The optimal spatial delineation method for the service level of urban park green space from the perspective of opportunity equity.

Urban park green spaces (UPGS) constitute a vital component of urban ecosystems, and the unequal distribution of UPGS can significantly impact the well-being of residents. Therefore, investigating the spatial delineation methods of UPGS service levels from the perspective of opportunity equity contributes to enhancing people's quality of life and promoting social harmony. Taking the Yingze District of Taiyuan City as an example, this study uses a modified accessibility measurement method of UPGS with the smallest clustered unit (building) as the service demand point and the UPGS entrance/exit as the service provision point, to establish a micro-scale evaluation framework for spatial equity considering the service radius and service quality of UPGS. The findings are as follows: after setting different service radius for UPGS at different levels, additional areas not covered by UPGS service were identified compared to setting the same service radius uniformly, which could prevent these areas from being overlooked in urban plans. After considering the quality of UPGS services, additional areas with low and high UPGS service levels were identified. Accurate spatial delineation of UPGS service level can avoid wasting public resources by including areas with high service levels in the scope of new UPGS requirements, while areas with low service levels lose opportunities for consideration in future urban infrastructure planning. This study emphasizes the residents' demand for both the quantity and quality of UPGS, facilitating an accurate assessment of whether urban residents can enjoy UPGS, the number of UPGS options available to them, and evaluate the quality of UPGS services experienced. Overall, this research provides new insights for evaluating the spatial equity of urban public facilities.

Dual Functioned Hexapeptide-Coated Lipid-Core Nanomicelles Suppress Toll-Like Receptor-Mediated Inflammatory Responses through Endotoxin Scavenging and Endosomal pH Modulation.

Excessive activation of Toll-like receptor (TLR) signaling pathways and the circulating endotoxin are key players in the pathogenesis of many acute and chronic inflammatory diseases. Regulation of TLR-mediated inflammatory responses by bioactive nanodevices represents a promising strategy for treating these diseases. In searching for novel, clinically applicable nanodevices with potent TLR inhibitory activities, three types of hexapeptide-modified nano-hybrids with different cores of phospholipid nanomicelles, liposomes, and poly(lactic-co-glycolic acid) nanoparticles are constructed. Interestingly, only the peptide-modified lipid-core nanomicelles (M-P12) display potent TLR inhibitory activities. Further mechanistic studies disclose that lipid-core nanomicelles have a generic property to bind to and scavenge lipophilic TLR ligands including lipopolysaccharide to block the ligand-receptor interaction and down-regulate the TLR signaling extracellularly. In addition, the peptide modification enables M-P12 a unique capability to modulate endosomal acidification upon being endocytosed into macrophages, which subsequently regulates the endosomal TLR signal transduction. In an acute lung injury mouse model, intratracheal administration of M-P12 can effectively target lung macrophages and reduce lung inflammation and injuries. This work defines a dual mechanism of action of the peptide-modified lipid-core nanomicelles in regulating TLR signaling, and provides new strategies for the development of therapeutic nanodevices for treating inflammatory diseases.

Phosphorus recovery and reuse in water bodies with simple ball-milled Ca-loaded biochar.

The demand to control eutrophication in water bodies and the risk of phosphorus scarcity have prompted the search for treatment technologies for phosphorus recovery. In this study, ball-milled Ca-loaded biochar (BMCa@BC) composites were prepared with CaO and corn stover biochar as raw materials by a new ball-milling method to recover phosphorus from water bodies. Experimental results demonstrated that BMCa@BC could efficiently adsorb phosphorus in water bodies with an excellent sorption capacity of 329 mg P/g. Hydrogen bonding, electrostatic attraction, complexation, and surface precipitation were involved in adsorption process. In addition, phosphorus recovered by BMCa@BC had high bioavailability (86.7 % of TP) and low loss (3.3 % of TP) and was a potential slow-release fertilizer. P-laden BMCa@BC significantly enhanced seed germination and growth in planting experiments, proving that it could be used as a substitute for P-based fertilizer. After five cycles of regeneration, BMCa@BC still showed good adsorption recovery and the P-enriched desorption solution could be recovered as Ca-P products with the fertilizer value. Overall, BMCa@BC has good cost-effectiveness and practical applicability in phosphorus recovery. This provides a new way to recover and reuse phosphorus effectively.

Silver nano-reporter enables simple and ultrasensitive profiling of microRNAs on a nanoflower-like microelectrode array on glass.

MicroRNAs (miRNAs) are small non-coding RNAs with ~ 22 nucleotides, playing important roles in the post-transcriptional regulation of gene expression. The expression profiles of many miRNAs are closely related to the occurrence and progression of cancer and can be used as biomarkers for cancer diagnosis and prognosis. However, their intrinsic properties, such as short length, low abundance and high sequence homology, represent great challenges in miRNA detection of clinical samples. To overcome these challenges, we developed a simple, ultrasensitive detection platform of electrochemical miRNAs chip (e-miRchip) with a novel signal amplification strategy using silver nanoparticle reporters (AgNRs) for multiplexed, direct, electronic profiling of miRNAs. A two-step hybridization strategy was used to detect miRNAs, where the target miRNA hybridizes with a stem-loop probe to unlock the probe first, and the opened stem-loop can further hybridize with AgNRs for signaling amplification. To enhance the detection sensitivity, the gold nanoflower electrodes (GNEs) were constructed in the microaperture arrays of the e-miRchips by electroplating. With the optimal size of the GNEs, the e-miRchip showed excellent performance for miR-21 detection with a detection limit of 0.56 fM and a linear range extended from 1 fM to 10 pM. The e-miRchip also exhibited good specificity in differentiating the 3-base mismatched sequences of the target miRNA. In addition, the e-miRchip was able to directly detect miR-21 expression in the total RNA extracts or cell lysates collected from lung cancer cells and normal cells. This work demonstrated the developed e-miRchip as an efficient and promising miniaturized point-of-care diagnostic device for the early diagnosis and prognosis of cancers.

Nano-Enabled Reposition of Proton Pump Inhibitors for TLR Inhibition: Toward A New Targeted Nanotherapy for Acute Lung Injury.

Toll-like receptor (TLR) activation in macrophages plays a critical role in the pathogenesis of acute lung injury (ALI). While TLR inhibition is a promising strategy to control the overwhelming inflammation in ALI, there still lacks effective TLR inhibitors for clinical uses to date. A unique class of peptide-coated gold nanoparticles (GNPs) is previously discovered, which effectively inhibited TLR signaling and protected mice from lipopolysaccharide (LPS)-induced ALI. To fast translate such a discovery into potential clinical applicable nanotherapeutics, herein an elegant strategy of "nano-enabled drug repurposing" with "nano-targeting" is introduced to empower the existing drugs for new uses. Combining transcriptome sequencing with Connectivity Map analysis, it is identified that the proton pump inhibitors (PPIs) share similar mechanisms of action to the discovered GNP-based TLR inhibitor. It is confirmed that PPIs (including omeprazole) do inhibit endosomal TLR signaling and inflammatory responses in macrophages and human peripheral blood mononuclear cells, and exhibits anti-inflammatory activity in an LPS-induced ALI mouse model. The omeprazole is then formulated into a nanoform with liposomes to enhance its macrophage targeting ability and the therapeutic efficacy in vivo. This research provides a new translational strategy of nano-enabled drug repurposing to translate bioactive nanoparticles into clinically used drugs and targeted nano-therapeutics for ALI.

The Modulatory Activity of Tryptophan Displaying Nanodevices on Macrophage Activation for Preventing Acute Lung Injury.

Macrophages play an important role in the initiation, progression and resolution of inflammation in many human diseases. Effective regulation of their activation and immune responses could be a promising therapeutic strategy to manage various inflammatory conditions. Nanodevices that naturally target macrophages are ideal agents to regulate immune responses of macrophages. Here we described a special tryptophan (Trp)-containing hexapeptide-coated gold nanoparticle hybrid, PW, which had unique immunomodulatory activities on macrophages. The Trp residues enabled PW higher affinity to cell membranes, and contributed to inducing mild pro-inflammatory responses of NF-κB/AP-1 activation. However, in the presence of TLR stimuli, PW exhibited potent anti-inflammatory activities through inhibiting multiple TLR signaling pathways. Mechanistically, PW was internalized primarily through micropinocytosis pathway into macrophages and attenuated the endosomal acidification process, and hence preferentially affected the endosomal TLR signaling. Interestingly, PW could induce the expression of the TLR negative regulator IRAK-M, which may also contribute to the observed TLR inhibitory activities. In two acute lung injury (ALI) mouse models, PW could effectively ameliorate lung inflammation and protect lung from injuries. This work demonstrated that nanodevices with thoughtful design could serve as novel immunomodulatory agents to manage the dysregulated inflammatory responses for treating many chronic and acute inflammatory conditions, such as ALI.

First detection of canine norovirus in dogs and a complete GVI.2 genome in mainland China.

Canine norovirus (CNV) is a diarrhea-causing pathogen in canines. In this study, 268 canine diarrheic fecal samples were collected from 13 pet hospitals across three provinces in China between March 2017 and May 2019, and 7.8% (21/268) samples were detected as CNV-positive by RT-PCR. Phylogenetic analysis of twenty-one CNV RdRp fragments showed that eighteen of the strains clustered in GVI.2, two clustered in GVI.1 and one clustered in GIV.2. The complete RdRp, VP1, and VP2 genes of four GVI.2 strains obtained from three provinces were successfully sequenced. Phylogenetic analyses based on the RdRp, VP1, and VP2 genes showed that the GVI.2 strains from this study were closely related to USA GVI.2 strains. The complete genome of GVI.2 strain Dog/M9/18/CH was successfully sequenced, it was 7905 nucleotides (nt) in length and shared 95.9% nt identity with the sole available, nearly full-length genome of GVI.2 strain genome. To our knowledge, this is first description of the molecular prevalence of CNV in mainland China, and the first report of a complete GVI.2 genome. These findings will extend our understanding of epidemics and the genetic evolution of CNV.

Genomic characterization of a nebovirus strain with a novel RdRp genotype in yaks.

Neboviruses (NeVs) are important causative agents of calf diarrhea that belong to the family Caliciviridae. In this study, we investigated the genomic characteristics of a NeV strain from yaks that has a novel RdRp genotype. The complete genome of this strain (YAK/NRG-A9/19/CH) is 7454 nt in length and shares 68.3%-79.7% nt sequence identity with those of other NeVs. The RNA-dependent RNA polymerase (RdRp) gene of this strain shares 66.5%-78.5% nt sequence identity (74.0%-89.3% aa sequence identity) with the eight available complete NeV RdRp sequences, and a phylogenetic analysis based on these sequences showed that the new strain formed an independent branch, indicating that the RdRp of strain YAK/NRG-A9/19/CH may represent a novel RdRp genotype of NeV. These results contribute to a further understanding of the molecular characteristics and genetic evolution of NeVs.

The effect of neo-adjuvant chemotherapy on the improvement of oral cancer patients and the predictive value of miR-182 on its efficacy.

PURPOSE: This study aimed to observe the effect of neo-adjuvant chemotherapy on the improvement of oral cancer patients and investigate the predictive value of miR-182 on its efficacy. METHODS: A total of 143 patients with advanced oral cancer admitted to Yidu Central Hospital of Weifang from September 2015 to July 2017 formed the study group. Among them, there were 62 cases in the control group (surgery+postoperative radiotherapy) and 81 cases in the study group (preoperative neo-adjuvant chemotherapy+surgery+postoperative radiotherapy). The treatment effect and adverse reactions of patients were compared between the two groups. RT-PCR was used to detect the expression levels of serum miR-182 of patients before and after treatment. The 1-year survival of patients in the two groups was recorded and compared by follow-up. RESULTS: The total effective rate of patients in the study group was significantly higher than that of patients in the control group (p<0.05). The incidence of adverse reactions of patients in the study group was significantly higher than in the control group (p<0.05). There was no significant difference in the prognostic 1-year survival rate between the two groups. After treatment, the expression of miR-182 was lower than before treatment and in the study group it was significantly lower than the control group (p<0.05). ROC curve analysis showed that the area under the curve of miR-182 in the predictive value of oral cancer was 0.756. When the cut-off value was less than 1.823, the optimal specificity was 70.18% and the sensitivity was 75.86%. CONCLUSION: Neo-adjuvant chemotherapy can significantly improve the therapeutic effect, but the incidence of adverse reactions increases. miR-182 may be involved in the occurrence and deterioration of oral cancer and is a good indicator for predicting the treatment efficacy of patients with oral cancer.

Prevalence and genomic characteristics of a novel reassortment mammalian orthoreovirus type 2 in diarrhea piglets in Sichuan, China.

Mammalian orthoreovirus (MRV), which can infect almost all mammals, is a zoonotic virus. In this study, six strains of type 2 MRV (MRV2) were isolated from 7 diarrhea piglets from a farm that had an outbreak of diarrhea in piglets in 2018, which tested negative for porcine epidemic diarrhea virus (PEDV), porcine transmissible gastroenteritis virus (TGEV), porcine deltacoronavirus (PDCoV), and porcine group A rotavirus (RAV). The MRV2 isolate infected neonatal piglets, in which it induced severe diarrhea, while the virus was detected in multiple organs of piglets. Moreover, the complete genome of an MRV2 isolate was obtained, which was a novel reassortant MRV strain of human MRV, porcine MRV, chamois MRV, bat MRV, and mink MRV based on the nucleotide identity and phylogenetic tree. The S1 gene of isolate had eight unique amino acid mutations compared with available MRV2 S1 in the GenBank. To investigate the prevalence of this MRV2, 78 samples of diarrhea feces were collected from 10 pig farms in seven regions of Sichuan province. The obtained results showed that the positive rate of samples was 14% (11/78), and positive rate of farms was 60% (6/10), while the amplified fragments shared the identical amino acid mutations with the isolated strain, thus suggesting that this MRV2 strain was already prevalent in Sichuan province. The present study was first to isolate a pig-derived type 2 MRV strain in China, obtaining the complete genome of this strain, which furthers our understanding of the MRV2 epidemic and evolution.

MicroRNA-216a inhibits the growth and metastasis of oral squamous cell carcinoma by targeting eukaryotic translation initiation factor 4B.

There is increasing evidence to suggest that microRNAs (miRNAs; miRs) are involved in the development of oral squamous cell carcinoma (OSCC). miR-216a has been identified as being involved in tumorigenesis, however, the mechanisms of miR-216a in various types of cancer, either as a tumor suppressor or as an oncogenic miRNA, and the specific regulatory role of miR-216a in OSCC remain to be elucidated. The present study demonstrated that the expression of miR-216a was significantly reduced in OSCC tissues and cell lines. Overexpression of miR-216a significantly suppressed the proliferation, colony formation, migration and invasion of the OSCC cells. In addition, eukaryotic translation initiation factor 4B (EIF4B) was identified as a direct target of miR-216a, which was observed to be upregulated in the OSCC tissues. Furthermore, overexpression of EIF4B significantly attenuated the antitumor effect of miR-216a, and a negative correlation was observed between miR-216a and EIF4B in the OSCC tissues. Taken together, these findings indicated that miR-216a has a suppressive role in OSCC cells by directly targeting EIF4B, and may function as a potential prognostic biomarker and novel therapeutic target.