Driving the effectiveness of public health emergency management strategies through cross-departmental collaboration: Configuration analysis based on 15 cities in China.

Background: Owing to the complexity of and changes associated with modern public health emergencies, cross-departmental collaborative governance is an inevitable choice for ensuring effective emergency management. In the context of emergency management research, the way in which taking full advantage of synergy can be used to enhance the effectiveness of emergency prevention and control approaches is an important issue that must be addressed urgently. Methods: Combined with China's responses to the management of public health emergencies, in this study, we construct a theoretical analysis framework involving three dimensions: information, organization, and environment. Our proposed framework relies on the fuzzy-set qualitative comparative analysis (fsQCA) method to analyze the mechanisms behind the prevention and control of coronavirus disease 2019 (COVID-19) cases across 15 cities located in typical provinces throughout China and explore the roles of cross-departmental collaboration in the processing of various elements as well as the effects of their combination on the action mechanisms for ensuring the effectiveness of emergency management approaches. Findings: The results show a significant conditional correlation between the effectiveness of emergency management and the factors affecting cross-departmental coordination. Based on the characteristics of multiple concurrent paths, the driving paths can be classified into four categories: organizational, environmental, environment-balanced, and organization environment-based dual-core categories. Conclusions: The effectiveness of public health emergency management is the result of multiple factors. Local governments should strengthen the coordination and integration of information, organization, and environment, improve the coordinated system associated with emergency management, promote the "two-wheel drive" of high-quality development as well as accurate prevention and control, explore and perfect the adaptive combinatorial optimization path, and effectively transform the advantages of linking multi-dimensional factors with governance efficiency.

Frequencies and Variations of Magnaporthe oryzae Avirulence Genes in Hunan Province, China.

Rice blast caused by Magnaporthe oryzae poses significant threaten to rice production. For breeding and deploying resistant rice varieties, it is essential to understand the frequencies and genetic variations of avirulence (AVR) genes in the pathogen populations. In this study, 444 isolates were collected from Hunan Province, China in 2012, 2015, and 2016, and their pathogenicity was evaluated by testing them on monogenic rice lines carrying resistance genes Pita, Pizt, Pikm, Pib, or Pi9. The frequencies of corresponding AVR genes AVRPizt, AVRPikm, AVRPib, AVRPi9, and AVRPita were characterized by amplification and sequencing these genes in the isolates. Both Pi9 and Pikm conferred resistance to >75% of the tested isolates, while Pizt, Pita, and Pib were effective against 55.63, 15.31, and 3.15% of the isolates, respectively. AVRPikm and AVRPi9 were detected in 90% of the isolates and AVRPita, AVRPizt, and AVRPib were present in 26.12, 66.22, and 79% of the isolates, respectively. Sequencing of AVR genes showed that most mutations were single nucleotide polymorphisms, transposon insertions, and insertion mutations. The variable sites of AVRPikm and AVRPita were mainly located in the coding sequence regions (CDS), and most were synonymous mutations. A 494-bp Pot2 transposon sequence insertion was found at the 87 bp position upstream of the start codon in AVRPib. Noteworthy, although no mutations were found in CDS of AVRPi9, a GC-rich inserted sequence of ∼200 bp was found at the 1,272 bp position upstream of the start codon in three virulent isolates. As AVRPikm and AVRPi9 were widely distributed with low genetic variation in the pathogen population, Pikm and Pi9 should be promising genes for breeding rice cultivars with blast resistance in Hunan.

Correction: 3-deazaneplanocin A protects against cisplatin-induced renal tubular cell apoptosis and acute kidney injury by restoration of E-cadherin expression.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

3-deazaneplanocin A protects against cisplatin-induced renal tubular cell apoptosis and acute kidney injury by restoration of E-cadherin expression.

3-deazaneplanocin A (3-DZNeP) has been used as an inhibitor of enhancer of zeste homolog 2 (EZH2). Here, we explore the role and underlying mechanisms action of 3-DZNeP in abrogating cisplatin nephrotoxicity. Exposure of cultured mouse renal proximal tubular epithelial cells (mTECs) to cisplatin resulted in dose and time-dependent cleavage of caspase-3, decrease of cell viability, and increase of histone H3 lysine 27 trimethylation (H3K27me3), whereas expression levels of EZH2, a major methyltransferase of H3K27me3, were not affected. Treatment with 3-DZNeP significantly inhibited cisplatin-induced activation of caspase-3, apoptosis, loss of cell viability but did not alter levels of EZH2 and H3K27me3 in cultured mTECs. 3-DZNeP treatment did not affect activation of extracellular signal-regulated kinase (ERK) 1/2, p38 or c-Jun N-terminal kinases (JNK) 1/2, which contribute to renal epithelial cell death, but caused dose-dependent restoration of E-cadherin in mTECs exposed to cisplatin. Silencing of E-cadherin expression by siRNA abolished the cytoprotective effects of 3-DZNeP. In contrast, 3-DZNeP treatment potentiated the cytotoxic effect of cisplatin in H1299, a non-small cell lung cancer cell line that expresses lower E-cadherin levels. Finally, administration of 3-DZNeP attenuated renal dysfunction, morphological damage, and renal tubular cell death, which was accompanied by E-cadherin preservation, in a mouse model of cisplatin nephrotoxicity. Overall, these data indicate that 3-DZNeP suppresses cisplatin-induced tubular epithelial cell apoptosis and acute kidney injury via an E-cadherin-dependent mechanism, and suggest that combined application of 3-DZNeP with cisplatin would be a novel chemotherapeutic strategy that enhances the anti-tumor effect of cisplatin and reduces its nephrotoxicity.

Characterization of Molecular Identity and Pathogenicity of Rice Blast Fungus in Hunan Province of China.

The blast (Magnaporthe oryzae) resistance (R) gene is the most economical and environmental method to control rice blast disease. Characterization of molecular identity and pathogenicity of M. oryzae benefits the deployment of effective blast R genes. In order to identify blast R genes that would be effective in Hunan Province,182 M. oryzae strains were analyzed with a Chinese differential system (CDS), repetitive element-based polymerase chain reaction (rep-PCR), and the presence and absence of avirulence (AVR) genes by PCR amplification with gene-specific primers. Identified blast R genes were validated with 24 monogenic lines (ML) carrying 24 major R genes. In total, 28 races (isolates) of M. oryzae was identified with CDS, and classified into 20 distinct groups with rep-PCR. Interestingly, AVR-Pia, AVR-Pik, AVR-Pizt, AVR-Pib, and AVR-Pi9 were detected in more than 86.8% of the isolates; AVR-Pita1 was in 51.3% and AVR-Pii was in only 2.5%. In contrast, pathogenicity assays on 24 ML demonstrated that Pi9, Piz5, Pikh, and Pikm were more effective, with resistant frequencies of 91.6, 91, 87.9, and 87.3%, respectively; Pia, Piks, Pit, Pi12, and Pib were less than 15%. These findings revealed the complexity of a genetic basis of rice blast resistance, and shed light on useful blast R genes in Hunan Province.

Enzymatically Degradable Polyester-Based Adhesives.

A designed 3,4-dihydroxyphenylalanine (DOPA) mimetic enzymatic degradable synthetic adhesive with good adhesion to soft tissue and metals made by a simple two-step reaction is presented in this article. This adhesive has degradable polycaprolactone-type of repeat units together with glycidyl methacrylate (GMA) and oligo(ethylene glycol) methacrylate (OEGMA) on the polymer backbone. Radical initiated copolymerization of 2-methylene-1,3-dioxepane (MDO), glycidyl methacrylate (GMA) and OEGMA followed by immobilization of catechol group on epoxy rings of GMA provided the adhesive material. Fe(acac)3 was proved to be the most effective cross-linking agent with lap shear strength of 13.13 ± 1.74 kPa and 218.4 ± 16.0 kPa on soft tissue (porcine skin) and metal (aluminum), respectively. The cross-linked adhesive showed good adhesion stability in pH 7 PBS buffer at 37 °C for at least 1 week. Because of the high adhesive strength, enzymatic degradability, and low toxicity, the material is a promising candidate for future studies as medical glue.

A rare example of the formation of polystyrene-grafted aliphatic polyester in one-pot by radical polymerization.

The radical copolymerization of cyclic ester ß-propiolactone (ß-PL) with styrene (St) at 120 °C, with a complete range of monomer ratios, is a rare example of a system providing graft copolymers (PSt-g-ß-PL) in one pot. The structure of the resulting ß-PL-St copolymers was proven by using a combination of different characterization techniques, such as 1D and 2D NMR spectroscopy and gel permeation chromatography (GPC), before and after alkaline hydrolysis of the polymers. The number of grafting points increased with an increasing amount of ß-PL in the feed. A significant difference in the reactivity of St and ß-PL and radical chain-transfer reactions at the polystyrene (PSt) backbone, followed by combination with the active growing poly(ß-PL) chains, led to the formation of graft copolymers by a grafting-onto mechanism.

Multifunctional nanocarrier based on clay nanotubes for efficient intracellular siRNA delivery and gene silencing.

RNA interference-mediated gene silencing relating to disease has recently emerged as a powerful method in gene therapy. Despite the promises, effective transport of siRNA with minimal side effects remains a challenge. Halloysites are cheap and naturally available aluminosilicate clay nanotubes with high mechanical strength and biocompatibility. In this study, a novel multifunctional nanocarrier based on functionalized halloysite nanotubes (f-HNTs) has been developed via electrostatic layer-by-layer assembling approach for loading and intracellular delivery of therapeutic antisurvivin siRNA and simultaneously tracking their intracellular transport, in which PEI-modified HNTs are used as gene vector, antisurvivin siRNA as gene therapeutic agent, and mercaptoacetic acid-capped CdSe quantum dots as fluorescent labeling probes. The successful assembly of the f-HNTs-siRNA complexes was systematically characterized by transmission electron microscopy (TEM), UV-visible spectrophotometry, Zeta potential measurement, fluorescence spectrophotometry, and electrochemical impedance spectroscopy. Confocal microscopy, biological TEM, and flow cytometry studies revealed that the complexes enabled the efficient intracellular delivery of siRNA for cell-specific gene silencing. MTT assays exhibited that the complexes can enhance antitumor activity. Furthermore, Western blot analysis showed that f-HNTs-mediated siRNA delivery effectively knocked down gene expression of survivin and thereby decreased the levels of target proteins of PANC-1 cells. Therefore, this study suggested that the synthesized f-HNTs were a new effective drug delivery system for potential application in cancer gene therapy.

Delivery of large molecules via poly(butyl cyanoacrylate) nanoparticles into the injured rat brain.

Poly(n-butyl-2-cyanoacrylate) (PBCA) nanoparticles have been successfully applied to deliver small-molecule drugs to the central nervous system (CNS). However, it is unclear whether PBCA nanoparticles can be used as the delivery system for large molecules to potentially treat traumatic brain injury (TBI). In this study, we tested the capacity of PBCA nanoparticles in passing through the blood-brain barrier (BBB) and transporting large molecules into normal and injured brains in the rat. We first synthesized PBCA nanoparticles by dispersion polymerization and then loaded the particles with either horseradish peroxidase (HRP, 44 kDa) or enhanced green fluorescent protein (EGFP, 29 kDa), which were further coated with polysorbate 80. Next, the polysorbate 80-coated HRP or EGFP-loaded PBCA nanoparticles were intravenously injected into the normal and brain-injured rats. We found that, at 45 min after injection, PBCA nanoparticle-delivered HRP or EGFP was hardly detected in the normal brains of the rats, but a small amount of EGFP carried by PBCA nanoparticles was noted in the normal brains 48 h after administration, which was further confirmed by immunolocalization with anti-EGFP antibodies. In contrast, at 4 h after TBI with a circulation time of 45 min, although the penetration of HRP or EGFP alone was hampered by the BBB, the PBCA nanoparticle-delivered HRP or EGFP was widely distributed near injured sites. Together, our findings provide histological evidence that PBCA nanoparticles can be used as an efficient delivery system for large molecules to overcome the barrier in the brain with TBI.

Functionalized halloysite nanotube-based carrier for intracellular delivery of antisense oligonucleotides.

Halloysites are cheap, abundantly available, and natural with high mechanical strength and biocompatibility. In this paper, a novel halloysite nanotube [HNT]-based gene delivery system was explored for loading and intracellular delivery of antisense oligodeoxynucleotides [ASODNs], in which functionalized HNTs [f-HNTs] were used as carriers and ASODNs as a therapeutic gene for targeting survivin. HNTs were firstly surface-modified with γ-aminopropyltriethoxysilane in order to facilitate further biofunctionalization. The f-HNTs and the assembled f-HNT-ASODN complexes were characterized by transmission electron microscopy [TEM], dynamic light scattering, UV-visible spectroscopy, and fluorescence spectrophotometry. The intracellular uptake and delivery efficiency of the complexes were effectively investigated by TEM, confocal microscopy, and flow cytometry. In vitro cytotoxicity studies of the complexes using MTT assay exhibited a significant enhancement in the cytotoxic capability. The results exhibited that f-HNT complexes could efficiently improve intracellular delivery and enhance antitumor activity of ASODNs by the nanotube carrier and could be used as novel promising vectors for gene therapy applications, which is attributed to their advantages over structures and features including a unique tubular structure, large aspect ratio, natural availability, rich functionality, good biocompatibility, and high mechanical strength.