Cu-promoted synthesis of triclosan-Mannich and Glaser adducts: anti-mycobacterial evaluation with in silico validations.

Aim: The WHO, Global tuberculosis report 2022 estimated number of tuberculosis (TB) cases reached 10.6 million in 2021, reflecting a 4.5% increase compared with the 10.1 million reported in 2020. The incidence rate of TB showed 3.6% rise from 2020 to 2021. Results/methodology: This manuscript discloses Cu-promoted single pot A3-coupling between triclosan (TCS)-based alkyne, formaldehyde and secondary amines to yield TCS-based Mannich adducts. Additionally, the coupling of TCS-alkynes in the presence of Cu(OAc)2 afforded the corresponding homodimers. Among tested compounds, the most potent one in the series 11 exhibited fourfold higher potency than rifabutin against drug-resistant Mycobacterium abscessus. The selectivity index was also substantially improved, being 26 (day 1) and 15 (day 3), which is four-times better than TCS.

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Strategic Analysis of Collaborative Networks in Spodoptera frugiperda (Lepidoptera: Noctuidae) Research for Improved Pest Management Strategies.

The fall armyworm (FAW) poses a significant global threat to food security, and economics. Timely detection is crucial, and this research explores innovative techniques like data analysis, remote sensing, satellite imagery, and AI with machine learning algorithms for predicting and managing outbreaks. Emphasizing the importance of community engagement and international collaboration, social network analysis (SNA) is employed to uncover collaborative networks in FAW management research. The study analyzes a decade of research, revealing trends, influential institutions, authors, and countries, providing insights for efficient FAW management strategies. The research highlights a growing interest in Spodoptera frugiperda (Smith and Abbott 1797) research, focusing on biological control, chemical insecticides, plant extracts, and pest resistance. Co-Citation analysis identifies key research concepts, while collaboration analysis emphasizes the contributions of actors and institutions, such as China, the USA, and Brazil, with international collaboration playing a vital role. Current research trends involve evolving resistance, insecticidal protein gene discovery, and bio-control investigations. Leveraging insights from collaborative networks is essential for formulating effective strategies to manage fall armyworm and ensure global food security. This comprehensive analysis serves as a valuable resource for researchers and stakeholders, guiding efforts to combat this pervasive agricultural pest.

Sustainable Harnessing of Waste Polycarbonate for Synthesizing Activated Furans to Generate Stenhouse Adducts on Polymer Surface.

Plastics are versatile materials, offering lightweight, durable, and affordable solutions across various industries. However, their non-degradable nature poses challenges by end of their life. This study presented an innovative carbonyl extraction method to utilize waste poly(bisphenol A carbonate) (PC) as reaction precursor to synthesis of activated furan as precursor for photoswitchable Stenhouse adducts. This innovative chemical strategy not only generated N,N'-functionalized barbiturates but also provided an eco-friendly and cost-effective alternative to traditional synthesis methods. The method presented hereby not only promotes sustainability by repurposing waste polycarbonate as carbonyl equivalent under green conditions but also yielded reusable bisphenol A (BPA). Furthermore, the derived activated furans exhibited their functionality by forming colored donor-acceptor Stenhouse adducts (DASAs) on aminated polymer surfaces. This work demonstrated a transition from a linear plastics economy toward a circular one, highlighting the potential of plastic waste as a resource for creating materials with improved properties.

Rational Design and Synthesis of Isatin-Chalcone Hybrids Integrated with 1H-1,2,3-Triazole: Anti-Proliferative Profiling and Molecular Docking Insights.

In this study, a series of isatin-chalcone linked triazoles were synthesized using Cu-promoted Azide-Alkyne Cycloaddition (CuAAC) reaction and evaluated for their cytotoxicity against various cancer cell lines. The most potent compound displayed approximately 2.5 times greater activity compared to both reference compounds against ovarian cancer cell lines. These findings were supported by caspase-mediated apoptosis and molecular docking analyses. Docking revealed comparable VEGFR-2 affinities for 5 b and 5-FU but highlighted stronger interaction of 5 b with EGFR, evident from its lower docking score. Overall, these results signify the notable anti-proliferative potential of most synthesized hybrids, notably emphasizing the efficacy of compound 5 b in suppressing cancer cell growth.

Amphiphilic, lauric acid-coupled pluronic-based nano-micellar system for efficient glipizide delivery.

Glipizide; an insulin secretagogue belonging to the sulfonylurea class, is a widely used antidiabetic drug for managing type 2 diabetes. However, the need for life-long administration and repeated doses poses challenges in maintaining optimal blood glucose levels. In this regard, orally active sustained-release nano-formulations can be a better alternative to traditional antidiabetic formulations. The present study explored an innovative approach by formulating orally active sustained-release nano-micelles using the amphiphilic lauric acid-conjugated-F127 (LAF127) block copolymer. LAF127 block copolymer was synthesized through esterification and thoroughly characterized before being employed to develop glipizide-loaded nano-micelles (GNM) via the thin-film hydration technique. The optimized formulation exhibited mean particle size of 341.40 ± 3.21 nm and depicted homogeneous particle size distribution with a polydispersity index (PDI) < 0.2. The formulation revealed a surface charge of -17.11 ± 6.23 mV. The in vitro release studies of glipizide from developed formulation depicted a sustained release profile. Drug loaded micelles exhibited a substantial reduction in blood glucose levels in diabetic rats for a duration of up to 24 h. Notably, neither the blank nano-micelles of LAF127 nor the drug loaded micelles manifested any indications of toxicity in healthy rats. This study provides an insight on suitability of synthesized LAF127 block copolymer for development of effective oral drug delivery systems for anti-diabetic activity without any significant adverse effects.

Association between Covishield vaccine and menstrual disturbance. Findings from a cross-sectional study among participants of Zero TB cohort in India.

BACKGROUND: The association between covid-19 vaccine and menstrual disturbance is unclear. METHODS: An in-person cross-sectional survey among female members ≥ 18 years enrolled in an ongoing Zero TB prospective cohort in Northern India who had received one or two doses of covid-19 vaccine was conducted to study the characteristics and association of menstrual disturbance within six months of receiving Covishield. RESULTS: Between June 29 and September 5, 2021, 339 females ≥ 18 years of age were administered the survey. Median age was 30 (IQR: 22-39) years; 84 % were between 18 and 49 and 16 % were ≥ 50 years old. There were 152 college students, 27 healthcare workers, and 160 nuns. Forty-two women (12 %) had received one dose and 297 (88 %) had received two doses of Covishield. Overall, 66 (20 %) women reported experiencing menstrual disturbance after receiving Covishield vaccine. The problems included early menstruation: 6 % (n = 19/339); late menstruation: 4 % (n = 14/339); and heavier bleeding: 5 % (n = 17/339). Disturbances lasted for less than seven days and cycles normalized in 1-3 months. There was no post-menopausal bleeding. There was no significant difference in menstrual disturbance based on receiving one vs. two doses of Covishield (OR: 1.58; 95 % CI: 0.55-4.57; p = 0.381). History of SARS-CoV-2 infection was not associated with the development of menstrual disturbance among the vaccinees (OR: 0.63; 95 % CI: 0.24-1.73; p = 0.379). Presence of emotional disturbance at baseline (OR: 31; 95 % CI: 3.52-267; p = 0.002) or previous history of dysmenorrhea (OR: 41; 95 % CI: 8.7-196; p < 0.001) was associated with menstrual disturbance in the vaccinees, indicating their potential to confound or bias study results. CONCLUSION: Menstrual problems were reported by Covishield vaccinees, but they were minor and reversible within three months and do not constitute a ground for vaccine hesitancy. Studies designed to assess causal link taking care to avoid selection bias or confounding are needed.

Design and performance analysis of an L-shaped radiator and defected ground antenna for enhancing wireless connectivity in brain implants.

Brain implantable wireless microsystems has potential to treat neurological diseases and maintain the quality of life. Highly efficient miniaturized antenna is the fundamental part of BID (brain implantable device) for reliable signaling of data through dissipative intracranial material. In this paper, a patch antenna with L-shaped defected ground is demonstrated. L-shaped radiator contributed to achieve the resonance at 2.45 GHz industrial scientific and medical (ISM) band. Antenna size is reduced to 10 × 10 × 0.25 mm3. The proposed L-shaped ground plane geometry is contributing in improving the radiation performance. |S11| value shifts from 15 dB to 30 dB after modifying the ground plane. Proposed structure attained the gain of -14 dBi when located between the Dura and CSF layers at the depth of 12 mm in human brain model. Full wave simulated antenna prototype is fabricated and measured for performance verification. Impedance bandwidth of 270 MHz and broadside radiation pattern (for transferring maximum electromagnetic energy away from tissue) are maintained by the proposed antenna. Brain tissue safety is ensured by specific absorption rate which is 0.709 W/kg and in compliance with the safety limits of 1.6 W/kg for 1-g averaged tissue. Proposed antenna structure is the promising candidate for medical implant technology.

Percutaneous Tenotomy for Chronic Tennis Elbow: A Minimally Invasive Technique with Better Outcomes - A Case Series.

Background: Tennis elbow (lateral epicondylitis elbow) is a self-limiting disease of indeterminate pathogenesis. Conservative therapy is the treatment of choice. In chronic tennis elbow with failure of conservative therapy; surgical treatment is a method of choice. Percutaneous tenotomy of extensor origin for patients with chronic tennis elbow is a minimally invasive technique with better long-term outcomes. Case Report: Ten patients (six males, four females) presented with chronic tennis elbow, who did not respond to conservative treatment/non-surgical intervention for more than 6 months underwent percutaneous tenotomy in an outpatient setting. Two patients were lost to follow-up at 2 months' post-operative. The remaining eight patients were evaluated at a mean follow-up of 3 years and assessed using the numerical rating scale, disabilities of the arm, shoulder and hand questionnaire ,and Oxford elbow score. These scores had a statistically significant difference in baseline to 3-year follow-up values (P < 0.05). No adverse outcomes, recurrence of symptoms, and signs of lateral epicondylitis elbow were noted and none required open surgical release. Conclusion: Percutaneous tenotomy, a minimally invasive technique is an effective and well-tolerated treatment for chronic tennis elbow and gives good pain relief and functional recovery.

Isatin-indoloquinoxaline click adducts with a potential to overcome platinum-based drug-resistance in ovarian cancer.

Herein, a series of isatin tethered indolo[2,3-b]quinoxaline hybrids was synthesized by considering the pharmacophoric features of known DNA intercalators and topoisomerase II inhibitors. The anti-proliferative properties of the synthesized compounds were evaluated against ovarian cancer cell lines (SKOV-3 and Hey A8). Four of the compounds exhibited promising anti-proliferative activities, with one of them being 10-fold more potent than cisplatin against drug-resistant Hey A8 cells. Further investigations were carried out to determine the DNA intercalating affinities of the most active compounds as potential mechanisms for their anti-proliferative activities. ADMET in silico studies were performed to assess the physicochemical, pharmacokinetics, and toxicity parameters of active compounds. This study, to the best of our knowledge, is the first report on the potential of isatin-indoloquinoxaline hybrids as structural blueprints for the development of new DNA intercalators. Additionally, it explores their potential to circumvent platinum-based resistance in ovarian cancer.

Tailoring selective triclosan azo-adducts: Design, synthesis, and anti-mycobacterial evaluation.

A series of triclosan azo-adducts were synthesized to investigate their structure-activity relationship against Mycobacterium tuberculosis and non-tuberculous mycobacteria. The series' most potent compound was four and sixteen times more active than triclosan and rifabutin against drug-resistant Mycobacterium abscessus, respectively, while being less cytotoxic to human macrophages than triclosan on day one. Additionally, one of the azo-adducts was twice as efficient against M. tuberculosis as triclosan and twice as effective against Mycobacterium marinum as isoniazid. Furthermore, the synthesized azo-adducts were equally effective against M. abscessus strains overexpressing InhA, suggesting that these compounds work through a distinct mechanism.

Special Issue "Hybrid Drugs: Design and Applications".

The widely held belief in the potential superiority of agents capable of modulating multiple biological targets has led to the adoption of molecular hybridization as an effective technique in the realm of drug discovery and development [...].

Stereo/regio-selective access to substituted 3-hydroxy-oxindoles with anti-proliferative assessment and in silico validation.

The manuscript focuses on a highly stereo-/regioselective approach for synthesizing a diverse array of substituted-3-hydroxy-2-oxindoles. The synthesized compounds were subsequently subjected to anti-proliferative assessment against various cell lines, including colorectal carcinoma, ovarian cancer, and human metastatic melanoma cancer. The structural characterization of the synthesized scaffolds was unambiguously confirmed using X-ray diffraction analysis. Among the synthesized compounds, one compound demonstrated exceptional potency within the series. It exhibited 1.2, 2.12, and 1.55 times greater potency than cisplatin against the HCT116, OVCAR10, and 1205Lu cell lines, respectively. These results were further supported by in vitro caspase-mediated apoptosis studies. Molecular docking studies of these compounds on the target VEGFR2 protein revealed their binding capability.

A Miniaturized Tri-Band Implantable Antenna for ISM/WMTS/Lower UWB/Wi-Fi Frequencies.

This study aims to design a compact antenna structure suitable for implantable devices, with a broad frequency range covering various bands such as the Industrial Scientific and Medical band (868-868.6 MHz, 902-928 MHz, 5.725-5.875 GHz), the Wireless Medical Telemetry Service (WMTS) band, a subset of the unlicensed 3.5-4.5 GHz ultra-wideband (UWB) that is free of interference, and various Wi-Fi spectra (3.6 GHz, 4.9 GHz, 5 GHz, 5.9 GHz, 6 GHz). The antenna supports both low and high frequencies for efficient data transfer and is compatible with various communication technologies. The antenna features an asynchronous-meandered radiator, a parasitic patch, and an open-ended square ring-shaped ground plane. The antenna is deployed deep inside the muscle layer of a rectangular phantom below the skin and fat layer at a depth of 7 mm for numerical simulation. Furthermore, the antenna is deployed in a cylindrical phantom and bent to check the suitability for different organs. A prototype of the antenna is created, and its reflection coefficient and radiation patterns are measured in fresh pork tissue. The proposed antenna is considered a suitable candidate for implantable technology compared to other designs reported in the literature. It can be observed that the proposed antenna in this study has the smallest volume (75 mm3) and widest bandwidth (181.8% for 0.86 GHz, 9.58% for 1.43 GHz, and 285.7% for the UWB subset and Wi-Fi). It also has the highest gain (-26 dBi for ISM, -14 dBi for WMTS, and -14.2 dBi for UWB subset and Wi-Fi) compared to other antennas in the literature. In addition, the SAR values for the proposed antenna are well below the safety limits prescribed by IEEE Std C95.1-1999, with SAR values of 0.409 W/Kg for 0.8 GHz, 0.534 W/Kg for 1.43 GHz, 0.529 W/Kg for 3.5 GHz, and 0.665 W/Kg for 5.5 GHz when the applied input power is 10 mW. Overall, the proposed antenna in this study demonstrates superior performance compared to existing tri-band implantable antennas in terms of size, bandwidth, gain, and SAR values.

Performance Analysis of an Aperture-Coupled THz Antenna for Diagnosing Breast Cancer.

The most important technique for exposing early-stage breast cancer is terahertz imaging. It aids in lowering the number of breast cancer-related fatalities and enhancing the quality of life. An essential component of developing the THz imaging system for high-quality photos is choosing the right sensor. In this article, a wideband antenna for microwave imaging of breast tissue with an operating frequency of 30 GHz (107 GHz to 137 GHz) is constructed and analyzed. An aperture-coupled antenna with an optimized ground aperture is proposed and analyzed, which made it possible to obtain better and consistent impedance matching in the wideband spectrum. The variation of backscattered signal energy in body tissue is assessed with healthy breast tissue and in the presence of malignant cells. A significant difference in energy scattering is observed for both situations. The suggested antenna's linear and stable time domain characteristics make it an appropriate component for THz imaging technology.

A Glimpse at the Quinoline-Hybridization Approach for the Development of New Antimalarials.

One of the most fatal infectious diseases, malaria, still poses a threat to about half of the world's population and is the leading cause of death worldwide. The use of artemisinin-based combination therapy has helped to significantly reduce the number of deaths caused by malaria, but the emergence of drug resistance threatens to undo this gain. In a bid to boost adherence, several new combination therapies with effectiveness against drug-resistant parasites are currently being tested in clinical settings. Nevertheless, notwithstanding these gains, malaria must be completely eradicated by a concerted international effort on several fronts. Quinoline-based compounds were the cornerstone of malaria chemotherapy until recently when resistance to these drugs severely hampered efforts to achieve a "Zero Malaria" world. The inappropriate use of available antimalarials is one of the factors responsible for resistance development and treatment failure, warranting the search for new chemical entities and alternative approaches to combat this threat. A vast number of solutions have emerged and one of them, quinoline-hybridization, is an effective method for introducing structural diversity, resulting in molecules with improved biological activities, reduced drug resistance, fewer drug-drug interactions, and improved safety and pharmacokinetic profiles. Choosing the ideal target combination and achieving a balanced activity toward them while preserving drug-like properties are the key challenges in the development of molecular hybrids. This review examines the highlights of quinoline hybridization, with some of the hybrids exhibiting remarkable in vitro and in vivo activities, emphasizing that it is a useful method for developing new anti-malarial lead compounds.

Quinoline-based heterocyclic hydrazones: Design, synthesis, anti-plasmodial assessment, and mechanistic insights.

A library of quinoline-based hydrazones bearing 1H-1,2,3-triazole core was designed, synthesized, and evaluated for their antiplasmodial activity against the drug-resistant Plasmodium falciparum W2 strain. The inclusion of pyrazine-2-carboxylic acid with a flexible propyl spacer afforded the most active scaffold with an IC50 value of 0.26 µM. Mechanistically, the compound inhibited heme to hemozoin formation, as demonstrated by UV-vis and mass spectral studies.

Fifty Most Influential Articles on Anorectal Malformations: A Tribute through Bibliometric Ranking.

Background: With the global assimilation of "publish and perish" culture into institutional academics, there has been an exponential rise in the publication numbers. There are ~2500 PUBMED entries related to "anorectal malformation (ARM)." The young clinician in his pursuit to translate experimental research to bedside often finds himself lost "in the midst of plenty." This bibliometric analysis has been conducted to codify the seminal work on ARM for future reference and pay tribute to the most impactful articles. Materials and Methods: Thomson Reuters Web of Science citation indexing database and research platform was used to retrieve the most cited articles in ARM using appropriate search strings. The characteristics (name of authors, the total number of authors, the title of publication, journal of publication, year of publication, etc.,) of the 50 top-cited articles were analyzed. Results: The analysis revealed that the Journal of Paediatric Surgery was leading the choice of journal for publication. While most of the publications originated from the United States of America, Alberto Pena was the most influential author. The most studied topic was on associated malformations, and the most common study design was cohort studies. Conclusion: The approach of citation analysis provided us an opportunity to retrieve the most influential articles on ARM. The trends in research in ARM have also been analyzed, spreading over five decades.

Synthesis, Anti-Plasmodial Activities, and Mechanistic Insights of 4-Aminoquinoline-Triazolopyrimidine Hybrids.

In the search of new antiplasmodial agents, a multitargeted approach was used in the synthesis of triazolopyrimidine- and 4-aminoquinolines-based hybrids. In vitro antiplasmodial evaluation on chloroquine-sensitive (3D7) and -resistant (W2) P. falciparum strains identified triazolopyrimidine-4-aminoquinoline hybrids to be the most potent in the series, outperforming bis-triazolopyrimidines. The active compounds were subjected to mechanistic studies with the plausible and expected targets including heme, PfCRT, and PfDHODH, that eventually validated the biological data. The active compound surpassed the antimalarial drug CQ by inhibiting the parasite's cellular process (hemozoin formation) and parasitic enzymes (PfCRT and PfDHODH), as confirmed by UV-vis and molecular modeling studies.

Designing quinoline-isoniazid hybrids as potent anti-tubercular agents inhibiting mycolic acid biosynthesis.

Isoniazid is a cornerstone of modern tuberculosis (TB) therapy and targets the enoyl ACP reductase InhA, a key enzyme in mycolic acid biosynthesis. InhA is still a promising target for the development of new anti-TB drugs. Herein, we report the design, synthesis, and anti-tubercular activity of new isoniazid hybrids. Among these, 1H-1,2,3 triazole-tethered quinoline-isoniazid conjugates 16a to 16g exhibited high activity against Mycobacterium tuberculosis with minimal inhibitory concentrations in the 0.25-0.50 µg/mL range and were bactericidal in vitro. Importantly, these compounds were well tolerated at high doses on mammalian cells, leading to high selectivity indices. The hybrids were dependent on functional KatG production to inhibit mycolic acid biosynthesis. Moreover, overexpression of InhA in M. tuberculosis resulted in high resistance levels to 16a-16g and reduced mycolic acid biosynthesis inhibition, similar to isoniazid. Overall, these findings suggest that the synthesized quinoline-isoniazid hybrids are promising anti-tubercular molecules, which require further pre-clinical evaluation.