Genomic, Molecular Networking-Based Metabolomic, and Bioactivity Profiling of Actinobacteria from Undisturbed Caves in Pakistan.

Caves are a unique ecosystem that harbor diverse microorganisms, and provide a challenging environment to the dwelling microbial communities, which may boost gene expression and can lead to the production of inimitable bioactive natural products. In this study, we obtained 59 actinobacteria from four different caves located in Bahadurkhel, District Karak, Pakistan. On the basis of taxonomic characteristics, 30 isolates were selected and screened for secondary metabolites production and bioactivity profiling.

Probing the Limit of the Number of Saturated Atoms for Achieving Hyperconjugative Aromaticity.

Aromaticity is a fundamental concept in organic chemistry. Hyperconjugative aromaticity, also known as hyperconjugation-induced aromaticity, has evolved from its origin from main group substituents to transition metal analogues, establishing itself as an important category of aromaticity. Additionally, aromatic compounds comprising two -carbon atoms have recently been reported both experimentally and computationally.

Multifunctional in vitro, in silico and DFT analyses on antimicrobial BagremycinA biosynthesized by Micromonospora chokoriensis CR3 from Hieracium canadense.

Among the actinomycetes in the rare genera, Micromonospora is of great interest since it has been shown to produce novel therapeutic compounds. Particular emphasis is now on its isolation from plants since its population from soil has been extensively explored. The strain CR3 was isolated as an endophyte from the roots of Hieracium canadense, and it was identified as Micromonospora chokoriensis through 16S gene sequencing and phylogenetic analysis.

Recent advances in the role of MXene based hybrid architectures as electrocatalysts for water splitting.

The development of non-noble metal based and cost-effective electrocatalysts for water splitting has attracted significant attention due to their potential in production of clean and green hydrogen fuel. Discovered in 2011, a family of two-dimensional transition metal carbides, nitrides, and carbonitrides, have demonstrated promising performance as electro catalysts in the water splitting process due to their high electrical conductivity, very large surface area and abundant catalytic active sites. However, their-long term stability and recyclability are limited due to restacking and agglomeration of MXene flakes.

Prevalence and antibiotics resistance status of Salmonella in raw meat consumed in various areas of Lahore, Pakistan.

This study reports the prevalence and antibiotics resistance status of Salmonella detected in raw meat from Lahore, Pakistan. Overall, N = 111 meat samples, were collected from local markets. Salmonella was recovered from 57 (51.

Bioactivity and Metabolomics Profiling of Endophytic Actinobacteria Isolated from Roots of the Medicinal Plants Dominant in South Asian Region.

Background: Plant-derived endophytic actinobacteria are the center of attention due to their capacity to produce diverse antimicrobial and anticancer compounds and their metabolites influence plant growth.

Methods: In this study, 40 endophytic actinobacteria strains were isolated from the roots of eight medicinal plants used as folk medicine in South Asian region. The isolates were characterized morphologically, biochemically and physiologically and the genus level identification of the selected strains was done by 16SrRNA gene sequencing.

Nickel-Catalyzed Regioselectivity-Switchable Hydroheteroarylation of Vinylarenes with Electron-Rich Heteroarenes.

We report the first example of a regioselectivity switch in the hydroheteroarylation of vinylarenes with electron-rich heteroarenes, including benzofurans, benzothiophenes, and indoles, using an expedient ligand-controlled strategy. In the presence of NaOBu, Ni(IMes)[P(OEt)]Br yields C2-alkylated heteroarenes with high branched selectivity, whereas the use of Ni(IPr)[P(OEt)]Br favors the formation of the corresponding linear products. This robust method also provides easy access to a range of C2-alkylated electron-rich heteroarenes without employing directing groups.

Rare Earth Amide-Catalyzed Direct Thioesterification of Aldehydes with Thiols under Mild Conditions.

Direct thioesterification of aldehydes with thiols catalyzed by readily accessible rare earth/lithium amide RE[N(SiMe)](μ-Cl)Li(THF) is developed, which enables the preparation of a range of thioesters (31 examples) under room temperature and solvent-free conditions, without using any additive or external oxidant. This method provides a straightforward and atom-efficient approach for the thioester synthesis.

Fatty acid based antimicrobials from Streptomyces sp. SORS-24, an endophyte isolated from Sonchus oleraceus.

Due to the rise in bacterial resistance towards various therapeutic agents, interest is now developing towards fatty acid based antimicrobials because of their non-specific mode of action. A strain SORS 24 isolated from Sonchus oleraceus (Sow thistle) showed significant activity against Escherichia coli ATCC 25922 (25 mm), Chlorella vulgaris (20 mm), Bacillus subtilis DSM 10 (ATCC 6051) and Pseudomonas sp. (15 mm).

siRNA drug delivery across the blood-brain barrier in Alzheimer's disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disease with a few FDA-approved drugs that provide modest symptomatic benefits and only two FDA-approved disease-modifying treatments for AD. The advancements in understanding the causative genes and non-coding sequences at the molecular level of the pathophysiology of AD have resulted in several exciting research papers that employed small interfering RNA (siRNA)-based therapy. Although siRNA is being sought by academia and biopharma industries, several challenges still need to be addressed.

Bioprospecting of desert actinobacteria with special emphases on griseoviridin, mitomycin C and a new bacterial metabolite producing Streptomyces sp. PU-KB10-4.

Background: Bioprospecting of actinobacteria isolated from Kubuqi desert, China for antibacterial, antifungal and cytotoxic metabolites production and their structure elucidation.

Results: A total of 100 actinobacteria strains were selectively isolated from Kubuqi desert, Inner Mongolia, China. The taxonomic characterization revealed Streptomyces as the predominant genus comprising 37 different species, along with the rare actinobacterial genus Lentzea.

Molecular modeling of pyrrolo-pyrimidine based analogs as potential FGFR1 inhibitors: a scientific approach for therapeutic drugs.

Fibroblast growth factor receptors 1 (FGFR1) is an emerging target for the development of anticancer drugs. Uncontrolled expression of FGFR1 is strongly associated with a number of different types of cancers. Apart from a few FGFR inhibitors, the FGFR family members have not been thoroughly studied to produce clinically effective anticancer drugs.

Ligand-Controlled Nickel-Catalyzed Tandem Isomerization/Regiodivergent Hydroheteroarylation of α-Alkenes with Heteroarenes.

We herein describe an accessible ligand-controlled nickel-catalyzed tandem isomerization/regiodivergent hydroheteroarylation of α-alkenes with a series of heteroarenes, wherein the NHC ligand of heteroleptic Ni(II) complexes of the type Ni(NHC)[P(OEt)]Br displayed significant effects on regulation. In the presence of NaOBu, Ni(IMes)[P(OEt)]Br enables C═C bond isomerization of α-alkenes over up to four sp carbon atoms to afford branched products, while Ni(IPr*)[P(OEt)]Br greatly deactivates α-alkene isomerization and favors the formation of linear products.

Synthesis and characterization of rare earth/lithium complexes stabilized by ethylenediamine-bridged bis(phenolate) ligands and their activity in catalyzing amidation reactions.

Rare earth/lithium complexes stabilized by ethylenediamine-bridged bis(phenolate) ligands have been synthesized and characterized. In addition to five rare earth/lithium amides isolated as major complexes, two other rare earth/lithium complexes bearing two phenolate ligands were also isolated. The activities of rare earth/lithium amides in catalyzing the amidation of aldehydes and amines were studied, which revealed that the yttrium/lithium complex was highly active for a wide range of substrates, generating 58 examples of amides in 42-99% yields under mild conditions (, room temperature, 3-hour reaction time, additive-free).

Cytotoxic Evaluation and Molecular Docking Studies of Aminopyridine Derivatives as Potential Anticancer Agents.

Background: The development of resistance to available anticancer drugs is increasingly becoming a major challenge and new chemical entities could be unveiled to compensate for this therapeutic failure.

Objectives: The current study demonstrated whether N-protected and deprotected amino acid derivatives of 2- aminopyridine could attenuate tumor development using colorectal cancer cell lines.

Methods: Biological assays were performed to investigate the anticancer potential of synthesized compounds.

Unintended consequences: quantifying the benefits, iatrogenic harms and downstream cascade costs of musculoskeletal MRI in UK primary care.

Objectives: The largest proportion of general practitioner (GP) magnetic resonance imaging (MRI) is musculoskeletal (MSK), with consistent annual growth. With limited supporting evidence and potential harms from early imaging overuse, we evaluated practice to improve pathways and patient safety.

Methods: Cohort evaluation of routinely collected diagnostic and general practice data across a UK metropolitan primary care population.

Taxonomic and Metabolomics Profiling of Actinobacteria Strains from Himalayan Collection Sites in Pakistan.

Actinobacteria have proven themselves as the major producers of bioactive compounds with wide applications. In this study, 35 actinobacteria strains were isolated from soil samples collected from the Himalayan mountains region in Pakistan. The isolated strains were identified by polyphasic taxonomy and were prioritized based on biological and chemical screening to identify the strains with ability to produce inimitable metabolites.

'Diagnostic downshift': clinical and system consequences of extrapolating secondary care testing tactics to primary care.

Numerous drivers push specialist diagnostic approaches down to primary care ('diagnostic downshift'), intuitively welcomed by clinicians and patients. However, primary care's different population and processes result in under-recognised, unintended consequences. Testing performs poorer in primary care, with indication creep due to earlier, more undifferentiated presentation and reduced accuracy due to spectrum bias and the 'false-positive paradox'.

Motilibacter deserti sp. nov. and Motilibacter aurantiacus sp. nov., two novel actinobacteria isolated from soil of Cholistan Desert and emended description of the genus Motilibacter.

Two novel actinobacterial strains, designated as E257 and K478, were isolated from hyper-arid soil samples collected in Cholistan Desert, Pakistan. Comparative analysis of 16S rRNA genes showed that strains E257 and K478 were assigned to the genus Motilibacter, being their closest relative M. rhizosphaerae RS-16 with 97.

sp. nov., a novel actinobacterium isolated from Cholistan desert soil.

A Gram-stain-positive, aerobic, catalase-positive, oxidase-negative, non-mycelium-forming, motile, rod-shaped with one polar flagellum actinobacterium, designated E918, was isolated from a desert soil collected in Cholistan desert, Pakistan. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain E918 belonged to the genus and was most closely related to CGMCC 1.15091 (97.

PCR-based Screening Approach: A Rapid Method to Detect the Biosynthetic Potential of Antimicrobials in Actinobacterial Strains.

This study aimed to investigate the PCR-based screening strategy for the prediction of the antimicrobial biosynthetic potential of the selected strains originated from an extreme environment (Cholistan Desert, Pakistan). The biosynthetic potential was determined by using both molecular and culture-dependent screening approaches. The four biosynthetic genes clusters, including the , , cyp P450 hydroxylase (), and glycopeptide genes, were investigated in the selected strains by PCR amplification, sequencing, and by subsequent bioinformatics approaches.

sp. nov., an actinomycete isolated from soil of the Cholistan Desert, and emended description of the genus .

A Gram-stain-positive, aerobic, non-motile and non-spore-forming actinobacterium, designated as F435, was isolated from soil sample collected from the Cholistan Desert, Pakistan. The taxonomic position of the strain was established by using a polyphasic taxonomic approach. The cells were coccoid-shaped and found in single or arrangement of pairs.

Green synthesis and biological evaluation of novel 5-fluorouracil derivatives as potent anticancer agents.

This study reports the formation of 5-FU co-crystals with four different pharmacologically safe co-formers; Urea, Thiourea, Acetanilide and Aspirin using methanol as a solvent. Two fabrication schemes were followed i.e.