Chondroitinase ABC combined with Schwann cell transplantation enhances restoration of neural connection and functional recovery following acute and chronic spinal cord injury

Schwann cell transplantation is considered one of the most promising cell-based therapy to repair injured spinal cord due to its unique growth-promoting and myelin-forming properties.A the Food and Drug Administration-approved Phase I clinical trial has been conducted to evaluate the safety of transplanted human autologous Schwann cells to treat patients with spinal cord injury.A major challenge for Schwann cell transplantation is that grafted Schwann cells are confined within the lesion cavity,and they do not migrate into the host environment due to the inhibitory barrier formed by injury-induced glial scar,thus limiting axonal reentry into the host spinal cord.Here we introduce a combinatorial strategy by suppressing the inhibitory extracellular environment with injection of lentivirus-mediated transfection of chondroitinase ABC gene at the rostral and caudal borders of the lesion site and simultaneously leveraging the repair capacity of transplanted Schwann cells in adult rats following a mid-thoracic contusive spinal cord injury.We report that when the glial scar was degraded by chondroitinase ABC at the rostral and caudal lesion borders,Schwann cells migrated for considerable distances in both rostral and caudal directions.Such Schwann cell migration led to enhanced axonal regrowth,including the serotonergic and dopaminergic axons originating from supraspinal regions,and promoted recovery of locomotor and urinary bladder functions.Importantly,the Schwann cell survival and axonal regrowth persisted up to 6 months after the injury,even when treatment was delayed for 3 months to mimic chronic spinal cord injury.These findings collectively show promising evidence for a combinatorial strategy with chondroitinase ABC and Schwann cells in promoting remodeling and recovery of function following spinal cord injury.

Transcriptome-based analysis of key signaling pathways affecting the formation of primordial germ cell in chickens

Bone morphogenetic protein 4(BMP4)can induce the formation of chicken primordial germ cells(PGCs)in vitro;however,its regulatory mechanism in poultry remains unknown.This study aimed to use RNA-seq to analyze PGCs in chicken embryos and iPGCs induced by BMP4 in vitro,clarify the internal regulatory factors of PGCs,analyze the mechanism of the formation of PGCs,and lay a theoretical foundation for the further optimization of PGCs induction systems.Embryonic stem cells(ESCs),PGCs and iPGCs induced by BMP4 in vitro were collected.The transcriptional maps of the three cell types were studied using RNA-seq.The results showed 6,142 genes differentially expressed between PGCs and iPGCs,of which 2,728 were upregulated in iPGCs and 3,414 were downregulated in iPGCs.Compared to that in ESCs,BMP4 was significantly upregulated in PGCs and iPGCs.KEGG results showed that both the TGF-βand Wnt signaling pathways were activated during the formation of PGCs in vitro and in vivo,and the activation was more significant during iPGCs induced by BMP4.The expression of Nodal,an inhibitory factor of TGF-βsignaling,was significantly decreased in PGCs and iPGCs,but was not expressed in iPGCs,which further supports our conclusion.Additionally,the Lysosome and PI3K-AKT signaling pathways were significantly enriched in PGCs and iPGCs,respectively.Further,transmission electron microscopy(TEM)results showed that the number of autolysosomes was significantly higher after the addition of BMP4,which is consistent with the KEGG results.Furthermore,the number of PGCs was significantly reduced after ATG14 was interfered in vivo and in vitro.In conclusion,this study screened out the key signaling pathways during the formation of PGCs,aiming to provide help for enriching the mechanism network regulating PGCs formation in chicken and laying a theoretical foundation for further improving the efficiency of inducing PGCs in vitro.

Gadoxetic acid-enhanced magnetic resonance imaging in the assessment of hepatic sinusoidal obstruction syndrome in a mouse model

BACKGROUND Neoadjuvant chemotherapy can cause hepatic sinusoidal obstruction syndrome(SOS)in patients with colorectal cancer liver metastases and increases posto-perative morbidity and mortality.AIM To evaluate T1 mapping based on gadoxetic acid-enhanced magnetic resonance imaging(MRI)for diagnosis of hepatic SOS induced by monocrotaline.METHODS Twenty-four mice were divided into control(n=10)and experimental(n=14)groups.The experimental groups were injected with monocrotaline 2 or 6 days before MRI.MRI parameters were:T1 relaxation time before enhancement;T1 relaxation time 20 minutes after enhancement(T_(1post));a reduction in T1 relaxation time(△T_(1)%);and first enhancement slope percentage of the liver parenchyma(ESP).Albumin and bilirubin score was determined.Histological results served as a reference.Liver parenchyma samples from the control and experimental groups were analyzed by western blotting,and organic anion transporter polypeptide 1(OATP1)was measured.RESULTS T_(1post),△T_(1)%,and ESP of the liver parenchyma were significantly different between two groups(all P<0.001)and significantly correlated with the total histological score of hepatic SOS(r=-0.70,0.68 and 0.79;P<0.001).△T_(1)%and ESP were positively correlated with OATP1 levels(r=0.82,0.85;P<0.001),whereas T_(1post) had a negative correlation with OATP1 levels(r=-0.83;P<0.001).INTRODUCTION Hepatic sinusoidal obstruction syndrome(SOS)is also known as hepatic veno-occlusive disease of the liver[1].The main pathological feature of hepatic SOS is damage to liver terminal vessels,and the clinical symptoms of it include ascites and abdominal pain[2].It was first proposed in 1979 as an early complication of hematopoietic stem cell transplantation[3].The prevalence ranges from 5%to 60%,and hepatic SOS is a potentially severe complication and can even lead to death in severe cases[4].Recently,systemic neoadjuvant chemotherapy became widely regarded as one of the causes hepatic SOS in the patients with advanced metastatic colorectal cancer[5,6],especially those were treated with oxaliplatin[7,8].Oxaliplatin-based preoperative chemotherapy is used for patients with colorectal liver metastases as the standard regimen[8,9],because it could improve tumor resection outcome by shrinking the metastatic sites and reducing recurrence rate[10].Nevertheless,chemotherapy-induced hepatic SOS has been associated with a higher risk of postresection morbidity[11],such as intraoperative bleeding,intraoperative transfusions,and postoperative liver failure[12].Therefore,it is important to detect and diagnose of hepatic SOS timely.Currently,the gold standard is still based on liver biopsy[13],but it is an invasive procedure and has several limitations and complications,such as hemorrhage[14].A noninvasive diagnostic modality is needed for the assessment of hepatic SOS.Some noninvasive tools have been used for diagnosis of hepatic SOS.Researchers have utilized a preoperative platelet count and aspartate aminotransferase to platelet ratio index[15].In addition,some imaging methods such as shear wave ultrasonography,computed tomography,and gadoxetic acid-enhanced magnetic resonance imaging(MRI)have been promoted as useful methods for evaluation of hepatic SOS[16-18].Recent studies with monocrotaline(MCT)-treated rats were conducted to investigate diagnosis and prediction of severity of SOS.For example,intravoxel incoherent motion diffusion-weighted imaging,non-Gaussian diffusion models,and T1 rho quantification[19,20].The MCT-induced hepatic SOS animal model was reproducible,with a detailed pathological scoring criteria[21].Gadoxetic acid is a hepatocyte-specific contrast substance,which can provide parenchymal contrast in the hepato-biliary phase.It is reported that gadoxetic acid is absorbed into the liver parenchyma via organic anion transporter polypeptide 1(OATP1)on the hepatocyte membranes[22-24].Recently,several authors have described the feasibility of gadoxetic acid-enhanced MRI for the diagnosis of oxaliplatin-induced hepatic SOS[25].They mainly diagnosed hepatic SOS based on the signal intensity of the hepatobiliary specific phase.However,there were several limitations due to the inconsistency between signal intensity of the liver parenchyma and the concentration of contrast agent for evaluation of the degree of hepatic SOS[26].Therefore,we measured T1 relaxation time on parametric mapping because it is linearly related to the concentration of the contrast agent and is not affected by other factors[27].Yang et al[28]demonstrated T1 mapping on gadoxetic acid-enhanced MRI for the assessment of oxaliplatin-induced liver injury in a C57BL/6 mouse model.However,the main pathological changes in their model were hepatocyte degeneration and fibrosis.Therefore,we aimed to explore the effectiveness of T1 mapping based on gadoxetic acid-enhanced MRI for the diagnosis of hepatic SOS in a C57BL/6 mouse model,as well as a possible relation between OATP1 Levels and MRI parameters.

Improvement in acupoint selection for acupuncture of nerves surrounding the injury site: electro-acupuncture with Governor vessel with local meridian acupoints

Peripheral nerve injury not only affects the site of the injury, but can also induce neuronal apop- tosis at the spinal cord. However, many acupuncture clinicians still focus only on the injury site, selecting acupoints entirely along the injured nerve trunk and neglecting other regions; this may delay onset of treatment efficacy and rehabilitation. Therefore, in the present study, we compared the clinical efficacy of acupuncture at Governor vessel and local meridian acupoints combined （GV/LM group） with acupuncture at local meridian acupoints alone （LM group） in the treatment of patients with peripheral nerve injury. In the GV/LM group （n = 15）, in addition to meridian acupoints at the injury site, the following acupoints on the Governor vessel were stimulated： Baihui （GV20）, Fengfu （GV16）, Dazhui （GV14）, and Shenzhu （GV12）, selected to treat nerve injury of the upper limb, and Jizhong （GV6）, Mingmen （GV4）, Yaoyangguan （GV3）, and Yaoshu （GV2） to treat nerve injury of the lower limb. In the LM group （n = 15）, only me- ridian acupoints along the injured nerve were selected. Both groups had electroacupuncture treatment for 30 minutes, once a day, 5 times per week, for 6 weeks. Two cases dropped out of the LM group. A good or excellent clinical response was obtained in 80% of the patients in the GV/ LM group and 38.5% of the LM group. In a second study, an additional 20 patients underwent acupuncture with the same prescription as the GV/LM group. Electomyographic nerve conduc- tion tests were performed before and after acupuncture to explore the mechanism of action of the treatment. An effective response was observed in 80.0% of the patients, with greater motor nerve conduction velocity and amplitude after treatment, indicating that electroacupuncture on specific Governor vessel acupoints promotes functional motor nerve repair after peripheral nerve injury. In addition, electromyography was performed before, during and after electroacu- puncture in one patient with radial nerve injury. After a single session, the patient＇s motor nerve conduction velocity increased by 23.2%, indicating that electroacupuncture at Governor vessel acupoints has an immediate therapeutic effect on peripheral nerve injury. Our results indicate that Governor vessel and local meridian acupoints used simultaneously promote functional repair after peripheral nerve injury. The mechanism of action may arise from an improvement of the local microenvironment in injured nervous tissue, as well as immediate effects of Governor vessel and local meridian acupoint stimulation to ensure the continuity between the peripheral and central nervous systems.

Epithelioid angiomyolipoma of the liver:Cross-sectional imaging findings of 10 immunohistochemically-verified cases

AIM： To retrospectively evaluate the computed tomography （CT）/magnetic resonance imaging （MRI） imaging features of epithelioid angiomyolipoma of the liver （Epi-HAML）, with pathology as a reference. METHODS： The CT/MRI findings （number, diameter, lobar location, and appearance of lesions） in a series of 10 patients with 12 pathologically proven epithelioid angiomyolipomas of the liver were retrospectively analyzed. The imaging features, including attenuation/ signal intensity characteristics, presence of fat, hypervascular, outer rim, and vessels within lesion, were evaluated and compared with that of non-Epi- HAML in 11 patients （13 lesions）. The Fisher exact test was used to compare difference in probability of imaging features between the two types. RESULTS： For 21 patients, CT images of 15 patients and MR images of six patients were available. No patient underwent two examinations. For the 15 patients with a CT scan, all HAML lesions in the two groups （10 Epi-HAML and seven non-Epi-HAML） manifested as hypoattenuation. For the six patients with MRI, all lesions （two Epi-HAML and six non-Epi- HAML） were hypointense on TlWI （fat suppression） and hyperintense on T2WI. There were 10 non-Epi-HAML, but only two Epi-HAML lesions showed the presence of fat, which significantly different between the two types （P = 0.005）. On the dynamic contrast enhancement （DCE） imaging, eight Epi-HAML, and 13 non-Epi lesions manifested as hypervascular. Punctate or curved vessels were displayed in 10 Epi-HAML as well as in nine non- Epi lesions and outer rim enhancement could be found with eight Epi-HAML as well as six non-Epi lesions. CONCLUSION： Little or no presence of adipose tissue was found to be an imaging feature of Epi- HAML, compared with the non-Epi type. In addition, hypervascularity with opacification of central punctiform or filiform vessels on DCE would be a characteristic enhancement pattern for Epi-HAML.

Characterization and in-situ formation mechanism of tungsten carbide reinforced Fe-based alloy coating by plasma cladding

The precursor carbonization method was first applied to prepare W–C compound powder to perform the in-situ synthesis of the WC phase in a Fe-based alloy coating. The in-situ formation mechanism during the cladding process is discussed in detail. The results reveal that fine and obtuse WC particles were successfully generated and distributed in Fe-based alloy coating via Fe/W–C compound powders. The WC particles were either surrounded by or were semi-enclosed in blocky M7C3 carbides. Moreover, net-like structures were confirmed as mixtures of M23C6 and α-Fe; these structures were transformed from M7C3. The coarse herringbone M6C carbides did not only derive from the decomposition of M7C3 but also partly originated from the chemical reaction at the α-Fe/M23C6 interface. During the cladding process, the phase evolution of the precipitated carbides was WC → M7C3 → M23C6 ＋ M6C.

Evidence for Multiple Underlying Fermi Surface and Isotropic Energy Gap in the Cuprate Parent Compound Ca2CuO2Cl2

The parent compounds of the high-temperature cuprate superconductors are Mott insulators.It has been generally agreed that understanding the physics of the doped Mott insulators is essential to understanding the mechanism of high temperature superconductivity.A natural starting point is to elucidate the basic electronic structure of the parent compound.Here we report comprehensive high resolution angle-resolved photoemission measurements on Ca_2CuO_2Cl_2,a Mott insulator and a prototypical parent compound of the cuprates.Multiple underl.ying Fermi surface sheets are revealed for the first time.The high energy waterfall-like band dispersions exhibit different behaviors near the nodal and antinodal regions.Two distinct energy scales are identified：a d-wave-like low energy peak dispersion and a nearly isotropic lower Hubbard band gap.These observations provide new information of the electronic structure of the cuprate parent compound,which is important for understanding the anomalous physical properties and superconductivity mechanism of the high temperature cuprate superconductors.

Understanding the Correlations between Social Attention and Topic Trends of Scientific Publications

Purpose： We propose and apply a simplified nowcasting model to understand the correlations between social attention and topic trends of scientific publications. Design/methodology/approach： First, topics are generated from the obesity corpus by using the latent Dirichlet allocation （LDA） algorithm and time series of keyword search trends in Google Trends are obtained. We then establish the structural time series model using data from January 2004 to December 2012, and evaluate the model using data from January 2013. We employ a state-space model to separate different non-regression components in an observational time series （i.e. the tendency and the seasonality） and apply the ＂spike and slab prior＂ and stepwise regression to analyze the correlations between the regression component and the social media attention. The two parts are combined using Markov-chain Monte Carlo sampling techniques to obtain our results. Findings： The results of our study show that （1） the number of publications on child obesity increases at a lower rate than that of diabetes publications; （2） the number of publication on a given topic may exhibit a relationship with the season or time of year; and （3） there exists a correlation between the number of publications on a given topic and its social media attention, i.e. the search frequency related to that topic as identified by Google Trends. We found that our model is also able to predict the number of publications related to a given topic.

Using Machine Reading to Understand Alzheimer's and Related Diseases from the Literature

Purpose： This paper aims to better understand a large number of papers in the medical domain of Alzheimer＇s disease （AD） and related diseases using the machine reading approach. Design/methodology/approach： The study uses the topic modeling method to obtain an overview of the field, and employs open information extraction to further comprehend the field at a specific fact level. Findings： Several topics within the AD research field are identified, such as the Human Immunodeficiency Virus （HIV）/Acquired Immune Deficiency Syndrome （AIDS）, which can help answer the question of how A1DS/HIV and AD are very different yet related diseases. Research limitations： Some manual data cleaning could improve the study, such as removing incorrect facts found by open information extraction. Practical implications： This study uses the literature to answer specific questions on a scientific domain, which can help domain experts find interesting and meaningful relations among entities in a similar manner, such as to discover relations between AD and AIDS/HIV. Origlnality/value： Both the overview and specific information from the literature are obtained using two distinct methods in a complementary manner. This combination is novel because previous work has only focused on one of them, and thus provides a better way to understand an important scientific field using data-driven methods.

Research Progress on the Solder Joint Reliability of Electronics Using in Deep Space Exploration

The spacecraft for deep space exploration missions will face extreme environments,including cryogenic temperature,intense radiation,wide-range temperature variations and even the combination of conditions mentioned above.Harsh environments will lead to solder joints degradation or even failure,resulting in damage to onboard electronics.The research activities on high reliability solder joints using in extreme environments can not only reduce the use of onboard protection devices,but effectively improve the overall reliability of spacecraft,which is of great significance to the aviation industry.In this paper,we review the reliability research on SnPb solder alloys,Sn-based lead-free solder alloys and In-based solder alloys in extreme environments,and try to provide some suggestions for the follow-up studies,which focus on solder joint reliability under extreme environments.

High-temperature continuous-wave operation of 1310 nm InAs/GaAs quantum dot lasers

Here we report 1.3μm electrical injection lasers based on InAs/GaAs quantum dots(QDs)grown on a GaAs substrate,which can steadily work at 110-℃without visible degradation.The QD structure is designed by applying the Stranski-Krastanow growth mode in solid source molecular beam epitaxy.The density of InAs QDs in the active region is increased from 3.8×10^(10)cm^(-2)to 5.9×10^(10)cm^(-2).As regards laser performance,the maximum output power of devices with lowdensity QDs as the active region is 65 m W at room temperature,and that of devices with the high-density QDs is 103 mW.Meanwhile the output power of high-density devices is 131 mW under an injection current of 4 A at 110-℃.

单篇论著的引文扩散

引文是连接科学知识的重要线索,为我们提供了理解知识产生、交流、转化乃至创新规律的金钥匙。引文不只是静态的统计分布,同时也是处于复杂科学系统中的动态增长过程。本文将引文理解为一种扩散过程,从多个维度重新审视引文扩散过程及其基本要素、量化方式与增长机理。引文扩散体系中至少包含以下要素:时间环境、首次被引、引文高峰、最终引文数量、引文累积速度、引文生命周期、文献网络/生态系统,以及引文起飞。引文在微观结构上以引文级联为基本单元,从引文感染性与引文流行性两个维度进行扩散,有广播型与感染型两种典型扩散方式。引文扩散模式的巨大差异性源于其内在机理的作用,对于优先连接机制、老化机制与适应性机制以及创新机制与模仿机制的认识与进一步探索,将有助于对引文扩散进程的理解。对引文扩散的探讨对于科研评估、科学预测、科技政策制定等科技活动具有潜在价值。

Radiofrequency ablation or microwave ablation combined with transcatheter arterial chemoembolization in treatment of hepatocellular carcinoma by comparing with radiofrequency ablation alone

Objective：To compare radiofrequency ablation （RFA） or microwave ablation （MWA） and transcatheter arterial chemoembolization （TACE） with RFA or MWA monotherapy in hepatocellular carcinoma （HCC）.Methods：A prospective,randomized,controlled trial was conducted on 94 patients with HCC ≤7 cm at a single tertiary referral center from June 2008 to June 2010 at the Department of Hepatobiliary Surgery,the Second Affiliated Hospital of Southeast University.The patients were randomly assigned into the TACERFA or TACE-MWA （combined treatment group） and the RFA-alone or MWA-alone groups （control group）.The primary end point was overall survival.The secondary end point was recurrence-free survival,and the tertiary end point was adverse effects.Results：Until the time of censor,17 patients in the TACE-RFA or TACE-MWA group had died.The median follow-up time of the patients who were still alive for the TACE-RFA or TACE-MWA group was 47.5±11.3 months （range,29 to 62 months）.The 1-,3-and 5-year overall survival for the TACE-RFA or TACE-MWA group was 93.6％,68.1％ and 61.7％,respectively.Twenty-five patients in the RFA or MWA group had died.The median follow-up time of the patients who were still alive for the RFA or MWA group was 47.0±12.9 months （range,28 to 62 months）.The 1-,3-and 5-year overall survival for the RFA or MWA group was 85.1％,59.6％ and 44.7％,respectively.The patients in the TACE-RFA or TACE-MWA group had better overall survival than the RFA or MWA group [hazard ratio （HR）,0.526; 95％ confidence interval （95％ CO,0.334-0.823; P=0.002],and showed better recurrence-free survival than the RFA or MWA group （HR,0.582; 95％ CI,0.368-0.895; P=0.008）.Conclusions：RFA or MWA combined with TACE in the treatment of HCC ≤7 cm was superior to RFA or MWA alone in improving survival by reducing arterial and portal blood flow due to TACE with iodized oil before RFA.

Decellularized optic nerve functional scaffold transplant facilitates directional axon regeneration and remyelination in the injured white matter of the rat spinal cord

Axon regeneration and remyelination of the damaged region is the most common repair strategy for spinal cord injury.However,achieving good outcome remains difficult.Our previous study showed that porcine decellularized optic nerve better mimics the extracellular matrix of the embryonic porcine optic nerve and promotes the directional growth of dorsal root ganglion neurites.However,it has not been reported whether this material promotes axonal regeneration in vivo.In the present study,a porcine decellularized optic nerve was seeded with neurotrophin-3-overexpressing Schwann cells.This functional scaffold promoted the directional growth and remyelination of regenerating axons.In vitro,the porcine decellularized optic nerve contained many straight,longitudinal channels with a uniform distribution,and microscopic pores were present in the channel wall.The spatial micro topological structure and extracellular matrix were conducive to the adhesion,survival and migration of neural stem cells.The scaffold promoted the directional growth of dorsal root ganglion neurites,and showed strong potential for myelin regeneration.Furthermore,we transplanted the porcine decellularized optic nerve containing neurotrophin-3-overexpressing Schwann cells in a rat model of T10 spinal cord defect in vivo.Four weeks later,the regenerating axons grew straight,the myelin sheath in the injured/transplanted area recovered its structure,and simultaneously,the number of inflammatory cells and the expression of chondroitin sulfate proteoglycans were reduced.Together,these findings suggest that porcine decellularized optic nerve loaded with Schwann cells overexpressing neurotrophin-3 promotes the directional growth of regenerating spinal cord axons as well as myelin regeneration.All procedures involving animals were conducted in accordance with the ethical standards of the Institutional Animal Care and Use Committee of Sun Yat-sen University(approval No.SYSU-IACUC-2019-B034)on February 28,2019.

Usefulness of two-point Dixon fat-water separation technique in gadoxetic acid-enhanced liver magnetic resonance imaging

AIM:To compare differences between volumetric interpolated breath-hold examination(VIBE) using two-point Dixon fat-water separation(Dixon-VIBE) and chemically selective fat saturation(FS-VIBE) with magnetic resonance imaging examination.METHODS:Forty-nine patients were included, who were scanned with two VIBE sequences(Dixon-VIBE and FS-VIBE) in hepatobiliary phase after gadoxetic acid administration.Subjective evaluations including sharpness of tumor, sharpness of vessels, strength and homogeneity of fat suppression, and artifacts that were scored using a 4-point scale.The liver-to-lesion contrast was also calculated and compared.RESULTS:Dixon-VIBE with water reconstruction had significantly higher subjective scores than FS-VIBE in strength and homogeneity of fat suppression(< 0.0001) but lower scores in sharpness of tumor(P < 0.0001), sharpness of vessels(P = 0.0001), and artifacts(P = 0.034).The liver-to-lesion contrast on Dixon-VIBE images was significantly lower than that on FS-VIBE(16.6% ± 9.4% vs 23.9% ± 12.1%, P = 0.0001).CONCLUSION:Dixon-VIBE provides stronger and more homogenous fat suppression than FS-VIBE, while has lower clarity of focal liver lesions in hepatobiliary phase after gadoxetic acid administration.

Luteolin prevents uric acid-induced pancreatic β-cell dysfunction

Elevated uric acid causes direct injury to pancreatic β-cells. In this study, we examined the effects of luteolin, an important antioxidant, on uric acid-induced β-cell dysfunction. We first evaluated the effect of luteolin on nitric oxide （NO） formation in uric acid-stimulated Min6 cells using the Griess method. Next, we performed transient transfection and reporter assays to measure transcriptional activity of nuclear factor （NF）-κB. Western blotting assays were also performed to assess the effect of luteolin on the expression of MafA and inducible NO synthase （iNOS） in uric acid-treated cells. Finally, we evaluated the effect of luteolin on uric acidinduced inhibition of glucose-stimulated insulin secretion （GSIS） in Min6 cells and freshly isolated mouse pancreatic islets. We found that luteolin significantly inhibited uric acid-induced NO production, which was well correlated with reduced expression of iNOS mRNA and protein. Furthermore, decreased activity of NF-κB was implicated in inhibition by luteolin of increased iNOS expression induced by uric acid. Besides, luteolin significantly increased MafA expression in Min6 cells exposed to uric acid, which was reversed by overexpression of iNOS. Moreover, luteolin prevented uric acidinduced inhibition of GSIS in both Min6 cells and mouse islets. In conclusion, luteolin protects pancreatic β-cells from uric acid-induced dysfunction and may confer benefit on the protection of pancreatic β-cells in hyperuricemiaassociated diabetes.

Traditional Chinese medicine ointment combined with tuina therapy in treatment of pain and swelling after total knee arthroplasty

BACKGROUND The most effective treatment for knee joint pain is total knee arthroplasty(TKA),but the risk of pain and swelling in patients after surgery is high.Ice application,ankle pump exercise and non-steroidal anti-inflammatory painkillers are the primary clinical treatments after surgery.However,long-term use of nonsteroidal anti-inflammatory pain relievers can easily cause gastrointestinal damage.Traditional Chinese medicine(TCM)ointments and tuina therapy integrate TCM and manipulation,which effectively promotes the penetration of TCM into the skin lesions,improves local blood circulation and inflammatory reaction and has good long-term effects on patients.AIM To evaluate the efficacy of TCM ointment combined with tuina therapy in the treatment of pain and swelling after TKA.METHODS The randomized controlled clinical trial enrolled 80 patients who underwent TKA via the same procedure.The patients were randomly divided among the treatment group(n=40)and the control group(n=40).The control group was given an analgesia pump in addition to oral painkillers as the postoperative intervention.The treatment group received TCM ointment with tuina therapy in addition to the analgesia pump and oral painkillers in the postoperative period.The following variables were recorded 3 d before surgery and 3 d,7 d and 14 d after surgery:Visual analogue scale(VAS)score;skin temperature;circumferences at 15 cm above and below the patella;maximum active knee flexion angle;and the knee injury and Osteoarthritis Outcome score(KOOS).RESULTS After treatment,VAS was significantly lower in the treatment group than the control group at 7 d(t=7.536,P<0.001)and 14 d(t=8.563,P<0.001).The skin temperature of participants in the treatment group was significantly lower than that in the control group at 7 d(t=2.968,P=0.004)and 14 d(t=4.423,P<0.001).The circumference values of the two positions in the treatment group were lower than those in the control group at 7 d[t=2.315,P=0.023(above);t=2.121,P=0.037(below)]and 14 d[t=2.374,P=0.020(above);t=2.095,P=0.039(below)].After 14 d of treatment,the maximum active knee flexion angle and KOOS of the two groups were significantly improved but were significantly higher in the treatment group(P<0.05 for both).CONCLUSION TCM ointment and tuina therapy have significant advantages over standard care in the treatment of pain and swelling after TKA.This additional treatment may improve knee function but additional studies are needed to confirm our observations.

Data-driven Discovery: A New Era of Exploiting the Literature and Data

In the current data-intensive era, the traditional hands-on method of conducting scientific research by exploring related publications to generate a testable hypothesis is well on its way of becoming obsolete within just a year or two. Analyzing the literature and data to automatically generate a hypothesis might become the de facto approach to inform the core research efforts of those trying to master the exponentially rapid expansion of publications and datasets. Here, viewpoints are provided and discussed to help the understanding of challenges of data-driven discovery.

Disappearance of Superconductivity and a Concomitant Lifshitz Transition in Heavily Overdoped Bi_2Sr_2CuO_6 Superconductor Revealed by Angle-Resolved Photoemission Spectroscopy

By partially doping Pb to effectively suppress the superstructure in single-layered cuprate Bi_2Sr_2CuO_(6+δ)(Pb-Bi2201) and annealing them in vacuum or in high pressure oxygen atmosphere, a series of high quality Pb-Bi2201 single crystals are obtained with T_c covering from 17 K to non-superconducting in the overdoped region. High resolution angle resolved photoemission spectroscopy measurements are carried out on these samples to investigate the evolution of the Fermi surface topology with doping in the normal state. Clear and complete Fermi surfaces are observed and quantitatively analyzed in all of these overdoped Pb-Bi2201 samples. A Lifshitz transition from holelike Fermi surface to electron-like Fermi surface with increasing doping is observed at a doping level of ~0.35. This transition coincides with the change that the sample undergoes superconducting-to-non-superconducting states.Our results reveal the emergence of an electron-like Fermi surface and the existence of a Lifshitz transition in heavily overdoped Bi2201 samples. This provides important information in understanding the connection between the disappearance of superconductivity and the Lifshitz transition in the overdoped region.

Evolution of incommensurate superstructure and electronic structure with Pb substitution in(Bi2-xPbx)Sr2CaCu2O8+δ superconductors

High-quality Bi2-xPbxSr2 CaCu2O8+δ(Bi2212) single crystals have been successfully grown by the traveling solvent floating zone technique with a wide range of Pb substitution(x = 0–0.8).The samples are characterized by transmission electron microscope(TEM) and measured by high resolution laser-based angle-resolved photoemission spectroscopy(ARPES) with different photon energies.A systematic evolution of the electronic structure and superstructure with Pb substitution has been revealed for the first time.The superstructure shows a significant change with Pb substitution and the incommensurate modulation vector(Q) decreases with increasing Pb substitution.In the meantime, the superstructure intensity from ARPES measurements also decreases dramatically with increasing Pb concentration.The superstructure in Bi2212 can be effectively suppressed by Pb substitution and it nearly disappears with a Pb substitution of x = 0.8.We also find that the superstructure bands in ARPES measurements depend sensitively on the photon energy of lasers used;they can become even stronger than the main band when using a laser photon energy of 10.897 eV.These results provide important information on the origin of the incommensurate superstructure and its control and suppression in bismuth-based high temperature superconductors.