Biodegradable Nanoflowers with Abaloparatide Spatiotemporal Management of Functional Alveolar Bone Regeneration.

Post-extraction alveolar bone atrophy greatly hinders the subsequent orthodontic tooth movement (OTM) or implant placement. In this study, we synthesized biodegradable bifunctional bioactive calcium phosphorus nanoflowers (NFs) loaded with abaloparatide (ABL), namely ABL@NFs, to achieve spatiotemporal management for alveolar bone regeneration. The NFs exhibited a porous hierarchical structure, high drug encapsulation efficacy, and desirable biocompatibility. ABL was initially released to recruit stem cells, followed by sustained release of Ca2+ and PO43- for in situ interface mineralization, establishing an osteogenic "biomineralized environment". ABL@NFs successfully restored morphologically and functionally active alveolar bone without affecting OTM. In conclusion, the ABL@NFs demonstrated promising outcomes for bone regeneration under orthodontic condition, which might provide a desirable reference of man-made "bone powder" in the hard tissue regeneration field.

Trivalent Nickel-Catalyzing Electroconversion of Alcohols to Carboxylic Acids.

The comprehension of activity and selectivity origins of the electrooxidation of organics is a crucial knot for the development of a highly efficient energy conversion system that can produce value-added chemicals on both the anode and cathode. Here, we find that the potential-retaining trivalent nickel in NiOOH (Fermi level, -7.4 eV) is capable of selectively oxidizing various primary alcohols to carboxylic acids through a nucleophilic attack and nonredox electron transfer process. This nonredox trivalent nickel is highly efficient in oxidizing primary alcohols (methanol, ethanol, propanol, butanol, and benzyl alcohol) that are equipped with the appropriate highest occupied molecular orbital (HOMO) levels (-7.1 to -6.5 eV vs vacuum level) and the negative dual local softness values (Δsk, -0.50 to -0.19) of nucleophilic atoms in nucleophilic hydroxyl functional groups. However, the carboxylic acid products exhibit a deeper HOMO level (<-7.4 eV) or a positive Δsk, suggesting that they are highly stable and weakly nucleophilic on NiOOH. The combination (HOMO, Δsk) is useful in explaining the activity and selectivity origins of electrochemically oxidizing alcohols to carboxylic acid. Our findings are valuable in creating efficient energy conversions to generate value-added chemicals on dual electrodes.

OsEIL2 balances rice immune responses against (hemi)biotrophic and necrotrophic pathogens via the salicylic acid and jasmonic acid synergism.

Plants typically activate distinct defense pathways against various pathogens. Heightened resistance to one pathogen often coincides with increased susceptibility to another pathogen. However, the underlying molecular basis of this antagonistic response remains unclear. Here, we demonstrate that mutants defective in the transcription factor ETHYLENE-INSENSITIVE 3-LIKE 2 (OsEIL2) exhibited enhanced resistance to the biotrophic bacterial pathogen Xanthomonas oryzae pv oryzae and to the hemibiotrophic fungal pathogen Magnaporthe oryzae, but enhanced susceptibility to the necrotrophic fungal pathogen Rhizoctonia solani. Furthermore, necrotroph-induced OsEIL2 binds to the promoter of OsWRKY67 with high affinity, leading to the upregulation of salicylic acid (SA)/jasmonic acid (JA) pathway genes and increased SA/JA levels, ultimately resulting in enhanced resistance. However, biotroph- and hemibiotroph-induced OsEIL2 targets OsERF083, resulting in the inhibition of SA/JA pathway genes and decreased SA/JA levels, ultimately leading to reduced resistance. Our findings unveil a previously uncharacterized defense mechanism wherein two distinct transcriptional regulatory modules differentially mediate immunity against pathogens with different lifestyles through the transcriptional reprogramming of phytohormone pathway genes.

APIP5 functions as a transcription factor and an RNA-binding protein to modulate cell death and immunity in rice.

Many transcription factors (TFs) in animals bind to both DNA and mRNA, regulating transcription and mRNA turnover. However, whether plant TFs function at both the transcriptional and post-transcriptional levels remains unknown. The rice (Oryza sativa) bZIP TF AVRPIZ-T-INTERACTING PROTEIN 5 (APIP5) negatively regulates programmed cell death and blast resistance and is targeted by the effector AvrPiz-t of the blast fungus Magnaporthe oryzae. We demonstrate that the nuclear localization signal of APIP5 is essential for APIP5-mediated suppression of cell death and blast resistance. APIP5 directly targets two genes that positively regulate blast resistance: the cell wall-associated kinase gene OsWAK5 and the cytochrome P450 gene CYP72A1. APIP5 inhibits OsWAK5 expression and thus limits lignin accumulation; moreover, APIP5 inhibits CYP72A1 expression and thus limits reactive oxygen species production and defense compounds accumulation. Remarkably, APIP5 acts as an RNA-binding protein to regulate mRNA turnover of the cell death- and defense-related genes OsLSD1 and OsRac1. Therefore, APIP5 plays dual roles, acting as TF to regulate gene expression in the nucleus and as an RNA-binding protein to regulate mRNA turnover in the cytoplasm, a previously unidentified regulatory mechanism of plant TFs at the transcriptional and post-transcriptional levels.

Variation in the physiological response of adult worker bees of different ages (Apis mellifera L.) to pyraclostrobin stress.

The social division of labor within the honeybee colony is closely related to the age of the bees, and the age structure is essential to the development and survival of the colony. Differences in tolerance to pesticides and other external stresses among worker bees of different ages may be related to their social division of labor and corresponding physiological states. Pyraclostrobin was widely used to control the fungal diseases of nectar and pollen plants, though it was not friend to honey bees and other pollinators. This work aimed to determine the effects of field recommended concentrations of pyraclostrobin on the activities of protective and detoxifying enzymes, on the expression of genes involved in nutrient metabolism, and immune response in worker bees of different ages determined to investigate the physiological and biochemical differences in sensitivity to pyraclostrobin among different age of worker bees. The result demonstrates that the tolerance of adult worker bees to pyraclostrobin was negatively correlated with their age, and the significantly reduced survival rate of forager bees (21 day-old) with continued fungicide exposure. The activities of protective enzymes (CAT and SOD) and detoxifying enzymes (CarE, GSTs and CYP450) in different ages of adult worker bees were significantly altered, indicating the physiological response and the regulatory capacity of worker bees of different ages to fungicide stress was variation. Compared with 1 and 8 day-old worker bees, the expression of nutrient-related genes (ilp1 and ilp2) and immunity-related genes (apidaecin and defensin1) in forager bees (21 day-old) was gradually downregulated with increasing pyraclostrobin concentrations. Moreover, the expression of vitellogenin and hymenoptaecin in forager bees (21 day-old) was also decreased in high concentration treatment groups (250 and 313 mg/L). The present study confirmed the findings of the chronic toxicity of pyraclostrobin on the physiology and biochemistry of worker bees of different ages, especially to forager bees (21 day-old). These results would provide important physiological and biochemical insight for better understanding the potential risks of pyraclostrobin on honeybees and other non-target pollinators.

Strategies to attenuate ciprofloxacin inhibition on enhanced biological phosphorus removal from wastewater and its recoverability.

The inhibiting effects of ciprofloxacin (CIP) on enhanced biological phosphorus removal (EBPR) were investigated with no change in reactor operation and with increased aeration rate and sludge retention time (SRT) to explore inhibition-alleviating solutions. Additionally, performance recoverability was evaluated. The results showed that the phosphorus removal efficiency in the presence of 0.002-0.092 mg/L CIP for 7 days was only 12.5%. Increasing the aeration rate relieved inhibition (33.5% phosphorus removal efficiency on Day 7), and increasing SRT slowed EBPR performance deterioration. The EBPR performance recovered from CIP inhibition and increases in the aeration rate and SRT resulted in different recovery phenomena. The maximum PO43--P release rate continued to decrease in the first 2 days of the recovery stage and then gradually increased. However, the maximum PO43--P uptake rate immediately increased at different rates among reactors, which might be attributed to variations in the microbial community structure, decreased poly-P content, and enhanced abundances of ABC transporters and quorum sensing. It was found that some microorganisms associated with phosphorus removal were more tolerant to CIP than glycogen accumulating organisms. Moreover, the increased relative abundance of the qepA gene indicated that the microorganisms in the EBPR system had strong antibiotic resistance capacity. The bacterial community structure was significantly affected by CIP and could not recover to the initial structure. The results help to provide technical support for the operation of the EBPR process in the presence of CIP and to increase the understanding of system recoverability.

pH-dependent mechanisms of sulfadiazine degradation by natural pyrite-driven heterogeneous Fenton-like reactions.

The development of a natural pyrite/peroxymonosulfate (PMS) system for the removal of antibiotic contamination from water represented an economic and green sustainable strategy. Yet, a noteworthy knowledge gap remained considering the underlying reaction mechanism of the system, particularly in relation to its pH sensitivity. Herein, this paper investigated the impacts of critical reaction parameters and initial pH levels on the degradation of sulfadiazine (SDZ, 3 mg/L) in the pyrite/PMS system, and elucidated the pH dependence of the reaction mechanism. Results showed that under optimal conditions, SDZ could be completely degraded within 5 min at a broad pH range of 3.0-9.0, with a pseudo-first-order reaction rate of >1.0 min-1. The low or high PMS doses could lower degradation rates of SDZ through the decreased levels of active species, while the amount of pyrite was positively correlated with the removal rate of SDZ. The diminutive concentrations of anions exerted minor impacts on the decomposition of SDZ within the pyrite PMS system. Mechanistic results demonstrated that the augmentation of pH levels facilitated the transition from the non-radical to the radical pathway within the natural pyrite/PMS system, while concurrently amplifying the role of •OH in the degradation process of SDZ. This could be attributed to the change in interface electrostatic repulsion induced by pH fluctuations, as well as the mutual transformation between active species. The stable presence of the relative content of Fe(II) in the used pyrite was ensured owing to the reduced sulfur species acting as electron donors, providing the pyrite/PMS system excellent reusability. This paper sheds light on the mechanism regulation of efficient removal of organic pollutants through pyrite PMS systems, contributing to practical application.

TGF-ß1 mediates tumor immunosuppression aggravating at the late stage post-high-light-dose photodynamic therapy.

Photodynamic therapy (PDT) is an emerging clinical treatment that is expected to become an important adjuvant strategy for the immunotherapeutic cancer treatment. Recently, numerous works have reported combination strategies. However, clinical data showed that the anti-tumor immune response of PDT was not lasting though existing. The immune activation effect will eventually turn to immunosuppressive effect and get aggravated at the late stage post-PDT. So far, the mechanism is still unclear, which limits the design of specific correction strategies and further development of PDT. Several lines of evidence suggest a role for TGF-ß1 in the immunosuppression associated with PDT. Herein, this study systematically illustrated the dynamic changes of immune states post-PDT within the tumor microenvironment. The results clearly demonstrated that high-light-dose PDT, as a therapeutic dose, induced early immune activation followed by late immunosuppression, which was mediated by the activated TGF-ß1 upregulation. Then, the mechanism of PDT-induced TGF-ß1 accumulation and immunosuppression was elucidated, including the ROS/TGF-ß1/MMP-9 positive feedback loop and CD44-mediated local amplification, which was further confirmed by spatial transcriptomics, as well as by the extensive immune inhibitory effect of local high concentration of TGF-ß1. Finally, a TGF-ß blockade treatment strategy was presented as a promising combinational strategy to reverse high-light-dose PDT-associated immunosuppression. The results of this study provide new insights for the biology mechanism and smart improvement approaches to enhance tumor photodynamic immunotherapy.

Iron intake and multiple health outcomes: Umbrella review.

Iron is an essential trace element, while excess iron can lead to different levels of physical abnormalities or diseases. This umbrella review aimed to conduct a systematic evaluation of the possible relationships between iron intake and various health outcomes. We retrieved PubMed, Embase, Web of Science, Scopus, and the Cochrane Database of Systematic Reviews from inception through May 2021. A total of 34 meta-analyses with 46 unique health outcomes were identified. Heme iron intake was positively associated with nine outcomes, including colorectal cancer, type 2 diabetes mellitus, and cardiovascular disease mortality, while dietary total iron intake could decrease the risk of colorectal adenoma, esophageal cancer, coronary heart disease, and depression. Iron supplementation was a protective factor against eight outcomes. However, it was associated with decreased length and weight gain. The quality of evidence for most outcomes was "low" or "very low" with the remaining eleven as "high" or "moderate". All outcomes were categorized as class III, IV, or NS based on evidence classification. Although high iron intake has been identified to be significantly associated with a range of outcomes, firm universal conclusions about its beneficial or negative effects cannot be drawn given the low quality of evidence for most outcomes.

SDC mediates DNA methylation-controlled clock pace by interacting with ZTL in Arabidopsis.

Molecular bases of eukaryotic circadian clocks mainly rely on transcriptional-translational feedback loops (TTFLs), while epigenetic codes also play critical roles in fine-tuning circadian rhythms. However, unlike histone modification codes that play extensive and well-known roles in the regulation of circadian clocks, whether DNA methylation (5mC) can affect the circadian clock, and the associated underlying molecular mechanisms, remains largely unexplored in many organisms. Here we demonstrate that global genome DNA hypomethylation can significantly lengthen the circadian period of Arabidopsis. Transcriptomic and genetic evidence demonstrate that SUPPRESSOR OF drm1 drm2 cmt3 (SDC), encoding an F-box containing protein, is required for the DNA hypomethylation-tuned circadian clock. Moreover, SDC can physically interact with another F-box containing protein ZEITLUPE (ZTL) to diminish its accumulation. Genetic analysis further revealed that ZTL and its substrate TIMING OF CAB EXPRESSION 1 (TOC1) likely act downstream of DNA methyltransferases to control circadian rhythm. Together, our findings support the notion that DNA methylation is important to maintain proper circadian pace in Arabidopsis, and further established that SDC links DNA hypomethylation with a proteolytic cascade to assist in tuning the circadian clock.

Anaerobic fermentation of aerobic granular sludge: Insight into the effect of granule size and sludge structure on hydrolysis and acidification.

Aerobic granular sludge (AGS) has different physicochemical properties and microbial communities compared to conventional activated sludge (CAS), which may result in different behaviors during anaerobic fermentation and require further investigation. This study investigated the effect of granule size and sludge structure on the hydrolysis and acidification of AGS. Experimental results show that AGS exhibited significantly higher soluble chemical oxygen demand (SCOD) dissolution and total volatile fatty acids (TVFA) production (330.6-430.3 mg/gVSS and 231.0-312.5 mgCOD/gVSS) compared to conventional activated sludge (CAS) (167.0 mg/gVSS and 133.3 mgCOD/gVSS). This is because AGS (90.6-96.9 mg/gVSS) had higher extracellular polymeric substances (EPS) content than CAS (81.2 mg/gVSS). EPS can not only serve as substrates but also release the trapped hydrolases. Moreover, the relative abundances of hydrolytic/acidogenic bacteria and genes were higher in AGS (0.46%-3.60% and 3.01 × 10-3%-4.04 × 10-3%) than in CAS (0.30% and 1.23 × 10-3%). The optimal granule size for AGS fermentation was found to be 500-1600 µm. The crushing of granule structure promoted the dissolution of small amounts of EPS and the release of some trapped hydrolases, thereby potentially enhancing the enzyme-substrate contacts and bacteria-substrate interactions. Therefore, the highest SCOD dissolution (510.6 mg/gVSS) and TVFA production (352.1 mgCOD/gVSS) from crushed 500-1600 µm AGS were observed. Overall, the findings of this study provide valuable insights into the recovery of organic carbon from AGS via anaerobic fermentation.

Abaloparatide and teriparatide enhance mandibular growth in adolescent rats with site-specific and mechano-related effects.

OBJECTIVE: Teriparatide (TPTD) and abaloparatide (ABL) are two osteoanabolic drugs targeting parathyroid hormone (PTH)1R signalling. This study aimed to investigate the effects of TPTD and ABL on the adolescent mandibular growth. METHOD: In total, 70 4-week-old male Sprague-Dawley rats were randomly divided into 14 groups, treated with intermittent TPDT or ABL at various doses, accompanied by mandibular advancement (MA) or not. 3D printing was used to fabricate an innovative splint for MA. After a 4-week treatment, morphological measurement, histological and immunohistochemical analysis were performed. Mandibular condylar chondrocytes (MCCs) were treated with TPTD or ABL, followed by CCK-8 assay, alcian blue staining, real time-PCR and immunofluorescent staining. RESULT: In vivo, TPTD or ABL alone increased the condylar length and cartilage thickness, with up-regulated SOX9 and COL II, whilst down-regulated COL X; however, when combined with MA, the promotive effects were attenuated. TPTD or ABL alone increased the mandibular body height and mandibular angle width, whilst increased the mandibular body length and alveolar bone width when combined with MA. In vitro, TPTD or ABL enhanced the MCC proliferation, glycosaminoglycan synthesis, COL II and SOX9 expression, whilst down-regulated COL X, Ihh and PTH1R expression. CONCLUSION: Both ABL and TPTD enhance mandibular growth in adolescent rats with site-specific and mechano-related effects, including propelling chondrogenesis at the condylar cartilage and promoting bone apposition at other mechano-responsive sites. They behave as promising drugs for mandibular growth modification, and in general ABL seems more potent than TPTD in this context.

Sleep duration and health outcomes: an umbrella review.

PURPOSE: To collect existing evidence on the relationship between sleep duration and health outcomes. METHODS: A thorough search was conducted in PubMed, Web of Science, Embase, and the Cochrane Database of Systematic Reviews from inception to January, 2021. Meta-analyses of observational and interventional studies were eligible if they examined the associations between sleep duration and human health. RESULTS: In total, this umbrella review identified 69 meta-analyses with 11 outcomes for cancers and 30 outcomes for non-cancer conditions. Inappropriate sleep durations may significantly elevate the risk for cardiovascular disease (CVD), cognitive decline, coronary heart disease (CHD), depression, falls, frailty, lung cancer, metabolic syndrome (MS), and stroke. Dose-response analysis revealed that a 1-h reduction per 24 hours is associated with an increased risk by 3-11% of all-cause mortality, CHD, osteoporosis, stroke, and T2DM among short sleepers. Conversely, a 1-h increment in long sleepers is associated with a 7-17% higher risk of stroke mortality, CHD, stroke, and T2DM in adults. CONCLUSION: Inappropriate sleep duration is a risk factor for developing non-cancer conditions. Decreasing and increasing sleep hours towards extreme sleep durations are associated with poor health outcomes.

Bismuth Vacancy-Induced Efficient CO2 Photoreduction in BiOCl Directly from Natural Air: A Progressive Step toward Photosynthesis in Nature.

Photocatalytic CO2 conversion into carbonaceous fuels through artificial photosynthesis is beneficial to global warming mitigation and renewable resource generation. However, a high cost is always required by special CO2-capturing devices for efficient artificial photosynthesis. For achieving highly efficient photocatalytic CO2 reduction (PCR) directly from natural air, we report rose-like BiOCl that is rich in Bi vacancies (VBi) assembled by nanosheets with almost fully exposed active {001} facets. These rose-like BiOCl with VBi assemblies provide considerable adsorption and catalytic sites, which hoists the CO2 capture and reduction capabilities, and thus expedites the PCR to a superior value of 21.99 µmol·g-1·h-1 CO generation under a 300 W Xe lamp within 5 h from natural air. The novel design and construction of a photocatalyst in this work could break through the conventional PCR system requiring compression and purification for CO2, dramatically reduce expenses, and open up new possibilities for the practical application of artificial photosynthesis.

Traction of impacted and stacked maxillary anterior teeth with precise biomechanics followed by torque control using gate spring.

Impaction of multiple maxillary anterior teeth is a rare condition; when it occurs, it impacts the patient's chewing function and smile esthetics, and it has always been problematic for clinicians. This case report presents an 11-year-old girl with impaction of 3 adjacent maxillary anterior teeth, including labiopalatally oriented maxillary right central and lateral incisors and a mesially inclined maxillary right canine. These 3 impacted and stacked teeth were sequentially aligned after surgical exposure and orthodontic traction, and the surrounding dentigerous cyst healed simultaneously. Precise and delicate biomechanics will control root movement and prevent root collision. Gate spring, a novel torquing auxiliary, was used for highly efficient root torque movements of the previously impacted incisors. After 32-month treatment, the patient's occlusion and esthetics greatly improved.

A Simple Aggregation-Induced Emission Nanoprobe with Deep Tumor Penetration for Hypoxia Detection and Imaging-Guided Surgery in Vivo.

The pan-cancer detection and precise visualization of tiny tumors in surgery still face great challenges. As tumors grow aggressively, hypoxia is a common feature of solid tumors and has supplied a general way for detecting tumors. Herein, we report a simple aggregation-induced emission nanoprobe-TPE-4NE-O that can specifically switch on their fluorescence in the presence of cytochrome P450 reductase, a reductase which is overexpressed under hypoxia conditions. The probe can selectively light up the hypoxia cells and has shown enhanced deep tumor penetration via charge conversion both in vitro and in vivo. After being modified with FA-DSPE-PEG, higher tumor uptake can be seen and FA-DSPE/TPE-4NE-O showed specific visualization to the hypoxia cancer cells. Excitingly, much brighter fluorescence was accumulated at the tumors in the FA-DSPE/TPE-4NE-O group, even though the tumor was as small as 2.66 mm. The excellent performance of FA-DSPE/TPE-4NE-O in detecting tiny tumors has made it possible for imaging-guided tumor resection. More importantly, the probe exhibited good biocompatibility with negligible organ damage and eliminated a hemolysis risk. The simple but promising probe has supplied a new strategy for pan-cancer detection and tiny tumor visualization, which have shown great potential in clinical translation.

Engineering broad-spectrum disease-resistant rice by editing multiple susceptibility genes.

Rice blast and bacterial blight are important diseases of rice (Oryza sativa) caused by the fungus Magnaporthe oryzae and the bacterium Xanthomonas oryzae pv. oryzae (Xoo), respectively. Breeding rice varieties for broad-spectrum resistance is considered the most effective and sustainable approach to controlling both diseases. Although dominant resistance genes have been extensively used in rice breeding and production, generating disease-resistant varieties by altering susceptibility (S) genes that facilitate pathogen compatibility remains unexplored. Here, using CRISPR/Cas9 technology, we generated loss-of-function mutants of the S genes Pi21 and Bsr-d1 and showed that they had increased resistance to M. oryzae. We also generated a knockout mutant of the S gene Xa5 that showed increased resistance to Xoo. Remarkably, a triple mutant of all three S genes had significantly enhanced resistance to both M. oryzae and Xoo. Moreover, the triple mutant was comparable to the wild type in regard to key agronomic traits, including plant height, effective panicle number per plant, grain number per panicle, seed setting rate, and thousand-grain weight. These results demonstrate that the simultaneous editing of multiple S genes is a powerful strategy for generating new rice varieties with broad-spectrum resistance.

A fungal effector and a rice NLR protein have antagonistic effects on a Bowman-Birk trypsin inhibitor.

Bowman-Birk trypsin inhibitors (BBIs) play important roles in animal and plant immunity, but how these protease inhibitors are involved in the immune system remains unclear. Here, we show that the rice (Oryza sativa) BBI protein APIP4 is a common target of a fungal effector and an NLR receptor for innate immunity. APIP4 exhibited trypsin inhibitor activity in vitro and in vivo. Knockout of APIP4 in rice enhanced susceptibility, and overexpression of APIP4 increased resistance to the fungal pathogen Magnaporthe oryzae. The M. oryzae effector AvrPiz-t interacted with APIP4 and suppressed APIP4 trypsin inhibitor activity. By contrast, the rice NLR protein Piz-t interacted with APIP4, enhancing APIP4 transcript and protein levels, and protease inhibitor activity. Our findings reveal a novel host defence mechanism in which a host protease inhibitor targeted by a fungal pathogen is protected by an NLR receptor.

Antigens reversibly conjugated to a polymeric glyco-adjuvant induce protective humoral and cellular immunity.

Fully effective vaccines for complex infections must elicit a diverse repertoire of antibodies (humoral immunity) and CD8+ T-cell responses (cellular immunity). Here, we present a synthetic glyco-adjuvant named p(Man-TLR7), which, when conjugated to antigens, elicits robust humoral and cellular immunity. p(Man-TLR7) is a random copolymer composed of monomers that either target dendritic cells (DCs) via mannose-binding receptors or activate DCs via Toll-like receptor 7 (TLR7). Protein antigens are conjugated to p(Man-TLR7) via a self-immolative linkage that releases chemically unmodified antigen after endocytosis, thus amplifying antigen presentation to T cells. Studies with ovalbumin (OVA)-p(Man-TLR7) conjugates demonstrate that OVA-p(Man-TLR7) generates greater humoral and cellular immunity than OVA conjugated to polymers lacking either mannose targeting or TLR7 ligand. We show significant enhancement of Plasmodium falciparum-derived circumsporozoite protein (CSP)-specific T-cell responses, expansion in the breadth of the αCSP IgG response and increased inhibition of sporozoite invasion into hepatocytes with CSP-p(Man-TLR7) when compared with CSP formulated with MPLA/QS-21-loaded liposomes-the adjuvant used in the most clinically advanced malaria vaccine. We conclude that our antigen-p(Man-TLR7) platform offers a strategy to enhance the immunogenicity of protein subunit vaccines.

The fungal pathogen Magnaporthe oryzae suppresses innate immunity by modulating a host potassium channel.

Potassium (K+) is required by plants for growth and development, and also contributes to immunity against pathogens. However, it has not been established whether pathogens modulate host K+ signaling pathways to enhance virulence and subvert host immunity. Here, we show that the effector protein AvrPiz-t from the rice blast pathogen Magnaporthe oryzae targets a K+ channel to subvert plant immunity. AvrPiz-t interacts with the rice plasma-membrane-localized K+ channel protein OsAKT1 and specifically suppresses the OsAKT1-mediated K+ currents. Genetic and phenotypic analyses show that loss of OsAKT1 leads to decreased K+ content and reduced resistance against M. oryzae. Strikingly, AvrPiz-t interferes with the association of OsAKT1 with its upstream regulator, the cytoplasmic kinase OsCIPK23, which also plays a positive role in K+ absorption and resistance to M. oryzae. Furthermore, we show a direct correlation between blast disease resistance and external K+ status in rice plants. Together, our data present a novel mechanism by which a pathogen suppresses plant host immunity by modulating a host K+ channel.