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Yue Pan - Top 30 Publications

Functional magnetic hybrid nanomaterials for biomedical diagnosis and treatment.

Magnetic nanomaterials integrating supplemental functional materials are called magnetic hybrid nanomaterials (MHNs). Such MHNs have drawn increasing attention due to their biocompatibility and the potential applications either as alternative contrast enhancing agents or effective heat nanomediators in hyperthermia therapy. The joint function comes from the hybrid nanostructures. Hybrid nanostructures of different modification can be easily achieved owing to the large surface-area-to-volume ratio and sophisticated surface characteristic. In this focus article, we mainly discussed the design and synthesis of MHNs and their applications as multimodal imaging probes and therapy agents in biomedicine. These MHNs consisting magnetic nanomaterials with functional nanocomponents such as noble metal or isotopes could perform not only superparamagnetism but also features that can be adapted in, for example, enhancing computed tomography contrast modalities, positron emission tomography, and single-photon emission computed tomography. The combination of several techniques provides more comprehensive information by both synergizing the advantages, such as quantitative evaluation, higher sensitivity and spatial resolution, and mitigating the disadvantages. Such hybrid nanostructures could also provide a unique nanoplatform for enhanced medical tracing, magnetic field, and light-triggered hyperthermia. Moreover, potential advantages and opportunities will be achieved via a combination of diagnostic and therapeutic agents within a single platform, which is so-called 'theranostics.' We expect the combination of unique structural characteristics and integrated functions of multicomponent magnetic hybrid nanomaterials will attract increasing research interest and could lead to new opportunities in nanomedicine and nanobiotechnology. For further resources related to this article, please visit the WIREs website.

Upconversion Modulation through Pulsed Laser Excitation for Anti-counterfeiting.

Lanthanide-doped upconversion nanomaterials are emerging as promising candidates in optoelectronics, volumetric display, anti-counterfeiting as well as biological imaging and therapy. Typical modulations of upconversion through chemical methods, such as controlling phase, composition, morphology and size enable us to rationally manipulate emission profiles and lifetimes of lanthanide ions by using continuous-wave laser excitation. Here we demonstrate that under pulsed laser excitation the emission color of NaYF4:Er/Tm (2/0.5%)@NaYF4 core-shell nanoparticles has an obvious transformation from green to red colors. Moreover, both pulse duration and repetition frequency are responsible for manipulating the upconversion emission color. The mechanism of the phenomena may be that the pulsed laser sequence triggers the emission levels to non-steady upconversion states first, and then cuts off the unfinished population process within the pulse duration. This pump source dependent and resultant tunable fluorescence emission enables NaYF4:Er/Tm (2/0.5%)@NaYF4 nanoparticles as a promising fluorophore in the transparent anti-fake printing.

Rationally Designed PI3Kα Mutants to Mimic ATR and Their Use to Understand Binding Specificity of ATR Inhibitors.

ATR, a protein kinase in the PIKK family, plays a critical role in the cell DNA-damage response and is an attractive anticancer drug target. Several potent and selective inhibitors of ATR have been reported showing significant antitumor efficacy, with most advanced ones entering clinical trials. However, due to the absence of an experimental ATR structure, the determinants contributing to ATR inhibitors' potency and specificity are not well understood. Here we present the mutations in the ATP-binding site of PI3Kα to progressively transform the pocket to mimic that of ATR. The generated PI3Kα mutants exhibit significantly improved affinity for selective ATR inhibitors in multiple chemical classes. Furthermore, we obtained the X-ray structures of the PI3Kα mutants in complex with the ATR inhibitors. The crystal structures together with the analysis on the inhibitor affinity profile elucidate the roles of individual amino acid residues in the binding of ATR inhibitors, offering key insights for the binding mechanism and revealing the structure features important for the specificity of ATR inhibitors. The ability to obtain structural and binding data for these PI3Kα mutants, together with their ATR-like inhibitor binding profiles, makes these chimeric PI3Kα proteins valuable model systems for structure-based inhibitor design.

Fatty acid DSF binds and allosterically activates histidine kinase RpfC of phytopathogenic bacterium Xanthomonas campestris pv. campestris to regulate quorum-sensing and virulence.

As well as their importance to nutrition, fatty acids (FA) represent a unique group of quorum sensing chemicals that modulate the behavior of bacterial population in virulence. However, the way in which full-length, membrane-bound receptors biochemically detect FA remains unclear. Here, we provide genetic, enzymological and biophysical evidences to demonstrate that in the phytopathogenic bacterium Xanthomonas campestris pv. campestris, a medium-chain FA diffusible signal factor (DSF) binds directly to the N-terminal, 22 amino acid-length sensor region of a receptor histidine kinase (HK), RpfC. The binding event remarkably activates RpfC autokinase activity by causing an allosteric change associated with the dimerization and histidine phosphotransfer (DHp) and catalytic ATP-binding (CA) domains. Six residues were found essential for sensing DSF, especially those located in the region adjoining to the inner membrane of cells. Disrupting direct DSF-RpfC interaction caused deficiency in bacterial virulence and biofilm development. In addition, two amino acids within the juxtamembrane domain of RpfC, Leu172 and Ala178, are involved in the autoinhibition of the RpfC kinase activity. Replacements of them caused constitutive activation of RpfC-mediated signaling regardless of DSF stimulation. Therefore, our results revealed a biochemical mechanism whereby FA activates bacterial HK in an allosteric manner, which will assist in future studies on the specificity of FA-HK recognition during bacterial virulence regulation and cell-cell communication.

Detection of Ketones by a Novel Technology: Dipolar Proton Transfer Reaction Mass Spectrometry (DP-PTR-MS).

Proton transfer reaction mass spectrometry (PTR-MS) has played an important role in the field of real-time monitoring of trace volatile organic compounds (VOCs) due to its advantages such as low limit of detection (LOD) and fast time response. Recently, a new technology of proton extraction reaction mass spectrometry (PER-MS) with negative ions OH(-) as the reagent ions has also been presented, which can be applied to the detection of VOCs and even inorganic compounds. In this work, we combined the functions of PTR-MS and PER-MS in one instrument, thereby developing a novel technology called dipolar proton transfer reaction mass spectrometry (DP-PTR-MS). The selection of PTR-MS mode and PER-MS mode was achieved in DP-PTR-MS using only water vapor in the ion source and switching the polarity. In this experiment, ketones (denoted by M) were selected as analytes. The ketone (molecular weight denoted by m) was ionized as protonated ketone [M + H](+) [mass-to-charge ratio (m/z) m + 1] in PTR-MS mode and deprotonated ketone [M - H](-) (m/z m - 1) in PER-MS mode. By comparing the m/z value of the product ions in the two modes, the molecular weight of the ketone can be positively identified as m. Results showed that whether it is a single ketone sample or a mixed sample of eight kinds of ketones, the molecular weights can be detected with DP-PTR-MS. The newly developed DP-PTR-MS not only maintains the original advantages of PTR-MS and PER-MS in sensitive and rapid detection of ketones, but also can estimate molecular weight of ketones. Graphical Abstract ᅟ.

From Graphite to Graphene Oxide and Graphene Oxide Quantum Dots.

Many methods have been reported for synthesizing graphene oxide (GO) and graphene oxide quantum dots (GOQDs) where a tedious operational procedure and long reaction time are generally required. Herein, a facile one-pot solvothermal method that allows selective synthesis of pure GO and pure GOQDs, respectively is demonstrated. What is more, the final product of either GO or differently sized GOQDs can be easily controlled by adjusting the reaction temperatures or reactant ratios, which is also feasible when enlarged to gram scale. The 2.5 nm GOQDs show excellent photoluminescence that can be utilized for bioimaging or distinctive detection of Eu(3+) and Tb(3+) from their respective mixtures with other rare earth and/or transition metal ions, at sub-ppm level.

Selective Carbonyl-C(sp(3) ) Bond Cleavage To Construct Ynamides, Ynoates, and Ynones by Photoredox Catalysis.

Carbon-carbon bond cleavage/functionalization is synthetically valuable, and selective carbonyl-C(sp(3) ) bond cleavage/alkynylation presents a new perspective in constructing ynamides, ynoates, and ynones. Reported here is the first alkoxyl-radical-enabled carbonyl-C(sp(3) ) bond cleavage/alkynylation reaction by photoredox catalysis. The use of novel cyclic iodine(III) reagents are essential for β-carbonyl alkoxyl radical generation from β-carbonyl alcohols, including alcohols with high redox potential (Epox >2.2 V vs. SCE in MeCN). β-Amide, β-ester, and β-ketone alcohols yield ynamides, ynoates, and ynones, respectively, for the first time, with excellent regio- and chemoselectivity under mild reaction conditions.

Two-Component Signaling System VgrRS Directly Senses Extracytoplasmic and Intracellular Iron to Control Bacterial Adaptation under Iron Depleted Stress.

Both iron starvation and excess are detrimental to cellular life, especially for animal and plant pathogens since they always live in iron-limited environments produced by host immune responses. However, how organisms sense and respond to iron is incompletely understood. Herein, we reveal that in the phytopathogenic bacterium Xanthomonas campestris pv. campestris, VgrS (also named ColS) is a membrane-bound receptor histidine kinase that senses extracytoplasmic iron limitation in the periplasm, while its cognate response regulator, VgrR (ColR), detects intracellular iron excess. Under iron-depleted conditions, dissociation of Fe3+ from the periplasmic sensor region of VgrS activates the VgrS autophosphorylation and subsequent phosphotransfer to VgrR, an OmpR-family transcription factor that regulates bacterial responses to take up iron. VgrR-VgrS regulon and the consensus DNA binding motif of the transcription factor VgrR were dissected by comparative proteomic and ChIP-seq analyses, which revealed that in reacting to iron-depleted environments, VgrR directly or indirectly controls the expressions of hundreds of genes that are involved in various physiological cascades, especially those associated with iron-uptake. Among them, we demonstrated that the phosphorylated VgrR tightly represses the transcription of a special TonB-dependent receptor gene, tdvA. This regulation is a critical prerequisite for efficient iron uptake and bacterial virulence since activation of tdvA transcription is detrimental to these processes. When the intracellular iron accumulates, the VgrR-Fe2+ interaction dissociates not only the binding between VgrR and the tdvA promoter, but also the interaction between VgrR and VgrS. This relieves the repression in tdvA transcription to impede continuous iron uptake and avoids possible toxic effects of excessive iron accumulation. Our results revealed a signaling system that directly senses both extracytoplasmic and intracellular iron to modulate bacterial iron homeostasis.

Selective Visualization of the Endogenous Peroxynitrite in an Inflamed Mouse Model by a Mitochondria-Targetable Two-Photon Ratiometric Fluorescent Probe.

Peroxynitrite (ONOO(-)) is a kind of reactive oxygen species (ROS) with super activity of oxidization and nitration, and overproduction of ONOO(-) is associated with pathogenesis of many diseases. Thus, accurate detection of ONOO(-) with high sensitivity and selectivity is imperative for elucidating its functions in health or disease states. Herein we for the first time present a new two-photon ratiometric fluorescent ONOO(-) probe (MITO-CC) based on FRET mechanism by combining rational design strategy and dye-screening approach. MITO-CC, with fast response rate (within 20 s), excellent sensitivity (detection limit = 11.30 nM) and outstanding selectivity toward ONOO(-), was successfully applied to ratiometric detection of endogenous ONOO(-) produced by HepG2/RAW264.7 cells and further employed for imaging oxidative stress in an inflamed mouse model. Therefore, probe MITO-CC could be a potential biological tool to explore the roles of ONOO(-) under different physiological and pathological settings.

PEGylated [email protected] Nanodendrites as Novel Theranostic Agents for Computed Tomography Imaging and Photothermal/Radiation Synergistic Therapy.

The integration of photothermal therapy (PTT) with radiation therapy (RT) in a single nanoscale platform is believed to have considerable potential for cancer therapy. In this work, the rationally designed PEGylated [email protected] nanodendrites (NDs) have been developed as a novel X-ray computed tomography (CT) and PTT/RT enhanced theranostic agent for cancer therapy. The absorption of [email protected] NDs was turned to the near-infrared region with the growth of Pt nanobranches and thus enhances the efficacy of PTT. Furthermore, because of the high atomic number (high Z) of Au as well as Pt, [email protected] NDs significantly enhanced lethal effects of RT by inducing a highly localized radiation dose within cancer cells. More importantly, the combination of [email protected] ND-enhanced RT with PTT suppressed cancer cell growth more efficiently than that RT or PTT alone did, indicating a synergistic effect. Meanwhile, the [email protected] NDs also possess significant CT imaging signal enhancement that has the potential to guide PTT/RT for cancers. The integrated strategy significantly improved CT and PTT/RT of cancer cells with mild laser and radiation. Because of these advantages, [email protected] NDs have become appealing and effective agents for cancer theranostic.

Factors Associated with HIV Testing Among Participants from Substance Use Disorder Treatment Programs in the US: A Machine Learning Approach.

HIV testing is the foundation for consolidated HIV treatment and prevention. In this study, we aim to discover the most relevant variables for predicting HIV testing uptake among substance users in substance use disorder treatment programs by applying random forest (RF), a robust multivariate statistical learning method. We also provide a descriptive introduction to this method for those who are unfamiliar with it. We used data from the National Institute on Drug Abuse Clinical Trials Network HIV testing and counseling study (CTN-0032). A total of 1281 HIV-negative or status unknown participants from 12 US community-based substance use disorder treatment programs were included and were randomized into three HIV testing and counseling treatment groups. The a priori primary outcome was self-reported receipt of HIV test results. Classification accuracy of RF was compared to logistic regression, a standard statistical approach for binary outcomes. Variable importance measures for the RF model were used to select the most relevant variables. RF based models produced much higher classification accuracy than those based on logistic regression. Treatment group is the most important predictor among all covariates, with a variable importance index of 12.9%. RF variable importance revealed that several types of condomless sex behaviors, condom use self-efficacy and attitudes towards condom use, and level of depression are the most important predictors of receipt of HIV testing results. There is a non-linear negative relationship between count of condomless sex acts and the receipt of HIV testing. In conclusion, RF seems promising in discovering important factors related to HIV testing uptake among large numbers of predictors and should be encouraged in future HIV prevention and treatment research and intervention program evaluations.

siRNA-mediated suppression of collagen type iv alpha 2 (COL4A2) mRNA inhibits triple-negative breast cancer cell proliferation and migration.

Triple-negative breast cancer (TNBC) is more aggressive than other breast cancer subtypes. Collagen type IV alpha 2 (COL4A2), a major component of the basement membrane, dynamically influences a wide range of biological processes, including cancer pathogenesis and progression. This study evaluated the effects of COL4A2 siRNA delivered by lentiviral vector to TNBC cells. COL4A2 siRNA lenti-viral vector was constructed and transfected into MDA-MB-231 and MDA-MB-468 cells. The COL4A2 mRNA levels were quantified by RT-PCR. CCK8 assay was performed to evaluate cell proliferation and migration. Cell migration and invasion assays were carried out using Transwell. Cell apoptosis and cell cycle analyses were conducted using flow cytometric approach. We found that COL4A2 mRNA levels were significantly down-regulated in MDA-MB-231 and MDA-MB-468 cells after transfection with COL4A2 siRNA. Furthermore, cell migration and proliferation were significantly decreased and the cell cycle was arrested. Our results indicated that COL4A2 siRNA significantly suppresses the migration and proliferation of TNBC cells. Inhibition of COL4A2 may be a new target for the prevention and treatment of TNBC.

Substance use and STI acquisition: Secondary analysis from the AWARE study.

Sexually transmitted infections (STIs) are significant public health and financial burdens in the United States. This manuscript examines the relationship between substance use and prevalent and incident STIs in HIV-negative adult patients at STI clinics.

The shape effect of magnetic mesoporous silica nanoparticles on endocytosis, biocompatibility and biodistribution.

Although the aspect ratio (AR) play a crucial role in determining biological effects of homogeneous nanomaterials, studies available concerning how the shape contributes to biological effect of heterogeneous nanomaterials is limited. To systematically clarify the shape influence on the endocytosis, biocompatibility and biodistribution of magnetic mesoporous silica nanoparticles (M-MSNPs), three FITC-labeled M-MSNPs with different aspect ratio (AR=1, 2, and 4) were specifically designed and constructed through altering the ratios of CTAB/TEOS in a modified so-gel method. We have demonstrated that long-rod M-MSNP2 possessed higher intracellular internalization amount than the short-rod M-MSNP1 and the sphere-like M-MSNP0 in both cancer cells and normal cells due to the difference in the endocytosis pathways. However, there are no significant shape effects on biocompatibility including cytotoxicity and hemolytic rate. Moreover, biodistribution in HepG2 tumor-bearing mice showed that M-MSNPs administrated intravenously were mainly presented in reticuloendothelial system (RES) organs including liver, spleen and kidney. In particular, sphere-like M-MSNP0 were easily trapped in the liver, while long-rod M-MSP2 exhibited more retention in the spleen. It is worth noting that rod-like M-MSNPs are preferentially accumulated in tumor sites than sphere-like M-MSNPs, indicating an improved drug delivery efficacy in cancer therapy. Our findings may provide useful data for deeply understanding the interaction between the different shapes and biological behavior of M-MSNPs, which is expected to give rise to a new generation of heterogeneous M-MSNPs with significantly enhanced efficacy and safety for the cancer theranostics.

Magnetically separable maghemite/montmorillonite composite as an efficient heterogeneous Fenton-like catalyst for phenol degradation.

To develop highly efficient and conveniently separable iron containing catalysts is crucial to remove recalcitrant organic pollutants in wastewater through a heterogeneous Fenton-like reaction. A maghemite/montmorillonite composite was synthesized by a coprecipitation and calcination method. The physiochemical properties of catalysts were characterized by XRD, TEM, nitrogen physisorption, thermogravimetric analysis/differential scanning calorimetry (TG/DSC), zeta potential, and magnetite susceptibility measurements. The influence of calcination temperatures and reaction parameters was investigated. The calcined composites retain magnetism because the presence of montmorillonite inhibited the growth of γ-Fe2O3 nanoparticles, as well as their phase transition. The catalytic activities for phenol degradation were significantly enhanced by calcinations, which strengthen the interaction between iron oxides and aluminosilicate framework and result in more negatively charged surface. The composite (73 m(2)/g) calcined at 350 °C had the highest catalytic activities, with more than 99 % phenol reduction after only 35 min reaction at pH 3.6. Simultaneously, this catalyst exhibited high stability, low iron leaching, and magnetically separable ability for consecutive usage, making it promising for the removal of recalcitrant organic pollutants in wastewater.

A Selective Near-Infrared Fluorescent Probe for In Vivo Imaging of Thiophenols from a Focused Library.

Thiophenols are highly toxic industrial materials that, once released, will accumulate in the environment, and ultimately in human bodies, thereby causing serious health problems. To achieve their selective and sensitive detection, a novel near-infrared (NIR) fluorescent probe (CCP-1) from a focused library was developed for thiophenol species. Our studies show that CCP-1 displays a thiophenol-triggered 28-fold fluorescence intensity enhancement at 706 nm, with a detection limit of 34 nm observed. It is also able to differentiate thiophenols from various other thiol-containing analytes including hydrogen sulfide, hydrogen persulfide, and aliphatic thiols. In total, the desirable properties (e.g., excitation/emission in the NIR region, good cell-membrane permeability, intracellular stability, and low cytotoxicity) make CCP-1 a potential candidate for thiophenol detection both in vitro and in vivo. In addition, CCP-1, for the first time, successfully visualized thiophenols in mice models of thiophenol inhalation.

Supramolecular Self-Assemblies with Nanoscale RGD Clusters Promote Cell Growth and Intracellular Drug Delivery.

In this work, we reported the generation of a novel supramolecular hydrogelator from a peptide derivative which consisted of a structural motif (e.g., Fc-FF) for supramolecular self-assembly and a functional moiety (e.g., RGD) for integrin binding. Following self-assembly in water at neutral pH, this molecule first tended to form metastable spherical aggregates, which subsequently underwent a morphological transformation to form high-aspect-ratio nanostructures over 2 h when aged at room temperature. More importantly, because of the presence of nanoscale RGD clusters on the surface of nanostructures, the self-assembled nanomaterials (e.g., nanoparticles and nanofibers) can be potentially used as a biomimetic matrix for cell culture and as a vector for cell-targeting drug delivery via multivalent RGD-integrin interactions.

Synthesis of Hierarchically Porous Sandwich-Like Carbon Materials for High-Performance Supercapacitors.

For the first time, hierarchically porous carbon materials with a sandwich-like structure are synthesized through a facile and efficient tri-template approach. The hierarchically porous microstructures consist of abundant macropores and numerous micropores embedded into the crosslinked mesoporous walls. As a result, the obtained carbon material with a unique sandwich-like structure has a relatively high specific surface (1235 m(2)  g(-1) ), large pore volume (1.30 cm(3)  g(-1) ), and appropriate pore size distribution. These merits lead to a comparably high specific capacitance of 274.8 F g(-1) at 0.2 A g(-1) and satisfying rate performance (87.7 % retention from 1 to 20 A g(-1) ). More importantly, the symmetric supercapacitor with two identical as-prepared carbon samples shows a superior energy density of 18.47 Wh kg(-1) at a power density of 179.9 W kg(-1) . The asymmetric supercapacitor based on as-obtained carbon sample and its composite with manganese dioxide (MnO2 ) can reach up to an energy density of 25.93 Wh kg(-1) at a power density of 199.9 W kg(-1) . Therefore, these unique carbon material open a promising prospect for future development and utilization in the field of energy storage.

Polymorphisms in PDLIM5 gene are associated with alcohol dependence, type 2 diabetes, and hypertension.

The PDZ and LIM domain 5 (PDLIM5) gene may play a role in alcohol dependence (AD), bipolar disorder, and major depressive disorder; however, no study has identified shared genetic variants within PDLIM5 gene among AD, type 2 diabetes (T2D), and hypertension. This study investigated the association of 72 single nucleotide polymorphism (SNPs) with AD (1066 AD cases and 1278 controls) in the Study of Addiction - Genetics and Environment (SAGE) sample and 47 SNPs with T2D (878 cases and 2686 non-diabetic) and hypertension (825 cases and 2739 non-hypertensive) in the Marshfield sample. Multiple logistic regression models in PLINK software were used to examine the associations of genetic variants with AD, T2D, and hypertension and SNP x alcohol consumption interactions for T2D and hypertension. Twenty-five SNPs were associated with AD in the SAGE sample (p < 0.05); rs1048627 showed the strongest association with AD (p = 5.53 × 10(-4)). Of the 25 SNPs, 5 SNPs showed associations with both AD in the SAGE sample and T2D in the Marshfield sample (top SNP rs11097432 with p = 0.00107 for T2D and p = 0.0483 for AD) while 6 SNPs showed associations with both AD in the SAGE sample and hypertension in the Marshfield sample (top SNP rs12500426 with p = 0.0119 for hypertension and p = 1.51 × 10(-3) for AD). SNP (rs6532496) showed significant interaction with alcohol consumption for hypertension. Our results showed that several genetic variants in PDLIM5 gene influence AD, T2D and hypertension. These findings offer the potential for new insights into the pathogenesis of AD, T2D, and hypertension.

Molecular Characterization and Viral Origin of the 2015 Dengue Outbreak in Xishuangbanna, Yunnan, China.

A total of 1067 serum samples were collected from febrile patients in Xishuangbanna, Yunnan, 2015. Of these, 852 cases were confirmed to be dengue NS1-positive. 76 structural protein genes were sequenced through RT-PCR based on the viral RNAs extracted from serum samples. Phylogenetic analysis revealed that all strains were classified as cosmopolitan genotype of DENV-2. After comparing with the DENV-2SS, 173 base substitutions were found in 76 sequences, resulting in 43 nonsynonymous mutations, of which 22 mutations existed among all samples. According to secondary structure prediction, 8 new possible nucelotide/protein binding sites were found and another 4 sites were lost among the 775 amino acids of DENV structural proteins as compared with DENV-2SS. Meanwhile, 6 distinct amino acid changes were found in the helix and strand regions, and the distribution of the exposed and buried regions was slightly altered. The results indicated that the epidemic dengue strains of Xishuangbanna in 2015 are most similar to the Indian strain in 2001 and the Sri Lankan strain in 2004. Moreover, it also show a very strong similarity to the epidemic strains of Fujian province in 1999 and 2010, which show that there is an internal recycling epidemic trend of DENV in China.

Molecular identification of human enteroviruses associated with aseptic meningitis in Yunnan province, Southwest China.

Human enteroviruses (EVs) are the major causative agents of aseptic meningitis. In this study, a total of 524 children were admitted to the children Kunming hospital (continental China) for aseptic meningitis manifestations in 2009 and 2010. An EV infection was diagnosed in 85/524 children (16.2 %) and the viruses detected were assigned to 16 serotypes. Most serotypes belonged to the enterovirus B species. Echovirus 9 was predominant (24.7 %), followed by coxsackievirus B5 (23.5 %) and then echovirus 30 (16.5 %). Echovirus 9 was firstly identified as the predominant serotype in sporadic aseptic meningitis which occurred in Yunnan, Southwest China. This work indicates the need to perform large-scale surveillance to gain a better insight into the epidemiology of enteroviruses associated with aseptic meningitis in China.

Distance effects in electrochemical micromachining.

Considering exponential dependence of currents on double-layer voltage and the feedback effect of the electrolyte resistance, a distance effect in electrochemical micromachining is found, namely that both time constant and double-layer voltage depend on the separation of electrodes. The double-layer voltage is the real voltage used in processing. Under DC voltage, the apparent voltages between two electrodes are constant for different separations, but the real voltages change with the separations. Small separations exert substantial effects on the real voltages. Accordingly, a DC-voltage small-separation electrochemical micromachining technique was proposed. The double-layer voltage drops sharply as the small separation increases. Thus, the electrochemical reactions are confined to electrode regions in very close proximity even under DC voltage. The machining precision can be significantly enhanced by reducing the voltage and separation between electrodes. With this technique, the machining of conducting materials with submicrometre precision was achieved.

Rapid and large-scale synthesis of bare Co3O4 porous nanostructures from an oleate precursor as superior Li-ion anodes with long-cycle lives.

In this study, we describe a rapid and environmentally friendly synthesis of bare Co3O4 nanocrystals derived from Co(ii) oleate complexes by calcination treatment. When directly used as anode materials for lithium-ion batteries (LIBs), the as-prepared nanocrystals could deliver a high reversible capacity of 980 mA h g(-1) after 250 cycles at a current density of 100 mA g(-1) and excellent cycling performance, which may be beneficial to promote the further development of the next generation of lithium ion batteries. The synthetic route can offer great advantages for the flash preparation of other metal oxide nanocrystals for energy storage application.

Attitudes, Beliefs, and Measures Taken by Parents to Protect Their Children from the Sun in Guangzhou City, China.

Excessive sun exposure can cause sunburn, suntan, skin photoaging, and even skin cancer. Skin photoaging conflicts with the human pursuit of a young and beautiful appearance. Some research data indicate that the incidence of skin cancer in the Chinese has been increasing, although it remains lower than in whites. To estimate the prevalence of sun protection used on Chinese children aged 3-13 years and identify its predictors, a population-based cross-sectional questionnaire was given to 3684 parents/guardians of children in Guangzhou, China, of which 3083 questionnaires were returned. Of those returned, 35.5% of parents/guardians reported regularly using sun protection on their children and the primary reason cited was to prevent sunburn. Hats and handheld umbrellas were the most frequently used measures; sunscreen was less common, and when used, 48.8% of parents/guardians still reapplied sunscreen on their children every 2.0-3.0 h. Parental age, parents using sun protection measures themselves when outdoors, and the child's sex were factors associated with regular use of sun protection on children. These results suggest that sun protection campaigns targeted toward parents and children need to be conducted in Guangzhou, or throughout China, to strengthen awareness about sun protection and address any inadequate protocols of sun protection.

Fractal vector optical fields.

We introduce the concept of a fractal, which provides an alternative approach for flexibly engineering the optical fields and their focal fields. We propose, design, and create a new family of optical fields-fractal vector optical fields, which build a bridge between the fractal and vector optical fields. The fractal vector optical fields have polarization states exhibiting fractal geometry, and may also involve the phase and/or amplitude simultaneously. The results reveal that the focal fields exhibit self-similarity, and the hierarchy of the fractal has the "weeding" role. The fractal can be used to engineer the focal field.

Arbitrarily tunable orbital angular momentum of photons.

Orbital angular momentum (OAM) of photons, as a new fundamental degree of freedom, has excited a great diversity of interest, because of a variety of emerging applications. Arbitrarily tunable OAM has gained much attention, but its creation remains still a tremendous challenge. We demonstrate the realization of well-controlled arbitrarily tunable OAM in both theory and experiment. We present the concept of general OAM, which extends the OAM carried by the scalar vortex field to the OAM carried by the azimuthally varying polarized vector field. The arbitrarily tunable OAM we presented has the same characteristics as the well-defined integer OAM: intrinsic OAM, uniform local OAM and intensity ring, and propagation stability. The arbitrarily tunable OAM has unique natures: it is allowed to be flexibly tailored and the radius of the focusing ring can have various choices for a desired OAM, which are of great significance to the benefit of surprising applications of the arbitrary OAM.

Bayesian logistic regression in detection of gene-steroid interaction for cancer at PDLIM5 locus.

The PDZ and LIM domain 5 (PDLIM5) gene may play a role in cancer, bipolar disorder, major depression, alcohol dependence and schizophrenia; however, little is known about the interaction effect of steroid and PDLIM5 gene on cancer. This study examined 47 single-nucleotide polymorphisms (SNPs) within the PDLIM5 gene in the Marshfield sample with 716 cancer patients (any diagnosed cancer, excluding minor skin cancer) and 2848 noncancer controls. Multiple logistic regression model in PLINK software was used to examine the association of each SNP with cancer. Bayesian logistic regression in PROC GENMOD in SAS statistical software, ver. 9.4 was used to detect gene- steroid interactions influencing cancer. Single marker analysis using PLINK identified 12 SNPs associated with cancer (P< 0.05); especially, SNP rs6532496 revealed the strongest association with cancer (P = 6.84 × 10⁻³); while the next best signal was rs951613 (P = 7.46 × 10⁻³). Classic logistic regression in PROC GENMOD showed that both rs6532496 and rs951613 revealed strong gene-steroid interaction effects (OR=2.18, 95% CI=1.31-3.63 with P = 2.9 × 10⁻³ for rs6532496 and OR=2.07, 95% CI=1.24-3.45 with P = 5.43 × 10⁻³ for rs951613, respectively). Results from Bayesian logistic regression showed stronger interaction effects (OR=2.26, 95% CI=1.2-3.38 for rs6532496 and OR=2.14, 95% CI=1.14-3.2 for rs951613, respectively). All the 12 SNPs associated with cancer revealed significant gene-steroid interaction effects (P < 0.05); whereas 13 SNPs showed gene-steroid interaction effects without main effect on cancer. SNP rs4634230 revealed the strongest gene-steroid interaction effect (OR=2.49, 95% CI=1.5-4.13 with P = 4.0 × 10⁻⁴ based on the classic logistic regression and OR=2.59, 95% CI=1.4-3.97 from Bayesian logistic regression; respectively). This study provides evidence of common genetic variants within the PDLIM5 gene and interactions between PLDIM5 gene polymorphisms and steroid use influencing cancer.

Pulse wave velocity in elastic and muscular arteries: tracking stability and association with anthropometric and hemodynamic measurements.

Pulse wave velocity (PWV) has been used as a measurement for arterial stiffness, a predictor of cardiovascular risk. Tracking describes the stability of a measurement over time. The purpose of this study was to evaluate the tracking stability of carotid-femoral (cfPWV), carotid-radial (crPWV) and carotid-distal (cdPWV) PWV in young adults and their associations with anthropometric and hemodynamic measurements. cfPWV, crPWV and cdPWV were measured by tonometric (SphygmoCor) technique in 531 subjects (aged 23.7±4.9 with 42.9% African Americans and 49.9% females). Out of these subjects, 142 subjects had all these 3 PWV measurements evaluated again during their next visit with an average follow-up time of 2 years. In the tracking analysis on the data from the 142 subjects, cfPWV displayed moderate to relatively high tracking ability (r=0.61, P<0.001), whereas crPWV and cdPWV only displayed low to moderate tracking coefficients (r=0.29 and r=0.36 respectively, P<0.001). In the association test on the data from the 531 subjects, all three PWV measurements showed significant correlations with age and obesity related measurements. cfPWV displayed stronger correlations with these parameters. In addition, all three PWVs showed significant correlations with systolic blood pressure, diastolic blood pressure, mean arterial pressure and pulse pressure with the exception that no correlation existed between crPWV and pulse pressure. The higher tracking ability of cfPWV and its higher association with obesity related measurements highlights the importance of using cfPWV compared with crPWV and cdPWV for research and clinical settings.

Janus "nano-bullets" for magnetic targeting liver cancer chemotherapy.

Tumor-targeted delivery of anti-cancer drugs with controlled drug release function has been recognized as a promising strategy for pursuit of increased chemotherapeutic efficacy and reduced adverse effects. Development of magnetic nanoparticulates as delivery carriers to accommodate cytotoxic drugs for liver cancer treatment has evoked immense interest with respect to their convenience in biomedical application. Herein, we engineered multifunctional Janus nanocomposites, characterized by a head of magnetic Fe3O4 and a body of mesoporous SiO2 containing doxorubicin (DOX) as "nano-bullets" (M-MSNs-DOX). This nanodrug formulation possessed nanosize with controlled aspect-ratio, defined abundance in pore structures, and superior magnetic properties. M-MSN-DOX was determined to induce selective growth inhibition to the cancer cell under magnetic field rather than human normal cells due to its preferable endocytosis by the tumor cells and pH-promoted DOX release in the interior of cancer cells. Ultimately, both subcutaneous and orthotropic liver tumor models in mice have demonstrated that the proposed Janus nano-bullets imposed remarkable suppression of the tumor growth and significantly reduced systematic toxicity. Taken together, this study demonstrates an intriguing targeting strategy for liver cancer treatment based on a novel Janus nano-bullet, aiming for utilization of nanotechnology to obtain safe and efficient treatment of liver cancer.

The western-type diet induces anti-HMGB1 autoimmunity in Apoe(-/-) mice.

Anti-HMGB1 autoimmunity plays a role in systemic lupus erythematosus (SLE). Because SLE increases atherosclerosis, we asked whether the same autoimmunity might play a role in atherogenesis.