Recent Development of Electrolytes for Aqueous Organic Redox Flow Batteries (Aorfbs): Current Status, Challenges, and Prospects.

In recent years, aqueous organic redox flow batteries (AORFBs) have attracted considerable attention due to advancements in grid-level energy storage capacity research. These batteries offer remarkable benefits, including outstanding capacity retention, excellent cell performance, high energy density, and cost-effectiveness. The organic electrolytes in AORFBs exhibit adjustable redox potentials and tunable solubilities in water. Previously, various types of organic electrolytes, such as quinones, organometallic complexes, viologens, redox-active polymers, and organic salts, were extensively investigated for their electrochemical performance and stability. This study presents an overview of recently published novel organic electrolytes for AORFBs in acidic, alkaline, and neutral environments. Furthermore, it delves into the current status, challenges, and prospects of AORFBs, highlighting different strategies to overcome these challenges, with special emphasis placed on their design, composition, functionalities, and cost. A brief techno-economic analysis of various aqueous RFBs is also outlined, considering their potential scalability and integration with renewable energy systems.

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.

An SNP based genotyping assay for genes associated with drought tolerance in bread wheat.

BACKGROUND: SnRK2 plays vital role in responding to adverse abiotic stimuli. The applicability of TaSnRK2.4 and TaSnRK2.9 was investigated to leverage the potential of these genes in indigenous wheat breeding programs. METHODS: Genetic diversity was assessed using pre-existing markers for TaSnRK2.4 and TaSnRK2.9. Furthermore, new markers were also developed to enhance their broader applicability. KASP markers were designed for TaSnRK2.4, while CAPS-based markers were tailored for TaSnRK2.9. RESULTS: Analysis revealed lack of polymorphism in TaSnRK2.4 among Pakistani wheat germplasm under study. To validate this finding, available gel-based markers for TaSnRK2.4 were employed, producing consistent results and offering limited potential for application in marker-assisted wheat breeding with Pakistani wheat material. For TaSnRK2.9-5A, CAPS2.9-5A-1 and CAPS2.9-5A-2 markers were designed to target SNP positions at 308 nt and 1700 nt revealing four distinct haplotypes. Association analysis highlighted the significance of Hap-5A-1 of TaSnRK2.9-5A, which exhibited association with an increased number of productive tillers (NPT), grains per spike (GPS), and reduced plant height (PH) under well-watered (WW) conditions. Moreover, it showed positive influence on NPT under WW conditions, GPS under water-limited (WL) conditions, and PH under both WW and WL conditions. High selection intensity observed for Hap-5A-1 underscores the valuable role it has played in Pakistani wheat breeding programs. Gene expression studies of TaSnRK2.9-5A revealed the involvement of this gene in response to PEG, NaCl, low temperature and ABA treatments. CONCLUSION: These findings propose that TaSnRK2.9 can be effectively employed for improving wheat through marker-assisted selection in wheat breeding efforts.

Benign-by-design plant extract-mediated preparation of copper oxide nanoparticles for environmentally related applications.

A facile, cost-competitive, scalable and novel synthetic approach is used to prepare copper oxide (CuO) nanoparticles (NPs) using Betel leaf (Piper betle) extracts as reducing, capping, and stabilizing agents. CuO-NPs were characterized using various analytical techniques, including Fourier-transform infrared (FTIR) spectroscopy, ultraviolet-visible (UV-Vis) spectroscopy, scanning electron microscopy (SEM), X-ray diffraction (XRD), high-resolution transmission electron microscopy (HRTEM), as well as photoluminescence (PL) measurements. The activity of CuO-NPs was investigated towards Congo red dye degradation, supercapacitor energy storage and antibacterial activity. A maximum of 89% photodegradation of Congo red dye (CR) was obtained. The nanoparticle modified electrode also exhibited a specific capacitance (Csp) of 179 Fg-1. Furthermore, the antibacterial potential of CuO NPs was evaluated against Bacillus subtilis and Pseudomonas aeruginosa, both strains displaying high antibacterial performance.

Green synthesis of ZnO nanocubes from Ceropegia omissa H. Huber extract for photocatalytic degradation of bisphenol An under visible light to mitigate water pollution.

Plastic pollution has become a major environmental problem because it does not break down and poses risks to ecosystems and human health. This study focuses on the environmentally friendly synthesis of ZnO nanocubes using an extract from Ceropegia omissa H. Huber plant leaves. The primary goal is to investigate the viability of these nanocubes as visible-light photocatalysts for the degradation of bisphenol A (BPA). The synthesized ZnO nanocubes have a highly crystalline structure and a bandgap of 3.1 eV, making them suitable for effective visible-light photocatalysis. FTIR analysis, which demonstrates that the pertinent functional groups are present, demonstrates the chemical bonding and reducing processes that take place in the plant extract. The XPS method also studies zinc metals, oxygen valencies, and binding energies. Under visible light irradiation, ZnO nanocubes degrade BPA by 86% in 30 min. This plant-extract-based green synthesis method provides a long-term replacement for traditional procedures, and visible light photocatalysis has advantages over ultraviolet light. The study's results show that ZnO nanocubes may be good for the environment and can work well as visible light photocatalysts to break down organic pollutants. This adds to what is known about using nanoparticles to clean up the environment. As a result, this study highlights the potential of using environmentally friendly ZnO nanocubes as a long-lasting and efficient method of reducing organic pollutant contamination in aquatic environments.

Green synthesis of tellurium-doped SnO2 nanoparticles with sulfurized g-C3 N4 : Insights into methylene blue photodegradation and antibacterial capability.

The construction of SnO2 nanoparticles (NPs), specifically Te-doped SnO2 NPs, using a simple and economical co-precipitation technique has been thoroughly described in this work. NH3 served as the reducing agent in this procedure, whilst polyethylene glycol served as the capping agent. The primary goals of our work were to investigate the physicochemical properties of the synthesized SnO2 NPs and assess their potential use as antibacterial agents and photocatalysts. Scanning electron microscopy-energy dispersive X-ray, ultraviolet light, Fourier transform infrared spectroscopy, X-ray diffraction (XRD), and other analytical techniques were used to thoroughly analyze the NPs. Based on the full width at half maximum of the most noticeable peaks in the XRD spectrum, the Debye-Scherrer equation was used to calculate the crystallite sizes, which indicated the presence of a single tetragonal SnO2 phase. Particularly noteworthy was the exceptional photocatalytic activity of graphene-assisted Te-doped SnO2 NPs, achieving an impressive decomposition efficiency of up to 98% in the photo-oxidation of methylene blue. Furthermore, our investigation delved into the antibacterial attributes of the synthesized SnO2 NPs against Escherichia coli and Staphylococcus aureus, demonstrating inhibitory effects on both bacteria strains. This suggests potential applications for these NPs in various environmental and medical contexts.

The key to sustainability: In-depth investigation of environmental quality in G20 countries through the lens of renewable energy, economic complexity and geopolitical risk resilience.

The world is currently facing urgent climate and environmental issues, such as global warming, ecosystem collapse, and energy shortages. In this context, this study selected data from 2000 to 2021 and employed the Method of Moment Quantile Regression (MMQR) to thoroughly investigate the impact of renewable energy consumption, economic complexity, and geopolitical risks on the ecological footprint of the Group of Twenty (G20) countries. The results indicate that in countries with lower quantiles, renewable energy consumption significantly reduces the ecological footprint, whereas its effect is not prominent in countries with higher quantiles. Economic complexity has a negative impact on the ecological footprint, and this impact becomes stronger as the quantile of the ecological footprint rises. Additionally, economic complexity moderates the effect of renewable energy on the ecological footprint. Geopolitical risks facilitate the growth of the ecological footprint. Likewise, robustness tests such as DOLS, FMOLS, and quantile regression confirm these estimates in the same framework. This study has conducted a profound analysis of global environmental issues, offering innovative perspectives and recommendations for achieving goals related to sustainable energy utilization, mitigating climate change, and improving the ecological environment. The findings of this research will guide policymakers in G20 countries to adopt more effective environmental protection measures, thereby contributing to the construction of a sustainable future.

2-{N-[(2,4,5-trichlorophenoxy) acetyl]-N-methylamino}-3-pyrrolidinepropanamide analogs as potential antagonists of Urotensin II receptor.

THE PURPOSE OF THE ARTICLE: To identify novel small molecule antagonists of Urotensin II receptor with acceptable pharmacological profile. MATERIALS AND METHODS: Structure-activity-relationship (SAR) studies on 2-{N-[(2,4,5-trichlorophenoxy) acetyl]-N-methylamino}-3-pyrrolidinepropanamide series were conducted and shortlisted compounds were synthesized and evaluated in in vitro cell-based assays. Human and mouse Urotensin II receptor overexpressing CHO cells were used for calcium release and radioligand binding assays. Initial molecules in this series had solubility and inter-species variability issue in the calcium release assay. We, therefore, conducted SAR to overcome these 2 issues and molecules with accepted in vitro profile were evaluated further in mouse pressor response model to generate the in vivo proof of concept for UII receptor antagonization. RESULTS AND CONCLUSIONS: We report herewith identification of 2-{N-[(2,4,5-trichlorophenoxy)acetyl]-N-methylamino}-3-pyrrolidinepropanamides series to obtain novel small molecule antagonists of Urotensin II receptor with acceptable pharmacological profile.

Structural Diversity, Spectral Data, and Pharmacological Effects of Genus Nigella.

Nigella is one of the most studied plants because of its pharmacological properties like anti-parasitic, anti-inflammatory, neuro-protective, hepatoprotective, and anti-cancerous. In this study, about 20 species of the genus Nigella were reviewed and among them, N. damascene, N. glandulifera, and N. sativa are widely studied for their phytochemical and pharmacological effects. This review describes the phytochemical composition of the genus Nigella, which constitutes many of the compounds including alkaloids, flavonoids, saponins, and terpenoids. The extracts produced by using different solvents and the isolated compounds displayed a wide range of biological activity. These compounds were identified by different spectral techniques. The spectral detail of some advanced techniques including EIS-MS, UV/VIS, IR, 13 C-NMR, and 1 H-NMR of some important phytoconstituents of Nigella spp. has been compiled for the first time in this review which will be helpful to explore and further investigate the chemical composition of this genus.

At Least 10-fold Higher Lubricity of Molecularly Thin D2O vs H2O Films at Single-Layer Graphene-Mica Interfaces.

Interfacial water is a widespread lubricant down to the nanometer scale. We investigate the lubricities of molecularly thin H2O and D2O films confined between mica and graphene, via the relaxation of initially applied strain in graphene employing Raman spectroscopy. Surprisingly, the D2O films are at least 1 order of magnitude more lubricant than H2O films, despite the similar bulk viscosities of the two liquids. We propose a mechanism based on the known selective permeation of protons vs deuterons through graphene. Permeated protons and left behind hydroxides may form ion pairs clamping across the graphene sheet and thereby hindering the graphene from sliding on the water layer. This explains the lower lubricity but also the hindering diffusivity of the water layer, which yields a high effective viscosity in accordance with findings in dewetting experiments. Our work elucidates an unexpected effect and provides clues to the behavior of graphene on hydrous surfaces.

Recent advancements in engineered biopolymeric-nanohybrids: A greener approach for adsorptive-remediation of noxious metals from aqueous matrices.

Industrial wastewater is causing serious health problems due to presence of large concentrations of toxic metals. Removal of these metals is still a big challenge using pristine natural biopolymers due to their low surface area, water solubility, and poor recovery. Developing biopolymeric composites with other materials has attained attention because they possess a high surface area and structural porosity, high reactivity, and less water solubility. In simple words, biopolymeric nanohybrids have great adsorption capacity for heavy metals. Biopolymeric materials are abundant, low cost, biodegradable, and possess different functional moieties (carboxyl, amine, hydroxyl, and carbonyl) which play a vital role to adsorb metal ions through various inter-linkages (i.e., electrostatic, hydrogen bonding, ion exchange, chelation, etc.). Biopolymeric nanohybrids have been proven a potent tool in environmental remediation such as the abatement of heavy metal ions from polluted water. Herein, we have reported the adsorption potential of various biopolymers (cellulose, chitosan, pectin, gelatin, and silk proteins) for the removal of heavy metals. This review discusses the suitability of biopolymeric nanohybrids as an adsorbent for heavy metals, their synthesis, modification, adsorption potential, and adsorption mechanism along with best fitted thermodynamic and kinetic models. The influence of pH, contact time, and adsorbent dose on adsorption potential has also been discussed in detail. Lastly, the challenges, research gaps and recommendations have been presented. This review concludes that biopolymers in combination with other materials such as metal-based nanoparticles, clay, and carbon-based materials are excellent materials to remove metallic ions from wastewater. Significant adsorption of heavy metals was obtained at a moderate pH (5-6). Contact time and adsorbent dose also affect the adsorption of heavy metals in certain ways. The Pseudo-first order model fits the data for the initial period of the first step of the reaction. Kinetic studies of different adsorption processes of various biopolymeric nanohybrids described that for majority of bionanohybrids, Pseudo-second order fitted the experimental data very well. Functionalized biopolymeric nanohybrids being biodegradable, environment friendly, cost-effective materials have great potential to adsorb heavy metal ions. These may be the future materials for environmental remediation.

First report of Fusarium equiseti causing leaf spots of Bitter gourd (Momordica charantia) in Pakistan.

Bitter gourd (Momordica charantia L.) is an important vegetable crop of the Cucurbitaceae family widely cultivated in Pakistan and around the world. In October 2020, a nutrition management trial of Bitter gourd cv. Seminis-200) was conducted on an area of 10,860 sq. ft. (99×110 feet) at the Agricultural Research farm of Bahauddin Zakariya University, Multan (30.2601° N, 71.5158° E), Pakistan. Symptoms of large, brown necrotic leaf spots were observed on the leaves of bitter gourd vines. The disease started from the yellowing of leaves within the reticulate venation and turned brown. Irregular brown leaf spots coalesced to form large necrotic areas followed by foliar chlorosis then wilting that occurred very late. There were no crown rot symptoms although there was slight discoloration of roots and when cut longitudinally, browning of tissues was observed. The disease was assessed visually with 37% incidence which resulted in poor quality and yield in terms of reduced size and yellowing of fruit. Infected vines along with the roots were collected for the isolation of pathogen. A total of 34 leaves and 22 root samples were collected from the field for isolation. The leaf, collar and root portions were cut into 0.5 to 1 cm in length and surface disinfected with 1% sodium hypochlorite (NaOCl) for 2-3 minutes followed by washing twice with autoclaved distilled water and after drying, placed on potato dextrose agar (PDA) medium, and incubated at 25±2 °C for one week. The fungal colonies of fluffy white growth with light orange pigment were isolated. For morphological characterization, a total of 4 pure cultures were isolated from leaves, collar region and root by single spore technique on carnation leaf agar (CLA) medium after 15 days of incubation at 25±2℃. Curved and thick-walled macroconidia with elongated or pointed apical characteristic foot-shaped basal cells were produced in sporodochia. Macroconidia with 5-7 septa measured 22.50-41.80 µm × 2.90-4.20 µm (n = 60). Thick, brown with roughened walls and subglobose ellipsoidal chlamydospores were observed in clumps or chains with the dimension of 5.8 to 10.8 µm (n = 20). On morphological characteristics, the fungus was identified as Fusarium equiseti (Corda) Sacc. according to Leslie and Summerell (2006). Two single spore isolates were used for molecular identification by amplifying ribosomal DNA of the internal transcribed spacer (ITS) region with ITS1/ITS4 primers (White et al. 1990) and for ß-tubulin gene region, primers T1/Bt-2b (O'Donnell and Cigelnik, 1997) were used. The obtained sequences were deposited in GenBank with accession numbers MW880179 and MW880198 from the ITS region and BLAST search in GenBank showed 100 and 98.11% alignment with previously published sequences of F. equiseti with accessions OM992323.1and MT558569.1 respectively. Accession number OM867571from the ß-tubulin region showed 100% sequence similarity with F. equiseti with accession MN653163.1. For pathogenicity, macroconidia from 2-week-old cultures on CLA medium were harvested to prepare spore suspension (1 × 106 conidia/ml). Koch's postulates were confirmed on nine bitter gourd plants (cv. Seminis-200) by applying spore suspension of fungal inoculum at 3-4 leaf stage separately on leaves by automizer, on collar region after making incision spore suspension was applied and in the root zone, 20ml spore suspension was added whereas distilled water was used as a control with three replications. Plants were kept under controlled conditions in the greenhouse with 65% to 75% humidity and the temperature was maintained at 32±2 °C for one week. After 7-8 days, inoculated plants began to exhibit symptoms of brown, necrotic leaf spots on the leaves of bitter gourd vines followed by yellowing of leaves that eventually turned brown. Roots showed slight discoloration and browning of vascular bundles and finally, the plants wilted after four weeks. while control plants remained symptomless. The symptoms resembled those noticed in the field. The fungus was re-isolated from leaves, collar region and roots, followed by morphological identification, and finally confirmed as F. equiseti. To the best of our knowledge, this is the first report of a leaf spot caused by F. equiseti in a bitter gourd from Pakistan. If the disease is not managed properly, it may cause a drastic effect on yield under favorable environmental conditions. The pathogen may also damage other cucurbitaceous crops cultivated in the area.

A Novel Design and Development of a Strip-Fed Circularly Polarized Rectangular Dielectric Resonator Antenna for 5G NR Sub-6 GHz Band Applications.

In this article, a rectangular dielectric resonator antenna (RDRA) with circularly polarized (CP) response is presented for 5G NR (New Radio) Sub-6 GHz band applications. A uniquely shaped conformal metal feeding strip is proposed to excite the RDRA in higher-order mode for high gain utilization. By using the proposed feeding mechanism, the degenerate mode pair of the first higher-order, i.e., TEδ13x at 4.13 GHz and TE1δ3y, at 4.52 GHz is excited to achieve a circularly polarized response. A circular polarization over a bandwidth of ~10%, in conjunction with a wide impedance matching over a bandwidth of ~17%, were attained by the antenna. The CP antenna proposed offers a useful gain of ~6.2 dBic. The achieved CP bandwidth of the RDRA is good enough to cover the targeted 5G NR bands around 4.4−4.8 GHz, such as n79. The proposed antenna configuration is modelled and optimized using computer simulation technology (CST). A prototype was built to confirm (validate) the performance estimated through simulation. A good agreement was observed between simulated and measured results.

Asymmetric impact of temperature on COVID-19 spread in India: Evidence from quantile-on-quantile regression approach.

The emergence of new coronavirus (SARS-CoV-2) has become a significant public health issue worldwide. Some researchers have identified a positive link between temperature and COVID-19 cases. However, no detailed research has highlighted the impact of temperature on COVID-19 spread in India. This study aims to fill this research gap by investigating the impact of temperature on COVID-19 spread in the five most affected Indian states. Quantile-on-Quantile regression (QQR) approach is employed to examine in what manner the quantiles of temperature influence the quantiles of COVID-19 cases. Empirical results confirm an asymmetric and heterogenous impact of temperature on COVID-19 spread across lower and higher quantiles of both variables. The results indicate a significant positive impact of temperature on COVID-19 spread in the three Indian states (Maharashtra, Andhra Pradesh, and Karnataka), predominantly in both low and high quantiles. Whereas, the other two states (Tamil Nadu and Uttar Pradesh) exhibit a mixed trend, as the lower quantiles in both states have a negative effect. However, this negative effect becomes weak at middle and higher quantiles. These research findings offer valuable policy recommendations.

Neurally Adjusted Ventilatory Assist: An Early Clue to Diagnosis of Congenital Central Hypoventilation Syndrome.

Congenital central hypoventilation syndrome (CCHS) is characterized by shallow breathing during sleep due to negligible ventilatory sensitivity to hypercarbia and hypoxemia. It is diagnosed using a genetic test for PHOX2B mutation, which is not easily available. Neurally adjusted ventilatory assist (NAVA) is a spontaneous ventilatory mode that was designed basically for better adapting the ventilator to the patient by using electrical activity of diaphragm (EAdi) signals. We report a case of a 6-month-old infant who presented with recurrent apneas, where differential decrease in EAdi discharges during sleep using NAVA served as an early clue to the diagnosis of CCHS. Definitive diagnosis was later confirmed by genetic testing. HOW TO CITE THIS ARTICLE: Rauf A, Gupta D, Sachdev A, Gupta N, Gupta S, Kumar P, et al. Neurally Adjusted Ventilatory Assist: An Early Clue to Diagnosis of Congenital Central Hypoventilation Syndrome. IJCCM 2019;23(11):536-537.

Non-monotonous Wetting of Graphene-Mica and MoS2-Mica Interfaces with a Molecular Layer of Water.

Hydration of interfaces with a layer of water is a ubiquitous phenomenon, which has important implications for numerous natural and technologically important processes. Nevertheless, at the nanoscale, the understanding of the wetting process is still limited, since it is experimentally difficult to follow. Here, graphene and monolayers of MoS2 deposited on dry mica are used to investigate wetting of the two-dimensional (2D) material-mica interfaces with a molecularly thin layer of water employing scanning force microscopy in different modes. Wetting occurs non-monotonously in time and space for both types of interfaces. It starts at relative humidities (RH) of 10-17% for graphenes and 8-9% for MoS2 and concludes with a homogeneous layer at 25-30 and 15-20%, respectively. Investigation of the process at the graphene-mica interface indicates that up to about 25% RH, initially a highly compliant and unstable layer of water spreads, which subsequently stabilizes by developing labyrinthine nanostructures. Moreover, these nanostructures exhibit distinct mechanical deformability and dissipation, which is ascribed to different densities of the confined water layer. The laterally structured morphology is explained by the interplay of counteracting long-range dipole-dipole repulsion and short-range line tension, with the latter causing at least in part by the mechanical deformation of the 2D material. The proposed origins of the interactions are common for thin layers of polar molecules at interfaces, implying that the lateral structuring of thin wetting layers at submonolayer concentrations may also be a quite general phenomenon.

Synthesis and evaluation of thiomannosides, potent and orally active FimH inhibitors.

FimH is a type I fimbrial lectin located at the tip of type-1 pili of Gram-negative uropathogenic Escherichia coli (UPEC) guiding its ability to adhere and infect urothelial cells. Accordingly, blocking FimH with small molecule inhibitor is considered as a promising new therapeutic alternative to treat urinary tract infections caused by UPEC. Herein, we report that compounds having the S-glycosidic bond (thiomannosides) had improved metabolic stability and plasma exposures when dosed orally. Especially compound 5h showed the potential to inhibit biofilm formation and also to disrupt the preformed biofilm. And compound 5h showed prophylactic effect in UTI model in mice.

Differential Effects of Escherichia coli Nissle and Lactobacillus rhamnosus Strain GG on Human Rotavirus Binding, Infection, and B Cell Immunity.

Rotavirus (RV) causes significant morbidity and mortality in children worldwide. The intestinal microbiota plays an important role in modulating host-pathogen interactions, but little is known about the impact of commonly used probiotics on human RV (HRV) infection. In this study, we compared the immunomodulatory effects of Gram-positive (Lactobacillus rhamnosus strain GG [LGG]) and Gram-negative (Escherichia coli Nissle [EcN]) probiotic bacteria on virulent human rotavirus (VirHRV) infection and immunity using neonatal gnotobiotic piglets. Gnotobiotic piglets were colonized with EcN, LGG, or EcN+LGG or uncolonized and challenged with VirHRV. Mean peak virus shedding titers and mean cumulative fecal scores were significantly lower in EcN-colonized compared with LGG-colonized or uncolonized piglets. Reduced viral shedding titers were correlated with significantly reduced small intestinal HRV IgA Ab responses in EcN-colonized compared with uncolonized piglets post-VirHRV challenge. However the total IgA levels post-VirHRV challenge in the intestine and pre-VirHRV challenge in serum were significantly higher in EcN-colonized than in LGG-colonized piglets. In vitro treatment of mononuclear cells with these probiotics demonstrated that EcN, but not LGG, induced IL-6, IL-10, and IgA, with the latter partially dependent on IL-10. However, addition of exogenous recombinant porcine IL-10 + IL-6 to mononuclear cells cocultured with LGG significantly enhanced IgA responses. The greater effectiveness of EcN in moderating HRV infection may also be explained by the binding of EcN but not LGG to Wa HRV particles or HRV 2/4/6 virus-like particles but not 2/6 virus-like particles. Results suggest that EcN and LGG differentially modulate RV infection and B cell responses.

Escherichia coli Nissle 1917 protects gnotobiotic pigs against human rotavirus by modulating pDC and NK-cell responses.

Lactobacillus rhamnosus GG (LGG), a gram-positive lactic acid bacterium, is one of the most widely used probiotics; while fewer gram-negative probiotics including Escherichia coli Nissle 1917 (EcN) are characterized. A mechanistic understanding of their individual and interactive effects on human rotavirus (HRV) and immunity is lacking. In this study, noncolonized, EcN-, LGG-, and EcN + LGG-colonized neonatal gnotobiotic (Gn) pigs were challenged with HRV. EcN colonization is associated with a greater protection against HRV, and induces the highest frequencies of plasmacytoid dendritic cells (pDCs), significantly increased NK-cell function and decreased frequencies of apoptotic and TLR4+ mononuclear cells (MNCs). Consistent with the highest NK-cell activity, splenic CD172+ MNCs (DC enriched fraction) of EcN-colonized pigs produced the highest levels of IL-12 in vitro. LGG colonization has little effect on the above parameters, which are intermediate in EcN + LGG-colonized pigs, suggesting that probiotics modulate each other's effects. Additionally, in vitro EcN-treated splenic or intestinal MNCs produce higher levels of innate, immunoregulatory and immunostimulatory cytokines, IFN-α, IL-12, and IL-10, compared to MNCs of pigs treated with LGG. These results indicate that the EcN-mediated greater protection against HRV is associated with potent stimulation of the innate immune system and activation of the DC-IL-12-NK immune axis.

Comparative In Vitro and In Vivo Studies of Porcine Rotavirus G9P[13] and Human Rotavirus Wa G1P[8].

UNLABELLED: The changing epidemiology of group A rotavirus (RV) strains in humans and swine, including emerging G9 strains, poses new challenges to current vaccines. In this study, we comparatively assessed the pathogenesis of porcine RV (PRV) G9P[13] and evaluated the short-term cross-protection between this strain and human RV (HRV) Wa G1P[8] in gnotobiotic pigs. Complete genome sequencing demonstrated that PRV G9P[13] possessed a human-like G9 VP7 genotype but shared higher overall nucleotide identity with historic PRV strains. PRV G9P[13] induced longer rectal virus shedding and RV RNAemia in pigs than HRV Wa G1P[8] and generated complete short-term cross-protection in pigs challenged with HRV or PRV, whereas HRV Wa G1P[8] induced only partial protection against PRV challenge. Moreover, PRV G9P[13] replicated more extensively in porcine monocyte-derived dendritic cells (MoDCs) than did HRV Wa G1P[8]. Cross-protection was likely not dependent on serum virus-neutralizing (VN) antibodies, as the heterologous VN antibody titers in the sera of G9P[13]-inoculated pigs were low. Thus, our results suggest that heterologous protection by the current monovalent G1P[8] HRV vaccine against emerging G9 strains should be evaluated in clinical and experimental studies to prevent further dissemination of G9 strains. Differences in the pathogenesis of these two strains may be partially attributable to their variable abilities to replicate and persist in porcine immune cells, including dendritic cells (DCs). Additional studies are needed to evaluate the emerging G9 strains as potential vaccine candidates and to test the susceptibility of various immune cells to infection by G9 and other common HRV/PRV genotypes. IMPORTANCE: The changing epidemiology of porcine and human group A rotaviruses (RVs), including emerging G9 strains, may compromise the efficacy of current vaccines. An understanding of the pathogenesis and genetic, immunological, and biological features of the new emerging RV strains will contribute to the development of new surveillance and prevention tools. Additionally, studies of cross-protection between the newly identified emerging G9 porcine RV strains and a human G1 RV vaccine strain in a susceptible host (swine) will allow evaluation of G9 strains as potential novel vaccine candidates to be included in porcine or human vaccines.