Berberine-loaded MSC-derived sEVs encapsulated in injectable GelMA hydrogel for spinal cord injury repair.

After spinal cord injury (SCI), local inflammatory response and fibrous scar formation severely hinder nerve regeneration. Berberine (Ber) has a powerful regulatory effect on the local microenvironment, but its limited solubility and permeability through the blood-brain barrier severely limit its systemic efficacy. Human umbilical cord mesenchymal stem cells (hUC-MSCs)-derived small extracellular vesicles (sEVs) are natural nanocarriers with high cargo loading capacity, and can cross the blood-brain barrier. Most importantly, sEVs can improve drug solubility and drug utilization. Therefore, they can overcome many defects of Ber application. This experiment aimed to design a Ber-carrying hUC-MSCs-derived sEVs and GelMA hydrogel. Ber was loaded into sEVs (sEVs-Ber) by ultrasonic co-incubation with a drug loading capacity (LC) of 15.07%. The unhindered release of up to 80% of sEVs-Ber from GelMA hydrogel was accomplished for up to 14 days. And they could be directly absorbed by local cells of injury, allowing for direct local delivery of the drug and enhancing its efficacy. The experimental results confirmed injecting GelMA-sEVs-Ber into spinal cord defects could exert anti-inflammatory effects by regulating the expression of inflammatory factors. It also demonstrated the anti-fibrotic effect of Ber in SCI for the first time. The modulatory effects of sEVs and Ber on the local microenvironment significantly promoted nerve regeneration and recovery of motor function in post-SCI rats. These results demonstrated that the GelMA-sEVs-Ber dual carrier system is a promising therapeutic strategy for SCI repair.

Development of a Visual Perception System on a Dual-Arm Mobile Robot for Human-Robot Interaction.

This paper presents the development of a visual-perception system on a dual-arm mobile robot for human-robot interaction. This visual system integrates three subsystems. Hand gesture recognition is utilized to trigger human-robot interaction. Engagement and intention of the participants are detected and quantified through a cognitive system. Visual servoing uses YOLO to identify the object to be tracked and hybrid, model-based tracking to follow the object's geometry. The proposed visual-perception system is implemented in the developed dual-arm mobile robot, and experiments are conducted to validate the proposed method's effects on human-robot interaction applications.

Species richness and endemism pattern of Fagaceae in Southwest China and their environmental interpretation.

How to accurately model species macro-richness patterns and endemism centers is a key focus of biodiversity conservation efforts and a hot biogeographical topic. Southwest China is one of regions with high Fagaceae species richness, the species diversity patterns and driving mechanisms are unclear. In this study, the distribution pattern of species richness (SR), weighted endemism (WE), and corrected weighted endemism (CWE) indices were estimated based on 7258 occurrence points of 161 Fagaceae species in Southwest China using both occurrence-to grid method and species distribution model (SDM). We used the spatial autoregressive (SAR) model to analyze the relationship between diversity indices and environmental factors. Overall, the three SDM-simulated diversity indices were more continuous in values than that of the occurrence-to grid method, though the distributions of those indices obtained by the two methods were similar. The areas with high SR value were mainly distributed in the south edge of Yunnan, north Guangxi and southwest Guangxi (62-89 species). The maximum of WE concentrated in south Yunnan and west Guangxi (1.77-5.02). The highest CWE (0.07-0.17) was found in southeast Tibet, Qinling-Daba Mountains, southwest Guangxi, and southeast Yunnan. The SAR models showed significant effect of precipita-tion in the driest month, standard deviations of seasonal temperature, altitude range and soil organic carbon content on SR. The effects of precipitation in the driest month, standard deviations of seaso-nal temperature, potential evaporation and altitude range on the WE were significant. The precipitation in the driest month, standard deviations of seasonal temperature, historical temperature change, coefficient of variation of enhanced vegetation index and altitude variation had significant effects on the CWE. The R2 of SAR model for SR, WE and CWE was 0.857, 0.733, 0.593, respectively, being higher than that of ordinary least squares (OLS) (R2=0.689, 0.425, 0.422). In conclusion, water availability, climate seasonality, habitat heterogeneity, historical climate change and soil condition were the most important factors limiting the distribution of SR and WE of Fagaceae in Southwest China. The SR and WE centers of Fagaceae were located in south and southeast Yunnan, southwest Guangxi, west Guangxi, Qinling-Daba Mountains, and southeast Tibet, where should be adequately protected.

Real Gentile Statistical Systems: N-Annulenes.

Gentile statistics, which is famous for its advantages in dealing with composite particle systems, is a kind of fractional statistics. Lately, researchers are concentrating on finding real systems that obey Gentile statistics. Five years ago, we discovered that the cyclic hydrocarbon polyenes called N-annulenes in the Hückel model had certain correspondence with Gentile oscillators. According to their rotation and dihedral symmetry, these two systems had the same energy levels and partition functions. In this paper, we give further discussions. We discuss the transformations of wave functions between N-annulenes and Gentile oscillators, the creation and annihilation operators in site pictures of N-annulenes, the coherent state, and the mathematical proofs of the intermediate commutation relations of operators. All of our works prove that N-annulenes in the Hückel model are real Gentile statistical systems and offer a new algebraic method to deal with the problems of electron-electron and electron-phonon interactions.

Inhibition of Streptococcus suis Adhesion and Biofilm Formation in Vitro by Water Extracts of Rhizoma Coptidis.

Streptococcus suis is difficult to treat and responsible for various infections in humans and pigs. It can also form biofilms and induce persistent infections. Rhizoma Coptidis is a medicinal plant widely used in Traditional Chinese Medicine. Although the inhibitory effects of Rhizoma Coptidis on biofilm formation have been investigated in several studies, the ability of Rhizoma Coptidis to inhibit S. suis biofilm formation and the underlying mechanisms have not yet been reported. In this study, we showed that sub-minimal inhibitory concentrations (25 and 50 µg mL-1) of water extracts of Rhizoma Coptidis (Coptis deltoidea C.Y.Cheng & P.K.Hsiao, obtained from Sichuan Province) were sufficient to inhibit biofilm formation, as shown in the tissue culture plate (TCP) method and scanning electron microscopy. Real-time PCR and iTRAQ were used to measure gene and protein expression in S. suis. Sub-minimum inhibitory concentrations (25 and 50 µg mL-1) of Rhizoma Coptidis water extracts inhibited S. suis adhesion significantly in an anti-adherence assay. Some genes, such as gapdh, sly, and mrp, and proteins, such as antigen-like protein, CPS16V, and methyltransferase H, involved in adhesion were significantly modulated in cells treated with 50 µg mL-1 of Rhizoma Coptidis water extracts compared to untreated cells. The results from this study suggest that compounds in Rhizoma Coptidis water extracts play an important role in inhibiting adhesion of S. suis cells and, therefore, biofilm formation.

Wnt signaling pathway involvement in genotypic and phenotypic variations in Waardenburg syndrome type 2 with MITF mutations.

Mutation in the gene encoding microphthalmia-associated transcription factor (MITF) lead to Waardenburg syndrome 2 (WS2), an autosomal dominantly inherited syndrome with auditory-pigmentary abnormalities, which is clinically and genetically heterogeneous. Haploinsufficiency may be the underlying mechanism for WS2. However, the mechanisms explaining the genotypic and phenotypic variations in WS2 caused by MITF mutations are unclear. A previous study revealed that MITF interacts with LEF-1, an important factor in the Wnt signaling pathway, to regulate its own transcription through LEF-1-binding sites on the MITF promoter. In this study, four different WS2-associated MITF mutations (p.R217I, p.R217G, p.R255X, p.R217del) that are associated with highly variable clinical features were chosen. According to the results, LEF-1 can activate the expression of MITF on its own, but MITF proteins inhibited the activation. This inhibition weakens when the dosage of MITF is reduced. Except for p.R217I, p.R255X, p.R217G, and p.R217del lose the ability to activate TYR completely and do not inhibit the LEF-1-mediated activation of the MITF-M promoter, and the haploinsufficiency created by mutant MITF can be overcome; correspondingly, the mutants' associated phenotypes are less severe than that of p.R217I. The dominant negative of p.R217del made it have a second-most severe phenotype. This study's data imply that MITF has a negative feedback loop of regulation to stabilize MITF gene dosage that involves the Wnt signaling pathway and that the interaction of MITF mutants with this pathway drives the genotypic and phenotypic differences observed in Waardenburg syndrome type 2 associated with MITF mutations.

Functional analysis of a SOX10 gene mutation associated with Waardenburg syndrome II.

Waardenburg syndrome (WS) is an autosomal dominant inherited non-syndromic type of hereditary hearing loss characterized by varying combinations of sensorineural hearing loss and abnormal pigmentation of the hair, skin, and inner ear. WS is classified into four subtypes (WS1-WS4) based on additional symptoms. WS2 is characterized by the absence of additional symptoms. Recently, we identified a SOX10 missense mutation c.422T > C (p.L141P) associated with WS2. We performed functional assays and found the mutant loses DNA-binding capacity, shows aberrant cytoplasmic and nuclear localization, and fails to interact with PAX3. Therefore, the mutant cannot transactivate the MITF promoter effectively, inhibiting melanin synthesis and leading to WS2. Our study confirmed haploinsufficiency as the underlying pathogenesis for WS2.

Sub-Minimum Inhibitory Concentrations of Rhubarb Water Extracts Inhibit Streptococcus suis Biofilm Formation.

Streptococcus suis is one of the most important swine pathogens, which can cause persistent infection by forming biofilms. In this study, sub-minimum inhibitory concentration (sub-MIC) of rhubarb water extracts were found to inhibit biofilm formation. Two-component signal transduction systems (TCSs), transcriptional regulators, and DNA binding proteins were compared under two conditions: (1) cells treated with sub-MIC rhubarb water extracts and (2) untreated cells. Using an isobaric tags for relative and absolute quantitation (iTRAQ) strategy, we found that TCSs constituent proteins of histidine kinase and response regulator were significantly down-regulated. This down-regulation can affect the transfer of information during biofilm formation. The transcriptional regulators and DNA binding proteins that can interact with TCSs and interrupt gene transcription were also significantly altered. For these reasons, the levels of protein expressions varied in different parts of the treated vs. untreated cells. In summary, rhubarb water extracts might serve as potential inhibitor for the control of S. suis biofilm formation. The change in TCSs, transcriptional regulators, and DNA binding proteins may be important factors in S. suis biofilm inhibition.

Sub-MICs of Azithromycin Decrease Biofilm Formation of Streptococcus suis and Increase Capsular Polysaccharide Content of S. suis.

Streptococcus suis (S. suis) caused serious disease symptoms in humans and pigs. S. suis is able to form thick biofilms and this increases the difficulty of treatment. After growth with 1/2 minimal inhibitory concentration (MIC) of azithromycin, 1/4 MIC of azithromycin, or 1/8 MIC of azithromycin, biofilm formation of S. suis dose-dependently decreased in the present study. Furthermore, scanning electron microscopy analysis revealed the obvious effect of azithromycin against biofilm formation of S. suis. Especially, at two different conditions (1/2 MIC of azithromycin non-treated cells and treated cells), we carried out comparative proteomic analyses of cells by using iTRAQ technology. Finally, the results revealed the existence of 19 proteins of varying amounts. Interestingly, several cell surface proteins (such as ATP-binding cassette superfamily ATP-binding cassette transporter (G7SD52), CpsR (K0FG35), Cps1/2H (G8DTL7), CPS16F (E9NQ13), putative uncharacterized protein (G7SER0), NADP-dependent glyceraldehyde-3-phosphate dehydrogenase (G5L259), putative uncharacterized protein (G7S2D6), amino acid permease (B0M0G6), and NsuB (G5L351)) were found to be implicated in biofilm formation. More importantly, we also found that azithromycin affected expression of the genes cps1/2H, cpsR and cps16F. Especially, after growth with 1/2 MIC of azithromycin and 1/4 MIC of azithromycin, the capsular polysaccharide content of S. suis was significantly higher.

Synthesis, characterization and in vitro evaluation of a series of novel polyrotaxane-based delivery system for artesunate.

A series of novel artesunate-polyrotaxanes (ATS-PRs) with folic acid capped, in which artesunate (ATS) was covalently bound to a cyclodextrin (CD) of the polyrotaxane (PR), were synthesized and were characterized by NMR, XRD, TG and DSC. The cytotoxicities of ATS-PRs on human colon cancer cell lines HT-29, SW480, HTC116 and DLD-1 showed that their antitumor activities were better than that of artesunate (ATS) and dihydroartemisinin (DHA). These ATS-PRs may provide a useful approach to the development of a highly effective drug candidate for the chemotherapy of human colon cancer.

Quantitative proteomic analysis of sub-MIC erythromycin inhibiting biofilm formation of S. suis in vitro.

Streptococcus suis (S. suis) is a swine pathogen and also a zoonotic agent. Biofilms of S. suis may cause persistent infections by the host immune system and antibiotics. Sub-minimal inhibitory concentration (sub-MIC) of erythromycin can inhibit biofilm formation in bacteria. Here, we performed comparative proteomic analyses of cells at two different conditions: sub-MIC erythromycin treated and nontreated cells. Using iTRAQ strategy, we found some novel proteins that involved in biofilm formation. 79 differentially expressed proteins were identified in sub-MIC erythromycin inhibiting planktonic cell when the protein had both a fold-change of more that a ratio >1.2 or <0.8 (p-value <0.05). Several cell surface proteins (such as Primosomal protein N', l-fucose isomerase, and ABC superfamily ATP binding cassette transporter, membrane protein), as well as those involved in Quorum-sensing, were found to be implicated in biofilm formation. Overall, our results indicated that cell surface proteins played an important role in biofilm formation. Quorum-sensing played a crucial role leading to biofilm formation. ABC superfamily ATP binding cassette transporter, membrane protein and comD might act as channels for erythromycin uptake in Quorum-sensing system. Thus, our data analyzed rough regulatory pathways of biofilm formation that might potentially be exploited to deal with biofilm infections of S. suis. This article is part of a Special Issue entitled: Microbial Proteomics. BIOLOGICAL SIGNIFICANCE: In this study, we identified many proteins involved in cell transport, biological regulation and signal transduction, stress responses and other metabolic processes that were not previously known to be associated with biofilm formation of S. suis and target spot of erythromycin. Therefore, our manuscript represents the most comprehensive analysis of protein profiles of biofilm formation of S. suis inhibited by sub-MIC erythromycin and provides new proteomic information about biofilm formation.

Synthesis, characterization, and in vitro evaluation of artesunate-ß-cyclodextrin conjugates as novel anti-cancer prodrugs.

A novel series of artesunate-ß-cyclodextrin (ATS-ß-CD) conjugates, in which artesunate (ATS) was coupled covalently to one of the primary hydroxyl groups of ß-cyclodextrin (ß-CD) through amino bond formation, were synthesized and characterized by (1)H NMR, HRMS, 2D NMR (ROESY), X-ray diffraction (XRD), and thermogravimetric analysis (TGA). The results showed that the aqueous solubility of ATS-ß-CD conjugates was 26-45 times better than that of free ATS. The cytotoxicity of the ATS-ß-CD conjugates was evaluated on human colon cancer cell lines HCT116, LOVO, SW480, and HT-29, and the results indicated that ATS-2NßCD exhibited a very high cytotoxicity against HCT116, LOVO, and HT-29 with IC50 values of 0.58, 1.62, and 5.18µmol/L, respectively. In addition, the supposition of better cytotoxicity was further supported by the control experiment of fluorescent cyclodextrin.

A novel polyrotaxane-based delivery system for scutellarin: preparation, characterization, and in vitro evaluation.

The safe and effective polyrotaxane-based drug delivery system could potentially increase the antiproliferative activity of antitumor medicine. A novel scutellarin-polyrotaxane (SCU-PR), in which scutellarin (SCU) was covalently bound to one of the hydroxyl groups of polyrotaxane (PR), was synthesized, and its characterization was further investigated by NMR, XRD, TG, DSC. The cytotoxicity of SCU-PR was assessed in vitro using human HCT116 and LOVO cell lines in results that the IC50 values of SCU-PR (1.03×10(-6) and 1.01×10(-6)mol/L, respectively), which compared with those of free SCU (7.80×10(-5) and 7.70×10(-5)mol/L, respectively), were lower. The valuable properties of SCU-PR will be potentially useful for its application on human colon cancer chemotherapies.

Scutellarin-cyclodextrin conjugates: synthesis, characterization and anticancer activity.

A series of scutellarin-cyclodextrin conjugates (SCU-CD conjugates), in which scutellarin was covalently bound to one of the primary hydroxyl groups of ß-CD, were prepared, and their structures were determined using NMR and MS. These conjugates were further characterized by XRD and TG. The results showed that the aqueous solubility of the conjugates was much higher than that of scutellarin, and the conjugates could hardly be hydrolyzed to scutellarin in aqueous solutions. The cytotoxicity of SCU-CD conjugates on human colon cancer cell lines HT-29, SW480, Lovo and HTC116 indicated that the antitumor activities of the conjugates were better than that of scutellarin. This high antitumor activity, along with the satisfactory aqueous solubility and high stability of the conjugates, will be potentially useful for their application on human colon cancer chemotherapies.

[Experience introduction of induced eruption on multiple adjacent impacted teeth in anterior maxillary bone].

OBJECTIVE: To study the method of induced eruption on multiple adjacent impacted teeth in anterior maxillary bone. METHODS: Twenty-two multiple adjacent impacted teeth of 9 cases were chosen. The position of the impacted teeth and the relationship to each other were assessed on X-ray images, oral examination and plaster model. The impacted teeth were extracted or induced erupted with the closed-eruption technique and fixed orthodontic appliances. RESULTS: Of 22 impacted teeth, 19 impacted teeth were moved into arches by induced eruption with the closed-eruption technique and fixed orthodontic appliances. There were not root adsorption or conglutination for 19 impacted teeth. Three impacted teeth with deformed root were extracted. The average time for treatment was 19 months. CONCLUSION: With correct diagnosis, reasonable design, the complicated impacted teeth could be moved into alignment with good esthetic and functional effect.