Morpho-Physiochemical Indices and Transcriptome Analysis Reveal the Role of Glucosinolate and Erucic Acid in Response to Drought Stress during Seed Germination of Rapeseed.

The global expansion of rapeseed seed quality has been focused on maintaining glucosinolate (GSL) and erucic acid (EA) contents. However, the influence of seed GSL and EA contents on the germination process under drought stress remains poorly understood. Herein, 114 rapeseed accessions were divided into four groups based on GSL and EA contents to investigate their performance during seed imbibition under drought stress. Our results revealed significant variations in seed germination-related traits, particularly with higher GSL and EA, which exhibited higher germination % (G%) and lower mean germination time (MGT) under drought stress conditions. Moreover, osmoregulation, enzymatic system and hormonal regulation were improved in high GSL and high EA (HGHE) versus low GSL and low EA (LGLE) seeds, indicating the essential protective role of GSL and EA during the germination process in response to drought stress. The transcriptional regulation mechanism for coordinating GSL-EA-related pathways in response to drought stress during seed imbibition was found to involve the differential expression of sugar metabolism-, antioxidant-, and hormone-related genes with higher enrichment in HGHE compared to LGLE seeds. GO enrichment analysis showed higher variations in transcription regulator activity and DNA-binding transcription factors, as well as ATP and microtubule motor activity in GSL-EA-related pathways. Furthermore, KEGG analysis identified cellular processes, environmental information processing, and metabolism categories, with varied gene participation between GSL, EA and GSL-EA-related pathways. For further clarification, QY7 (LGLE) seeds were primed with different concentrations of GSL and EA under drought stress conditions. The results showed that 200 µmol/L of GSL and 400 µmol/L of EA significantly improved G%, MGT, and seedling fresh weight, besides regulating stress and fatty acid responsive genes during the seed germination process under drought stress conditions. Conclusively, exogenous application of GSL and EA is considered a promising method for enhancing the drought tolerance of LGLE seeds. Furthermore, the current investigation could provide a theoretical basis of GSL and EA roles and their underlying mechanisms in stress tolerance during the germination process.

Peutz-Jeghers syndrome with polyps in the stomach, duodenum, and small and large intestine: a case report.

BACKGROUND: Peutz-Jeghers syndrome is a rare hereditary condition characterized by gastrointestinal polyps and pigmented oral lesions. The case contributes to a deeper understanding of Peutz-Jeghers syndrome and underscores the significance of interdisciplinary collaboration for accurate diagnosis and tailored therapeutic strategies. CASE DESCRIPTION: We present a case of a 15-year-old Afghan female patient with multiple polyps throughout the gastrointestinal tract and mucocutaneous pigmentation. Despite previous medical visits and colonoscopies, her symptoms persisted. A multidisciplinary team discussed the case and recommended further investigations and interventions. A polypectomy was performed, confirming the presence of hamartomatous polyps. The patient was diagnosed with Peutz-Jeghers syndrome, but during the course of treatment she went through complications and was managed surgically as well. CONCLUSION: Timely polyp removal and lifelong surveillance are crucial in managing Peutz-Jeghers syndrome. Further research and genetic analysis are needed to improve understanding and management of this rare disorder.

CRISPR-Cas9 based molecular breeding in crop plants: a review.

Traditional crop breeding techniques are not quickly boosting yields to fulfill the expanding population needs. Long crop lifespans hinder the ability of plant breeding to develop superior crop varieties. Due to the arduous crossing, selecting, and challenging processes, it can take decades to establish new varieties with desired agronomic traits. Develop new plant varieties instantly to reduce hunger and improve food security. As a result of the adoption of conventional agricultural techniques, crop genetic diversity has decreased over time. Several traditional and molecular techniques, such as genetic selection, mutant breeding, somaclonal variation, genome-wide association studies, and others, have improved agronomic traits associated with agricultural plant productivity, quality, and resistance to biotic and abiotic stresses. In addition, modern genome editing approaches based on programmable nucleases, CRISPR, and Cas9 proteins have escorted an exciting new era of plant breeding. Plant breeders and scientists worldwide rely on cutting-edge techniques like quick breeding, genome editing tools, and high-throughput phenotyping to boost crop breeding output. This review compiles discoveries in numerous areas of crop breeding, such as using genome editing tools to accelerate the breeding process and create yearly crop generations with the desired features, to describe the shift from conventional to modern plant breeding techniques.

Customized plant microbiome engineering for food security.

Plant microbiomes play a vital role in promoting plant growth and resilience to cope with environmental stresses. Plant microbiome engineering holds significant promise to increase crop yields, but there is uncertainty about how this can best be achieved. We propose a step-by-step approach involving customized direct and indirect methods to condition soils and to match plants and microbiomes. Although three approaches, namely the development of (i) 'plant- and microbe-friendly' soils, (ii) 'microbe-friendly' plants, and (iii) 'plant-friendly' microbiomes, have been successfully tested in isolation, we propose that the combination of all three may lead to a step-change towards higher and more stable crop yields. This review aims to provide knowledge, future directions, and practical guidance to achieve this goal via customized plant microbiome engineering.

A Cross-Sectional Study of Potential Antimicrobial Resistance and Ecology in Gastrointestinal and Oral Microbial Communities of Young Normoweight Pakistani Individuals.

Antimicrobial resistance (AMR) is a major global public health concern mainly affecting low- and middle-income countries (LMICs) due to lack of awareness, inadequate healthcare and sanitation infrastructure, and other environmental factors. In this study, we aimed to link microbial assembly and covariates (body mass index, smoking, and use of antibiotics) to gut microbiome structure and correlate the predictive antimicrobial gene prevalence (piARG) using PICRUSt2. We examined the gastrointestinal and oral microbial profiles of healthy adults in Pakistan through 16S rRNA gene sequencing with a focus on different ethnicities, antibiotic usage, drinking water type, smoking, and other demographic measures. We then utilised a suite of innovative statistical tools, driven by numerical ecology and machine learning, to address the above aims. We observed that drinking tap water was the main contributor to increased potential AMR signatures in the Pakistani cohort compared to other factors considered. Microbial niche breadth analysis highlighted an aberrant gut microbial signature of smokers with increased age. Moreover, covariates such as smoking and age impact the human microbial community structure in this Pakistani cohort.

Variable level of genetic dominance controls important agronomic traits in rice populations under water deficit condition.

Plant hybridization is an important breeding technique essential for producing a genotype (hybrid) with favorable traits (e.g., stress tolerance, pest resistance, high yield potential etc.) to increase agronomic, economic and commercial values. Studying of genetic dominance among the population helps to determine gene action, heritability and candidate gene selection for plant breeding program. Therefore, this investigation was aimed to evaluate gene action, heritability, genetic advance and heterosis of rice root, agronomic, and yield component traits under water deficit conditions. In this study, crossing was performed among the four different water-deficit tolerant rice genotypes to produce better hybrid (F1), segregating (F2) and back-cross (BC1 and BC2) populations. The Giza 178, WAB56-204, and Sakha104 × WAB56-104 populations showed the better physiological and agronomical performances, which provided better adaptability of the populations to water deficit condition. Additionally, the estimation of heterosis and heterobeltiosis of some quantitative traits in rice populations were also studied. The inheritance of all studied traits was influenced by additive gene actions. Dominance gene actions played a major role in controlling the genetic variance among studied traits in both crossed populations under well-watered and drought conditions. The additive × additive type of gene interactions was essential for the inheritance of root length, root/shoot ratio, 1,000-grain weight, and sterility % of two crossed populations under both conditions. On the contrary, the additive × dominance type of gene interactions was effective in the inheritance of all studied traits, except duration in Giza178 × Sakha106, and plant height in Sakha104 × WAB56-104 under water deficit condition. In both crosses, the dominance × dominance type of gene interactions was effective in the inheritance of root volume, root/shoot ratio, number of panicles/plant and 1,000-grain weight under both conditions. Moreover, dominance × dominance type of gene interaction played a major role in the inheritance of root length, number of roots/plant, plant height, panicle length, number of filled grain/panicle and grain yield/plant in Giza178 × Sakha106 under both conditions. The studied traits in both crossed populations indicated better genetic advance as they showed advanced qualitative and quantitative characters in rice populations under water deficit condition. Overall, our findings open a new avenue of future phenotypic and genotypic association studies in rice. These insights might be useful to the plant breeders and farmers for developing water deficit tolerant rice cultivars.

Metal organic frameworks as promising sensing tools for electrochemical detection of persistent heavy metal ions from water matrices: A concise review.

Water bodies are being polluted rapidly by disposal of toxic chemicals with their huge entrance into drinking water supply chain. Among these pollutants, heavy metal ions (HMIs) are the most challenging one due to their non-biodegradability, toxicity, and ability to biologically hoard in ecological systems, thus posing a foremost danger to human health. This can be addressed by robust, sensitive, selective, and reliable sensing of metal ions which can be achieved by Metal organic frameworks (MOF) based electrochemical sensors. In the present era, MOFs have caught greater interest in a variety of applications including sensing of hazardous pollutants such as heavy metal ions. So, in this review article, types, synthesis and working mechanism of MOF based sensors is explained to give general overview with updated literature. First time, detailed study is done for sensing of metal ions such as chromium, mercury, zinc, copper, manganese, palladium, lead, iron, cadmium and lanthanide by MOFs based electrochemical sensors. The use of MOFs as electrochemical sensors has attractive success story along with some challenges of the area. Considering these challenges, we attempted to highlight the milestone achieved and shortcomings along with future prospective of the MOFs for employing it in electrochemical sensing devices for HMIs. Finally, challenges and future prospects have been discussed to promote the development of MOFs-based sensors in future.

An orally active, small-molecule TNF inhibitor that disrupts the homotrimerization interface improves inflammatory arthritis in mice.

Excessive signaling by the proinflammatory cytokine TNF is involved in several autoimmune diseases, including rheumatoid arthritis (RA). However, unlike the approved biologics currently used to treat this and other conditions, commercially available small-molecule inhibitors of TNF trimerization are cytotoxic or exhibit low potency. Here, we report a TNF-inhibitory molecule (TIM) that reduced TNF signaling in vitro and was an effective treatment in a mouse model of RA. The initial lead compound, TIM1, attenuated TNF-induced apoptosis of human and mouse cells by delaying the induction of proinflammatory NF-κB and MAPK signaling and caspase 3- and caspase 8-dependent apoptosis. TIM1 inhibited the secretion of the proinflammatory cytokines IL-6 and IL-8 by disrupting TNF homotrimerization, thereby preventing its association with the TNF receptor. In a mouse model of collagen-induced polyarthritis, the more potent TIM1 analog TIM1c was orally bioavailable and reduced paw swelling, histological indicators of knee joint pathology, inflammatory infiltration of the joint, and the overall arthritis index. Orally delivered TIM1c showed immunological effects similar to those elicited by intraperitoneal injection of the FDA-approved TNF receptor decoy etanercept. Thus, TIM1c is a promising lead compound for the development of small-molecule therapies for the treatment of RA and other TNF-dependent systemic inflammation disorders.

Improving crop productivity and nitrogen use efficiency using sulfur and zinc-coated urea: A review.

Nitrogen (N) is an important macro-nutrient required for crop production and is considered an important commodity for agricultural systems. Urea is a vital source of N that is used widely across the globe to meet crop N requirements. However, N applied in the form of urea is mostly lost in soil, posing serious economic and environmental issues. Therefore, different approaches such as the application of urea coated with different substances are used worldwide to reduce N losses. Urea coating is considered an imperative approach to enhance crop production and reduce the corresponding nitrogen losses along with its impact on the environment. In addition, given the serious food security challenges in meeting the current and future demands for food, the best agricultural management strategy to enhance food production have led to methods that involve coating urea with different nutrients such as sulfur (S) and zinc (Zn). Coated urea has a slow-release mechanism and remains in the soil for a longer period to meet the demand of crop plants and increases nitrogen use efficiency, growth, yield, and grain quality. These nutrient-coated urea reduce nitrogen losses (volatilization, leaching, and N2O) and save the environment from degradation. Sulfur and zinc-coated urea also reduce nutrient deficiencies and have synergetic effects with other macro and micronutrients in the crop. This study discusses the dynamics of sulfur and zinc-coated urea in soil, their impact on crop production, nitrogen use efficiency (NUE), the residual and toxic effects of coated urea, and the constraints of adopting coated fertilizers. Additionally, we also shed light on agronomic and molecular approaches to enhance NUE for better crop productivity to meet food security challenges.

Versatile roles of polyamines in improving abiotic stress tolerance of plants.

In recent years, extreme environmental cues such as abiotic stresses, including frequent droughts with irregular precipitation, salinity, metal contamination, and temperature fluctuations, have been escalating the damage to plants' optimal productivity worldwide. Therefore, yield maintenance under extreme events needs improvement in multiple mechanisms that can minimize the influence of abiotic stresses. Polyamines (PAs) are pivotally necessary for a defensive purpose under adverse abiotic conditions, but their molecular interplay in this remains speculative. The PAs' accretion is one of the most notable metabolic responses of plants under stress challenges. Recent studies reported the beneficial roles of PAs in plant development, including metabolic and physiological processes, unveiling their potential for inducing tolerance against adverse conditions. This review presents an overview of research about the most illustrious and remarkable achievements in strengthening plant tolerance to drought, salt, and temperature stresses by the exogenous application of PAs. The knowledge of underlying processes associated with stress tolerance and PA signaling pathways was also summarized, focusing on up-to-date evidence regarding the metabolic and physiological role of PAs with exogenous applications that protect plants under unfavorable climatic conditions. Conclusively, the literature proposes that PAs impart an imperative role in abiotic stress tolerance in plants. This implies potentially important feedback on PAs and plants' stress tolerance under unfavorable cues.

Mitigation of the salinity stress in rapeseed (Brassica napus L.) productivity by exogenous applications of bio-selenium nanoparticles during the early seedling stage.

In recent years, much attention has been directed toward using nanoparticles (NPs) as one of the most effective strategies to improve plant growth, especially under salt stress conditions. Further research has been conducted to develop NPs using various chemical ways; accordingly, knowledge about the beneficial effect of bioSeNPs in rapeseed is obscure. Selenium (Se) is a vital micronutrient with a series of physiological and antioxidative properties. Seed priming is emerging as a low-cost, efficient, and environment-friendly seed treatment in nanotechnology. The current study was carried out to examine the promising effects of nanopriming via bioSeNPs on the expression level of aquaporin genes, seed microstructure, seed germination, growth traits, physiochemical attributes, and minerals uptake of two rapeseed cultivars under salinity stress conditions. Our investigation monitored the positive effects of bioSeNPs on the expression level of aquaporin genes (BnPIP1-1 and BnPIP2-1) and water uptake during the seed imbibition (4 and 8 h of priming), which indicated higher imbibition potential and germination promotion with bioSeNPs application (most effective at 150 µmol/L). The total performance index was significantly enhanced with nano-treatments in rapeseed seedlings. Collectively, nano-application improved seed microstructure, seed germination, and photosynthetic efficiency directly correlated with higher seedlings biomass, especially with a higher concentration of bioSeNPs. The enhancement in α-amylase and free amino acid contents in nanoprimed seeds resulted in rapid seed germination. Moreover, bioSeNPs increased the osmotic adjustment and enhanced the efficiency of the plant's defense system by improving the activity of enzymatic and non-enzymatic antioxidants, thus enhancing ROS scavenging under salt stress. The obtained results may indicate the strengthening of seed vigor, improving seedling growth and physiochemical attributes via bioSeNPs. Our findings displayed that bioSeNPs modulated the Na+ and K+ uptake, which improved the rapeseed growth and showed a close relationship with the low contents of toxic Na+ ion; thus, it prevented oxidative damage due to salt stress. This comprehensive data can add more knowledge to understand the mechanisms behind plant-bioSeNPs interaction and provide physiological evidence for the beneficial roles of nanopriming using bioSeNPs on rapeseed germination and seedling development under salinity stress conditions. Such studies can be used to develop simple prepackaged nano primer products, which can be used before sowing to boost seed germination and crop productivity under stress conditions.

Improving Drought Stress Tolerance in Ramie (Boehmeria nivea L.) Using Molecular Techniques.

Ramie is one of the most significant fiber crops and contributes to good quality fiber. Drought stress (DS) is one of the most devastating abiotic factors which is accountable for a substantial loss in crop growth and production and disturbing sustainable crop production. DS impairs growth, plant water relation, and nutrient uptake. Ramie has evolved a series of defense responses to cope with DS. There are numerous genes regulating the drought tolerance (DT) mechanism in ramie. The morphological and physiological mechanism of DT is well-studied; however, modified methods would be more effective. The use of novel genome editing tools like clustered regularly interspaced short palindromic repeats (CRISPR) is being used to edit the recessive genes in crops to modify their function. The transgenic approaches are used to develop several drought-tolerant varieties in ramie, and further identification of tolerant genes is needed for an effective breeding plan. Quantitative trait loci (QTLs) mapping, transcription factors (TFs) and speed breeding are highly studied techniques, and these would lead to the development of drought-resilient ramie cultivars. The use of hormones in enhancing crop growth and development under water scarcity circumstances is critical; however, using different concentrations and testing genotypes in changing environments would be helpful to sort the tolerant genotypes. Since plants use various ways to counter DS, investigating mechanisms of DT in plants will lead to improved DT in ramie. This critical review summarized the recent advancements on DT in ramie using novel molecular techniques. This information would help ramie breeders to conduct research studies and develop drought tolerant ramie cultivars.

Trehalose: a promising osmo-protectant against salinity stress-physiological and molecular mechanisms and future prospective.

Salt stress is one of the leading threats to crop growth and productivity across the globe. Salt stress induces serious alterations in plant physiological, metabolic, biochemical functioning and it also disturbs antioxidant activities, cellular membranes, photosynthetic performance, nutrient uptake and plant water uptake and resulting in a significant reduction in growth and production. The application of osmoprotectants is considered as an important strategy to induce salt tolerance in plants. Trehalose (Tre) has emerged an excellent osmolyte to induce salinity tolerance and it got considerable attention in recent times. Under salinity stress, Tre helps to maintain the membrane integrity, and improves plant water relations, nutrient uptake and reduces the electrolyte leakage and lipid per-oxidation. Tre also improves gas exchange characteristics, protects the photosynthetic apparatus from salinity induced oxidative damages and brings ultra-structure changes in the plant body to induce salinity tolerance. Moreover, Tre also improves antioxidant activities and expression of stress responsive proteins and genes and confers salt tolerance in plants. Additionally, Tre is also involved in signaling association with signaling molecules and phytohormones and resultantly improved the plant performance under salt stress. Thus, it is interesting to understand the role of Tre in mediating the salinity tolerance in plants. Therefore, in this review we have summarized the different physiological and molecular roles of Tre to induce salt tolerance in plants. Moreover, we have also provided the information on Tre cross-talk with various osmolytes and hormones, and its role in stress responsive genes and antioxidant activities. Lastly, we also shed light on research gaps that need to be addressed in future studies. Therefore, this review will help the scientists to learn more about the Tre in changing climate conditions and it will also provide new insights to insights that could be used to develop salinity tolerance in plants.

Nutritional Value, Phytochemical Potential, and Therapeutic Benefits of Pumpkin (Cucurbita sp.).

Pumpkin is a well-known multifunctional ingredient in the diet, full of nutrients, and has opened new vistas for scientists during the past years. The fruit of pumpkin including the flesh, seed, and peel are a rich source of primary and secondary metabolites, including proteins, carbohydrates, monounsaturated fatty acids, polyunsaturated fatty acids, carotenoids, tocopherols, tryptophan, delta-7-sterols, and many other phytochemicals. This climber is traditionally used in many countries, such as Austria, Hungary, Mexico, Slovenia, China, Spain, and several Asian and African countries as a functional food and provides health promising properties. Other benefits of pumpkin, such as improving spermatogenesis, wound healing, antimicrobial, anti-inflammatory, antioxidative, anti-ulcerative properties, and treatment of benign prostatic hyperplasia have also been confirmed by researchers. For better drug delivery, nanoemulsions and niosomes made from pumpkin seeds have also been reported as a health promising tool, but further research is still required in this field. This review mainly focuses on compiling and summarizing the most relevant literature to highlight the nutritional value, phytochemical potential, and therapeutic benefits of pumpkin.

Novel Plant Breeding Techniques Shake Hands with Cereals to Increase Production.

Cereals are the main source of human food on our planet. The ever-increasing food demand, continuously changing environment, and diseases of cereal crops have made adequate production a challenging task for feeding the ever-increasing population. Plant breeders are striving their hardest to increase production by manipulating conventional breeding methods based on the biology of plants, either self-pollinating or cross-pollinating. However, traditional approaches take a decade, space, and inputs in order to make crosses and release improved varieties. Recent advancements in genome editing tools (GETs) have increased the possibility of precise and rapid genome editing. New GETs such as CRISPR/Cas9, CRISPR/Cpf1, prime editing, base editing, dCas9 epigenetic modification, and several other transgene-free genome editing approaches are available to fill the lacuna of selection cycles and limited genetic diversity. Over the last few years, these technologies have led to revolutionary developments and researchers have quickly attained remarkable achievements. However, GETs are associated with various bottlenecks that prevent the scaling development of new varieties that can be dealt with by integrating the GETs with the improved conventional breeding methods such as speed breeding, which would take plant breeding to the next level. In this review, we have summarized all these traditional, molecular, and integrated approaches to speed up the breeding procedure of cereals.

Biosynthetic pathways of triterpenoids and strategies to improve their Biosynthetic Efficiency.

"Triterpenoids" can be considered natural products derived from the cyclization of squalene, yielding 3-deoxytriterpenes (hydrocarbons) or 3-hydroxytriterpenes. Triterpenoids are metabolites of these two classes of triterpenes, produced by the functionalization of their carbon skeleton. They can be categorized into different groups based on their structural formula/design. Triterpenoids are an important group of compounds that are widely used in the fields of pharmacology, food, and industrial biotechnology. However, inadequate synthetic methods and insufficient knowledge of the biosynthesis of triterpenoids, such as their structure, enzymatic activity, and the methods used to produce pure and active triterpenoids, are key problems that limit the production of these active metabolites. Here, we summarize the derivatives, pharmaceutical properties, and biosynthetic pathways of triterpenoids and review the enzymes involved in their biosynthetic pathway. Furthermore, we concluded the screening methods, identified the genes involved in the pathways, and highlighted the appropriate strategies used to enhance their biosynthetic production to facilitate the commercial process of triterpenoids through the synthetic biology method.

Comparative efficacy of bio-selenium nanoparticles and sodium selenite on morpho-physiochemical attributes under normal and salt stress conditions, besides selenium detoxification pathways in Brassica napus L.

Selenium nanoparticles (SeNPs) have attracted considerable attention globally due to their significant potential for alleviating abiotic stresses in plants. Accordingly, further research has been conducted to develop nanoparticles using chemical ways. However, our knowledge about the potential benefit or phytotoxicity of bioSeNPs in rapeseed is still unclear. Herein, we investigated the effect of bioSeNPs on growth and physiochemical attributes, and selenium detoxification pathways compared to sodium selenite (Se (IV)) during the early seedling stage under normal and salt stress conditions. Our findings showed that the range between optimal and toxic levels of bioSeNPs was wider than Se (IV), which increased the plant's ability to reduce salinity-induced oxidative stress. BioSeNPs improved the phenotypic characteristics of rapeseed seedlings without the sign of toxicity, markedly elevated germination, growth, photosynthetic efficiency and osmolyte accumulation versus Se (IV) under normal and salt stress conditions. In addition to modulation of Na+ and K+ uptake, bioSeNPs minimized the ROS level and MDA content by activating the antioxidant enzymes engaged in ROS detoxification by regulating these enzyme-related genes expression patterns. Importantly, the main effect of bioSeNPs and Se (IV) on plant growth appeared to be correlated with the change in the expression levels of Se-related genes. Our qRT-PCR results revealed that the genes involved in Se detoxification in root tissue were upregulated upon Se (IV) treated seedlings compared to NPs, indicating that bioSeNPs have a slightly toxic effect under higher concentrations. Furthermore, bioSeNPs might improve lateral root production by increasing the expression level of LBD16. Taken together, transamination and selenation were more functional methods of Se detoxification and proposed different degradation pathways that synthesized malformed or deformed selenoproteins, which provided essential mechanisms to increase Se tolerance at higher concentrations in rapeseed seedlings. Current findings could add more knowledge regarding the mechanisms underlying bioSeNPs induced plant growth.

Structural insights into the distinctive RNA recognition and therapeutic potentials of RIG-I-like receptors.

RNA viruses, including the coronavirus, develop a unique strategy to evade the host immune response by interrupting the normal function of cytosolic retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs). RLRs rapidly detect atypical nucleic acids, thereby triggering the antiviral innate immune signaling cascade and subsequently activates the interferons transcription and induction of other proinflammatory cytokines and chemokines. Nonetheless, these receptors are manipulated by viral proteins to subvert the host immune system and sustain the infectivity and replication potential of the virus. RIG-I senses the single-stranded, double-stranded, and short double-stranded RNAs and recognizes the key signature, a 5'-triphosphate moiety, at the blunt end of the viral RNA. Meanwhile, the melanoma differentiation-associated gene 5 (MDA5) is triggered by longer double stranded RNAs, messenger RNAs lacking 2'-O-methylation in their 5'-cap, and RNA aggregates. Therefore, structural insights into the nucleic-acid-sensing and downstream signaling mechanisms of these receptors hold great promise for developing effective antiviral therapeutic interventions. This review highlights the critical roles played by RLRs in viral infections as well as their ligand recognition mechanisms. In addition, we highlight the crosstalk between the toll-like receptors and RLRs and provide a comprehensive overview of RLR-associated diseases as well as the therapeutic potential of RLRs for the development of antiviral-drugs. Moreover, we believe that these RLR-based antivirals will serve as a step toward countering the recent coronavirus disease 2019 pandemic.

A Critical Review: Recent Advancements in the Use of CRISPR/Cas9 Technology to Enhance Crops and Alleviate Global Food Crises.

Genome editing (GE) has revolutionized the biological sciences by creating a novel approach for manipulating the genomes of living organisms. Many tools have been developed in recent years to enable the editing of complex genomes. Therefore, a reliable and rapid approach for increasing yield and tolerance to various environmental stresses is necessary to sustain agricultural crop production for global food security. This critical review elaborates the GE tools used for crop improvement. These tools include mega-nucleases (MNs), such as zinc-finger nucleases (ZFNs), and transcriptional activator-like effector nucleases (TALENs), and clustered regularly interspaced short palindromic repeats (CRISPR). Specifically, this review addresses the latest advancements in the role of CRISPR/Cas9 for genome manipulation for major crop improvement, including yield and quality development of biotic stress- and abiotic stress-tolerant crops. Implementation of this technique will lead to the production of non-transgene crops with preferred characteristics that can result in enhanced yield capacity under various environmental stresses. The CRISPR/Cas9 technique can be combined with current and potential breeding methods (e.g., speed breeding and omics-assisted breeding) to enhance agricultural productivity to ensure food security. We have also discussed the challenges and limitations of CRISPR/Cas9. This information will be useful to plant breeders and researchers in the thorough investigation of the use of CRISPR/Cas9 to boost crops by targeting the gene of interest.

Toll-Like Receptors as a Therapeutic Target in the Era of Immunotherapies.

Toll-like receptors (TLRs) are the pattern recognition receptors, which are activated by foreign and host molecules in order to initiate the immune response. They play a crucial role in the regulation of innate immunity, and several studies have shown their importance in bacterial, viral, and fungal infections, autoimmune diseases, and cancers. The consensus view from an immunological perspective is that TLR agonists can serve either as a possible therapeutic agent or as a vaccine adjuvant toward cancers or infectious diseases and that TLR inhibitors may be a promising approach to the treatment of autoimmune diseases, some cancers, bacterial, and viral infections. These notions are based on the fact that TLR agonists stimulate the secretion of proinflammatory cytokines and in general, the development of proinflammatory responses. Some of the TLR-based inhibitory agents have shown to be efficacious in preclinical models and have now entered clinical trials. Therefore, TLRs seem to hold the potential to serve as a perfect target in the era of immunotherapies. We offer a perspective on TLR-based therapeutics that sheds light on their usefulness and on combination therapies. We also highlight various therapeutics that are in the discovery phase or in clinical trials.