A Comprehensive Examination of Heterocyclic Scaffold Chemistry for Antitubercular Activity.

Tuberculosis is a communicable disease which affects humans particularly the lungs and is transmitted mainly through air. Despite two decades of intensive research aimed at understanding and combating tuberculosis, persistent biological uncertainties continue to hinder progress. Nowadays, heterocyclic compounds have proven themselves in effective treatment of tuberculosis because of their wide range of biological and pharmacological activities. Antituberculosis or antimycobacterial agents encompass a broad array of compounds utilized singly or in conjunction to combat Mycobacterium infections, spanning from tuberculosis to leprosy. Here, we summarize the synthesis of various heterocyclic compounds which includes the greener synthetic route as well as use of nano compounds as catalyst along with their anti TB activities.

MicroRNA-mediated regulation of nonsense-mediated mRNA decay factors: Insights into microRNA prediction tools and profiling techniques.

Nonsense-mediated mRNA decay (NMD) stands out as a prominent RNA surveillance mechanism within eukaryotes, meticulously overseeing both RNA abundance and integrity by eliminating aberrant transcripts. These defective transcripts are discerned through the concerted efforts of translating ribosomes, eukaryotic release factors (eRFs), and trans-acting NMD factors, with Up-Frameshift 3 (UPF3) serving as a noteworthy component. Remarkably, in humans, UPF3 exists in two paralogous forms, UPF3A (UPF3) and UPF3B (UPF3X). Beyond its role in quality control, UPF3 wields significant influence over critical cellular processes, including neural development, synaptic plasticity, and axon guidance. However, the precise regulatory mechanisms governing UPF3 remain elusive. MicroRNAs (miRNAs) emerge as pivotal post-transcriptional gene regulators, exerting substantial impact on diverse pathological and physiological pathways. This comprehensive review encapsulates our current understanding of the intricate regulatory nexus between NMD and miRNAs, with particular emphasis on the essential role played by UPF3B in neurodevelopment. Additionally, we bring out the significance of the 3'-untranslated region (3'-UTR) as the molecular bridge connecting NMD and miRNA-mediated gene regulation. Furthermore, we provide an in-depth exploration of diverse computational tools tailored for the prediction of potential miRNA targets. To complement these computational approaches, we delineate experimental techniques designed to validate predicted miRNA-mRNA interactions, empowering readers with the knowledge necessary to select the most appropriate methodology for their specific research objectives.

Comparative analysis of CBNAAT (GeneXpert) and Ziehl-Nielsen staining test as diagnostic modalities of tuberculosis.

Background: As centuries and millennia passed, tuberculosis remains the major health threat for millions of people. Due to this resurgence of tuberculosis, scientists around the globe have intensified their research efforts to curb down the transmission of this disease and that is the reason which led to the development of new and efficient diagnostic tools, one such being the rapid cartridge-based nucleic acid amplification test which can give the real-time results and that too in a short period of time. These diagnostic tools which are based on the latest technologies help in paving the way to eliminate tuberculosis by early detection method and further prevent the transmission. Aim: In this study, we did a comparative analysis of the effectiveness of CBNAAT technique in the early detection of Mycobacterium tuberculosis over the conventional method of Ziehl-Nielsen microscopy as diagnostic modalities. Materials and Methods: Comparative analysis of CBNAAT (GeneXpert) and Ziehl-Nielsen staining test was done as diagnostic modalities using standard protocols. Results: Out of total 300 samples, 153 were female, 146 were male, while one was transgender. For all these samples, the positivity rates were 48% for the CBNAAT technique and 21.3% for ZN staining method, respectively. For extrapulmonary samples, positivity rates were 49.1% and 11.86% for CBNAAT and ZN microscopy, respectively, while the same for pulmonary samples was 47.7% and 23.6%, respectively. Conclusions: ZN microscopy and CBNAAT are both initial tests for the detection of Mycobacterium tuberculosis, but the introduction of CBNAAT is a boon for peripheral sites. The higher positivity rate of CBNAAT over ZN staining is the icing on the cake with the ability to detect even those cases that could be missed by the latter.

Quasi-2D Bi0.775Ln0.225O1.5 (Ln = La, Pr, Nd, Sm, Eu): reversible iodine intercalation and their evaluation as the anode in the lithium-ion battery system.

Layered materials with a robust structure and reversible intercalation behavior are highly sought-after in applications involving energy conversion and storage systems, energy converting devices, supercapacitors, batteries, superconductors, photonic materials, and catalysis involving hydrogen evolution reaction (HER), oxygen evolution reaction (OER), oxygen reduction reaction (ORR), solar cells and sensors. In the current study, quasi-2D rhombohedral Bi0.775Ln0.225O1.5 (Ln = La, Pr, Nd, Sm, and Eu) samples, synthesized by a solution combustion route, have been demonstrated to intercalate iodine reversibly. A solid-vapor reaction was employed to intercalate iodine at moderate temperatures, and deintercalation occurred on heating at higher temperatures. Expansion of the rhombohedral c-axis by ∼10 Šoccurred, and the iodine between the interlayers existed as triiodide ions (I3-) in an unsymmetrical fashion. The amount of intercalated iodide has been determined from thermogravimetric analysis. Electron microscopic analysis confirmed these systems' intercalation and subsequent lattice expansion. In the diffuse reflectance spectra, charge transfer from the triiodide ions to the host oxide was noticed, and it caused the absorption edge to fall beyond the visible region for the intercalated samples. XPS analysis of iodine intercalated Bi0.775Pr0.225O1.5 has shown the mixed valence states for Pr and the existence of I3- along with some IO3- species. The quasi-2D structure was stable during the thermal deintercalation process. The evaluation of iodine intercalated Bi0.775Ln0.225O1.5 (Ln = La, Pr, Nd, Sm, and Eu) samples as anode material in the lithium-ion battery system has given quite promising results, exhibiting fast Li+-ion diffusion, low charge transfer resistance, good reversible capacity, capacity retention (after cycling back to 10 mA g-1), and structural stability (after long cycles).

Novel amino- and hydroxy-functionalized 1,2,4-trioxanes and their antimalarial activity against multidrug-resistant Plasmodium yoelii nigeriensis in Swiss mice via intramuscular and oral route.

Following the economic and social state of humanity, Malaria is categorized as one of the life-threatening illness epidemics in under developed countries. For the eradication of the same, 1,2,4-trioxanes 17a1-a2, 17b1-b2, 17c1-c2 15a-c, 18 and 19 have been synthesized continuing the creation of a novel series. Additionally, these novel compounds were tested for their effectiveness against the multidrug-resistant Plasmodium yoelii nigeriensis in mice model using both oral and intramuscular (im) administration routes. The two most potent compounds of the series, 17a1 and 17a2, demonstrated 100 % protection at 48 mg/kg x 4 days via oral route, which is twice as potent as artemisinin. In this model artemisinin provided 100 % protection at a dose of 48 mg/kg × 4 days and 80 % protection at 24 mg/kg × 4 days via im route.

External electric field, a potential catalyst for C-N cross-coupling reaction.

The present work investigates the role of the external electric field (EEF) in boosting the C-N cross-coupling reaction between 2-chlorobenzoic acid and propylamine, by computing the reaction rates and energy barrier. The investigation suggests that the reaction can become barrierless by choosing an electric field in the appropriate direction, resulting in a quadrillionfold increase in the reaction rate in the presence of an EEF. We also found that the efficiency of the electric field depends on the dipole moment of the reactants, and hence, the results of the present work are general in nature and should be applicable to a variety of C-N cross-coupling reactions.

Happiness index of medical students and related factors in Andaman and Nicobar Islands, India.

BACKGROUND: Happiness is an important factor for everyone's good health and general well-being. Medical students need to manage a lengthy medical curriculum, clinical postings, and the stressful environment of hospital setting, which may have considerable effects on their happiness. No such studies have been conducted in the remotely located Andaman and Nicobar (A and N) islands. Hence, the current study was conducted to determine the level of happiness and associated factors among medical college students of the Andaman and Nicobar islands. METHODS AND MATERIALS: A cross-sectional study was conducted among 315 medical students of the A and N islands. The happiness of students was measured using the Oxford Happiness Questionnaire. Chi-square test and multiple logistic regression were used for data analysis. RESULTS: Among all the students, 42.5% were happy. There was a significant association between happiness and the relationship of students with family and friends, physical exercise, spiritual beliefs, the presence of stress, and traumatic events. The multiple logistic regression revealed that good relationship with friends increased the odds of happiness of students significantly with an adjusted odd ratio (OR) of 3.204 (1.641-6.257), whereas the presence of stress decreased the happiness of students significantly with an adjusted OR of 0.430 (0.254-0.730). CONCLUSION: Good relations with friends emerged as a positive predictor of happiness, whereas stress emerged as a negative predictor of happiness among the students. Hence, human relationships, stress management, physical exercise or sports, and orientation to spiritual health should be given emphasis in the medical curriculum.

Adjunct therapy with all-trans-retinoic acid improves therapeutic efficacy through immunomodulation while treating tuberculosis with antibiotics in a murine model.

Tuberculosis (TB) is the second leading infectious killer after COVID-19. Standard anti-tubercular drugs exhibit various limitations like toxicity, lengthy, and unresponsive to dormant and drug resistant organisms. Here, we report that all-trans-retinoic acid (ATRA) improves M.tb clearance in mice while treating with anti-tubercular drug isoniazid (INH). Interestingly, ATRA promoted activities of lysosomes, mitochondria, and production of various inflammatory mediators in macrophages. Furthermore, ATRA upregulated the expression of genes of lipid metabolic pathways in macrophages. Along this line, we registered that ATRA activated MEK/ERK pathway in macrophages in-vitro and MEK/ERK and p38 MAPK pathways in the mice. Finally, ATRA induced both Th1 and Th17 responses in lungs and spleens of M.tb-infected mice. Taken together, these data indicated that ATRA provides beneficial adjunct therapeutic value by modulating MEK/ERK and p38 MAPK pathways and thus warrants further testing for human use.

Nitrogen-Enriched Biguanidine-Functionalized Cobalt Ferrite Nanoparticles as a Heterogeneous Base Catalyst for Knoevenagel Condensation under Solvent-Free Conditions.

Designing efficient, economical heterogeneous catalysts for the Knoevenagel condensation reaction is highly significant owing to the importance of reaction products in industries as well as pharmaceutics. Herein, we have designed and synthesized biguanidine-functionalized basic magnetically retrievable cobalt ferrite nanoparticles (CFNPs) for the synthesis of Knoevenagel condensation products using benzaldehydes and active methylene compounds (malononitrile/ethyl cyanoacetate/cyanoacetamide). Several advanced techniques, such as Fourier transform infrared (FT-IR), thermogravimetric analysis (TGA), powder X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and vibration sample magnetometry (VSM), were utilized to precisely characterize the catalyst. The robust features of the current approach involve outstanding catalytic performance, solvent-free reaction conditions, ease of catalyst retrievability, easy workup procedure, large substrate tolerance, high turnover frequency (TOF) values (up to 486.88 h-1), values of green chemistry metrics such as E-factor (0.15), reaction mass efficiency (RME) value (87.07%), carbon efficiency (93.4%), and atom economy (AE) value (88.10%) close to their ideal values, and recyclability up to eight runs without a considerable reduction in activity, boosting the appeal of this approach from a commercial and ecological point of view.

Recurrent pancreatitis secondary to hypertriglyceridemia: A case report and case review.

Key Clinical Message: Managing acute pancreatitis secondary to hypertriglyceridemia in pregnancy is challenging. The use of intravenous insulin along with lipid lowering drugs can be an option in settings where plasmapharesis and gene therapy are unavailable. Abstract: Acute pancreatitis secondary to hypertriglyceridemia is rare but various studies have highlighted it as the third most common cause following gallstones and alcohol consumption. Managing acute pancreatitis is always challenging; even more challenging during pregnancy. We present a case of a 31-year- old female with a history of recurrent pancreatitis secondary to hypertriglyceridemia with a current episode of acute pancreatitis at 21 weeks of gestation.

Life span of Neoendo Flex and ProTaper Next rotary files with reciprocating motion in single-rooted teeth.

Background: Cleaning and shaping represent a vital step in the endodontic procedure. In routine endodontic therapy, the fracture of nickel-titanium (NiTi) instruments is a procedural problem creating a major obstacle to therapy. Aim: This study examines the life span of one Neoendo Flex and ProTaper Next (PTN) rotary file using reciprocating motion and compares the time required by both file systems for canal preparation. Materials and Methods: One hundred maxillary permanent central incisors were selected. In that, fifty teeth are utilized in a reciprocating motion (RM) with the PTN file (n = 25) and Neoendo Flex file (n = 25). To check fractured resistance and the overall root canal preparation time, fifty more teeth are employed in continuous motion (CM) with canals prepared using PTN (n = 25) and Neoendo Flex (n = 25). All canals are prepared following the sequence of respective files. Later, the fracture mechanism of the files was inspected using a scanning electron microscope. Results: In an RM motion, both PTN and Neoendo Flex files can be used in a minimum of 25 canals in single-rooted teeth. Statistical analysis using the Mann-Whitney U-test showed no significant difference in total time taken by PTN and Neoendo Flex in both motions. Conclusion: Within the limitation of this study, the RM was found to be better than CM with less incidence of instrument fracture.

Spontaneous fundal rupture in an unscarred uterus in a female with twin pregnancy after in-vitro fertilization: a case report.

Spontaneous uterine rupture in an unscarred uterus is very rare. It is found to be rarer after in-vitro fertilization. It is associated with significant morbidity and mortality if not diagnosed and treated promptly. Case presentation: Thirty three years female with twin pregnancy following in-vitro fertilization after 11 years of marriage presented to emergency department with lower abdominal pain at 36 weeks 3 days of gestation and was planned for emergency caesarean section for precious twin pregnancy in labour. Clinical findings and investigation: She was vitally stable and on palpation of abdomen, there was generalized tenderness along with guarding. All the investigations were within normal limits. Intervention and outcome: Emergency caesarean section was performed under subarachnoid block which revealed a 6×2 cm fundal uterine rupture with no active bleeding which was repaired in layers. The babies were extracted with a lower uterine segment incision. First twin cried immediately after birth while the second one needed resuscitation and mechanical ventilation due to perinatal asphyxia. Conclusion: Even though rare in a previously unscarred uterus, uterine rupture can present in different forms and thus, requires vigilant evaluation of the patient and prompt intervention to avoid significant maternal or foetal morbidity and mortality.

Hole and Electron Doping Outcomes in Bi2YO4Cl.

Recognizing the deficiency in the hole and electron doping outcomes in layered bismuth-based oxyhalides intergrowths, the current study was addressed to the doping of Ca2+ and Zr4+ for Y3+ in Bi2YO4Cl. The samples were rapidly synthesized by a sol-gel auto combustion method and characterized extensively. Up to 30 mol % Y could be substituted with Ca in tetragonal symmetry and without the appearance of any additional phase. The unit cell parameters varied nonlinearly with the elongation of the Y-O bond. The Raman spectra supported the local site distortion. The calcium-substituted samples displayed selected area electron diffraction characteristics similar to those of Bi2YO4Cl. A blueshift of the absorption edge was noticed with increasing calcium content yielding optical band gap values in the 2.40-2.57 eV range. The creation of 10% Bi5+ in Bi2Y0.70Ca0.30O4Cl was established with the help of XPS measurements and redox titrations. The higher reactivity of Bi5+ in an aqueous solution has been demonstrated for the oxidation of As(III) to As(V). Electron doping through Zr4+ incorporation was possible up to 30 mol % in Bi2YO4Cl. The Y-O bonds are contracted, and the Bi-O bonds are elongated with increasing Zr4+ content. Zr4+'s incorporation induced a local distortion. The color of the sample changed from bright yellow to deep yellow with Zr inclusion, resulting in a progressive decrease in optical band gap values. The introduction of electrons caused the reduction of 13.6% of Bi(III) to Bi(0). These results have established the vulnerability of Bi2O2 chains to charge carriers in Bi2YO4Cl. Density functional theory (DFT) calculations were implemented to understand the electronic and optical properties of the pristine and doped compounds. From the band structure calculations, the chosen compounds were found to be indirect band gap semiconductors. The results of the DFT calculations were in good agreement with the experiment; however, for the doped cases, virtual crystal approximation has been used considering uniform doping at the Y-site.

Design, Synthesis, Antimicrobial Evaluation of Novel 2-Oxo-4-Substituted Aryl-Azetidine Benzotriazole Derivatives.

A series of compounds was synthesized and characterized to explore new antimicrobial agents. These compounds were evaluated by using the agar cup plate method. The most active compound exhibited a zone of inhibition 18±0.09 mm and 19±0.09 mm against E. Coli and S. aureus, respectively. To gain insights into the intermolecular interactions, molecular docking studies were performed at the active site of the glucosamine fructose 6 phosphate synthase (GlcN 6 p) enzyme (PDB Id: 1XFF). The results of the molecular docking studies are in agreement with the pharmacological evaluation with potent compounds, exhibiting docking scores of -11.2. However, deformability, B-factor and covariance computations showed a result that the most active compound favored molecular connections with the protein. Therefore, our research is important for the development of antimicrobial agents.

Piperazine-1,2,3-triazole scaffolds: design, synthesis, anticancer and antimicrobial evaluation.

Aim: The objective of the present study is to design and synthesize diverse piperazine-1,2,3-triazole scaffolds as key pharmacophores possessing antimicrobial/anticancer activities. Materials & methods: Twenty-four scaffolds were synthesized via a click-inspired synthetic protocol and were assayed for anticancer activity using the methyl thiazolyl tetrazolium assay and for antimicrobial potency by serial dilution. Results: Among all the tested 1,2,3-triazole scaffolds, compounds 7i (IC50: 5.22 ± 0.05 µM) and 7a (IC50: 5.34 ± 0.13 µM) exhibited good anticancer activity, and 7x also showed notable antimicrobial activity. Molecular docking studies of potent analogs 7i and 7a were performed to provide an insight into their binding interactions. Conclusion: Compound 7x is considered a valuable lead compound for further optimization of anticancer and antimicrobial agents.

Calixarene-Metal Complexes in Lactide Polymerization: The Story so Far.

Polylactide synthetic procedures have lately gained attention, possibly due to their biocompatibility and the environmental problems associated with fossil-fuel-based polymers. Polylactides can be obtained from natural sources such as cassava, corn, and sugar beet, and polylactides can be manufactured in a laboratory using a variety of processes that begin with lactic acid or lactide. One of the most effective synthetic pathways is through a Lewis acid catalyzed ring-opening polymerization of lactides to obtain a well-defined polymer. In this regard, calixarenes, because of their easy functionalization and tunable properties, have been widely considered to be a suitable 3D molecular scaffold for new metal complexes that can be used for lactide polymerization. This review summarizes the progress made in applying some metal-calixarene complexes in the ring-opening polymerization of lactide.

An Approach to Evaluate Pb Tolerance and Its Removal Mechanisms by Pleurotus opuntiae.

Widespread lead (Pb) contamination prompts various environmental problems and accounts for about 1% of the global disease burden. Thus, it has necessitated the demand for eco-friendly clean-up approaches. Fungi provide a novel and highly promising approach for the remediation of Pb-containing wastewater. The current study examined the mycoremediation capability of a white rot fungus, P. opuntiae, that showed effective tolerance to increasing concentrations of Pb up to 200 mg L-1, evidenced by the Tolerance Index (TI) of 0.76. In an aqueous medium, the highest removal rate (99.08%) was recorded at 200 mg L-1 whereas intracellular bioaccumulation also contributed to the uptake of Pb in significant amounts with a maximum of 24.59 mg g-1. SEM was performed to characterize the mycelium, suggesting changes in the surface morphology after exposure to high Pb concentrations. LIBS indicated a gradual change in the intensity of some elements after exposure to Pb stress. FTIR spectra displayed many functional groups including amides, sulfhydryl, carboxyl, and hydroxyl groups on the cell walls that led to binding sites for Pb and indicated the involvement of these groups in biosorption. XRD analysis unveiled a mechanism of biotransformation by forming a mineral complex as PbS from Pb ion. Further, Pb fostered the level of proline and MDA at a maximum relative to the control, and their concentration reached 1.07 µmol g-1 and 8.77 nmol g-1, respectively. High Pb concentration results in oxidative damage by increasing the production of ROS. Therefore, the antioxidant enzyme system provides a central role in the elimination of active oxygen. The enzymes, namely SOD, POD, CAT, and GSH, served as most responsive to clear away ROS and lower the stress. The results of this study suggested that the presence of Pb caused no visible adverse symptoms in P. opuntiae. Moreover, biosorption and bioaccumulation are two essential approaches involved in Pb removal by P. opuntiae and are established as worthwhile agents for the remediation of Pb from the environment.

An inclusive outlook on the fate and persistence of pesticides in the environment and integrated eco-technologies for their degradation.

Intensive and inefficient exploitation of pesticides through modernized agricultural practices has caused severe pesticide contamination problems to the environment and become a crucial problem over a few decades. Due to their highly toxic and persistent properties, they affect and get accumulated in non-target organisms, including microbes, algae, invertebrates, plants as well as humans, and cause severe issues. Considering pesticide problems as a significant issue, researchers have investigated several approaches to rectify the pesticide contamination problems. Several analyses have provided an extensive discussion on pesticide degradation but using specific technology for specific pesticides. However, in the middle of this time, cleaner techniques are essential for reducing pesticide contamination problems safely and environmentally friendly. As per the research findings, no single research finding provides concrete discussion on cleaner tactics for the remediation of contaminated sites. Therefore, in this review paper, we have critically discussed cleaner options for dealing with pesticide contamination problems as well as their advantages and disadvantages have also been reviewed. As evident from the literature, microbial remediation, phytoremediation, composting, and photocatalytic degradation methods are efficient and sustainable and can be used for treatment at a large scale in engineered systems and in situ. However, more study on the bio-integrated system is required which may be more effective than existing technologies.

Beta glucan as an immune stimulant in tumor microenvironment - Insight into lessons and promises from past decade.

Cancer is characterized by a perturbed immune landscape. Inside tumor microenvironment, immune system is reprogrammed to facilitate tumor growth and survival rather than eliminating it. This immune evasive mechanism needs to be reversed to normal for effective anticancer therapeutic strategy. Immunotherapy has emerged as a novel strategy for redeployment of immune cells against cancer. However, they suffer in their efficacy, response rate and side effects. This necessitated us to turn toward natural repertoires which can act as a substitute to conventional immunotherapeutics. Beta glucan, a polysaccharide derived from mushroom, serves the role of immunomodulator inside tumor microenvironment. It acts as pathogen associated molecular pattern and bind to various pattern recognition receptors expressed on surface of immune cells thereby facilitating their activation and crosstalk. This result in resurgence of suppressed immune surveillance in the tumor milieu. In this review, we highlight in brief the advances and limitation of cancer immunotherapy. Alongside, we have discussed the detailed mechanistic principle and recent advances underlying restoration of immune functionality by beta glucan.

High-Affinity DNA Nanomatrix: A Platform Technology for Synergistic Drug Delivery and Photothermal Therapy.

With the advent of nucleosome/nucleotide intercalating drugs, DNA-based nanocarriers have recently gained impetus. However, most of the newly proposed DNA nanosystems are rather complex, thereby having low scalability and translatability. In this study, we propose a simple DNA nanomatrix core encapsulated within a chitosan shell, which is expected to enhance the encapsulation efficiency of intercalating drugs. This has been demonstrated using proflavine hemisulfate (PfHS), a model intercalating agent that shows improved ROS generation, among other anticancerous properties. The release of the drug from the nanomatrix is triggered by providing a heat trigger using IR-792 perchlorate, a known NIR photothermal sensitizer.