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The immunogenicity of subunit vaccines can be augmented by formulating them into nanoparticles. We conjugated recombinant trimetric influenza A/Aichi/2/68(H3N2) hemagglutinin (HA) onto functionalized gold nanoparticle (AuNP) surfaces in a repetitive, oriented configuration. To further improve the immunogenicity, we generated Toll-like receptor 5 (TLR5) agonist flagellin (FliC)-coupled AuNPs as particulate adjuvants. Intranasal immunizations with an AuNP-HA and AuNP-FliC particle mixture elicited strong mucosal and systemic immune responses that protected hosts against lethal influenza challenges. Compared with the AuNP-HA alone group, the addition of AuNP-FliC improved mucosal B cell responses as characterized by elevated influenza specific IgA and IgG levels in nasal, tracheal, and lung washes. AuNP-HA/AuNP-FliC also stimulated antigen-specific interferon-γ (IFN-γ)-secreting CD4 + cell proliferation and induced strong effector CD8 + T cell activation. Our results indicate that intranasal co-delivery of antigen and adjuvant-displaying AuNPs enhanced vaccine efficacy by inducing potent cellular immune responses. [ABSTRACT FROM AUTHOR]

Recurring influenza viruses pose an annual threat to public health. A time-saving, cost-effective and egg-independent influenza vaccine approach is important particularly when responding to an emerging pandemic. We fabricated coated, two-layer protein nanoclusters from recombinant trimeric hemagglutinin from an avian-origin H7N9 influenza A virus as an approach for vaccine development in response to an emerging pandemic. Assessment of the virus-specific immune responses and protective efficacy in mice immunized with the nanoclusters demonstrated that the vaccine candidates were highly immunogenic, able to induce protective immunity and long-lasting humoral antibody responses to this virus without the use of adjuvants. Because the advantages of the highly immunogenic coated nanoclusters also include rapid productions in an egg-independent system, this approach has great potential for influenza vaccine production not only in response to an emerging pandemic, but also as a replacement for conventional seasonal influenza vaccines. [ABSTRACT FROM AUTHOR]

Universal influenza vaccines are urgently needed to prevent recurrent influenza epidemics and inevitable pandemics. We generated double-layered protein nanoparticles incorporating two conserved influenza antigens—nucleoprotein and neuraminidase—through a two-step desolvation-crosslinking method. These protein nanoparticles displayed immunostimulatory properties to antigen-presenting cells by promoting inflammatory cytokine (IL-6 and TNF-α) secretion from JAWS II dendric cells. The nanoparticle immunization induced significant antigen-specific humoral and cellular responses, including antigen-binding and neutralizing antibodies, antibody- and cytokine (IFN-γ and IL-4)-secreting cells, and NP 147 – 155 tetramer-specific cytotoxic T lymphocyte (CTL) responses. Co-administration of monophosphoryl lipid A (MPLA, a toll-like receptor 4 agonist) with the protein nanoparticles further improved immune responses and conferred heterologous and heterosubtypic influenza protection. The MPLA-adjuvanted nanoparticles reduced lung inflammation post-infection. The results demonstrated that the combination of MPLA and conserved protein nanoparticles could be developed into an improved universal influenza vaccine strategy. MPLA-adjuvanted double-layered nucleoprotein-neuraminidase (NP-NA) protein nanoparticles were fabricated through a facile two-step desolvation-crosslinking method. These protein nanoparticles displayed immunostimulatory properties to dendric cells and induced significant antigen-specific humoral and cellular responses in mice, conferring improved cross-protection against divergent influenza viruses. The MPLA-adjuvanted NP-NA protein nanoparticles could be a synergistic piece of the universal influenza vaccine puzzle. [Display omitted] [ABSTRACT FROM AUTHOR]

Nanoscale zero-valent iron (nZVI) might generate positive and negative effects on plant growth, since it acts as either hazardous or growth-promotion role. It is still unclear whether such dual roles can be mediated by arbuscular mycorrhizal fungi (AMF) in plant-AMF symbiosis. We first identified that in 1.5 g kg−1 nZVI (≤1.5 g kg−1 positively), maize biomass was increased by 15.83%; yet in 2.0 g kg−1 nZVI, it turned to be declined by 6.83%, relative to non-nZVI condition (CK, p < 0.05), showing a negative effect. Interestingly, the inoculation of AMF massively improved biomass by 45.18% in 1.5 g kg−1 nZVI, and relieved the growth inhibition by 2.0 g kg−1 nZVI. The event of water use efficiency followed similar trend as that of biomass. We found that proper concentration of nZVI can positively interact with rhizosphere AMF carrier, enabling more plant photosynthetic carbon to be remobilized to mycorrhiza. The scanning of transmission electron microscopy showed that excessive nZVI can infiltrate into root cortical cells and disrupt cellular homeostasis mechanism, significantly increasing iron content in roots by 76.01% (p < 0.05). Simultaneously, the images of scanning electron microscopy showed that nZVI were attached on root surface to form an insoluble iron ion (Fe3+) layer, hindering water absorption. However, they were efficiently immobilized and in situ intercepted by extraradical hyphae in mycorrhizal-nZVI symbiosis, lowering iron translocation efficiency by 6.07% (p < 0.05). Herein, the optimized structure remarkably diminished aperture blockage at root surface and improved root activities by 30.06% (p < 0.05). Particularly, next-generation sequencing demonstrated that appropriate amount of nZVI promoted the colonization and development of Funneliformis mosseae as dominant species in rhizosphere, confirming the positive interaction between AMF and nZVI, and its regulatory mechanism. Therefore, dual effects of nZVI can be actively mediated by AMF via rhizosphere interactions. The findings provided new insights into the safe and efficient application of nanomaterials in agriculture. [Display omitted] [ABSTRACT FROM AUTHOR]

Biological soil crust (BSC) as a nature-based strategy has a great potential to restore soil and water in arid and semi-arid natural ecosystems. Yet, little is known about its effects on soil fertility and productivity as affected by the BSC inoculation in agroecosystems. We hypothesis that BSC inoculation can improve soil quality, while increasing crop productivity and economic benefits in semiarid rainfed region. To address this issue, we carried out field experiment using forage maize (Zea mays L.) from 2018 to 2019, with four treatments as follows: 1) conventional flat planting (control, CK), 2) flat planting with the inoculation of BSC (BSC), 3) ridge-furrow planting (RF), and 4) sectional ridge-furrow planting (SRF). The results showed that BSC inoculation significantly enhanced maize shoot and root biomass by 53–63 % and 30–67 % accordingly (P < 0.05), compared with CK in two growing seasons.Also, BSC treatment slightly increased soil water content and soil temperature, while significantly decreasing soil pH and soil bulk density, relative to CK, RF and SRF (P < 0.05). Compared with CK, the BSC inoculation markedly improved soil microbial biomass carbon by 54 % and nitrogen by 52%, soil organic carbon by 21 %, and total nitrogen by 30% respectively (P < 0.05) Critically, the contents of above four parameters were 42 %, 32 %, 19 % and 32 % greater in BSC than RF and SRF, respectively (P < 0.05). Simultaneously, the BSC significantly decreased soil C/N ratio by 7 %, while SRF and RF slightly decreased C/N ratio by 0.2 % and 2 % only, in comparison with CK. Interestingly, soil C&N mineralization efficiency were significantly greater in the BSC treatment than CK, RF and SRF (P < 0.05). In addition, the economic benefit under BSC was the highest relative to other three planting systems In conclusion, BSC can be used as a nature-based strategy (NbS) to improve soil properties, promote microbial C&N uptake and utilization via enhancing C&N mineralization and lowering C-N ratio. In conclusion, BSC can act as a green solution to achieve high productivity and promote soil fertility in semiarid agricultural ecosystem. • Biological soil crust (BSC) as nature-based strategy was tested in forage maize field. • BSC significantly enhanced forage maize biomass than flat planting (control). • BSC significantly enhanced carbon & nitrogen mineralization than control. • BSC also showed similar ecological advantages over natural ridge-furrow planting strategies. • BSC is a promising nature-based strategy to restore the functionality of semiarid ecosystem. [ABSTRACT FROM AUTHOR]

Abstract: Influenza vaccines with broad cross-protection are urgently needed. The highly conserved ectodomain of the influenza matrix protein 2 (M2e) can be a promising candidate if its low immunogenicity was overcome. In this study, we generated protein nanoclusters self-assembled from conformation-stabilized M2e tetramers (tM2e) to improve its immunogenicity. The resulting nanoclusters showed an average hydrodynamic diameter of 227nm. Vaccination with the nanoclusters by an intranasal route elicited high levels of serum antigen-specific IgG in mice (approximately 100-fold higher than that obtained with soluble tM2e), as well as antigen-specific T cell and mucosal antibody responses. The immunity conferred complete protection against lethal challenge with homo- as well as heterosubtypic viruses. These results demonstrate that nanoclusters assembled from conformation-stabilized M2e are promising as a potential universal influenza A vaccine. Self-assembly into nanoclusters represents a novel approach for increasing the immunogenicity of vaccine antigens. From the Clinical Editor: In order to develop more effective influenza vaccination, the highly conserved ectodomain of M2e could be a promising candidate. Unfortunately, it is a weak antigen for vaccination purposes. In this study, self-assembled protein nanoclusters of tM2e were generated and tested. The nanoclusters demonstrated superior vaccination properties, with complete protection against lethal challenge in the studied rodent model, raising hope for the introduction of similar vaccines to challenge human influenza outbreaks. [Copyright &y& Elsevier]

Influenza viral infection causes acute upper respiratory diseases in humans, posing severe risks to global public health. However, current vaccines provide limited protection against mismatched circulating influenza A viruses. Here, the immune responses induced in mice by novel double-layered protein nanoparticles were investigated. The nanoparticles were composed of influenza nucleoprotein (NP) cores and hemagglutinin (HA) or matrix 2 protein ectodomain (M2e) shells. Vaccination with the nanoparticles significantly enhanced M2e-specific serum antibody titers and concomitant ADCC responses. Robust NP-specific T cell responses and robust HA neutralization were also detected. Moreover, vaccination with a trivalent nanoparticle combination containing two routinely circulated HA, conserved M2e, and NP reduced lung virus titers, pulmonary pathologies, and weight loss after homologous virus challenge. This combination also improved survival rates against heterologous and heterosubtypic influenza virus challenges. Our results demonstrate that the trivalent combination elicited potent and long-lasting immune responses conferring influenza viral cross-protection. The double-layered protein nanoparticles combination composed of conserved NP as core and two routinely circulated HAs and conserved M2e as shell induces broad immune protection against divergent influenza A viruses. [Display omitted] [ABSTRACT FROM AUTHOR]

The first influenza virus infection (imprinting) can lead to long-term immune memory and influence subsequent vaccinations and infections. Previously, we reported a polyethyleneimine (PEI)-Aichi hemagglutinin (HA)/CpG (PHC) nanoparticle with cross-protective potential against homologous and heterologous influenza strains. Here we studied how influenza immune imprinting influences the antibody responses to the PHC vaccination and the protection against heterosubtypic virus challenges. We found that pre-existing virus immunity can maintain or synergize the vaccine-induced antibody titers, depending on the imprinting virus HA phylogenetic group. The HA group 1 virus (PR8, H1N1)-imprinted mice displayed comparable antigen-specific antibody responses to those without imprinting post-PHC vaccination. In contrast, the group 2 virus (Phi, H3N2)-imprinted mice showed significantly more robust and balanced antibodies post-vaccination, conferring complete protection against body weight loss and lung inflammation upon heterosubtypic reassortant A/Shanghai/2/2013 (rSH, H7N9) virus challenge. Our findings suggest that influenza imprinting from the same HA phylogenetic group can synergize subsequent vaccination, conferring heterosubtypic protection. [ABSTRACT FROM AUTHOR]

Chemokines are an extensive family of small proteins which, in conjunction with their receptors, guide the chemotactic activity of various immune cells throughout the body. CCL28, β- or CC chemokine, is involved in the host immunity at various epithelial and mucosal linings. The unique roles of CCL28 in several facets of immune responses have attracted considerable attention and may represent a promising approach to combat various infections. CCL28 displays a broad spectrum of antimicrobial activity against gram-negative and gram-positive bacteria, as well as fungi. Here, we will summarize various research findings regarding the antimicrobial activity of CCL28 and the relevant mechanisms behind it. We will explore how the structure of CCL28 is involved with this activity and how this function may have evolved. CCL28 displays strong homing capabilities for B and T cells at several mucosal and epithelial sites, and orchestrates the trafficking and functioning of lymphocytes. The chemotactic and immunomodulatory features of CCL28 through the interactions with its chemokine receptors, CCR10 and CCR3, will also be discussed in detail. Thus, in this review, we emphasize the dual properties of CCL28 and suggest its role as an anchoring point bridging the innate and adaptive immunity. [ABSTRACT FROM AUTHOR]

Biological soil crust (BSC) establishment as a nature-based strategy (NbS) may restore the functionality of degraded soils in semiarid agroecosystems. However, this issue is little documented. To address this issue, a BSC-inoculated (broken-skin inoculation, moss) field experiment was conducted in a semiarid alfalfa (Medicago sativa L.) field in 2018 and 2019, with the treatments as follows: 1) conventional flat planting (control), 2) flat planting with BSC inoculation (BSC), 3) ridge-furrow planting (RF) and 4) sectional ridge-furrow planting (SRF). The result showed that compared with the control, alfalfa biomass was evidently increased in BSC, RF and SRF treatments at the second growing season. Relative to the control, the BSC treatment harvested the highest soil total porosity, mean weight diameter, and macroaggregate proportion (>2 mm) (p < 0.05; significantly greater than RF and SRF). Also, the BSC inoculation remarkably improved soil microbial biomass carbon (C) & nitrogen (N), soil organic C and total N by 46%, 35%, 16% and 29% respectively, also significantly greater than RF and SRF (p < 0.05). This phenomenon was tightly correlated with the optimized soil C fractions as affected by the BSC inoculation, since dissolved organic C, oxidizable organic C, particulate organic C, light fraction organic C and heavy fraction organic C were promoted by 17%, 29%, 13%, 40% and 14% in the BSC treatment respectively, relative to the control (p < 0.05). Therefore, the BSC inoculation significantly improved soil quality in alfalfa field. This outcome was closely associated with the increased soil cohesion and microaggregate proportion, and decreased soil C-N ratio under the BSC. The optimized physiochemical properties boosted C mineralization and the utilization of soil C & N by microbial organisms. Therefore, the BSC establishment can act as a promising NbS to conserve the degraded soils in semiarid agroecosystems. [Display omitted] • Biological soil crust (BSC) as nature-based strategy was tested in alfalfa field. • BSC improved stability of soil physical structure relative to flat planting. • BSC significantly enhanced soil liable carbon and microbial carbon & nitrogen. • BSC showed ecological advantages over natural ridge-furrow planting strategies. • BSC is a promising nature-based strategy to restore the degraded semiarid soils. [ABSTRACT FROM AUTHOR]

Incorporation of membrane-anchored flagellin molecules into the surfaces of influenza virus-like particles (VLP) was previously reported to promote T helper (Th) 1-biased IgG antibody production and protective efficacy of co-presented vaccine antigens. Herein, we investigated the potential adjuvant effects and mechanisms of flagellin-expressing VLP (FliC-VLP) as an independent component on influenza vaccination in wild-type and mutant mouse models. FliC-VLP adjuvanted influenza vaccination was highly effective in promoting the induction of Th1-biased IgG isotype switched antibodies, enhanced protection, and long-lasting IgG antibody responses in both wild-type and CD4-knockout mice. In contrast, the adjuvant effects of soluble flagellin were Th2-biased and required CD4 T helper cells. The adjuvant effects of FliC-VLP were less dependent on CD4 T cells and flagellin-mediated innate immune signaling pathways. The results suggest that FliC-VLP might play an effective adjuvant role in an immune competent condition as well as in a defect of CD4 T cells. [ABSTRACT FROM AUTHOR]

Vaccinations are expected to aid in building immunity against pathogens. This objective often requires the addition of an adjuvant with certain vaccine formulations containing weakly immunogenic antigens. Adjuvants can improve antigen processing, presentation, and recognition, thereby improving the immunogenicity of a vaccine by simulating and eliciting an immune response. Chemokines are a group of small chemoattractant proteins that are essential regulators of the immune system. They are involved in almost every aspect of tumorigenesis, antitumor immunity, and antimicrobial activity and also play a critical role in regulating innate and adaptive immune responses. More recently, chemokines have been used as vaccine adjuvants due to their ability to modulate lymphocyte development, priming and effector functions, and enhance protective immunity. Chemokines that are produced naturally by the body’s own immune system could serve as potentially safer and more reliable adjuvant options versus synthetic adjuvants. This review will primarily focus on chemokines and their immunomodulatory activities against various infectious diseases and cancers. [ABSTRACT FROM AUTHOR]

In our previous study, we designed a series of pyrazole derivatives as novel COX-2 inhibitors. In order to obtain novel dual inhibitors of COX-2 and 5-LOX, herein we designed and synthesized 20 compounds by hybridizing pyrazole with substituted coumarin who was reported to exhibit 5-LOX inhibition to select potent compounds using adequate biological trials sequentially including selective inhibition of COX-2 and 5-LOX, anti-proliferation in vitro , cells apoptosis and cell cycle. Among them, the most potent compound 11g (IC 50 = 0.23 ± 0.16 μM for COX-2, IC 50 = 0.87 ± 0.07 μM for 5-LOX, IC 50 = 4.48 ± 0.57 μM against A549) showed preliminary superiority compared with the positive controls Celecoxib (IC 50 = 0.41 ± 0.28 μM for COX-2, IC 50 = 7.68 ± 0.55 μM against A549) and Zileuton (IC 50 = 1.35 ± 0.24 μM for 5-LOX). Further investigation confirmed that 11g could induce human non-small cell lung cancer A549 cells apoptosis and arrest the cell cycle at G2 phase in a dose-dependent manner. Our study might contribute to COX-2, 5-LOX dual inhibitors thus exploit promising novel cancer prevention agents. [ABSTRACT FROM AUTHOR]

Plant–plant competitive and facilitative interactions might strongly affect the biodiversity effect and field productivity of intercropping system under the condition of limited resources such as available phosphorus (P). To test this hypothesis, the maize–grass pea intercropping system with five P application gradients (from low- to high-P) was experimentally investigated and the global meta-analysis validation was simultaneously performed. The main objectives of this study included as: 1) to examine the characteristics of plant–plant interaction variations along soil P addition gradients; 2) to identify the shift from interspecific complementarity to selection effect regarding the productivity and nutrient uptake and its driving mechanism; 3) to verify the universality of above phenomenon via global meta-analysis and explore the general pattern of P-dependent plant–plant interactions in the intercropping systems. Regardless of growing seasons, the total net effect of intercropping system was always >0, showing net facilitative effects of plant–plant interactions on field productivity and nutrient uptake efficiency, relative to monoculture systems. On average, the yield, biomass, N and P uptake were elevated by 3.0–13.7%, 3.2–12.8%, 7.5–20.1% and 5.6–18.9% in intercropping respectively, relative to those of monoculture. On the other hand, the contribution of complementarity effect to the total net effect was up to 78.7%, much more than that of selection effect (21.3%). The relative interaction index tended to decline remarkably with increasing soil P availability (from 0.097–0.126 to 0.027–0.029), suggesting that the facilitation (rather than the competition) dominated in intercropping under the low-P condition. Furthermore, the intercropped grass pea decreased the harvest index and allocated more biomass to vegetative growth as a result of the enhanced interspecific competition under the P-sufficient condition. Finally, the meta-analysis demonstrated that intercropping system had greater relative benefits regarding field productivity and N/P acquisition and utilization than monoculture system. In the meanwhile, the intensity of interspecific facilitative effect was enhanced under the P-deficient condition. Field observations presented the evidences regarding the P-dependent plant-plant interactions and its effects on field productivity in the maize-grass pea intercropping system. The meta-analysis confirmed that high P application decreased the interspecific facilitative effects in terms of field productivity and nutrient utilization in the intercropping systems. But the low-P condition led to the opposite trend, i.e. facilitative effect dominated in the intercropping for greater productivity efficiency. Graphical abstract elucidates the plant-plant interaction pattern in maize-grass pea intercropping system according to field observation and meta-analysis [Display omitted] • Effect of interspecific competition & facilitation on field productivity along soil P gradients in intercropping system is unclear • To examine how the plant–plant interactions affected crop productivity and nutrient uptake via field observations & meta-analyses • Intercropping led to greater net effects on productivity and N/P uptake efficiency via facilitative interactions than monoculture • Complementarity effect was dominant to ensure productivity benefit in low-P soil, yet competitive effect dominated in high-P soil • P-dependent plant-plant interaction efficiently mediated relative field productivity and resource benefits in intercropping system. [ABSTRACT FROM AUTHOR]

The relative intensity of facilitative effect among coexisting plant species is frequently affected by soil water and nutrient availability, such as nitrogen (N), phosphorus (P), potassium (K), and organic fertilizer. However, to date, the general pattern of nutrient gradient effects on plant–plant interactions remains inconsistent or even opposite in the intercropping systems. To address this issue, we performed a global meta-analysis and three experiments to investigate the production efficiency of intercropping along fertilizer input gradient (low vs. high) by assessing the land equivalent ratio (LER). Trial 1 included five P gradient in the maize–grass pea intercropping system. Trial 2 consisted of two N gradient in the maize–wheat, maize–soybean and wheat–soybean intercropping systems. Trial 3 contained two water and three P gradients in the same intercropping systems as Trial 1. The meta-analysis result indicated that the average LER for yield (LER Y), biomass (LER B), N uptake (LER N), and P uptake (LER P) were 1.49, 1.25, 1.35, and 1.66, respectively. It implied that intercropping would save 49 %, 25 %, 35 % and 66 % lands to achieve the same yield, biomass, N and P uptake amount as monoculture, respectively. Also, high fertilizer inputs significantly decreased the relative productivity and nutrient uptake. Average effect sizes of high inputs on LER Y , LER B , LER N , and LER P were up to − 0.0505 (−0.0550 to −0.0461), − 0.0267 (−0.0303 to −0.0230), − 0.0321 (−0.0395 to −0.0247) and − 0.0237 (−0.0370 to −0.0103), respectively. These negative values demonstrated that the LER markedly declined under the high-nutrient conditions. On the other hand, the results of Trial 1 confirmed that the LER Y , LER B , LER N , and LER P tended to decrease significantly with increasing P addition. In Trial 2 , the LER Y of intercropping systems tended to significantly decrease with increasing N application. In Trial 3 , the LER Y , LER B , LER N , and LER P also displayed a descending trend with increasing P addition and soil water availability. Collectively, the three trials confirmed the reliability and universality of the meta-analysis conclusions. This study provided a broad support for the hypothesis of the nutrient-dependent relative benefits in intercropping systems. [Display omitted] • Average land equivalent ratio was greater than 1 in meta-analysis database. • High nutrient input decreased the land equivalent ratio relative to low input. • Field and pot-culture trials confirmed the reliability of meta-analysis results. • Relative productivity benefits were species specific and context dependent. • Results confirmed the universality of stress gradient hypothesis in intercropping. [ABSTRACT FROM AUTHOR]

The increasingly acquired resistance to vemurafenib and side effects of known inhibitors motivate the search for new and more effective anti-melanoma drugs. In this Letter, virtual screening and scaffold growth were combined together to achieve new molecules as BRAF V600E inhibitors. Along with docking simulation, a primary screen in vitro was performed to filter the modifications for the lead compound, which was then substituted, synthesized and evaluated for their inhibitory activity against BRAF V600E and several melanoma cell lines. Out of the obtained compounds, derivative 3l was identified as a potent BRAF V600E inhibitor and exerted an anticancer effect through BRAF V600E inhibition. The following biological evaluation assays confirmed that 3l could induce cell apoptosis and marked DNA fragmentation. Furthermore, 3l could arrest the cell cycle at the G0/G1 phase in melanoma cells. The docking simulation displayed that 3l could tightly bind with the crystal structure of BRAF V600E at the active site. Overall, the biological profile of 3l suggests that this compound may be developed as a potential anticancer agent. [ABSTRACT FROM AUTHOR]

A series of novel 5-phenyl-1 H -pyrazol derivatives ( 5a – 5x ) containing cinnamamide moiety were synthesized and their biological activities as potential tubulin polymerization inhibitors were evaluated. Among them, compound 5j exhibited the most potent inhibitory activity with an IC 50 value of 1.02 μM for tubulin, which was superior to that of Colchicine (IC50 = 1.34 μM). Docking simulation was performed to insert compound 5j into the crystal structure of tubulin at colchicine binding site to determine the probable binding model. 3D-QSAR model was also built to provide more pharmacophore understanding that could be used to design new agents with more potent tubulin inhibitory activity. [ABSTRACT FROM AUTHOR]

The influenza epidemics pose a significant threat to public health. Of them, type B influenza coincided with several severe flu outbreaks. The efficacy of the current seasonal flu vaccine is limited due to the antigenicity changes of circulating strains. In this study, we generated structure-stabilized HA stalk antigens from influenza B and fabricated double-layered protein nanoparticles as universal influenza B vaccine candidates. In vitro studies found that the resulting protein nanoparticles were effectively taken up to activate dendritic cells. Nanoparticle immunization induced broadly reactive immune responses conferring robust and sustained cross-immune protection against influenza B virus strains of both lineages. The results reveal the potential of layered protein nanoparticles incorporated with structure-stabilized constant antigens as a universal influenza vaccine with improved immune protective potency and breadth. [ABSTRACT FROM AUTHOR]

Plant-plant interactions in the intercropping system can significantly affect crop productivity. However, it is poorly understood how the interactions affect the land equivalent ratios (LER) in the cereal-legumes and cereal-cereal intercropping systems in semi-arid agroecosystems. A two-year (2019–2020) field experiment was conducted in the Dryland Agricultural Experimental Station of Lanzhou University, a semiarid rainfed site of northwest China, to quantify the impact of crop diversification on land equivalent ratio, and its moisture-dependent mechanisms in three intercropping systems of maize-wheat, maize-soybean and wheat-soybean. The soybean-involved intercropping systems showed positive interactions, which substantially promoted crop productivity of maize and wheat by 18.1–20.9%. The soil water in soybean strips can be used by intercropped wheat or maize, which in turn promoted soil water storage (SWS) in maize or wheat strips by 0.6% and 11.0% respectively, during the co-growth period. This further improved the photosynthetic rate (Pn), instantaneous growth rate (IGR), and water use efficiency (WUE) for each species and thereafter elevated the land equivalence ratio (LER>1). However, in the wheat-maize intercropping system, interspecific competition was dominated with wheat as dominant species and maize as inferior one respectively. The competition plundered available water of maize strips (SWS decreased by 10.5%), and thus decreased its Pn and WUE by 12.7% and 20.0% (P < 0.05), respectively. Importantly, maize yield and LER were not improved via the compensation effect during the post-harvest period of wheat. While soil water was to some extent restored, the Pn and IGR of intercropped maize were still lower than those of monoculture maize. This trend resulted in maize yield loss during the reproductive period, and ultimately lower LER. For the first time, we found a rarely reported phenomenon, i.e. negative relationships between crop diversity and land equivalent ratios in semiarid agroecosystem, since the yield loss caused by competition was not compensated during the co-growth period. Therefore, a positive relationship between crop diversification and land equivalent ratio required rational crop species configuration, in terms of the tradeoff between crop diversity and its productivity at agricultural landscape scale. A graphical abstract of the effects of different intercropping systems on soil water utilization, plant physiological activity and productivity. Note: The light blue to dark blue bars indicates the amount of water stored in the soil, LER is Land equivalent ratio, WUE is water use efficiency, IGR is instantaneous growth rate, Pn is photosynthetic rate, Ch II is chlorophyll content. Compensation refers to the process of resource acquisition through temporal and spatial niche differences between crops. Competition refers to the crops are competing resource to against each other. [Display omitted] • Crop diversification and productivity were investigated in intercropping system. • Intercropped soybean improved land equivalent ratio by compensating water use. • Intercropped wheat inhibited physiological vigor, growth and yield of maize. • Maize yield was not compensated to cover system productivity after wheat harvest. • Soybean-involved species configuration facilitated crop diversity and productivity. [ABSTRACT FROM AUTHOR]

Note: P (phosphorus), W (water), + (positive or increase), – (negative or decrease). [Display omitted] • Plant facilitation was found in the intercropping system of maize and grass pea. • Facilitation shifted from +/+, +/0 to +/- from low to high water and P gradients. • In low P, rhizosphere soil acidification of grass pea fostered P mineralization. • Soil microbial biomass P was improved for higher productivity in +/+ facilitation. • Soil water and phosphorus availability altered interspecific facilitation model. Plant-plant facilitation is widely studied to increase productivity and resource utilization in cereal-legume intercropping system. However, physiological and ecological mechanisms driving interspecific interaction shift along the environmental gradients is largely unknown. To clarify this issue, we first tested plant-plant facilitation along with four phosphorus (P) gradients in maize-grass pea intercropping system. Results illustrated a progressive transition of seed yield-based facilitation from mutually facilitated (+/+) to maize facilitated but grass pea as facilitator (+/-) along with low to high P gradients. Secondly, above trend was evidently enhanced when combining with drought stress gradients, in which severe drought amplified facilitative effects, whereas the magnitude of facilitation was relatively weak under well-watered condition. Interestingly, biomass-based facilitation transition did not synchronize with seed-based one, in which occurred in a broader threshold range of water and P gradients. Specifically, total yield, biomass, N and P uptake increased by 0.5%, 4.1%, 1.8% and 2.9% under the sufficient P and water availability, whereas these indicators increased by 25.3%, 18.5%, 20.5% and 21.4% in P and water deficient soils. And the total net effect was positive under all the environmental conditions. Rhizosphere interaction plays a crucial role in facilitation judgment, and the driving mechanism was associated with soil acidification and microbial community promotion under P-deficient condition. Under low soil moisture and available P, soil acidification and lower rhizosphere soil pH of intercropped maize were observed. Rhizosphere phosphatase secretion were significantly activated in P-deficient soils and accelerated the mineralization of soil organophosphorus, and the microbial biomass P was improved for stronger facilitation. Taken together, our findings confirmed the P and water driven facilitation shift along with stress gradients and highlighted the roles of rhizosphere interaction in affecting species diversity advantage. In conclusion, our work provided a relatively full picture for plant facilitation evaluation and more accurate management regarding intercropping productivity. [ABSTRACT FROM AUTHOR]

A novel benzofuranone fluorescent probe, BFO-SFT , for monitoring sulfite in living cells and mice is described which operates over a wide pH range and exhibits a red-shifted emission maximum. The response of the probe BFO-SFT was relatively rapid (within 20 min) and exhibited a good linear correlation of 0–10 Eq (100 μM) with reliable accuracy (R2 = 0.9934). The probe also showed high sensitivity (Limit of detection = 152 nM) and selectivity. With low cytotoxicity, BFO-SFT was successfully applied into the biological imaging of sulfite in living MCF-7 cells and in BALB/C Nude mice. [Display omitted] • A benzofuranone-based fluorescent probe, BFO-SFT , was developed for monitoring sulfite. • The benzofuranone backbone achieved the purposes of introducing red-shift and wide pH window (7.0–10.0). • Reliable linear range, high sensitivity and high selectivity towards sulfite. • Applied into the biological imaging of sulfite in living MCF-7 cells and in BALB/C Nude mice. [ABSTRACT FROM AUTHOR]

Spatial structural variations in ridge-furrow unit size and its ratio can result in the drastic fluctuation of soil hydrothermal status, and thereby affect water use and yield formation in dryland crops. Previous studies were little focused on the responses of dryland wheat productivity to the structural changes in ridge-furrow plastic mulching (RFM) system and its mechanism in semiarid eastern African Plateau (EAP). A two-year field experiment was conducted in Juja, a semiarid area in Kenya from 2015 to 2016. There were seven treatments of ridge-furrow width and ratios in randomized block design as follows: (1) 40 cm ridge width and 20 cm furrow width (R 4 F 2 , the same below), (2) R 3 F 2 , (3) R 2 F 2 , (4) R 3 F 4 , (5) R 2 F 4 , (6) R 3 F 6 and (7) R 2 F 6 , and conventional flat planting without mulching as control (CK). The results showed that R 4 F 2 , R 3 F 2 , R 2 F 2 , R 3 F 4 and R 2 F 4 treatments significantly improved soil water storage and temperature across two growing seasons compared with CK (P < 0.05). Among all the treatments, R 3 F 2 and R 2 F 2 obviously achieved the highest plant height, leaf area, aboveground biomass (AgB), grain yield and water use efficiency (WUE) (P < 0.05). Also, R 2 F 2 had the highest economic benefits in all treatments. The optimal ridge-furrow ratio appeared to be 1.32–1.38, 1.28–1.31, 1.39–1.49, 1.37–1.45 and 1.46–1.56 for wheat yield, AgB, WUE Y , WUE B and harvest index (HI), respectively. In addition, wheat yield, AgB, WUE and HI tended to decrease linearly with the increased ridge-furrow unit size. In conclusion, ridge-furrow ratio of 1–1.5 (R 2 F 2 to R 3 F 2) in combination with the minimum ridge-furrow unit size proved to be the optimum RFM system for the best dryland wheat productivity in accordance to regional soil and climate characteristics in semiarid EAP and other similar areas of the world. • RFM system significantly increased wheat productivity and WUE in semiarid EAP. • The optimal ridge-furrow ratio was 1.32–1.38 and 1.39–1.49 for yield and WUE. • Wheat yield and WUE decreased linearly with the increasing ridge-furrow unit size. • Ridge-furrow ratio of 1–1.5 combined with a minimum ridge-furrow unit was the optimum RFM system for wheat productivity. [ABSTRACT FROM AUTHOR]

Cysteine (Cys) is an indispensable small organic molecule containing sulfhydryl groups, which has essential regulatory effects on the physiological process of human body. In this work, a red emission fluorescent probe TCFQ-Cys was designed and exploited based on 2-(3-cyano-4,5,5-trimethylfuran-2(5 H)-ylidene) malononitrile-derivatives. The probe could effectively monitor Cys through the typical acrylate cleavage. The detecting system showed a red emission at 633 nm and the fluorescence was stable within the pH range of 6–9. The detection could be completed in 30 min. TCFQ-Cys presented high sensitivity with a detection limit of 0.133 μM and high selectivity towards Cys from other biological mercaptans. The most important feature was that the system had a wide linear range of 0–300 μM, which covered the physiological requirements of Cys detection. Subsequently, we conducted the biological imaging of Cys in MCF-7 cells and Caenorhabditis elegans (C. elegans). Therefore, TCFQ-Cys had a practical application prospect for further investigating the physiological function of Cys. A red emission fluorescent probe TCFQ-Cys was develop to monitor the Cys level through the typical acrylate cleavage. The detecting system showed a red emission at 633 nm and the fluorescence was stable within the pH range of 6–9. The detection could be complete in 30 min. TCFQ-Cys presented high sensitivity with a detection limit of 0.133 μM and high selectivity towards Cys than other biological mercaptans. The most important feature was that the system had a wide linear range of 0–300 μM, which covered the physiological requirements of Cys detection. Subsequently, we conducted the biological imaging of Cys in MCF-7 cells and Caenorhabditis elegans (C. elegans). Therefore, TCFQ-Cys had a practical application prospect in further investigating the physiological function of Cys. Image 1 • A red emission fluorescent probe for real-time detection of cysteine. • The probe could semiquantitatively determine the cysteine level in living cells. • The probe could image endogenous cysteine in situ in Caenorhabditis elegans. • Exhibiting wide linear range, long wavelength emission and low detection limit. [ABSTRACT FROM AUTHOR]

Allometry is extensively used to describe the scaling relationship between individual size and metabolite allocation. Micro-field rain-harvesting system can improve soil water availability and thus alter the allocation of individual biomass among organs. Yet the eco-physiological mechanism based on allometric scaling theory has been little investigated under various mulching conditions. A field experiment was conducted using maize variety Yuyuan7879 in Juja, Kenya for two growing seasons (cross-year) from 2015 to 2016, and from 2016 to 2017 respectively. Four treatments were designed as ridge-furrow mulching (RFM) with black plastic mulching (RFMB), transparent plastic mulching (RFMT), grass straw mulching (RFMG) and conventional flat planting (CK). We found that RFMB, RFMT and RFMG significantly increased grain yield by 106%, 109% and 32% in 2015, and 101%, 96% and 30% in 2016 respectively, in comparison with CK. Mulching treatments improved soil temperature and moisture and significantly increased crop water productivity (CWP). Mulching treatments drastically changed the allometric relationship between metabolic rate (leaf biomass) and individual size (lgy = αlgx + lgβ), and optimized the size-dependent reproductive allocation. In the relationship between leaf biomass (y-axis) vs aboveground biomass (x-axis), mulching treatments significantly declined the value of α (α < 1; P < 0.01), suggesting that less photosynthetic product was allocated in leaves in mulching treatments than in CK. As for the allometric relationship between grain yield and aboveground biomass, the α was generally significantly more than 1 in RFMB and RFMT, and significantly less than 1 in RFMG and CK, demonstrating that more photosynthates were allocated to reproductive growth under plastic mulching. Also, the variation of allometric relationship between reproductive and vegetative biomass provided further evidence that plastic mulching facilitated substance transportation from vegetative to reproductive organs. In conclusion, plastic mulching significantly improved soil hydrothermal condition, increased individual reproductive allocation and ultimately improved grain yield and CWP at population level. • Micro-field rainwater-harvesting system (MFRHs) substantially improved soil water availability in rainfed maize field. • MFRHs boosted crop water productivity and yields in maize in semiarid Kenya. • Individual modified allometric relationship between leaf or seed vs body size to allocate more mass to grain under MFRHs. • Allometric relationship provided new insights into interpretation of raising production under MFRHs. [ABSTRACT FROM AUTHOR]

Overall survival, graft survival and HCC recurrence outcome data were collected. Graft survival (defined as time to either graft failure or patient death) was 73.8%, and overall survival was 79%. For graft survival, recipient body mass index (BMI) (HR 0.932, CI 0.884-0.098, p=0.01), and donor BMI (HR 1.051, CI 1.006-1.097, p=0.026) were significant variables on multivariate analysis. [Extracted from the article]