compounds showed moderate to weak inhibition against both enzymes. Acarbose was used as the positive control in this study. The enzyme kinetic studies showed non-competitive and un-competitive types of inhibition mechanism against α-amylase and α-glucosidase enzymes, respectively. In silico studies have demonstrated the involvement of these molecules in numerous binding interactions within the active site of the enzyme.

Abstract In this study, 5-amino-nicotinic acid derivatives (1–13) have been designed and synthesized to evaluate their inhibitory potential against α-amylase and α-glucosidase enzymes. The synthesized compounds (1–13) exhibited promising α-amylase and α-glucosidase activities. IC50 values for α-amylase activity ranged between 12.17 ± 0.14 to 37.33 ± 0.02 µg/mL ± SEM while for α-glucosidase activity the IC50 values were ranged between 12.01 ± 0.09 to 38.01 ± 0.12 µg/mL ± SEM. In particular, compounds 2 and 4–8 demonstrated significant inhibitory activities against α-amylase and α-glucosidase and the inhibitory potential of these compounds was comparable to the standard acarbose (10.98 ± 0.03 and 10.79 ± 0.17 µg/mL ± SEM, respectively). In addition, the impact of substituent on the inhibitory potential of these compounds was assessed to establish structure activity relationships. Studies in molecular simulations were conducted to better comprehend the binding properties of the compounds. All the synthesized compounds were extensively characterized with modern spectroscopic methods including 1H-NMR, 13C–NMR, FTIR, HR-MS and elemental analysis.

α-Glucosidase enzyme is a therapeutic target for diabetes mellitus and its inhibitors play a vital role in the treatment of this disease. A new series of aryl-oxadiazole Schiff bases (1–18) were synthesized and evaluated for α-glucosidase inhibitory potential. Fifteen compounds 1–8, 11–13, and 15–18 showed excellent inhibition with IC50 values ranging from 0.30 ± 0.2 to 35.1 ± 0.80 µM as compared to the standard inhibitor acarbose (IC50 = 38.45 ± 0.80 µM), nonetheless, the remaining compounds were found to have moderate activity. Among the series, compounds 7 (IC50 = 0.30 ± 0.2 μM) with hydroxy groups at phenyl rings on either side of the oxadiazole ring was identified as the most potent inhibitor of α-glucosidase. The molecular docking studies were conducted to understand the binding mode of active inhibitors with the active site of enzyme and results supported the experimental data. Keywords: Synthesis, Aryl-oxadiazole Schiff bases, α-glucosidase, Molecular docking, Structure-activity relationship (SAR)

Amberlite XAD-2 functionalized by coupling through -C=N- spacer with isatin via an environmental friendly protocol. The modified resin was used for the evaluation of its sorption capacity towards toxic Cr (VI) ions using spectrophotometer. pH, volume, sorbent amount, initial concentration of Cr(VI) ions, and agitation time were optimized. The Freundlich and Dubinin- Radushkevich models gave better fit to isotherm data than Langmuir model. The evaluation of kinetic data indicated pseudo-first-order kinetics followed by sorption process. Thermodynamic parameters were also evaluated. Maximum recovery was obtained at 10 mL of 0.1M NaOH. Spiking methodology was used to confirm the validity of proposed method. The results revealed that developed method can be used for the removal of Cr(VI) ions efficiently from water, as well as reused for three cycles.

Abstract Films of SiGe nanocrystals (NCs) in oxide have the advantage of tuning the energy band gap by adjusting SiGe NCs composition and size. In this study, SiGe-SiO2 amorphous films were deposited by magnetron sputtering on Si substrate followed by rapid thermal annealing at 700, 800 and 1000 °C. We investigated films with Si:Ge:SiO2 compositions of 25:25:50 vol.% and 5:45:50 vol.%. TEM investigations reveal the major changes in films morphology (SiGe NCs with different sizes and densities) produced by Si:Ge ratio and annealing temperature. XPS also show that the film depth profile of SiGe content is dependent on the annealing temperature. These changes strongly influence electrical and photoconduction properties. Depending on annealing temperature and Si:Ge ratio, photocurrents can be 103 times higher than dark currents. The photocurrent cutoff wavelength obtained on samples with 25:25 vol% SiGe ratio decreases with annealing temperature increase from 1260 nm in SWIR for 700 °C annealed films to 1210 nm for those at 1000 °C. By increasing Ge content in SiGe (5:45 vol%) the cutoff wavelength significantly shifts to 1345 nm (800 °C annealing). By performing measurements at 100 K, the cutoff wavelength extends in SWIR to 1630 nm having high photoresponsivity of 9.35 AW−1.

A convenient and facile CuCl2·2H2O catalyzed one-pot synthetic strategy was designed for the conversion of readily available dimedone into highly functionalized N-arylhydrazinecarbothioamide based indazole derivatives. The product yields were found to be moderate to good without purification requirements. Structural features of the synthetic compounds were confirmed by various spectroscopic techniques such as 1H NMR, 13C NMR, EI-MS, FAB-MS, HREI-MS, and HRFAB-MS. The reaction intermediates were also quenched and characterized. Plausible reaction mechanisms were also discussed. Keywords: One-pot synthesis, Dimedone, Indazole, Carbothioamides

Benzimidazole derivatives 1–20 were synthesized and evaluated for antiglycation and antioxidant potentials. Among the series some analogs showed antiglycating potential ranging in between 182.30 ± 1.20 and 473.51 ± 2.17 when compared with standard rutin (IC50 value 295.09 ± 1.04 µM) and for antioxidant potential ranging between 22.42 ± 0.26 and 82.30 ± 1.33 when compare with standard Propyl gallate (IC50 value 29.20 ± 1.25). Compound 2, 6, 10 and 19 showed potent antioxidant and antiglycation inhibitory potentials. Compounds 7, 11, 13, 15 and 20 showed moderate antiglycating potential with IC50 values 473.51 ± 2.17, 325.20 ± 1.70, 440.0 ± 3.60, 370.60 ± 2.80 and 415.20 ± 3.20 μM, and these compounds also showed excellent antioxidant potential with IC50 values 73.51 ± 1.17, 45.63 ± 0.92, 82.30 ± 1.33, 75.41 ± 1.51, 40.60 ± 0.80 and 64.92 ± 1.41 μM respectively. The remaining compounds 1, 3, 4, 5, 8, 9, 12, 14, 16, 17and 18 were found inactive. Keywords: Synthesis, Benzimidazole, Antiglycating, Antioxidant, SAR

Cardiac amyloidosis is a rare disease which is under diagnosed in this region. This study was aimed to assess the clinical presentation, cardiac magnetic resonance imaging findings and prognosis of patients with cardiac amyloidosis in Pakistani population presenting to a tertiary care setting. A total of eight patients were included with the confirmed diagnosis of cardiac amyloidosis on CMR, after reviewing the CMR data of Aga Khan University Hospital from January 2011 to August 2019. Mean age was 51 + 11.5 years with the majority (75%) being male. All patients presented with heart failure. Sub optimal myocardial nulling on late gadolinium images was the most common finding on CMR. Late gadolinium enhancement was diffuse transmural in 5 patents (62.5%) and diffuse sub-endocardial in 3 patients (37.5%). On a mean follow up of 14 + 10 months, 3 patients (37.5%) died while 7 patients (87.5%) had hospital admissions due heart failure.

New benzimidazole analogues (1–18) were synthesized and characterized through different spectroscopic techniques such as 1H NMR, 13C NMR and HREI-MS. All analogues were screened for β-glucuronidase inhibitory potential. All analogues showed varied degree of inhibitory potentials with IC50 values ranging between 1.10 ± 0.10 to 39.60 ± 0.70 μM when compared with standard D-saccharic acid-1,4- lactone having IC50 value 48.30 μM. Analogues 17, 11, 9, 6, 1 and 13 having IC50 values 1.10 ± 0.10, 1.70 ± 0.10, 2.30 ± 0.10, 5.30 ± 0.20, 6.20 ± 0.20 and 8.10 ± 0.20 μM respectively, showed excellent β-glucuronidase inhibitory potential many folds better than the standard. All other analogues also showed good inhibitory potential better as compared to standard. Structure activity relationships (SAR) has been established for all compounds. The results from molecular docking studies supports the established SAR and developed a strong correlation with the results from in to vitro assay. The molecular docking results clearly highlighted how substituents like nitro and chloro affect the binding position of the active compounds in the active site. The docking results were also used to properly establish the effect of bulky substituents of least active compounds on reduced β-glucuronidase inhibitory activity. Compounds 1–18 were found non-toxic.

The ongoing pandemic that initiated in Wuhan, China, has been an international public health emergency since January 2020. India has been battling a brutal COVID-19's second wave since April 2021. The healthcare system was struggling with a substantial increase in COVID-19 cases when the lack of necessary resources further aroused a major setback. Opportunistic fungal infections, specifically mucormycosis and candidiasis have become a pressing matter of concern. Recent cases of aspergillosis have also heightened public alarm. Hence, call for an immediate response to this public health crisis is the need of the hour by establishing countrywide surveillance, diagnostic, and management system, as well as public awareness to alleviate the burden of COVID-19 and fungal infections in India.