The expression and significance of PD-L1 in condyloma acuminatum.

BACKGROUND: It has been reported that programmed death-ligand 1 (PD-L1) is highly expressed in cells during viral infection, which helps the virus escape host immunity. However, the relationship between human papillomavirus (HPV) and PD-L1 in condyloma acuminatum and whether they participate in immunosuppression have not been reported. In this paper, we aimed to explore the expression and significance of PD-L1 in condyloma acuminatum. METHODS: The expression of PD-L1 in the wart of condyloma acuminatum patients and the foreskin of healthy individuals was evaluated. Lentivirus transfection was used to introduce the HPV11-E7 gene into HaCaT cells to investigate whether HPV infection could affect the expression of PD-L1. The successfully constructed HPV11-E7 HaCaT cells were cocultured with Jurkat cells, and Jurkat cell apoptosis and proliferation as well as the Jurkat cell cycle were evaluated by flow cytometry and cell counting kit-8 (CCK-8) assays. RESULTS: PD-L1 was highly expressed in keratinocytes of genital warts. Through the construction of a cell model, we found that HPV11-E7 could upregulate the expression of PD-L1 in HaCaT cells. Furthermore, HPV11-E7 HaCaT cells can promote the apoptosis of Jurkat cells, inhibit the proliferation of Jurkat cells and mediate the cell cycle arrest of Jurkat cells through the PD-1/PD-L1 signalling pathway. CONCLUSIONS: HPV infection may upregulate PD-L1 expression in the keratinocytes of genital warts and participate in the inhibition of local T-cell function.

Syringic acid promotes cartilage extracellular matrix generation and attenuates osteoarthritic cartilage degradation by activating TGF-ß/Smad and inhibiting NF-κB signaling pathway.

Osteoarthritis (OA) is a common chronic degenerative disease which is characterized by the disruption of articular cartilage. Syringic acid (SA) is a phenolic compound with anti-inflammatory, antioxidant, and other effects including promoting osteogenesis. However, the effect of SA on OA has not yet been reported. Therefore, the purpose of our study was to investigate the effect and mechanism of SA on OA in a mouse model of medial meniscal destabilization. The expressions of genes were evaluated by qPCR or western blot or immunofluorescence. RNA-seq analysis was performed to examine gene transcription alterations in chondrocytes treated with SA. The effect of SA on OA was evaluated using destabilization of the medial meniscus model of mice. We found that SA had no obvious toxic effect on chondrocytes, while promoting the expressions of chondrogenesis-related marker genes. The results of RNA-seq analysis showed that extracellular matrix-receptor interaction and transforming growth factor-ß (TGF-ß) signaling pathways were enriched among the up-regulated genes by SA. Mechanistically, we demonstrated that SA transcriptionally activated Smad3. In addition, we found that SA inhibited the overproduction of lipopolysaccharide-induced inflammation-related cytokines including tumor necrosis factor-α and interleukin-1ß, as well as matrix metalloproteinase 3 and matrix metalloproteinase 13. The cell apoptosis and nuclear factor-kappa B (NF-κB) signaling were also inhibited by SA treatment. Most importantly, SA attenuated cartilage degradation in a mouse OA model. Taken together, our study demonstrated that SA could alleviate cartilage degradation in OA by activating the TGF-ß/Smad and inhibiting NF-κB signaling pathway.

Increasing the Accessibility of Internal Catalytic Sites in Covalent Organic Frameworks by Introducing a Bicontinuous Mesostructure.

Introducing continuous mesochannels into covalent organic frameworks (COFs) to increase the accessibility of their inner active sites has remained a major challenge. Here, we report the synthesis of COFs with an ordered bicontinuous mesostructure, via a block copolymer self-assembly-guided nanocasting strategy. Three different mesostructured COFs are synthesized, including two covalent triazine frameworks and one vinylene-linked COF. The new materials are endowed with a hierarchical meso/microporous architecture, in which the mesochannels exhibit an ordered shifted double diamond (SDD) topology. The hierarchically porous structure can enable efficient hole-electron separation and smooth mass transport to the deep internal of the COFs and consequently high accessibility of their active catalytic sites. Benefiting from this hierarchical structure, these COFs exhibit excellent performance in visible-light-driven catalytic NO removal with a high conversion percentage of up to 51.4 %, placing them one of the top reported NO-elimination photocatalysts. This study represents the first case of introducing a bicontinuous structure into COFs, which opens a new avenue for the synthesis of hierarchically porous COFs and for increasing the utilization degree of their internal active sites.

Biosynthesis of Multifunctional Transformable Peptides for Inducing Tumor Cell Apoptosis.

Engineered nanomaterials hold great promise to improve the specificity of disease treatment. Herein, a fully protein-based material is obtained from nonpathogenic Escherichia coli (E. coli), which is capable of morphological transformation from globular to fibrous in situ for inducing tumor cell apoptosis. The protein-based material P1 is comprised of a ß-sheet-forming peptide KLVFF, pro-apoptotic protein BAK, and GFP along with targeting moieties. The self-assembled nanoparticles of P1 transform into nanofibers in situ in the presence of cathepsin B, and the generated nanofibrils favor the dimerization of functional BH3 domain of BAK on the mitochondrial outer membrane, leading to efficient anticancer activity both in vitro and in vivo via mitochondria-dependent apoptosis through Bcl-2 pathway. To precisely manipulate the morphological transformation of biosynthetic molecules in living cells, a spatiotemporally controllable anticancer system is constructed by coating P1-expressing E. coli with cationic conjugated polyelectrolytes to release the peptides in situ under light irradiation. The biosynthetic peptide-based enzyme-catalytic transformation strategy in vivo would offer a novel perspective for targeted delivery and shows great potential in precision disease therapeutics.

A Low-Carbon and Economic Dispatch Strategy for a Multi-Microgrid Based on a Meteorological Classification to Handle the Uncertainty of Wind Power.

In a modern power system, reducing carbon emissions has become a significant goal in mitigating the impact of global warming. Therefore, renewable energy sources, particularly wind-power generation, have been extensively implemented in the system. Despite the advantages of wind power, its uncertainty and randomness lead to critical security, stability, and economic issues in the power system. Recently, multi-microgrid systems (MMGSs) have been considered as a suitable wind-power deployment candidate. Although wind power can be efficiently utilized by MMGSs, uncertainty and randomness still have a significant impact on the dispatching and operation of the system. Therefore, to address the wind power uncertainty issue and achieve an optimal dispatching strategy for MMGSs, this paper presents an adjustable robust optimization (ARO) model based on meteorological clustering. Firstly, the maximum relevance minimum redundancy (MRMR) method and the CURE clustering algorithm are employed for meteorological classification in order to better identify wind patterns. Secondly, a conditional generative adversarial network (CGAN) is adopted to enrich the wind-power datasets with different meteorological patterns, resulting in the construction of ambiguity sets. Thirdly, the uncertainty sets that are finally employed by the ARO framework to establish a two-stage cooperative dispatching model for MMGS can be derived from the ambiguity sets. Additionally, stepped carbon trading is introduced to control the carbon emissions of MMGSs. Finally, the alternative direction method of multipliers (ADMM) and the column and constraint generation (C&CG) algorithm are adopted to achieve a decentralized solution for the dispatching model of MMGSs. Case studies indicate that the presented model has a great performance in improving the wind-power description accuracy, increasing cost efficiency, and reducing system carbon emissions. However, the case studies also report that the approach consumes a relative long running time. Therefore, in future research, the solution algorithm will be further improved for the purpose of raising the efficiency of the solution.

A Thiophene Backbone Enables Two-Dimensional Poly(arylene vinylene)s with High Charge Carrier Mobility.

Linear conjugated polymers have attracted significant attention in organic electronics in recent decades. However, despite intrachain π-delocalization, interchain hopping is their transport bottleneck. In contrast, two-dimensional (2D) conjugated polymers, as represented by 2D π-conjugated covalent organic frameworks (2D c-COFs), can provide multiple conjugated strands to enhance the delocalization of charge carriers in space. Herein, we demonstrate the first example of thiophene-based 2D poly(arylene vinylene)s (PAVs, 2DPAV-BDT-BT and 2DPAV-BDT-BP, BDT=benzodithiophene, BT=bithiophene, BP=biphenyl) via Knoevenagel polycondensation. Compared with 2DPAV-BDT-BP, the fully thiophene-based 2DPAV-BDT-BT exhibits enhanced planarity and π-delocalization with a small band gap (1.62 eV) and large electronic band dispersion, as revealed by the optical absorption and density functional calculations. Remarkably, temperature-dependent terahertz spectroscopy discloses a unique band-like transport and outstanding room-temperature charge mobility for 2DPAV-BDT-BT (65 cm2  V-1 s-1 ), which far exceeds that of the linear PAVs, 2DPAV-BDT-BP, and the reported 2D c-COFs in the powder form. This work highlights the great potential of thiophene-based 2D PAVs as candidates for high-performance opto-electronics.

Genetic mutation of TRPV2 induces anxiety by decreasing GABA-B R2 expression in hippocampus.

Transient receptor potential vanillic acid 2 (TRPV2) are well recognized for their contributions to neuronal development, cardiac function, immunity and cancer. However, the precise roles for this thermo TRPchannels in neurological disorder remain unknown. In this study, we employed the CRISPR/Cas9 system to generate genetic mutations of TRPV2. Genetic mutation of TRPV2 resulted in autistic-like phenotypes in mice accompanied with the disordered electrical signals recorded by multi-channels in vivo. To determine possible molecular mechanisms, western blotting was further used to assess the possible involvement of several autism-related proteins. The significantly decreased expression of the R2 subunit of the GABA-B receptor in the hippocampus was observed. Together, our findings suggest that genetic mutation of TRPV2 induces autism-like behavior, results in decreased expression of the R2 subunit of the GABA-B receptor.

Identification of four insertion sites for foreign genes in a pseudorabies virus vector.

BACKGROUND: Pseudorabies virus (PRV) is a preferred vector for recombinant vaccine construction. Previously, we generated a TK&gE-deleted PRV (PRVΔTK&gE-AH02) based on a virulent PRV AH02LA strain. It was shown to be safe for 1-day-old piglets with maternal PRV antibodies and 4 ~ 5 week-old PRV antibody negative piglets and provide rapid and 100 % protection in weaned pigs against lethal challenge with the PRV variant strain. It suggests that PRVTK&gE-AH02 may be a promising live vaccine vector for construction of recombinant vaccine in pigs. However, insertion site, as a main factor, may affect foreign gene expression. RESULTS: In this study, we constructed four recombinant PRV-S bacterial artificial chromosomes (BACs) carrying the same spike (S) expression cassette of a variant porcine epidemic diarrhea virus strain in different noncoding regions (UL11-10, UL35-36, UL46-27 or US2-1) from AH02LA BAC with TK, gE and gI deletion. The successful expression of S gene (UL11-10, UL35-36 and UL46-27) in recombinant viruses was confirmed by virus rescue, PCR, real-time PCR and indirect immunofluorescence. We observed higher S gene mRNA expression level in swine testicular cells infected with PRV-S(UL11-10)ΔTK/gE and PRV-S(UL35-36)ΔTK/gE compared to that of PRV-S(UL46-27)ΔTK/gE at 6 h post infection (P < 0.05). Moreover, at 12 h post infection, cells infected with PRV-S(UL11-10)ΔTK/gE exhibited higher S gene mRNA expression than those infected with PRV-S(UL35-36)ΔTK/gE (P = 0.097) and PRV-S(UL46-27)ΔTK/gE (P < 0.05). Recovered vectored mutant PRV-S (UL11-10, UL35-36 and UL46-27) exhibited similar growth kinetics to the parental virus (PRVΔTK&gE-AH02). CONCLUSIONS: This study focuses on identification of suitable sites for insertion of foreign genes in PRV genome, which laids a foundation for future development of recombinant PRV vaccines.

Association between healthy eating index-2015 and various cognitive domains in US adults aged 60 years or older: the National Health and Nutrition Examination Survey (NHANES) 2011-2014.

BACKGROUND: Diet, as a modifiable factor, plays an important role in cognitive function. However, the association between adherence to the 2015-2020 Dietary Guidelines for Americans (DGA), measured by Healthy Eating Index (HEI)-2015, and cognitive function remains unclear. This study aims to explore whether HEI-2015 is associated with various cognitive domains and whether such association is modified by age, gender, or ethnicity in the US adults aged 60 years or older using data from the National Health and Nutrition Examination Survey (NHANES) 2011-2014. METHODS: HEI-2015 scores were calculated from 24-h dietary recall interviews. Cognitive function was evaluated by Digit Symbol Substitution Test (DSST, a measure of processing speed), Animal Fluency Test (AFT, a measure of executive function), a subtest from Consortium to Establish a Registry for Alzheimer's disease (CERAD, a measure of memory), and a composite-z score calculated by summing z scores of individual tests. The associations between HEI-2015 scores and cognitive performance were explored using multiple linear regression models. RESULTS: A total of 2450 participants aged 60 years or older were included. Participants with higher HEI-2015 scores were more likely to have higher DSST, AFT as well as composite-z scores (P<0.05). Significant interaction effects were identified between HEI-2015 and ethnicity in specific cognitive domains (Pinteraction<0.05). Among HEI-2015 components, higher intakes of whole fruits and seafood and plant protein were associated with better cognitive performance (P<0.05). CONCLUSION: Higher adherence to DGA is associated with better cognitive performance, especially regarding processing speed and executive function among the US adults aged 60 years or older.

Association between Healthy Eating Index-2015 and physical frailty among the United States elderly adults: the National Health and Nutrition Examination Survey (NHANES) 2011-2014.

BACKGROUND: Diet plays an important role in the development of age-related chronic diseases. However, the association between diet quality assessed by Healthy Eating Index (HEI)-2015, the latest version of HEI, and physical frailty among the general United States (US) elderly adults remains unclear. AIMS: The present study aims to explore the association between HEI-2015 and physical frailty in elderly adults using data from National Health and Nutrition Examination Survey (NHANES) 2011-2014. METHODS: HEI-2015 scores were calculated from 2 days 24-h recall interviews. Physical frailty status was assessed by four criteria developed by Fried et al.: exhaustion, weakness, low body mass, and low physical activity, and then categorized into robust (0 criteria), pre-frail (1-2 criteria), or frail (3-4 criteria). The binary and multinomial logistic regressions were used to examine the odds of frailty status. RESULTS: A total of 2345 participants aged 60 years or older were included. According to the 4-items frailty criteria, 51.1% participants were robust, 42.1% were pre-frail, and 6.8% were frail. Compared to the lowest HEI-2015 quartile, the elderly adults in the higher quartile had a lower odds of physical frailty (P < 0.05). Regarding the frailty criterion separately, higher HEI-2015 was associated with lower odds of exhaustion, weakness, low physical activity and unintentional weight loss, respectively (P < 0.05). Among 13 HEI-2015 components, adherence to the recommended intake of whole fruits and total vegetables components were less likely to be physically frail (P < 0.05). CONCLUSION: Higher HEI-2015 was inversely associated with lower odds of physical frailty in the US elderly adults.

Cytochrome P450 Mediated Bioactivation of Rutaevin, a Bioactive and Potentially Hepatotoxic Component of Evodia Rutaecarpa.

Rutaevin is one of the major bioactive constituents isolated from Evodia rutaecarpa, a well-known herbal medicine that has been widely prescribed for the treatment of gastrointestinal disorders in China. However, oral administration of rutaevin has been shown to cause hepatotoxicity in mice. Bioactivation was suggested to be involved in rutaevin-induced hepatotoxicity. The aim of this study was to investigate the bioactivation of rutaevin in rat and human liver microsomes fortified with NADPH. Rutaevin was metabolized into the reactive intermediate cis-butene-1,4-dial (BDA) that was dependent on NADPH. The rutaevin-derived BDA intermediate was trapped by nucleophiles such as glutathione (GSH), N-acetyl-lysine (NAL), and methoxylamine (MOA) in the microsomal incubation system. A total of 10 conjugates resulting from the conjugation of the intermediate with GSH, NAL, or MOA were detected and structurally characterized by liquid chromatography combined with high-resolution tandem mass spectrometry. M1, structurally confirmed by NMR spectroscopic analysis, was identified as a cyclic mono(GSH) conjugate of the BDA intermediate, which was also found in the biliary samples of rutaevin-treated rats. Further inhibitory experiments suggested that ketoconazole showed strong inhibitory effect on the formation of the rutaevin-derived BDA intermediate. CYP3A4 was demonstrated to be the major enzyme responsible for rutaevin bioactivation by using cDNA-expressed human recombinant cytochrome P450 enzymes. Additionally, it was found that rutaevin was a mechanism-based inactivator of CYP3A4, with inactivation parameters of KI = 15.98 µM, kinact = 0.032 min-1, and t1/2 inact = 21.65 min. In summary, these findings are of great significance in understanding the bioactivation mechanism of rutaevin, the potential mechanism of rutaevin-caused hepatotoxicity, and the drug-drug interactions associated with rutaevin mainly via CYP3A4 inactivation.

Deletion of Kv10.2 Causes Abnormal Dendritic Arborization and Epilepsy Susceptibility.

The abnormal function of the voltage-gated potassium channel Kv10.2 can induce epilepsy. However, the physiological function of Kv10.2 in the central nervous system remains unclear. In this study, we found that Kv10.2 knockout (KO) increased the complexity of neurons in the CA3 subarea of hippocampus. Kv10.2 KO led to enlarged somata, elongated dendritic length, and increased the number of dendritic tips in cultured rat hippocampus neurons. Kv10.2 KO also increased Synapsin I and PSD95 protein density in cultured rat hippocampal neurons. Whole cell patch-clamp recordings of brain slices in the CA3 subarea of hippocampus revealed that Kv10.2 KO increased the amplitude of spontaneous excitatory postsynaptic currents (sEPSC) and miniature excitatory postsynaptic currents (mEPSC), depolarized the resting membrane potential and increased the action potential firing, reduced the rheobase and increased the input resistance, which results in enhanced neuronal excitability. Furthermore, we made electroencephalogram (EEG) recordings of brain activity in freely moving rats before and after inducing seizures by pentylenetetrazole (PTZ) injection. Kv10.2 KO rats dramatically increased the EEG amplitude during epilepsy. Behavioral observation after seizure induction revealed that Kv10.2 KO rats demonstrated shortened onset latency, prolonged duration, and increased seizure severity when compared with wild type rats. Therefore, this study provides a new link between Kv10.2 and neuronal morphology and higher intrinsic excitability.

Rescuing Kv10.2 protein changes cognitive and emotional function in kainic acid-induced status epilepticus rats.

Voltage-gated potassium (Kv) channels are widely expressed in the central and peripheral nervous system and are crucial mediators of neuronal excitability. Importantly, these channels also actively participate in cellular and molecular signaling pathways that regulate the life and death processes of neurons. The current study used a kainic acid (KA)-induced temporal lobe epilepsy model to examine the role of the Kv10.2 gene in status epilepticus (SE). Lentiviral plasmids containing the coding sequence region of the KCNH5 gene (LV-KCNH5) were injected into the CA3 subarea of the right dorsal hippocampus within 24 h in post-SE rats to rescue Kv10.2 protein expression. Open-field and elevated plus maze test results indicated that anxiety-like behavior was ameliorated in the KA + LV-KCNH5 group rats compared with the SE group rats, and working memory was improved in the Y-maze test. However, the spatial reference memory of the LV-KCNH5 group rats did not improve in the Morris water maze test, and no difference was found in the light-dark transition box test. The results of this study indicate that Kv10.2 protein may play an important role in epilepsy, providing new potential therapeutic directions and drug targets for epilepsy treatment.

Supramolecular Photothermal Effects: A Promising Mechanism for Efficient Thermal Conversion.

Supramolecular assemblies have been very successful in regulating the photothermal conversion efficiency of organic photothermal materials in a simple and flexible way, compared with conventional molecular synthesis. In these assemblies, it is the inherent physiochemical mechanism that determines the photothermal conversion, rather than the assembly strategy. This Minireview summarizes supramolecular photothermal effects, which refer to the unique features of supramolecular chemistry for regulating the photothermal conversion efficiency. Emphasis is placed on the mechanisms of how self-assembly affects the photothermal performance. The supramolecular photothermal effects on various types of light-harvesting species are discussed in detail. The timely interpretation of supramolecular photothermal effects is promising for the future design of the photothermal materials with high efficiency, precision, and multiple functionalities for a wide array of applications.

Covalently Assembled Dipeptide Nanoparticles with Adjustable Fluorescence Emission for Multicolor Bioimaging.

Peptide self-assembly, inspired by the naturally occurring fabrication principle, remains the most attractive in constructing fluorescent nanoagents towards bioimaging. However, the noncovalent interactions that drive peptide self-assembly are usually susceptible to the complex physiological environment; thus leading to disassembly and dysfunction of fluorescent nanoagents. Herein, a covalently crosslinked assembly strategy for fabrication of stable peptide-based nanoparticles with adjustable emission is introduced. In the process of cationic diphenylalanine peptide (H-Phe-Phe-NH2 ⋅HCl) self-assembly, glutaraldehyde is used as a crosslinker and the resulting product of the Schiff base reaction can be fluorescent. More importantly, the emission wavelength can be readily tuned by controlling the covalent reaction time. It has been demonstrated that the nanoparticles are stable, even after intracellular uptake, and can be used for sustainable multicolor fluorescent imaging. The strategy with integrating peptide self-assembly and covalent crosslinking could be promising for the design and engineering of functional fluorescent nanoparticles with robust physiological stability and adjustable emission towards improved bioimaging applications.

Increased Expression of Kv10.2 in the Hippocampus Attenuates Valproic Acid-Induced Autism-Like Behaviors in Rats.

The role of potassium channels provides suggestive evidence for the etiology of autism. The voltage-gated potassium channel Kv10.2 (KCNH5) is widely expressed in the brain. However, the inherent relationship between Kv10.2 and autism is still unclear. Herein, a rat valproic acid (VPA)-induced autism spectrum disorder model was established. The expression level of Kv10.2 was obviously decreased in the hippocampus of VPA rats. Kv10.2 was mainly localized in neurons. Subsequently, a recombinant lentivirus expressing Kv10.2 was used to upregulate the expression of Kv10.2 in the hippocampus of VPA-exposed rats. The results were promising as injection of the Kv10.2 lentivirus in the hippocampus relieved anxiety and stereotypical behavior, and improved the social and exploratory abilities of rats that were prenatally exposed to VPA. In addition, spectral analysis of electroencephalogram data revealed that animals exposed to VPA exhibited increased high-frequency activity compared with the control rats, and this activity recovered to a certain extent after upregulation of Kv10.2 expression by lentivirus injection. These results suggest that changes in Kv10.2 may play an important role in the etiology of autism, thus providing a promising direction for further research on autism.

A gD&gC-substituted pseudorabies virus vaccine strain provides complete clinical protection and is helpful to prevent virus shedding against challenge by a Chinese pseudorabies variant.

BACKGROUND: Since 2011, pseudorabies caused by a variant PRV has re-emerged in many Chinese Bartha-K61-vaccinated pig farms. An efficacious vaccine is necessary to control this disease. We described the construction of a gD&gC-substituted pseudorabies virus (PRV B-gD&gCS) from the Bartha-K61 (as backbone) and AH02LA strain (as template for gD and gC genes) through bacterial artificial chromosome (BAC) technology using homologous recombination. The growth kinetics of PRV B-gD&gCS was compared with Bartha-K61. Its safety was evaluated in 28-day-old piglets. Protection efficacy was tested in piglets by lethal challenge with AH02LA at 7 days post vaccination, including body temperature, clinical symptoms, virus shedding, mortality rate, and lung lesions. RESULTS: The results showed that a BAC clone of Bartha-K61 and a B-gD&gCS clone were successfully generated. The growth kinetics of PRV B-gD&gCS strain on ST (Swine testicular) cells was similar to that of the Bartha-K61 strain. No piglets inoculated intramuscularly with PRV B-gD&gCS strain exhibited any clinical symptoms or virus shedding. After AH02LA challenge, all piglets in PRV B-gD&gCS and Bartha-K61 groups (n = 5 each) survived without exhibiting any clinical symptoms and high body temperature. More importantly, PRV B-gD&gCS strain completely prevented virus shedding in 2 piglets and reduced virus shedding post challenge in the other 3 piglets as compared with Bartha-K61 group. CONCLUSIONS: Our results suggest that PRV B-gD&gCS strain is a promising vaccine candidate for the effective control of current severe epidemic pseudorabies in China.

MiR-539-5p negatively regulates migration of rMSCs induced by Bushen Huoxue decoction through targeting Wnt5a.

Bone fractures are very common, and above 5% of the fractures are impaired, leading to nonunions and severe disablilities. The traditional Chinese medicine Bushen Huoxue decoction (BHD) has been used to treat fracture in China. Our previous report has found that BHD promotes migration of rat mesenchymal stem cells (rMSCs) by activating Wnt5a signaling pathway. However, whether and how miRNAs are involved in modulating rMSCs migration induced by BHD has not been explored. In the present study, miRNA microarray analysis and further validation by real-time quantitative RT-PCR revealed that miR-539-5p was down-regulated in BHD-induced rMSCs. Transfection of miR-539-5p mimics suppressed rMSCs migration while the miR-539-5p inhibitor promoted rMSCs migration. Our results suggested that miR-539-5p was a negative regulator of migration of rMSCs induced by BHD. Target prediction analysis tools and Dual-luciferase reporter gene assay identified Wnt5a as a direct target of miR-539-5p. MiR-539-5p inhibited the expression of the Wnt5a and its downstream signaling molecules including JNK, PKC and CaMKII, which played a critical role in regulating migration of rMSCs. Taken together, our results demonstrate that miR-539-5p negatively regulates migration of rMSCs induced by BHD through targeting Wnt5a. These findings provide evidence that miR-539-5p should be considered as an important candidate target for the development of preventive or therapeutic approaches against bone nonunions.

Profiling the miRNA-mRNA-lncRNA interaction network in MSC osteoblast differentiation induced by (+)-cholesten-3-one.

BACKGROUND: Our previous study showed that (+)-cholesten-3-one (CN) has the potential to induce the osteoblastic differentiation of mesenchymal stem cells (MSCs). However, the roles of CN in targeting miRNA-mRNA-lncRNA interactions to regulate osteoblast differentiation remain poorly understood. RESULTS: A total of 77 miRNAs (36 upregulated and 41 downregulated) and 295 lncRNAs (281 upregulated and 14 downregulated) were significantly differentially expressed during CN-induced MSC osteogenic differentiation. Bioinformatic analysis identified that several pathways may play vital roles in MSC osteogenic differentiation, such as the vitamin D receptor signalling, TNF signalling, PI3K-Akt signalling, calcium signalling, and mineral absorption pathways. Further bioinformatic analysis revealed 16 core genes, including 6 mRNAs (Vdr, Mgp, Fabp3, Fst, Cd38, and Col1a1), 5 miRNAs (miR-483, miR-298, miR-361, miR-92b and miR-155) and 5 lncRNAs (NR_046246.1, NR_046239.1, XR_086062.1, XR_145872.1 and XR_146737.1), that may play important roles in regulating the CN-induced osteogenic differentiation of MSCs. Verified by the luciferase reporter, AR-S, qRT-PCR and western blot assays, we identified one miRNA (miR-298) that may enhance the osteogenic differentiation potential of MSCs via the vitamin D receptor signalling pathway. CONCLUSIONS: This study revealed the global expression profile of miRNAs and lncRNAs involved in the Chinese medicine active ingredient CN-induced osteoblast differentiation of MSCs for the first time and provided a foundation for future investigations of miRNA-mRNA-lncRNA interaction networks to completely illuminate the regulatory role of CN in MSC osteoblast differentiation.

Highly Conjugated Three-Dimensional Covalent Organic Frameworks Based on Spirobifluorene for Perovskite Solar Cell Enhancement.

Highly conjugated three-dimensional covalent organic frameworks (3D COFs) were constructed based on spirobifluorene cores linked via imine bonds (SP-3D-COFs) with novel interlacing conjugation systems. The crystalline structures were confirmed by powder X-ray diffraction and detailed structural simulation. A 6- or 7-fold interpenetration was formed depending on the structure of the linking units. The obtained SP-3D-COFs showed permanent porosity and high thermal stability. In application for solar cells, simple bulk doping of SP-3D-COFs to the perovskite solar cells (PSCs) substantially improved the average power conversion efficiency by 15.9% for SP-3D-COF 1 and 18.0% for SP-3D-COF 2 as compared to the reference undoped PSC, while offering excellent leakage prevention in the meantime. By aid of both experimental and computational studies, a possible photoresponsive perovskite-SP-3D-COFs interaction mechanism was proposed to explain the improvement of PSC performance after SP-3D-COFs doping.