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Reactor neutrino experiments play a crucial role in advancing our knowledge of neutrinos. In this Letter, the evolution of the flux and spectrum as a function of the reactor isotopic content is reported in terms of the inverse-beta-decay yield at Daya Bay with 1958 days of data and improved systematic uncertainties. These measurements are compared with two signature model predictions: the Huber-Mueller model based on the conversion method and the SM2018 model based on the summation method. The measured average flux and spectrum, as well as the flux evolution with the ^{239}Pu isotopic fraction, are inconsistent with the predictions of the Huber-Mueller model. In contrast, the SM2018 model is shown to agree with the average flux and its evolution but fails to describe the energy spectrum. Altering the predicted inverse-beta-decay spectrum from ^{239}Pu fission does not improve the agreement with the measurement for either model. The models can be brought into better agreement with the measurements if either the predicted spectrum due to ^{235}U fission is changed or the predicted ^{235}U, ^{238}U, ^{239}Pu, and ^{241}Pu spectra are changed in equal measure.

We present a new determination of the smallest neutrino mixing angle θ_{13} and the mass-squared difference Δm_{32}^{2} using a final sample of 5.55×10^{6} inverse beta-decay (IBD) candidates with the final-state neutron captured on gadolinium. This sample is selected from the complete dataset obtained by the Daya Bay reactor neutrino experiment in 3158 days of operation. Compared to the previous Daya Bay results, selection of IBD candidates has been optimized, energy calibration refined, and treatment of backgrounds further improved. The resulting oscillation parameters are sin^{2}2θ_{13}=0.0851±0.0024, Δm_{32}^{2}=(2.466±0.060)×10^{-3}  eV^{2} for the normal mass ordering or Δm_{32}^{2}=-(2.571±0.060)×10^{-3}  eV^{2} for the inverted mass ordering.

This Letter reports the first measurement of high-energy reactor antineutrinos at Daya Bay, with nearly 9000 inverse beta decay candidates in the prompt energy region of 8-12 MeV observed over 1958 days of data collection. A multivariate analysis is used to separate 2500 signal events from background statistically. The hypothesis of no reactor antineutrinos with neutrino energy above 10 MeV is rejected with a significance of 6.2 standard deviations. A 29% antineutrino flux deficit in the prompt energy region of 8-11 MeV is observed compared to a recent model prediction. We provide the unfolded antineutrino spectrum above 7 MeV as a data-based reference for other experiments. This result provides the first direct observation of the production of antineutrinos from several high-Q_{β} isotopes in commercial reactors.

The prediction of reactor antineutrino spectra will play a crucial role as reactor experiments enter the precision era. The positron energy spectrum of 3.5 million antineutrino inverse beta decay reactions observed by the Daya Bay experiment, in combination with the fission rates of fissile isotopes in the reactor, is used to extract the positron energy spectra resulting from the fission of specific isotopes. This information can be used to produce a precise, data-based prediction of the antineutrino energy spectrum in other reactor antineutrino experiments with different fission fractions than Daya Bay. The positron energy spectra are unfolded to obtain the antineutrino energy spectra by removing the contribution from detector response with the Wiener-SVD unfolding method. Consistent results are obtained with other unfolding methods. A technique to construct a data-based prediction of the reactor antineutrino energy spectrum is proposed and investigated. Given the reactor fission fractions, the technique can predict the energy spectrum to a 2% precision. In addition, we illustrate how to perform a rigorous comparison between the unfolded antineutrino spectrum and a theoretical model prediction that avoids the input model bias of the unfolding method.

The establishment of a possible connection between neutrino emission and gravitational-wave (GW) bursts is important to our understanding of the physical processes that occur when black holes or neutron stars merge. In the Daya Bay experiment, using the data collected from December 2011 to August 2017, a search was performed for electron-Antineutrino signals that coincided with detected GW events, including GW150914, GW151012, GW151226, GW170104, GW170608, GW170814, and GW170817. We used three time windows of 10, 500, and 1000 s relative to the occurrence of the GW events and a neutrino energy range of 1.8 to 100 MeV to search for correlated neutrino candidates. The detected electron-Antineutrino candidates were consistent with the expected background rates for all the three time windows. Assuming monochromatic spectra, we found upper limits (90% confidence level) of the electron-Antineutrino fluence of (1.13-2.44)×1011 cm-2 at 5 MeV to 8.0×107 cm-2 at 100 MeV for the three time windows. Under the assumption of a Fermi-Dirac spectrum, the upper limits were found to be (5.4-7.0)×109 cm-2 for the three time windows.

The prediction of reactor antineutrino spectra will play a crucial role asreactor experiments enter the precision era. The positron energy spectrum of3.5 million antineutrino inverse beta decay reactions observed by the Daya Bayexperiment, in combination with the fission rates of fissile isotopes in thereactor, is used to extract the positron energy spectra resulting from thefission of specific isotopes. This information can be used to produce aprecise, data-based prediction of the antineutrino energy spectrum in otherreactor antineutrino experiments with different fission fractions than DayaBay. The positron energy spectra are unfolded to obtain the antineutrino energyspectra by removing the contribution from detector response with the Wiener-SVDunfolding method. Consistent results are obtained with other unfolding methods.A technique to construct a data-based prediction of the reactor antineutrinoenergy spectrum is proposed and investigated. Given the reactor fissionfractions, the technique can predict the energy spectrum to a 2% precision. Inaddition, we illustrate how to perform a rigorous comparison between theunfolded antineutrino spectrum and a theoretical model prediction that avoidsthe input model bias of the unfolding method.

Hua-Xi Zou,1,2,* Tie Hu,1,2,* Jia-Yi Zhao,2,3,* Bai-Quan Qiu,2,4 Chen-Chao Zou,2,4 Qi-Rong Xu,1 Ji-Chun Liu,1,2 Song-Qing Lai,1,2 Huang Huang1,2 1Department of Cardiovascular Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, People’s Republic of China; 2Institute of Cardiovascular Diseases, Jiangxi Academy of Clinical Medical Sciences, The First Affiliated Hospital of Nanchang University, Nanchang, People’s Republic of China; 3Medical Innovation Experimental Program, Huan Kui College, Nanchang University, Nanchang, People’s Republic of China; 4Department of Cardiovascular Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Huang Huang; Song-Qing Lai, Email jack19871212@hotmail.com; ndyfy03743@ncu.edu.cnIntroduction: Sepsis is currently a common condition in emergency and intensive care units, and is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Cardiac dysfunction caused by septic myocardial injury (SMI) is associated with adverse prognosis and has significant economic and human costs. The pathophysiological mechanisms underlying SMI have long been a subject of interest. Recent studies have identified ferroptosis, a form of programmed cell death associated with iron accumulation and lipid peroxidation, as a pathological factor in the development of SMI. However, the current understanding of how ferroptosis functions and regulates in SMI remains limited, particularly in the absence of direct evidence from human heart.Methods: We performed a sequential comprehensive bioinformatics analysis of human sepsis cardiac transcriptome data obtained through the GEO database. The lipopolysaccharide-induced mouse SMI model was used to validate the ferroptosis features and transcriptional expression of key genes.Results: We identified widespread dysregulation of ferroptosis-related genes (FRGs) in SMI based on the human septic heart transcriptomes, deeply explored the underlying biological mechanisms and crosstalks, followed by the identification of key functional modules and hub genes through the construction of protein-protein interaction network. Eight key FRGs that regulate ferroptosis in SMI, including HIF1A, MAPK3, NOX4, PPARA, PTEN, RELA, STAT3 and TP53, were identified, as well as the ferroptosis features. All the key FRGs showed excellent diagnostic capability for SMI, part of them was associated with the prognosis of sepsis patients and the immune infiltration in the septic hearts, and potential ferroptosis-modulating drugs for SMI were predicted based on key FRGs.Conclusion: This study provides human septic heart transcriptome-based evidence and brings new insights into the role of ferroptosis in SMI, which is significant for expanding the understanding of the pathobiological mechanisms of SMI and exploring promising diagnostic and therapeutic targets for SMI.Keywords: septic myocardial injury, ferroptosis, heart transcriptome, key genes, database

Jun-Chen Liu, Hong-Jing Yu Department of Clinical Pharmacy, The First People’s Hospital of Jiande, Jiande, People’s Republic of ChinaCorrespondence: Hong-Jing Yu, Department of Medical Oncology, The First People’s Hospital of jiande, No. 599 Yanzhou Avenue, Xin’anjiang street, Jiande, Zhejiang, 311600, People’s Republic of China, Tel +86 15869196365, Fax +86-571-64721520, Email hongjingyu1560@163.comAbstract: Immune checkpoint inhibitors (ICIs) have been shown to be significant in improving the overall survival rate in certain malignancies with poor prognoses. However, only 20– 40% of patients achieve long-term benefits, highlighting the relevance of the factors that influence the treatment, which can help clinicians improve their results and guide the development of new immune checkpoint therapies. In this study, the current pharmacokinetic aspects associated with the ICIs and the factors influencing clinical efficacy were characterised, including in terms of drug metabolism, drug clearance, hormonal effects and immunosuppressive effects.Keywords: immune checkpoint inhibitors, pharmacokinetics, influencing factors

A high precision calibration of the nonlinearity in the energy response of the Daya Bay Reactor Neutrino Experiment's antineutrino detectors is presented in detail. The energy nonlinearity originates from the particle-dependent light yield of the scintillator and charge-dependent electronics response. The nonlinearity model is constrained by γ calibration points from deployed and naturally occurring radioactive sources, the β spectrum from 12B decays, and a direct measurement of the electronics nonlinearity with a new flash analog-to-digital converter readout system. Less than 0.5% uncertainty in the energy nonlinearity calibration is achieved for positrons of kinetic energies greater than 1 MeV.

This Letter reports the first extraction of individual antineutrino spectra from ^{235}U and ^{239}Pu fission and an improved measurement of the prompt energy spectrum of reactor antineutrinos at Daya Bay. The analysis uses 3.5×10^{6} inverse beta-decay candidates in four near antineutrino detectors in 1958 days. The individual antineutrino spectra of the two dominant isotopes, ^{235}U and ^{239}Pu, are extracted using the evolution of the prompt spectrum as a function of the isotope fission fractions. In the energy window of 4-6 MeV, a 7% (9%) excess of events is observed for the ^{235}U (^{239}Pu) spectrum compared with the normalized Huber-Mueller model prediction. The significance of discrepancy is 4.0σ for ^{235}U spectral shape compared with the Huber-Mueller model prediction. The shape of the measured inverse beta-decay prompt energy spectrum disagrees with the prediction of the Huber-Mueller model at 5.3σ. In the energy range of 4-6 MeV, a maximal local discrepancy of 6.3σ is observed.

This work reports a precise measurement of the reactor antineutrino flux using 2.2 million inverse beta decay (IBD) events collected with the Daya Bay near detectors in 1230 days. The dominant uncertainty on the neutron detection efficiency is reduced by 56% with respect to the previous measurement through a comprehensive neutron calibration and detailed data and simulation analysis. The new average IBD yield is determined to be (5.91±0.09)×10-43 cm2/fission with total uncertainty improved by 29%. The corresponding mean fission fractions from the four main fission isotopes U235, U238, Pu239, and Pu241 are 0.564, 0.076, 0.304, and 0.056, respectively. The ratio of measured to predicted antineutrino yield is found to be 0.952±0.014±0.023 (1.001±0.015±0.027) for the Huber-Mueller (ILL-Vogel) model, where the first and second uncertainty are experimental and theoretical model uncertainty, respectively. This measurement confirms the discrepancy between the world average of reactor antineutrino flux and the Huber-Mueller model.

This Letter reports the first extraction of individual antineutrino spectra from ^{235}U and ^{239}Pu fission and an improved measurement of the prompt energy spectrum of reactor antineutrinos at Daya Bay. The analysis uses 3.5×10^{6} inverse beta-decay candidates in four near antineutrino detectors in 1958 days. The individual antineutrino spectra of the two dominant isotopes, ^{235}U and ^{239}Pu, are extracted using the evolution of the prompt spectrum as a function of the isotope fission fractions. In the energy window of 4-6 MeV, a 7% (9%) excess of events is observed for the ^{235}U (^{239}Pu) spectrum compared with the normalized Huber-Mueller model prediction. The significance of discrepancy is 4.0σ for ^{235}U spectral shape compared with the Huber-Mueller model prediction. The shape of the measured inverse beta-decay prompt energy spectrum disagrees with the prediction of the Huber-Mueller model at 5.3σ. In the energy range of 4-6 MeV, a maximal local discrepancy of 6.3σ is observed.

The Daya Bay Collaboration responds to comments posted by S. Parke and R.Zukanovich Funchal regarding our use of Delta(m^2_ee).

Li-Jun Wang,1,* Bai-Quan Qiu,1,* Ming-Ming Yuan,2,* Hua-Xi Zou,1 Cheng-Wu Gong,1 Huang Huang,2 Song-Qing Lai,3 Ji-Chun Liu1 1Department of Cardiothoracic Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, People’s Republic of China; 2Department of Cardiothoracic Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, People’s Republic of China; 3Institute of Cardiovascular Diseases, The First Affiliated Hospital of Nanchang University, Nanchang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ji-Chun Liu, Department of Cardiothoracic Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, People’s Republic of China, Tel +86 13907913502, Email liujichun999@yeah.net Song-Qing Lai, Institute of Cardiovascular Diseases, The First Affiliated Hospital of Nanchang University, Nanchang, People’s Republic of China, Tel +86 13699562160, Email ndyfy03743@ncu.edu.cnPurpose: Dilated cardiomyopathy (DCM) is a type of cardiomyopathy that can easily cause heart failure and has a high mortality rate. Therefore, there is an urgent need to study the underlying mechanism of action of dilated cardiomyopathy. In the present study, we aimed to explore potential miRNA–mRNA pairs and drugs related to DCM.Methods: The Microarray data were collected from the Gene Expression Omnibus (GEO) database. Bioinformatics analysis differentially expressed miRNAs and mRNAs in each microarray were obtained. The target genes of miRNAs were obtained from the miRWalk 2.0 database, and the intersection of these two gene sets (miRNA target genes and differentially expressed mRNAs in the microarray) was obtained. Pathway and Gene Ontology (GO) enrichment analyses were performed in the KOBAS database. Cytoscape software was used to construct the miRNA–mRNA network, and the final hub genes were obtained. Furthermore, we predicted several candidate drugs related to hub genes using DSigDB database. To confirm the abnormal expression of hub genes, qRT-PCR was performed.Results: In total, eight differentially expressed miRNAs and 92 differentially expressed mRNAs were identified. In addition, 47 differentially expressed miRNA target genes were identified. According to the analysis results of the miRNA-mRNA network, we identified hsa-miR-551b-3p, hsa-miR-770-5p, hsa-miR-363-3p, PIK3R1, DDIT4, and CXCR4 as hub genes in DCM. Several candidate drugs, which are related to the hug genes, were identified.Conclusion: In conclusion, in our study, we identified several hub genes that may be involved in the pathogenesis of DCM. Several drugs related to these hub genes may be used as clinical therapeutic candidates.Keywords: dilated cardiomyopathy, miRNA, mRNA, public database, drugs

We report a measurement of electron antineutrino oscillation from the Daya Bay Reactor Neutrino Experiment with nearly 4 million reactor ν[over ¯]_{e} inverse β decay candidates observed over 1958 days of data collection. The installation of a flash analog-to-digital converter readout system and a special calibration campaign using different source enclosures reduce uncertainties in the absolute energy calibration to less than 0.5% for visible energies larger than 2 MeV. The uncertainty in the cosmogenic ^{9}Li and ^{8}He background is reduced from 45% to 30% in the near detectors. A detailed investigation of the spent nuclear fuel history improves its uncertainty from 100% to 30%. Analysis of the relative ν[over ¯]_{e} rates and energy spectra among detectors yields sin^{2}2θ_{13}=0.0856±0.0029 and Δm_{32}^{2}=(2.471_{-0.070}^{+0.068})×10^{-3}  eV^{2} assuming the normal hierarchy, and Δm_{32}^{2}=-(2.575_{-0.070}^{+0.068})×10^{-3}  eV^{2} assuming the inverted hierarchy.

A search for a time-varying νe signal was performed with 621 days of data acquired by the Daya Bay Reactor Neutrino Experiment over 704 calendar days. The time spectrum of the measured νe flux normalized to its prediction was analyzed with a Lomb-Scargle periodogram, which yielded no significant signal for periods ranging from 2 hours to nearly 2 years. The normalized time spectrum was also fit for a sidereal modulation under the Standard Model Extension (SME) framework to search for Lorentz and CPT violation (LV-CPTV). Limits were obtained for all six flavor pairs ēμ,ēτ, μτ, ēē,μμ and ττ by fitting them one at a time, constituting the first experimental constraints on the latter three. Daya Bay's high statistics and unique layout of multiple directions from three pairs of reactors to three experimental halls allowed the simultaneous constraint of individual SME LV-CPTV coefficients without assuming others contribute negligibly, a first for a neutrino experiment.

Neutrons produced by cosmic ray muons are an important background forunderground experiments studying neutrino oscillations, neutrinoless doublebeta decay, dark matter, and other rare-event signals. A measurement of theneutron yield in the three different experimental halls of the Daya Bay ReactorNeutrino Experiment at varying depth is reported. The neutron yield in DayaBay's liquid scintillator is measured to be $Y_n=(10.26\pm 0.86)\times10^{-5}$, $(10.22\pm 0.87)\times 10^{-5}$, and $(17.03\pm 1.22)\times10^{-5}~\mu^{-1}~$g$^{-1}~$cm$^2$ at depths of 250, 265, and 860meters-water-equivalent. These results are compared to other measurements andthe simulated neutron yield in Fluka and Geant4. A global fit including theDaya Bay measurements yields a power law coefficient of $0.77 \pm 0.03$ for thedependence of the neutron yield on muon energy.

The Daya Bay Experiment consists of eight identically designed detectors located in three underground experimental halls named as EH1, EH2, EH3, with 250, 265 and 860 meters of water equivalent vertical overburden, respectively. Cosmic muon events have been recorded over a two-year period. The underground muon rate is observed to be positively correlated with the effective atmospheric temperature and to follow a seasonal modulation pattern. The correlation coefficient α, describing how a variation in the muon rate relates to a variation in the effective atmospheric temperature, is found to be αEH1 = 0.362±0.031, αEH2 = 0.433±0.038 and αEH3 = 0.641±0.057 for each experimental hall.

The Daya Bay experiment has observed correlations between reactor core fuel evolution and changes in the reactor antineutrino flux and energy spectrum. Four antineutrino detectors in two experimental halls were used to identify 2.2 million inverse beta decays (IBDs) over 1230 days spanning multiple fuel cycles for each of six 2.9 GW_{th} reactor cores at the Daya Bay and Ling Ao nuclear power plants. Using detector data spanning effective ^{239}Pu fission fractions F_{239} from 0.25 to 0.35, Daya Bay measures an average IBD yield σ[over ¯]_{f} of (5.90±0.13)×10^{-43}  cm^{2}/fission and a fuel-dependent variation in the IBD yield, dσ_{f}/dF_{239}, of (-1.86±0.18)×10^{-43}  cm^{2}/fission. This observation rejects the hypothesis of a constant antineutrino flux as a function of the ^{239}Pu fission fraction at 10 standard deviations. The variation in IBD yield is found to be energy dependent, rejecting the hypothesis of a constant antineutrino energy spectrum at 5.1 standard deviations. While measurements of the evolution in the IBD spectrum show general agreement with predictions from recent reactor models, the measured evolution in total IBD yield disagrees with recent predictions at 3.1σ. This discrepancy indicates that an overall deficit in the measured flux with respect to predictions does not result from equal fractional deficits from the primary fission isotopes ^{235}U, ^{239}Pu, ^{238}U, and ^{241}Pu. Based on measured IBD yield variations, yields of (6.17±0.17) and (4.27±0.26)×10^{-43}  cm^{2}/fission have been determined for the two dominant fission parent isotopes ^{235}U and ^{239}Pu. A 7.8% discrepancy between the observed and predicted ^{235}U yields suggests that this isotope may be the primary contributor to the reactor antineutrino anomaly.

Wen-Shuo Kuo, 1, 2 Chia-Yuan Chang, 3 Jui-Chang Liu, 4 Jian-Hua Chen, 5, 6,* Edmund Cheung So, 5– 7,* Ping-Ching Wu 8,* 1School of Chemistry and Materials Science, Nanjing University of Information Science and Technology, Nanjing, Jiangsu 210044, People’s Republic of China; 2Allergy & Clinical Immunology Research Center, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan Republic of China; 3Department of Mechanical Engineering, National Cheng Kung University, Tainan 701, Taiwan Republic of China; 4Department of Biochemistry and Molecular Biology, National Cheng Kung University, Tainan 701, Taiwan Republic of China; 5Department of Anesthesia & Medicine Research, An Nan Hospital, China Medical University, Tainan 709, Taiwan Republic of China; 6Department of Anesthesia, China Medical University, Taichung 404, Taiwan Republic of China; 7Graduate Institute of Medical Sciences, Chang Jung Christian University, Tainan 711, Taiwan Republic of China; 8Department of Biomedical Engineering, National Cheng Kung University, Tainan 701, Taiwan Republic of China*These authors contributed equally to this workCorrespondence: Jian-Hua Chen; Ping-Ching Wu Email aptx4869jfk@gmail.com; wbcxyz@bme.ncku.edu.twBackground: Multidrug-resistant (MDR) bacterial strain is a serious medical problem. Methicillin-resistant Staphylococcus aureus (MRSA) is resistant to many antibiotics and is often associated with several diseases such as arthritis, osteomyelitis, and endocarditis. The development of an alternative treatment for eliminating MDR bacteria such as MRSA has attracted a considerable amount of research attention. Moreover, the development of a material for highly efficient generation of reactive oxygen species (ROS) involving two-photon photodynamic therapy (PDT) is currently desirable.Materials and Methods: We present an example demonstrating that the use of water-soluble C 60(OH) 30 fullerenol with a 0.89 singlet oxygen quantum yield serving as a photosensitizer in PDT has the superior ability in effectively generating ROS.Results: It has ultra-low energy (228.80 nJ pixel− 1) and can perform 900 scans under two-photon excitation (TPE) in the near-infrared region (760 nm) to completely eliminate the MDR species. Furthermore, the favorable two-photon properties are absorption of approximately 760 nm in wavelength, absolute cross-section of approximately 1187.50 Göeppert–Mayer units, lifetime of 6.640 ns, ratio of radiative to nonradiative decay rates of approximately 0.053, and two-photon stability under TPE.Conclusion: This enabled water-soluble C 60(OH) 30 fullerenol to act as a promising two-photon photosensitizer proceeding with PDT to easily eliminate MDR species.Keywords: methicillin-resistant Staphylococcus aureus, two-photon photodynamic therapy, water-soluble fullerenol, two-photon excitation, near-infrared region

Wen-Shuo Kuo,1,2,* Tien-Sung Yeh,3,* Chia-Yuan Chang,4 Jui-Chang Liu,2 Chang-Hsin Chen,5 Edmund Cheung So,6,7 Ping-Ching Wu8 1School of Chemistry and Materials Science, Nanjing University of Information Science and Technology, Nanjing 210044, Jiangsu, People’s Republic of China; 2Allergy & Clinical Immunology Research Center, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan, Republic of China; 3Department of Physical Medicine and Rehabilitation, An Nan Hospital, China Medical University, Tainan 709, Taiwan, Republic of China; 4Department of Mechanical Engineering, National Cheng Kung University, Tainan 701, Taiwan, Republic of China; 5AbVision Inc., Milpitas, CA 95035, USA; 6Department of Anesthesia & Medicine Research, An Nan Hospital, China Medical University, Tainan 709, Taiwan, Republic of China; 7Graduate Institute of Medical Sciences, Chang Jung Christian University, Tainan 711, Taiwan, Republic of China; 8Department of Biomedical Engineering, National Cheng Kung University, Tainan, 701, Taiwan, Republic of China*These authors contributed equally to this workCorrespondence: Edmund Cheung So; Ping-Ching Wu Email edmundsotw@gmail.com; wbcxyz@bme.ncku.edu.twBackground: Although graphene quantum dots (GQDs) have received considerable research attention for their applications in various fields, the use of GQDs, such as nitrogen-doped GQDs (N-GQDs) and amino-functionalized N-GQDs (amino-N-GQDs), as photosensitizers to facilitate photodynamic therapy (PDT) has received limited research intention. To address this research gap, this study prepared novel amino-N-GQDs and investigated their properties.Methods: The amino-N-GQDs subjected to two-photon excitation (TPE) exhibited remarkable bactericidal capability in PDT. The bonding compositions of nitrogen and the amino-functionalized group played a critical role in their antimicrobial effects.Results: Compared with amino-group-free N-GQDs and amino-N-free GQDs, the amino-N-GQDs generated a higher amount of reactive oxygen species, demonstrating their superior efficacy for two-photon PDT. Additionally, the intrinsic luminescence properties and high photostability of the amino-N-GQDs demonstrate their suitability as an effective two-photon contrast agent for tracking bacteria during two-photon biomedical imaging.Conclusion: The amino-N-GQD and their remarkable properties may provide an efficient alternative approach for observing and easily eliminating malignant microbes in the future.Keywords: nitrogen atom-doped graphene quantum dots, amino-functionalized and nitrogen atom-doped graphene quantum dots, two-photon photodynamic therapy, two-photon contrast agent, two-photon biomedical imaging

Wei-Chang Xu,1,* Xiao Dong,1,* Jing-Li Ding,2 Ji-Chun Liu,1 Jian-Jun Xu,1 Yan-Hua Tang,1 Ying-Ping Yi,3 Chao Lu,1 Wei Yang,1 Jue-Sheng Yang,1 Yi Gong,1 Jian-Liang Zhou1 1Department of Cardiovascular Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, China; 2Department of Gastroenterology, The Second Affiliated Hospital of Nanchang University, Nanchang, China; 3Department of Science and Education, The Second Affiliated Hospital of Nanchang University, Nanchang, China *These authors contributed equally to this work Background: Macrophages play important roles in the immune response to, and successful implantation of, biomaterials. Titanium nanotubes are considered promising heart valve stent materials owing to their effects on modulation of macrophage behavior. However, the effects of nanotube-regulated macrophages on endothelial cells, which are essential for stent endothelialization, are unknown. Therefore, in this study we evaluated the inflammatory responses of endothelial cells to titanium nanotubes prepared at different voltages. Methods and results: In this study we used three different voltages (20, 40, and 60 V) to produce titania nanotubes with three different diameters by anodic oxidation. The state of macrophages on the samples was assessed, and the supernatants were collected as conditioned media (CM) to stimulate human umbilical vein endothelial cells (HUVECs), with pure titanium as a control group. The results indicated that titanium dioxide (TiO2) nanotubes induced macrophage polarization toward the anti-inflammatory M2 state and increased the expression of arginase-1, mannose receptor, and interleukin 10. Further mechanistic analysis revealed that M2 macrophage polarization controlled by the TiO2 nanotube surface activated the phosphatidylinositol 3-kinase/AKT and extracellular signal-regulated kinase 1/2 pathways through release of vascular endothelial growth factor to influence endothelialization. Conclusion: Our findings expanded our understanding of the complex influence of nanotubes in implants and the macrophage inflammatory response. Furthermore, CM generated from culture on the TiO2 nanotube surface may represent an integrated research model for studying the interactions of two different cell types and may be a promising approach for accelerating stent endothelialization through immunoregulation. Keywords: TiO2 nanotubes, axitinib, stent implant, endothelial cells, conditioned medium

Accelerator mass spectrometry (AMS) measurement of 59Ni has been established at CIAE with the HI-13 tandem accelerator and the recently developed ΔE-Q3D detection system. 59Ni standard and commercial NiO samples were measured to check the performance of the ΔE-Q3D detection system on 59Ni isobar separation and suppression. An overall suppression factor of about 107 for the interfering isobar 59Co resulting in detection sensitivity as low as 3.8 × 10 -13 atomic ratio (59Ni/Ni) has been obtained. Based on these techniques, the AMS measurement method of 59Ni with high sensitivity is developed. © 2013 Chinese Physical Society and the Institute of High Energy Physics of the Chinese Academy of Sciences and the Institute of Modern Physics of the Chinese Academy of Sciences and IOP Publishing Ltd. © 2013 Chinese Physical Society.

Xiaowu Wang,1,* Bo Xu,1,* Hongliang Liang,1 Shuyun Jiang,1 Hongmei Tan,1 Xinrong Wang,1 Xia Wang,2 Shiqiang Yu,1 Jincheng Liu1 1Department of Cardiovascular Surgery, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, Shaanxi, People’s Republic of China; 2Department of Health Statistics, Faculty of Preventive Medicine, Fourth Military Medical University, Xi’an 710032, Shaanxi, People’s Republic of China *These authors contributed equally to this work Purpose: Oral warfarin anticoagulation is a long-term treatment that is required after heart valve replacement. This treatment can prevent serious complications, such as embolism, thereby increasing patients’ postoperative survival rates and quality of life. Patients treated with artificial mechanical heart valve replacement were followed up over the phone at different times after the procedure, which is an effective method for preventing accidents related to postoperative oral warfarin anticoagulation. Our goal was to determine a method for providing theoretical guidance to patients on oral warfarin anticoagulation following heart valve replacement. Patients and methods: The participants of this study were patients who received artificial mechanical heart valve replacements and were followed up for 2 years after the procedure. Patient adherence to medical advice was calculated, and the distribution characteristics of adherence to prescribed timing, prescribed dose, and regular clinical follow-up among patients of both sexes and of different ages, regions, and educational levels attained were compared. Results: Univariate and multifactorial logistic regression analyses were used to evaluate the factors influencing adherence. Our analyses showed that adherence to oral warfarin anticoagulation in patients after heart valve replacement is influenced by sex, age, residential location, and educational attainment. The medication habits of patients can be evaluated accordingly via phone follow-up. As such, dose adjustment recommendations can be provided, significantly increasing the adherence to oral warfarin anticoagulation in patients after heart valve replacement. Conclusion: Adherence to oral warfarin anticoagulation among patients after heart valve replacement is affected by sex, age, type of residence, and educational level, as well as adherence to clinical follow-up over the phone. The follow-up sessions help establish good doctor–patient communication, which is critical for timely medication guidance, thus shortening medication administration delays and decreasing the overall length of therapy. Keywords: warfarin, artificial mechanical heart valve replacement, AMHVR, telephone follow-up, adherence, distribution characteristics

The sealed tube zinc reduction method for converting CO2 to graphite for AMS 14C measurements was originally developed for rapid production of graphite in biomedical tracer experiments. The method was usually thought to have low precision and a high background. We have modified the zinc reduction method originally outlined in Vogel [J.S. Vogel, Radiocarbon 34 (3) (1992) 344] by carefully controlling the amounts of reagents (zinc, titanium hydride and Co or Fe catalyst) and now routinely obtain a precision of 2-3‰ and a relatively low background of ∼50,000 14C years when analyzing for 14C at the Keck Carbon Cycle AMS facility at UC Irvine. Fractionation of carbon isotopes does occur during graphitization and depends on the graphitization yield, which can be affected by the amounts of reagents used and other conditions. The δ13C of our zinc-reduced graphite is usually lighter by 2-3‰ than the CO2 from which it is made, but this is corrected for in our system by simultaneous measurement of 13C/12C along with 14C/12C by the spectrometer. This method is suitable for 14C enriched samples, as well as natural abundance 14C samples, especially those with modern 14C contents. With improved precision and background, we believe that many disciplines can benefit from this technique because of its low cost and rapid production of graphite. © 2007 Elsevier B.V. All rights reserved.