Predictive Value of Serum microRNA-29b-3p in Recurrence of Atrial Fibrillation After Radiofrequency Catheter Ablation.

Objective: Atrial fibrillation (AF) is a common arrhythmia. This study explored serum miR-29b-3p expression in AF patients and its value in predicting AF recurrence after radiofrequency catheter ablation (RFCA). Methods: Totally 100 AF patients who underwent RFCA were enrolled, with 100 individuals without AF as controls. Serum miR-29b-3p expression in participants was determined using RT-qPCR. The correlation between miR-29b-3p and atrial fibrosis markers (FGF-21/FGF-23) was assessed by Pearson analysis. The diagnostic efficacy of serum miR-29b-3p and FGF-21/FGF-23 in predicting AF recurrence after RFCA was analyzed by the receiver operating characteristic (ROC) curves. The Kaplan-Meier method was adopted to evaluate the effect of miR-29b-3p expression on the incidence of AF recurrence after RFCA. The independent risk factors for AF recurrence after RFCA were analyzed by logistic regression analysis. Results: Serum miR-29b-3p was poorly expressed in AF patients. After RFCA, AF patients showed elevated serum miR-29b-3p expression. Serum miR-29b-3p expression in AF patients negatively correlated with serum FGF-21 and FGF-23 concentrations. The cut-off values of serum miR-29b-3p, FGF-21, and FGF-23 in identifying AF recurrence were 0.860 (sensitivity: 100.00%, specificity: 39.71%), 222.2 pg/mL (sensitivity: 96.88%, specificity: 32.35%) and 216.3 ng/mL (sensitivity: 53.13%, specificity: 70.59%), respectively. Patients with low miR-29b-3p expression had a significantly higher incidence of AF recurrence than patients with high miR-29b-3p expression. Serum miR-29b-3p expression was one of the independent risk factors for AF recurrence after RFCA. Conclusion: Low miR-29b-3p expression in AF patients has certain predictive values and is one of the independent risk factors for AF recurrence after RFCA.

A new intestinal supplement 'Synbiotics' therapeutically regulates gut microbiota and activates PPARs pathway to inhibit Alzheimer's disease progression in mouse models.

We aimed to investigate the role of Synbiotic preparations on the interaction of gut microbiota with AD development. APP/PS1 mice were randomized into APP/PS1 and Synbiotics groups, and C57BL/6J mice were used as wild type (WT) control group. The mice in the Synbiotics group and the APP/PS1 group were given Synbiotics and xylo-oligosaccharides for 3 months, respectively. The mice in the WT group were given the same amount of normal saline. Cognitive function was measured. Positron emission computed tomography/magnetic resonance imaging (PET/MRI) was used to detect fasting blood glucose level. Immunohistochemical assay, ELISA, western blot and qRT-PCR were carried out to detect inflammatory factors. DNA extraction of fecal sample was performed to carry out sequencing. Bioinformatics analysis, metabolites sample preparation and Liquid Chromatograph Mass Spectrometer (LC/MS) analysis were also performed. Synbiotics treatment can significantly ameliorate learning and memory competence by inhibiting Aß protein deposition. Different bacteria in the intestine were significantly improved and changes in gut microbiota can affect the intestinal metabolism to affect multiple potential pathways after Synbiotics treatment. Synbiotics treatment can activate peroxisome proliferator activated receptor (PPARs) signaling pathway and significantly reduce neuroinflammation in APP/PS1 mice brains. Synbiotics treatment can effectively reduce neuro-inflammatory response through the regulation of intestinal microflora to delay AD development.

Analyzing the value of delayed 18 F-FDG PET/CT images in diagnosing small colorectal cancer liver metastases in patients with hypothyroidism based on diagnostic accuracy and image standardized uptake value.

PURPOSE: The objective of this study was to investigate the value of delayed 18F fluorodeoxyglucose PET/computed tomography (18F-FDG PET/CT) images in patients with small colorectal cancer liver metastases (CRLMs) with hypothyroidism. METHOD: We performed a retrospective analysis of 66 small-CRLM patients with hypothyroidism and 66 small-CRLM patients with euthyroidism, all of whom underwent dual-time-point 18 F-FDG PET/CT imaging. First, the diagnostic accuracy of PET/CT early imaging and PET/CT delayed imaging on lesions was analyzed. Next, the correlation of metabolic parameters between PET/CT early imaging and PET/CT delayed imaging was analyzed according to the grouping of all lesions. Finally, PET/CT parameters were analyzed for correlation with thyroid hormones. RESULTS: The diagnostic accuracy of delayed imaging in small-CRLM patients with hypothyroidism is not as good as that in small-CRLM patients with euthyroidism; PET/CT metabolic parameters are also unfavorable for the diagnosis of small-CRLM. For small-CRLM patients with hypothyroidism, the greater the thyroid-stimulating hormone level, the greater the uptake of 18 F-FDG in normal liver tissue, and the smaller the ratio of tumor lesion uptake to normal liver tissue uptake. CONCLUSION: PET/CT-delayed imaging has better performance than early imaging in small-CRLM patients with euthyroidism. However, the more severe the hypothyroidism, the worse the diagnostic delayed imaging performance. The scan time can be extended appropriately to optimize the imaging efficacy.

A promising self-nanoemulsifying adjuvant with plant-derived saponin D boosts immune response and exerts an anti-tumor effect.

Objectives: The low immunogenicity of tumor antigens and unacceptable toxicity of adjuvants has hindered the application and development of tumor vaccines. Hence, we designed a novel anti-tumor vaccine composed of a plant-derived immunostimulant molecular nanoadjuvant (a self-nanoemulsifying system, SND) and the antigen OVA, to reinvigorate the immune response and inhibit tumor progression. Methods: In this study, this novel nanoadjuvant with Saponin D (SND) was designed and prepared by low-energy emulsification methods. Several important characteristics of the SND, including morphology, size, polymer dispersity index (PDI), zeta potential, and stability, were estimated, and the cytotoxicity of the SND was evaluated by MTT assay. Additionally, the immune response in terms of antibody titer levels and cellular immunity were evaluated in vivo after immunization with the vaccine, and the preventative and therapeutic effects of this novel vaccine against tumors were estimated. Finally, the antigen release profile was determined by IVIS imaging and by in vivo assay. Results: This SND nanoadjuvant had good characteristics including the average particle size of 26.35 ± 0.225 nm, narrow distribution of 0.221 ± 1.76, and stability zeta potential of -12.9 ± 0.83 mV. And also, it had good stability (size, PDI, zeta potential, antigen stability) and low toxicity in vitro and in vivo, and delayed antigen release in vivo. The humoral immune response (IgG, IgG1, IgG2a, and IgG2b) and cellular immune level (cytokines of splenocytes including IFN-γ, IL-4, IL-1ß andIL-17A) were both improved greatly after injected immunization at 0, 14, 28 days with the novel nanoadjuvant and antigen OVA. Importantly, this novel nanoadjuvant combined with OVA might lead to the induction of the prevent and treatment efficacy in the E.G7-OVA tumor-bearing mice. Conclusions: These results suggested that this novel nanoadjuvant encapsulated natural plant immunostimulant molecular OPD could be a good candidate of tumor vaccine adjuvant for reinvigorating the immune response and powerfully inhibiting tumor growth effect.

Tubeimuside I improves the efficacy of a therapeutic Fusobacterium nucleatum dendritic cell-based vaccine against colorectal cancer.

Introduction: Fusobacterium nucleatum (F. nucleatum) infection has been confirmed to be associated with the development, chemoresistance, and immune evasion of colorectal cancer (CRC). The complex relationship between the microorganism, host cells, and the immune system throughout all stages of CRC progression, which makes the development of new therapeutic methods difficult. Methods: We developed a new dendritic cell (DC) vaccine to investigate the antitumor efficacy of CRC immunotherapy strategies. By mediating a specific mode of interaction between the bacteria, tumor, and host, we found a new plant-derived adjuvant, tubeimuside I (TBI), which simultaneously improved the DC vaccine efficacy and inhibited the F. nucleatum infection. Encapsulating TBI in a nanoemulsion greatly improved the drug efficacy and reduced the drug dosage and administration times. Results: The nanoemulsion encapsulated TBI DC vaccine exhibited an excellent antibacterial and antitumor effect and improved the survival rate of CRC mice by inhibiting tumor development and progression. Discussion: In this study, we provide a effective strategy for developing a DC-based vaccine against CRC and underlies the importance of further understanding the mechanism of CRC processes caused by F. nucleatum.

MicroRNA-31 induced by Fusobacterium nucleatum infection promotes colorectal cancer tumorigenesis.

Persistent Fusobacterium nucleatum infection is associated with the development of human colorectal cancer (CRC) and promotes tumorigenicity, but the underlying mechanisms remain unclear. Here, we reported that F. nucleatum promoted the tumorigenicity of CRC, which was associated with F. nucleatum-induced microRNA-31 (miR-31) expression in CRC tissues and cells. F. nucleatum infection inhibited autophagic flux by miR-31 through inhibiting syntaxin-12 (STX12) and was associated with the increased intracellular survival of F. nucleatum. Overexpression of miR-31 in CRC cells promoted their tumorigenicity by targeting eukaryotic initiation factor 4F-binding protein 1/2 (eIF4EBP1/2), whereas miR-31 knockout mice were resistant to the formation of colorectal tumors. In conclusion, F. nucleatum, miR-31, and STX12 form a closed loop in the autophagy pathway, and continuous F. nucleatum-induced miR-31 expression promotes the tumorigenicity of CRC cells by targeting eIF4EBP1/2. These findings reveal miR-31 as a potential diagnostic biomarker and therapeutic target in CRC patients with F. nucleatum infection.

The impact of digital logistics under the big environment of economy.

Digital logistics techniques are important for business applications that contribute to economic growth. The modern supply chain or logistics seeks to implement a large-scale smart infrastructure incorporating data, physical objects, information, products, and business progressions. The business applications are utilized various intelligent techniques to maximize the logistic process. However, the logistic process suffers due to transportation costs, quality, and multinational transportation. These factors frequently affect the region's economic growth. In addition, most cities are located in remote areas that receive improper logistic support, which minimizes business growth. So, this work analyzes the impact of digital logistics on the region's economy. The Yangtze River economic belt region, which includes almost 11 cities, is chosen for analysis. The gathered information is processed by Dynamic Stochastic Equilibrium with Statistical Analysis Modelling (DSE-SAM), which predicts the correlation and influence of digital logistics on economic development. Here, the judgment matrix is constructed to reduce the difficulties of data standardization and normalization processes. Then entropy model and statistical correlation analysis are utilized to improve the overall impact analysis process. Finally, the developed DSE-SAM based created system efficiency is compared with the other economic models, such as Spatial Durbin Model (SDM), Coupling Coordination Degree Model (CCDM), and Collaborative Degree Model (CDM). The results of the suggested DSE-SAM model achieve a high correlation of urbanization, logistics, and ecology in the Yangtze River economic belt region compared to other regions.

In Vitro Cellular Activity Evaluation of the Nanoemulsion Vaccine Adjuvant Ophiopogonin D.

As a principal ingredient of vaccines, adjuvants can directly induce or enhance the powerful, widespread, innate, and adaptive immune responses associated with antigens. Ophiopogonin D (OP-D), a purified component extracted from the plant Ophiopogon japonicus, has been found to be useful as a vaccine adjuvant. The problems of the low solubility and toxicity of OP-D can be effectively overcome by using a low-energy emulsification method to prepare nanoemulsion ophiopogonin D (NOD). In this article, a series of in vitro protocols for cellular activity evaluation are examined. The cytotoxic effects of L929 were determined using a cell counting kit-8 assay. Then, the secreted cytokine levels and corresponding immune cell numbers after the stimulation and culture of splenocytes from immunized mice were detected by ELISA and ELISpot methods. In addition, the antigen uptake ability in bone marrow-derived dendritic cells (BMDCs), which were isolated from C57BL/6 mice and matured after incubation with GM-CSF plus IL-4, was observed by laser scanning confocal microscopy (CLSM). Importantly, macrophage activation was confirmed by measuring the levels of IL-1ß, IL-6, and tumor necrosis factor alpha (TNF-α) cytokines by ELISA kits after coculturing peritoneal macrophages (PMs) from blank mice with the adjuvant for 24 h. It is hoped that this protocol will provide other researchers with direct and effective experimental approaches to evaluate the cellular response efficacies of novel vaccine adjuvants.

Long non-coding RNA EVADR induced by Fusobacterium nucleatum infection promotes colorectal cancer metastasis.

Both Fusobacterium nucleatum (F. nucleatum) and long non-coding RNA (lncRNA) EVADR are associated with colorectal cancer (CRC), but their relationship with CRC metastasis and the mechanisms by which EVADR promotes CRC metastasis are poorly understood. Here, we report that F. nucleatum promotes colorectal cancer cell metastasis to the liver and lung and that it can be detected in CRC-metastasis colonization in mouse models. Furthermore, F. nucleatum upregulates the expression of EVADR, which can increase the metastatic ability of CRC cells in vivo and in vitro. Mechanistically, elevated EVADR serves as a modular scaffold for the Y-box binding protein 1 (YBX1) to directly enhance the translation of epithelial-mesenchymal transition (EMT)-related factors, such as Snail, Slug, and Zeb1. These findings suggest that EVADR induced by F. nucleatum promotes colorectal cancer metastasis through YBX1-dependent translation. The EVADR-YBX1 axis may be useful for the prevention and treatment of patients with F. nucleatum-associated CRC metastasis.

Effect of humic and calcareous substance amendments on the availability of cadmium in paddy soil and its accumulation in rice.

Humic substances (HS) are widely known as important components in soil and significantly affect the mobility of metals due to their large surface area and abundant organic functional groups. Calcareous substances (CSs) are also commonly used as robust and cost-effective amendments for increasing the pH of acidic soils and decreasing the mobility of metals in soils. In this study, we developed a new remediation scheme for cadmium (Cd)-contaminated soil remediation by coupling HS and CS. The results showed that regardless of the addition of fulvic acid (FA), all the CS-containing treatments significantly increased the soil pH by 0.32-0.60, and the concentration of bioavailable Cd decreased in the moderately (field experiment soil, maximum 62%) and highly (pot experiment soil, maximum 57%) Cd-contaminated soils. The Cd content in rice (Oryza sativa L.) tissues significantly decreased after all the treatments. The bioaccumulation factors (BAFs) decreased by over 50% in the roots, stems, leaves and husks in all treatments, while the translocation factors (TFs) only significantly decreased in the highly contaminated soil. Among all treatments, the two HS+CS treatments (FA+CaCO3 and FA+CaO) had the greatest effect on decreasing the concentration of bioavailable Cd in soil and Cd in brown rice grains. The suggested mechanism for the effectiveness of coupled HS and CS was that CS first mitigated the pH and precipitated Cd, followed by a complexation effect between HS and Cd. Although the Cd in rice grains in both cases was higher than the standard limit, HS+CS remediation can be advocated as a robust, simple and cost-effective scheme for Cd remediation if the additive dose is slightly increased, as this approach can simultaneously improve the pH of acidic soil and adsorb Cd in soil.

Antimicrobial limonoids from the seeds of Cipadessa cinerascensa.

Phytochemical investigation on the 90% EtOH extract of the seeds of Cipadessa cinerascensa led to the isolation of three new limonoids, cinerascenoids A-C (1-3). Structural elucidation of all the compounds were performed by spectral methods such as 1 D and 2 D (1H-1H COSY, HMQC, and HMBC) NMR spectroscopy. All the limonoids were in vitro evaluated for their antimicrobial activities against six pathogenic microorganisms. Limonoids 1 and 2 exhibited some activities against three Gram negative bacteria with MIC values less than 60 µg/ml.

Identification of GROWTH-REGULATING FACTOR transcription factors in lettuce (Lactuca sativa) genome and functional analysis of LsaGRF5 in leaf size regulation.

BACKGROUND: GROWTH-REGULATING FACTORs (GRFs), a type of plant-specific transcription factors, play important roles in regulating plant growth and development. Although GRF gene family has been identified in various plant species, a genome-wide analysis of this family in lettuce (Lactuca sativa L.) has not been reported yet. RESULTS: Here we identified 15 GRF genes in lettuce and performed comprehensive analysis of them, including chromosomal locations, gene structures, and conserved motifs. Through phylogenic analysis, we divided LsaGRFs into six groups. Transactivation assays and subcellular localization of LsaGRF5 showed that this protein is likely to act as a transcriptional factor in the cell nucleus. Furthermore, transgenic lettuce lines overexpressing LsaGRF5 exhibited larger leaves, while smaller leaves were observed in LsaMIR396a overexpression lines, in which LsaGRF5 was down-regulated. CONCLUSIONS: These results in lettuce provide insight into the molecular mechanism of GRF gene family in regulating leaf growth and development and foundational information for genetic improvement of the lettuce variations specialized in leaf character.

Dynamics of soil bacteria and fungi communities of dry land for 8 years with soil conservation management.

Microorganisms play an important role in nutrient cycling and ecosystem stability. This experiment studied the conservation management approaches [control without fertilizer (CK); fertilizer and different mulching based straw mulching (SM), plastic mulching (PM), ridge-furrow with plastic mulching (RFPFM), and green manure (GM)] effects on the soil microbial community structures in spring corn (Zea Mayis) dry land. The results showed that the bacterial phylum mainly included Proteobacteria (28.2%-36.8%), Acidobacteriota (9.1%-17.9%), Bacteroidota (5.6%-8.9%) and Actinobacteria (3.1-6.2%). The most richness fungal components were Ascomycota (35.2%-44.2%), Basidiomycota (3.3%-12%) and Mortierellomycota (3.4%-6.6%). Additionally, the highest Chao1 and abundance-based coverage estimator (ACE) indexes of bacteria (2931.9 and 2953.7) and fungi (1083.316 and 1100.650) were present in RFPFM that indicating the richest microbial abundance, the highest Shannon and Simpson indexes was exist in PM (9.332 and 0.996) for bacteria and RFPFM (6.753 and 0.974) for fungi. Therefore, this study reveals the conservation management of fertilizer addition and mulching management obviously promoted microbial diversity and altered the superior microbial distribution that provides a potential way for agricultural sustainable management approaches in production practice during circular economy.

Evaluation of N2O emission from rainfed wheat field in northwest agricultural land in China.

The net greenhouse gas (NGHG) emissions and net greenhouse gas intensity (NGHGI) were investigated via the determination of nitrous oxide (N2O) emission in loess soil under rainfed winter wheat monocropping system during 3 years of field study in Northwest China. Five treatments were carried out: control (N0), conventional nitrogen (N) application (NCon), optimized N application with straw (SNOpt), optimized N application with straw and 5% of dicyanodiamide (SNOpt + DCD), and optimized N rate of slow release fertilizer with straw (SSRFOpt). Over a 3-year period, the NGHG emissions were achieved 953, 1322, 564, and 1162 kg CO2-eq ha-1, simultaneously, and the NGHGI arrived 158, 223, 86, and 191 kg CO2-eq t-1 grain in NCon, SNOpt, SNOpt + DCD, and SSROpt grain, respectively. Contrasted with conventional farming system, optimized farming methods reduced 32% of N fertilizer use without significant decrease in grain yield, but brought about 38% increase in N2O emissions, up to 28% gained in soil CH4 uptake. Thus, it was observed that the straw incorporation performs noticeable increased in N2O emissions in the winter wheat cropping season. Among the optimized N fertilizer rates compared with the SNOpt treatment, the SNOpt +DCD and SSROpt treatments decreased in N2O emissions by approximately 55% and 13%, respectively. Additionally, the N2O emission factor across over a 3-year period was 0.41 ± 0.08% derived from N fertilizer, and it was half of IPCC default values for upland corps. It is expected possibly due to low precipitation and soil moisture with the monocropping system. The 25% higher in the amount of rainfall (almost 300 mm in 2013-2014) during a cropping season underwent into 1-2-fold increase in N2O emissions from N-fertilized plots. As the statistical differences among annual cumulative emissions coincided with that during winter wheat growing season, it can be concluded that crop growing season is a vital important period for the determination of N2O emissions from under rainfed monocropping system.

Alteration of microRNA-4474/4717 expression and CREB-binding protein in human colorectal cancer tissues infected with Fusobacterium nucleatum.

Colorectal cancer (CRC) is a common and highly lethal form of cancer. Although the etiologic role of Fusobacterium nucleatum (F. nucleatum) in the development of CRC has been elucidated, the specific tumor molecules involved in the progression of CRC induced by F. nucleatum have not been identified. This study investigated several miRNAs and genes involved in the progression of F. nucleatum-induced CRC by Affymetrix miRNA microarray technology and GeneChip Human Transcriptome Array 2.0. The results suggest that miR-4474 and miR-4717 are up-regulated in CRC tissues in response to F. nucleatum infection, compared with the control group (paracancerous tissues), while other genes associated with signaling pathways in cancer, including CREB-binding protein (CREBBP), STAT1, PRKACB, CAMK2B, JUN, TP53 and EWSR1, were dysregulated. Bioinformatic analysis identified CREBBP as the primary aberrantly expressed gene in F. nucleatum-induced CRC. Consistent with the microarray analysis results, real-time RT-PCR analysis demonstrated that the expression of miR-4474/4717 was upregulated while that of CREBBP mRNA was downregulated in CRC patients infected with F. nucleatum. Additionally, CREBBP was identified as a novel target of miR-4474/4717. The results of this study suggest that miR-4474 and miR-4717 are involved in the progression of F. nucleatum-induced CRC by posttranscriptionally regulating the target gene CREBBP.

Epitope-loaded nanoemulsion delivery system with ability of extending antigen release elicits potent Th1 response for intranasal vaccine against Helicobacter pylori.

BACKGROUND: Helicobacter pylori (H. pylori) infection remains a global public health issue, especially in Asia. Due to the emergence of antibiotic-resistant strains and the complexity of H. pylori infection, conventional vaccination is the best way to control the disease. Our previous study found that the N-acetyl-neuroaminyllactose-binding hemagglutinin protein (HpaA) is an effective protective antigen for vaccination against H. pylori infection, and intranasal immunization with the immunodominant HpaA epitope peptide (HpaA 154-171, P22, MEGVLIPAGFIKVTILEP) in conjunction with a CpG adjuvant decreased bacterial colonization in H. pylori-infected mice. However, to confer more robust and effective protection against H. pylori infection, an optimized delivery system is needed to enhance the P22-specific memory T cell response. RESULTS: In this study, an intranasal nanoemulsion (NE) delivery system offering high vaccine efficacy without obvious cytotoxicity was designed and produced. We found that this highly stable system significantly prolonged the nasal residence time and enhanced the cellular uptake of the epitope peptide, which powerfully boosted the specific Th1 responses of the NE-P22 vaccine, thus reducing bacterial colonization without CpG. Furthermore, the protection efficacy was further enhanced by combining the NE-P22 vaccine with CpG. CONCLUSION: This epitope-loaded nanoemulsion delivery system was shown to extend antigen release and elicit potent Th1 response, it is an applicable delivery system for intranasal vaccine against H. pylori.

Development of a safety and efficacy nanoemulsion delivery system encapsulated gambogic acid for acute myeloid leukemia in vitro and in vivo.

This study aimed to improve the solubility, reduce the side effects and enhance the efficacy of gambogic acid against acute myeloid leukemia in vitro and in vivo. This oil-in-water nanoemulsion (average size 17.20 ±â€¯0.11 nm, zeta potential 4.17 ±â€¯0.82 mV) containing Tween-80, glycol, squalene and gambogic acid with improving 4000 times solubility was prepared by pseudoternary phase diagrams. We found that this nanoemulsion successfully encapsulated gambogic acid; it was stable and showed an obvious delayed release effect for the drug in three different phosphate-buffered saline (pH = 2.0, 5.8 and 7.4). The half inhibiting concentration (IC50) of this nanoemulsion (480.7 µg/mL and 408 µg/mL) were 1.67 times and 1.98 times higher than those of its water solution (287 µg/mL and 206 µg/mL) after acting on the toxicity standard cell line (L929 line) for 24 h and 48 h, respectively. Importantly, acute injection toxicity indicated that the half lethal dose (LD50) of this nanoemulsion (23.25 mg/kg, 95% LD50, 21.7-25.16 mg/kg) was 1.26 times higher than that of its water solution (18.59 mg/kg, 95% LD50, 16.84-20.53 mg/kg). Compared with its suspension, the bioavailability of this nanoemulsion was 318.2%. Furthermore, this nanoemulsion had a better efficacy against the acute myeloid leukemia in vitro and in vivo by improving the time and percent of survival (MV4-11 engrafts mice) and reducing half inhibiting concentration values in acute myeloid leukemia such as Jurket, HL-60 and MV4-11 cells. Our studies suggested that this nanoemulsion may be a promising therapeutic medicine for acute myeloid leukemia.

Chitosan-polyvinyl alcohol nanoscale liquid film-forming system facilitates MRSA-infected wound healing by enhancing antibacterial and antibiofilm properties.

INTRODUCTION: Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most predominant and fatal pathogens at wound infection sites. MRSA is difficult to treat because of its antibiotic resistance and ability to form biofilms at the wound site. METHODS: In this study, a novel nanoscale liquid film-forming system (LFFS) loaded with benzalkonium bromide was produced based on polyvinyl alcohol and chitosan. RESULTS: This LFFS showed a faster and more potent effect against MRSA252 than benzalkonium bromide aqueous solution both in vitro and in vivo. Additionally, the LFFS had a stronger ability to destroy biofilms (5 mg/mL) and inhibit their formation (1.33 µg/mL). The LFFS inflicted obvious damage to the structure and integrity of MRSA cell membranes and caused increases in the release of alkaline phosphate and lactate dehydrogenase in the relative electrical conductivity and in K+ and Mg2+ concentrations due to changes in the MRSA cell membrane permeability. CONCLUSION: The novel LFFS is promising as an effective system for disinfectant delivery and for application in the treatment of MRSA wound infections.

An immunopotentiator, ophiopogonin D, encapsulated in a nanoemulsion as a robust adjuvant to improve vaccine efficacy.

As an ingredient of vaccines, adjuvants are indispensable for enhancing and directly inducing robust and extensive adaptive immune responses associated with vaccine antigens. In this study, we initially determined that a new molecular immunopotentiator, ophiopogonin D (OP-D), enhanced the antibody response to antigen. Because OP-D has certain disadvantages, including poor solubility, we next encapsulated OP-D in a nanoemulsion adjuvant (nanoemulsion-encapsulated OP-D, NOD) using low-energy emulsification methods. The NOD thus produced was small, with an average size of 76.45 nm, and exhibited good distribution (PdI value 0.16), significantly increasing the solubility of OP-D. Furthermore, NOD exhibited reduced cellular toxicity and acute toxicity. Our results showed that a fusion antigen of MRSA (HlaH35LIsdB348-465) formulated with NOD significantly improved humoral and cellular immune responses compared to those observed in the antigen/OP-D and antigen/AlPO4 groups. Compared with antigen/OP-D, the antigen formulated with NOD more effectively promoted antigen uptake by dendritic cells (DCs) and the activation of antigen-presenting cells (APCs). Moreover, the NOD-formulated antigen had ideal protective efficacy in a MRSA sepsis model by inducing more potent antibody responses and a Th1/Th17-biased CD4+ T cell immune response. Therefore, these results suggest that NOD is a promising and robust adjuvant platform for a MRSA vaccine. STATEMENT OF SIGNIFICANCE: We first identified a new powerful immunopotentiator, Ophiopogonin D, among dozens of natural products and then used nanotechnology to construct a highly efficient and low toxic adjuvant system (NOD). Our approach intersects natural medicinal chemistry, nanomaterials and immunology, revealing that a strong adjuvant activity of this adjuvant system was verified in vitro and in vivo, and the application of MRSA subunit vaccine model for survival experiments achieved a 100% protection rate. This research illustrate that NOD is a promising and robust adjuvant platform for subunit vaccines.

Pursuing sustainable productivity with millions of smallholder farmers.

Sustainably feeding a growing population is a grand challenge, and one that is particularly difficult in regions that are dominated by smallholder farming. Despite local successes, mobilizing vast smallholder communities with science- and evidence-based management practices to simultaneously address production and pollution problems has been infeasible. Here we report the outcome of concerted efforts in engaging millions of Chinese smallholder farmers to adopt enhanced management practices for greater yield and environmental performance. First, we conducted field trials across China's major agroecological zones to develop locally applicable recommendations using a comprehensive decision-support program. Engaging farmers to adopt those recommendations involved the collaboration of a core network of 1,152 researchers with numerous extension agents and agribusiness personnel. From 2005 to 2015, about 20.9 million farmers in 452 counties adopted enhanced management practices in fields with a total of 37.7 million cumulative hectares over the years. Average yields (maize, rice and wheat) increased by 10.8-11.5%, generating a net grain output of 33 million tonnes (Mt). At the same time, application of nitrogen decreased by 14.7-18.1%, saving 1.2 Mt of nitrogen fertilizers. The increased grain output and decreased nitrogen fertilizer use were equivalent to US$12.2 billion. Estimated reactive nitrogen losses averaged 4.5-4.7 kg nitrogen per Megagram (Mg) with the intervention compared to 6.0-6.4 kg nitrogen per Mg without. Greenhouse gas emissions were 328 kg, 812 kg and 434 kg CO2 equivalent per Mg of maize, rice and wheat produced, respectively, compared to 422 kg, 941 kg and 549 kg CO2 equivalent per Mg without the intervention. On the basis of a large-scale survey (8.6 million farmer participants) and scenario analyses, we further demonstrate the potential impacts of implementing the enhanced management practices on China's food security and sustainability outlook.