Era of the 4D animal model

Revealing the entire dynamics of pathogenesis is critical for understanding,preventing and treating human disease but is limited by systematic clinical sampling.This drawback can be overcome with animal model studies.Recent advances in phenotyping,omics and bioinformatics technologies promote the development of the 4D animal model to simulate and digitally display the spatiotemporal landscapes of phenotypes and molecular dynamics in human diseases and reveal novel targets for diagnosis and therapy.In this commentary,the origin,supporting technologies,content,function and application,and advantages of 4D animal models over clinical studies and traditional animal models,as well as their limitations,are presented.

DNA氧化损伤8-羟鸟嘌呤与肿瘤的发生发展

有氧代谢有机体细胞无法避免活性氧(reactive oxygen species,ROS)的伤害。ROS会造成多种形式的DNA损伤,其中鸟嘌呤G的氧化产物8-羟鸟嘌呤(8-oxoG)是频度最高的一种DNA氧化损伤,由特异性的糖苷酶OGG1识别并开启碱基切除修复通路完成修复。8-oxoG如果没有及时修复,可能会在复制的过程中引入G:C配对到T:A配对的碱基颠换突变。因此8-oxoG的积累或OGG1修复功能异常被认为会影响基因功能,进而导致肿瘤或衰老相关疾病的发生,然而直接实验证据却极为有限。近年来一系列研究表明,8-oxoG倾向于产生在基因的调控区,在这种情形下,8-oxoG可视为一种表观遗传学修饰,而OGG1则是这一信息的特异性读取者,OGG1对底物的识别、结合或切除会引发DNA构象或组蛋白修饰的改变,进而引起基因表达的上调或下调。因此,除了潜在的遗传毒性,鸟嘌呤氧化损伤与肿瘤的关联与其通过表观遗传学机制引发基因表达的异常密切相关。本文对8-oxoG及修复酶OGG1与肿瘤发生发展的关联机制进行了分析与总结,旨在提示研究人员从新的视角解读DNA氧化损伤与肿瘤的关系,并为肿瘤的治疗提供新的思路和靶点。

绿色溢价是否存在?--来自中国绿色债券市场的证据

2016年以来,中国绿色债券市场取得了快速的发展。本文以2016年1月1日至2020年5月31日发行的绿色债券为样本,使用绿色债券与普通债券匹配的方法研究了中国绿色债券溢价。结果表明绿色债券收益率利差较匹配的普通债券收益率利差平均低17个基点,说明绿色债券有助于降低企业融资成本。绿色溢价随着时间的推移越来越显著,市场表现出逐渐学习和熟悉的过程。本文发现未经第三方认证的绿色债券相比经过认证的绿色债券收益率利差显著更低,规模较小和净资产收益率较低的公司更倾向于申请第三方认证,表明绿色认证市场可能存在逆向选择问题。本文的发现为发展我国绿色债券市场和完善绿色认证制度提供了参考。

Precipitation behaviors of X70 acicular ferrite pipeline steel

The morphology, structure, and chemical composition of precipitates in the final microstructure of Nb-V-Ti microalloyed X70 acicular ferrite pipeline steel were investigated using transmission electron microscopy （TEM） and energy dispersive X-ray spectroscopy （EDS）. Precipitates observed by TEM can be classified into two groups. The large precipitates are complex compounds that comprise square-shaped TiN precipitate as core with fine Nb-containing precipitate nucleated on pre-existing TiN precipitate as caps on one or more faces at high temperature. In contrast, the fine and spherical Nb carbides and/or carbonitrides precipitate heterogeneously on dislocations and sub-boundaries at low temperature. From the analysis in terms of thermodynamics, EDS and chemical cornposition of the steel, NbC precipitation is considered to be the predominant precipitation behavior in the tested steel under the processing conditions of this research.

Preparation of CeO_2-Modified Mg(Al)O-Supported Pt–Cu Alloy Catalysts Derived from Hydrotalcite-Like Precursors and Their Catalytic Behavior for Direct Dehydrogenation of Propane

A series of PtCuCeMgAl quintuple hydrotalcite-like compounds with different Ce contents were synthesized by one-pot method. After calcining and reduction, CeO_2-modified Mg(Al)O-supported Pt–Cu alloy catalysts were obtained. To understand the effect of Cu and Ce, the structure and physico-chemistry properties of the catalysts were characterized and analyzed, and the catalytic behaviors were investigated in a direct dehydrogenation of propane to propene. The results show that the Pt^(4+), Cu^(2+), and Ce^(3+) ions can be incorporated into the brucite-like layers and the Ce content significantly affects the interaction strength between Pt and Cu and the dehydrogenation performance of propane. Under the reaction conditions, the highest propane conversion(45%) with 89% selectivity to propene and a 40% propene yield were achieved with a 0.3 wt% Ce-modified PtCu/Mg(Al)O catalyst. The improved catalytic performance is related to the easy formation of Pt–Cu alloy phase, excellent resistance to sintering, and coke deposits of active components modified by CeO_2.

Rational design strategies of Cu-based electrocatalysts for CO_(2) electroreduction to C_(2) products

Electrochemical reduction of CO_(2)(CO_(2)RR)to high value-added chemicals is an effective way to remove excess CO_(2) from the atmosphere.Due to the unique propensity of Cu for valuable hydrocarbons,Cu-based electrocatalysts are the most potential catalysts that allow the conversion of CO_(2) into a variety of C_(2) products such as ethylene and ethanol.Rational design of Cu-based catalysts can improve their directional selectivity to C_(2) products.Hence,in this review,we summarize the recent progress in the mechanistic studies of Cu-based catalysts on reducing CO_(2) to C_(2) products.We focus on three key strategies for efficiently enhancing electrocatalytic performance of Cu-based catalysts,including tuning electronic structure,surface structure,and coordination environment.The correlation between the structural characteristics of Cu-based catalysts and their activity and selectivity to C_(2) products is discussed.Finally,we discuss the challenges in the field of CO_(2) electroreduction to C_(2) products and provide the perspectives to design efficient Cu-based catalysts in the future.

Dehydrogenation of isobutane to isobutene over a Pt-Cu bimetallic catalyst in the presence of LaAlO_(3) perovskite

In this study,isobutane dehydrogenation to isobutene reaction was carried out in a series of PtCu bimetallic catalysts prepared by coimpregnation method.The catalysts were characterized by means of several techniques,including XRD,N_(2) adsorptiondesorption,TEM,XPS,H2TPR and TG.The results show that the existence of LaAlO_(3) perovskite can enhance the dispersion and sintering resistance of metal nanoparticles and facilitate the transfer of carbon deposits from active sites to the support.Interestingly,the perovskite nanoparticles can also inhibit the reduction of CuOx and the formation of PtCu alloys,resulting in the suitable interaction between Pt and Cu.The PtCu/LaAlO_(3)/SiO_(2)catalyst exhibits the optimal dehydrogenation performance with an isobutane conversion of 47%and isobutene selectivity of 92%after 310 min reaction,which was ascribed to the unique role of LaAlO_(3) perovskite as well as the appropriate PtCu interaction.

Highly Dispersed Pt Species with Excellent Stability and Catalytic Performance by Reducing a Perovskite-Type Oxide Precursor for CO Oxidation

A new scheme for the preparation of highly dispersed precious metal catalysts is proposed in this work. Samples of LaCo_(1-x)Pt_xO_3/SiO_2( x = 0.03, 0.05, 0.07, 0.09, and 0.10) were prepared through a simple method of citrate acid complexation combined with impregnation. In a nanocrystallite of LaCo_(1-x)Pt_xO_3, ions of lanthanum, cobalt, and platinum are evenly mixed at the atomic level and confined within the nanocrystallite. In the reduction process, platinum ions were reduced and migrated onto the surface of the nanocrystallite, and the platinum should be highly dispersed owing to the even mixing of the platinum ions in the precursor. When x = 0.05 or lower, the highest dispersion of Pt could be achieved. The highly dispersed Pt is stable, because of the strong interaction between Pt atoms and the support. The catalysts were characterized by BET surface area, temperature-programmed reduction, X-ray diff raction, transmission electron microscopy, CO temperatureprogrammed desorption, and turnover frequency. Compared with general precious metal Pt catalysts, the LaCo_(0.95)Pt_(0.05)O _3/SiO_2 catalyst exhibited better activity for CO oxidation, and it maintained stability at a high temperature of 400 ℃ for 250h with complete CO conversion.

Clinical and molecular research of neuroacanthocytosis

Neuroacanthocytosis is an autosomal recessive or dominant inherited disease characterized by widespread, non-specific nervous system symptoms, or spiculated ＂acanthocytic＂ red blood cells. The clinical manifestations typically involve chorea and dystonia, or a range of other movement disorders. Psychiatric and cognitive symptoms may also be present. The two core neuroacanthocytosis syndromes, in which acanthocytosis is atypical, are autosomal recessive chorea-acanthocytosis and X-linked McLeod syndrome. Acanthocytes are found in a smaller proportion of patients with Huntington＇s disease-like 2 and pantothenate kinase-associated neurodegeneration. Because the clinical manifestations are diverse and complicated, in this review we present features of inheritance, age of onset, neuroimaging and laboratory findings, as well as the spectrum of central and peripheral neurological abnormalities and extraneuronal involvement to help distinguish the four specific syndromes.

Role of 5-hydroxytryptamine expression in cerebellar Purkinje cells in obstructive sleep apnea syndrome

In the present study, electrical stimulation to the rat insular cortex induced apnea or respiratory disturbance, reduced amplitude of genioglossal electromyogram, and decreased electromyogram integrals. In addition, arterial blood gas analysis showed arterial blood acidosis, reduced pH values, increased alkali reserve negative values, decreased peripheral blood 5-hydroxytryptamine content, and increased 5-hydroxytryptamine expression in cerebellar Purkinje cells. Following lidocaine injection to block the habenular nucleus, abnormalities in breath, genioglossal electromyogram, and blood gas values disappeared, and peripheral blood 5-hydroxytryptamine content returned to levels prior to electric stimulation. However, 5-hydroxytryptamine expression in cerebellar Purkinje cells remained high. The results suggested that 5-hydroxytryptamine expression in Purkinje cells did not correlate with ventilation function involving insular cortex and habenular nucleus.

A comparison of H^+-restacked nanosheets and nanoscrolls derived from K_4Nb_6O_(17) for visible-light degradation of dyes

H＋-restacked nanosheets and nanoscrolls peeled from K4Nb6O17 display different structures and surface characters. The two restacked samples with increased surface areas have an amazing visible-light response for the photodegradation of dyes, which is superior to commercial TiO2 （P25） and Nb205. By comparison, H＋/nanosheets have a relatively faster photodegradation rate originated from large and smooth basal plane. The work reveals that dye adsorbed on the unfolded nanosheets can effectively harvest sunlight. Due to facile preparation, low-cost and high photocatalytic efficiency, H＋/nanosheets and H＋/nanoscrolls might be used for the visible light-driven degradation of organic dyes as a substitute for TiO2 in industry.

Inactivation of FOXO1 induces T follicular cell polarization and involves angioimmunoblastic T cell lymphoma

Objective:Angioimmunoblastic T cell lymphoma(AITL)is an aggressive form of non-Hodgkin lymphoma derived from mature T cells.However,the underlying pathogenesis of AITL remains unresolved.We aimed to explore the role of FOXO1-mediated signaling in the tumorigenesis and progression of AITL.Methods:FOXO1 expression was assessed using immunohistochemistry on a total of 46 AITL tissue samples.Retroviruses encoding FOXO1 shRNA were used to knockdown FOXO1 expression in CD4^+T cells.Flow cytometric assays analyzed the proliferation and survival of FOXO1 knockdown CD4^+T cells.Furthermore,we performed adoptive T-cell transfer experiments to identify whether inactivation of FOXO1 induced neoplastic follicular-helper T(Tfh)cell polarization and function.Results:Patients with low FOXO1 protein levels were prone to have an advanced tumor stage(P=0.049),higher ECOG ps(P=0.024),the presence of bone marrow invasion(P=0.000),and higher IPI(P=0.035).Additionally,the survival rates of patients in the FOXO1 high-expression group were significantly better than those in the FOXO1 low-expression group(χ^2=5.346,P=0.021).We also observed that inactivation of FOXO1 increased CD4^+T cell proliferation and altered the survival and cell-cycle progression of CD4^+T cells.Finally,we confirmed that inactivation of FOXO1 induces Tfh cell programing and function.Conclusions:Inactivation of FOXO1 in AITL plays a key role in the tumorigenesis and progression of AITL.We propose that FOXO1 expression could be a useful prognostic marker in AITL patients to predict poor survival,and to design appropriate therapeutic strategies.

Recurrent ascites due to spontaneous intraperitoneal bladder rupture after pelvic radiation therapy for cervical cancer

Radiation cystitis is one of the major complications following radiotherapy for cervical cancer. However, spontaneous intraperitoneal bladder rupture as a result of radiation cystitis following radiotherapy for cervical cancer is extremely rare. Case presentation: We report a 52-year-old patient who received radiation therapy for cervical cancer 15 years prior to presentation. Eight years prior to presentation, she developed recurrent abdominal distension, oliguria, and ascites. Following ascites drainage and supportive treatment, all symptoms were relieved. However, all symptoms subsequently recurred every few months. The patient underwent exploratory laparotomy twice. The first exploratory laparotomy in July 2015 found no specific abnormalities. The second exploratory laparotomy in November 2016 found an intraperitoneal bladder rupture, and the patient underwent surgical repair. The ascites subsequently resolved. Conclusion: The occurrence of spontaneous intraperitoneal bladder rupture after radiation therapy for cervical cancer is rare. The prognosis is good when diagnosis and treatment are prompt.

Postoperative sequential chemotherapy and radiotherapy for locally advanced gastric cancer

Objective The aim of the study was to evaluate the role of postoperative sequential chemotherapy and radiotherapy in patients with locally advanced gastric cancer.Methods From January 2003 to December 2010, 146 gastric cancer patients at our institution(Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China) received postoperative sequential chemotherapy and radiotherapy after radical surgery. Radiotherapy was administered as a dose of 4500 cGy in 25 fractions. For patients with positive margins, the dose was raised to 5040 cGy in 28 fractions. Three cycles of m FOLFOX or PF(cisplatin, 5-fluorouracil) chemotherapy regimen were applied before and after radiotherapy. Three-and 5-year survival rates were analyzed; any adverse effects with respect to hematology, hepatic and renal function, or the gastrointestinal tract that occurred during the treatment were evaluated.Results This cohort consisted of non-metastatic patients: 104 men and 42 women with a median age of 51.0 years. The full course of sequential chemotherapy and radiotherapy(4500–5040 cGy) was completed by 129 patients(88.4%). Seventeen regional relapses(9.8%) and 46 distant relapses(23.8%) were recorded. Fifty patients(34.2%) died during follow-up. The 3-and 5-year overall survival rates(OS) were 60% and 54%, and disease-free survival rates(DFS) were 53% and 47%, respectively. There were no significant differences in survival rate with respect to age, sex, histopathology, N stage, site of the tumor, or margin status. Multivariate analysis showed that only the depth of tumor invasion(T stage) was an independent prognostic factor for OS(P = 0.009) and DFS(P = 0.006). The rates of grades 3 and 4 neutropenia and vomiting were 9.6% and 3.4%, respectively, during the treatment.Conclusion Postoperative sequential chemotherapy with an m FOLFOX or PF regimen and radiotherapy were found to be an effective means of treating advanced gastric cancer patients with T3–T4 disease. The adverse effects of this treatment were tolerable.

Novel Pt-Ni Bimetallic Catalysts Pt(Ni)-LaFeO_3/SiO_2 via Lattice Atomic-Confined Reduction for Highly Efficient Isobutane Dehydrogenation

In this study, a series of novel Pt-Ni bimetallic catalysts supported on LaFeO_3/SiO_2 with different amounts of Ni were prepared by the lattice atomic-confined reduction of LaFe_(1-x)(Ni, Pt)_xO_3/SiO_2 perovskite precursors and applied in isobutane dehydrogenation to isobutene reaction. The catalysts were characterized by X-ray diffraction, H_2-temperature-programmed reduction, Brunauer-Emmett-Teller analysis, transmission electron microscopy, energy dispersive X-ray, CO chemisorption, X-ray photoelectron spectroscopy, and thermogravimetric analysis. The as-synthesized Pt-Ni bimetallic catalysts possessed smaller most probable particle size with tunable Pt-Ni interaction, depending on the Ni content. The catalyst with Ni content of 3.0 wt% showed excellent activity and stability(the isobutane conversion and isobutene selectivity remained at about 38% and 92%, respectively, after 310 min) for the isobutane dehydrogenation reaction. It also provided approximately six times turnover frequency of the catalyst without Ni. The excellent activity and stability of the 3.0 wt% Ni-containing catalyst can be attributed to its small metal nanoparticles with high dispersion and suitable Pt-Ni interaction. Moreover, the Pt(Ni)-LaFeO_3/SiO_2 catalyst with Ni content of 3.0 wt% had been run for more than 35 h without obvious loss of activity,indicating its long-term stability, and the decrease in the Pt-Ni interaction that accompanied the formation of the FeNi alloy phase was thought to be responsible for the slight decrease in activity.

伊立替康为基础的化疗方案治疗转移性结直肠癌的疗效与常见毒副反应的相关性研究(英文)

Objective:The aim of our study was to investigate if common toxicities are correlated to objective response rate(ORR) in metastatic colorectal cancer(mCRC) patients treated by irinotecan based regimens.Methods:Univariate and multivariate logistic regression analyses were performed to evaluate correlations between common toxicities and binary ORR in 106 mCRC patients from a prospective cohort treated with irinotecan based regimens.Results:The most frequent severe toxicities(Grade 3/4) were as follows:neutropenia(27.4%),diarrhea(16.9%),leucopenia(12.6%),vomiting(3.2%) and thrombocytopenia(2.1%).Thrombocytosis was observed in 25(26.3%) patients.ORR was 25.3%.Thrombocytopenia(P = 0.014),line of chemotherapy(P = 0.028) and thrombocytosis(P = 0.033) were correlated with ORR in univariate analysis.In multivariate analysis,thrombocytopenia(odds ratio [OR] = 8.600,95% confidence interval [CI] = 1.705-43.385,P = 0.009) and first line chemotherapy(OR = 5.155,95% CI = 1.153-23.256,P = 0.032) positively related to ORR.Conclusion:Thrombocytopenia may be an indicator of ORR in mCRC patients treated by irinotecan plus 5-fluorouracil/capecitabine.Evidence is not strong enough to prove that irinotecan based regimens-induced diarrhea,leucopenia,neutropenia or vomiting is associated with ORR.

Erratum to Inactivation of FOXO1 induces T follicular cell polarization and involves angioimmunoblastic T cell lymphoma

In the published article1,an error appeared in Acknowledgments on page 753.We omitted Natural Science Foundation of Guangdong Province from Acknowledgments,and we updated it as below.We apologize for the errors and for any confusion it may have caused.

10 Gb/s classical secure key distribution based on temporal steganography and private chaotic phase scrambling

Secure distribution of high-speed digital encryption/decryption keys over a classical fiber channel is strongly pursued for realizing perfect secrecy communication systems.However,it is still challenging to achieve a secret key rate in the order of tens of gigabits per second to be comparable with the bit rate of commercial fiber-optic systems.In this paper,we propose and experimentally demonstrate a novel solution for high-speed secure key distribution based on temporal steganography and private chaotic phase scrambling in the classical physical layer.The encryption key is temporally concealed into the background noise in the time domain and randomly phase scrambled bit-by-bit by a private chaotic signal,which provides two layers of enhanced security to guarantee the privacy of key distribution while providing a high secret key rate.We experimentally achieved a record classical secret key rate of 10 Gb/s with a bit error rate lower than the hard-decision forward error correction(HD-FEC)over a 40 km standard single mode fiber.The proposed solution holds great promise for achieving high-speed key distribution in the classical fiber channel by combining steganographic transmission and chaotic scrambling.