Designer probiotics: Opening the new horizon in diagnosis and prevention of human diseases.

Probiotic microorganisms have been used for therapeutic purposes for over a century, and recent advances in biotechnology and genetic engineering have opened up new possibilities for developing therapeutic approaches using indigenous probiotic microorganisms. Diseases are often related to metabolic and immunological factors, which play a critical role in their onset. With the help of advanced genetic tools, probiotics can be modified to produce or secrete important therapeutic peptides directly into mucosal sites, increasing their effectiveness. One potential approach to enhancing human health is through the use of designer probiotics, which possess immunogenic characteristics. These genetically engineered probiotics hold promise in providing novel therapeutic options. In addition to their immunogenic properties, designer probiotics can also be equipped with sensors and genetic circuits, enabling them to detect a range of diseases with remarkable precision. Such capabilities may significantly advance disease diagnosis and management. Furthermore, designer probiotics have the potential to be used in diagnostic applications, offering a less invasive and more cost-effective alternative to conventional diagnostic techniques. This review offers an overview of the different functional aspects of the designer probiotics and their effectiveness on different diseases and also, we have emphasized their limitations and future implications. A comprehensive understanding of these functional attributes may pave the way for new avenues of prevention and the development of effective therapies for a range of diseases.

Rheumatoid arthritis synovial fluid shows enrichment of T-cells producing GMCSF which are polyfunctional for TNFα and IFNγ.

OBJECTIVES: GMCSF+T-cells may be involved in pathogenesis of rheumatoid arthritis (RA), and polyfunctionality may be a marker of pathogenicity. Although, higher frequencies of CD4+GMCSF+ T-cells have been reported, there are no data on CD8+GMCSF+ T-cells or polyfunctionality.Our objective was to enumerate frequencies of CD8+GMCSF+ T cells in RA blood and synovial fluid (SF), and assess their polyfunctionality, memory phenotype and cytotoxic ability. METHODS: This study included RA patients (blood samples,in some with paired synovial fluid (SF)), healthy controls (HC) (blood) and SpA patients (SF). In some RA patients' blood was sampled twice, before and 16-24 weeks after methotrexate (MTX) treatment. After mononuclear cell isolation from blood and SF, ex-vivo stimulation using PMA/Ionomycin was done, and cells were stained (surface and intracellular after permeabilisation/fixation). Subsequently, frequencies of GMCSF+CD8+ and CD4+ T-cells, polyfunctionality (TNFα, IFNγ, IL-17), phenotype (memory) and perforin/granzyme expression were assessed by flowcytometry. RESULTS: There was no significant difference in frequencies of GMCSF+CD8+ (3.7, 4.1%, p=0.540) or GMCSF+CD4+ T-cells (4.5, 5.2%, p=0.450) inblood of RA and HC. However, there was significant enrichment of both CD8+GMCSF+ (5.8, 3.9%, p=0.0045) and CD4+GMCSF+ (8.5, 4.5%, p=0.0008) T-cells inSF compared to blood in RA patients. Polyfunctional triple cytokine positive TNFα+IFNγ+GMCSF+CD8+T-cells (81, 36%, p=0.049) and CD4+T-cells (48, 32%, p=0.010) was also higher in SF compared to blood in RA. CD8+ T cells showed higher frequency of effector-memory phenotype and granzyme-B expression in RA-SF. On longitudinal follow-up, blood CD4+GMCSF+ T-cells significantly declined (4.6, 2.9%, p=0.0014) post-MTX. CONCLUSIONS: We report a novel finding of enrichment of CD8+GMCSF+ in addition to CD4+GMCSF+ T-cells in RA-SF. These cells showed higher polyfunctionality for TNFα and IFNγ, and effector memory phenotype suggesting their involvement in RA pathogenesis.

In-silico identification and exploration of small molecule coumarin-1,2,3-triazole hybrids as potential EGFR inhibitors for targeting lung cancer.

Globally, lung cancer is a significant public health concern due to its role as the leading cause of cancer-related mortalities. The promising target of EGFR for lung cancer treatment has been identified, providing a potential avenue for more effective therapies. The purpose of the study was to design a library of 1843 coumarin-1,2,3-triazole hybrids and screen them based on a designed pharmacophore to identify potential inhibitors targeting EGFR in lung cancer with minimum or no side effects. Pharmacophore-based screening was carried out and 60 hits were obtained. To gain a better understanding of the binding interactions between the compounds and the targeted receptor, molecular docking was conducted on the 60 screened compounds. In-silico ADME and toxicity studies were also conducted to assess the drug-likeness and safety of the identified compounds. The results indicated that coumarin-1,2,3-triazole hybrids COUM-0849, COUM-0935, COUM-0414, COUM-1335, COUM-0276, and COUM-0484 exhibit dock score of - 10.2, - 10.2, - 10.1, - 10.1, - 10, - 10 while reference molecule - 7.9 kcal/mol for EGFR (PDB ID: 4HJO) respectively. The molecular docking and molecular dynamics simulations revealed that the identified compounds formed stable interactions with the active site of EGFR, indicating their potential as inhibitors. The in-silico ADME and toxicity studies showed that the compounds had favorable drug-likeness properties and low toxicity, further supporting their potential as therapeutic agents. Finally, we performed DFT studies on the best-selected ligands to gain further insights into their electronic properties. The findings of this study provide important insights into the potential of coumarin-1,2,3-triazole hybrids as promising EGFR inhibitors for the management of lung cancer.

Review on advancements of pyranopyrazole: synthetic routes and their medicinal applications.

Pyranopyrazoles are among the most distinguished, biologically potent, and exciting scaffolds in medicinal chemistry and drug discovery. Synthesis and design of pyranopyrazoles using functional modifications via multicomponent reactions (MCRs) are thoroughly found in synthetic protocols by forming new C-C, C-N, and C-O bonds. This review aims to focus on the biological importance of pyranopyrazoles as well as on a diverse synthetic approach for their synthesis using various catalytic systems such as acid-catalyzed, base-catalyzed, ionic liquids and green media-catalyzed, nano-particle-catalyzed, metal oxide-supported catalysts, and silica-supported catalysts. In this review, we have summarized data on the advancements in synthesizing pyranopyrazole from the last two decades to the mid-2023 and research papers describing the importance of these scaffolds. This review will be significant for synthetic organic chemists and researchers working in organic chemistry.

Growth performance, meat quality and hematological parameters of broiler chickens fed safflower seed.

The aim of the current study was to determine the effects of dietary supplementation of safflower seed (SS) on the growth performance and hematological parameters of broiler birds along with the physicochemical, textural and sensory attributes of chicken meat. A total of 200 male chickens (7-days-old) were distributed into 5 groups (40 chickens in each) with 5 replicates of 8 chicks in a 42-day experiment. Each group was allocated to one of 5 dietary treatments, i.e., 0, 2.5, 5, 7.5, and 10% SS. The experimental diets were formulated for starter (7 to 21 days) and finisher (22 to 42 days) phases. Inclusion of SS in the diet improved growth performances in treatment groups between 7 and 42 days. The highest and lowest body weights were observed at the 5% SS and 0% SS levels, respectively. The physicochemical attributes of breast and thigh meat were found (P > 0.05) except for crude fat. The crude fat was significantly (P < 0.05) increased with increasing levels of SS in the diet. The inclusion of SS in the diet did not negatively impact the textural properties, i.e., hardness, cohesiveness, springiness, gumminess, chewiness, and shear force of breast and thigh meat. There was no significant difference in the sensory parameters of cooked chicken meat with increasing levels of SS in the diet. The results demonstrated a significant (P < 0.01) improvement in hematological parameters in the blood samples of broiler chickens fed diet supplemented with various levels of SS for five weeks. These findings suggest that, SS may be used as an oil seed for broiler chicken feed.

Ultralow Catalytic Loading for Optimised Electrocatalytic Performance of AuPt Nanoparticles to Produce Hydrogen and Ammonia.

The hydrogen evolution and nitrite reduction reactions are key to producing green hydrogen and ammonia. Antenna-reactor nanoparticles hold promise to improve the performances of these transformations under visible-light excitation, by combining plasmonic and catalytic materials. However, current materials involve compromising either on the catalytic activity or the plasmonic enhancement and also lack control of reaction selectivity. Here, we demonstrate that ultralow loadings and non-uniform surface segregation of the catalytic component optimize catalytic activity and selectivity under visible-light irradiation. Taking Pt-Au as an example we find that fine-tuning the Pt content produces a 6-fold increase in the hydrogen evolution compared to commercial Pt/C as well as a 6.5-fold increase in the nitrite reduction and a 2.5-fold increase in the selectivity for producing ammonia under visible light excitation relative to dark conditions. Density functional theory suggests that the catalytic reactions are accelerated by the intimate contact between nanoscale Pt-rich and Au-rich regions at the surface, which facilitates the formation of electron-rich hot-carrier puddles associated with the Pt-based active sites. The results provide exciting opportunities to design new materials with improved photocatalytic performance for sustainable energy applications.

Advanced diagnostic methods for identification of bacterial foodborne pathogens: contemporary and upcoming challenges.

It is a public health imperative to have safe food and water across the population. Foodborne infections are one of the primary causes of sickness and mortality in both developed and developing countries. An estimated 100 million foodborne diseases and 120 000 foodborne illness-related fatalities occur each year in India. Several factors affect foodborne illness, such as improper farming methods, poor sanitary and hygienic conditions at all levels of the food supply chain, the lack of preventative measures in the food processing industry, the misuse of food additives, as well as improper storage and handling. In addition, chemical and microbiological combinations also play a key role in disease development. But recent disease outbreaks indicated that microbial pathogens played a major role in the development of foodborne diseases. Therefore, prompt, rapid, and accurate detection of high-risk food pathogens is extremely vital to warrant the safety of the food items. Conventional approaches for identifying foodborne pathogens are labor-intensive and cumbersome. As a result, a range of technologies for the rapid detection of foodborne bacterial pathogens have been developed. Presently, many methods are available for the instantaneous detection, identification, and monitoring of foodborne pathogens, such as nucleic acid-based methods, biosensor-based methods, and immunological-based methods. The goal of this review is to provide a complete evaluation of several existing and emerging strategies for detecting food-borne pathogens. Furthermore, this review outlines innovative methodologies and their uses in food testing, along with their existing limits and future possibilities in the detection of live pathogens in food.

From a Collapse-Prone, Insulating Ni-MOF-74 Analogue to Crystalline, Porous, and Electrically Conducting PEDOT@MOF Composites.

Electrically conductive porous metal-organic frameworks (MOFs) show great promise in helping advance electronics and clean energy technologies. However, large porosity usually hinders long-range charge transport, an essential criterion of electrical conductivity, underscoring the need for new strategies to combine these two opposing features and realize their diverse potentials. All previous strategies to boost the conductivity of porous MOFs by introducing redox-complementary guest molecules, conducting polymers, and metal nanoparticles have led to a significant loss of frameworks' porosity and surface areas, which could be otherwise exploited to capture additional guests in electrocatalysis and chemiresistive sensing applications. Herein, we demonstrate for the first time that the in situ oxidative polymerization of preloaded 3,4-ethylenedioxythiophene (EDOT) monomers into the polyethylenedioxythiophene (PEDOT) polymer inside the hexagonal cavities of an intrinsically insulating Ni2(NDISA) MOF-74 analogue (NDISA = naphthalenediimide N,N-disalicylate), which easily collapses and becomes amorphous upon drying, simultaneously enhanced the crystallinity, porosity, and electrical conductivity of the resulting PEDOT@Ni2(NDISA) composites. At lower PEDOT loading (∼22 wt %), not only did the Brunauer-Emmett-Teller surface area of the PEDOT@Ni2(NDISA) composite (926 m2/g) more than double from that of evacuated pristine Ni2(NDISA) (387 m2/g), but also its electrical conductivity (1.1 × 10-5 S/cm) soared 105 times from that of the pristine MOF, demonstrating unprecedented dual benefits of our strategy. At higher PEDOT loading (≥33 wt %), the electrical conductivity of Ni2(NDISA)⊃PEDOT composites further increased modestly (10-4 S/cm), but their porosity dropped precipitously as large amounts of PEDOT filled up the hexagonal MOF channels. Thus, our work presents a simple new strategy to simultaneously boost the structural stability, porosity, and electrical conductivity of intrinsically insulating and collapse-prone MOFs by introducing small amounts of conducting polymers that can not only reinforce the MOF scaffolds and prevent them from collapsing but also help create a much coveted non-native property by providing charge carriers and charge transport pathways.

Quorum sensing inhibitors as Therapeutics: Bacterial biofilm inhibition.

The overuse and inappropriate use of antibiotics to treat bacterial infections has led to the development of multiple drug resistant strains. Biofilm is a complex microorganism aggregation defined by the presence of a dynamic, sticky, and protective extracellular matrix made of polysaccharides, proteins, and nucleic acids. The infectious diseases are caused by bacteria that flourish within quorum sensing (QS) mediated biofilms. Efforts to disrupt biofilms have enabled the identification of bioactive molecules produced by prokaryotes and eukaryotes. The QS system is quenched predominantly by these molecules. The phenomenon is also termed as quorum sensing (QS). Both synthetic and natural substances have been discovered to be useful in QS. This review describes natural and synthetic quorum sensing inhibitors (QSIs) with the potential to treat bacterial infections. It includes the discussion on quorum sensing, mechanism of quorum sensing, effect of substituents on the activity. These discoveries could result in effective therapies using far lower dosages of medications, particularly antibiotics, are currently needed.

Synthesis, Biological Evaluation and in Silico Study of N-(2- and 3-Pyridinyl)benzamide Derivatives as Quorum Sensing Inhibitors against Pseudomonas aeruginosa.

The effectiveness of treating bacterial infections is seriously threatened by the emergence of bacterial resistance to chemical treatment. Growth of microbes in biofilm is one of the main causes of resistance to antimicrobial drugs. Quorum sensing (QS) inhibition, which targets the QS signalling system by obstructing cell-cell communication, was developed as an alternative treatment by creating innovative anti-biofilm drugs. Therefore, the goal of this study is to develop novel antimicrobial drugs that are effective against Pseudomonas aeruginosa by inhibiting QS and acting as anti-biofilm agents. In this study, N-(2- and 3-pyridinyl)benzamide derivatives were selected to design and syntheses. Antibiofilm activity was revealed by all the synthesized compounds and the biofilm was visibly impaired, and the OD595nm readings of solubilized biofilm cells presented a momentous difference between the treated and untreated biofilms. The best anti-QS zone was observed for compound 5d and found to be 4.96 mm. Through in silico research, the physicochemical characteristics and binding manner of these produced compounds were examined. For the purpose of understanding the stability of the protein and ligand complex, molecular dynamic simulation was also carried out. The overall findings showed that N-(2- and 3-pyridinyl)benzamide derivatives could be the key to creating effective newer anti-quorum sensing drugs that are effective against different bacteria.

Synthesis, in Silico Study and Biological Evaluation of N-(Benzothiazol/Thiazol-2-yl)benzamide Derivatives as Quorum Sensing Inhibitors against Pseudomonas aeruginosa.

The development of bacterial resistance to chemical therapy poses a severe danger to efficacy of treating bacterial infections. One of the key factors for resistance to antimicrobial medications is growth of bacteria in biofilm. Quorum sensing (QS) inhibition was created as an alternative treatment by developing novel anti-biofilm medicines. Cell-cell communication is impeded by QS inhibition, which targets QS signaling pathway. The goal of this work is to develop newer drugs that are effective against Pseudomonas aeruginosa by decreasing QS and acting as anti-biofilm agents. In this investigation, N-(benzo[d]thiazol-2-yl)benzamide/N-(thiazol-2-yl)benzamide derivatives 3a-h were designed and synthesized in good yields. Further, molecular docking analyses revealed that binding affinity values were founded -11.2 to -7.6 kcal/mol that were moderate to good. The physicochemical properties of these prepared compounds were investigated through in-silico method. Molecular dynamic simulation was also used to know better understanding of stability of the protein and ligand complex. Comparing N-(benzo[d]thiazol-2-yl)benzamide 3a to salicylic acid (4.40±0.10) that was utilised as standard for quorum sensing inhibitor, the anti-QS action was found greater for N-(benzo[d]thiazol-2-yl)benzamide 3a (4.67±0.45) than salicylic acid (4.40±0.10). Overall, research results suggested that N-(benzo[d]thiazol-2-yl)benzamide/N-(thiazol-2-yl)benzamide derivatives 3a-h may hold to develop new quorum sensing inhibitors.

Crop establishment and diversification strategies for intensification of rice-based cropping systems in rice-fallow areas in Odisha.

Context or problem: In the Indian state of Odisha, rice-based system productivity is poor due to: (i) low rice yield in the monsoon (wet) season (2-4 t ha-1 compared to 6-8 t ha-1 in Punjab or Haryana); and (ii) limited cropping during the post-monsoon (dry) season (59% of the wet season rice area is left fallow in the dry season). Objective: Our study identifies strategies for increasing rice-based system productivity through: (i) alternative crop establishment methods in the wet season (Dry-Direct Seeded Rice or DSR, and mechanical puddled transplanted rice or PTR-M) to traditional methods such as broadcasting followed by post-emergence tillage (locally known as beushening) and manual random puddled transplanted rice (PTR-R); (ii) to identify rice-fallow areas suitable for pulse and oilseed cultivation in the dry season; and (iii) to evaluate the performance of short-duration pulses (green gram, Vigna radiata; black gram, Vigna mungo), and oilseeds (Brassica rapa var. toria, Helianthus annuus) in rice-fallow areas in the dry season. Methods: On-farm experiments were conducted between 2017 and 2019 in three districts of Odisha (Bhadrak, Cuttack and Mayurbhanj) to evaluate DSR compared to beushening and PTR-R; and PTR-M compared to PTR-R and manual line puddled transplanted rice (PTR-L) in the wet season. The data from Landsat-8 Operational Land Imager (OLI) and Sentinel-1satellite sensors was used to identify rice-fallow areas, and the daily SMAP (Soil Moisture Active Passive) L-band soil moisture was used for mapping suitable rice-fallow areas for growing pulses and oilseeds. Short duration crops were evaluated in suitable rice-fallow areas. Results: In the wet season, DSR (range -4 to + 53%) had a significant effect on rice yield over beushening. Similarly, PTR-M consistently increased rice yield by 16-26% over PTR-R, and by 5-23% over PTR-L. In the dry season, pulse crops (green gram and black gram) performed well compared to Indian mustard under rainfed cultivation. However, under irrigated conditions, dry-season rice yield was more productive than the rice equivalent yield of green gram, black gram and sunflower. We found that 1.03 M ha (i.e., ∼50%) of total rice-fallow areas of 2.1 M ha were suitable for growing short duration green gram and black gram in the dry season. Conclusions: We conclude that system productivity and cropping intensity can be increased by adoption of DSR and PTR-M in the wet season, and growing of green gram and black gram in the dry season. Implications: Odisha state can potentially produce an additional 0.67 million tonnes pulses if suitable rice-fallow areas are brought under green gram and black gram cultivation in the dry the season.

Assessment of Probiotic and Antioxidant Potential of Indigenous Lactobacillus Strains Isolated from Human Faecal Samples.

This study aimed to isolate and characterize probiotic Lactobacilli from human faecal samples of Jammu region of India and evaluation of their antioxidative properties. A total of 29 Lactobacillus strains were isolated and tested for their ability to withstand different pH levels, high concentrations of bile salt and lysozyme along with their adhesion ability to different hydrocarbons and auto-aggregation. Selected probiotic Lactobacillus isolates were further examined for their antioxidant potential using ABTS, DPPH methods, and the ability to scavenge superoxide and hydroxyl radicals. The results showed that Lactobacillus LpJ1 (7.93 ± 0.23) and LpJ5 (7.93 ± 0.59) had the highest cell viability at a pH of 2.5, while Lactobacillus LpJ16 (7.91 ± 0.48) had the highest resistance to bile salts. Many of the isolates also demonstrated good tolerance to lysozyme. The adhesion abilities of these isolates were characterized by cell surface hydrophobicity and auto aggregation which ranged between 50.32% to 77.8% and 51.02% to 78.95% respectively. In addition, Lactobacillus LpJ5 and LpJ8 showed excellent antioxidant activity. Based on these findings, the selected probiotic strains could be potential candidates for use in functional food to reduce oxidative stress.

Electrically Conductive π-Intercalated Graphitic Metal-Organic Framework Containing Alternate π-Donor/Acceptor Stacks.

Two-dimensional graphitic metal-organic frameworks (GMOF) often display impressive electrical conductivity chiefly due to efficient through-bond in-plane charge transport, however, less efficient out-of-plane conduction across the stacked layers creates large disparity between two orthogonal conduction pathways and dampens their bulk conductivity. To address this issue and engineer higher bulk conductivity in 2D GMOFs, we have constructed via an elegant bottom-up method the first π-intercalated GMOF (iGMOF1) featuring built-in alternate π-donor/acceptor (π-D/A) stacks of CuII -coordinated electron-rich hexaaminotriphenylene (HATP) ligands and non-coordinatively intercalated π-acidic hexacyano-triphenylene (HCTP) molecules, which facilitated out-of-plane charge transport while the hexagonal Cu3 (HATP)2 scaffold maintained in-plane conduction. As a result, iGMOF1 attained an order of magnitude higher bulk electrical conductivity and much smaller activation energy than Cu3 (HATP)2 (σ=25 vs. 2 S m-1 , Ea =36 vs. 65 meV), demostrating that simultaneous in-plane (through-bond) and out-of-plane (through πD/A stacks) charge transport can generate higher electrical conductivity in novel iGMOFs.

Insight of oral vaccines as an alternative approach to health and disease management: An innovative intuition and challenges.

Vaccination is the most suitable and persuasive healthcare program for the prohibition of various deadly diseases. However, the higher production cost and purification strategies are out of reach for the developing nations. In this scenario, development of edible vaccine turns out to be the most promising alternative for remodeling the pharmaceutical industry with reduced production and purification costs. Generally, oral route of vaccination is mostly preferred due to its safety, compliance, low manufacturing cost and most importantly the ability to induce immunity in both systemic and mucosal sites. Genetically modified microorganisms and plants could efficiently be used as vehicles for edible vaccines. Edible vaccines are supposed to reduce the risk associated with traditional vaccines. Currently, oral vaccines are available in the market for several viral and bacterial diseases like cholera, hepatitis B, malaria, rabies etc. Herein, the review focuses on the breakthrough events in the area of edible vaccines associated with dietary microbes and plants for better control over diseases.

Himalayan Microbiomes for Agro-environmental Sustainability: Current Perspectives and Future Challenges.

The Himalayas are one of the most mystical, yet least studied terrains of the world. One of Earth's greatest multifaceted and diverse montane ecosystems is also one of the thirty-four global biodiversity hotspots of the world. These are supposed to have been uplifted about 60-70 million years ago and support, distinct environments, physiography, a variety of orogeny, and great biological diversity (plants, animals, and microbes). Microbes are the pioneer colonizer of the Himalayas that are involved in various bio-geological cycles and play various significant roles. The applications of Himalayan microbiomes inhabiting in lesser to greater Himalayas have been recognized. The researchers explored the applications of indigenous microbiomes in both agricultural and environmental sectors. In agriculture, microbiomes from Himalayan regions have been suggested as better biofertilizers and biopesticides for the crops growing at low temperature and mountainous areas as they help in the alleviation of cold stress and other biotic stresses. Along with alleviation of low temperature, Himalayan microbes also have the capability to enhance plant growth by availing the soluble form of nutrients like nitrogen, phosphorus, potassium, zinc, and iron. These microbes have been recognized for producing plant growth regulators (abscisic acid, auxin, cytokinin, ethylene, and gibberellins). These microbes have been reported for bioremediating the diverse pollutants (pesticides, heavy metals, and xenobiotics) for environmental sustainability. In the current perspectives, present review provides a detailed discussion on the ecology, biodiversity, and adaptive features of the native Himalayan microbiomes in view to achieve agro-environmental sustainability.

Probiotics as a biotherapeutics for the management and prevention of respiratory tract diseases.

Respiratory diseases are responsible for a greater mortality rate around the world. Viral or bacterial infections in the respiratory tract have been identified as major causative agents for death and disability among the population. Respiratory tract infections (RTIs) cause severe respiratory ailments starting from coldlike symptoms, eventually affecting the lungs and other viscera, and are mainly categorized into two types depending on the affected area: upper RTIs and lower RTIs. Respiratory viruses belong to several viral families such as influenza virus, enterovirus, adenovirus, respiratory syncytial virus, and recently severe acute respiratory syndrome coronavirus 2. Studies have indicated that people with good immune functions are less prone to respiratory infections and also their recovery rate is quicker. Innate and acquired immune systems actively participate in the recognition and elimination of the pathogenic agents. In the present context, the potential of probiotics is recognized as viable microorganisms that support the balance of the beneficial microbial population in the gastrointestinal tract and promote host immunity. The probiotics have long been known to regulate bodily immune functions and have been used against general RTIs such as cough, pharyngitis, laryngitis, pneumonia, and asthma. In addition, intervention with probiotics could directly affect the composition of the gut microbiota that have been shown to palliate respiratory diseases by modulating pulmonary immune activities through the gut-lung axis, and therefore, probiotics could become an alternative therapeutic approach for RTIs.

Structural modification aimed for improving solubility of lead compounds in early phase drug discovery.

Many lead compounds fail to reach clinical trials despite being potent because of low bioavailability attributed to their insufficient solubility making solubility a primary and crucial factor in early phase drug discovery. Solubility improvement of poorly soluble lead compounds without losing potency is a challenging task for the medicinal chemist in a drug discovery setup. Solubility is an important factor not only to dissipate or liquefy a substance but also to attain an optimal concentration of drug in systemic circulation required for the desired therapeutic effect. It has been estimated that more than forty percent of newly developed molecules are practically insoluble in water. Molecules with poor solubility not only cause difficulty for in vitro and in vivo assays but also add significant burdens to drug development in the form of longer time taken and increased cost to optimize the solubility. To tackle this problem, different techniques are being used such as physical, chemical, and miscellaneous methods to enhance solubility. Among them, the medicinal chemistry approach focussed on structural modification is a versatile and unique approach in way that it can also improve other pharmacokinetic/physicochemical parameters simultaneously. In this review, we have begun with brief introduction of solubility and its role followed by recent successful examples of different structural modification tactics reported in the literature including synthesis of prodrugs, hydrophilic and ionizable group insertion, addition & removal of hydrogen bonding, bioisosterism, disruption of molecular symmetry and planarity. Moreover, we have included a section on the obstacles in the solubility optimization and also summarised different in silico tools with potential application in solubility prediction. Overall, this review encompasses various successfully used solubility optimization examples using structure modification.

Phase evolution in thermally annealed Ni/Bi multilayers studied by X-ray absorption spectroscopy.

The thin films of Ni and Bi are known to form NiBi3 and NiBi compounds spontaneously at the interface, which become superconducting below 4.2 K and show ferromagnetism either intrinsically or due to Ni impurities. Formation of NiBi3 and NiBi is a slow diffusion reaction, which means the local environment around Ni and Bi atoms may vary with time and temperature. In this report, we assess the feasibility of using X-ray Absorption Spectroscopy (XAS) as a tool to track the changes in local bonding environment in NiBi3 and NiBi. Thermal annealing at temperatures up to 500 °C was used to induce changes in the local environment in NiBi3 system. Consequent decomposition of NiBi3 into NiO and Bi has been tracked through changes in structural and magnetization behavior, which matched well with the findings of XAS. In addition, the magnetic hysteresis measurements indicated that NiO should be the dominant phase when NiBi3 is annealed at 500 °C. This was corroborated from XAS and was found to be >90%. The shift in K-edge of Ni in annealed samples was attributed to increasing charge state on Ni atom, which was ascertained by Bader charge analysis using Density Functional Theory (DFT). This study correlating macroscopic properties of NiBi3 with local bonding environment of the system indicates that XAS can be a very reliable tool for studying dynamics of diffusion in the NiBi3 system.

Minerals solubilizing and mobilizing microbiomes: A sustainable approach for managing minerals' deficiency in agricultural soil.

Agriculture faces challenges to fulfil the rising food demand due to shortage of arable land and various environmental stressors. Traditional farming technologies help in fulfilling food demand but they are harmful to humans and environmental sustainability. The food production along with agro-environmental sustainability could be achieved by encouraging farmers to use agro-environmental sustainable products such as biofertilizers and biopesticides consisting of live microbes or plant extract instead of chemical-based inputs. The eco-friendly formulations play a significant role in plant growth promotion, crop yield and repairing degraded soil texture and fertility sustainably. Mineral solubilizing microbes that provide vital nutrients like phosphorus, potassium, zinc and selenium are essential for plant growth and development and could be developed as biofertilizers. These microbes could be plant associated (rhizospheric, endophytic and phyllospheric) or inhabit the bulk soil and diverse extreme habitats. Mineral solubilizing microbes from soil, extreme environments, surface and internal parts of the plant belong to diverse phyla such as Ascomycota, Actinobacteria, Basidiomycota, Bacteroidetes, Chlorobi, Cyanobacteria, Chlorophyta, Euryarchaeota, Firmicutes, Gemmatimonadetes, Mucoromycota, Proteobacteria and Tenericutes. Mineral solubilizing microbes (MSMs) directly or indirectly stimulate plant growth and development either by releasing plant growth regulators; solubilizing phosphorus, potassium, zinc, selenium and silicon; biological nitrogen fixation and production of siderophores, ammonia, hydrogen cyanide, hydrolytic enzymes and bioactive compound/secondary metabolites. Biofertilizer developed using mineral solubilizing microbes is an eco-friendly solution to the sustainable food production system in many countries worldwide. The present review deals with the biodiversity of mineral solubilizing microbes, and potential roles in crop improvement and soil well-being for agricultural sustainability.