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The Industrial Internet has grown rapidly in recent years, and attacks against the Industrial Internet have also increased. When compared with the traditional Internet, the industrial Internet has a more complex network structure, and the traditional graph neural network attack behavior detection model cannot well adapt to the complex network environment. To make the model better adapt to the complex network environment, this paper proposes the E-minBatch GraphSAG model. First, the application layer source port and source IP address is used as source nodes, the application layer target port and target IP address are used as target nodes, and the remaining traffic information is used as edge information to complete the construction of the graph structure data, and then the constructed graph structure data is presampled to select the edge information that needs to be aggregated next, followed by using the AGG aggregation function to aggregate the information in the domain generated by the presampling process. Finally, the information of two adjacent nodes is aggregated as edge information to classify the edges. Increase the number of IP addresses in the UNSW-NB15 dataset, and then use it for model training and testing. The experimental results show that the accuracy of the model reaches 99.49% in a relatively complex network environment. In this paper, the E-minBatch GraphSAG model is presented in an attempt to solve the problem of attack detection in the complex industrial Internet environment.

For a static and spherically symmetric black hole, a photon sphere is composed of circular null geodesics of fixed radius, and plays an important role in observing the black hole. Recently, in an Einstein-Maxwell-scalar model with a non-minimal coupling between the scalar and electromagnetic fields, a class of hairy black holes has been found to possess two unstable and one stable circular null geodesics on the equatorial plane, corresponding to three photon spheres outside the event horizon. In this paper, we study quasinormal modes of the scalar field, which are associated with these circular null geodesics, in the hairy black hole spacetime. In the eikonal regime with $l\gg1$, the real part of the quasinormal modes is determined by the angular velocity of the corresponding circular geodesics. The imaginary part of the quasinormal modes associated with the unstable circular null geodesics encodes the information about the Lyapunov exponent of the corresponding circular geodesics. Interestingly, we find long-lived and sub-long-lived modes, which are associated with the stable and one of the unstable circular null geodesics, respectively. Due to tunneling through potential barriers, the damping times of the long-lived and sub-long-lived modes can be exponentially and logarithmically large in terms of $l$, respectively., Comment: 25 pages, 4 figures, 1 table, references added

Gangqiang Guo,1,&ast; Huijing Wang,2,&ast; Xinya Tong,1,&ast; Lele Ye,1 Xinyu Shi,1 Su Fang,1 Ya Hu,3 Fei Han,2 Chaosheng Chen,3 Ning Ding,1 Bofeng Su,3 Xiangyang Xue,1 Huidi Zhang3 1Wenzhou Collaborative Innovation Center of Gastrointestinal Cancer in Basic Research & Precision Medicine, Wenzhou Key Laboratory of Cancer-Related Pathogens & Immunity, Department of Microbiology and Immunology, Institute of Molecular Virology and Immunology, Institute of Tropical Medicine, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, 325035, People’s Republic of China; 2Kidney Disease Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310058, People’s Republic of China; 3Department of Nephrology, First Affiliated Hospital, Wenzhou Medical University, Wenzhou, 325000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bofeng Su; Huidi ZhangDepartment of Nephrology, First Affiliated Hospital, Wenzhou Medical University, Wenzhou, 325000, People’s Republic of China, Email 24449681@qq.com; hd_zhang@163.comObjective: Enhancer RNAs (eRNAs), a class of non-coding RNAs, play indispensable roles in regulating target gene transcription and maintaining cell identity in cooperation with promoters. In this study, we investigated the transcriptional landscape and potential functions of eRNAs in peripheral blood mononuclear cells (PBMCs) from patients with systemic lupus erythematosus (SLE).Methods: PBMCs from five patients with stable SLE, five patients with active SLE, and ten healthy individuals (HCs) were subjected to RNA-sequencing. Putative regulators, differential expression, and pathways were analyzed. eRNAs that were significantly upregulated were first validated by RT-qPCR in 12 samples. Then, candidate eRNAs were confirmed in a validation cohort of 45 samples. We conducted comprehensive pathway analyses to explore the correlations between the candidate eRNAs and SLE pathology.Results: By analyzing eRNA transcript data from PBMCs from SLE patients and HCs, we identified various eRNAs and functional super-enhancers potentially related with SLE. The SLE-specificity of eRNAs seemed to be largely driven by SLE-specific transcription factors (TFs). A Venn diagram of eRNAs differentially expressed in stable, active, and total SLE vs HCs revealed that 13 and 23 eRNAs were commonly upregulated and downregulated, respectively, in patients with stable SLE and those with active SLE. The commonly upregulated eRNAs participate in regulating SLE-related pathways. Only eRNA TCONS_00034326 was significantly (P < 0.05) upregulated in PBMCs of patients with SLE when compared with those of HCs as indicated by RT-qPCR. The area under the receiver-operating curve of TCONS_00034326 for distinguishing SLE patients from HCs was 0.691. Through its putative SLE-related master TF, TCONS_00034326 is involved in multiple SLE-relevant signaling pathways, especially tumor necrosis factor signaling.Conclusion: This study unraveled the transcriptional landscape of eRNAs, eRNA-related TFs, and super-enhancers in PBMCs from SLE patients and HCs. We identified a panel of SLE-relevant eRNAs, providing potential targets in SLE pathogenesis.Keywords: enhancer RNA, eRNA, systemic lupus erythematosus, SLE, PBMCs, transcription factors, TFs, super-enhancer

Weida Fu,&ast; Shurong Zheng,&ast; Jieyu Zhou, Kangkang Lu, Yiqiao Lu, Guilong Guo Department of Breast Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guilong Guo, Department of Breast Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China, Tel/Fax +86-13867709361, Email guoguilong@sina.comAbstract: Male breast carcinoma metastatic to the choroid is very rare and often related to poor prognosis. Herein, we report the findings in a Chinese male breast cancer patient who developed choroidal metastasis, and give opinions on systemic treatments. A 45-year-old Chinese male represented with difficulty breathing and visual impairment in the left eye 6 years after his breast cancer surgery and postoperative adjuvant treatment. PET/CT revealed multi-organs metastasis of the patient. The IHC indicated the lung lesion to be originated from the breast (ER+/PR+/HER2-). Eye examination provided evidence for breast cancer choroidal metastasis. Two cycles of TX (docetaxel + capecitabine) followed by two courses of GP (gemcitabine + cis-platinum) were applied as salvage chemotherapy. Metastases in his lung and bone remained stable. As for choroidal metastasis, a regimen of CDK4/6 inhibitor (Palbociclib) plus fulvestrant was recommended to the patient, which led to a good response. Notably, CDK4/6 inhibitor combined with endocrine therapy may be considered as an effective treatment for hormonal receptor-positive breast cancer patients with choroidal metastasis. We recommend that eye examination should not be neglected in breast cancer patients.Keywords: choroidal metastasis, male breast cancer, systemic therapy, CDK4/6 inhibitor, case report

Longbing Yang,1 Zhuqing Tian,1 Luoxiong Zhou,1,2 Lijuan Zhu,1 Chaoqin Sun,1 Mingjiao Huang,1 Jian Peng,1,3 Guo Guo1,3,4 1School of Basic Medical Sciences, The Key and Characteristic Laboratory of Modern Pathogen Biology, Guizhou Medical University, Guiyang, 550025, People’s Republic of China; 2School of Public Health, Guizhou Medical University, Guiyang, 550025, People’s Republic of China; 3Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Guizhou Medical University, Guiyang, 550025, People’s Republic of China; 4Translational Medicine Research Center, Guizhou Medical University, Guiyang, 550025, People’s Republic of ChinaCorrespondence: Guo GuoBuilding Wuben, School of Basic Medical Sciences, Guizhou Medical University, College Town, Gui’an New District, Guiyang, 550025, People’s Republic of China, Tel/fax +86 851 882 59268, Email guoguojsc@163.comBackground: Cryptococcus neoformans is a common human fungal pathogen in immunocompromised people, as well as a prevalent cause of meningitis in HIV-infected individuals. With the emergence of clinical fungal resistance and the shortage of antifungal drugs, it is urgent to discover novel antifungal agents. AMP-17, a novel antimicrobial peptide from Musca domestica, has antifungal activity against C. neoformans. However, its antifungal and anti-biofilm activities remain unclear. Thus, this study aimed to evaluate the antifungal activity of AMP-17 against planktonic cells and biofilms of C. neoformans.Methods: The minimum inhibitory concentration (MIC), the biofilm inhibitory and eradicating concentration (BIC and BEC) were determined by the broth microdilution assay or the 2, 3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) reduction assay, respectively. The inhibitory and killing activities of AMP-17 against C. neoformans were investigated through the time-inhibition/killing kinetic curves. The potential antifungal mechanism of AMP-17 was detected by flow cytometry, scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM). The efficiency of AMP-17 against biofilm formation or preformed biofilm was evaluated by crystal violet staining and XTT reduction assays. The morphology of pre-biofilms was tested by optical microscopy (OM) and CLSM.Results: AMP-17 exhibited in vitro antifungal activity against C. neoformans planktonic cells and biofilms, with MICs of 4∼ 16 μg/ml, BIC80 and BEC80 of 16∼ 32 μg/ml, 64∼ 128 μg/ml, respectively. In addition, the 2× and 4× MIC of AMP-17 exhibited similar inhibition levels compared to the 2× and 4× MIC of the clinical drugs FLC and AMB in C. neoformans growth. Moreover, the time-kill results showed that AMP-17 (8× MIC) did not significantly eliminate colony forming units (CFU) after 6 h of treatment; however, there was 2.9-log reduction in CFU of C. neoformans. Furthermore, increasing of the permeability of the fungal cell membrane was observed with the treatment of AMP-17, since the vast change as fungal leakage and cell membrane disruption. However, the DNA binding assay of AMP-17 indicated that the peptide did not target DNA. Besides, AMP-17 was superior in inhibiting and eradicating biofilms of C. neoformans compared with FLC.Conclusion: AMP-17 exhibited potential in vitro antifungal activity against the planktonic cells and biofilms of C. neoformans, and it may disrupt fungal cell membranes through multi-target interactions, which provides a promising therapeutic strategy and experimental basis for Cryptococcus-associated infections.Keywords: antimicrobial peptides, AMP-17, Cryptococcus neoformans, antifungal mechanism, anti-biofilm

Giant anomalous Hall effect (AHE) and magneto-optical activity can emerge in magnets with topologically non-trivial degeneracies. However, identifying the specific band structure features like Weyl points, nodal lines or planes which generate the anomalous response is a challenging issue. Since the low-energy interband transitions can govern the static AHE, we addressed this question in the prototypical magnetic Weyl semimetal Co$_3$Sn$_2$S$_2$ also hosting nodal lines by broadband polarized reflectivity and magneto-optical Kerr effect spectroscopy with a focus on the far-infrared range. In the linear dichroism spectrum we observe a strong resonance at 40\,meV, which also shows up in the optical Hall conductivity spectrum and primarily determines the static AHE, thus, confirms its intrinsic origin. Our material-specific theory reproduces the experimental data remarkably well and shows that strongly tilted nodal line segments around the Fermi energy generate the resonance. While the Weyl points only give vanishing contributions, these segments of the nodal lines gapped by the spin-orbit coupling dominate the low-energy optical response.

CD3+CD56+ natural killer T (NKT)-like cells are a group of CD3+ T cells sharing characteristics of NK and T cells and constitute a major component of host antitumor immune response in human cancer. However, the nature, function and clinical relevance of CD3+CD56+ NKT-like cells in human gastric cancer (GC) remain unclear. In this study, we showed that the frequencies of CD3+CD56+NKT-like cells in GC tumors were significantly decreased and low levels of tumor-infiltrating CD3+CD56+ NKT-like cells were positively correlated with poor survival and disease progression. Most CD3+CD56+NKT-like cells in GC tumors were CD45RA-CD27+/- central/effectormemory cells with decreased activity and lower expression levels of CD69, NKG2D and DNAM-1 than those in non-tumor tissues. We further observed that tumor-infiltrating CD3+CD56+ NKT-like cells had impaired effector function as shown by decreased IFN-γ, TNF-α, granzyme B and Ki-67 expression. Moreover, in vitro studies showed that soluble factors released from GC tumors could induce the functional impairment of CD3+CD56+ NKT-like cells. Collectively, our data indicate that decreased tumorinfiltrating CD3+CD56+ NKT-like cells with impaired effector function are associated with tumor progression and poor survival of GC patients, which may contribute to immune escape of GC.

Zhenjun Xu,1,&ast; Kai Zhong,2,&ast; Guanjun Guo,1,&ast; Can Xu,1 Zhizhao Song,1 Dongjin Wang,1 Jun Pan1 1Department of Thoracic and Cardiovascular Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, 210008, People’s Republic of China; 2Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, 210008, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jun Pan; Zhenjun XuDepartment of Thoracic and Cardiovascular Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, 321 Zhongshan Road, Nanjing, 210008, People’s Republic of ChinaTel +86 25 68182222-60721Fax +86 25 83105117Email pj791028@163.com; xzj881225@163.comBackground: Aortic dissection (AD) is a threatening and catastrophic vascular disease with high mortality rate and limited therapeutic strategies. There is emerging evidence showing that circular RNAs play crucial role in regulating various cardiovascular diseases. However, the biological functions and molecular mechanisms of circRNAs in AD still remains elusive. The purpose of this study was to illustrate the potential functional roles and mechanisms of hsa_circ_TGFBR2 in vitro and in vivo.Methods: The vascular smooth muscle cells (VSMCs) and AD-VSMCs were isolated from normal aorta and AD tissues. The expression of circ_TGFBR2, miR-29a and KLF4 were detected by realtime polymerase chain reaction (RT-PCR) and fluorescence in situ hybridization (FISH). Cell proliferation was assessed by CCK-8 assay, colony formation and EDU assay. Cell migration was evaluated through transwell assay. Dual-luciferase reporter assay and RNA pulldown were performed to identify the interaction between circ_TGFBR2 and miR-29a or between miR-29a and KLF4. The wild-type sequence of circ_TGFBR2 or KLF4 were cloned into the luciferase reporter plasmid, and the activity was measured using dual-luciferase reporter assay system. And for RNA pulldown, the relative RNA enrichment of circ_TGFBR2 and miR-29a were confirmed using RT-PCR. Western Blot measured the expression of phenotype switch-related proteins. AD rat model induced by β-aminopropionitrile monofumarate (BAPN) was used to verify the role and mechanism of circ_TGFBR2.Results: Circ_TGFBR2 inhibited cell proliferation and migration of AD-VSMCs cells. Overexpression of circ_TGFBR2 promoted the expression of contractile markers (α-SMA, SM22α) and inhibited the expression of synthetic markers (MGP, OPN) in AD-VSMCs cells. Circ_TGFBR2 served as a sponge for miR-29a targeting KLF4. MiR-29a mimics rescued biological roles induced by circ_TGFBR2 overexpression. The in vivo experiments revealed that overexpression of TGFBR2 suppressed the progression of AD and increased the expression of contractile markers while inhibited the expression of synthetic markers.Conclusion: Our study revealed that circ_TGFBR2 regulated VSMCs phenotype switch and suppressed the progression of AD.Keywords: aortic dissection, circ_TGFBR2, miR-29a, KLF4, vascular smooth muscle cells

Donglu Zhao, Qi Xing, Hang Song, Yan Zhao, Guiying Guo No. 4 Ward of Hematology Department, Institute of Hematology and Oncology, Harbin First Hospital, Harbin 150010, Heilongjiang Province, People’s Republic of ChinaCorrespondence: Donglu ZhaoNo. 4 Ward of Hematology Department, Institute of Hematology and Oncology, Harbin First Hospital, No. 149 Diduan Street, Daoli District, Harbin 150010, Heilongjiang Province, People’s Republic of ChinaTel +86-13936254716Email zhaodonglu123@163.comBackground: Long noncoding RNA LINC00265 or miR-4500 is involved in the pathogenesis of many cancers. However, their functions in acute lymphoblastic leukemia (ALL) remain unknown. In this study, we investigated how LINC00265 and miR-4500 regulate the malignant characteristics of ALL.Methods: Real-time PCR was used in examining the expression of LINC00265 in ALL cell lines and blood of patients with ALL. Cell proliferation, cell migration, and xenograft tumor assays were performed to verify the function of LINC00265 subjected to overexpressing and silencing experiments. The ceRNA mechanism with LINC00265/miR-4500/STAT3 was investigated through luciferase and RNA pull-down assays. Finally, the function of the LINC00265/miR-4500/STAT3 axis subjected to overexpressing and silencing assays was determined through cell proliferation, cell migration, and xenograft tumor assays.Results: LINC00265 was highly expressed in ALL cell lines and blood of patients with ALL and facilitated the proliferation, migration, invasion, and growth of xenograft tumors of ALL cells. The silencing of LINC00265 expression with LINC00265 siRNA significantly inhibited the malignancy of the ALL cells. RNA pull-down and luciferase assays demonstrated that LINC00265 competitively targeted miR-4500 and enhanced STAT3 expression. Furthermore, miR-4500 inhibitors or overexpressed LINC00265 up-regulated STAT3 expression, and miR-4500 mimics or STAT3 shRNAs eliminated the LINC00265-induced malignancy of the ALL cells.Conclusion: Mechanistically, LncRNA LINC00265 can competitively interact with miR-4500 and thereby up-regulates STAT3 signaling and enhances the malignancy of tumors.Keywords: acute lymphoblastic leukemia, LINC00265, miR-4500, cell proliferation

Gengxuan Guo,1 Qunxi Gong,2 Sipan Li,1 Xuedong Liang1 1School of Business, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 2The Economy and Enterprise Development Institute, Sichuan University, Chengdu, Sichuan, People’s Republic of ChinaCorrespondence: Xuedong Liang Email liangxuedong@scu.edu.cnPurpose: Previous studies on negative workplace gossip have neglected the role of gossip receivers. The current study aims to explore the interpersonal interaction mechanism between gossip receivers and communicators. Drawing on social information processing theory, we propose a theoretical model for the relationships between negative workplace gossip, psychological safety, ostracism, and coworker-exchanges.Participants and Methods: Multi-wave data of 386 employees from eight service-oriented companies in China supported the proposed framework. Critical incident techniques and time-lag method were used for data collection. SPSS and Mplus were employed for hypothesis test.Results: The empirical results indicated that negative workplace gossip was positively related to gossip receivers’ ostracism (sender-oriented), among which receivers’ psychological safety (sender-oriented) played a mediating role. In addition, the coworker exchange relationship moderated the relationship between negative workplace gossip and ostracism, and the psychological safety of interviewees also plays a mediating role. Specifically, the effect of negative workplace gossip on psychological safety and the mediating effect of psychological safety were stronger when the coworker exchange relationship was higher.Conclusion: Drawing on social information processing theory, the present study constructed a process model of the recipients’ sender-oriented ostracism reactions to negative workplace gossip, which helps explain the cognitive psychological mechanism and the boundary conditions of the above “perception-interpretation-behavior” social information process model. The above framework contributes to both theory and practice.Keywords: negative workplace gossip, psychological safety, ostracism, coworker exchange relationship

Background Accurate and up-to-date assessment of demographic metrics is crucial for understanding a wide range of social, economic, and public health issues that affect populations worldwide. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 produced updated and comprehensive demographic assessments of the key indicators of fertility, mortality, migration, and population for 204 countries and territories and selected subnational locations from 1950 to 2019. Methods 8078 country-years of vital registration and sample registration data, 938 surveys, 349 censuses, and 238 other sources were identified and used to estimate age-specific fertility. Spatiotemporal Gaussian process regression (ST-GPR) was used to generate age-specific fertility rates for 5-year age groups between ages 15 and 49 years. With extensions to age groups 10-14 and 50-54 years, the total fertility rate (TFR) was then aggregated using the estimated age-specific fertility between ages 10 and 54 years. 7417 sources were used for under-5 mortality estimation and 7355 for adult mortality. ST-GPR was used to synthesise data sources after correction for known biases. Adult mortality was measured as the probability of death between ages 15 and 60 years based on vital registration, sample registration, and sibling histories, and was also estimated using ST-GPR. HIV-free life tables were then estimated using estimates of under-5 and adult mortality rates using a relational model life table system created for GBD, which closely tracks observed age-specific mortality rates from complete vital registration when available. Independent estimates of HIV-specific mortality generated by an epidemiological analysis of HIV prevalence surveys and antenatal clinic serosurveillance and other sources were incorporated into the estimates in countries with large epidemics. Annual and single-year age estimates of net migration and population for each country and territory were generated using a Bayesian hierarchical cohort component model that analysed estimated age-specific fertility and mortality rates along with 1250 censuses and 747 population registry years. We classified location-years into seven categories on the basis of the natural rate of increase in population (calculated by subtracting the crude death rate from the crude birth rate) and the net migration rate. We computed healthy life expectancy (HALE) using years lived with disability (YLDs) per capita, life tables, and standard demographic methods. Uncertainty was propagated throughout the demographic estimation process, including fertility, mortality, and population, with 1000 draw-level estimates produced for each metric. Findings The global TFR decreased from 2.72 (95% uncertainty interval [UI] 2.66-2.79) in 2000 to 2.31 (2.17-2.46) in 2019. Global annual livebirths increased from 134.5 million (131.5-137.8) in 2000 to a peak of 139.6 million (133.0-146.9) in 2016. Global livebirths then declined to 135.3 million (127.2-144.1) in 2019. Of the 204 countries and territories included in this study, in 2019, 102 had a TFR lower than 2.1, which is considered a good approximation of replacement-level fertility. All countries in sub-Saharan Africa had TFRs above replacement level in 2019 and accounted for 27.1% (95% UI 26.4-27.8) of global livebirths. Global life expectancy at birth increased from 67.2 years (95% UI 66.8-67.6) in 2000 to 73.5 years (72.8-74.3) in 2019. The total number of deaths increased from 50.7 million (49.5-51.9) in 2000 to 56.5 million (53.7-59.2) in 2019. Under-5 deaths declined from 9.6 million (9.1-10.3) in 2000 to 5.0 million (4.3-6.0) in 2019. Global population increased by 25.7%, from 6.2 billion (6.0-6.3) in 2000 to 7.7 billion (7.5-8.0) in 2019. In 2019, 34 countries had negative natural rates of increase; in 17 of these, the population declined because immigration was not sufficient to counteract the negative rate of decline. Globally, HALE increased from 58.6 years (56.1-60.8) in 2000 to 63.5 years (60.8-66.1) in 2019. HALE increased in 202 of 204 countries and territories between 2000 and 2019. Interpretation Over the past 20 years, fertility rates have been dropping steadily and life expectancy has been increasing, with few exceptions. Much of this change follows historical patterns linking social and economic determinants, such as those captured by the GBD Socio-demographic Index, with demographic outcomes. More recently, several countries have experienced a combination of low fertility and stagnating improvement in mortality rates, pushing more populations into the late stages of the demographic transition. Tracking demographic change and the emergence of new patterns will be essential for global health monitoring. Copyright (C) 2020 The Author(s). Published by Elsevier Ltd.

Huiling Ma,1,2 Xinyu Zhao,1 Longbing Yang,1 Peipei Su,1 Ping Fu,1,3 Jian Peng,1,3 Na Yang,4 Guo Guo1,3,4 1Key and Characteristic Laboratory of Modern Pathogen Biology, School of Basic Medical Sciences, Guizhou Medical University, Guiyang 550025, People’s Republic of China; 2Department of Pathogen Biology and Immunology, School of Basic Medical Sciences, Sanquan College of Xinxiang Medical University, Xinxiang 453003, People’s Republic of China; 3Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Guizhou Medical University, Guiyang 550025, People’s Republic of China; 4School of Food Science, Guizhou Medical University, Guiyang 550025, People’s Republic of ChinaCorrespondence: Guo Guo Tel +86 13765024379Email guoguojsc@163.comBackground: Candida albicans is associated with high mortality among immunocompromised patients. Resistance to and toxic side effects of antifungal drugs require the development of alternative antifungal agents. AMP-17 is a novel antimicrobial peptide derived from Musca domestica that exerts excellent antifungal effects against the Candida species. In this article, we discuss the potential mechanism of AMP-17 against C. albicans from the perspective of affecting the latter’s cell external structure.Methods: Recombinant AMP-17 was prepared by prokaryotic expression system, and its anti-C. albicans activity was detected by microdilution method. Microscopy and scanning electron microscopy were used to examine morphological changes in C. albicans. Cell wall-specific staining method was used to detect the change of cell wall integrity of C. albicans after AMP-17 treatment. AMP-17-induced damage to the C. albicans cell membrane was analyzed by fluorescent probes and glycerol assay kit. The expression of genes related to fungal cell wall and cell-membrane synthesis was detected by qRT-PCR.Results: Morphological observations showed that the growth of C. albicans was significantly inhibited in AMP-17-treated cells; the cells appeared aggregated and dissolved, with severe irregularities in shape. Furthermore, AMP-17 damaged the integrity of C. albicans cell walls. The cell wall integrity rate of AMP-17-treated cells was only 21.7% compared to untreated cells. Moreover, the change of membrane dynamics and permeability suggested that the cell membrane was disrupted by AMP-17 treatment. Genetic analysis showed that after AMP-17 treatment, the cell wall synthesis-related gene FKS2 of C. albicans was up-regulated 3.46-fold, while the cell membrane ergosterol synthesis-related genes ERG1, ERG5, ERG6, and MET6 were down-regulated 5.88-, 17.54-, 13.33-, and 7.14-fold, respectively.Conclusion: AMP-17 treatment disrupted the cell wall integrity and membrane structure of C. albicans and is likely a novel therapeutic option for prevention and control of C. albicans infections.Keywords: AMP-17, C. albicans, cell wall, membrane dynamics and permeability

Di Chuan,* Yuelong Wang,* Rangrang Fan, Liangxue Zhou, Haifeng Chen, Jianguo Xu, Gang Guo State Key Laboratory of Biotherapy and Cancer Center and Department of Neurosurgery, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu 610041, People’s Republic of China*These authors contributed equally to this workCorrespondence: Gang Guo; Liangxue ZhouState Key Laboratory of Biotherapy and Cancer Center, and Department of Neurosurgery, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, No. 17, Block 3, Southern Renmin Road, Chengdu 610041, People’s Republic of ChinaTel +86 28-8516 4063Fax +86 28 85164060Email guogang@scu.edu.cn; liangxue_zhou@126.comBackground: Duraplasty is one of the most critical issues in neurosurgical procedures because the defect of dura matter will cause many complications. Electrospinning can mimic the 3D structure of the natural extracellular matrix whose structure is similar to that of dura matter. Poly(L-lactic acid) (PLLA) has been used to fabricate dura matter substitutes and showed compatibility to dural tissue. However, the mechanical properties of the PLLA substitute cannot match the mechanical properties of the human dura mater.Methods and Results: We prepared stereocomplex nanofiber membranes based on enantiomeric poly(lactic acid) and poly(D-lactic acid)-grafted tetracalcium phosphate via electrospinning. X-ray diffraction results showed the formation of stereocomplex crystallites (SC) in the composite nanofiber membranes. Scanning electron microscope observation images showed that composites nanofibers with higher SC formation can keep its original morphologies after heat treatment, suggesting the heat resistance of composite nanofiber membranes. Differential scanning calorimeter tests confirmed that the melting temperature of composite nanofiber membranes was approximately 222°C, higher than that of PLLA. Tensile testing indicated that the ultimate tensile strength and the elongation break of the stereocomplex nanofiber membranes were close to human dura matter. In vitro cytotoxicity studies proved that the stereocomplex nanofiber membranes were non-toxic. The neuron-like differentiation of marrow stem cells on the stereocomplex nanofiber membranes indicated its neuron compatibility.Conclusion: The stereocomplex nanofiber membranes have the potential to serve as a dura mater substitute.Keywords: poly(lactic acid), dura matter substitute, stereocomplex crystallites, electrospinning

Guangxiu Guo,* Sujuan Dai,* Qing Chen Department of Pathology, The People’s Hospital of Ganzhou, Gannan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Guangxiu GuoDepartment of Pathology, The People’s Hospital of Ganzhou, 18 Meiguan Road, Gannan 341000, People’s Republic of ChinaEmail drguangxiuguo@163.comObjective: Long noncoding RNAs (lncRNAs) are emerging as a class of important biological regulators. lncRNAs participate in diverse biological functions and disease processes, especially those leading to tumorigenesis. In this study, we investigate the role of linc00261 in the pathogenesis of breast cancer.Methods: linc00261 and NME1 expression levels were determined in breast cancer tissue and adjacent normal tissue using qRT-PCR. Cell proliferation and migration were analyzed using MTT and transwell assays, respectively. Epithelial–mesenchymal transition markers were examined via Western blotting assay. RNA pull-down was used to examine the interaction between linc00261 and the NME1 mRNA transcript.Results: linc00261 is expressed in lower levels on breast cancer tissues than in para-carcinoma tissues. Reintroduction of linc00261 can inhibit the migration of breast cancer cells and arrest their proliferation. Additionally, linc00261 knockdown is sufficient to cause breast carcinoma tumorigenesis. We also found that linc00261 interacts with NME1 mRNA, protecting it from degradation. This protection leads to increased cellular levels of NME1, which functions as suppressor of tumor metastasis.Conclusion: Taken together, these data demonstrate detailed mechanistic links between the linc00261/NME1 axis and tumorigenesis and show that linc00261 might serve as a novel therapeutic target.Keywords: linc00261, NME1, breast cancer, E-cadherin, N-cadherin

Yuanyuan Zhang, Yang Hu, Min Li, Jieman Wang, Gengshuo Guo, Fang Li, Boyang Yu, Junping Kou Jiangsu Key Laboratory of TCM Evaluation and Translational Research, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, People’s Republic of ChinaCorrespondence: Boyang Yu; Junping KouJiangsu Key Laboratory of TCM Evaluation and Translational Research, China Pharmaceutical University, Nanjing 211198, People’s Republic of ChinaTel +86 25-86185157Fax +86 25-86185158Email boyangyu59@163.com; junpingkou@cpu.edu.cnIntroduction: Traditional Chinese medicine (TCM) provides unique advantages for treatment of ischemic stroke, an aging-related vascular disease. Shengmai powder (GRS) is composed of three active components, specifically, ginsenoside Rb1, ruscogenin and schisandrin A, at a ratio of 6:0.75:6. The main objective of this study was to evaluate the effects of GRS on blood–brain barrier (BBB) dysfunction under conditions of middle cerebral artery occlusion/reperfusion (MCAO/R).Methods: C57BL/6J mice subjected to MCAO/R were used as a model to assess the protective effects of varying doses of GRS (6.4, 12.8, and 19.2 mg/kg) on BBB dysfunction.Results: GRS reduced cerebral infarct volume and degree of brain tissue damage, improved behavioral scores, decreased water content and BBB permeability, and restored cerebral blood flow. Moreover, GRS promoted expression of zona occludens-1 (ZO-1) and claudin-5 while inhibiting matrix metalloproteinase 2/9 (MMP-2/9) expression and myosin light chain (MLC) phosphorylation. In vitro, GRS (1, 10, and 100 ng/mL) enhanced the viability of bEnd.3 cells subjected to oxygen glucose deprivation/reoxygenation (OGD/R) and decreased sodium fluorescein permeability.Conclusion: Consistent with in vivo findings, ZO-1 and claudin-5 were significantly upregulated by GRS in bEnd.3 cells under OGD/R and MMP-2/9 levels and MLC phosphorylation reduced through the Rho-associated coil-forming protein kinase (ROCK)/cofilin signaling pathway. Based on the collective findings, we propose that the TCM compound, GRS, plays a protective role against I/R-induced BBB dysfunction.Keywords: GRS, ischemic stroke, blood–brain barrier, endothelial, tight junctions, ROCK/cofilin

Xin Duan, Guangcheng Guo, Xinhong Pei, Xinxing Wang, Lin Li, Youyi Xiong, Xinguang Qiu Department of Breast Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of ChinaCorrespondence: Xinguang QiuDepartment of Breast Surgery, The First Affiliated Hospital of Zhengzhou University, No. 1 East Jianshe Road, Zhengzhou, Henan 450000, People’s Republic of ChinaTel +86 371-67967247Email xfcl6782619qiang@163.comBackground: Baicalin is a natural compound from the roots of Scutellaria lateriflora Georgi, which plays anti-cancer role in multiple cancers. However, the exact role and potential underlying mechanism of baicalin in breast cancer (BC) remain poorly understood.Methods: Thirty BC patients were recruited in this study. MCF-10A, MCF-7 and MDA-MB-231 cells were used to investigate the anti-cancer role of baicalin in vitro. Cell viability, migration, invasion and apoptosis were measured by MTT, trans-well and flow cytometry, respectively. The expression levels of microRNA-338-3p (miR-338-3p) and microrchidia family CW-type zinc-finger 4 (MORC4) were measured by quantitative real-time polymerase chain reaction or Western blot. The interaction between miR-338-3p and MORC4 was explored by luciferase reporter assay and RNA immunoprecipitation.Results: We found that Baicalin treatment inhibited cell viability, migration and invasion but promoted apoptosis of BC cells. The expression of miR-338-3p was decreased in BC tissues and cells and miR-338-3p overexpression suppressed cell viability, migration and invasion but induced apoptosis. MiR-338-3p expression was reversed by baicalin exposure and inhibition of miR-338-3p attenuated the role of baicalin in viability, apoptosis, migration and invasion. MORC4 mRNA level was increased in BC tissues and cells, which was decreased by baicalin exposure. MORC4 was a target of miR-338-3p and its overexpression alleviated the effect of miR-338-3p on cell viability, apoptosis, migration and invasion.Conclusion: In conclusion, baicalin suppressed cell viability, migration and invasion but promoted apoptosis in BC cells by regulating miR-338-3p and MORC4, indicating the promising pharmacological value of baicalin in BC treatment.Keywords: breast cancer, baicalin, miR-338-3p, MORC4 &nbsp

On-demand spin orientation with long polarized lifetime and easily detectable signal is an ultimate goal for spintronics. However, there still exists a trade-off between controllability and stability of spin polarization, awaiting a significant breakthrough. Here, we demonstrate switchable optomagnet effects in (Fe$_{1-x}$Zn$_{x}$)$_{2}$Mo$_{3}$O$_{8}$, from which we can obtain tunable magnetization, spanning from -40$\%$ to 40$\%$ of a saturated magnetization that is created from zero magnetization in the antiferromagnetic state without magnetic fields. It is accomplishable via utilizing circularly-polarized laser pulses to excite spin-flip transitions in polar antiferromagnets that have no spin canting, traditionally hard to control without very strong magnetic fields. The spin controllability in (Fe$_{1-x}$Zn$_{x}$)$_{2}$Mo$_{3}$O$_{8}$ originates from its polar structure that breaks the crystal inversion symmetry, allowing distinct on-site $d$-$d$ transitions for selective spin flip. By chemical doping, we exploit the phase competition between antiferromagnetic and ferrimagnetic states to enhance and stabilize the optomagnet effects, which result in long-lived photoinduced Kerr rotations. The present study, creating switchable giant optomagnet effects in polar antiferromagnets, sketches a new blueprint for the function of antiferromagnetic spintronics.

Quasiparticle poisoning, expected to arise during the measurement of the Majorana zero-mode state, poses a fundamental problem for the realization of Majorana-based quantum computation. Parafermions, a natural generalization of Majorana fermions, can encode topological qudits immune to quasiparticle poisoning. While parafermions are expected to emerge in superconducting fractional quantum Hall systems, they are not yet attainable with current technology. To bypass this problem, we employ a photonic quantum simulator to experimentally demonstrate the key components of parafermion-based universal quantum computation. Our contributions in this paper are twofold. First, by manipulating the photonic states, we realize Clifford-operator Berry phases that correspond to braiding statistics of parafermions. Second, we investigate the quantum contextuality in a topological system for the first time by demonstrating the contextuality of parafermion-encoded qudit states. Importantly, we find that the topologically encoded contextuality opens the way to magic state distillation, while both the contextuality and the braiding-induced Clifford gates are resilient against local noise. By introducing contextuality, our photonic quantum simulation provides the first step toward a physically robust methodology for realizing topological quantum computation.

Genuine multipartite entanglement represents the strongest type of entanglement, which is an essential resource for quantum information processing. Standard methods to detect genuine multipartite entanglement, e.g., entanglement witnesses, state tomography, or quantum state verification, require full knowledge of the Hilbert space dimension and precise calibration of measurement devices, which are usually difficult to acquire in an experiment. The most radical way to overcome these problems is to detect entanglement solely based on the Bell-like correlations of measurement outcomes collected in the experiment, namely, device-independently (DI). However, it is difficult to certify genuine entanglement of practical multipartite states in this way, and even more difficult to quantify it, due to the difficulty to identify optimal multipartite Bell inequalities and protocols tolerant to state impurity. In this work, we explore a general and robust DI method which can be applied to various realistic multipartite quantum state in arbitrary finite dimension, while merely relying on bipartite Bell inequalities. Our method allows us both to certify the presence of genuine multipartite entanglement and to quantify it. Several important classes of entangled states are tested with this method, leading to the detection of genuinely entangled states. We also certify genuine multipartite entanglement in weakly-entangled GHZ states, thus showing that the method applies equally well to less standard states.

The precious rare edible fungus Morchella conica is popular worldwide for its rich nutrition, savory flavor, and varieties of bioactive components. Due to its high commercial, nutritional, and medicinal value, it has always been a hot spot. However, the molecular mechanism and endophytic bacterial communities in M. conica were poorly understood. In this study, we sequenced, assembled, and analyzed the genome of M. conica SH. Transcriptome analysis reveals significant differences between the mycelia and fruiting body. As shown in this study, 1,329 and 2,796 genes were specifically expressed in the mycelia and fruiting body, respectively. The Gene Ontology (GO) enrichment showed that RNA polymerase II transcription activity-related genes were enriched in the mycelium-specific gene cluster, and nucleotide binding-related genes were enriched in the fruiting body-specific gene cluster. Further analysis of differentially expressed genes in different development stages resulted in finding two groups with distinct expression patterns. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment displays that glycan degradation and ABC transporters were enriched in the group 1 with low expressed level in the mycelia, while taurine and hypotaurine metabolismand tyrosine metabolism-related genes were significantly enriched in the group 2 with high expressed level in mycelia. Moreover, a dynamic shift of bacterial communities in the developing fruiting body was detected by 16S rRNA sequencing, and co-expression analysis suggested that bacterial communities might play an important role in regulating gene expression. Taken together, our study provided a better understanding of the molecular biology of M. conica SH and direction for future research on artificial cultivation.

Xiaohong Xu,1 Vinothkumar Rajamanickam,1 Sheng Shu,1 Zhoudi Liu,1 Tao Yan,1 Jinxin He,1 Zhiguo Liu,1 Guilong Guo,2 Guang Liang,1 Yi Wang1 1Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, People’s Republic of China; 2Department of Surgical Oncology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, People’s Republic of ChinaCorrespondence: Yi WangChemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, People’s Republic of ChinaTel/Fax +8657785773060Email yi.wang1122@wmu.edu.cnBackground: Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer which is associated with poor patient outcome and lack of targeted therapy. Our laboratory has synthesized a series of indole-2-carboxamide derivatives. Among this series, compound LG25 showed a favorable pharmacological profile against sepsis and inflammatory diseases. In the present study, we investigated the chemotherapeutic potential of LG25 against TNBC utilizing in vitro and in vivo models.Methods: Changes in cell viability, cell cycle phases and apoptosis were analyzed using MTT, clonogenic assay, FACS and Western blotting assays. The anti-cancer effects of LG25 were further determined in a xenograft mouse model.Results: Our findings reveal that LG25 reduced TNBC viability in a dose-dependent manner. Flow cytometric and Western blot analyses showed that LG25 enhances G2/M cell cycle arrest and induced cell apoptosis. In addition, LG25 treatment significantly inhibited Akt/mTOR phosphorylation and nuclear translocation of nuclear factor-κB (NF-κB). These inhibitory activities of LG25 were confirmed in mice implanted MDA-MB-231 TNBC cells.Conclusion: Our studies provide experimental evidence that indole-2-carboxamide derivative LG25 effectively targeted TNBC in preclinical models by inducing cell cycle arrest and apoptosis, through suppressing Akt/mTOR/NF-κB signaling pathway.Keywords: indole analog, triple-negative breast cancer, cell cycle arrest, apoptosis, Akt, mTOR

Jian Peng,1–3 Huiling Long,3 Weiwei Liu,2,3 Zhaoying Wu,1,3 Tao Wang,3 Zhu Zeng,1–3 Guo Guo,2,3 Jianwei Wu31Key Laboratory of Biology and Medical Engineering, Department of Biotechnology, School of Biology & Engineering, Guizhou Medical University, Guiyang 550004, People’s Republic of China; 2Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Guizhou Medical University, Guiyang 550004, People’s Republic of China; 3Key and Characteristic Laboratory of Modern Pathogen Biology, Department of Human Parasitology, School of Basic Medical Sciences, Guizhou Medical University, Guiyang 550004, People’s Republic of China Background: A case of Acinetobacter baumannii (A. baumannii), known as gram-negative bacteria, causes a range of nosocomial infections. Due to the continuous detection of multi-drug resistant A. baumannii in the clinic, there is an urgent need to find alternative therapies, including broad-spectrum antibacterial peptides (AMP). Recently it has been found that the peptide Cec4has good antibacterial activity against A. baumannii, but the antibacterial mechanism remains elusive.Materials and methods: The basic structure of Cec4 was analyzed by circular dichroism (CD) spectroscopy, and the potential antibacterial mechanism of Cec4 was detected by flow cytometry, transmission electron microscopy, fluorescence and confocal microscopy. The minimum inhibitory concentration (MIC) of antimicrobial peptides against various A. baumannii was determinated with broth microdilution techniques. The biofilm formation and the sensitivity detection of biofilms to antimicrobial peptides were detected by crystal violet staining.Results: In this study, the main secondary structure of the antibacterial peptide Cec4 is α-helix (99.7%) in the hydrophobic environment. Furthermore, after the treatment with Cec4, an amount of leakage of A. baumannii and the destruction of its cell membrane were detected. Moreover, it was observed that FITC-Cec4 can enter the cell, and more cells were held in the G1 phase with peptide Cec4. However, the DNA binding assay of the peptide Cec4 indicates that the peptide does not target DNA. In addition, peptide Cec4 was superior in reducing adherent biofilms of A. baumannii compared to conventional antibiotics and has no cytotoxicity.Conclusion: It is apparent that the antibacterial peptide Cec4 may achieve rapid sterilization by multi-target interaction and presents an attractive therapeutic option for the prevention and control of A. baumannii infections.Keywords: antimicrobial peptides, A. baumannii, antibacterial mechanism, cell membrane

This paper presents the first major and trace element compositions of mantle-derived garnet xenocrysts from the diamondiferous No. 30 kimberlite pipe in the Wafangdian region, and these are used to constrain the nature and evolution of mantle metasomatism beneath the North China Craton (NCC). The major element data were acquired using an electron probe micro-analyzer and the trace element data were obtained using laser ablation inductively coupled plasma-mass spectrometry. Based on Ni-in-garnet thermometry, equilibrium temperatures of 1107–1365 °C were estimated for peridotitic garnets xenocrysts from the No. 30 kimberlite, with an average temperature of 1258 °C, and pressures calculated to be between 5.0 and 7.4 GPa. In a CaO versus Cr2O3 diagram, 52% of the garnets fall in the lherzolite field and 28% in the harzburgite field; a few of the garnets are eclogitic. Based on rare earth element patterns, the lherzolitic garnets are further divided into three groups. The compositional variations in garnet xenocrysts reflect two stages of metasomatism: early carbonatite melt/fluid metasomatism and late kimberlite metasomatism. The carbonatite melt/fluids are effective at introducing Sr and the light rare earth elements, but ineffective at transporting much Zr, Ti, Y, or heavy rare earth elements. The kimberlite metasomatic agent is highly effective at element transport, introducing, e.g., Ti, Zr, Y, and the rare earth elements. Combined with compositional data for garnet inclusions in diamonds and megacrysts from the Mengyin and Wafangdian kimberlites, we suggest that these signatures reflect a two-stage evolution of the sub-continental lithospheric mantle (SCLM) beneath the NCC: (1) early-stage carbonatite melt/fluid metasomatism resulting in metasomatic modification of the SCLM and likely associated with diamond crystallization; (2) late-stage kimberlite metasomatism related to the eruption of the 465 Ma kimberlite.

The rational assessment and determination of strata and surface influence range of underground coal mining is straightly associated to the safe production of the wellbore, the reuse of mine land and the regional development. With the depth of coal mining in the world increasing, if the boundary curve of strata and surface movement continues to be considered as a straight line, there will be a great deviation from the real situation, which will seriously waste the land resources of mining area. To solve this issue, the numerical simulation methods were employed to investigate the stratum and surface movement boundary curves of deep caving and backfilling mining in this paper. The findings indicated that: 1) The strata and surface movement boundary of deep caving and backfilling mining were all curves, and they were in accordance with the exponential function, but the influence range of strata and surface movement of deep different mining methods were different; 2) The backfilling rate of deep backfilling mining had an influence on movement boundary of strata and surface. With the backfilling rate decreasing, the influence range of strata and surface movement boundary were increased. 3) The research results were applied to a case in order to confirm the new methods for determining the influence range of strata and surface movement of deep mining. Example application shows that the safe production of the wellbore not only can be guaranteed, but also the reuse area of the mine field can be enhanced.

Objective: Establish reference ranges for the Elecsys (R) soluble fms-like tyrosine kinase-1 (sFlt-1)/placental growth factor (PlGF) immunoassay ratio in twin pregnancies. Methods: Data analyzed were from 3 prospective studies: Prediction of Short-Term Outcome in Pregnant Women with Suspected Preeclampsia (PE) (PROGNOSIS), Study of Early-onset PE in Spain (STEPS), and a multicenter case-control study. Median, 5th, and 95th percentiles for sFlt-1, PlGF, and the sFlt-1/PlGF ratios were determined for normal twin pregnancies for 7 gestational windows and compared with the previous data for singleton pregnancies. Results: The reference range analysis included 269 women with normal twin pregnancies. Before 29 weeks' gestation, median, 5th, and 95th percentiles for sFlt-1/PlGF ratios did not differ between twin and singleton pregnancies. From 29 weeks' gestation to delivery, median, 5th, and 95th percentiles for sFlt-1/PlGF ratios were substantially higher in twin versus singleton pregnancies. sFlt-1 values were higher in women with twin pregnancies across all gestational windows. PlGF values were similar or higher in twin versus singleton pregnancies; PlGF concentrations increased from 10 weeks + 0 days to 28 weeks + 6 days' gestation. Conclusions: Reference ranges for the sFlt-1/PlGF ratio are similar in women with twin and singleton pregnancies until 29 weeks' gestation but appear higher in twin pregnancies thereafter.

Xuanxuan Dai,1,* Junru Zhang,2,* Guilong Guo,1 Yuepiao Cai,3 Ri Cui,3 Changtian Yin,1 Weidong Liu,3 Rajamanickam Vinothkumar,3 Tingting Zhang,3 Guang Liang,3 Xiaohua Zhang1 1Department of Thyroid and Breast Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325035, China; 2College of Pharmacy, Binzhou Medical University, Yantai, Shandong 264003, China; 3Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China *These authors contributed equally to this work Introduction: Targeted therapies using epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) have revolutionized the treatment of non-small cell lung cancer (NSCLC) patients harboring EGFR mutations, leading to the approval of gefitinib and erlotinib as standard first-line clinical treatment. Inevitably, a considerable proportion of patients develop resistance to EGFR-TKIs due to the acquisition of secondary mutations within EGFR. Therefore, alternative strategies to target NSCLC are desperately needed. Materials and methods: In this study, we have evaluated the effect of a reactive oxygen species (ROS)-inducing agent WZ35, a mono-carbonyl analog of curcumin, to target an inherent biological property of cancer cells, increased oxidative stress. To study whether WZ35 can inhibit NSCLC tumorigenesis, we used gefitinib- and erlotinib-resistant cell line H1975.Results: In this study, we show that WZ35 treatment dramatically decreases cell viability and induces apoptosis in H1975 cells through the generation of ROS. We also found that the ­antitumor activity of WZ35 involved ROS-mediated activation of the endoplasmic reticulum stress pathway and mitochondrial dysfunction. Furthermore, WZ35 significantly inhibited H1975 xenograft tumor growth through the inhibition of cell proliferation and induction of apoptosis. Discussion: These findings show that WZ35 may be a promising candidate for the treatment of EGFR-TKI-resistant NSCLC. Keywords: epidermal growth factor receptor, reactive oxygen species, mono-carbonyl analog of curcumin, ER stress, mitochondrial dysfunction, apoptosis, NSCLC

Lin Yang,1–3 Zhenchong Xiong,1–3 Wenzhuo He,1–3 Kunqian Xie,1–3 Shousheng Liu,1–3 Pengfei Kong,1–3 Chang Jiang,1–3 Guifang Guo,1–3,* Liangping Xia1–3,* 1Department of VIP, Sun Yat-sen University Cancer Center, Guangzhou, China; 2State Key Laboratory of Oncology in Southern China, Guangzhou, China; 3Collaborative Innovation Center for Cancer Medicine, Guangzhou, China *These authors contributed equally to this work Background: Studies have indicated a variation in colon cancer pathology with increased age. More findings have also suggested differences in genetics, biology, and demography in terms of ethnicity. Large-scale studies closely examining tumor location shift with aging and ethnicity are scarce. Objective: We compared the tumor location shift with aging and the difference in survival based on tumor location by age group among the African-American, White, and Asian/Pacific Islander patients with colorectal cancer. Materials and methods: We collected 270,390 cases from the Surveillance, Epidemiology, and End Results database between 2004 and 2014. Ethnicity distribution between younger (age 12, and right-sided colon cancer were more common in patients aged ≥70 years. More adverse prognosis was found in younger patients compared to older patients. Tumor location frequency differed based on age; the most pronounced differences were found in White patients. The right-sided colon cancer survival inferiority was present only in White patients. Conclusion: Our findings support the premise of etiological and carcinogenic differences based on tumor location and between younger and older patients. Keywords: age, proximal shift, tumor location, ethnicity, SEER, colorectal cancer

Cheng Peng,1,* Liangyou Gu,1,* Lei Wang,2 Qingbo Huang,1 Baojun Wang,1 Gang Guo,1 Yang Fan,1 Yu Gao,1 Xin Ma,1 Xu Zhang1 1Department of Urology, State Key Laboratory of Kidney Diseases, Chinese PLA General Hospital, Chinese PLA Medical Academy, Beijing, People’s Republic of China; 2Department of Urology, Chinese PLA 534 Hospital, Luoyang, People’s Republic of China *These authors contributed equally to this work Purpose: The clinical benefit of targeted molecular therapy (TMT) in renal cell carcinoma (RCC) with an inferior vena cava (IVC) tumor thrombus remains controversial. The aim of this study was to investigate the effects of presurgical TMT on the heights and levels of IVC thrombi, and to assess its impact on surgical strategy. Patients and methods: We retrospectively reviewed data from 18 patients with RCC involving IVC tumor thrombi who were treated at our hospital with presurgical TMT followed by an IVC thrombectomy. The changes in heights and levels of the IVC thrombi were compared using computed tomography or magnetic resonance imaging. Clinicopathological factors were also evaluated to assess their association with TMT efficacy. Results: The tumor thrombus levels before TMT were stage I in 1 patient (5.6%), II in 12 patients (66.7%), III in 4 patients (22.2%), and IV in 1 patient (5.6%). After a median of two treatment cycles (range: 1–3), the thrombus height decreased measurably in 11 patients (61.1%) with an average shrinkage of 17.7%. The thrombus height remained stable in five patients (27.8%) and was enlarged in two (11.1%). Downstaging of the thrombus level occurred in four patients (22.2%); the surgical strategy was modified in three patients (16.7%) to avoid cardiopulmonary bypass and complicated liver mobilization under robot-assisted laparoscopy. Furthermore, a higher neutrophil count tended to be associated with a worse clinical TMT-associated outcome (P=0.056). Conclusion: Our data suggest a limited influence of presurgical TMT with a positive benefit in RCC patients with level III and IV thrombus. Thrombus-level regression may potentially alter the surgical strategy, especially robotic surgery. However, our findings require validation with additional prospective investigations. Keywords: presurgical TMT, surgical strategy, sorafenib, sunitinib

Gang Guo,1,* Moushun Fu,2,* Shuxiang Wei,3 Ruiwan Chen4 1Department of Ophthalmology, Tongjiang Hospital of Guangdong, Foshan, 2Department of Otorhinolaryngology, Tongjiang Hospital of Guangdong, Foshan, 3Department of Endocrinology, Tongjiang Hospital of Guangdong, Foshan, 4Department of Radiotherapy, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China *These authors contributed equally to this work Background: Diabetes mellitus (DM) has been identified to be both a risk factor and a prognostic factor in a variety of malignancies, but its association with the risk and outcome of nasopharyngeal carcinoma (NPC) is still unclear. To elucidate this issue, we systematically reviewed the evidence concerning the association between DM status and NPC.Materials and methods: We identified studies by a literature search of PubMed, Embase, and ISI Web of Knowledge through May 31, 2017, and by searching the reference lists of pertinent articles. Odds ratios (ORs) and hazard ratios (HRs) with 95% CIs were used to estimate the effect size. Heterogeneity across studies was evaluated by the Cochran’s Q and I2 statistics.Results: A total of nine studies were included. Four studies with a total sample size of 221,611 reported the effect of DM on NPC risk, and the other five studies with a sample size of 9,442 reported the impact of DM on survival in NPC patients. All included studies were retrospective, and mostly conducted in Asian populations. Meanwhile, condition of metformin usage was not considered in all studies. A pooled OR of 0.65 (95% CI: 0.43–0.98, P=0.04) revealed an inverse association between DM and NPC. Additionally, pooled analyses of studies investigating the prognosis value of DM revealed that preexisting DM had no effect on overall survival (HR =1.17, 95% CI: 0.94–1.46, P=0.16), local recurrence-free survival (HR =1.16, 95% CI: 0.80–1.67, P=0.44), and distant metastasis-free survival (HR =1.14, 95% CI: 0.92–1.40, P=0.22).Conclusion: Our results suggested that DM patients might have decreased NPC risk, and have little impact on prognosis of NPC patients. This conclusion should be limited to Asian population. Our results also suggest that more attention should be paid to metformin medication in further studies in order to clarify whether the effects of DM on NPC risk and prognosis are influenced by the anticancer effect of metformin. Keywords: diabetes mellitus, nasopharyngeal carcinoma, risk factor, prognosis factor, a meta-analysis, evidence based medicine&nbsp

Yijie Huang,1,* Yexi Chen,2,* Xiaoqi Lin,2 Qingjun Lin,2 Ming Han,2 Guohu Guo2 1Department of General Surgery, Guangdong General Hospital, Guangzhou, 2Department of General Surgery, The Second Affiliated Hospital of Shantou University Medical College, Shantou, People’s Republic of China *These authors contributed equally tothis work Abstract: Stomatin-like protein 2 (SLP-2) gene was significantly upregulated in a variety of tumor tissues and found to be involved in proliferation and metastasis. However, its functional role in hepatocellular carcinoma (HCC) remains unknown. Our study was to investigate the function of SLP-2 in cell proliferation, migration, invasion, cell apoptosis, and the process of epithelial–mesenchymal transition (EMT) in HCC. SLP-2 mRNA and protein expression in HCC were assessed by qRT-PCR and immunohistochemical staining. In vitro, we determined cell proliferation, migration, invasion, and cell apoptosis by CCK-8, transwell, and flow cytometry assays, respectively. SLP-2 was found to be upregulated at both mRNA and protein levels in HCC tissues, and its aberrant overexpression was linked with poor prognosis in patients with HCC. SLP-2 downregulation by siRNAs significantly suppressed cell proliferation, migration, invasion, anti-apoptosis abilities, and inhibited EMT process in vitro. In conclusion, the present study demonstrated the overexpression of SLP-2 in HCC tissues for the first time. As an effective regulator involved in cell proliferation, migration, invasion, cell apoptosis, and EMT, SLP-2 could be a novel therapeutic target for patients with HCC who express high levels of SLP-2. Keywords: hepatocellular carcinoma, stomatin-like protein 2, prognosis, proliferation, migration, epithelial–mesenchymal transition&nbsp

Jie You,1,2,* Huxiang Zhang,3,* Yanyan Shen,2,* Chuanzhi Chen,2 Wenyue Liu,4 Minghua Zheng,5 Sven Van Poucke,6 Guilong Guo,2 Zonghai Huang1 1Department of General Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, 2Department of Oncological Surgery, 3Department of Pathology, 4Department of Endocrinology, 5Department of Hepatology, Liver Research Center, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China; 6Department of Anesthesiology, Intensive Care, Emergency Medicine and Pain Therapy, Ziekenhuis Oost-Limburg, Genk, Belgium *These authors contributed equally to this work Objective: The aim of this study was to evaluate the prognostic value of both platelet to lymphocyte ratio (PLR) and metabolic syndrome (MetS) in colorectal cancer (CRC) patients.Patients and methods: We retrospectively enrolled 1,163 CRC patients. Preoperative values of PLR were stratified into three groups according to cut-off values of 120 and 220. The Kaplan–Meier analysis was used to calculate cumulative survival rate related to PLR and MetS. Cox proportional hazard regression models were used to analyze potential risk factors and the prognosis associated with PLR and MetS in CRC patients.Results: PLR was significantly higher in the MetS(+) group as compared to MetS(–) group (P=0.039). An elevated PLR was significantly associated with mortality (P=0.014), but not the existence of MetS (P=0.235). In multivariate regression analysis, PLR was an independent risk factor for overall survival (OS) (P=0.046). For the subgroup with a PLR >220, MetS was an independent predictor for both OS and disease-free survival (P=0.039 and P=0.047, respectively) by multivariate analysis adjusting for confounding covariates. In addition, the presence of MetS was associated with a 2-fold increased risk of mortality and tumor recurrences (hazard ratio [HR] =2.0 and HR =1.9, P

Jiaxing Wang,1,* Huaijuan Zhou,2,* Geyong Guo,1 Tao Cheng,1 Xiaochun Peng,1 Xin Mao,1 Jinhua Li,2–4 Xianlong Zhang1 1Department of Orthopaedics, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai Jiao Tong University, 2State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai, 3Department of Orthopaedics and Traumatology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, 4University of Chinese Academy of Sciences, Beijing, China *These authors contributed equally to this work Abstract: Bloodstream infection, especially with implants involved, is an often life-threatening condition with high mortality rates, imposing a heavy burden on patients and medical systems. Herein, we firstly deposited homogeneous vanadium metal, V2O3, VO2, and V2O5 nanofilms on quartz glass by magnetron sputtering. Using these platforms, we further investigated the potential antimicrobial efficiency of these nano-VOx films and the interactions of human erythrocytes and bacteria (methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa) with our samples in a novel cell–bacteria coculture model. It was demonstrated that these nano-VOx precipitated favorable antibacterial activity on both bacteria, especially on S. aureus, and this effect increased with higher vanadium valence. A possible mechanism accountable for these results might be elevated levels of vanadium-induced intracellular reactive oxygen species. More importantly, based on hemolysis assays, our nano-VOx films were found to be able to kill prokaryotic cells but were not toxic to mammalian cells, holding the potential for the prevention of implant-related hematogenous infections. As far as we know, this is the first report wherein such nano-VOx films have assisted human erythrocytes to combat bacteria in a valence-dependent manner. Additionally, vanadium ions were released from these nano-VOx films in a sustained manner, and low-valence films possessed better biocompatibility with human fibroblasts. This work may provide new insights for biomedical applications of inorganic vanadium compounds and attract growing attention in this field. From the perspective of surface modification and functionalization, this study holds promise to avail the prophylaxis of bloodstream infections involving implantable biomedical devices. Keywords: surface modification, red blood cell, antibacterial activities, vanadium, nano­materials

JingLun Li,1 JiaoJiao Deng,2 JinXian Yuan,1 Jie Fu,1 XiaoLing Li,2 AiPing Tong,2 YueLong Wang,2 YangMei Chen,1 Gang Guo2 1Department of Neurology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 2State Key Laboratory of Biotherapy and Cancer Center, and Department of Neurosurgery, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, People’s Republic of China Abstract: Spinal cord injury (SCI) commonly leads to lifelong disability due to the limited regenerative capacity of the adult central nervous system. Nanomicelles can be used as therapeutic systems to provide effective treatments for SCI. In this study, a novel triblock monomethyl poly(ethylene glycol)-poly(L-lactide)-poly(trimethylene carbonate) copolymer was successfully synthesized. Next, polymeric nanomicelles loaded with zonisamide (ZNS), a Food and Drug Administration-approved antiepileptic drug, were prepared and characterized. The ZNS-loaded micelles (ZNS-M) were further utilized for the treatment of SCI in vitro and in vivo. The obtained ZNS-M were ~50nm in diameter with good solubility and dispersibility. Additionally, these controlled-release micelles showed significant antioxidative and neuron-protective effects in vitro. Finally, our results indicated that ZNS-M treatment could promote motor function recovery and could increase neuron and axon density in a hemisection SCI model. In summary, these results may provide an experimental basis for the use of ZNS-M as a clinically applicable therapeutic drug for the treatment of SCI in the future. Keywords: spinal cord injury, zonisamide, nanomicelles

© 2018 Elsevier B.V. A new metal-free organic molecular as co-catalyst was developed, which could drastically enhance the photocatalytic performance of photocatalyst (eg. g-C 3 N 4 , MoS 2 and TiO 2 ). The enhancing photocatalytic activity was evaluated for photocatalytic degradation of organic dyes. It showed ultra-high photocatalytic rate (4.17 mg/g·min) and ultra-short time (about 6.0 min) for photocatalytic degradation of organic dyes (25 mg/ml). The enhanced photocatalytic performance was attributed to suppress recombination of photogenerated charges and provide a new photoredox reaction pathway under molecular co-catalyst assistance. The study represents a facile method to develop ultra-effectively photocatalyst for applications in production of green and renew-able energy carrier, H 2 from water, reduction of CO 2 , synthesis of fine chemicals and remediation of environmental pollutants.

© 2019 Hydrogen Energy Publications LLC In this contribution, we reported the preparation of a novel conducting polymer hydrogel (CPH) by a sol-gel method, which was subsequently employed to fabricate a flexible all-solid-state supercapacitor device. Taking advantage of the synergistic effects of the different components in the conducting polymer hydrogel and the merits of the proposed synthesis strategies, the prepared supercapacitor device with CPH as electrode exhibited high area-normalized capacitance (2.2 F cm −2 ), high gravimetric capacitance (1573.6 F g −1 ) as well as high energy density of 0.18 mWh cm −2 (or 128.7 Wh Kg −1 ) at 0.08 mW cm −2 (or 55.1 W kg −1 ). This study did not only represent a novel all-solid-state, high performance, flexible supercapacitor with potential applications in flexible energy-related devices, but also developed a new method for enhancing capacitances and mechanical stability of all-solid-state flexible supercapacitor.

Magneto-transport study has been performed in ZrTe5 single crystals. The observed Shubnikov-de Hass quantum oscillation at low temperature clearly demonstrates the existence of a nontrivial band with small effective mass in ZrTe5. Furthermore, we also revealed the 3D anisotropic nature of high-field Landau level splitting in ZrTe5, very different from the 2D behavior measured in previous transport studies. Besides these, an abnormal large enhancement of magnetoresistance appears at high temperatures, which is believed to arise from the Lifshitz transition induced two-carrier transport in ZrTe5. Our study provides more understanding of the physical properties of ZrTe5 and sheds light on potential application of ZrTe5 in spintronics., Comment: 14 pages,5 figures

High porosity will bring about a great deal of contributions for metal-bonded grinding wheels. In this research, cellular structures, including octahedron, truncated octahedron, and stellated octahedron, are chosen as porous structures for a grinding wheel and fabricated using selective laser melting (SLM) with diamond/AlSi10Mg mixed powders. Moreover, the microstructure and bonding condition of SLM-fabricated composite are investigated. Additionally, morphological properties, mechanical properties, and permeability of three different porous structures are studied and compared with each other based on experiment and simulation. It is revealed that the microstructure of SLM-fabricated composite exhibits anisotropic due to the layered manufacturing essence. Furthermore, the cladding state of diamond grits is good and strong interface forms between diamond and AlSi10Mg. Besides, both mechanical performance and permeability of octahedron structure are the best, making it a potential structure for a high-performance porous grinding wheel.

Unsteady flow is the most common and complicated form of fluid motion in nature. This paper takes the beaches of key waterways in the middle and lower reaches of the Yangtze River as the research object, analyzes the water surface distribution and average flow velocity distribution near the beach, and analyzes the differences. The relationship between the flow pattern of the steep slope and the water flow pattern of the entire survey area and the steep slope of the beach and its nearby water flow structure. The water flow near the beach is divided into four major blocks: the swelling water area, the falling water area, the backwater area and the maximum flow rate area. The water flow structure characteristics and the cause of each block are analyzed.

Xiaoling Li,1 Xianlong Ye,2 Jianying Qi,2 Rangrang Fan,1 Xiang Gao,1 Yunzhou Wu,2 Liangxue Zhou,1 Aiping Tong,1 Gang Guo1 1State Key Laboratory of Biotherapy and Cancer Center, Department of Neurosurgery, West China Hospital, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu, People’s Republic of China; 2College of Life Science, Northeast Agriculture University, Harbin, People’s Republic of China Abstract: Wound healing is a complex multifactorial process that relies on coordinated signaling molecules to succeed. Epidermal growth factor (EGF) is a mitogenic polypeptide that stimulates wound repair; however, precise control over its application is necessary to reduce the side effects and achieve desired therapeutic benefits. Moreover, the extensive oxidative stress during the wound healing process generally inhibits repair of the injured tissues. Topical applications of antioxidants like curcumin (Cur) could protect tissues from oxidative damage and significantly improve tissue remodeling. To achieve much accelerated wound healing effects, we designed a novel dual drug co-loaded in situ gel-forming nanoparticle/hydrogel system (EGF-Cur-NP/H) which acted not only as a supportive matrix for the regenerative tissue, but also as a sustained drug depot for EGF and Cur. In the established excisional full-thickness wound model, EGF-Cur-NP/H treatment significantly enhanced wound closure through increasing granulation tissue formation, collagen deposition, and angiogenesis, relative to normal saline, nanoparticle/hydrogel (NP/H), Cur-NP/H, and EGF-NP/H treated groups. Inconclusion, this study provides a biocompatible in situ gel-forming system for efficient topical application of EGF and Cur in the landscape of tissue repair. Keywords: epidermal growth factor, EGF, curcumin, wound healing, thermosensitive hydrogel, nanoparticles&nbsp

Yunfei Xia,1,* Rulan Yin,1,2,* Ting Fu,1,2 Lijuan Zhang,1,2 Qiuxiang Zhang,1,2 Genkai Guo,1 Liren Li,2 Zhifeng Gu11Department of Rheumatology, Affiliated Hospital of Nantong University, 2School of Nursing, Nantong University, Nantong, People’s Republic of China *These authors contributed equally tothis work Objective: Nonadherence in rheumatoid arthritis (RA) patients using disease-modifying antirheumatic drugs (DMARDs) may lead to joint damage and function loss. The aim of this cross-sectional study was to explore Chinese RA patients’ adherence rates and investigate potential risk factors for nonadherence.Methods: A total of 122 RA patients were recruited from the Affiliated Hospital of Nantong University from January 2014 to April 2015. Patients were asked to complete a set of standardized self-report questionnaires (Compliance Questionnaire on Rheumatology, Health Assessment Questionnaire, Short Form-36 questionnaire, 28-joint Disease Activity Score, Hospital Anxiety and Depression Scale, and Visual Analog Scale). Independent samples t-tests, chi-square analyses, and logistic regression modeling were used to analyze these data.Results: Based on Compliance Questionnaire on Rheumatology, 38% of the patients adhered to DMARDs. Adherence was associated with education, income, depression, and the total number of DMARDs. Other demographic and clinical characteristics were not associated with adherence. Logistic regression models identified income, depression, and the total number of DMARDs as predictors of medication nonadherence.Conclusion: In this study, 62% of patients with RA were not adherent to their DMARD prescription. Education, income, depression, and the total number of DMARDs were associated with medication adherence, and income, depression, and the total number of DMARDs were independent predictors of medication adherence in patients with RA. These findings could help medical personnel develop helpful interventions to improve adherence in RA patients by paying more attention to the patients with theseaccompanyingrisk factors and, finally, improve RA patients’ quality of life.Keywords: rheumatoid arthritis, disease-modifying antirheumatic drugs, adherence

Rangrang Fan,1,* Aiping Tong,1,* Xiaoling Li,1 Xiang Gao,1 Lan Mei,1 Liangxue Zhou,1 Xiaoning Zhang,2 Chao You,1 Gang Guo1 1State Key Laboratory of Biotherapy and Cancer Center, Department of Neurosurgery, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, People’s Republic of China; 2Department of Pharmacology and Pharmaceutical Sciences, School of Medicine, Tsinghua University, and Collaborative Innovation Center for Biotherapy, Beijing, People’s Republic of China *These authors contributed equally tothis work Abstract: Intraperitoneal chemotherapy was explored in clinical trials as a promising strategy to improve the therapeutic effects of chemotherapy. In this work, we developed a biodegradable and injectable drug-delivery system by coencapsulation of docetaxel (Doc) and LL37 peptide polymeric nanoparticles (Doc+LL37 NPs) in a thermosensitive hydrogel system for colorectal peritoneal carcinoma therapy. Firstly, polylactic acid (PLA)-Pluronic L35-PLA (PLA-L35-PLA) was explored to prepare the biodegradable Doc+LL37 NPs using a water-in-oil-in-water double-emulsion solvent-evaporation method. Then, biodegradable and injectable thermosensitive PLA-L64-PLA hydrogel with lower sol–gel transition temperature at around body temperature was also prepared. Transmission electron microscopy revealed that the Doc+LL37 NPs formed with the PLA-L35-PLA copolymer were spherical. Fourier-transform infrared spectra certified that Doc and LL37 were encapsulated successfully. X-ray diffraction diagrams indicated that Doc was encapsulated amorphously. Intraperitoneal administration of Doc+LL37 NPs–hydrogel significantly suppressed the growth of HCT116 peritoneal carcinomatosis in vivo and prolonged the survival of tumor-bearing mice. Our results suggested that Doc+LL37 NPs–hydrogel may have potential clinical applications. Keywords: intraperitoneal chemotherapy, injectable, nanoparticles, hydrogel, coencapsulation

Geometric phases, generated by cyclic evolutions of quantum systems, offer an inspiring playground for advancing fundamental physics and technologies alike. The exotic statistics of anyons realized in physical systems can be interpreted as a topological version of geometric phases. However, non-Abelian statistics has not yet been demonstrated in the laboratory. Here, we use an all-optical quantum system that simulates the statistical evolution of Majorana fermions. As a result, we experimentally realize non-Abelian Berry phases with the topological characteristic that they are invariant under continuous deformations of their control parameters. We implement a universal set of Majorana-inspired gates by performing topological and nontopological evolutions and investigate their resilience against perturbative errors. Our photonic experiment, though not scalable, suggests the intriguing possibility of experimentally simulating Majorana statistics with scalable technologies.

Anesthesia and surgery (A + S) are risk factors for patients to develop postoperative delirium (POD). However, the pathogenesis of POD remains largely to be determined. We employed battery of behavioral tests including open-filed test (OFT), elevated plus maze test (EPMT) and buried food test (BFT) to investigate the role of oxidative stress in the development of POD and to explore the therapeutic target for POD in mice after A + S (simple laparotomy under 1.4% isoflurane anesthesia). We initially found that 6 hours after A + S, mice failed to alter the behavioral changes in OFT and the adenosine triphosphate (ATP) level in hippocampus. After hierarchical cluster analysis, however, there was a significant change in the behavior tests between POD unsusceptible (non-POD) and susceptible (POD-like) mice. Interestingly, cyclosporine A, an inhibitor of mitochondrial permeability transition pore (mPTP) opening, exerted pharmacologically beneficial effects on symptoms, decreased reactive oxygen species (ROS) and ATP, and increased superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) levels in the hippocampus of POD-like mice. These findings suggest that abnormally activated oxidative stress might be involved in the underlying mechanisms of POD. Novel therapeutic agents targeting inhibition of oxidative stress would provide an available strategy for POD treatment.

The aim of the present study was to identify genes that could be used for the normalisation of qRT-PCR data in barley, using RNAseq data (NCBI accession number PRJNA400519: RNA sequencing of Hordeum vulgare L. under low nitrogen stress). The particular interest was in genes that were stably expressed under different nitrogen conditions, including low-nitrogen stress.

Fangxin Liao,1,2,* Wenzhuo He,1,2,* Chang Jiang,1,2 Chenxi Yin,1,2 GuifangGuo,1,2 Xuxian Chen,1,2 Huijuan Qiu,1,2 Yuming Rong,1,2 Bei Zhang,1,2 Dazhi Xu,1,3 Liangping Xia1,21State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 2VIP Region, 3Gastric and Pancreatic Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China*These authors contributed equally to this workAbstract: Although lipid disequilibrium has been documented for several types of cancer including colorectal cancer (CRC), it remains unknown whether lipid parameters are associated with the outcome of metastatic CRC (mCRC) patients. Here, we retrospectively examined the lipid profiles of 453 mCRC patients and investigated whether any of the lipid parameters correlated with the outcome of mCRC patients. Pretreatment serum lipids, including triglyceride, cholesterol, high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C), were collected in 453 initially mCRC patients. The LDL-C to HDL-C ratio (LHR) was calculated and divided into the first, second, and third tertiles. Univariate and multivariate analyses were performed to evaluate the impact of lipids on overall survival (OS) and progression-free survival (PFS). Nearly two-fifths of the patients (41.3%) exhibited elevations in LDL-C while most patients (88.3%) showed normal HDL-C levels. Decreased HDL-C (P=0.542) and increased LDL-C (P=0.023) were prognostic factors for poor OS, while triglyceride (P=0.542) and cholesterol (P=0.215) were not. Multivariate analysis revealed that LDL-C (P=0.031) was an independent prognostic factor. Triglyceride, cholesterol, HDL-C, and LDL-C did not correlate with PFS. Among patients with elevations in LDL-C levels, patients in the third tertile of the LHR had a markedly shorter median OS compared to those in the first or second tertile (P=0.012). Thus, increased LDL-C level is an independent prognostic factor for poor prognosis in mCRC patients, and a high LHR predicts poor prognosis for initially mCRC patients with elevations in LDL-C.Keywords: high low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, metastatic colorectal cancer

Yun Fei Li,1,2,* Hong Wu Sun,1,2,* Rong Gao,1–3,* Kai Yun Liu,1,2 Hua Qi Zhang,4 Qi Huan Fu,1,2 Sheng Li Qing,1,2 Gang Guo,1,2 Quan Ming Zou1,2,* 1National Engineering Research Center of Immunological Products, 2Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, 3Department of Biomedical Engineering, Third Military Medical University of Chinese PLA, Chongqing, People’s Republic of China; 4Wanzhou Institute for Food and Drug Control of Chongqing, Wanzhou, Chongqing, People’s Republic of China *These authors contributed equally tothis work Abstract: The aim of this study was to prepare a novel nanoemulsion loaded with poorly water-soluble chlorhexidine acetate (CNE) to improve its solubility, and specifically enhance the antimicrobial activity against Streptococcus mutans in vitro and in vivo. In this study, a novel CNE nanoemulsion with an average size of 63.13 nm and zeta potential of −67.13 mV comprising 0.5% CNE, 19.2% Tween 80, 4.8% propylene glycol, and 6% isopropyl myristate was prepared by the phase inversion method. Important characteristics such as the content, size, zeta potential, and pH value of CNE did not change markedly, stored at room temperature for 1 year. Also, compared with chlorhexidine acetate water solution (CHX), the release profile results show that the CNE has visibly delayed releasing effect in both phosphate-buffered saline and artificial saliva solutions (P

Much attention has focussed on the conversion of human pluripotent stem cells (PSCs) to a more naïve developmental status. Here we provide a method for resetting via transient histone deacetylase inhibition. The protocol is effective across multiple PSC lines and can proceed without karyotype change. Reset cells can be expanded without feeders with a doubling time of around 24 h. WNT inhibition stabilises the resetting process. The transcriptome of reset cells diverges markedly from that of primed PSCs and shares features with human inner cell mass (ICM). Reset cells activate expression of primate-specific transposable elements. DNA methylation is globally reduced to a level equivalent to that in the ICM and is non-random, with gain of methylation at specific loci. Methylation imprints are mostly lost, however. Reset cells can be re-primed to undergo tri-lineage differentiation and germline specification. In female reset cells, appearance of biallelic X-linked gene transcription indicates reactivation of the silenced X chromosome. On reconversion to primed status, $XIST$-induced silencing restores monoallelic gene expression. The facile and robust conversion routine with accompanying data resources will enable widespread utilisation, interrogation, and refinement of candidate naïve cells.

The first known magnetic mineral, magnetite, has unusual properties, which have fascinated mankind for centuries; it undergoes the Verwey transition around 120 K with an abrupt change in structure and electrical conductivity. The mechanism of the Verwey transition, however, remains contentious. Here we use resonant inelastic X-ray scattering over a wide temperature range across the Verwey transition to identify and separate out the magnetic excitations derived from nominal Fe2+ and Fe3+ states. Comparison of the experimental results with crystal-field multiplet calculations shows that the spin–orbital dd excitons of the Fe2+ sites arise from a tetragonal Jahn-Teller active polaronic distortion of the Fe2+O6 octahedra. These low-energy excitations, which get weakened for temperatures above 350 K but persist at least up to 550 K, are distinct from optical excitations and are best explained as magnetic polarons., The Verwey transition of magnetite is complex due to the coexistence of strong correlations and electron-phonon coupling. Here, the authors use resonant inelastic X-ray scattering to show evidence for magnetic polarons in magnetite and provide insight into the nature of the transition.