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Pherosphaera fitzgeraldii, the Dwarf Mountain Pine, is a critically endangered conifer restricted to cliff ledges within waterfall spray zones in the Greater Blue Mountains Area of New South Wales, Australia. This species is under threat from pollution, invasive weeds, and limited recruitment, which are contributing to its declining population. Using a comprehensive conservation genomic approach, we assessed the population health of P. fitzgeraldii and developed strategic recommendations for its management.Genomic analysis of P. fitzgeraldii revealed the presence of two distinct genetic groups despite the limited distribution of the species. This genetic structure aligns with prevailing wind currents, indicating potential restrictions to pollen or seed exchange between subpopulations. Furthermore, limited gene flow was observed even among nearby subpopulations, emphasizing the risk of increased genetic differentiation due to ongoing isolation. Clonality is widespread in some subpopulations, and all subpopulations displayed signs of inbreeding and genetic depletion despite subdioecy, indicative of historical constraints on gene flow and small population sizes.We offer genomic-based recommendations for prioritizing conservation sites, enhancing genetic diversity in ex situ collections, and guiding future management. Further studies to uncover the sex determination mechanism of P. fitzgeraldii could help maintain balanced sex ratios in ex situ collections and support future genetic rescue efforts. This study underscores the value of genomics in informing protection and recovery of unique threatened species.

This study aimed to comprehensively assess the phytochemical composition, employing gas chromatography–mass spectrometry (GC–MS) and reverse-phase high-performance liquid chromatography (RP-HPLC) analyses, molecular docking, ADMET analysis, and antioxidant activity evaluation, of three Solanum species (Solanum forsskalii [SF], Solanum villosum [SV], and Solanum incanum [SI]) from the diverse flora of Saudi Arabia. Two solvents, hydro-methanolic (HME) and hydro-acetonic extract, were utilized for extraction, finding HME more efficient, especially for SV. GC–MS analysis identified diverse compounds, with palmitic acid, linoleic acid, methyl palmitate, cis-13-octadecenoic acid, and oleic acid as the main constituents. RP-HPLC quantified 12 phenolic compounds, identifying chlorogenic acid, rutin, and p-coumaric acid as abundant. Antioxidant assays showed HME extracts to be more effective in both diphenyl 1-picrylhydrazyl and ABTS assays, with SV exhibiting the strongest antioxidant effect, followed by SF and SI. Pearson correlation analysis indicated a positive correlation between phenolic content and antioxidant activity (r = 0.6067–0.8927). Molecular docking simulations demonstrated robust binding energies between predominant compounds and Cyt-c, underscoring their potential as effective antioxidants. ADMET analysis showcased varied profiles, suggesting promising pharmaceutical prospects. This study explores the phytochemical profiles of these Solanum species, emphasizing their strong antioxidant capacity as natural sources of phenolic compounds, advancing our understanding of their promising medicinal applicability.

Watermelon white rind is considered the most underutilised fruit resource as it is usually discarded as waste due to its unappealing flavour. Utilising watermelon rind by generating new products could decrease the amount of biological waste, thus recognising the rind’s potential economic value in various industries, mainly in the food and cosmeceutical industries. Therefore, this study aimed to determine the optimum conditions for extracting watermelon rind. The watermelon rind sample was dried using an oven before extracting the rind. Four factors were used: time, solvent concentration, solid-to-solvent ratio and drying time. These factors were set in Design-Expert version 13 to get the optimum conditions for the best extraction yield. The response surface methodology reveals that four conditions which are 30 mins extraction time, 90 % ethanol concentration, 40 % solvent-to-solid ratio, and 45 hrs sample drying time, showed maximum extract yield at 22 % when extracted using a sonication technique.

Abstract: Aims: We evaluated the in vitro antioxidant and antimicrobial potential of Schimpera arabica extract and fractions (2‐Hexadecen‐1‐ol and beta sitosterol). Methods and Results: Free radical scavenging activity was estimated by using ABTS and DPPH methods, reducing power and iron chelation was studied to investigate antioxidant potential of the extracts. Well‐diffusion method was utilized to evaluate the antimicrobial activity of the extracts. Gas chromatography‐mass spectroscopy analysis of the extract revealed the presence of 27 compounds. Phenolic and flavonoid contents were found in high amount (7·6–18 mg GAE, mg g−1; 3·2–10·8 mg catechin, mg g−1) in dry plant material. Conclusions: Among all the extracts, 2‐Hexadecen‐1‐ol and beta sitosterol were the major constituents of crude extract and exhibited significant antioxidant potential as well antimicrobial activity; however, all other fractions also exhibited fare degree of antioxidant potential. 93% DPPH was scavenged by 100 μg ml−1 of the ethyl acetate fraction; in ABTS assay chelation was 86·2 and 88% in ferric chloride reducing power assay. Significance and Impact of the Study: Schimpera arabica is naturally present and used in food preparation in most Arabian nations. The characterization of S. arabica would provide an insight into its medicinal use as home remedial for bacterial infection and as antioxidant. Significant and comparable antimicrobial activity was demonstrated by both 2‐Hexadecen‐1‐ol and beta sitosterol fractions. The results suggest that S. arabica contain a good amount of natural antioxidants of medicinal importance. However, further investigations are needed to characterize the further activity of 2‐Hexadecen‐1‐ol and beta sitosterol in vivo. [ABSTRACT FROM AUTHOR]

The medicinal plant Haloxylon salicornicum is utilized for therapeutic purposes. We previously reported the antioxidant potential of hexane fraction and methanol extracts of the same species. However, since these solvents could be clinically toxic, the current findings investigated the pharmacological effects of the water fraction. The pain relieving, antioxidant, anti-inflammatory, and antipyretic potential of H. salicornicum water extract (HEW) were studied at two concentrations (250 and 500 mg/kg) in rodents. The carrageenan stimulated rat paw edema assay was exercised to assess anti inflammatory potential in rats; yeast-stimulated hyperthermia was utilized to test antipyretic activity in mice; analgesic properties were assessed based on acetic acid-induced writhing, tail flicking, and hot-plate test; and antioxidant potential was examined with the 2,2-diphenyl-1-picrylhydrazyl assay. We found that 500 mg/kg HEW inhibited edema by 44.03%. Yeast-induced hyperthermia in mice was reduced by 250 and 500 mg/kg HEW after 30, 60, and 120 min with significant level of (P < 0.001) compared to rectal temperature of yeast administered group. The high dose of HEW (500 mg/kg) improved the reaction time of mice in the hot-plate test from 6.66 ± 0.33 to 11.33 ± 0.49 s after 120 min. In the acetic acid-stimulated writhing test, 250 and 500 mg/kg HEW decreased writhing by 32.71% and 51.40%, respectively, after 20 min. HEW also showed antioxidant effects. These results demonstrate that HEW is bioactive and has therapeutic potential for treating a variety of ailments.

Background: Genetic and environmental factors are proposed to be involved in cedar pollen allergy sensitization and onset. The impact of these factors will provide key information for the prevention of cedar pollen sensitization and allergy onset, which we investigated in this cross-sectional study. Methods: Subjects were 382 young adult volunteers who completed a self-administered questionnaire on self-reported subjective symptoms of pollinosis, physician-diagnosed pollinosis, and background factors. We also measured their serum IgE antibody titers specific for cedar, cypress, and mites. Factors associated with subjective symptoms, physician diagnosis, and the three specific antigens were determined using both univariate and multivariate analyses. Results: Sensitization to cedar, cypress, and mites, defined as specific IgE levels of class 1 or above, was found in 78.8%, 64.4%, and 56.0% of subjects, respectively. The prevalence of cedar pollinosis was 41.2% based on subjective symptoms and 22.2% based on physician diagnosis. Factors associated with increased cedar pollen sensitization were mite sensitization, comorbid allergic rhinitis, and family history of cedar pollinosis. Risk-reducing factors for cedar pollen sensitization were keeping a cat, number of common colds, and hours of sleep. Risk-increasing factors for both subjective pollinosis symptoms and physician-diagnosed pollinosis were comorbid allergic rhinitis and family history of cedar pollinosis. Conclusions: Sensitization to cedar pollen in this population was extremely high. Both common and distinct factors were associated with sensitization to pollen and with the development of pollinosis. The distinct factors were associated with sensitization to cedar and cypress antigens. Keywords: Association, Factors, Japanese cedar pollinosis, Sensitization, Specific IgE antibody

In this study we determined the treatment effect of clofibrate in low birth weight neonate with hyperbilirubinemia. In a randomized double blind placebo - controlled study, 60 low birth weight neonates who were jaundiced and had hyperbilirubinemia were selected. The treatment group received a single oral dose of clofibrate (100 mg/kg) and the control group received sterile water as placebo. Also both group received Phototherapy in addition of the treatment. Serum bilirubin level was measured at entrance to study and 12, 24, 48 and 72 hours of study. Serum bilirubin decreased in 72 hours in clofibrate group that it was nearly significant (p= 0.061), but there were no significant difference between two groups in 12, 24, 48 hours of study (p= 0.7, p= 0.22, p= 0.19 respectively). Duration of phototherapy in clofibrate group was significantly shorter than control group (p= 0.023). Based on physical exam and liver function tests no side effects were seen. Our result showed that there wasn't significant difference between two groups after administration of single dose of clofibrate (100 mg/ kg) in 12, 24, 48 and 72 hour. Although effect of clofibrate on treatment of jaundice wasn't significant between two groups, duration of phototherapy has been decreased significantly in clofibrate groups. [ABSTRACT FROM AUTHOR]

Purpose: This research aimed to survey the usage of UNESCO cultural diversity declaration among public librarians of Isfahan province in Iran to find their detailed bonds on each of building blocks of the Declaration and give some recommendation to enhance their commitment to it. Methodology: Survey method was used to reach the aims of research. The population of study included all staff at the public libraries of Isfahan (n = 544). Based on Cochran formula for determination of sample size, we selected 110 librarians by random stratified sampling method. The tool for collecting data was researcher-developed Questionnaire based on UNESCO cultural diversity declaration components with the Likert scale, that the face validity of questionnaire was approved by experts and its reliability of it approved by means of measurement of Cronbach's alpha coefficient (0.97). Findings: Findings revealed that the mean usage of UNESCO cultural diversity declaration among public librarians of Isfahan province is lower than the average (2.88). “Safeguarding linguistic diversity and giving support to expression in creation, production and dissemination of information” is the most application and “promoting cultural diversity in cyberspace” has the least usage and meaningfulness among public librarians. Also, there was no significant difference in viewpoints of librarians by gender and age about usage of UNESCO cultural diversity, librarians with different academic degree of education had significantly different viewpoints. Originality/Value: Showing public librarians’ low level bonds to UNESCO cultural diversity declaration can be mentioned as a value of this research. Albeit, librarians’ commitment to “Safeguarding linguistic diversity and giving support to expression in creation, production and dissemination of information” was a prominent finding.

During the initiation of any legacy evolution project one of the key challenges faced by project engineer is with respect to estimating the effort, cost and time required for execution and completion of the project. Especially in this highly competitive world of software renovation markets, the ability to come up with accurate estimate for the project is one of the most desired competencies from any project engineer. One of the major inputs for the project engineer in deciding the estimated effort and time, cost is the size of the work product and individual decomposed code components coming out of the project. The accuracy in the project's estimation will depend on how accurately the size of components is estimated. One of the contributing factors for failure of software evolution projects is that, may projects get estimated based on personal working experience of project engineer. This paper presents components and size based effort estimation modeling that is beneficial in estimating a legacy code and components for evolution. [ABSTRACT FROM AUTHOR]

Background Single nucleotide polymorphism (SNPs) are considered as one of the underlying causes of male infertility. Proper sperm chromatin packaging which involves replacement of histones with protamines has profound effect on male fertility. Over 20 SNPs have been reported for the protamine 1 and 2. Materials and methods The aim of this study was to evaluate the frequency of two previously reported SNPs using polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) approach in 35, 96 and 177 normal, oligozoospermic and azoospermic individuals. These SNPs are: 1. A base pair substitution (G) at position 197 instead of T in protamine type 1 Open reading frame (ORF) including untranslated region, which causes an Arg residue change to Ser residue in a highly conserved region. 2. cytidine nucleotide change to thymidine in position of 248 of protamine type 2 ORF which caused a nonsense point mutation. Results The two mentioned SNPs were not present in the studied population, thus concluding that these SNPs can not serves as molecular markers for male infertility diagnosis. Conclusion The results of our study reveal that in a selected Iranian population, the SNP G197T and C248T are completely absent and are not associated with male infertility and therefore these SNPs may not represent a molecular marker for genetic diagnosis of male infertility.

The strong association between gut microbiota (GM) and brain functions such as mood, behaviour, and cognition has been well documented. Gut-brain axis is a unique bidirectional communication system between the gut and brain, in which gut microbes play essential role in maintaining various molecular and cellular processes. GM interacts with the brain through various pathways and processes including, metabolites, vagus nerve, HPA axis, endocrine system, and immune system to maintain brain homeostasis. GM dysbiosis, or an imbalance in GM, is associated with several neurological disorders, including anxiety, depression, and Alzheimer's disease (AD). Conversely, AD is sustained by microglia-mediated neuroinflammation and neurodegeneration. Further, GM and their products also affect microglia-mediated neuroinflammation and neurodegeneration. Despite the evidence connecting GM dysbiosis and AD progression, the involvement of GM in modulating microglia-mediated neuroinflammation in AD remains elusive. Importantly, deciphering the mechanism/s by which GM regulates microglia-dependent neuroinflammation may be helpful in devising potential therapeutic strategies to mitigate AD. Herein, we review the current evidence regarding the involvement of GM dysbiosis in microglia activation and neuroinflammation in AD. We also discuss the possible mechanisms through which GM influences the functioning of microglia and its implications for therapeutic intervention. Further, we explore the potential of microbiota-targeted interventions, such as prebiotics, probiotics, faecal microbiota transplantation, etc., as a novel therapeutic strategy to mitigate neuroinflammation and AD progression. By understanding and exploring the gut-brain axis, we aspire to revolutionize the treatment of neurodegenerative disorders, many of which share a common theme of microglia-mediated neuroinflammation and neurodegeneration., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Coumarins, abundantly distributed in a plethora of biologically active compounds, serve as a fundamental motif in numerous natural products, drugs, and therapeutic leads. Despite their small size, they exhibit a diverse range of biological activities, intriguing researchers with their immense pharmacological potential., Purpose: This study consolidates the evidence regarding the essential role of coumarins in modern drug discovery, exploring their broad-spectrum pharmaceutical effects, structural versatility, and mechanisms of action across various domains., Methods: For literature search, we utilized PubMed, Google scholar, and SciFinder databases. Keyword and keyword combinations such as "coumarins", "natural coumarins", "specific natural coumarins for particular diseases", and "therapeutic effects" were employed to retrieve relevant studies. The search encompassed articles published between 2005 and 2023. Selection criteria included studies reporting on the pharmacological activities of natural coumarins against various diseases., Results: The results highlight the therapeutic potential of natural coumarins against various diseases, demonstrating anti-cancer, anti-oxidant, and anti-inflammatory activities. They also act as monoamine oxidase inhibitors and phosphodiesterase inhibitors, and as anti-thrombotic, anti-diabetic, and hepatoprotective agents. They also show efficacy against diabetic nephropathy, neurodegenerative diseases, microbial infections and many other diseases., Conclusion: This review underscores the significant role of natural coumarins in medicinal chemistry and drug discovery. Their diverse biological activities and structural versatility make them promising therapeutic agents. This study serves as a catalyst for further research in the field, aiming to address emerging challenges and opportunities in drug development., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Wnt signaling is one of the key regulators of bone development and homeostasis. Wnt signaling regulates key biological events, including stem cell fate and osteoblast and osteoclast activity, leading to the maintenance of bone mass and strength. Wnt ligands are secreted glycoproteins that bind to Frizzled (FZD) receptors and their coreceptors, lipoprotein receptor-related proteins-5/6 (LRP5/6). Binding of Wnts to FZD triggers canonical (β-catenin-dependent) and noncanonical (β-catenin-independent) pathways. In canonical Wnt signaling, stabilized β-catenin translocates to the nucleus, where it promotes osteoblast differentiation by activating target genes, including Runx2 and Osterix. The negative regulators of Wnt or so-called Wnt antagonists, including CXXC5, sFRP, sclerostin, DKK1, and Notum, compete for Fzd binding, attenuating Wnt signaling. The critical roles of Wnt signaling in bone homeostasis have been established by various bone diseases caused by mutations in Wnt signaling pathways. Loss-of-function mutations in the LRP5 gene cause osteoporosis-pseudoglioma syndrome, whereas gain-of-function mutations are linked to osteopetrosis characterized by high bone density. Sclerosteosis and Van Buchem disease are caused by mutations affecting the SOST gene, which encodes sclerostin, a natural inhibitor of Wnt signalling. Loss-of-function mutations in SOST result in excessive bone growth, markedly increased bone density, and other skeletal abnormalities due to uncontrolled Wnt activity. Considering the clinical relevance of Wnt signaling, targeting Wnt inhibitors is being intensely pursued using small molecules that act by inhibiting endogenous Wnt agonists. We used a computational biology approach to review current data on pharmacophores of Wnt antagonists, assessing their potential as therapeutic candidates for postmenopausal osteoporosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Despite advancements in oncology, predicting recurrence-free survival (RFS) in head and neck (H&N) cancer remains challenging due to the heterogeneity of tumor biology and treatment responses. This study aims to address the research gap in the prognostic efficacy of traditional clinical predictors versus advanced radiomics features and to explore the potential of weighted fusion techniques for enhancing RFS prediction. We utilized clinical data, radiomic features from CT and PET scans, and various weighted fusion algorithms to stratify patients into low- and high-risk groups for RFS. The predictive performance of each model was evaluated using Kaplan-Meier survival analysis, and the significance of differences in RFS rates was assessed using confidence interval (CI) tests. The weighted fusion model with a 90% emphasis on PET features significantly outperformed individual modalities, yielding the highest C-index. Additionally, the incorporation of contextual information by varying peritumoral radii did not substantially improve prediction accuracy. While the clinical model and the radiomics model, individually, did not achieve statistical significance in survival differentiation, the combined feature set showed improved performance. The integration of radiomic features with clinical data through weighted fusion algorithms enhances the predictive accuracy of RFS outcomes in head and neck cancer. Our findings suggest that the utilization of multi-modal data helps in developing more reliable predictive models and underscore the potential of PET imaging in refining prognostic assessments. This study propels the discussion forward, indicating a pivotal step toward the adoption of precision medicine in cancer care.

This review explores the recent advancements in the design and synthesis of pseudo-natural products (pseudo-NPs) by employing innovative principles and strategies, heralding a transformative era in chemistry and biology. Pseudo-NPs, produced through in silico fragmentation and the de novo recombination of natural product fragments, reveal compounds endowed with distinct biological activities. Their advantage lies in transcending natural product structures, fostering diverse possibilities. Research in this area over the past decade has yielded unconventional combinations of natural product fragments, leading to the identification of novel compounds possessing unique scaffolds and biological significance, thereby contributing to the discovery of new therapeutics. The pseudo-NPs exert potent biological effects through various signaling pathways. In chemical biology and medicinal chemistry, designing pseudo-NPs is an important strategy, harnessing molecular hybridization and bioinspired synthesis to generate diverse compounds with remarkable biological activities, underscoring their immense potential in drug discovery and development., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Mitochondrial dysfunction plays a pivotal role in the development of age-related diseases, particularly neurodegenerative disorders. The etiology of mitochondrial dysfunction involves a multitude of factors that remain elusive. This review centers on elucidating the role(s) of excitotoxicity, oxytosis/ferroptosis and neurodegeneration within the context of mitochondrial bioenergetics, biogenesis, mitophagy and oxidative stress and explores their intricate interplay in the pathogenesis of neurodegenerative diseases. The effective coordination of mitochondrial turnover processes, notably mitophagy and biogenesis, is assumed to be critically important for cellular resilience and longevity. However, the age-associated decrease in mitophagy impedes the elimination of dysfunctional mitochondria, consequently impairing mitochondrial biogenesis. This deleterious cascade results in the accumulation of damaged mitochondria and deterioration of cellular functions. Both excitotoxicity and oxytosis/ferroptosis have been demonstrated to contribute significantly to the pathophysiology of neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's Disease (HD), Amyotrophic Lateral Sclerosis (ALS) and Multiple Sclerosis (MS). Excitotoxicity, characterized by excessive glutamate signaling, initiates a cascade of events involving calcium dysregulation, energy depletion, and oxidative stress and is intricately linked to mitochondrial dysfunction. Furthermore, emerging concepts surrounding oxytosis/ferroptosis underscore the importance of iron-dependent lipid peroxidation and mitochondrial engagement in the pathogenesis of neurodegeneration. This review not only discusses the individual contributions of excitotoxicity and ferroptosis but also emphasizes their convergence with mitochondrial dysfunction, a key driver of neurodegenerative diseases. Understanding the intricate crosstalk between excitotoxicity, oxytosis/ferroptosis, and mitochondrial dysfunction holds potential to pave the way for mitochondrion-targeted therapeutic strategies. Such strategies, with a focus on bioenergetics, biogenesis, mitophagy, and oxidative stress, emerge as promising avenues for therapeutic intervention.

The tau-tubulin kinase 1 (TTBK1) protein is a casein kinase 1 superfamily member located at chromosome 6p21.1. It is expressed explicitly in the brain, particularly in the cytoplasm of cortical and hippocampal neurons. TTBK1 has been implicated in the phosphorylation and aggregation of tau in Alzheimer's disease (AD). Considering its significance in AD, TTBK1 has emerged as a promising target for AD treatment. In the present study, we identified novel TTBK1 inhibitors using various computational techniques. We performed a virtual screening-based docking study followed by E-pharmacophore modeling, cavity-based pharmacophore, and ligand design techniques and found ZINC000095101333 , LD7 , LD55 , and LD75 to be potential novel TTBK1 lead inhibitors. The docking results were complemented by Molecular Mechanics/Generalized Born Surface Area (MMGBSA) calculations. The molecular dynamics (MD) simulation studies at a 500 ns scale were carried out to monitor the behavior of the protein toward the identified ligands. Pharmacological and ADME/T studies were carried out to check the drug-likeness of the compounds. In summary, we identified a new series of compounds that could effectively bind the TTBK1 receptor. The newly designed compounds are promising candidates for developing therapeutics targeting TTBK1 for AD.

This review explores the significance of trifluoromethylnitrones in synthesizing fluorine-containing compounds, with a particular focus on trifluoromethylated heterocycles. It explores the versatility of trifluoromethylnitrones, especially in [3 + 2] cycloaddition reactions, highlighting their unique reactivity with various dienophile substrates. Trifluoromethylnitrones are valuable precursors for the rapid synthesis of medicinally important trifluoromethylated heterocycles, including isoxazolidines, dihydroisoxazoles, oxathiazolidines, β-lactams, and aziridines. These heterocycles, in turn, serve as synthons for synthesizing trifluoromethylated lactams and aminoalcohols. Additionally, nitrone chemistry extends to synthesizing trifluoromethylated nucleosides and trifluorinated organoborane heterocycles, demonstrating their versatility. While sharing similarities with trifluorodiazoethane reactivity, trifluoromethylnitrones offer distinct advantages by enabling the synthesis of heterocycles typically inaccessible with trifluorodiazoethane.

Huntington's disease (HD) is a neurodegenerative genetic disorder characterized by a mutation in the huntingtin (HTT) gene, resulting in the production of a mutant huntingtin protein (mHTT). The accumulation of mHTT leads to the development of toxic aggregates in neurons, causing cell dysfunction and, eventually, cell death. Peptide therapeutics target various aspects of HD pathology, including mHTT reduction and aggregation inhibition, extended CAG mRNA degradation, and modulation of dysregulated signaling pathways, such as BDNF/TrkB signaling. In addition, these peptide therapeutics also target the detrimental interactions of mHTT with InsP3R1, CaM, or Caspase-6 proteins to mitigate HD. This Perspective provides a detailed perspective on anti-HD therapeutic peptides, highlighting their design, structural characteristics, neuroprotective effects, and specific mechanisms of action. Peptide therapeutics for HD exhibit promise in preclinical models, but further investigation is required to confirm their effectiveness as viable therapeutic strategies, recognizing that no approved peptide therapy for HD currently exists.

Antibiotic resistance against Mycobacterium tuberculosis ( M.tb. ) has been a significant cause of death worldwide. The Enhanced intracellular survival (EIS) protein of the bacteria is an acetyltransferase that multiacetylates aminoglycoside antibiotics, preventing them from binding to the bacterial ribosome. To overcome the EIS-mediated antibiotics resistance of M.tb ., we compiled 888 alkaloids and derivatives from five different databases and virtually screened them against the EIS receptor. The compound library was filtered down to 87 compounds, which underwent additional analysis and filtration. Moreover, the top 15 most prominent phytocompounds were obtained after the drug-likeness prediction and ADMET screening. Out of 15, nine compounds confirmed the maximum number of hydrogen bond interactions and reliable binding energies during molecular docking. Additionally, the Molecular dynamics (MD) simulation of nine compounds showed the three most stable complexes, further verified by re-docking with mutated protein. The density functional theory (DFT) calculation was performed to identify the HOMO-LUMO energy gaps of the selected three potential compounds. Finally, our selected top lead compounds i.e., Alkaloid AQC2 (PubChem85634496), Nobilisitine A (ChEbi68116), and N-methylcheilanthifoline (ChEbi140673) demonstrated more favourable outcomes when compared with reference compounds (i.e., 39b and 2i) in all parameters used in this study. Therefore, we anticipate that our findings will help to explore and develop natural compound therapy against multi and extensively drug-resistant strains of M.tb .Communicated by Ramaswamy H. Sarma.