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Based on the land economic density of 892 town units, the spatial pattern of the land economic density in Zhejiang Province is analyzed using the coefficient of variation, spatial classification, and spatial correlation methods, and the influencing factors are analyzed using a spatial regression model. The results are as follows: (1) The coefficients of variation were 2.6 and 3.1 in 2014 and 2019, respectively, indicating that the degree of imbalance of the town's industrial economy at the county level increased. (2) The distribution of the high-level agglomeration areas was characterized by one core area and two sub-core areas. The main core area was located at the junction of Hangzhou City, Shaoxing City, and Jiaxing City, and the two sub-core areas were located in Yuyao City and the main urban area of Ningbo City. In addition, several small-scale agglomeration areas composed of medium and high-level units were distributed in Wenzhou City. (3) The high-value agglomeration and low-value agglomeration distribution in the spatial correlation patterns was identified using the spatial auto-correlation method. The hot spots and sub-hot spots were distributed in Northern Zhejiang, and the cold spots formed a large-scale agglomeration in Quzhou City, Lishui City, Taizhou City, and several other cities in Southern Zhejiang. (4) Compared with the county scale, the spatial scope of the high-level areas in Northern Zhejiang shrunk significantly at the township scale, and the high-level agglomeration areas along the southeast coast changed into a cluster of several townships. (5) According to the geographically weighted regression (GWR) model, the importance of influencing factors is as follows: population density > regional area > industrial output value per capita > total population > proportion of secondary and tertiary personnel > total employees. [ABSTRACT FROM AUTHOR]

Fabricating highly oriented 2D nanosheet arrays is crucial for boosting their performance in electronics, catalysis, optics, and energy conversion, while it remains a challenge due to the high surface energy often leads to random aggregation or interlaced structure. In this study, it is found that the exposed facet of Fe2O3 can greatly influence the interface growth arrangement of bimetallic hydroxide (NiCo(OH)2) nanosheets. The NiCo(OH)2 nanosheets tend to parallel‐standing on the cubic and spindle Fe2O3 while random‐ and interlaced‐standing on the Fe2O3 hexagonal nanoplates and microspheres. The theoretical simulation further indicates the orientation of deposited hydroxide sheets is decided explicitly by the interfacial lattice match/mismatch. Compared to the common interlaced structure of nanosheets, the parallel‐standing nanosheet arrays reduce grain boundaries and improve the charge transfer efficiency. As a result, the derived NiCoP cages exhibit a promising oxygen evolution reaction performance with an overpotential of 255 mV at 10 mA cm−2, and the maximum current density of 400 mA cm−2 with the overpotential of 319 mV. [ABSTRACT FROM AUTHOR]

The massive use of fossil fuels releases a great amount of CO2, which substantially contributes to the global warming. For the global goal of putting CO2 emission under control, effective utilization of CO2 is particularly meaningful. Electrocatalytic CO2 reduction reaction (eCO2RR) has great potential in CO2 utilization, because it can convert CO2 into valuable carbon‐containing chemicals and feedstock using renewable electricity. The catalyst design for eCO2RR is a key challenge to achieving efficient conversion of CO2 to fuels and useful chemicals. For a typical heterogeneous catalyst, surface and interface engineering is an effective approach to enhance reaction activity. Herein, the development and research progress in CO2 catalysts with focus on surface and interface engineering are reviewed. First, the fundaments of eCO2RR is briefly discussed from the reaction mechanism to performance evaluation methods, introducing the role of the surface and interface engineering of electrocatalyst in eCO2RR. Then, several routes to optimize the surface and interface of CO2 electrocatalysts, including morphology, dopants, atomic vacancies, grain boundaries, surface modification, etc. are reviewed and representative examples are given. At the end of this review, we share our personal views in future research of eCO2RR. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a common disease worldwide and is treated commonly with methotrexate (MTX). CS12192 is a novel JAK3 inhibitor discovered by Chipscreen Biosciences for the treatment of autoimmune diseases. In the present study, we examined the therapeutic effect of CS12192 against RA and explored if the combinational therapy of CS12192 and MTX produced a synergistic effect against RA in rat collagen-induced arthritis (CIA). Arthritis was induced in male Sprague-Dawley rats by two intradermal injections of bovine type II collagen (CII) and treated with MTX, CS12192, or the combination of CS12192 and MTX daily for two weeks. Effects of different treatments on arthritis score, X-ray score, pathology, and expression of inflammatory cytokines and biomarkers were examined. We found that treatment with either CS12192 or MTX produced a comparable therapeutic effect on CIA including: (1) significantly lowering the arthritis score, X-ray score, serum levels of rheumatic factor (RF), C-reactive protein (CRP), and anti-nuclear antibodies (ANA); (2) largely alleviating histopathological damage, reducing infiltration of Th17 cells while promoting Treg cells; (3) inhibiting the expression of inflammatory cytokines and chemokines such as IL-1β, TNF-α, IL-6, CCL2, and CXCL1. All these inhibitory effects were further improved by the combinational therapy with MTX and CS12192. Of importance, the combinational treatment also resulted in a marked switching of the Th17 to Treg and the M1 to M2 immune responses in synovial tissues of CIA. Thus, when compared to the monotherapy, the combination treatment with CS12192 and MTX produces a better therapeutic effect against CIA with a greater suppressive effect on T cells and macrophage-mediated joint inflammation. [ABSTRACT FROM AUTHOR]

Background: Atrial fibrillation is a well-documented complication following cardiac surgery. It is associated with increased inpatient and long-term mortality. There have been few prior studies on perioperative atrial fibrillation following burn surgery in severely burned patients. The purpose of this study was to identify the incidence, predictors, and prognosis of perioperative atrial fibrillation after burn surgery in severely burned patients.Methods: Patients aged older than 18 years with 30% burned total body surface area (TBSA) were enrolled in this study. Patients who had a previous history of atrial fibrillation or atrial fibrillation on the preoperative electrocardiogram were excluded. We reviewed medical records retrospectively, and the data of 214 patients were studied.Results: A total of 214 critically ill burned patients and 1132 operations were available for analysis during the 5-year study period; 12 (1.1%) patients were diagnosed with newly developed atrial fibrillation after a burn operation, of whom 4 patients showed paroxysmal atrial fibrillation (all related to surgical stimulation) and none changed to persistent atrial fibrillation. The incidence of perioperative atrial fibrillation was associated with TBSA%, full-thickness TBSA%, and hypertension. Multiple logistic regression analysis indicated that TBSA% (OR=13.851, P < 0.001) and full-thickness TBSA% (OR=15.223, P = 0.018) were independent predictors for developing perioperative atrial fibrillation. All of our patients had at least one risk factor, with blood volume variation or burn sepsis occurring most commonly. Perioperative atrial fibrillation developed after a median of 0 days after burn surgery. Three patients died, and the causes of death were noncardiovascular events such as sepsis and multiple organ failure.Conclusion: Atrial fibrillation was a relatively rare complication among severely burned patients admitted to surgery and was associated with TBSA% and full thickness TBSA%. All of our patients exhibited at least one of the modifiable risk factors for atrial fibrillation, confirming the importance of optimization of electrolytes and fluid status and limitation of sympathetic activation. [ABSTRACT FROM AUTHOR]

A series of deferasirox derivatives of 1,2,4‐triazole (5 a–i,6 a–g) were designed and synthesized by the ring‐opening rearrangement reaction of phenyl hydrazine or its substituents and imines, compounds 5 d–i, 6 e–g are previously unknown. Obtained derivatives were characterized by IR, 1H NMR, 13C NMR, and Mass spectral. The antibacterial activities of all compounds against Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Candida albicans and Aspergillus niger were experimentally evaluated. Most of them exhibited potential antimicrobial activity and promising antifungal activity. Especially, 6 f and 6 g showed the best antimicrobial activity (MIC90=0.125–2.0 μg/mL) against Staphylococcus aureus, Staphylococcus epidermidis and Escherichia coli, while compounds 6 c, 6 e showed excellent antifungal activity (MIC90=0.5–2.0 μg/mL). The molecular docking analysis further revealed that all the synthesized derivatives have shown potential binding affinities. [ABSTRACT FROM AUTHOR]

Transforming growth factor-β (TGF-β) plays a critical role in the pathological processes of various diseases. However, the signaling mechanism of TGF-β in the pathological response remains largely unclear. In this review, we discuss advances in research of Smad7, a member of the I-Smads family and a negative regulator of TGF-β signaling, and mainly review the expression and its function in diseases. Smad7 inhibits the activation of the NF-κB and TGF-β signaling pathways and plays a pivotal role in the prevention and treatment of various diseases. Specifically, Smad7 can not only attenuate growth inhibition, fibrosis, apoptosis, inflammation, and inflammatory T cell differentiation, but also promotes epithelial cells migration or disease development. In this review, we aim to summarize the various biological functions of Smad7 in autoimmune diseases, inflammatory diseases, cancers, and kidney diseases, focusing on the molecular mechanisms of the transcriptional and posttranscriptional regulation of Smad7. [ABSTRACT FROM AUTHOR]

The high stability of the dual-excited synchronous generator (DESG) can enhance the reliability of power supply for critical users. Based on the traditional synchronous generator (TSG), a DESG with two sets of symmetrical field windings on the rotor is presented in this paper. The rotor slots are spaced equally over the whole rotor surface of DESG, which is different from the structure of TSG. Such structures of DESG are expected to enhance the reliability and give the electromagnetic performances, such as air-gap flux density and electromotive force (emf) that are close to those of TSG. For this purpose the relationship between the excitation magnetomotive forces (mmf) of the single- and dual-axis excited DESG is investigated. The mmf with a different rotor pitch is calculated by the finite-element simulation, and the simulation results agree with those by the theoretical derivation. The excitation air-gap flux density, emf, and the magnetic saturation in stator and rotor cores are calculated under different excitation modes, and the results are compared with those of TSG. In order to validate the simulation results, the emf of 10 kW DESG model machine is measured under different excitation modes. This paper provides the theoretical basis for the design and manufacture of large DESGs. [ABSTRACT FROM AUTHOR]

At present, rheumatoid arthritis (RA) is considered a type of autoimmune disease. Its pathology is not certain, and effective drugs with less toxicity have not been established. The establishment and application of animal models are effective methods for RA research, especially using animal models similar to humans. Arthritis is more heterogeneous, and this is an important starting point when discussing animal models for arthritis. Animal models are instrumental in understanding the etiology and pathogenetic mechanisms of RA. Appropriate animal models should be selected according to experiments because they have different traits. Various methods have been applied to induce arthritis in animal experimental models, which have provided important insights into the etiopathogenetic mechanisms of human RA. This review was written to give a broad introduction of the current stage of RA model and hope to offer beneficial help for RA-related research. [ABSTRACT FROM AUTHOR]

Abstract: Icaritin is a native compound from Epimedium Genus, a traditional Chinese herbal medicine which is effective in treating asthma, autoimmune diseases and viral infections. In the present paper, the immunosuppressive effects of icaritin were found through in vitro and in vivo studies. Icaritin could dose-dependently inhibit murine CD4+ T cells proliferation stimulated with mitogens or specific antigen ovabumin (OVA). Icaritin at 0.25–25μM could down-regulate T cell activation marker CD25 expression and inhibit IL-2 production. It could also reduce the Th1 cytokine IFN-γ production significantly if the T cells were activated by ConA or anti-CD3; while the inhibition of IL-4 secretion was only seen on anti-CD3 activated T cells treated with low concentrations of icaritin. In vivo study showed that treatment of icaritin at 10mg/kg/day on mice could suppress the immune response with prolonged allograft skin survival. Further study demonstrated that it reduced the alloantigen-induced splenocytes proliferation and Th1/Th2 cytokines. It could also increase NF-AT luciferase activity in Jurkat-NF-AT-luc T cells. The above results suggested that icaritin might be used to treat Th1 dominated immune diseases by interfering T cells activation with mechanism different to CsA. [Copyright &y& Elsevier]

Abstract: To elucidate the effects of particle size and surface charge on cellular uptake and biodistribution of polymeric nanoparticles (NPs), rhodamine B (RhB) labeled carboxymethyl chitosan grafted NPs (RhB-CMCNP) and chitosan hydrochloride grafted NPs (RhB-CHNP) were developed as the model negatively and positively charged polymeric NPs, respectively. These NPs owned well defined particle sizes (150–500 nm) and Zeta potentials (−40 mV – +35 mV). FITC labeled protamine sulfate (FITC-PS) loaded RhB-CMCNP and camptothecin (CPT) loaded RhB-CHNP with high encapsulation efficiency were prepared. The fluorescence stability in plasma and towards I− was investigated, and the result indicated it was sufficient for qualitative and quantitative analysis. NPs with high surface charge and large particle size were phagocytized more efficiently by murine macrophage. Slight particle size and surface charge differences and different cell lines had significant implications in the cellular uptake of NPs, and various mechanisms were involved in the uptake process. In vivo biodistribution suggested that NPs with slight negative charges and particle size of 150 nm were tended to accumulate in tumor more efficiently. These results could serve as a guideline in the rational design of drug nanocarriers with maximized therapeutic efficacy and predictable in vivo properties, in which the control of particle size and surface charge was of significance. [Copyright &y& Elsevier]

In this study, a novel series of 7-azaindole-1,2,3-triazole bearing N-benzamide derivatives 3a–3r were synthesized and fully characterized by 1H NMR, 13C NMR, and MS. The prepared compounds were tested against A549 and HepG2 cell lines by using MTT assay in vitro anticancer activity. Compounds 3d, 3l, 3q, and 3r exhibited the most promising, with IC50 (7.83, 7.58, 9.47, and 8.65 μM, respectively) against A549 compared with Gefitinib (IC50, 6.77 μM) and IC50 (6.98, 6.69, 10.18, and 7.97 μM, respectively) against HepG2 compared with Sorafenib (IC50, 5.65 μM). Further molecular docking studies showed that compounds 3d, 3l, 3q, and 3r can bind well to protein targets 3LXY, 4AGD, and 3WZE, so these compounds have the potential to be developed into multi-targeted kinase inhibitor. [ABSTRACT FROM AUTHOR]

By designing the morphology and architecture of employed electrocatalysts, the development of high-performance hydrogen evolution reaction (HER) electrocatalysts for electrolytes with a wide pH range is practical significance for future energy conversion technologies. Herein, we synthesize an electrocatalyst composing of two-dimensional (2D) ultrathin ternary pyrite-type cobalt phosphosulfide nanosheets and conductive carbon black (CoPS NSs/C) by the one-step phosphosulfide process. Thanks to the introduction of the C, the composite not only presents a unique three-dimensional (3D) interconnected reticulum structure but also effectively reduces the thickness of nanosheets. The as-synthesized electrocatalyst exhibits remarkable small overpotential toward HER in wide pH range. Meanwhile, the electrocatalyst owns higher charge transfer rate and excellent stability. The good performance is mainly attributed to the combination of the advantages of both 2D nanosheets and 3D interconnected reticulum structure, which offers larger surface area, sufficient active sites and more contaction with electrolytes. This work provides a new method for preparing ultrathin ternary transition-metal phosphosulfide (TMPS) nanosheets, and offers a facile route for improving electrocatalytic activity by designing synergistic morphology of 2D and 3D. Image 1 • The electrocatalyst design strategy of synergistic 2D and 3D morphology is provided. • Synergistic 2D and 3D morphology engineering build novel interconnected network structure. • CoPS NSs/C with 3D structure constructed by 2D CoPS nanosheets is successfully prepared. • CoPS NSs/C electrocatalyst owns an intriguing HER activity over wide pH range. [ABSTRACT FROM AUTHOR]

Background: This meta-analysis investigated the influence of exercise on cognitive function in people living with diabetes. Methods: Stringent criteria for literature inclusion and exclusion were defined. Searches were conducted across four English databases to gather randomized controlled trials investigating exercise interventions for cognitive function in people living with diabetes. Outcome indicators from 1193 subjects across 12 articles were analyzed using RevMan 5.4 software. Results: Exercise intervention demonstrated the ability to mitigate cognitive decline in people living with diabetes, with a combined effect size (standardized mean difference) of 0.91, 95% CI: 0.28, 1.54, P < 0.00001. The intervention effect showed significant modulation by intervention content (I2 = 95%), intervention duration (I2 = 95%), intervention frequency (I2 = 95%), and intervention cycle (I2 = 96%). Among these factors, multi-component exercise, sessions >40 minutes, exercise frequency >4 times per week, and sustained exercise for >6 months were paramount, all with P < 0.05. Conclusion: Exercise intervention emerges as a viable strategy for delaying cognitive decline in people living with diabetes. Its efficacy is subject to modulation by various variables. Optimal intervention includes multi-component exercise, individual sessions lasting 40–60 minutes, exercising >4 times a week, and continuous exercise for over 6 months. [ABSTRACT FROM AUTHOR]

To compare the visual performance after implantation of three aberration-correcting aspherical intraocular lens (IOL). Seventy-seven eyes of 77 cataract patients were divided into three groups: 26 eyes implanted with a non-constant aberration IOL (LUCIA 601P IOL, Zeiss Company, Germany); 26 eyes implanted with a spherical aberration −0.18μm IOL (CT ASPHINA 509M, Zeiss Company, Germany) and 27 eyes implanted with a spherical aberration −0.27μm IOL (AMO Tecnis ZCB00, Johnson & Johnson Surgical Vision, USA). Three months after operation, the distance visual acuity, wavefront aberrometry, contrast sensitivity, intraocular stray light, IOL decentration, and tilt were evaluated. Three months postoperatively, no statistically significant differences were found in uncorrected distance visual acuity and corrected distance visual acuity (p≥.83). The RMS for total ocular coma was statistically significantly lower in the Lucia group (p=.03) and spherical aberration was statistically significantly lower in the Tecnis group (p<.01). No statistically significant differences were observed among the three lenses in higher order aberration (p=.85) and in contrast sensitivity under both photopic and mesopic lighting conditions (p≥.05). The intraocular stray light was statistically significantly better in the Lucia group (p=.04). No statistically significant differences were observed with respect to IOL decentration (p=.75) and tilt (p=.89). Cataract surgery with non-constant aberration IOL resulted in lower coma and better intraocular stray light than with the spherical aberration −0.18μm and −0.27μm IOLs despite equivalent postoperative levels of visual acuity and contrast sensitivity. [ABSTRACT FROM AUTHOR]

Aim. To observe the clinical efficacy and safety of phacoemulsification surgery combined with intravitreal injection of conbercept in cataract patients with DME. Methods. This is a prospective clinical cohort study. Thirty-five cataract patients (49 eyes) with DME were divided into two groups. The observation group (23 eyes) underwent a cataract phacoemulsification surgery combined with intravitreal injection of conbercept 0.5 mg; the control group (26 eyes) underwent a cataract phacoemulsification surgery only. The visual acuity, central macular thickness (CMT), IOP, and anterior chamber flare were examined before surgery and 1 week and one month after surgery. Results. The UCVA and BCVA in Log MAR in the observation group were lower than those in the control group at 1 week (p = 0.032 ; p = 0.041) and 1 month (p = 0.035 ; p = 0.039), respectively, after the surgery. The CMT of the observation group changed from 492.7 ± 32.2 μm before surgery to 341.6 ± 59.9 μm one week after surgery and 374.8 ± 48.3 μm one month after surgery. The CMT of control group increased after surgery. There was no significant difference in IOP and flare between the two groups at all following times. Conclusion. In patients with DME, undergoing a cataract surgery combined with intravitreal injection of conbercept is safe and effective for visual improvement and CMT declination with relatively fewer IOP and flare fluctuation. [ABSTRACT FROM AUTHOR]

Sex allocation theory as applied to local resource competition (LRC) predicts that parents should skew investment towards philopatric offspring when local resources are abundant. Alternatively, parents should allocate resources to the dispersing sex when local resources are deficient in order to limit competition among relatives. Nest sites have been shown to be the primary factor limiting populations of secondary cavity-nesting birds. In this study, we manipulated nestbox density to test its effect on the sex allocation patterns of the great tit, Parus major , a species in which female offspring are more likely to disperse than male offspring. We also investigated the relationship between the brood sex ratio and the time of breeding, which has been shown in many studies to influence sex allocation. Consistent with the LRC prediction, parents invested more in male offspring and produced a male-biased sex ratio in the area where nestboxes were abundant. In our study, the reproductive success of great tits declined as the season progressed; however, the time of breeding had no effect on the sex ratio of the offspring. Overall, the results of our study suggest that nestbox availability can influence sex allocation in great tits, and may also represent a relatively common phenomenon in other secondary cavity-nesting birds. [ABSTRACT FROM AUTHOR]

Background: Rheumatoid arthritis (RA) is a chronic autoimmune disease. We previously revealed that the natural compound artemisitene (ATT) exhibits excellent broad anticancer activities without toxicity on normal tissues. Nevertheless, the effect of ATT on RA is undiscovered. Herein, we aim to study the effect and potential mechanism of ATT on RA management. Methods: A collagen‐induced arthritis (CIA) mouse model was employed to confirm the anti‐RA potential of ATT. Cell Counting Kit‐8 (CCK‐8) and 5‐ethynyl‐2'‐deoxyuridine (EdU) assays, cell cycle and apoptosis analysis, immunofluorescence, migration and invasion assays, quantitative real‐time PCR (RT‐qPCR), Western blot, RNA‐sequencing (RNA‐seq) analysis, plasmid construction and lentivirus infection, and methylated RNA immunoprecipitation and chromatin immunoprecipitation assays, were carried out to confirm the effect and potential mechanism of ATT on RA management. Results: ATT relieved CIA in mice. ATT inhibited proliferation and induced apoptosis of RA‐fibroblast‐like synoviocytes (FLSs). ATT restrained RA‐FLSs migration and invasion via suppressing epithelial–mesenchymal transition. RNA‐sequencing analysis and bioinformatics analysis identified intercellular adhesion molecule 2 (ICAM2) as a promoter of RA progression in RA‐FLSs. ATT inhibits RA progression by suppressing ICAM2/phosphoinositide 3‐kinase (PI3K)/protein kinase B (AKT)/p300 pathway in RA‐FLSs. Moreover, ATT inhibited methyltransferase‐like 3 (METTL3)‐mediated N6‐methyladenosine methylation of ICAM2 mRNA in RA‐FLSs. Interestingly, p300 directly facilitated METTL3 transcription, which could be restrained by ATT in RA‐FLSs. Importantly, METTL3, ICAM2 and p300 expressions in synovium tissues of RA patients were related to clinical characteristics and therapy response. Conclusions: We provided strong evidence that ATT has therapeutic potential for RA management by suppressing proliferation, migration and invasion, in addition to inducing apoptosis of RA‐FLSs through modulating METTL3/ICAM2/PI3K/AKT/p300 feedback loop, supplying the fundamental basis for the clinical application of ATT in RA therapy. Moreover, METTL3, ICAM2 and p300 might serve as biomarkers for the therapy response of RA patients. [ABSTRACT FROM AUTHOR]

Efficient and simple operation electrocatalysts for the oxygen evolution reaction (OER) are essential components of renewable energy technologies. Here, a novel, simple, and efficient routine is presented for the first time by constructing a high-efficiency anode catalyst for OER. With the aid of high intensity ultrasound, a uniformly loading, conductive multiwalled carbon nanotubes/metal/transition metal-oxide (CNTs-Au@Co 3 O 4 ) tubular hybrids is synthesized. In alkaline media, the materials catalyze OER with an onset potential of 1.56 V vs. reversible hydrogen electrode (RHE) and overpotential only of 350 mV to achieve a stable current density of 10 mA cm −2 for at least 25 h. The unusual catalytic activity and stability is due to the following elements. Firstly, the tubular architecture not only provides sufficient active centers for OER, but also improves rapid mass/charge transport. Secondly, Co 3 O 4 layer protects Au nanoparticles (NPs) against detachment. In addition, we also prove that the highest electronegativity metal Au accelerate the formation of catalytic active sites of Co IV species for OER. It is believed that this simple preparation method paves a way to fabricate a range of CNTs/metal/metal-oxide based composites as superior OER catalysts. [ABSTRACT FROM AUTHOR]

Background: Rheumatoid arthritis is a progressive and systemic autoimmune disease seriously compromises human health. Fibroblast like synoviocytes are the major effectors of proliferation and inflammation in rheumatoid arthritis synovial tissue. Shikonin has anti-inflammatory and immunomodulatory activities. But, its role on synovitis of rheumatoid arthritis is unknown. Methods: The DBA/1 male mice were randomly divided into the following three groups (n = 6): (1) the normal control group of mice, (2) the CIA (collagen-induced arthritis) group in which mice suffered from arthritis induced by collagen, (3) the SKN (shikonin) group of mice which got arthritis and given intragastrically with shikonin 4 mg/kg per day continuously for 20 days,(4) the MTX (methotrexate) group of mice which got arthritis and orally administration with shikonin 0.5 mg/kg once two days continuously for 20 days. The therapeutic effect of shikonin on collagen induced arthritis mice was tested by arthritis incidence rate, arthritis score and inflammatory joint histopathology. The invasion, adhesion and migration of fibroblast like synoviocytes induced by tumor necrosis factor-α were applied to measure the anti-synovitis role of shikonin. The effect of shikonin on expression of interleukin-6, interleukin-1β and tumor necrosis factor-α was measured by enzyme linked immunosorbent assay. The interaction between shikonin and suppressor of cytokine signaling 1 was verified by molecular docking. The signaling pathways activated by shikonin were measured by western blot. Results: Shikonin decreased the arthritis score and arthritis incidence, and inhibited inflammation of inflamed joints in collagen induced arthritis mice. And shikonin reduced the number of vimentin+cells in collagen induced arthritis mice inflamed joints. Meanwhile, shikonin suppressed tumor necrosis factor-α-induced invasion, adhesion and migration of fibroblast like synoviocytes and reduced the expression of interleukin-6, interleukin-1β and tumor necrosis factor-α. And we found that shikonin targeted suppressor of cytokine signaling 1. More interestingly, shikonin blocked the phosphorylation of Janus kinase 1/signal transducer andactivator of transcription 1/signal transducer andactivator of transcription 6 in synovial tissues and in fibroblast like synoviocytes. Conclusion: Shikonin represents a promising new anti-rheumatoid arthritis drug candidate that has anti-synovitis effect in collagen induced arthritis mice and inhibits tumor necrosis factor-α-induced fibroblast like synoviocytes by targeting suppressor of cytokine signaling 1/ Janus kinase/signal transducer andactivator of transcription signaling pathway. These findings demonstrate that shikonin has anti-synovitis effect and has great potential to be a new drug for the treatment of rheumatoid arthritis. [ABSTRACT FROM AUTHOR]

Background & Aim: Shortage of donor hepatocytes limits hepatocyte transplantation for clinical application. Induced hepatic stem cells (iHepSCs) have capacities of self‐renewal and bipotential differentiations. Here, we investigated whether iHepSCs could be extensively expanded, and whether they could differentiate into sufficient functional hepatocytes as donors for transplantation therapy after their extensive expansions. Methods: Murine extensively expanded iHepSCs (50‐55 passages) were induced to differentiate into iHepSC‐Heps under a chemically defined condition. iHepSC‐Heps were proved for carrying morphological hepatocyte characters and hepatocytic functions including low‐density lipoprotein uptake, glycogen storage, CLF secretion, ICG uptake and release, Alb secretion, urea synthesis and metabolism‐relative gene expressions respectively. Next, both iHepSCs and iHepSC‐Heps were transplanted into Fah‐/‐ mice respectively. Both liver repopulation and alleviation of liver function were compared between two transplantation groups. Results: Murine iHepSCs still maintained the capacities of self‐renewal and bipotential differentiations after extensive expansion. The efficiency for the functional hepatocyte differentiation from extensively expanded iHepSCs reached to 72.64%. Transplantations of both extensively expanded iHepSCs and iHepSC‐Heps resulted in liver engraftment in Fah‐/‐ mice. Survival rate of Fah‐/‐ mice recipients and level of liver repopulation were 50% and 20.32 ± 4.58% respectively in iHepSC‐Heps group, while 33% and 10.4 ± 4.3% in iHepSCs group. Conclusions: Extensively expanded iHepSCs can efficiently differentiate into hepatocytes in chemical defined medium. Transplantation of iHepSC‐Heps was more effective and more efficient than transplantation of iHepSCs in Fah‐/‐ mice. Our results suggested an innovative system to obtain sufficient hepatocytes through hepatic differentiation of iHepSCs generated by lineage reprogramming. [ABSTRACT FROM AUTHOR]

This research was designed to investigate the fracture healing pattern in a rheumatoid arthritis (RA) rat model. A mid‐shaft femur fracture (RA + F) model and normal fracture (NF) model as control were established. Micro‐CT, H&E staining, TB staining, SO staining, tartrate‐resistant acid phosphates, and immunohistochemistry test were performed. In the micro‐CT images and H&E stains, fracture gaps were evident in the RA + F group 4 and 8 weeks after fracture. In detail, the bone mineral density, the ratio of bone volume to tissue volume, and trabecular thickness of the RA + F group were significantly lower than those of the NF group at all time points. Trabecular number value was significantly lower in the RA + F group 4 weeks after surgery in comparison with that of the NF group. Furthermore, the structure model index test result of the RA + F group was significantly higher than that of the NF group at all time points. TB staining and SO staining test results showed that the NF group had more cartilaginous callus in the earlier stage of bone healing process (4 weeks), and less cartilage callus formation in the later stage (8 weeks) in comparison with that of the RA + F group. Osteoclasts statistics score in the NF group were obviously lower than that of the RA + F group at all time points. MMP‐3 and OPN protein levels of the fracture area in the RA + F group were significantly higher than those in the NF group. This study improves the understanding of the bone healing characteristics in patients with RA. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2876–2885, 2018. [ABSTRACT FROM AUTHOR]

A thin porous film inorganic-organic heterostructure photocathode has been successfully fabricated and applied in photoelectrochemical (PEC) water splitting. Our work optimized the best structure of CuBi 2 O 4 (CBO) base on FTO (fluorine doped tin oxide). Furthermore, it was passivated with polythiophene (PTh), a kind of conducting polymers of excellent environmental and thermal stability, to decrease the capture ability of surface state for photogenerated charge. Benefiting from the high light capture rate of porous structure of CBO and low electron-hole recombination rate of CBO/PTh heterojunctions, the as-fabricated FTO/CBO/PTh electrode delivers excellent PEC performance with a ultimate photocurrent density of 0.41 mA cm −2 at 0.3 V vs RHE (reversible hydrogen electrode) doubled to that of pure FTO/CBO electrode, which would be due to the significantly improved light absorption and rapid separation efficiency. [ABSTRACT FROM AUTHOR]

Objective GTS-21, a selective α7 nicotinic acetylcholine receptor agonist, has recently been established as a promising treatment for inflammation. However, the detailed molecular mechanism of GTS-21 in suppressing pro-inflammatory cytokine production is only partially explored. The study aimed to analyze cytokine expression suppressed by GTS-21 with lipopolysaccharide (LPS)-induced inflammation in vitro and to gain insights into the role of Akt/NF-κB signaling pathway in this process. Materials and methods Cell Counting Kit-8 (CCK-8) assay was performed to detect drug cytotoxicity. RAW 264.7 cells were stimulated with LPS and treated with GTS-21. Interleukin (IL)-1β, IL-6, or tumor necrosis factor (TNF)-α production was detected using enzyme-linked immunosorbent assay. Western blot was used to assess the expression patterns of signal transduction protein. Nuclear translocation of nuclear factor (NF)-κB was analyzed by confocal fluorescence microscopy. In addition, α7 nicotinic acetylcholine receptors (α7 nAChR) were detected on RAW264.7, and the α7 nAChR-specific antagonist was adopted to verify whether the effect of GTS-21 was mediated by α7 nAChR. Results The CCK-8 assay showed that GTS-21 did not significantly affect cell proliferation. The production of IL-1β, IL-6, and TNF-α decreased after being treated with GTS-21 in LPS-stimulated RAW 264.7 cells. GTS-21 also suppressed LPS-induced phosphorylation of NF-κBp65, IKKα/β, IκBα, and Akt, as well as NF-κB p65 nuclear translocation. Moreover, α7 nAChR was expressed on the surfaces of RAW264.7 cells, and the α7 nAChR-specific antagonist almost completely prohibited the inhibitory effect of GTS-21 on NF-κB activation. Conclusion These findings indicate that GTS-21 suppresses LPS-induced inflammation by inhibiting the Akt/NF-κB signal pathway through α7 nAChR. GTS-21 has a potential application in inflammatory disease therapy. [ABSTRACT FROM AUTHOR]

Receptor activator of NF-κB ligand (RANKL) is essential for osteoclastogenesis. Targeting RANKL signaling pathways has been an encouraging strategy for treating lytic bone diseases such as osteoporosis and rheumatoid arthritis (RA). Sinomenine (SIN), derived from Chinese medicinal plant Sinomenioum acutum, is an active compound to treat RA, but its effect on osteoclasts has been hitherto unknown. In the present study, SIN was found to ameliorate M. tuberculosis H37Ra (Mt)-induced bone loss in rats with a decreased serum level of TRACP5b and RANKL, and an increased level of osteoprotegerin (OPG). In vitro study also showed that SIN could inhibit RANKL-induced osteoclast formation and bone resorption. The osteoclastic specific marker genes induced by RANKL including c-Src, MMP-9, TRACP were inhibited by SIN in a dose dependent manner. Signal transduction studies showed that SIN could obviously reduce the expression of RANK adaptor molecule TRAF6 and down-regulate RANKL-induced NF-κB activation. It decreased the RANKL-induced p38, JNK posphorylation but not ERK1/2 posphorylation. SIN could also reduce RANKL-mediated calcium influx which is associated with TRAF6/c-Src complex. Finally, SIN suppressed RANKL induced AP-1 and NFAT transcription, as well as the gene expression of NFATc1 and AP-1 components (Fra-1, Fra-2, c-Fos). The protein expression of c-Fos and TRAF6 were also inhibited by SIN after RANKL stimulation. Taken together, SIN could attenuate osteoclast formation and Mt-induced bone loss by mediating RANKL signaling pathways. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a chronic, systemic inflammatory disorder that may affect many tissues and organs. Without treatment, inflammation leads to cartilage damage, bone erosions, joint destruction, and impaired movement. Because of the limited success of disease-modifying anti-rheumatic drugs, the exploration of new anti-rheumatic drugs with high efficacy and less toxicity is eagerly needed. Genistein, the major active compound from soybean, has received much attention due to its potential beneficial effects on some of the degenerative diseases. It has been found that genistein has anti-inflammatory, antiangiogenesis, antiproliferative, antioxidant, immunomodulatory, pain relief, and joint protection properties. Hence, significant advances have been made, both by in vitro and in vivo studies showing that genistein is a promising agent for RA treatment. [ABSTRACT FROM AUTHOR]

Abstract: The abnormal proliferation and polarization of Th17/Th1 subsets are believed to contribute to the progression of multiple sclerosis. We demonstrated that neural stem cells (NSCs) could inhibit CD4+T cells from mice of experimental autoimmune encephalomyelitis to proliferate and polarize into Th17 but promote their apoptosis and to generate regulatory T cells in response to myelin antigen via releasing prostaglandin E2 by activated Th1-derived IFN-γ. The study indicated that NSCs play a negatively regulatory role in T cell responses and provided novel evidence for the therapeutic mechanisms underlying the usage of NSCs to treat autoimmune diseases of central nervous system. [Copyright &y& Elsevier]

Examines the existence of hepatic stem cells (HSC) in the spleens of mice. Replacement demands of cellular losses; Role of HSC in hepatocarcinogenesis; Preparation of donor cells.

Peripheral nerve injury (PNI) is encountered relatively commonly in the clinic and often results in long-term functional deficits. Research to develop methods to improve regeneration following nerve injury is ongoing. Numerous studies have shown that adipose-derived stem cells (ADSCs) promote the regeneration of peripheral nerve injury; however, the mechanism is unclear. Autophagy, a highly conserved intracellular process responsible for maintaining cellular homeostasis, and Schwann cells (SCs), play important roles in regeneration after PNI. In the present study, we explored the effect and mechanism of exosomes produced by adipose-derived stem cells (ADSC-Exos) on autophagy of SCs in PNI, as well as their effect on the regeneration of the nerve myelin sheath. The levels of autophagy and the expression of karyopherin subunit alpha 2 (Kpna2) in SCs increased markedly after the sciatic nerve was injured in SCs (SNI-SCs). The enhanced autophagy and the upregulated Kpna2 in SNI-SCs were inhibited after treatment with ADSC-Exos in vivo and in vitro. The effect of ADSC-Exos on inhibiting SC autophagy was blocked by overexpression of Kpna2 in SNI-SCs. Using quantitative real-time reverse transcription PCR, ADSC-Exos were demonstrated to contain a large amount of miRNA-26b, which was predicted to regulate Kpna2 on the TargetScan website. The effect of ADSC-Exos on inhibiting SCs autophagy was blocked after the silencing of miRNA-26b. Moreover, ADSC-Exos promoted the regeneration of the myelin sheath by inhibiting SC autophagy in rat SNI models. In conclusion, our results indicated that ADSC-Exos promote the regeneration of the myelin sheath by moderately reducing autophagy of injured SCs via miRNA-26b downregulation of Kpna2. [ABSTRACT FROM AUTHOR]

• A novel AgVO 3 /Mo-BiVO 4 photoanode is firstly fabricated. • The as-obtained photoanode achieves excellent photoelectrochemical performance. • p-n heterojunction and Mo dopant can meliorate the intrinsic deficiency of BiVO 4. • The huge potential of AgVO 3 in PEC water splitting is unraveled. BiVO 4 is largely restricted by its intrinsic poor electron mobility and sluggish surface reaction. Aiming at eliminating the deficiency of BiVO 4 , we assemble a novel composite photoanode through simultaneous bulk and surface modification. In detail, controllable Mo doping is manipulated through a spin-coating method, and AgVO 3 nanoparticles are loaded by successive ionic layer adsorption and reaction (SILAR) process. The as-prepared photoanode boosts the photocurrent density by 7 folds at 1.23 V vs. RHE and moves the onset potential negatively by 387 mV compared to the bare BiVO 4. Furthermore, the charge injection efficiency is substantially boosted to 49% at 1.23 V RHE , nearly 5 times as that of pure BiVO 4. With detailed physical and electrochemical characterization, we reveal the essential reason for the boosted photoelectrochemical activity. Appropriate Mo doping can simultaneously enhance the carrier density and electron mobility of BiVO 4. Specifically, more (0 4 0) facet are exposed for retarding charge recombination and increasing photocatalytic reaction sites. Then the simple SILAR process grows AgVO 3 nanoparticles homogeneously with uniform diameter of 3–5 nm on BiVO 4 , forming p-n heterojunction to accelerate charge separation, and abundant oxygen vacancy emerged on the surface, which has been demonstrated as active sites for water oxidation reaction. [ABSTRACT FROM AUTHOR]

• Encapsulating the FeVO 4 -passivated layer on ZnO nanorod as PEC photoanode. • Heterojunction and surface passivated layer promote charge separation/transfer ability. • The optimized photoelectrode acquires superior water splitting performance and photostability characteristic. Among many novel and promising semiconductors, the triclinic iron vanadate (FeVO 4) has been rarely applied in the field of solar water splitting due to its poor charge carrier separation ability. In this work, we prepared FeVO 4 -passivated ZnO heterojunction nanorods (FVO/ZnO NRs) photoanodes by simple spin-coating and calcination method for the first time. The optimal photoanode exibihits stable and effective PEC water oxidation performance, compared to pristine ZnO, affording 130 mV negative shift in onset potential and 2.4 folds augment in photocurrent density. Particularly, X-ray photoelectron spectroscopy and Mott-Schottky test reveal the establishment of heterojunction, which subdue photo-induced carriers bulk recombination and improve the charge separation efficiency. Open-circuit photovoltage and electrochemical impedance spectroscopy were recorded to further clarify that the FeVO 4 -passivated layer eliminates the surface trapping state, thus increasing the photovoltage and promoting the interface charge transfer kinetics. These demonstrations are expected to provide new thread for the rational application of new photoanode candidates and to optimize PEC performance. [ABSTRACT FROM AUTHOR]

Communications using the orbital angular momentum (OAM) of radio waves have attracted much attention in recent years. In this paper, a novel millimeter-wave dual OAM mode antenna is cleverly designed, using which a 60 GHz wireless communication link with two separate OAM channels is experimentally demonstrated. The main body of the dual OAM antenna is a traveling-wave ring resonator using two feeding ports fed by a 90° hybrid coupler. A parabolic reflector is used to focus the beams. All the antenna components are fabricated by 3D printing technique and the electro-less copper plating surface treatment process. The performances of the antenna, such as S-parameters, near-fields, directivity, and isolation between the two OAM modes are measured. Experimental results show that this antenna can radiate two coaxially propagating OAM modes beams simultaneously. The multiplexing and de-multiplexing are easily realized in the antennas themselves. The two OAM mode channels have good isolation of more than 20 dB, thus ensuring the reliable transmission links at the same time. [ABSTRACT FROM AUTHOR]