Determination of diethylstilbestrol in environmental water based on electrochemical senser modified with vanadium based metal organic framework material composite.

In this research, the MIL-47/ACET/Nafion/GCE electrochemical senser for the determination of diethylstilbestrol (DES) was prepared with vanadyl sulfate (VOSO4·nH2O) and terephthalic acid (H2BDC) as the main raw materials, compounded with acetylene black (ACET) and perfluorosulfonic acid polymer (Nafion). The compound DES belongs to the category of estrogens, and prolonged exposure to the environment can have detrimental effects on the physiological functioning of both humans and animals. Due to the strong DES enrichment performance of MIL-47(V-MOFs) with large specific surface area, in addition to the excellent conductivity and electrocatalysis of composite materials, this modified senser had good electrochemical response to DES. With differential pulse voltammetry, in optimum condition of 0.1 M NaH2PO4-Na2HPO4at pH = 7.0, potential interval of -1.0 to 1.0 V, enrichment time of 120 s and enrichment potential of 0.2 V, there was a good linear relationship between peak current and the concentration of DES over the range of 0.1 and 50µM, and the limit of detection was 0.008µM. The sensor accurately detected DES in actual water samples, with recovery rates ranging from 89.21% to 105.3%. The electrochemical sensor was simple to prepare and had practical significance for the detection of DES in water. The research results of the sensor provide another alternative analytical means for the sensitive detection of DES in the environment, which is important for maintaining public health.

Single-atom iron boosts electrochemiluminescence for ultrasensitive carcinoembryonic antigen detection.

A simple and ultrasensitive sandwich-type electrochemiluminescence (ECL) immunosensor has been developed using porous three-dimensional gold nanoparticles (Au NPs) iron(Fe)-zinc(Zn) metal-organic frameworks (Au NPs-FeZn-MOFs@luminol) as high-efficiency ECL signal probes with Fe single-atom catalysts (SACs) (Fe-N-C SACs) as potentially advanced coreaction accelerators and dissolved oxygen as a coreaction agent to realize an H2O2-free amplification method for detecting carcinoembryonic antigen (CEA). The cathodic ECL of luminol, which was usually negligible, increased first. Because the Fe-N-C SACs exhibited an outstanding catalytic performance and a unique electronic structure, different reactive oxygen species (ROS) were generated via the oxygen reduction reaction. ROS oxidized the luminol anions to luminol anion radicals, preventing the time-consuming luminol electrochemical oxidation. Furthermore, the luminol anion radicals generated in situ reacted with ROS to produce potent cathodic ECL emissions. The immunosensor exhibited favorable analytical accuracy (detection range: 0.1 pg mL-1 - 80 ng mL-1), and its detection limit for serum samples was 0.031 pg mL-1 (S/N = 3). Consequently, the proposed strategy offers a new approach for early screening of CEA.

Manipulating Crystallographic Orientation via Cross-Linkable Ligand for Efficient and Stable Perovskite Solar Cells.

The crystallographic orientation of polycrystalline perovskites is found to be strongly correlated with their intrinsic properties; therefore, it can be used to effectively enhance the performance of perovskite-based devices. Here, a facile way of manipulating the facet orientation of polycrystalline perovskite films in a controllable manner is reported. By incorporating a cross-linkable organic ligand into the perovskite precursor solution, the crystal orientation disorder can be reduced in the resultant perovskite films to exhibit the prominent (001) orientation with a preferred stacking mode. Moreover, the as-formed low-dimensional perovskites (LDPs) between the organic ligand and the excess lead iodide can passivate the defects around the grain boundaries. Consequently, highly efficient p-i-n structured perovskite solar cells (PSCs) can be made in both rigid and flexible forms from modified perovskites to show high power conversion efficiencies (PCE) of 24.12% and 23.23%, respectively. The devices also exhibit superior long-term stability in a humid environment (with T90  > 1000 h) and under thermal stress (retaining 87% of its initial PCE after 1000 h). More importantly, the ligand enables the derived LDPs to be crosslinked (under 254 nm UV illumination) to demonstrate excellent mechanical bending durability in flexible devices.

Chlorocholine Perchlorate is an Organic Ferroelectric with Two-Step Ladder-like Dielectric, Second Harmonic Generation Effects, and Ferroelectricity.

The organic salt chlorocholine perchlorate [ClCH2 CH2 N(CH3 )3 ⋅ClO4 ] (CCP) is found to be a molecular ferroelectric with a high theoretical spontaneous polarization (Ps) value up to 17.09 µC cm-2 . CCP exhibits two successive order-disorder phase transition at 332 and 365 K with space groups changing from Cc to Cmc21 and then P63 /mmc, accompanied by unusual two-step ladder-like dielectric, SHG signal with obvious "on/off" contrasts. These findingings provides a further instance of exploring successive thermal-stimuli multi-responsive switching materials applied as switches and sensors.

Bispecific antibody targeting both B7-H3 and PD-L1 exhibits superior antitumor activities.

Clinical application of PD-1 and PD-L1 monoclonal antibodies (mAbs) is hindered by their relatively low response rates and the occurrence of drug resistance. Co-expression of B7-H3 with PD-L1 has been found in various solid tumors, and combination therapies that target both PD-1/PD-L1 and B7-H3 pathways may provide  additional therapeutic benefits. Up to today, however, no bispecific antibodies targeting both PD-1 and B7-H3 have reached the clinical development stage. In this study, we generated a stable B7-H3×PD-L1 bispecific antibody (BsAb) in IgG1-VHH format by coupling a humanized IgG1 mAb against PD-L1 with a humanized camelus variable domain of the heavy-chain of heavy-chain antibody (VHH) against human B7-H3. The BsAb exhibited favorable thermostability, efficient T cell activation, IFN-γ production, and antibody-dependent cell-mediated cytotoxicity (ADCC). In a PBMC humanized A375 xenogeneic tumor model, treatment with BsAb (10 mg/kg, i.p., twice a week for 6 weeks) showed enhanced antitumor activities compared to monotherapies and, to some degree, combination therapies. Our results suggest that targeting both PD-1 and B7-H3 with BsAbs increases their specificities to B7-H3 and PD-L1 double-positive tumors and induces a synergetic effect. We conclude that B7-H3×PD-L1 BsAb is favored over mAbs and possibly combination therapies in treating B7-H3 and PD-L1 double-positive tumors.

Dermoscopy and reflection confocal microscope features of pigmented prurigo.

BACKGROUND: Pigmented prurigo (PP) is a chronic and recurrent inflammatory skin disease. PP is not common clinically, but it is easily misdiagnosed because of its diversified clinical manifestations in different stages. MATERIALS AND METHODS: We retrospectively analyzed the clinical, histopathological, dermoscopy, and reflectance confocal microscopy (RCM) features of 20 patients diagnosed as PP. RESULTS: The female predominance ratio was revealed with male to female of 1:4. Seven female patients were on a diet (without staple food) and one patient had a history of diabetes. Eight cases were suffered in spring, six cases in winter, three cases in summer, and three cases in autumn. Multiple sites were involved in 13 cases. Four patients had urticarial papules and plaques. Nineteen patients had erythematous papules with reticular distribution, of which 14 cases accompanied reticulate hyperpigmentation, four cases with papulovesicle, and two cases accompanied with pustules. One patient only showed reticulate hyperpigmentation. In the early lesions, dermatoscopy showed pink oval lesions, punctate or linear vessels, and pale yellow rings around the skin lesions. RCM is characterized by spongiosis, spongy vesicle, neutrophils scattered in the epidermis, which was consistent with epidermis spongiosis, neutrophils infiltrating into the upper epidermis and necrotic keratinocytes in histopathology. In the fully developed lesions, dermatoscopy showed pink lesions with brown pigment granules in the center and linear vessels in the edge. RCM showed that demarcation of epidermis and dermis is not clear, and inflammatory cells can be seen in the upper dermis and histopathologically lesions assumed a patchy lichenoid pattern, and the inflammatory cells infiltrating the dermis were dominated by lymphocytes. In the late lesions, dermatoscopy showed grainy grayish-brown or yellowish-brown pigmentation surrounding the hair follicle merging with each other. RCM showed that pigment granules were increased on the ring of basal cells, inflammatory cells were sparsely infiltrated in the dermal papilla and superficial layer, and epidermis slightly hyperplastic, with melanophages and a few lymphocytes infiltrating the superficial dermis in histopathology. CONCLUSION: PP is easily misdiagnosed and not always occurs in those on a restrictive diet. A combination of dermatoscopy and RCM is helpful for its diagnosis of PP.

Evaluating the role of subacromial impingement in rotator cuff tendinopathy: development and analysis of a novel rat model.

BACKGROUND: Subacromial impingement of the rotator cuff caused by variations in acromial anatomy or altered glenohumeral kinematics leads to inflammation and degeneration of the rotator cuff, ultimately contributing to the development of tendinopathy. However, the underlying cellular and molecular changes in the impinged tendon remain poorly understood. Because the rat is an accepted model for rotator cuff studies, we have developed a rat model to study rotator cuff tendinopathy. METHODS: Forty-four adult male Sprague-Dawley rats were allocated to one of 4 study groups: intact control group (group 1, n = 11); bilateral subacromial surgical clip placement to induce supraspinatus impingement for 2 weeks (group 2, n = 11), 4 weeks (group 3, n = 11), and 8 weeks (group 4, n = 11). Bilateral shoulder specimens were harvested for biomechanical testing, histology, and quantitative real-time polymerase chain reaction (qRT-PCR) analysis. RESULTS: Radiography confirmed that all microvascular clips remained in stable position in the subacromial space. Gross inspection of supraspinatus tendon specimens in the impingement groups revealed changes in tendon morphology at the enthesis and midsubstance. Biomechanical evaluation demonstrated decreased supraspinatus tendon failure force and tissue stiffness at all time points compared with control tendons. Semiquantitative scoring of histologic specimens demonstrated significant, persistent tendinopathic changes over 8 weeks. qRT-PCR analysis of impinged tendon specimens demonstrated upregulation of gene expression for Col3 and Mmp14 in the impingement groups compared with control groups. In muscle samples, significant upregulation was seen in the expression of genes that are commonly associated with muscle atrophy (MuRF1 and Ube2b) and fatty infiltration (Fabp4, Pparg2, and Klf15). CONCLUSION: This new rat subacromial impingement model creates cellular and molecular changes consistent with the development of rotator cuff tendinopathy. The results of this study may serve as a baseline for future investigation.

Co-assembled Monolayers as Hole-Selective Contact for High-Performance Inverted Perovskite Solar Cells with Optimized Recombination Loss and Long-Term Stability.

Self-assembled monolayers (SAMs) have been widely employed as an effective way to modify interfaces of electronic/optoelectronic devices. To achieve a good control of the growth and molecular functionality of SAMs, we develop a co-assembled monolayer (co-SAM) for obtaining efficient hole selection and suppressed recombination at the hole-selective interface in inverted perovskite solar cells (PSCs). By engineering the position of methoxy substituents, an aligned energy level and favorable dipole moment can be obtained in our newly synthesized SAM, ((2,7-dimethoxy-9H-carbazol-9-yl) methyl) phosphonic acid (DC-PA). An alkyl ammonium containing SAM is co-assembled to further optimize the surface functionalization and interaction with perovskite layer on top. A champion device with an excellent power conversion efficiency (PCE) of 23.59 % and improved device stability are achieved. This work demonstrates the advantage of using co-SAM in improving performance and stability of PSCs.

Baicalin prevents LPS-induced activation of TLR4/NF-κB p65 pathway and inflammation in mice via inhibiting the expression of CD14.

Previous studies have shown that baicalin, an active ingredient of the Chinese traditional medicine Huangqin, attenuates LPS-induced inflammation by inhibiting the activation of TLR4/NF-κBp65 pathway, but how it affects this pathway is unknown. It has been shown that CD14 binds directly to LPS and plays an important role in sensitizing the cells to minute quantities of LPS via chaperoning LPS molecules to the TLR4/MD-2 signaling complex. In the present study we investigated the role of CD14 in the anti-inflammatory effects of baicalin in vitro and in vivo. Exposure to LPS (1 µg/mL) induced inflammatory responses in RAW264.7 cells, evidenced by marked increases in the expression of MHC II molecules and the secretion of NO and IL-6, and by activation of MyD88/NF-κB p65 signaling pathway, as well as the expression of CD14 and TLR4. These changes were dose-dependently attenuated by pretreatment baicalin (12.5-50 µM), but not by baicalin post-treatment. In RAW264.7 cells without LPS stimulation, baicalin dose-dependently inhibit the protein and mRNA expression of CD14, but not TLR4. In RAW264.7 cells with CD14 knockdown, baicalin pretreatment did not prevent inflammatory responses and activation of MyD88/NF-κB p65 pathway induced by high concentrations (1000 µg/mL) of LPS. Furthermore, baicalin pretreatment also inhibited the expression of CD14 and activation of MyD88/NF-κB p65 pathway in LPS-induced hepatocyte-derived HepG2 cells and intestinal epithelial-derived HT-29 cells. In mice with intraperitoneal injection of LPS and in DSS-induced UC mice, oral administration of baicalin exerted protective effects by inhibition of CD14 expression and inflammation. Taken together, we demonstrate that baicalin pretreatment prevents LPS-induced inflammation in RAW264.7 cells in CD14-dependent manner. This study supports the therapeutic use of baicalin in preventing the progression of LPS-induced inflammatory diseases.

Knockdown of Bcl-2-Associated Athanogene-3 Can Enhance the Efficacy of BGJ398 via Suppressing Migration and Inducing Apoptosis in Gastric Cancer.

BACKGROUND: Gastric cancer (GC) is one of the most common malignancies of the digestive tract worldwide, and cancer cell resistance against anticancer drugs remains a major challenge for GC treatment. Nvp-BGJ398 (BGJ398) is considered as a common drug for cancer treatment; however, Bcl-2-associated athanogene-3 (BAG3) plays an important role in drug resistance. AIMS: To investigate the function of BAG3 on the sensitivity of GC cells to BGJ398. METHODS: The expression of BAG3 in GC cells and GC resistance cells was examined by qRT-PCR and western blot. The resistance to BGJ398 was detected by viability assay, and a half-maximal inhibitory concentration (IC50) was calculated. The cell migration and apoptosis were determined by wound-healing assay and flow cytometry assay. RESULTS: BAG3 was highly expressed in drug-resistant cells Fu97R and Snu16R. BAG3 was also associated with sensitivity of Snu16 cells to BGJ398, promoting migration but inhibiting apoptosis. However, knockdown of heat shock transcription factor 1 (HSF1) suppressed BAG3 expression and lowered the sensitivity to BGJ398 in Snu16R cells. Knockdown of BAG3 inhibited tumor growth and cell apoptosis but induced cell apoptosis and amplified the sensitivity to BGJ398 in Snu16R cells, followed by enhancing BGJ398-induced antitumor function in a Snu16R-derived xenograft mouse model. CONCLUSION: The mechanism of resistance to BGJ398 in GC is mediated by BAG3/HSF1, and combined treatment with shBAG3 could improve the efficacy of BGJ398 in GC. Thus, BAG3-targeted therapy improves the antitumor efficacy of BGJ398, which might provide a novel therapeutic strategy for GC.

Bilateral pulmonary embolism without deep venous thrombosis was observed after knee arthroscopy: a case report.

BACKGROUND: Symptomatic pulmonary embolism (PE) after knee arthroscopy is extremely rare. If the embolism is not treated promptly, the patient may die. Bilateral pulmonary embolism with associated pulmonary infarct without concomitant deep vein thrombosis has never been reported following routine knee arthroscopy. CASE PRESENTATION: A 50-year-old female patient with no other risk factors other than hypertension, obesity, varicose veins in the ipsilateral lower extremities and elevated triglyceride (TG) presented to our ward. She had experienced sudden chest tightness, polypnea and fainting after going to the bathroom the morning of the second postoperative day and received emergency medical attention. Colour ultrasonography of the extremities showed no deep vein thrombosis. Lung computed tomography angiography (CTA) showed multiple embolisms scattered in both pulmonary artery branches. Thus, emergency interventional thrombolysis therapy was performed, followed by postoperative symptomatic treatment with drugs with thrombolytic, anticoagulant and protective activities. One week later, lung CTA showed a significant improvement in the PEs compared with those in the previous examination. Since the aetiology of PE and no obvious symptoms were discerned, the patient was discharged. CONCLUSION: Although knee arthroscopy is a minimally invasive and quick procedure, the risk factors for PE in the perioperative period should be considered and fully evaluated to enhance PE detection. Moreover, a timely diagnosis and effective treatment are important measures to prevent and cure PE after knee arthroscopy. Finally, clear guidelines regarding VTE thromboprophylaxis following knee arthroscopy in patients with a low risk of VTE development are needed.

[Application of Automated Machine Learning Based on Radiomics Features of T2WI and RS-EPI DWI to Predict Preoperative T Staging of Rectal Cancer].

OBJECTIVE: To explore the radiomics features of T2 weighted image (T2WI) and readout-segmented echo-planar imaging (RS-EPI) plus difusion-weighted imaging (DWI), to develop an automated mahchine-learning model based on the said radiomics features, and to test the value of this model in predicting preoperative T staging of rectal cancer. METHODS: The study retrospectively reviewed 131 patients who were diagnosed with rectal cancer confirmed by the pathology results of their surgical specimens at West China Hospital of Sichuan University between October, 2017 and December, 2018. In addition, these patients had preoperative rectal MRI. Tumor regions from preoperative MRI were manually segmented by radiologists with the ITK-SNAP software from T2WI and RS-EPI DWI images. PyRadiomics was used to extract 200 features-100 from T2WI and 100 from the apparent diffusion coefficient (ADC) calculated from the RS-EPI DWI. MWMOTE and NEATER were used to resample and balance the dataset, and 13 cases of T 1-2 stage simulation cases were added. The overall dataset was divided into a training set (111 cases) and a test set (37 cases) by a ratio of 3∶1. Tree-based Pipeline Optimization Tool (TPOT) was applied on the training set to optimize model parameters and to select the most important radiomics features for modeling. Five independent T stage models were developed accordingly. Accuracy and the area under the curve ( AUC) of receiver operating characteristic (ROC) were used to pick out the optimal model, which was then applied on the training set and the original dataset to predict the T stage of rectal cancer. RESULTS: The performance of the the five T staging models recommended by automated machine learning were as follows: The accuracy for the training set ranged from 0.802 to 0.838, sensitivity, from 0.762 to 0.825, specificity, from 0.833 to 0.896, AUC, from 0.841 to 0.893, and average precision (AP) from 0.870 to 0.901. After comparison, an optimal model was picked out, with sensitivity, specificity and AUC for the training set reaching 0.810, 0.875, and 0.893, respectively. The sensitivity, specificity and AUC for the test set were 0.810, 0.813, and 0.810, respectively. The sensitivity, specificity and AUC for the original dataset were 0.810, 0.830, and 0.860, respectively. CONCLUSION: Based on the radiomics data of T2WI and RS-EPI DWI, the model established by automated machine learning showed a fairly high accuracy in predicting rectal cancer T stage.

Regulating Surface Termination for Efficient Inverted Perovskite Solar Cells with Greater Than 23% Efficiency.

Passivating surface and bulk defects of perovskite films has been proven to be an effective way to minimize nonradiative recombination losses in perovskite solar cells (PVSCs). The lattice interference and perturbation of atomic periodicity at the perovskite surfaces often significantly affect the material properties and device efficiencies. By tailoring the terminal groups on the perovskite surface and modifying the surface chemical environment, the defects can be reduced to enhance the photovoltaic performance and stability of derived PVSCs. Here, we report a rationally designed bifunctional molecule, piperazinium iodide (PI), containing both R2NH and R2NH2+ groups on the same six-membered ring, behaving both as an electron donor and an electron acceptor to react with different surface-terminating ends on perovskite films. The resulting perovskite films after defect passivation show released surface residual stress, suppressed nonradiative recombination loss, and more n-type characteristics for sufficient energy transfer. Consequently, charge recombination is significantly suppressed to result in a high open-circuit voltage (VOC) of 1.17 V and a reduced VOC loss of 0.33 V. A very high power conversion efficiency (PCE) of 23.37% (with 22.75% certified) could be achieved, which is the highest value reported for inverted PVSCs. Our work reveals a very effective way of using rationally designed bifunctional molecules to simultaneously enhance the device performance and stability.

DiscoverSL: an R package for multi-omic data driven prediction of synthetic lethality in cancers.

SUMMARY: Synthetic lethality is a state when simultaneous loss of two genes is lethal to a cancer cell, while the loss of the individual genes is not. We developed an R package DiscoverSL to predict and visualize synthetic lethality in cancers using multi-omic cancer data. Mutation, copy number alteration and gene expression data from The Cancer Genome Atlas project were combined to develop a multi-parametric Random Forest classifier. The effects of selectively targeting the predicted synthetic lethal genes is tested in silico using shRNA and drug screening data from cancer cell line databases. The clinical outcome in patients with mutation in primary gene and over/under-expression in the synthetic lethal gene is evaluated using Kaplan-Meier analysis. The method helps to identify new therapeutic approaches by exploiting the concept of synthetic lethality. AVAILABILITY AND IMPLEMENTATION: DiscoverSL package with user manual and sample workflow is available for download from github url: https://github.com/shaoli86/DiscoverSL/releases/tag/V1.0 under GNU GPL-3. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Oroxindin inhibits macrophage NLRP3 inflammasome activation in DSS-induced ulcerative colitis in mice via suppressing TXNIP-dependent NF-κB pathway.

Oroxindin is a flavonoid isolated from the traditional Chinese medicine Huang-Qin, which has shown various pharmacological activities including anti-inflammatory, antitumor, antioxidant, etc. Thus far, the effect of oroxindin on colonic inflammation and the underlying mechanism remain unknown. In this study, we investigated the tissue distribution of oroxindin and its therapeutic effects on ulcerative colitis (UC) as well as the underlying mechanisms. UC model was established in mice by administrating dextran sulfate sodium (DSS) in drinking water for 7 d. We first showed that oroxindin was largely absorbed by the colon as an active ingredient after normal mice received Huang-Qin-Tang, a traditional Chinese medicine decoction. UC mice were then treated with oroxindin (12.5, 25, 50 mg ·kg-1 ·d-1, i.g.) for 10 d. We found that oroxindin treatment greatly suppressed massive macrophages infiltration and attenuated pathological changes in colonic tissue. Furthermore, oroxindin treatment significantly inhibited the generation of IL-1ß and IL-18 in the colon via inhibiting the nucleotide-binding oligomerization domain-like receptor 3 (NLRP3) inflammasome formation and activation. In cultured macrophages, LPS induced NLRP3 inflammasome formation and caspase-1 activation, which were suppressed by oroxindin (12.5-50 µM). In LPS-treated macrophages, oroxindin dose-dependently restored the expression of TXNIP protein, leading to suppressing TXNIP-dependent NF-κB activation. In conclusion, these results demonstrate that oroxindin could be absorbed by the colon and attenuate inflammatory responses via inhibiting NLRP3 inflammasome formation and activation, which is related to the inhibitory effect on TXNIP-dependent NF-κB-signaling pathway. Hence, oroxindin has the potential of becoming an effective drug for treating UC.

Genetically-modified bone mesenchymal stem cells with TGF-ß3 improve wound healing and reduce scar tissue formation in a rabbit model.

Extensive scar tissue formation often occurs after severe burn injury, trauma, or as one of complications after surgical intervention. Despite significant therapeutic advances, it is still a significant challenge to manage massive scar tissue formation while also promoting normal wound healing. The goal of this study was to investigate the therapeutic effect of bone mesenchymal stem cells (BMSCs) that were genetically modified to overexpress transforming growth factor-beta 3 (TGF-ß3), an inhibitor of myofibroblast proliferation and collagen type I deposition, on full-thickness cutaneous wound healing in a rabbit model. Twenty-four rabbits with surgically-induced full-thickness cutaneous wounds created on the external ear (1.5 × 1.5 cm, two wounds/ear) were randomized into four groups: (G1), wounds with no special treatment but common serum-free culture medium as negative controls; (G2), topically-applied recombinant adenovirus, expressing TGF-ß3/GFP; (G3), topically-applied BMSCs alone; (G4), topically-applied BMSCs transfected with Ad-TGF-ß3/GFP (BMSCsTGF-ß3); and (G5), an additional normal control (n = 2) with neither wound nor treatment on the external ear skin. The sizes of wounds on the ear tissues were grossly examined, and the scar depth and density of wounds were histologically evaluated 21, 45, and 90 days after surgical wound creation. Our results demonstrated that G4 significantly reduced the wound scar depth and density, compared to G1~3. Numbers of cells expressing GFP significantly increased in G4, compared to G2. The protein expression of TGF-ß3 and type III collagen in G4 significantly increased, while the ratio of type I to type III collagen was also significantly reduced, which is similar to the tissue architecture found in G5, as compared the other treatment groups. In conclusion, transplantation of BMSCsTGF-ß3 remarkably improves wound healing and reduces skin scar tissue formation in an animal model, which may potentially provide an alternative in the treatment of extensive scar tissue formation after soft tissue injury.

IL-18 cleavage triggers cardiac inflammation and fibrosis upon ß-adrenergic insult.

Aims: Rapid over-activation of ß-adrenergic receptor (ß-AR) upon stress leads to cardiac inflammation, a prevailing factor that underlies heart injury. However, mechanisms by which acute ß-AR stimulation induce cardiac inflammation still remain unknown. Here, we set out to identify the crucial role of inflammasome/interleukin (IL)-18 in initiating and maintaining cardiac inflammatory cascades upon ß-AR insult. Methods and results: Male C57BL/6 mice were injected with a single dose of ß-AR agonist, isoproterenol (ISO, 5 mg/kg body weight) or saline subcutaneously. Cytokine array profiling demonstrated that chemokines dominated the initial cytokines upregulation specifically within the heart upon ß-AR insult, which promoted early macrophage infiltration. Further investigation revealed that the rapid inflammasome-dependent activation of IL-18, but not IL-1ß, was the critical up-stream regulator for elevated chemokine expression in the myocardium upon ISO induced ß1-AR-ROS signalling. Indeed, a positive correlation was observed between the serum levels of norepinephrine and IL-18 in patients with chest pain. Genetic deletion of IL-18 or the up-stream inflammasome component NLRP3 significantly attenuated ISO-induced chemokine expression and macrophage infiltration. In addition, IL-18 neutralizing antibodies selectively abated ISO-induced chemokines, proinflammatory cytokines and adhesion molecules but not growth factors. Moreover, blocking IL-18 early after ISO treatment effectively attenuated cardiac inflammation and fibrosis. Conclusion: Inflammasome-dependent activation of IL-18 within the myocardium upon acute ß-AR over-activation triggers cytokine cascades, macrophage infiltration and pathological cardiac remodelling. Blocking IL-18 at the early stage of ß-AR insult can successfully prevent inflammatory responses and cardiac injuries.

A Facile Photoluminescent Probe for Picric Acid Detection Using Carbon Nanodots Prepared by Sichuan Bergamot.

A facile photoluminescent probe for picric acid (PA) detection was developed using photoluminescent carbon nanodots (C-dots), which was obtained from a traditional Chinese medicinal material Sichuan Bergamot via a one-step hydrothermal method for the first time. The as-prepared photoluminescent C-dots show favorable blue color photoluminescence with the maximum emission at 440 nm. It has been successfully applied as a photoluminescent probe for the detection of PA. This photoluminescent probe exhibits excellent sensitivity and selectivity toward PA from 0.4 µM to 80 µM with correlation coefficient (r) of 0.9987. The limit of detection (LOD) for PA is 82 nM. Furthermore, the proposed C-dots for photoluminescent probe detection of PA in real water samples (river water, refinery wastewater and pharmaceutical factory wastewater) by adding 5 µM and 20 µM PA with satisfactory recoveries from 99.5% to 101.5%. These novel photoluminescent C-dots is promising in environmental analysis of PA.

Simultaneous Detection of Hydroquinone and Catechol Using Platinum Nanoparticles Decorated Graphene/Poly-Cyclodextrin/Multiwalled Carbon Nanotubes (MWCNTs) Nanocomposite Based Biosensor.

Graphene cyclodextrin prepolymer (pre-CD)-multiwall carbon nanotubes (Gr-CDP-MWCNTs) nanocomposites modified on glassy carbon electrode (Gr-CDP-MWCNTs/GCE) are prepared and then platinum particles (PtNPs) are electrodeposited on it. The simultaneous determination of hydroquinone (HQ) and catechol (CC) at PtNPs/Gr-CDP-MWCNTs/GCE is reported in the present work. Synergistic effect of nanomaterials, host-guest chemical reaction ability of CDP, the stacking interaction between detected molecules and Gr-MWCNTs surface are considered as the main reasons of successfully simultaneous detection of HQ and CC. Cyclic voltammetry (CV), scanning electron microscopy (SEM) and different pulse voltammetry (DPV) are employed to characterize the proposed PtNPs/Gr-CDP-MWCNTs electrochemical biosensor. The prepared PtNPs/Gr-CDP-MWCNTs sensor shows linear response ranges of 0.05-27.2 µM and 0.1-27.2 µM and have low detection limits (S/N = 3) of 0.015 µM and 0.03 µM for simultaneous electrochemical determination of HQ and CC, respectively. It is also applied for the measurement of HQ and CC in local river water samples with recoveries from 98.0 to 102.0% and from 99.3 to 101.5%.

Biomechanical, Histologic, and Molecular Evaluation of Tendon Healing in a New Murine Model of Rotator Cuff Repair.

PURPOSE: To develop a clinically relevant, robust murine model of rotator cuff tendon repair to examine cellular and molecular mechanisms of healing. METHODS: Sixty C57BL/6 male mice underwent rotator cuff transection and repair using microsurgical techniques. A modified Kessler suturing technique was used prior to tendon detachment. Sutures were passed through 2 intersecting bone tunnels that were made at the tendon attachment site. Mice were sacrificed at 2 and 4 weeks with subsequent biomechanical, histologic, micro-CT, and gene expression evaluations. RESULTS: Failure forces in the 2- and 4-week groups were 36% and 75% of the intact tendon, respectively. Histologic evaluation revealed complete reattachment of the tendon with no observable gap. Healing occurred by formation of fibrovascular tissue at the tendon-bone interface, similar to larger animal models. Molecular analysis revealed gene expression consistent with gradual healing of the reattached tendon over a period of 4 weeks. Comparisons were made using 1-way analysis of variance. CONCLUSIONS: This model is distinguished by use of microsurgical suturing techniques, which provides a robust, reproducible, and economic animal model to study various aspects of rotator cuff pathology. CLINICAL RELEVANCE: Improvement of clinical outcomes of rotator cuff pathology requires in-depth understanding of the underlying cellular and molecular mechanisms of healing. This study presents a robust murine model of supraspinatus repair to serve as a standard research tool for basic and translational investigations into signaling pathways, gene expression, and the effect of biologic augmentation approaches.