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1.
Artigo em Inglês | MEDLINE | ID: mdl-32434772

RESUMO

OBJECTIVE: The present study focused on the development of a poloxamer 407 thermosensitive hydrogel loaded with keratinocyte growth factor-2 (KGF-2) and fibroblast growth factor-21 (FGF-21) as a therapeutic biomaterial in a scald-wound model of type-2 diabetes in Goto-Kakizaki (GK) rats. RESEARCH DESIGN AND METHODS: In this study, a poloxamer 407 thermosensitive hydrogel loaded with KGF-2 and/or FGF-21 was prepared and its physical and biological properties were characterized. The repairing effects of this hydrogel were investigated in a scald-wound model of type-2 diabetes in GK rats. The wound healing rate, epithelialization, and formation of granulation tissue were examined, and biomarkers reflecting regulation of proliferation and inflammation were quantified by immunostaining and Western blotting. T tests and analyses of variance were used for statistical analysis via Graphpad Prism V.6.0. RESULTS: A 17.0% (w/w) poloxamer 407 combined with 1.0% (w/w) glycerol exhibited controlled release characteristics and a three-dimensional structure. A KGF-2/FGF-21 poloxamer hydrogel promoted cellular migration without apoptosis. This KGF-2/FGF-21 poloxamer hydrogel also accelerated wound healing of scalded skin in GK rats better than that of a KGF-2 or FGF-21 hydrogel alone due to accelerated epithelialization, formation of granulation tissue, collagen synthesis, and angiogenesis via inhibition of inflammatory responses and increased expression of alpha-smooth muscle actin (α-SMA), collagen III, pan-keratin, transforming growth factor-ß (TGF-ß), vascular endothelial growth factor (VEGF), and CD31. CONCLUSIONS: A KGF-2/FGF-21 poloxamer hydrogel accelerated wound healing of scalded skin in GK rats, which was attributed to a synergistic effect of KGF-2-mediated cellular proliferation and FGF-21-mediated inhibition of inflammatory responses. Taken together, our findings provide a novel and potentially important insight into improving wound healing in patients with diabetic ulcers.

2.
Artigo em Inglês | MEDLINE | ID: mdl-32406239

RESUMO

In this study, an ingenious core-shell structure microneedle (CSMN) array was designed to synergistically boost robust immune response by the intralesional codelivery of photosensitizer and indoleamine 2,3-dioxygenase (IDO) blockade. Photosensitizer indocyanine green was encapsulated into chitosan nanoparticles (ICG-NPs), followed by concentrating on the tip shell of microneedles. 1-Methyl-tryptophan was loaded into the cross-linked poly(vinyl pyrrolidone) and poly(vinyl alcohol) gel as the microneedle core. Through the direct deposition of the ICG-NP-loaded tips into the tumor site with uniform spatial distribution, the CSMNs effectively converted the near-infrared laser into heat to ablate primary tumors, generated tumor-associated antigens and damage-associated molecular patterns, and promoted the maturation of dendritic cells and the secretion of immunostimulatory cytokines. The IDO blockade further reversed the IDO-mediated immunosuppression, ultimately arousing an effective systematic immune response. The in vivo results showed that 80% of the melanoma tumor was eradicated, followed by a relapse-free survival in more than 120 days. Of note, this synergistic strategy significantly inhibited lung metastasis and controlled the development of already metastasized tumors. Our work provides a new, generalizable framework for using the microneedle-based photothermal therapy to initiate antitumor immunity and sensitize tumors to IDO blockade.

3.
Anal Chem ; 2020 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-32380823

RESUMO

Interparticle distance (ID) is generally used for spatial evaluation on the dispersion of nanofillers in polymer nanocomposites (PNCs) in order to gain in-depth insight into fundamental understanding of reinforcement and structure-property correlation. However, currently available methods mainly rely on two-dimensional observation technologies or simulation methods. Herein, using layered double hydroxides (LDHs) in low-density polyethylene (LDPE) as a model matrix, we developed a novel spatial ID determination method through a post labeling fluorescent imaging technique. The spatial ID of LDH nanofillers was achieved by a MATLAB program based on the 3D coordinates of LDH nanofillers in PNCs. The spatial ID data indicated the varied dispersion states of LDH nanofillers from "random", "even", to "clustered" in PNCs. More importantly, the so-called exceptional performances of PNCs at high loading of LDH nanofillers can be reasonably explained in combination with the mechanical studies. This proposed approach could undoubtedly provide valuable information in elucidating the structure-property correlation in PNCs. We believe that this work would be a guide to design advanced PNC materials.

4.
Zhongguo Gu Shang ; 33(5): 479-84, 2020 May 25.
Artigo em Chinês | MEDLINE | ID: mdl-32452190

RESUMO

OBJECTIVE: To construct a dynamic knee joint finite element model based on CT image data and verify the validity of the model. To provide a simulation model and basic data for biomechanical research of the knee joint by further finite element analysis. METHODS: The CT data of a healthy male knee joint was selected. With the help of Mimics 19.0 and Hypermesh 12.0 software, a high simulation finite element model of knee joint was established following steps, including geometric reconstruction, reverse engineering, meshing and material characterization. The dynamic knee flexion model was generated by determining the boundary conditions and torque loading, and the validity of themodel was confirmed. The biomechanical changes of the tibiofemoral and patellofemoral joints under different knee flexion angles were analyzed by applying the loads (500 N) to the finite element model during knee flexion. RESULTS: A finite element model of knee joint was established based on CT images and anatomical characteristics. The model included three-dimensional elements such as bone, ligament, cartilage, meniscus and patellar retinaculum. The different finite element models of knee flexion states were produced by applying different torques after establishing boundary conditions. According to equivalent conditions (knee flexion 30 degrees, quadriceps tendon under 200 N stretch), the peak stress value of patella was 2.209 MPa and the average Mises stress was 1.132 MPa; the peak stress value of femoral trochlear was 1.405 MPa and the average Mises stress was 0.936 MPa. The validity of the model was proved by the difference between the model and previous studies of 1% to 13.5%. Dynamic model loading showed that the Mises stressof tibiofemoral joint decreased with the increase of knee flexion angle, while the Mises stress of patellofemoral joint was positively correlated with knee flexion angle. The Mises stress of cartilage stress planes at different knee flexion angles was significantly different(P<0.05). CONCLUSION: The finite element model established in this study is more comprehensive and can effectively simulate the biomechanical characteristics of dynamic knee joint, which provides support for further simulation mechanics researches of the knee joint.

5.
Chemosphere ; 255: 127006, 2020 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-32417517

RESUMO

The extensive use of antibiotics globally and their residues in the environment has become a serious concern. Intensive animal farming is considered to be a major contributor to the increased environmental burden of antibiotics. Although some antibiotic investigations have been advancing around the world, as an important agricultural country, the information on these pollutants in animal farms are very limited in China. Previous studies have explored few antibiotic residues in livestock farms, whereas information on some antibiotics has remained unknown. The current study analyzed residues of 32 common veterinary antibiotics in manure and manure-based fertilizers collected from Jiangsu Province, China. In most of the manure and fertilizer samples, sulfamethazine and tetracycline were present, with high concentration up to 5650 and 1920 µg·kg-1, respectively. These detected antibiotics have weak relationships with physicochemical properties. Ciprofloxacin, enrofloxacin, sulfamethazine, and sulfachlorpyridazine, hence pose a high potential risk to crops based on the toxicological data of organisms and plants in the soil environment. However, soil invertebrate, such as earthworms, Planococcus Citri. and Folsomia fimeraria., had low ecological risks. Our results showed the presence of antibiotics in livestock and poultry farms plus the potential risks to the soil ecosystem. Therefore, the findings can provide guidelines for monitoring antibiotic residues in agroecosystems, as well as insights into the associated ecological risks of using the two products.

6.
QJM ; 2020 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-32442308

RESUMO

BACKGROUND: COVID-19 is a global pandemic but the follow-up data of discharged patients was barely described. AIMS: To investigate clinical outcomes, distribution of quarantine locations, and the infection status of the contacts of COVID-19 patients after discharge. DESIGN: A prospective cohort study. METHODS: Demographics, baseline characteristics of 131 COVID-19 patients discharged from February 3 to 21, 2020 in Wuhan, China were collected and analyzed by reviewing the medical records retrospectively. Post-hospitalization data related to clinical outcomes, quarantine locations and close contact history were obtained by following up the patients every week up to 4 weeks. RESULTS: 53 (40.05%) patients on discharge had cough (29.01%), fatigue (7.63%), expectoration (6.11%), chest tightness (6.11%), dyspnea (3.82%), chest pain (3.05%), and palpitation (1.53%). These symptoms constantly declined in 4 weeks post discharge. Transient fever recurred in 11 (8.4%) patients. 78 (59.5%) discharged patients underwent chest CT and 2 (1.53%) showed deterioration. 94 (71.8%) patients received SARS-CoV-2 retest and 8 (6.10%) reported positive. 7 (2.29%) patients were re-admitted because of fever or positive SARS-CoV-2 retest. 121 (92.37%) and 4 (3.05%) patients were self-quarantined at home or community spots following discharge, with totally 167 closely contacted persons free of COVID-19 at the endpoint of study. CONCLUSIONS: The majority of COVID-19 patients after discharge were in the course of recovery. Readmission was required in rare cases due to suspected recurrence of COVID-19. Although no contacted infection observed, appropriate self-quarantine and regular reexamination are necessary, particularly for those who have recurred symptoms.

7.
Ann Clin Lab Sci ; 50(2): 199-204, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32366557

RESUMO

OBJECTIVE: Drug resistance is the main limitation for dopamine agonist therapy with prolactinoma. Transsphenoidal surgery is an additional operation that circumvents this limitation. To characterize distinctive clinical features of resistant prolactinoma in different levels of Ki-67, a retrospective analysis of 423 patients who were diagnosed and surgically treated at Shandong Provincial Hospital Affiliated to Shandong University from January 2007 to June 2017 was performed. METHODS: Patients were subdivided into Ki-67≥3% group (High) and Ki-67<3% group (Low) according to Ki-67 labeling values. RESULTS: Tumors in the High group were larger (P=0.001), associated with more frequent headaches and dizziness (P=0.004), more visual impairment (P=0.008), more polyuria and polydipsia (P=0.029), and had a higher percentage of invasion (P=0.003) than patients in the Low group. However, the prolactin normalization rate in the High group was significantly lower (P=0.042). More frequent recurrence was observed in the High group (P=0.018). CONCLUSIONS: These observations suggest the importance of investigating Ki-67 in patients with resistant prolactinoma. The treatment of resistant prolactinomas with higher level of Ki-67 is still a challenge.

8.
Artigo em Inglês | MEDLINE | ID: mdl-32249073

RESUMO

OBJECTIVE: The aim of the present study was to explore the etiology and risk factors of extubation failure (ExF) in low birth weight (LBW) infants undergoing congenital heart surgery. DESIGN: Retrospective, comparative study. SETTING: A Cantonese cardiac center in China. PARTICIPANTS: The cases of all LBW infants undergoing congenital heart surgery admitted to the authors' neonatal intensive care unit from January 2010 to September 2018 were reviewed retrospectively. ExF was defined as reintubation within 72 hours after extubation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Demographic, preoperative, perioperative, and postoperative data were collected. The exclusion criteria were surgical ligation of patent ductus arteriosus and no extubation attempt. Risk factors for ExF were analyzed with univariate and multivariate logistic regression analysis. Ninety-nine infants met the inclusion criteria; the study comprised 66 males and 33 females, including 60 premature infants. ExF occurred in 16 of 99 infants for various kinds of reasons. Infants with ExF had longer postoperative intensive care unit length of stay (LOS) (p < 0.001) and total hospital LOS (p = 0.022). The multivariate logistic regression analysis identified preoperative mechanical ventilation (odds ratio 9.3; 95% confidence interval 1.11-79.52; p = 0.040) and prolonged mechanical ventilation before the first attempted extubation (odds ratio 6.48; 95% confidence interval 1.20-35.17; p = 0.030) as risk factors for ExF. CONCLUSIONS: The prevalence of ExF is very high in LBW infants undergoing congenital cardiac surgery. ExF in LBW infants is associated with an increase in hospital LOS. Presumed reasons for failed extubation are diverse. Preoperative mechanical ventilation and prolonged mechanical ventilation before the first attempted extubation were independent risk factors for ExF.

9.
Artigo em Inglês | MEDLINE | ID: mdl-32329564

RESUMO

Solubilization locations play a critical role in developing advanced surfactants and improving solubilization power in micelle-based applications. However, the current polarity-based techniques for measuring solubilization locations could come to conflicting conclusions. The key challenge is the unpredictable polarities in the micellar microenvironment. Now, an approach that is independent of micellar polarities is used to measure solubilization locations by covalently linking tetraphenylethylene (TPE) to the alkyl chain end of cationic surfactants. The solubilization locations of solubilized acceptors in the TPE-cored spherical micelles were accurately measured by calculating the Förster resonance energy transfer distance between anchored TPE donors and solubilized acceptors. Solubilization locations of solubilized substances in the micellar interior and at the micellar surface depend on their size and hydrophobicity, respectively.

10.
Oncogene ; 39(21): 4286-4298, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32291411

RESUMO

It has been well established that the von Hippel-Lindau/hypoxia-inducible factor α (VHL-HIFα) axis and epidermal growth factor receptor (EGFR) signaling pathway play a critical role in the pathogenesis and progression of renal cell carcinoma (RCC). However, few studies have addressed the relationship between the two oncogenic drivers in RCC. SET and MYND domain-containing protein 3 (SMYD3) is a histone methyltransferase involved in gene transcription and oncogenesis, but its expression and function in RCC remain unclear. In the present study, we found that SMYD3 expression was significantly elevated in RCC tumors and correlated with advanced tumor stage, histological and nuclear grade, and shorter survival. Depletion of SMYD3 inhibited RCC cell proliferation, colony numbers, and xenograft tumor formation, while promoted apoptosis. Mechanistically, SMYD3 cooperates with SP1 to transcriptionally promote EGFR expression, amplifying its downstream signaling activity. TCGA data analyses revealed a significantly increased SMYD3 expression in primary RCC tumors carrying the loss-of-function VHL mutations. We further showed that HIF-2α can directly bind to the SMYD3 promoter and subsequently induced SMYD3 transcription and expression. Taken together, we identify the VHL/HIF-2α/SMYD3 signaling cascade-mediated EGFR hyperactivity through which SMYD3 promotes RCC progression. Our study suggests that SMYD3 is a potential therapeutic target and prognostic factor in RCC.

11.
Phys Rev Lett ; 124(13): 134803, 2020 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-32302182

RESUMO

We propose and demonstrate a novel scheme to produce ultrashort and ultrastable MeV electron beam. In this scheme, the electron beam produced in a photocathode radio frequency (rf) gun first expands under its own Coulomb force with which a positive energy chirp is imprinted in the beam longitudinal phase space. The beam is then sent through a double bend achromat with positive longitudinal dispersion where electrons at the bunch tail with lower energies follow shorter paths and thus catch up with the bunch head, leading to longitudinal bunch compression. We show that with optimized parameter sets, the whole beam path from the electron source to the compression point can be made isochronous such that the time of flight for the electron beam is immune to the fluctuations of rf amplitude. With a laser-driven THz deflector, the bunch length and arrival time jitter for a 20 fC beam after bunch compression are measured to be about 29 fs (FWHM) and 22 fs (FWHM), respectively. Such an ultrashort and ultrastable electron beam allows us to achieve 50 femtosecond (FWHM) resolution in MeV ultrafast electron diffraction where lattice oscillation at 2.6 THz corresponding to Bismuth A_{1g} mode is clearly observed without correcting both the short-term timing jitter and long-term timing drift. Furthermore, oscillating weak diffuse scattering signal related to phonon coupling and decay is also clearly resolved thanks to the improved temporal resolution and increased electron flux. We expect that this technique will have a strong impact in emerging ultrashort electron beam based facilities and applications.

12.
Artigo em Inglês | MEDLINE | ID: mdl-32298053

RESUMO

OBJECTIVE: Little is known about the intrinsic electrophysiological properties of hypothalamic hamartoma (HH) in vivo and seizure network since only few cases using stereoelectroencephalography (SEEG) electrodes exploring both cortex and HH have been published. To elucidate these issues, we analyzed simultaneous SEEG recordings in HH and cortex systematically. METHODS: We retrospectively investigated data from 15 consecutive patients with SEEG electrodes into the HH for the treatment purpose of radiofrequency thermocoagulation treatment. Additional SEEG electrodes were placed into the cortex in 11 patients to assess extra-HH involvement. Interictal discharges within the HH and anatomo-electroclinical correlations during seizures of each patient were qualitatively and quantitatively analyzed. RESULTS: Overall, 77 electrodes with 719 contacts were implanted, and 33 spontaneous seizures were recorded during long-term SEEG monitoring. Interictally, distinct electrophysiological patterns, including isolated intermittent spikes/sharp waves, burst spike and wave trains, paroxysmal fast discharges, periodic discharges, and high-frequency oscillations, were identified within the HH. Notably, synchronized or independent interictal discharges in the cortex were observed. Regarding the ictal discharges, the electrical onset pattern within the HH always started with abrupt giant shifts superimposed on low-voltage fast activity across patients. The gelastic seizure network mainly involved the HH, orbitofrontal areas, and cingulate gyrus. Seizures with automatisms and impaired awareness primarily propagated to mesial temporal lobes. Moreover, independent ictal discharges arising from the mesial temporal lobe were detected in three out of nine patients. INTERPRETATION: This study comprehensively reveals intrinsic electrophysiological patterns and epileptogenic networks in vivo, providing new insights into the mechanisms underlying cortical and subcortical epileptogenesis.

13.
Nanoscale Horiz ; 2020 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-32314991

RESUMO

A novel carbon dot-based luminescence probe for singlet oxygen (1O2) with a conventional optical detector has been implemented through the specific formation of electronically excited carbonyls from the breakdown of unstable endoperoxide intermediates, and its application in the real-time in vivo monitoring of 1O2 in photodynamic therapy (PDT) is achieved. More attractively, the relationship between the dynamics details of photosensitizer-generated 1O2 and the PDT efficacy has been established through a modified multiple-target survival model, enabling a direct and easy estimate of the surviving fraction of tumor cells from the generation dynamics of 1O2. Both in vitro and in vivo therapy results revealed that the rapid generation dynamics of 1O2 rather than its cumulative amount is responsible for better treatment efficacy in PDT. Overall, the deeper insight into the important roles of the generation dynamics of 1O2 in the PDT efficacy is irreplaceably advantageous in substantially reduced risks from deleterious treatment-related side effects by screening advanced photosensitizers and determining the light exposure end point.

14.
ACS Appl Mater Interfaces ; 12(16): 18363-18374, 2020 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-32242658

RESUMO

The development of novel antimicrobials is a top priority to address the growing epidemic of multidrug-resistant pathogens. Since cationic nonamphiphilic star-shaped antimicrobials are promising molecular scaffolds that provide a high charge density in binding anionic bacterial bilayers, this research aimed to further increase their membrane perturbation capability by introducing guanidinium groups to the antimicrobials via enhancing membrane insertion. In particular, computational simulation and experimental investigations revealed that our designed guanidinium-rich alternating copolypeptide, four-armed poly(arginine-alt-glycine), can interact with both the headgroups and unsaturated tails of phospholipids in bacterial membranes through multiple interactions, including electrostatic, cation-π, and T-shaped π-π interactions, allowing it to penetrate deeper inside the biologically inaccessible high-energy barrier of the hydrophobic lipid bilayer interior to cause membrane permeabilization and precipitation of the bacterial cytoplasm. Furthermore, glycine was observed to have a unique effect in enhancing the performance of arginine-based copolypeptide. Four-armed poly(arginine-alt-glycine) exhibited broad-spectrum antimicrobial activity, high bactericidal efficiency, and negligible hemolysis. The in vivo antibacterial performance of the copolypeptide was superior to that of doxycycline in a mouse model of Pseudomonas aeruginosa skin infection, accompanied by negligible local and systemic toxicity. Our results demonstrate that this guanidinium-rich, nonamphiphilic, star-shaped structure may promote the development of next-generation antimicrobials.

15.
Drug Deliv ; 27(1): 632-641, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32329376

RESUMO

When antibiotic-resistant pathogenic bacteria pose a high threat to human health, bacterial multidrug efflux pumps become major contributors to the high-level antibiotic resistance in most microorganisms. Since traditional antibiotics are still indispensable currently, we report a dual drug delivery system to maximize the antibacterial efficacy of antibiotics by inhibiting efflux pumps in bacteria before their exposure to antibiotics. In this research, a microsphere/hydrogel composite was constructed from ciprofloxacin (Cip)-loaded poly (lactic-co-glycolic acid) (PLGA) microspheres and ginsenoside Rh2 (G-Rh2) dispersed thermo-sensitive hydrogel to treat skin infections. In vitro drug release studies indicated that while G-Rh2 in hydrogel presented a faster and short-term release manner to rapidly inhibit the NorA efflux pumps, Cip showed a sustained and long-term release behavior to provide a local high concentration gradient for facilitating drug percutaneous penetration. The combination of Cip and G-Rh2 demonstrated a high degree of synergism against both methicillin-sensitive Staphylococcus aureus (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA), hence significantly improving their in vitro antibacterial activity and efficiency. Moreover, the antibacterial performance of the microsphere/hydrogel composite with a sequential release profile is superior to that of other formulations in mouse model of MRSA skin infections, indicating its great potential to treat antibiotic-resistant skin infections.

16.
Protein Cell ; 2020 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-32277346

RESUMO

Dysregulation of circadian rhythms associates with cardiovascular disorders. It is known that deletion of the core circadian gene Bmal1 in mice causes dilated cardiomyopathy. However, the biological rhythm regulation system in mouse is very different from that of humans. Whether BMAL1 plays a role in regulating human heart function remains unclear. Here we generated a BMAL1 knockout human embryonic stem cell (hESC) model and further derived human BMAL1 deficient cardiomyocytes. We show that BMAL1 deficient hESC-derived cardiomyocytes exhibited typical phenotypes of dilated cardiomyopathy including attenuated contractility, calcium dysregulation, and disorganized myofilaments. In addition, mitochondrial fission and mitophagy were suppressed in BMAL1 deficient hESC-cardiomyocytes, which resulted in significantly attenuated mitochondrial oxidative phosphorylation and compromised cardiomyocyte function. We also found that BMAL1 binds to the E-box element in the promoter region of BNIP3 gene and specifically controls BNIP3 protein expression. BMAL1 knockout directly reduced BNIP3 protein level, causing compromised mitophagy and mitochondria dysfunction and thereby leading to compromised cardiomyocyte function. Our data indicated that the core circadian gene BMAL1 is critical for normal mitochondria activities and cardiac function. Circadian rhythm disruption may directly link to compromised heart function and dilated cardiomyopathy in humans.

17.
Int Immunopharmacol ; 82: 106340, 2020 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-32146316

RESUMO

Nerve growth factor (NGF) is a neurotrophic factor that is thought to have a broad role in the nervous system and tumors, and has recently been described as a mediator of inflammation. It is not clear whether or not NGF participates in apoptosis of articular chondrocytes. In this study, we determined if NGF affects ASIC1a expression and NF-κB P65 activation in rat chondrocytes, and measured the effectiveness of NGF on apoptotic protein expression in acid-induced chondrocytes. NGF was shown to up-regulate the level of ASIC1a in a dose- and time-dependent fashion. Simultaneously, NGF activated NF-κB P65 in chondrocytes. Additionally, the elevated ASIC1a expression induced by NGF was eliminated by the NF-κB inhibitor (PDTC) in chondrocytes. Moreover, NGF reduced cell viability and induced LDH release under the premise of acid-induced articular chondrocytes. Furthermore, NGF could enhance cleaved-caspase 9 and cleaved-PARP expression in acid-pretreated chondrocytes, and which could be inhibited by using psalmotoxin 1(PcTX1) or PDTC. Together, these results indicated that NGF may up-regulate ASIC1a expression through the NF-κB signaling pathway, and further promote acid-induced apoptosis of chondrocytes.

18.
J Mater Chem B ; 8(13): 2573-2588, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32147675

RESUMO

A deep partial thickness (DPT) burn injury refers to burn damage involving the epidermis and major dermis, whose prognosis depends greatly on wound management. Lack of effective management can lead to an elongated healing process and aggravated scar formation, which can severely disturb patients, both physically and mentally. A dressing with good water absorption and moderate mechanical properties is crucial for healing promotion, and the prevention of scar formation is highly desirable. In this project, a hyaluronic acid combined lyotropic liquid crystal based spray dressing (HLCSD) loaded with the anti-fibrotic drug pirfenidone (PFD) has been designed. HLCSD is expected to achieve the goals of both wound healing promotion and scar prophylaxis. Its water absorption capacity, mechanical properties, drug release behavior and phase transition are fully evaluated. HLCSD possesses low viscosity for spray administration and high levels of water absorption for exudate absorption. An in situ gel composed of self-assembled lattice nanostructures provides excellent mechanical protection to promote the healing process and steady PFD release to exert a scar prophylaxis effect. The benefit of HLCSD on the wound healing rate is verified in vivo. In the DPT burn wound model we established, HLCSD also exhibits excellent healing promotion effects, and PFD-loaded HLCSD shows scar prophylaxis effects and displays an ideal prognosis, with skin as smooth as healthy skin. The healing promotion of HLCSD is considered to be related to the alleviation of inflammation, with an obviously shortened inflammation phase, with contributions from water management, mechanical protection and anti-inflammation by HLCSD. The scar prophylaxis of PFD-loaded HLCSD is proven to be related to the regulation of collagen synthesis and degradation, involving key cytokines like TGF-ß and MMP-1. Taken together, the PFD-loaded HLCSD with healing promotion and scar prophylaxis offers significant promise as a spray dressing for DPT burn injuries.

19.
Phys Rev Lett ; 124(8): 080502, 2020 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-32167353

RESUMO

Quantum teleportation transfers and processes quantum information through quantum entanglement channels. It is one of the most versatile protocols in quantum information science and leads to many remarkable applications, particularly the one-way quantum computing. Here, we show, for the first time, that the concept of teleportation can also be used to facilitate an important classical computing task, sampling random quantum circuits, which is highly relevant to prove the near-term demonstration of quantum computational supremacy. In our method, the classical computation in the physical-qubit state space is converted to simulate teleportation in logical-qubit state space, resulting in a much smaller number of qubits involved in classical computing. We tested this new method on 1D and 2D lattices up to 1000 qubits. This Letter presents a new quantum-inspired classical computing technology and is helpful to design and optimize classically hard quantum sampling experiments.

20.
J Bone Joint Surg Am ; 2020 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-32187124

RESUMO

BACKGROUND: For stage-II scapholunate advanced collapse (SLAC) and scaphoid nonunion advanced collapse (SNAC) patterns of wrist arthritis, the optimal method of surgical treatment remains unclear. Previous literature has demonstrated similar clinical outcomes between proximal row carpectomy (PRC) and 4-corner arthrodesis (FCA), making the risk of reoperation a focus of particular interest. In the present study, the primary null hypothesis was that there would be no difference in the rate of conversion to total wrist arthrodesis between PRC and FCA. Additionally, we hypothesized that the rate of secondary surgical procedures would be similar between the 2 procedures. METHODS: The national Veterans Health Administration Corporate Data Warehouse was utilized to identify 2,449 patients who underwent either PRC or FCA between 1992 and 2016. With use of operative reports to identify the arthritis pattern, only cases of stage-II SLAC/SNAC were included. All complications and subsequent surgical procedures were confirmed by manual chart review. Propensity score analyses with matching weights were utilized to balance the PRC and FCA cohorts. The rates of conversion to wrist arthrodesis and secondary surgical procedures were calculated. RESULTS: Of the 1,168 patients with stage-II SLAC/SNAC arthritis, 933 wrists underwent PRC and 257 wrists underwent FCA. Ten-year survival free of total wrist arthrodesis in the matching PRC (251 procedures) and FCA (251 procedures) cohorts was 94.3% (95% confidence interval [CI], 92.3% to 96.3%) and 94.1% (95% CI, 90.8% to 97.4%), respectively. Survival free of a secondary surgical procedure other than wrist arthrodesis was 99.7% (95% CI, 99.3% to 100.0%) for PRC and 83.5% (95% CI, 78.2% to 88.8%) for FCA. CONCLUSIONS: PRC and FCA demonstrated similarly low rates of conversion to total wrist arthrodesis. In contrast, the rate of secondary surgical procedures following FCA was significantly higher compared with PRC. Given the historically similar clinical outcomes between PRC and FCA, the results of the present study show that PRC may be a preferable treatment for stage-II SLAC/SNAC wrist arthritis. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

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