Search

Equitable access to quality health services is a fundamental right of every citizen. As access to quality health services is an important domain of universal health coverage. Clinical audit is a crucial tool for maintaining a high standard of care in the hospital. This study aims to highlight the discrepancies between actual practice and standard in order to identify the changes needed to improve the quality of care and to implement the changes of Radiology department in central government hospital of Nepal. A descriptive, cross-sectional survey encompassing central government hospital was conducted. A structured online questionnaire comprising 41 questions was employed and classified into 2 sections, encompassing demographic data and clinical audit tool. Microsoft Excel and SPSS V.25 were used to analyze the data, and frequencies were computed. Of the 31 central government hospitals in Nepal, 19 (61.3%) are located in Bagmati province. Six of the thirty-one hospital radiography staff members have completed at least BLS or ACLS training. There is no biomedical engineering support at 8 Hospital. Hospitals that have adopted RIS or PACS are 41.9%. There are no personnel radiation dose monitoring devices in 22 out of 31 hospitals. Only six hospitals provide staff members with recurring radiation protection training. In the imaging sector, 74.2% of hospitals have an obvious radiation hazard warning for expectant moms. This study highlights the relatively medium level of clinical audit in central government hospital of Nepal. However, the identified lack of knowledge pertaining to the clinical audit emphasizes the need for further education and training in this area. To address this gap, we recommend the establishment of comprehensive orientation of clinical audit for radiology professionals. Encouraging equitable and high-quality healthcare will aid in achieving the Sustainable Development Goals (SDGs) through clinical audit. [ABSTRACT FROM AUTHOR]

Alzheimer's disease is the most common form, accounting for 60-70% of 55 million dementia cases. Even though the precise pathophysiology of AD is not completely understood, clinical trials focused on antibodies targeting aggregated forms of β amyloid (Aβ) have demonstrated that reducing amyloid plaques can arrest cognitive decline in patients in the early stages of AD. In this study, we provide an overview of current research and innovations for controlled release from nano-biomaterial-assisted chimeric antigen receptor macrophage (CAR-M) therapeutic strategies targeted at AD. Nano-bio materials, such as iron-oxide nanoparticles (IONPs), can be made selectively (Hp-Hb/mannose) to bind and take up Aβ plaques like CAR-M cells. By using nano-bio materials, both the delivery and stability of CAR-M cells in brain tissue can be improved to overcome the barriers of the BBB and enhance therapeutic effects. By enhancing the targeting capabilities and stability of CAR-M cells, mRNA-loaded nano-biomaterials can significantly improve the efficacy of immunotherapy for plaque reduction in AD. This novel strategy holds promise for translating preclinical successes into clinical applications, potentially revolutionising the management of AD.

Organofluorine compounds are increasingly found in diverse fields, such as pharmaceuticals, agrochemicals, and materials science. gem -Difluoroallenes, which have gem -difluoro alkenes and allenes-like properties, offer a distinct and adaptable platform for novel synthetic transformations. Their distinctiveness is highlighted by various strategies, where the gem -difluoro group's presence plays a pivotal role in successful reactions. This review article presents a comprehensive overview of the latest progress in utilizing gem -difluoroallenes for selective additions, defluorination, as well as cycloaddition and cyclization reactions. We also discuss the limitations and future directions in this area, inspiring further exploration and innovation.

Decaprenylphosphoryl-β-d-ribose-2'-epimerase (DprE1) is a druggable target which is being exploited for the development of new anti-TB agents. In the present work, we report developing a pharmacophore model and performing virtual screening of Asinex database using the developed pharmacophore model to get eight hits as potential DprE1 inhibitors. The hits were used as leads to design new 3-phenylpyrazolo[1,5- a ]pyrimidine-2,7(1 H ,4 H )-dione based potential anti-TB agents. On the basis of the identified lead molecules, a total of 18 compounds were synthesized and evaluated for their anti-TB activity by using MABA. ADMET predictions for all the compounds revealed that these compounds have drug-like and lead-like properties. One of the final compounds was found to exhibit potent anti-TB activity against Mycobacterium bovis .Communicated by Ramaswamy H. Sarma.

The Mycobacterium cell wall is a capsule-like structure comprising of various layers of biomolecules such as mycolic acid, peptidoglycans, and arabinogalactans, which provide the Mycobacteria a sort of cellular shield. Drugs like isoniazid, ethambutol, cycloserine, delamanid, and pretomanid inhibit cell wall synthesis by inhibiting one or the other enzymes involved in cell wall synthesis. Many enzymes present across these layers serve as potential targets for the design and development of newer anti-TB drugs. Some of these targets are currently being exploited as the most druggable targets like DprE1, InhA, and MmpL3. Many of the anti-TB agents present in clinical trials inhibit cell wall synthesis. The present article covers a systematic perspective of developing cell wall inhibitors targeting various enzymes involved in cell wall biosynthesis as potential drug candidates for treating Mtb infection., (© 2024 John Wiley & Sons Ltd.)

Introduction: The prevalence of breast cancer presents a substantial global health concern, underscoring the ongoing need for the development of inventive therapeutic remedies., Methods: In this investigation, an array of novel indazole-pyridine hybrids (5a-h) have been designed and synthesized to assess their potential as candidates for treating breast cancer. Subsequently, we have conducted biological evaluations to determine their cytotoxic effects on the human MCF-7 breast cancer cell line. Furthermore, in silico analysis was conducted to estimate the inhibition potential of the compounds against TrkA (Tropomyosin receptor kinase A), a specific molecular target associated with breast cancer, through molecular docking. In silico physicochemical and pharmacokinetic predictions were made to assess the compounds' drug-like properties., Results: Compound 5a emerged as the most active compound among the others with GI50 < 10 μg/ml. Besides, compound 5a showed high binding energy (BE -10.7 kcal/mol) against TrkA and was stabilized within the TrkA binding pocket through hydrophobic, H-bonding, and van der Waals interactions. In silico physicochemical and pharmacokinetic prediction studies indicated that compound 5a obeyed both Lipinski's and Veber's rule and displayed a versatile pharmacokinetic profile, implying compound 5a to appear as a viable candidate and that it could be further refined to develop therapeutic agents for potentially treating breast cancer., Conclusion: This study offers a promising direction for the advancement of innovative breast cancer treatments, highlighting the effectiveness of indazole-pyridine hybrids as potential anticancer agents. Further optimization and preclinical development are necessary to advance these compounds to clinical trials., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Multi-target directed ligands (MTDLs) have recently been popularized due to their outstanding efficacy in combating the complicated features of Alzheimer's disease. This study details the synthesis of piperazine-quinoline-based MTDLs through a multicomponent Petasis reaction, targeting multiple factors such as AChE, BuChE, metal chelation to restore metal dyshomeostasis, and antioxidant activity. Some of the synthesized compounds exhibited notable inhibitory activity against AChE and BuChE enzymes at specific concentrations. Among the synthesized compounds compound (95) containing a 4-chloroaniline moiety and a 4-methoxybenzyl group displayed the most promising inhibitory activities against AChE (IC 50 3.013 µM) and BuChE (IC 50  = 3.144 µM). Compound (83) featuring 2-methoxyaniline and 4-fluorobenzyl substituents, exhibited the highest BuChE inhibition (IC 50 1.888 µM). Notably, compound (79) demonstrated 93-times higher selectivity for BuChE over AChE. Molecular docking and molecular dynamics simulations were also performed to explore the binding modes and stability of these compounds with the AChE amd BuChE proteins. Further, kinetics study was performed against AChE for comounds (83 and 95) which indicated mixed inhibition of the enzyme by these compounds, Amongs the synthesized compounds, nine compounds were assessed for their antioxidant activity, displaying significant antioxidant properties with IC 50 values ranging from 156 µM to 310 µM. Moreover, all the compounds demonstrated metal chelating tendency with Cu +2 , Zn +2 , Fe +2 , Fe +3 and Al +3 . This study provides insights into the design of novel MTDLs, highlighting compound (95) as a potential candidate for combating Alzheimer's disease., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

We have demonstrated a Pd(0)-catalyzed Heck/C(sp 3 )-H activation cascade for the synthesis of spirocyclopropyl oxindoles in high yields from easily accessible ortho -bromoacrylamides. The formation of spirocyclopropyl oxindole is guided by an unconventional four-membered palladacycle through C(sp 3 )-H activation. The reaction exhibits a wide range of substrate scope and operates efficiently with a mere 0.5 mol % of Pd-catalyst. In addition, the use of microwave conditions facilitates rapid completion of the reaction. Furthermore, this spirocyclopropanation strategy can be coupled with [3 + 2] cycloaddition to produce spiropyrrolidine oxindoles, offering a valuable approach for the preparation of alkaloids such as (±)-horsfiline and (±)-coerulescine.

Background: Disabled 2 (DAB2) is a multifunctional protein that has emerged as a critical component in the regulation of tumor growth. Its dysregulation is implicated in various types of cancer, underscoring its importance in understanding the molecular mechanisms underlying tumor development and progression. This review aims to unravel the intricate molecular mechanisms by which DAB2 exerts its tumor-suppressive functions within cancer signaling pathways., Methods and Results: We conducted a comprehensive review of the literature focusing on the structure, expression, physiological functions, and tumor-suppressive roles of DAB2. We provide an overview of the structure, expression, and physiological functions of DAB2. Evidence supporting DAB2's role as a tumor suppressor is explored, highlighting its ability to inhibit cell proliferation, induce apoptosis, and modulate key signaling pathways involved in tumor suppression. The interaction between DAB2 and key oncogenes is examined, elucidating the interplay between DAB2 and oncogenic signaling pathways. We discuss the molecular mechanisms underlying DAB2-mediated tumor suppression, including its involvement in DNA damage response and repair, regulation of cell cycle progression and senescence, and modulation of epithelial-mesenchymal transition (EMT). The review explores the regulatory networks involving DAB2, covering post-translational modifications, interactions with other tumor suppressors, and integration within complex signaling networks. We also highlight the prognostic significance of DAB2 and its role in pre-clinical studies of tumor suppression., Conclusion: This review provides a comprehensive understanding of the molecular mechanisms by which DAB2 exerts its tumor-suppressive functions. It emphasizes the significance of DAB2 in cancer signaling pathways and its potential as a target for future therapeutic interventions., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Theranostics refers to the combination of diagnostic biomarkers with therapeutic agents that share a specific target expressed by diseased cells and tissues. Nuclear medicine is an exciting component explored for its applicability in theranostic concepts in clinical and research investigations. Nuclear theranostics is based on the employment of radioactive compounds delivering ionizing radiation to diagnose and manage certain diseases employing binding with specifically expressed targets. In the realm of personalized medicine, nuclear theranostics stands as a beacon of potential, potentially revolutionizing disease management. Studies exploring the theranostic profile of radioactive compounds have been presented in this review along with a detailed explanation of radioactive compounds and their theranostic applicability in several diseases. It furnishes insights into their applicability across diverse diseases, elucidating the intricate interplay between these compounds and disease pathologies. Light is shed on the important milestones of nuclear theranostics beginning with radioiodine therapy in thyroid carcinomas, MIBG labelled with iodine in neuroblastoma, and several others. Our perspectives have been put forth regarding the most important theranostic agents along with emerging trends and prospects., (© 2024 Walter de Gruyter GmbH, Berlin/Boston.)

Background: The tropomyosin receptor kinases (TRKs) are crucial for many cellular functions, such as growth, motility, differentiation, and metabolism. Abnormal TRK signalling contributes to a variety of human disorders, most evidently cancer. Comprehensive genomic studies have found numerous changes in the genes that code for TRKs like MET, HER2/ErbB2, and EGFR, among many others. Precision medicine resistance, relapse occurring because of the protein point mutations, and the existence of multiple molecular feedback loops are significant therapeutic hurdles to the long-term effectiveness of TRK inhibitors as general therapeutic agents for the treatment of cancer., Objective: This review is carried out to highlight the role of tropomyosin receptor kinase in cancer and the function of TRK inhibitors in the intervention of cancer., Methods: Literature research has been accomplished using Google Scholar and databases like ScienceDirect, WOS, PubMed, SciFinder, and Scopus., Results: In this review, we provide an overview of the main molecular and functional properties of TRKs and their inhibitors. It also discusses how these advancements have affected the development and use of novel treatments for malignancies and other conditions caused by activated TRKs. Several therapeutic strategies, including the discovery and development of small-molecule TRK inhibitors belonging to various chemical classes and their activity, as well as selectivity towards the receptors, have been discussed in detail., Conclusion: This review will help the researchers gain a fundamental understanding of TRKs, how this protein family works, and the ways to create chemical moieties, such as TRK inhibitors, which can serve as tailored therapies for cancer., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The emergence of drug resistance against the frontline antimalarials is a major challenge in the treatment of malaria. In view of emerging reports on drug-resistant strains of Plasmodium against artemisinin combination therapy, a dire need is felt for the discovery of novel compounds acting against novel targets in the parasite. In this study, we identified a novel series of quinolinepiperazinyl-aryltetrazoles (QPTs) targeting the blood stage of Plasmodium . In vitro anti-plasmodial activity screening revealed that most of the compounds showed IC 50 < 10 μM against chloroquine-resistant Pf INDO strain, with the most promising lead compounds 66 and 75 showing IC 50 values of 2.25 and 1.79 μM, respectively. Further, compounds 64-66, 68, 75-77 and 84 were found to be selective (selectivity index >50) in their action against Pf over a mammalian cell line, with compounds 66 and 75 offering the highest selectivity indexes of 178 and 223, respectively. Explorations into the action of lead compounds 66 and 75 revealed their selective cidal activity towards trophozoites and schizonts. In a ring-stage survival assay, 75 showed cidal activity against the early rings of artemisinin-resistant Pf Cam3.1 R539T . Further, 66 and 75 in combination with artemisinin and pyrimethamine showed additive to weak synergistic interactions. Of these two in vitro lead molecules, only 66 restricted rise in the percentage of parasitemia to about 10% in P. berghei -infected mice with a median survival time of 28 days as compared to the untreated control, which showed the percentage of parasitemia >30%, and a median survival of 20 days. Promising antimalarial activity, high selectivity, and additive interaction with artemisinin and pyrimethamine indicate the potential of these compounds to be further optimized chemically as future drug candidates against malaria., Competing Interests: The authors declare no conflict of interests., (This journal is © The Royal Society of Chemistry.)

A new and efficient method has been developed to synthesize dispiro[oxindole/acenaphthylenone-benzofuranone]pyrrolidine compounds. This is done by triggering the 1,3-dipolar cycloaddition reaction of azomethine ylides by reacting isatin/acenaphthoquinone with L-picolinic acid/L-proline/sarcosine/L-thioproline/tetrahydroisoquinolines, in a highly regioselective manner in an ionic liquid [DBU][Ac] with 4'-chloro-auron[2-(4-chlorobenzylidene)benzofuran-3(2H)-one]. Single-crystal X-ray diffraction data support the proposed structures of the new compounds. The heterocycles derived from amino acids such as L-picolinic acid, L-proline, and L-thioproline showed significant inhibitory effects against six human solid tumors, including lung, breast, cervix, colon, and others. These new structures were also tested in the active sites of the MDM2 receptor to further study their antiproliferative effects., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

We have developed an efficient Cu/ N , N -bidentate imine ligand catalytic system for C(sp 3 )-C(sp) coupling to obtain internal alkynes, di/trisubstituted allenes and strained bridged cyclic lactams in moderate to excellent yields from readily available alkyl(benzyl) bromides in one-pot transformation. Density Functional Theory (DFT) assisted mechanistic study along with control experiments support the involvement of bialkynylated copper species which undergo single electron transfer (SET) with alkyl halides to generate radical intermediate in the reaction. The N , N -bidentate imine ligand plays a vital role in stabilization of intermediate copper complex and facilitates the product formation.

Herein, we have demonstrated an operationally simple Pd-catalyzed double-Heck reaction between N -( o -bromoaryl)acrylamide derivatives and α-fluoro/trifluoromethyl acrylates to enable monofluoro/trifluoromethyl alkene tethered 3,3-disubstituted oxindoles in a stereoselective manner. Remarkably, the reaction proceeds well without any external ligand in an open-air atmosphere. Control experiments and spectroscopic analysis are performed to understand the reaction mechanism.

Metal- and additive-free, photoinduced decarboxylative radical alkylation-cyclization of CF 3 -acrylamides with alkyl redox-active esters provided the corresponding quaternary CF 3 -oxindole derivatives in good yields. Notably, diaryliodonium salts also efficiently participated in the arylation-cyclization of CF 3 -acrylamides in environmentally benign H 2 O as a solvent. The present approach has been extended for the concise synthesis of CF 3 -attached indoline alkaloid analogues, i.e., CF 3 -(±)-desoxyeseroline, CF 3 -(±)-esermethole, and CF 3 -(±) progesterone receptor antagonists. The preliminary mechanistic studies revealed that the reaction is likely to proceed through initial photoexcitation of redox-active ester/diaryliodonium salts followed by the SET process with acrylamide.

The selection of a protein structure is an important step for the success of the drug discovery process using structure-based design. Selection of the right crystal structure is critical as multiple crystal structures are available for the same protein in the Protein Data Bank (PDB). In this communication, we have discussed a systematic approach for selecting the right type of protein structure. Selecting crystal structures of TACE, 11β-HSD1, DprE1, and SARS-CoV-2 M pro enzymes for some case studies have been discussed for illustration., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

In the present work, a hit molecule obtained from zinc 'clean drug-like database' by systematically performed computational studies was modified chemically to obtain different derivatives (VS1-VS25). Structures of synthesized derivatives were confirmed by IR, 1 H-NMR, 13 C-NMR, 13 C-DEPT, MS, and elemental analysis. All the synthesized compounds were biologically evaluated for their antidepressant activity by using tail suspension test and forced swimming test in albino mice. All these derivatives showed moderate to good antidepressant activity. The most potent compound (VS25) among the synthesized compounds showed better antidepressant potential than the standard drugs moclobemide, imipramine, and fluoxetine. To understand the time-dependent interactions of this most active compound with MAO-A molecular dynamics was carried out and reported here. Additionally, acute oral toxicity was performed for the most active compound as per OECD guidelines., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

A Cu-based catalyst system convergently couples gem -difluoroalkenes with phenols under aerobic conditions to deliver α,α-difluorinated-α-phenoxyketones, an unstudied hybrid fluorinated functional group. Composed of α,α-difluorinated ketone and α,α-difluorinated ether moieties, these compounds have rarely been reported as a synthetic intermediate. Computational predictions and later experimental corroboration suggest that the phenoxy-substituted fluorinated ketone's sp 3 -hybridized hydrate form is energetically favored relative to the respective nonether variant and that perturbation of the electronic character of the ketone can further encourage the formation of the hydrate. The more facile conversion between ketone and hydrate forms suggests that analogues should readily covalently inhibit proteases and other enzymes. Further functionalization of the ketone group enables access to other useful fluorinated functional groups.

In this contribution, we report the design, synthesis and cytotoxicity studies of a series of N-[3-(benzimidazol-2-yl-amino)phenyl]amine and N-[3-(benzoxazol-2-ylamino)phenyl]amine derivatives. In vitro cytotoxicity assay of 26 selected compounds was carried out at National Cancer Institute (NCI), USA. Out of them, compounds 10e (NSC D-762842/1) and 11s (NSC D-764942/1) have shown remarkable cytotoxicity with GI 50 values ranging between "0.589-14.3 µM" and "0.276-12.3 µM," respectively, in the representative nine subpanels of human tumor cell lines. Further, flow cytometry analysis demonstrated that compound 10e exerted cell cycle arrest at G2/M phase and showed dose-dependent enhancement in apoptosis in K-562 leukemia cancer cells., (© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Overactivation of Wnt/β-catenin signaling by accumulated β-catenin in the nucleus has been shown to play a crucial role in the etiology of cancer. Interaction of β-catenin with Transcription factor 4 (TCF4) is a key step for the activation of Wnt genes in response to upstream signals of the Wnt/β-catenin pathway. Hence, down regulation of Wnt/β-catenin signaling or targeting downstream events by selective β-catenin/TCF4 protein-protein interaction inhibitors could be a potential therapeutic strategy against such cancers. In this study structure-based drug design approach was followed to design novel 4,7-disubstituted 8-methoxyquinazoline-based derivatives which could act as potential cytotoxic agents inhibiting the β-catenin/TCF4 protein-protein interactions. Fifteen compounds possessing 4,7-disubstituted 8-methoxyquinazoline scaffold were synthesized. Cytotoxic potential of the synthesised derivatives were determined against constitutively activated β-catenin/TCF4 signaling pathway cancer cells (HCT116 and HepG2) using the sulforhodamine B assay. The most potent compound (18B) was selected for detailed biological evaluation. Cell morphology, Hoechst 33342 and Annexin V/PI staining were used to detect apoptosis, while inhibition of cell migration was assessed by in vitro wound healing assay against HCT116 and HepG2 cells. Effect on β-catenin/TCF mediated transcriptional activity was assessed by TOPFlash/FOPFlash assay, TCF4 and β-catenin protein expression by immunocytofluorescence, and Wnt target genes (like c-MYC and Cyclin D1) mRNA levels by RT-PCR against HCT116 cells. Cytotoxic potency of the most potential compound (18B) against primary human gallbladder cancer cells was also evaluated. The derivatives showed interactions with active site residues of β-catenin and were capable of hindering the TCF4 binding, thereby disrupting β-catenin/TCF4 interactions. Cytotoxic potencies (IC 50 ) of these derivatives ranged from 5.64 ± 0.68 to 23.18 ± 0.45 μM against HCT116 and HepG2 cells respectively. Compound (18B), the most potent compound among the series, induced apoptosis and inhibited cell migration against HCT116 and HepG2 cells. Mechanistic studies indicated that compound (18B) downregulated β-catenin/TCF4 signaling pathway, β-catenin and TCF4 protein expression, and mRNA levels of c-MYC andCyclin D1 in HCT116 cells and showed cytotoxicity against primary human gallbladder cancer cells with IC 50 value of 8.50 ± 1.44 μM. Thus, novel 4,7-disubstituted 8-methoxyquinazoline derivatives were identified as potential cytotoxic agents with potencies comparable to that of imatinib mesylate. Compound (18B) represents a promising lead molecule as anticancer agent against colon, hepatocellular and gallbladder cancers targeting β-catenin/TCF4 signaling pathway., (Copyright © 2022. Published by Elsevier Inc.)

To confront a disease like Alzheimer's disease having complex pathogenesis, development of multitarget-directed ligands has emerged as a promising drug discovery approach. In our endeavor towards the development of multitarget-directed ligands for Alzheimer's disease, a series of indoloquinoxaline derivatives were designed and synthesized. In vitro cholinesterase inhibition studies revealed that all the synthesized compounds exhibited moderate to good cholinesterase inhibitory activity. 6-(6-(Piperidin-1-yl)hexyl)-6 H -indolo[2,3- b ]quinoxaline 9f was identified as the most potent and selective BuChE inhibitor (IC 50 = 0.96 µM, selectivity index = 0.17) that possessed 2 fold higher BuChE inhibitory activity compared to the commercially approved reference drug donepezil (IC 50 = 1.87 µM). Moreover, compound 9f is also endowed with self-induced Aβ 1-42 aggregation inhibitory activity (51.24% inhibition at 50 μM concentration). Some of the compounds of the series also displayed moderate anti-oxidant activity. To perceive a putative binding mode of the compound 9f , molecular docking studies were carried out, and the results pointed out significant interactions of compound 9f with the enzymes in the binding sites of cholinesterases as well as Aβ 1-42 . Additionally, compound 9f exhibited favorable in silico ADMET properties. Put together these findings project compound 9f as a potential multitarget-directed ligand in the direction of developing novel anti-AD drugs.Communicated by Ramaswamy H. Sarma.

Heat stress (HS) is one of the major abiotic stresses affecting the production and quality of wheat. Rising temperatures are particularly threatening to wheat production. A detailed overview of morpho-physio-biochemical responses of wheat to HS is critical to identify various tolerance mechanisms and their use in identifying strategies to safeguard wheat production under changing climates. The development of thermotolerant wheat cultivars using conventional or molecular breeding and transgenic approaches is promising. Over the last decade, different omics approaches have revolutionized the way plant breeders and biotechnologists investigate underlying stress tolerance mechanisms and cellular homeostasis. Therefore, developing genomics, transcriptomics, proteomics, and metabolomics data sets and a deeper understanding of HS tolerance mechanisms of different wheat cultivars are needed. The most reliable method to improve plant resilience to HS must include agronomic management strategies, such as the adoption of climate-smart cultivation practices and use of osmoprotectants and cultured soil microbes. However, looking at the complex nature of HS, the adoption of a holistic approach integrating outcomes of breeding, physiological, agronomical, and biotechnological options is required. Our review aims to provide insights concerning morpho-physiological and molecular impacts, tolerance mechanisms, and adaptation strategies of HS in wheat. This review will help scientific communities in the identification, development, and promotion of thermotolerant wheat cultivars and management strategies to minimize negative impacts of HS.

With the aim to combat a multi-faceted neurodegenerative Alzheimer's disease (AD), a series of carbazole-based semicarbazide and hydrazide derivatives were designed, synthesized and assessed for their cholinesterase (ChE) inhibitory, antioxidant and biometal chelating activity. Among them, ( E )-2-((9-ethyl-9 H -carbazol-3-yl)methylene)- N -(pyridin-2-yl)hydrazinecarbothioamide ( 62 ) and ( E )-2-((9-ethyl-9 H -carbazol-3-yl)methylene)- N -(5-chloropyridin-2-yl)hydrazinecarbothioamide ( 63 ) emerged as the premier candidates with good ChE inhibitory activities (IC 50 values of 1.37 µM and 1.18 µM for h AChE, IC 50 values of 2.69 µM and 3.31 µM for Eq BuChE, respectively). All the test compounds displayed excellent antioxidant activity (reduction percentage of DPPH values for compounds ( 62 ) and ( 63 ) were 85.67% and 84.49%, respectively at 100 µM concentration). Compounds ( 62 ) and ( 63 ) conferred specific copper ion chelating property in metal chelation study. Molecular docking studies of compounds ( 62 ) and ( 63 ) indicate strong interactions within the active sites of both the ChE enzymes. Besides that, these compounds also exhibited significant in silico drug-like pharmacokinetic properties. Thus, taken together, they can serve as a starting point in the designing of multifunctional ligands in pursuit of potential anti-AD agents that might further prevent the progression of ADs.Communicated by Ramaswamy H. Sarma.

Gene therapy has the therapeutic potential to address a multitude of health problems, and it also has utility in different domains of science. However, its applications are plagued due to the absence of a suitable, safe, efficient, selective, and universal vector, which could help in delivering the desired nucleic acid cargo to the site of action. Though viral vectors are efficient, they pose various health risks. Different types of synthetic agents have been tried as nucleic acid vectors by researchers but with limited success. Gemini amphiphiles (GAs) are a class of synthetic surfactants having biscationic heads with attached hydrophilic and lipophilic groups. Herein, we synthesized two classes of GAs differing in the chemical nature and length of the linkers, head groups, and lipophilic chains. The resulting compounds were evaluated for their efficiency to transfect A549 and HeLa cell lines with a β-galactosidase reporter plasmid. A 3-oxypentyl linker, a monohydroxyethyl head group, and a tetradecyl moiety as the lipophilic chain offered the best transfection efficiency (compound 10BIII ). Dioleoylphosphatidylethanolamine (DOPE) as the helper lipid improved the transfection efficacy of the GAs in the absence of serum. In the presence of serum, DOPE and cholesterol, as the helper lipids, improved the transfection efficacy of the resulting formulations. The synthesized GAs showed concentration-dependent toxicity in the MTT assay. Biodistribution studies using 99 m Tc-labeled lipoplexes indicated that the lipoplexes got concentrated in some vital organs such as the spleen, liver, and lungs., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)

Decarboxylative coupling reactions using readily available (hetero)aryl carboxylic acids are a highly efficient approach for the formation of new C-C and C-X bonds. These decarboxylative coupling reactions eliminate CO2 as a by-product, resulting in a greener and environmentally more benign approach than conventional coupling reactions. In this review, we summarize the recent developments in ipso-decarboxylative C-X (X = O/N/halo/S/Se/P/CN) bond formations using (hetero)aryl carboxylic acids. Furthermore, we highlight the current limitations and future research opportunities of aryl-decarboxylative coupling reactions.