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1.
J Am Podiatr Med Assoc ; 110(1): Article9, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32073320

RESUMO

Ganglion cysts have been recorded in many areas throughout the body. Intratendinous ganglion cysts in the foot are very rare. We present the case of 51-year-old woman with a recurrent right foot ganglion cyst. Surgical excision revealed a ganglion cyst in the tendon sheath of the extensor digitorum longus. It is important to be aware of potential tendon involvement for ganglion cysts, as surgeons must be prepared to perform tendon repairs in addition to mass excisions if the tendon is compromised.

2.
ACS Appl Mater Interfaces ; 12(5): 5462-5475, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-31927945

RESUMO

Islet transplantation has been considered the most promising therapeutic option with the potential to restore the physiological regulation of blood glucose concentrations in type 1 diabetes treatment. However, islets suffer from oxidative stress and nonspecific inflammation in the early stage of transplantation, which attributed to the leading cause of islet graft failure. Our previous study reported that bilirubin exerted antioxidative and anti-inflammatory effects on hypothermic preserved islets, which inspire us to utilize bilirubin to address the survival issue of grafted islets. However, the application of bilirubin for islet transplantation is limited by its poor solubility and fast clearance. In this study, we designed a supramolecular carrier (PLCD) that could improve the solubility of bilirubin and slowly release bilirubin to protect islets after cotransplantation. PLCD was synthesized by conjugating activated ß-cyclodextrin (ß-CD) to the side chain of ε-polylysine (PLL) and acted as a carrier to load bilirubin via host-guest interactions. The constructed bilirubin supramolecular system (PLCD-BR) significantly improved the solubility and prolonged the action time of bilirubin. In vitro results confirmed that PLCD-BR coculture substantially enhanced the resistance of islets to excessive oxidative stress and proinflammatory stimulation and maximumly maintained the islet function. In vivo, PLCD could prolong drug duration at the transplant site, and the localized released bilirubin could protect the islets from oxidative stress and suppress the production of inflammatory cytokines. Crucially, islet transplantation with PLCD-BR significantly extended the stable blood glucose time of diabetic mice and produced a faster glucose clearance compared to those cotransplanted with free bilirubin. Additionally, immunohistochemical analysis showed that PLCD-BR had superior antioxidative and anti-inflammatory abilities and beneficial effects on angiogenesis. These findings demonstrate that the PLCD-BR has great potentials to support successful islet transplantation.

3.
Adv Exp Med Biol ; 1232: 375-381, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31893434

RESUMO

The value of optical redox imaging (ORI) of cells/tissues based on the intrinsic fluorescences of NADH (nicotinamide adenine dinucleotide) and oxidized flavoproteins (containing flavin adenine dinucleotide, i.e., FAD) has been demonstrated for potential biomedical applications including diagnosis, prognosis, and determining treatment response. However, the Chance redox scanner (a 3D cryogenic tissue imager) is limited by spatial resolution (~50 µm), and tissue ORI using fluorescence microscopy (single or multi-photon) is limited by the light penetration depth. Furthermore, viable or snap-frozen tissues are usually required. In this project, we aimed to study whether ORI may be achieved for unstained fixed tissue using a state-of-the-art modern Serial Two-Photon (STP) Tomography scanner that can rapidly acquire multi-plane images at micron resolution. Tissue specimens of mouse muscle, liver, and tumor xenografts were harvested and fixed in 4% paraformaldehyde (PFA) for 24 h. Tissue blocks were scanned by STP Tomography under room temperature to acquire the autofluorescence signals (NADH channel: excitation 750 nm, blue emission filter; FAD channel: excitation 860 nm, green emission filter). We observed remarkable signals with significant intra-tissue heterogeneity in images of NADH, FAD and redox ratio (FAD/(NADH+FAD)), which are worthy of further investigation for extracting biological information.


Assuntos
Tecnologia Biomédica , NAD , Imagem Óptica , Animais , Tecnologia Biomédica/instrumentação , Tecnologia Biomédica/métodos , Estudos de Viabilidade , Flavina-Adenina Dinucleotídeo , Xenoenxertos/diagnóstico por imagem , Camundongos , Oxirredução , Fótons
4.
J Hazard Mater ; 384: 121475, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31776078

RESUMO

In this work, a pre-wetting induced superhydrophilic/superlipophilic micro-patterned membrane with surface-loaded BiVO4 nanoparticles (Bi/PDA@PT) was successfully prepared by electrospinning and polydopamine (PDA) surface modification technology for highly efficient emulsified oily wastewater separation. The results showed that the as-prepared membranes exhibited micro hole-patterned structures and the BiVO4 nanoparticles were uniformly deposited on the surfaces of fibers to construct hierarchical porous structures by using PDA as an adhesive polymeric bridge. During the separation process of emulsified oily wastewater, the hierarchical porous structures in membranes significantly improved the separation flux, which was nearly 2-3 times than that of the non-patterned membranes. Based on the existence of PDA, the membranes exhibited prewetting-induced superoleophobicity under water and superhydrophobicity under oil, which made it possible for them to separate both water-in-oil and oil-in-water emulsified oily wastewater selectively and efficiently. Moreover, the BiVO4 nanoparticles loaded on the membranes could degrade the oily contaminants adsorbed on the membranes (nearly 100%) under visible light. All these attractive features demonstrate that the Bi/PDA@PT membranes show a great potential for sustainable and efficient emulsified oily wastewater separation.

5.
Int J Med Microbiol ; 310(1): 151357, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31570247

RESUMO

Understanding the evolutionary path of M. catarrhalis from macrolide-susceptible to macrolide-resistant organism, is important for hindering macrolide resistance from propagation. Multilocus sequence typing (MLST), pulsed-field gel electrophoresis (PFGE) and whole genome SNP typing (WGST), as useful and practical typing tools, have both advantages and disadvantages. We studied the utility of these 3 typing methods, including the level of agreement, consistency and drawbacks, in characterizing M. catarrhalis clones and clonal complexes. We focused on four clonal complexes [CC224, CC363, CC449 (CCN10) and CC446 (CCN08)] and found that PFGE and WGST had a high level of agreement and a proper consistency of the same clone or very closely related clones, while MLST is less discriminatory for different clones. Furthermore, we also established an evolutionary distance cut-off value for "The same clone". Moreover, we detected macrolide-resistant M. catarrhalis in CC224, which had previously been considered as a macrolide-susceptible clonal complex. A higher number of isolates belonged to ST215 compared to ST446, implying that ST215 is more likely to be the primary founder. Our study also demonstrated that all the four clonal complexes belong to the M. catarrhalis lineage 1, which is considered to be related to increased virulence potential and serum resistance. We also observed that copB II was highly related to CC449 and LOS type B was mainly confined in CC224. In conclusion, these findings provide further insight into the evolutionary characteristics of M. catarrhalis.

6.
Adv Mater ; 32(6): e1903983, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31879999

RESUMO

Cylindrical vector vortex beams, a particular class of higher-order Poincaré sphere beams, are generalized forms of waves carrying orbital angular momentum with inhomogeneous states-of-polarization on their wavefronts. Conventional methods as well as the more recently proposed segmented/interleaved shared-aperture metasurfaces for vortex beam generation are either severely limited by bulky optical setups or by restricted channel capacity with low efficiency and mode number. Here, a noninterleaved vortex multiplexing approach is proposed, which utilizes superimposed scattered waves with opposite spin states emanating from all meta-atoms in a coherent manner, counter-intuitively enabling ultrahigh-capacity, high-efficiency, and flexible generation of massive vortex beams with structured state-of-polarization. A series of exemplary prototypes, implemented by sub-wavelength-thick metasurfaces, are demonstrated experimentally, achieving kaleidoscopic vector vortex beams. This methodology holds great promise for structured wavefront shaping, vortex generation, and high information-capacity planar photonics, which may have a profound impact on transformative technological advances in fields including spin-Hall photonics, optical holography, compressive imaging, electromagnetic communication, and so on.

7.
Drug Deliv ; 27(1): 54-65, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31858849

RESUMO

Didymin is a dietary flavonoid that first found in citrus fruits, and possesses antioxidant properties. Our preliminary experiments first discovered that didymin was able to sensitize the resistant cancer cells against chemotherapeutics and combat multidrug resistance. However, its poor aqueous solubility and resultant low bioavailability limit its potentials as an adjuvant phytochemical drug for chemotherapy. Thus, this study prepared the inclusion complex of didymin with ß-cyclodextrin and 2-hydroxypropyl-ß-cyclodextrin to improve its bioavailability and then evaluate their chemosensitization effects. The didymin inclusion complexes formulation was prepared and their host-guest structure was characterized by FT-IR, PXRD, DSC, and SEM techniques. In vitro/in vivo results demonstrated that didymin inclusion complex enhanced its water solubility and orally bioavailability. Furthermore, didymin inclusion complex exerted considerable chemosensitivity potency, and improve the anti-tumor effects of chemotherapeutics in vivo. Therefore, didymin inclusion complex could provide a safe, effective, economical, and adjuvant drug for future treatment of chemoresistant cancers.

8.
Biosci Rep ; 40(1)2020 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-31872855

RESUMO

Jinlong capsule (JLC), a type of herbal medicine, is considered to be a promising adjuvant therapy for hepatocellular carcinoma (HC). Although an analysis of the published literature has been performed, the exact effects and safety of JLC are yet to be systematically investigated. Therefore, a wide-ranging systematic search of electronic databases to draw conclusions was performed. Data from 29 trials, including 2488 patients with advanced HC, were analyzed. The results indicated that, compared with conventional treatment alone, the combination of conventional treatment and JLC markedly improved overall patient response (odds ratio (OR) 2.06 [95% confidence interval (CI) 1.71-2.49]; P<0.00001), disease control rate (DCR) (OR 2.17 [95% CI 1.74-2.71]; P<0.00001) and quality of life (QoL) (OR 2.71 [95% CI 2.05-3.58]; P<0.00001), and significantly prolonged 6- (P=0.01), 12- (P<0.00001), 24- (P=0.001) and 36-month (P<0.0001) overall survival (OS) rates. The immune function of patients was also significantly enhanced after combined conventional therapy and JLC treatment, indicated by clearly increased percentages of CD3+ (P<0.0001), CD4+ (P<0.00001) and natural killer (NK) cells (P=0.0003), and CD4+/CD8+ ratio (P<0.00001). The incidence of leukopenia (P<0.00001), hepatotoxicity (P=0.005), and myelosuppression (P=0.0007) was lower in HC patients injected with JLC, whereas other adverse events did not differ significantly between the two groups (P>0.05). In summary, results of this meta-analysis suggest that the combination of conventional treatment and JLC is more effective for the treatment of HC than conventional treatment alone.

9.
Artif Cells Nanomed Biotechnol ; 48(1): 218-229, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31851840

RESUMO

Decellularized extracellular matrix (dECM) has been considered as a promising scaffold in xenotransplantation, yet natural tissue dECM is often mechanically weak and rapidly degraded, compromising the outcomes. How to restore the mechanical strength and optimise the in vivo degradation, but maintain the microstructure and maximumly suppress the immune rejection, remains challenging. For this aim, we prepared and characterised various crosslinked decellularized rabbit uterus matrix (dUECM) and evaluated in vivo performance after uterus xenotransplantation from rabbit to rat. Naturally derived genipin (GP) and procyanidins (PC) were chosen to crosslink the dUECM, producing significant mechanical enhanced crosslinked-dUECM along with prolonged enzymatic degradation rate. Xenogeneic subcutaneous graft studies revealed that PC- and GP-crosslinked dUECM experienced significant cell infiltration and caused low immune reactions, indicating the desired biocompatibility. In vivo transplantation of GP- and PC-crosslinked dUECM to a uterus circular excised rat yielded excellent recellularization ability and promoted uterus regeneration after 90 days. While the reconstruction efficacy of crosslinked dUECM is highly depended on the crosslinking degree, crosslinking condition must be carefully evaluated to balance the role of crosslinked dECM in mechanical and biological support for tissue regeneration promotion.

10.
Urol Int ; : 1-12, 2019 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-31825927

RESUMO

OBJECTIVE: To investigate the diagnostic role of magnetic resonance imaging (MRI)-targeted biopsy (TB) for prostate cancer (PCa) in biopsy-naïve men. MATERIALS AND METHODS: Own control studies and randomized controlled trials (RCTs) up to December 2018 were identified via a systematic search of PubMed, Embase, Ovid, and the Cochrane Library. We pooled relative sensitivity (or risk ratio [RR]) to compare diagnostic efficiency for PCa and clinically significant PCa (csPCa) between TB and systematic biopsy (SB). The independent role of either biopsy pathway was evaluated for participants with positive/negative MRI. RESULTS: Thirty-one studies consisting of 25 own control studies and 6 RCTs were included. We identified 4,020 biopsy-naïve men with positive MRI who underwent two biopsies concurrently, with PCa/csPCa detection rates of 65.90 and 45.13%, respectively. TB and SB did not differ in the detection of any PCa (RR 0.98, 95% confidence interval [CI] 0.92-1.05). However, TB detected more csPCa (RR 1.19, 95% CI 1.10-1.30) and more PCa with a Gleason score ≥3+4 (RR 1.20, 95% CI 1.07-1.34). Using a combined test as a reference, omitting SB resulted in detecting 12.81% less csPCa and 20.76% less clinically insignificant PCa (cinsPCa), and omitting TB resulted in detecting 25.69% less csPCa and 10.8% more cinsPCa. For patients with negative MRI, omitting SB led to underdetection of 30.29% of any PCa (10.9% of csPCa). CONCLUSIONS: Combining TB and SB increased the diagnostic accuracy of csPCa for biopsy-naïve men with positive MRI, and omitting SB for patients with a negative MRI would lead to the underdetection of nearly 10% of csPCa.

11.
Artif Cells Nanomed Biotechnol ; 47(1): 4293-4304, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31810396

RESUMO

Instability of silk fibroin nanoparticles (SFNPs) in physiologic condition hinders its application as drug delivery vehicle. Herein, indocyanine green (ICG) loaded silk fibroin nanoparticles (ICG-SFNPs) was firstly prepared and then crosslinked by proanthocyanidins to obtain the stable ICG-CSFNPs for killing the residual tumour niche under near infra-red irradiation (NIR) after surgery. The particle size and zeta potentials of ICG-CSFNPs was 120.1 nm and -40.4 mV, respectively. Moreover, ICG-CSFNPs exhibited good stability of particle size in the physiological medium. Meanwhile, the stable photothermal properties of ICG-CSFNPs were not compromised even after several cycles of NIR. Few of the ICG-CSFNPs were phagocytized by RAW264.7 macrophage in vitro, while they were easily internalized by C6 glioma cells, resulting in their significant toxicity on tumour cells after NIR. The pharmacokinetic study showed that ICG-CSFNPs had a longer blood circulation time than ICG-SFNPs, making them more distribution in glioma after intravenous administration in vivo. Meanwhile, the pharmacological study showed the more effective inhibition of tumour growth was exhibited by ICG-CSFNPs in C6 glioma-bearing mice after NIR. Overall, the cross-linked nanoparticles of silk fibroin may be a promising vehicle of ICG for photothermal therapy of glioma after surgical resection.

12.
Ann Clin Lab Sci ; 49(6): 785-793, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31882430

RESUMO

Diabetes-induced hyperglycemia has a direct damaging effect on ovarian function. Despite its deadly impact on ovaries, the mechanism of this condition has not been fully elucidated. Glucose transporters are involved in glucose uptake and utilization. Many transporters have been detected in the ovaries, but their roles in diabetes-induced ovarian impairment are still unclear. In this study, the goal is to analyze glucose transporter expression in the ovarian follicles of type 1 diabetes mellitus patients and determine their roles within ovarian function impairment. The ovarian function of a mouse model of type 1 diabetes mellitus was evaluated by observing its estrus cycle, follicular development, and ovulation. Subtypes of the glucose transporter (GLUT2, GLUT3, GLUT4, SGLT1, and SGLT2), adenosine monophosphate-activated protein kinase (AMPK), and phosphorylated AMPK (Thr172) were found to be simultaneously present in follicle cells. Compared with nondiabetic control mice, the diabetic mice showed a dysregulated estrus cycle and a significantly higher number of abnormal ova. Furthermore, the expression of multiple glucose transporters was lower than that of phosphorylated AMPK. Phosphorylated AMPK possessed more follicular granulosa cells and oocytes of diabetic mice than in those of the control mice. These results suggest that diabetes-induced hyperglycemia reduces the capability of ovarian follicle cells by downregulating glucose transporter expression, causing decreased glucose uptake and energy deprivation. This impact can potentially impair egg maturation and ovulation.

13.
Medicine (Baltimore) ; 98(44): e17748, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31689828

RESUMO

BACKGROUND: Previous evidence directly evaluating the efficacy and safety of abiraterone and enzalutamide treatment for castration-resistant prostate cancer (CRPC) is limited. We aim to include more randomized controlled trials (RCTs) to comprehensively assess the efficacy and safety of abiraterone and enzalutamide treatment. METHODS: PubMed, Embase, and ClinicalTrial.gov were systematically searched. Pooled hazard ratios (HRs) were calculated using Stata 12.0 software. The comparison of the prostate-specific antigen (PSA) response rate and adverse events (AEs) between the treatment and control groups were performed using RevMan 5.3 software. RESULTS: Eight eligible RCTs with 6,490 patients were selected. Pooled HRs were 0.72 for overall survival, 0.45 for radiographic progression-free survival (rPFS), and 0.36 for PSA PFS. abiraterone and enzalutamide could significantly increase the PSA response rate OR = 8.67, 95%CI 4.42-17.04) and any AE occurrence (OR = 1.98, 95%CI 1.46-2.68). The treatment group had more occurrence of fatigue (OR = 1.34, 95%CI 1.20-1.49), back pain (OR = 1.15, 95%CI 1.01-1.15), hot flush (OR = 1.76, 95%CI 1.50-2.06), diarrhea (OR=1.22, 95%CI 1.07-2.40) and arthralgia (OR = 1.34, 95%CI 1.16-1.54). Particularly, AEs of special interest including any grade hypertension (OR = 2.06, 95%CI 1.71-2.47), hypokalemia (OR = 1.80, 95%CI 1.42-2.30) and fluid retention or edema (OR = 1.38, 95%CI 1.17-1.63) also occurred less in the control group. Moreover, a higher incidence of high-grade hypertension (OR = 2.60, 95%CI 1.79-3.79) and extremity pain (OR = 4.46, 95%CI 2.81-7.07) was observed in the treatment group. CONCLUSION: The survival benefits of abiraterone and enzalutamide for CRPC were evident and promising, while the risk of AE occurrence was also acceptably higher in the treatment group than in the placebo group.


Assuntos
Androstenos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Feniltioidantoína/análogos & derivados , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Adulto , Idoso , Intervalo Livre de Doença , Humanos , Masculino , Pessoa de Meia-Idade , Feniltioidantoína/uso terapêutico , Intervalo Livre de Progressão , Modelos de Riscos Proporcionais , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
14.
J Food Sci ; 84(12): 3601-3607, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31730276

RESUMO

Sturgeon meat has been found to be suitable as surimi raw materials. The present study determined the modori phenomenon in sturgeon surimi gels and identified its relationship with cathepsins. In all heat-treated gels (25 to 90 °C, at 5 °C intervals), the 40 °C-incubated sturgeon surimi gel showed the weakest gel properties and water-holding capacity (P < 0.05), a rough protein gel network under SEM, and the highest protein solubility and trichloroacetic acid-soluble peptides content (P < 0.05). SDS-PAGE indicated that the myosin heavy chain band of sturgeon surimi gels was almost completely degraded at 40 °C. Moreover, the highest cathepsin L activity was observed in 40 °C-treated sturgeon surimi gels (P < 0.05). Our results suggested that the modori phenomenon in sturgeon surimi gels occurred at 40 °C, which was partially attributed to cathepsin L, thereby allowing for the better exploitation and utilization of sturgeon surimi.

15.
Elife ; 82019 11 11.
Artigo em Inglês | MEDLINE | ID: mdl-31709980

RESUMO

In many daily tasks, we make multiple decisions before reaching a goal. In order to learn such sequences of decisions, a mechanism to link earlier actions to later reward is necessary. Reinforcement learning (RL) theory suggests two classes of algorithms solving this credit assignment problem: In classic temporal-difference learning, earlier actions receive reward information only after multiple repetitions of the task, whereas models with eligibility traces reinforce entire sequences of actions from a single experience (one-shot). Here, we show one-shot learning of sequences. We developed a novel paradigm to directly observe which actions and states along a multi-step sequence are reinforced after a single reward. By focusing our analysis on those states for which RL with and without eligibility trace make qualitatively distinct predictions, we find direct behavioral (choice probability) and physiological (pupil dilation) signatures of reinforcement learning with eligibility trace across multiple sensory modalities.

16.
Biosci Rep ; 39(10)2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31652456

RESUMO

A close relation between microRNA-151a-3p (miR-151a-3p) and nasopharyngeal carcinoma (NPC) has been reported, however, the molecular mechanism is still unclear. The aim of the present study was to explore the mechanism in the promotion of miR-151a-3p to NPC progression. The levels of miR-151-3p in several NPC cell lines were detected in order to screen an experimental cell line. MiR-151a-3p mimic and inhibitor were constructed and transfected into 5-8F cells and cell proliferation were detected by Cell Counting Kit-8 (CCK-8). The apoptosis rate, cell migration and invasion were determined by flow cytometry, wound healing and Transwell assays. The predicted target was further verified by luciferase reporter assay. Real-time quantification-PCR and Western blot were carried out for mRNA and protein level analysis. Tumor protein p53 was co-transfected to verify the functions of miR-151a-3p. The miR-151a-3p level in NPC tissues was much higher than that in adjacent tissues. After transfecting cells with miR-151a-3p mimic, the cell proliferation and patients' survival rate were much increased, and this was accompanied by the increase in B-cell lymphoma 2 (Bcl-2) and decreases in Bax and cleaved caspase-3 (P<0.01). Moreover, the migration rate and number of invaded cells were also remarkably increased, however, the miR-151a-3p inhibitor had opposite effects on the 5-8F cells. Noticeably, p53 was revealed as a potential target of miR-151a-3p. Co-transfection of P53 could partially reverse the promotive effects of miR-151a-3p on NPC cell progression. Our data indicated that blocking p53 expression and mediated signal pathways contribute to the positive effects of miR-151a-3p on NPC cell proliferation, migration and invasion.

17.
Am J Transplant ; 2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31596034

RESUMO

Lymphocyte depletion has been shown to control costimulation blockade-resistant rejection but, in some settings, to exacerbate antibody-mediated rejection (AMR). We have used alemtuzumab, which depletes T and B cells, combined with belatacept and rapamycin and previously reported control of both costimulation blockade-resistant rejection and AMR. To evaluate this regimen's effect on B cell signatures, we investigated 40 patients undergoing this therapy. B cell counts and phenotypes were interrogated using flow cytometry, and serum was analyzed for total IgG, IgM, and donor-specific alloantibody (DSA). Alemtuzumab induction produced pan-lymphocyte depletion; B cells repopulated faster and more completely than T cells. Reconstituting B cells were predominantly naïve, and memory B cells were significantly reduced (P = .001) post repopulation. Two B cell populations with potential immunomodulatory effects-regulatory (CD38hi CD24hi IgMhi CD20hi ) and transitional B cells (CD19+ CD27- IgD+ CD38hi )-were enriched posttransplant (P = .001). Total serum IgG decreased from baseline (P = .016) while IgM levels remained stable. Five patients developed DSAs within 36 months posttransplant, but none developed AMR. Baseline IgG levels in these patients were significantly higher than those in patients without DSAs. These findings suggest that belatacept and rapamycin together limit homeostatic B cell activation following B cell depletion and may lessen the risk of AMR. This regimen warrants prospective, comparative study. ClinicalTrials.gov NCT00565773.

18.
Cell Res ; 29(11): 911-926, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31591447

RESUMO

Primary germ layers have the potential to form all tissues in the mature organism, and their formation during gastrulation requires precise epigenetic modulation of both proximal and distal regulatory elements. Previous studies indicated that spatial and temporal patterns of gene expression in the gastrula predispose individual regions to distinct cell fates. However, the underlying epigenetic mechanisms remain largely unexplored. Here, we profile the spatiotemporal landscape of the epigenome and transcriptome of the mouse gastrula. We reveal the asynchronous dynamics of proximal chromatin states during germ layer formation as well as unique gastrula-specific epigenomic features of regulatory elements, which have strong usage turnover dynamics and clear germ layer-specific signatures. Importantly, we also find that enhancers around organogenetic genes, which are weakly expressed at the gastrulation stage, are frequently pre-marked by histone H3 lysine 27 acetylation (H3K27ac) in the gastrula. By using the transgenic mice and genome editing system, we demonstrate that a pre-marked enhancer, which is located in the intron of a brain-specific gene 2510009E07Rik, exhibits specific enhancer activity in the ectoderm and future brain tissue, and also executes important function during mouse neural differentiation. Taken together, our study provides the comprehensive epigenetic information for embryonic patterning during mouse gastrulation, demonstrates the importance of gastrula pre-marked enhancers in regulating the correct development of the mouse embryo, and thus broadens the current understanding of mammalian embryonic development and related diseases.

19.
Opt Express ; 27(18): 26044-26049, 2019 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-31510464

RESUMO

An all-fiber linearly polarized supercontinuum (SC) laser source with 93 W average output power and spectrum ranging from 520 nm to 2300 nm is experimentally demonstrated. The linearly-polarized SC is generated in a piece of 2.6 m long polarization-maintaining photonic crystal fiber (PM-PCF), pumped by a polarization-maintaining picosecond Yb-doped master oscillator power amplifier (PM-MOPA). The source exhibits a flat spectrum from 600 nm to 1880 nm at -10 dB level except for the residual pump peak. A new method is proposed to measure the polarization extinction ratio (PER) of each single wavelength of the broadband supercontinuum at a high-power level, resulting in larger than 16 dB PER from 900 nm to 1600 nm and larger than 15 dB PER from 540 nm to 650 nm. To our knowledge, this is the first demonstration of hundred-watt level linearly polarized visible SC and the first demonstration of PER measurement of each single wavelength within such a wide spectrum range.

20.
J Mater Chem B ; 7(40): 6125-6138, 2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31553023

RESUMO

The diabetic non-healing wound is one of the most common complications of diabetics. The long-term stimulus of oxidative stress, inflammation and infection caused by the hyperglycemic microenvironment in the wound site always leads to a delayed healing process of the diabetic wound. To address this issue, in this study, we prepared an asiatic acid (AA)-embedded aligned porous poly(l-lactic acid) (PLLA) electrospun fibrous scaffold (AA-PL) for accelerating diabetic wound healing. The results showed that the electrospun fibers with nanopores on the surfaces were aligned in a single direction, while the AA was well embedded in the fibers and can be continuously released from them. The in vitro results revealed that the AA-PL scaffolds can effectively alleviate the H2O2-induced oxidative stress damage to HaCat cells and downregulate the LPS-induced pro-inflammatory cytokine (IL-1ß, TNF-α, IL6) gene expression in RAW 264.7 macrophage cells. Moreover, the growth of E. coli and S. aureus could be inhibited by the AA-PL scaffolds. The in vivo study further demonstrated that the AA-PL scaffolds can accelerate the re-epithelization, angiogenesis and extracellular matrix formation of a wound by relieving the high oxidative stress, inflammation and infection in the diabetic wound site. This study suggests that the combination of hierarchical structures (nanopores on the aligned fibers) with the controllable release of AA from the scaffolds is an efficient and innovative strategy for the treatment of diabetic non-healing wounds.

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