A super minigene with a short promoter and truncated introns recapitulates essential features of transcription and splicing regulation of the SMN1 and SMN2 genes.

Here we report a Survival Motor Neuron 2 (SMN2) super minigene, SMN2Sup, encompassing its own promoter, all exons, their flanking intronic sequences and the entire 3'-untranslated region. We confirm that the pre-mRNA generated from SMN2Sup undergoes splicing to produce a translation-competent mRNA. We demonstrate that mRNA generated from SMN2Sup produces more SMN than an identical mRNA generated from a cDNA clone. We uncover that overexpression of SMN triggers skipping of exon 3 of SMN1/SMN2. We define the minimal promoter and regulatory elements associated with the initiation and elongation of transcription of SMN2. The shortened introns within SMN2Sup preserved the ability of camptothecin, a transcription elongation inhibitor, to induce skipping of exons 3 and 7 of SMN2. We show that intron 1-retained transcripts undergo nonsense-mediated decay. We demonstrate that splicing factor SRSF3 and DNA/RNA helicase DHX9 regulate splicing of multiple exons in the context of both SMN2Sup and endogenous SMN1/SMN2. Prevention of SMN2 exon 7 skipping has implications for the treatment of spinal muscular atrophy (SMA). We validate the utility of the super minigene in monitoring SMN levels upon splicing correction. Finally, we demonstrate how the super minigene could be employed to capture the cell type-specific effects of a pathogenic SMN1 mutation.

Diverse targets of SMN2-directed splicing-modulating small molecule therapeutics for spinal muscular atrophy.

Designing an RNA-interacting molecule that displays high therapeutic efficacy while retaining specificity within a broad concentration range remains a challenging task. Risdiplam is an FDA-approved small molecule for the treatment of spinal muscular atrophy (SMA), the leading genetic cause of infant mortality. Branaplam is another small molecule which has undergone clinical trials. The therapeutic merit of both compounds is based on their ability to restore body-wide inclusion of Survival Motor Neuron 2 (SMN2) exon 7 upon oral administration. Here we compare the transcriptome-wide off-target effects of these compounds in SMA patient cells. We captured concentration-dependent compound-specific changes, including aberrant expression of genes associated with DNA replication, cell cycle, RNA metabolism, cell signaling and metabolic pathways. Both compounds triggered massive perturbations of splicing events, inducing off-target exon inclusion, exon skipping, intron retention, intron removal and alternative splice site usage. Our results of minigenes expressed in HeLa cells provide mechanistic insights into how these molecules targeted towards a single gene produce different off-target effects. We show the advantages of combined treatments with low doses of risdiplam and branaplam. Our findings are instructive for devising better dosing regimens as well as for developing the next generation of small molecule therapeutics aimed at splicing modulation.

Utilization of dietary mixed-linkage ß-glucans by the Firmicute Blautia producta.

The ß-glucans are structurally varied, naturally occurring components of the cell walls, and storage materials of a variety of plant and microbial species. In the human diet, mixed-linkage glucans [MLG - ß-(1,3/4)-glucans] influence the gut microbiome and the host immune system. Although consumed daily, the molecular mechanism by which human gut Gram-positive bacteria utilize MLG largely remains unknown. In this study, we used Blautia producta ATCC 27340 as a model organism to develop an understanding of MLG utilization. B. producta encodes a gene locus comprising a multi-modular cell-anchored endo-glucanase (BpGH16MLG), an ABC transporter, and a glycoside phosphorylase (BpGH94MLG) for utilizing MLG, as evidenced by the upregulation of expression of the enzyme- and solute binding protein (SBP)-encoding genes in this cluster when the organism is grown on MLG. We determined that recombinant BpGH16MLG cleaved various types of ß-glucan, generating oligosaccharides suitable for cellular uptake by B. producta. Cytoplasmic digestion of these oligosaccharides is then performed by recombinant BpGH94MLG and ß-glucosidases (BpGH3-AR8MLG and BpGH3-X62MLG). Using targeted deletion, we demonstrated BpSBPMLG is essential for B. producta growth on barley ß-glucan. Furthermore, we revealed that beneficial bacteria, such as Roseburia faecis JCM 17581T, Bifidobacterium pseudocatenulatum JCM 1200T, Bifidobacterium adolescentis JCM 1275T, and Bifidobacterium bifidum JCM 1254, can also utilize oligosaccharides resulting from the action of BpGH16MLG. Disentangling the ß-glucan utilizing the capability of B. producta provides a rational basis on which to consider the probiotic potential of this class of organism.

An in silico approach for identification of lead compound as FtsZ inhibitor.

The remarkable conservation of the FtsZ among Gram-positive and Gram-negative bacteria, a crucial GTPase in bacterial cell division, has emerged as a promising antibacterial drug target to combat antibacterial resistance. There have been several coordinated efforts to develop inhibitors against FtsZ which can also serve as potential candidates for future antibiotics. In the present study, a natural product-like library (≈50,000 compounds) was employed to conduct HTVS against Staphylococcus aureus FtsZ protein (PDB Id: 6KVP). Additionally, molecular docking was carried out in two modes, SP and XP docking, using the Schrödinger suite. The glide scores of ligands obtained by XP docking were further summarized and compared with the control ligands (ZI1- co-crystal and PC190723-a compound undergoing clinical trial). Using the Prime-MM-GBSA approach, BFE calculations were performed on the top XP-scored ligands (≈598 compounds). These hits were also evaluated for ADMET parameters using the Qikprop algorithm, SwissADME, and in silico carcinogenicity testing using Carcinopred-El. Based on the results, ligand 4-FtsZ complex was considered for the 300 ns MDS analysis to get insights into its binding modes within the catalytic pocket of FtsZ protein. The analysis revealed that the amide linkage sandwiched between the triazole and 1-oxa-8-azaspirodecan-8-ium moiety (Val203) as well as the aminoethyl group present at 1st position on the triazole moiety (Leu209, Leu200, Asp210, and Ala202) were responsible for the FtsZ inhibitory activity, owing to their crucial interactions with key amino acid residues. Further, the complex also displayed good protein-ligand stability, ultimately predicting ligand 4 as a potent lead compound for the inhibition of FtsZ. Thus, our in silico findings will serve as a framework for in-depth in-vitro and in-vivo investigations encouraging the development of FtsZ inhibitors as a new generation of antibacterial agents.

2D Zinc Oxide - Synthesis, Methodologies, Reaction Mechanism, and Applications.

Zinc oxide (ZnO) is a thermally stable n-type semiconducting material. ZnO 2D nanosheets have mainly gained substantial attention due to their unique properties, such as direct bandgap and strong excitonic binding energy at room temperature. These are widely utilized in piezotronics, energy storage, photodetectors, light-emitting diodes, solar cells, gas sensors, and photocatalysis. Notably, the chemical properties and performances of ZnO nanosheets largely depend on the nano-structuring that can be regulated and controlled through modulating synthetic strategies. Two synthetic approaches, top-down and bottom-up, are mainly employed for preparing ZnO 2D nanomaterials. However, owing to better results in producing defect-free nanostructures, homogenous chemical composition, etc., the bottom-up approach is extensively used compared to the top-down method for preparing ZnO 2D nanosheets. This review presents a comprehensive study on designing and developing 2D ZnO nanomaterials, followed by accenting its potential applications. To begin with, various synthetic strategies and attributes of ZnO 2D nanosheets are discussed, followed by focusing on methodologies and reaction mechanisms. Then, their deliberation toward batteries, supercapacitors, electronics/optoelectronics, photocatalysis, sensing, and piezoelectronic platforms are further discussed. Finally, the challenges and future opportunities are featured based on its current development.

3D incoherent imaging using an ensemble of sparse self-rotating beams.

Interferenceless coded aperture correlation holography (I-COACH) is one of the simplest incoherent holography techniques. In I-COACH, the light from an object is modulated by a coded mask, and the resulting intensity distribution is recorded. The 3D image of the object is reconstructed by processing the object intensity distribution with the pre-recorded 3D point spread intensity distributions. The first version of I-COACH was implemented using a scattering phase mask, which makes its implementation challenging in light-sensitive experiments. The I-COACH technique gradually evolved with the advancement in the engineering of coded phase masks that retain randomness but improve the concentration of light in smaller areas in the image sensor. In this direction, I-COACH was demonstrated using weakly scattered intensity patterns, dot patterns and recently using accelerating Airy patterns, and the case with accelerating Airy patterns exhibited the highest SNR. In this study, we propose and demonstrate I-COACH with an ensemble of self-rotating beams. Unlike accelerating Airy beams, self-rotating beams exhibit a better energy concentration. In the case of self-rotating beams, the uniqueness of the intensity distributions with depth is attributed to the rotation of the intensity pattern as opposed to the shifts of the Airy patterns, making the intensity distribution stable along depths. A significant improvement in SNR was observed in optical experiments.

Identification of two putative novel deltapartitiviruses and an enamovirus in coriander transcriptomes.

Coriander is a herbaceous spice and condiment crop also known for its medicinal properties. The present study identified two putative novel deltapartitiviruses and an enamovirus tentatively named as Coriandrum sativum deltapartitivirus 1, 2 (CsDPV1, 2) and Coriandrum sativum enamovirus (CsEV) in the publicly available transcriptome-assembled contigs derived from coriander grown in India. CsDPV1 and 2 contained tripartite and bipartite genomes, respectively, with each genome segment encoding a single open reading frame (ORF). CsEV contained five ORFs encoding proteins P0, P1, P2, P3 and P5. Phylogenetic analysis revealed three distinct subgroups of deltapartitiviruses wherein CsDPV1 and 2 grouped in subgroup 3 and 1, respectively, whilst CsEV formed a distinct sub-clade within enamoviruses. Further, the presence of CsDPV2 in fruit samples of one of the cultivars from where the virus was identified was confirmed through RT-PCR assay and Sanger sequencing. The study highlights the need for further studies on understanding the importance and the biological properties of identified novel viruses.

Advancement in precision diagnosis and therapeutic for triple-negative breast cancer: Harnessing diagnostic potential of CRISPR-cas & engineered CAR T-cells mediated therapeutics.

Cancer is characterized by uncontrolled cell growth, disrupted regulatory pathways, and the accumulation of genetic mutations. These mutations across different types of cancer lead to disruptions in signaling pathways and alterations in protein expression related to cellular growth and proliferation. This review highlights the AKT signaling cascade and the retinoblastoma protein (pRb) regulating cascade as promising for novel nanotheranostic interventions. Through synergizing state-of-the-art gene editing tools like the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas system with nanomaterials and targeting AKT, there is potential to enhance cancer diagnostics significantly. Furthermore, the integration of modified CAR-T cells into multifunctional nanodelivery systems offers a promising approach for targeted cancer inhibition, including the eradication of cancer stem cells (CSCs). Within the context of highly aggressive and metastatic Triple-negative Breast Cancer (TNBC), this review specifically focuses on devising innovative nanotheranostics. For both pre-clinical and post-clinical TNBC detection, the utilization of the CRISPR-Cas system, guided by RNA (gRNA) and coupled with a fluorescent reporter specifically designed to detect TNBC's mutated sequence, could be promising. Additionally, a cutting-edge approach involving the engineering of TNBC-specific iCAR and syn-Notch CAR T-cells, combined with the co-delivery of a hybrid polymeric nano-liposome encapsulating a conditionally replicative adenoviral vector (CRAdV) against CSCs, could present an intriguing intervention strategy. This review thus paves the way for exciting advancements in the field of nanotheranostics for the treatment of TNBC and beyond.

Gold nanoparticle assisted colorimetric biosensors for rapid polyethylene terephthalate (PET) sensing for sustainable environment to monitor microplastics.

The extremely widespread and ubiquitous nature of plastics, estimated to boost its global production by 26 billion tons till 2050. The large chunks of plastic waste that decomposed down to micro- or nano plastics (MNPs) leads to various ill effects on biological entities. The conventional PET detection methods lack rapid detection of microplastics due to variances in microplastic features, long-drawn-out sample pre-processing procedures and complex instrumentation. Therefore, an instantaneous colorimetric evaluation of microplastic will ensures the simplicity of conducting assays on field. Several nanoparticle-based biosensors that detects proteins, nucleic acids, metabolites operate on either cluster or disperse state of nanoparticle. However, gold nanoparticle (AuNPs) emerges an ideal scaffold for sensory element in lateral flow biosensors due to their simple surface functionalization, unique optoelectronic properties and varied colour spectrum depending on morphologies and aggregation state. In this paper an effort has been made in the form of a hypothesis using in silico tools as a basis to detect polyethylene terephthalate (PET) - most abundant type of microplastic using gold nanoparticle based lateral flow biosensor. We retrieved sequences of PET-binding synthetic peptides and modelled their 3-D structure using I-Tasser server. The best protein model for each peptide sequences are docked with PET monomers - BHET, MHET and other PET polymeric ligands, to evaluate their binding affinities. The synthetic peptide SP 1 (WPAWKTHPILRM) docked with BHET and (MHET)4 exhibits 1.5-fold increases in binding affinity as compared to reference PET anchor peptide Dermaseptin SI (DSI). The GROMACS molecular dynamics simulation studies of synthetic peptide SP 1 - BHET & - (MHET)4 complexes for 50 ns further confirmed the stable binding. RMSF, RMSD, hydrogen bonds, Rg and SASA analysis provides useful structural insights of the SP 1 complexes as compared to reference DSI. Furthermore, SP 1 functionalized AuNP-based colorimetric device was described in detail for detection of PET.

Smart and intelligent optical materials for sensing applications.

This special issue (SI) entitled 'Smart and intelligent optical materials for sensing applications', published by Luminescence, Wiley focuses on the recent advancement of smart and intelligent optical materials for the fabrication of sensor technology for use in numerous fields such as pharmaceutical, biomedical, and environmental. Also, detailed highlights of their prospects in the fields, for example, of personalized health care, wearable devices, and plant stress monitoring are given. This SI includes 46 peer-reviewed articles, of which 15 are reviews written by well established researchers with expertise in the field, and the remaining 31 are research articles from world-leading scientists.

Potentialities of fluorescent carbon nanomaterials as sensor for food analysis.

Food safety and quality are among the most significant and prevalent research areas worldwide. The fabrication of appropriate technical procedures or devices for the recognition of hazardous features in foods is essential to safeguard food materials. In the recent era, developing high-performance sensors based on carbon nanomaterial for food safety investigation has made noteworthy progress. Hence this review briefly highlights the different detection approaches (colorimetric sensor, fluorescence sensor, surface-enhanced Raman scattering, surface plasmon resonance, chemiluminescence, and electroluminescence), functional carbon nanomaterials with various dimensions (quantum dots, graphene quantum dots) and detection mechanisms. Further, this review emphasizes the assimilation of carbon nanomaterials with optical sensors to identify multiple contaminants in food products. The insights of carbon-based nanomaterials optical sensors for pesticides and insecticides, toxic metals, antibiotics, microorganisms, and mycotoxins detection are described in detail. Finally, the opportunities and future perspectives of nanomaterials-based optical analytical approaches for detecting various food contaminants are discussed.

Quantification of Phytochemicals and Metal Ions as well as the Determination of Volatile Compounds, Antioxidant, Antimicrobial and Antacid Activities of the Mimosa pudica L. Leaf: Exploration of Neglected and Under-Utilized Part.

Mimosa pudica L. (MP) is well-known plant in traditional medicinal system, especially in India. Unfortunately, leaves of MP are less explored. To determine the food and nutritional value of the neglected part of Mimosa pudica L. (MP), that is MP leaves, phytochemicals and metal ions of MP were quantified by newly developed HPLC and ICPOES-based methods. The content of phytochemicals observed using HPLC analysis for chlorogenic acid, catechin, and epicatechin was 141.823 (±8.171), 666.621 (±11.432), and 293.175 (±12.743) µg/g, respectively. Using GC/MS/MS analysis, fatty acid like oleic acid were identified. In ICP-OES analysis, a significant content of Na, K, Ca, Cu, Fe, Mg, Mn, and Zn was observed. The observed TPC and TFC for MP leaf extracts was 44.327 (±1.041) mg GAE/ g of wt. and 214.217 (±4.372) mg QCE/ g of wt., respectively. The DPPH assay depicted a strong antioxidant activity of MP leaf extracts with IC50 values of 0.796 (±0.081) mg/mL and a TEAC value of 0.0356 (±0.0003). A significant antacid activity (666 mg MP+400 mg CaCO3 >400 mg CaCO3 ≫666 mg Gelusil) of MP leaves was noticed. The methanolic extract of MP leaves demonstrated anti-microbial activity against Staphylococcus aureus (15±2mm), Pseudomonas aeruginosa (12±2mm) and Escherichia coli (10±2mm). In silico studies confirmed the in vitro results obtained for antioxidant, antiacid, and anti-microbial activities. In addition, in silico studies revealed the anti-cancerous and anti-inflammatory potential of the MP leaves. In summary, this study demonstrated the medicinal significance of MP leaves and the conversion of agro-waste or the under-utilized part of MP into pharmaceutical potent materials. Consequently, the present study highlighted that MP leaves alone have medicinal importance with good nutritional utility and possess large promise in the pharma industry along with improving bio-valorization and the environment.

A Comparative Analysis of Phytochemicals, Metal Ions, Volatile Metabolites in Heart Wood, Stem Bark and Leaves of Salix alba L. along with in Vitro Antioxidant, Antacid, Antimicrobial Activities for Sake of Environment Conservation by Substitution of Stem Bark With Leaf.

The genus of Salix is used in food, medicine and nutraceuticals, and standardized by using the single marker compound Salicin only. Stem bark is the official part used for the preparation of various drugs, nutraceuticals and food products, which may lead to overexploitation and damage of tree. There is need to search substitution of the stem bark with leaf of Salix alba L. (SA), which is yet not reported. Comparative phytochemicals viz. Salicin, Procyanidin B1 and Catechin were quantified in the various parts of SA viz. heart wood (SA-HW), stem bark (SA-SB) and leaves (SA-L) of Salix alba L.by using newly developed HPLC method. It was observed that SA-HW and SA-L contained far better amount of Salicin, Procyanidin B and Catechin as compared to SA-SB (SA-HW~SA-L≫SA-SB). Essential and toxic metal ions of all three parts were analysed using newly developed ICP-OES method, where SA-L were founded as a rich source of micronutrients and essential metal ions as compared to SA-SB and SA-HW. GC-MS analysis has shown the presence of fatty acids and volatile compounds. The observed TPC and TFC values for all three parts were ranged from 2.69 to 32.30 mg GAE/g of wt. and 37.57 to 220.76 mg QCE/g of wt. respectively. In DPPH assay the IC50 values of SA-SB, SA-HW, and SA-L were 1.09 (±0.02), 5.42 (±0.08), and 8.82 (±0.10) mg/mL, respectively. The order of antibacterial activities against E. coli, S. aureus, P. aeruginosa, and B. subtilis strains was SA-L>SA-HW>SA-SB with strong antibacterial activities against S. aureus, and B. subtilis strains. The antacid activities order was SA-L>SA-SB>SA-HW. The leaves of SA have shown significant source of nutrients, phytochemicals and medicinal properties than SA-HW and SA-SB. The leaves of SA may be considered as substitute of stem bark to save the environment or to avoid over exploitation, but after the complete pharmacological and toxicological studies.

Macroalgal dietary glycans: potential source for human gut bacteria and enhancing immune system for better health.

Macroalgae are the diverse group of photosynthetic algae found at the intertidal regions of oceans. Recent advances suggest that macroalgal derived glycans have tremendous potential to maintain gut microbiome and immune system. The human gut bacteria harbor unique arsenals for utilizing a variety of macroalgal glycans, and produce a variety of oligosaccharides in vivo. Those oligosaccharides interact with immune cell receptors, and also are available for microbial fermentation, thus play magnificent roles in balancing the gut homeostasis. However, this area of research is still in infancy condition in term to understand their molecular interactions. For wooing this area, we urge to emphasize more studies on mechanistic level sympathetic of depolymerizing marine dietary glycans by gut bacteria and elucidating molecular aspect of glycans to cell receptors interactions. This will invent new nutraceutical strategies to purposefully manipulate the microbial composition to improve health. Therefore, review focuses on the recent development of mechanistic understanding of human gut bacterial communities for utilizing macroalgal derived glycans. Recent trends of application of glycans in modulating immune system at mechanistic level and their available evidences are discussed.

Plant-soil-microbes: A tripartite interaction for nutrient acquisition and better plant growth for sustainable agricultural practices.

Plants can achieve their proper growth and development with the help of microorganisms associated with them. Plant-associated microbes convert the unavailable nutrients to available form and make them useful for plants. Besides nutrient acquisition, soil microbes also inhibit the pathogens that cause harm to plant growth and induces defense response. Due to the beneficial activities of soil nutrient-microbe-plant interactions, it is necessary to study more on this topic and develop microbial inoculant technology in the agricultural field for better crop improvement. The soil microbes can be engineered, and plant growth-promoting rhizobacteria (PGPR) and plant growth-promoting bacteria (PGPB) technology can be developed as well, as its application can be improved for utilization as biofertilizer, biopesticides, etc., instead of using harmful chemical biofertilizers. Moreover, plant growth-promoting microbe inoculants can enhance crop productivity. Although, scientists have discussed several tools and techniques by omics and gene editing approaches for crop improvement to avoid biotic and abiotic stress and make the plant healthier and more nutritive. However, beneficial soil microbes that help plants with the nutrient acquisition, development, and stress resistance were ignored, and farmers started utilizing chemical fertilizers. Thus, this review attempts to summarize the interaction system of plant microbes, the role of beneficiary soil microbes in the rhizosphere zone, and their role in plant health promotion, particularly in the nutrition acquisition of the plant. The review will also provide a better understanding of soil microbes that can be exploited as biofertilizers and plant growth promoters in the field to create environmentally friendly, sustainable agriculture systems.

Smart and emerging nanomaterials-based biosensor for SARS-CoV-2 detection.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a primary cause of the COVID-19 pandemic. To date, various detection approaches are already present, and many other techniques are also being developed for the rapid and real-time detection of COVID-19 infection in the wake of this pandemic. Hence, this featured review will provide an overview of COVID-19, its biomarkers, current diagnostic techniques, and emerging smart nanomaterials-based biosensing approaches; apart from this, it will also extend some light on future perspectives of biosensing technologies for SARS-CoV-2 diagnosis.

Intrarectal Capsazepine Administration Modulates Colonic Mucosal Health in Mice.

Antagonism of transient receptor potential vanniloid-1 (TRPV1) and desensitization of transient receptor potential ankyrin-1 (TRPA1) nociceptors alleviate inflammatory bowel diseases (IBD)-associated chronic pain. However, there is limited literature available about their role in regulating the mucosal layer, its interaction with host physiology, and luminal microbial community. The present study focuses on the effects' intra rectal administration of capsazepine (modulator of TRPA1/TRPV1 expressing peptidergic sensory neurons) on colonic mucus production and gut health. We performed histological analysis, gut permeability alteration, gene expression changes, metabolite profiling, and gut microbial abundance in the ileum, colon, and cecum content of these animals. Intra rectal administration of capsazepine modulates TRPA1/TRPV1-positive nociceptors (behavioral pain assays) and resulted in damaged mucosal lining, increased gut permeability, and altered transcriptional profile of genes for goblet cell markers, mucus regulation, immune response, and tight junction proteins. The damage to mucosal lining prevented its role in enterosyne (short chain fatty acids) actions. These results suggest that caution must be exercised before employing TRPA1/TRPV1 modulation as a therapeutic option to alleviate pain caused due to IBD.

Biochemical Basis of Xylooligosaccharide Utilisation by Gut Bacteria.

Xylan is one of the major structural components of the plant cell wall. Xylan present in the human diet reaches the large intestine undigested and becomes a substrate to species of the gut microbiota. Here, we characterised the capacity of Limosilactobacillus reuteri and Blautia producta strains to utilise xylan derivatives. We showed that L. reuteri ATCC 53608 and B. producta ATCC 27340 produced ß-D-xylosidases, enabling growth on xylooligosaccharide (XOS). The recombinant enzymes were highly active on artificial (p-nitrophenyl ß-D-xylopyranoside) and natural (xylobiose, xylotriose, and xylotetraose) substrates, and showed transxylosylation activity and tolerance to xylose inhibition. The enzymes belong to glycoside hydrolase family 120 with Asp as nucleophile and Glu as proton donor, as shown by homology modelling and confirmed by site-directed mutagenesis. In silico analysis revealed that these enzymes were part of a gene cluster in L. reuteri but not in Blautia strains, and quantitative proteomics identified other enzymes and transporters involved in B. producta XOS utilisation. Based on these findings, we proposed a model for an XOS metabolism pathway in L. reuteri and B. producta strains. Together with phylogenetic analyses, the data also revealed the extended xylanolytic potential of the gut microbiota.

Phytomedicines explored under in vitro and in silico studies against coronavirus: An opportunity to develop traditional medicines.

The widespread COVID-19 pandemic, caused by novel coronavirus SARS-CoV-2, has emanated as one of the most life-threatening transmissible diseases. Currently, the repurposed drugs such as remdesivir, azithromycine, chloroquine, and hydroxychloroquine are being employed in the management of COVID-19 but their adverse effects are a matter of concern. In this regard, alternative treatment options i.e., traditional medicine, medicinal plants, and their phytochemicals, which exhibit significant therapeutic efficacy and show a low toxicity profile, are being explored. The current review aims at unraveling the promising medicinal plants, phytochemicals, and traditional medicines against SARS-CoV-2 to discover phytomedicines for the management of COVID-19 on the basis of their potent antiviral activities against coronaviruses, as demonstrated in various biochemical and computational chemical biology studies. The review consists of integrative and updated information on the potential traditional medicines against COVID-19 and will facilitate researchers to develop traditional medicines for the management of COVID-19.

Human Survival Motor Neuron genes generate a vast repertoire of circular RNAs.

Circular RNAs (circRNAs) perform diverse functions, including the regulation of transcription, translation, peptide synthesis, macromolecular sequestration and trafficking. Inverted Alu repeats capable of forming RNA:RNA duplexes that bring splice sites together for backsplicing are known to facilitate circRNA generation. However, higher limits of circRNAs produced by a single Alu-rich gene are currently not predictable due to limitations of amplification and analyses. Here, using a tailored approach, we report a surprising diversity of exon-containing circRNAs generated by the Alu-rich Survival Motor Neuron (SMN) genes that code for SMN, an essential multifunctional protein in humans. We show that expression of the vast repertoire of SMN circRNAs is universal. Several of the identified circRNAs harbor novel exons derived from both intronic and intergenic sequences. A comparison with mouse Smn circRNAs underscored a clear impact of primate-specific Alu elements on shaping the overall repertoire of human SMN circRNAs. We show the role of DHX9, an RNA helicase, in splicing regulation of several SMN exons that are preferentially incorporated into circRNAs. Our results suggest self- and cross-regulation of biogenesis of various SMN circRNAs. These findings bring a novel perspective towards a better understanding of SMN gene function.