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This study explores the effect of Al-buffered layers on the crystal structure and superconductivity of MgB2. The unique Mg1-xAlxB2 phase formed at a thickness of 190 nm is a promising technique for thin-film fabrication. The upper critical field (Hc2) of Mg1-xAlxB2 is suppressed, which corresponds to a change in interband scattering, as confirmed by X-ray diffraction and extended X-ray absorption fine structure results. By contrast, the thicker samples with the Al-buffer layer, which contain MgB2 on the top surface, show an improvement in Hc2 compared to the pure sample because the grain boundaries act as flux pinning sources. The observed reduction in the electron–phonon coupling constants correlates with Tc suppression in the Al-buffered samples. A Meissner force curve reveal larger London penetration depth (λL) in Al-buffered films than in pure MgB2 samples. Particularly, the Mg1-xAlxB2 sample, exhibits a λL value at 0 K of 1009.68 nm, resulting in a thermodynamic critical field (Hc) of 0.026 T. Higher-thickness Al-buffered film samples, which have a MgB2 layer on the top surface, displays λL and Hc values in close agreement with those of a pure MgB2 film.

The growing interest in microalgae and cyanobacteria biomass as an alternative to traditional animal feed is hindered by high production costs. Using wastewater (WW) as a cultivation medium could offer a solution, but this approach risks introducing harmful substances into the biomass, leading to significant safety concerns. In this study, we addressed these challenges by selectively extracting nitrates and phosphates from WW using drinking water treatment residuals (DWTR) and chitosan. This method achieved peak adsorption capacities of 4.4 mg/g for nitrate and 6.1 mg/g for phosphate with a 2.5 wt% chitosan blend combined with DWTR-nitrogen. Subsequently, these extracted nutrients were employed to cultivate Spirulina platensis, yielding a biomass productivity rate of 0.15 g/L/d, which is comparable to rates achieved with commercial nutrients. By substituting commercial nutrients with nitrate and phosphate from WW, we can achieve a 18 % reduction in the culture medium cost. While the cultivated biomass was initially nitrogen-deficient due to low nitrate levels, it proved to be protein-rich, accounting for 50 % of its dry weight, and contained a high concentration of free amino acids (1260 mg/g), encompassing all essential amino acids. Both in vitro and in vivo toxicity tests affirmed the biomass's safety for use as an animal feed component. Future research should aim to enhance the economic feasibility of this alternative feed source by developing efficient adsorbents, utilizing cost-effective reagents, and implementing nutrient reuse strategies in spent mediums.

This study examines how different types of NPOs influence local governments’ hazard mitigation efforts. Based on Marquis et al. (2013), we categorized NPOs into three types and analyzed a county-level dataset (N=1,626) with fixed-effect Poisson regression. Findings indicate that counties with a greater number of NPOs working for enhancing the overall community’s social welfare are more likely to develop hazard mitigation projects. In contrast, the prevalence of elite-oriented NPOs that focus on selective community constituents is negatively associated with local governments’ hazard mitigation project development. This study provides important implications for the critical roles of NPOs in facilitating hazard mitigation efforts in relationships with local governments.

Thin-film high-entropy alloy (HEA) superconductors have recently attracted a lot of attention, but their critical current density and potential usefulness in engineering applications has remained unclear. Here, the authors fabricate HEA films with remarkably high critical current density and resistance to radiation damage.

In cognitive radio (CR) systems, compressed sensing (CS) has emerged as a promising approach for detecting wireless spectrum that is underutilized (i.e., sparse in the frequency domain). The use of CS techniques is believed to reduce the sensing time at minimal hardware overhead compared to the traditional sweeping spectrum scanner, which is a simple energy detector that scans the frequency bins sequentially. Although the sweeping spectrum scanners can be parallelized to reduce the total scanning time, time-multiplexing is still necessary to cover the very large scanning bandwidth. By contrast, the CS spectrum scanner captures the entire spectrum concurrently to detect the occupied frequency bins. Despite the recent popularity of CS spectrum sensing techniques, no published work is available that rigorously compares the performance of these two sensing schemes under similar hardware constraints and same available total sensing time. This paper makes such a comparison and shows that the multi-channel sweeping spectrum scanner outperforms the CS scanner except at the high input signal-to-noise ratios when the two scanners become comparable. The advantage of the sweeping scanner is that although it observes each frequency bin for a shorter time, each sensing is more reliable and not corrupted by the folding of other frequency bins as in the CS scanner.

In this study, an artificial stream mesocosm consisting of a head tank, faster-flowing riffle section, gravel section, pool section, lower-run section, and tail tank was installed to simulate a chemical spill in a river. The responses of freshwater periphyton algae, crustacea (Moina macrocopa), freshwater worm (Limnodrilus hoffmeisteri), benthic midge (Glyptotendipes tokunagai), and fish (Zacco platypus and Aphyocypris chinensis) were observed after exposure to benzyl chloride (classified as an accident preparedness substance, APS) at concentrations of 1, 2, and 4 µL/L for 22.5 h. Higher concentrations increased the inhibition (photosynthetic efficiency decrease) of periphyton algae and the mortality of M. macrocopa, whereas the reproduction of the female cladoceran decreased in the 4 µL/L treatment. Mortality of fish did not occur or was lower (≤20%) at all concentrations; however, toxic symptoms were observed for some time after chemical exposure termination and later, symptoms receded. G. tokunagai mortality increased at all concentrations except the control after seven days, and no significant toxic effects were observed in L. hoffmeisteri. The hazardous concentration of benzyl chloride was calculated as 94 µg/L. This study showed the different sensitivities of each species to benzyl chloride. The findings can assist in environmental risk assessment of APSs after chemical spills to protect Korean aquatic species.

Abstract We investigated a high-quality MgB2 thin film with a thickness of ~1000 nm on an Al2O3 substrate using optical spectroscopy. We measured the reflectance spectra of the film at various temperatures both below, and above, the superconducting transition temperature, T c $$\simeq $$ ≃ 40 K. An earlier study showed that when the sample surface is exposed to air the optical properties of the surface change immediately, however, the saturated change is negligibly small in the far-infrared region. The optical conductivity spectrum in the normal state shows two (narrow and broad) Drude modes, with the narrow Drude mode being dominant in the low frequency region below 1000 cm−1. Our study, which uses a good-quality sample, provides more reliable data on the optical properties of MgB2, in a similar spectral range. The optical data is analyzed further using an extended Drude model, and the electron-phonon spectral density function, α 2 F(ω), is extracted. The spectral density function α 2 F(ω) features two peaks: a small one near 114 cm−1, and a strong peak around the 550 cm−1 where the B-B bond stretching phonon exists. Our data in the superconducting state does not show the expected energy shift of the onset of scattering associated with the α 2 F(ω) peaks.

Hydroxy fatty acids (HFAs) have numerous industrial applications but are absent in most vegetable oils. Physaria lindheimeri accumulating 85% HFA in its seed oil makes it a valuable resource for engineering oilseed crops for HFA production. To discover lipid genes involved in HFA synthesis in P. lindheimeri, transcripts from developing seeds at various stages, as well as leaf and flower buds, were sequenced. Ninety-seven percent clean reads from 552,614,582 raw reads were assembled to 129,633 contigs (or transcripts) which represented 85,948 unique genes. Gene Ontology analysis indicated that 60% of the contigs matched proteins involved in biological process, cellular component or molecular function, while the remaining matched unknown proteins. We identified 42 P. lindheimeri genes involved in fatty acid and seed oil biosynthesis, and 39 of them shared 78–100% nucleotide identity with Arabidopsis orthologs. We manually annotated 16 key genes and 14 of them contained full-length protein sequences, indicating high coverage of clean reads to the assembled contigs. A detailed profiling of the 16 genes revealed various spatial and temporal expression patterns. The further comparison of their protein sequences uncovered amino acids conserved among HFA-producing species, but these varied among non-HFA-producing species. Our findings provide essential information for basic and applied research on HFA biosynthesis.

Study DesignProspective randomized noninferiority trial.PurposeTo evaluate whether the union rate of anterior cervical discectomy and fusion (ACDF) using a polyetheretherketone (PEEK) cage filled with a mixture of hydroxyapatite (HA) and demineralized bone matrix (DBM) is inferior to that of a mixture of β-tricalcium phosphate (β-TCP) and HA.Overview of LiteratureThere have been no clinical trials investigating the outcomes of a mixture of HA and DBM in a PEEK cage in ACDF.MethodsEighty-five eligible patients were randomly assigned to group B (n=43), in which a PEEK cage with a mixture of HA and DBM was used, or group C (n=42), in which a PEEK cage with a mixture of HA and β-TCP was used. The primary study endpoint was the fusion rate, which was assessed with dynamic radiographs and computed tomography (CT) scans. Secondary endpoints included pain intensity using a visual analogue scale, functional outcome using a neck disability index score, laboratory tests of inflammatory profiles, and the infection rate.ResultsSeventy-seven patients (38 in group B and 39 in group C) were included in the final analysis. One year postoperatively, bone fusion was achieved in 87% of group B patients and 87% of group C patients on dynamic radiographs, and 87% of group B patients and 72% of group C patients on CT scans (p=1.00 and 0.16, respectively). There were also no between-groups differences with respect to the secondary endpoints.ConclusionsA HA/DBM mixture inside a PEEK cage can provide noninferior outcomes compared to a HA/TCP mixture in ACDF.

Keywords:acute renal cortical necrosis; antifibrinolytic drug; tranexamic acid [ABSTRACT FROM PUBLISHER]

This paper describes a method to estimate conservation voltage reduction (CVR) factors using data measured in power distribution systems. A direct method is proposed to estimate CVR factors using only data measured at the moment of the transformer tap change. The mean absolute deviation (MAD) direct method is proposed to consider direct methods and load variations. The proposed methods do not necessitate intentional tap changes for testing purposes. Instead, the voltage and load changes that occur when the tap changes, for voltage regulation purposes, are measured and utilized in the CVR factor calculation. The proposed methods were tested using data obtained from the Korea Electric Power Corporation (KEPCO) system, and the results revealed that CVR factors for both active power and reactive power could be estimated using data measured in power distribution systems. Results of the CVR factor estimation for the active power revealed that the highest CVR factors occurred in winter, during which a large quantity of heating loads exist. In addition, the estimated CVR factors for the reactive power were higher than the estimated CVR factors for the active power because reactive power is more sensitive to voltage changes.

'Taedong Valley' is a high yielding and processing potato cultivar, which is a clonal selection resulting from a cross between 'W870' and 'A88431-1'. It is a medium maturating cultivar with medium plant height and light green foliage. 'Taedong Valley' has profuse flowering habit and light purple flowers. Tubers are smooth, round, and with yellow skin, light yellow flesh, medium eye depth. Tubers have medium dormancy and good keeping quality. 'Taedong Valley' has stable yield under wide range of climatic conditions. It is resistant to common scab and potato virus Y, but moderately susceptible to late blight. It is also resistant to most of the disorders, particularly dehiscence, hollow heart and internal brown spots. This cultivar has high level of tuber uniformity and capable of yielding 43.6 t/ha which is about 9.0% higher than the control potato cultivar 'Atlantic' under optimum agronomical practices. [ABSTRACT FROM AUTHOR]

In 2005, the Korea Disease Control and Prevention Agency (KDCA) launched "Health Care Facility Counseling Project on People Living with human immunodeficiency virus (HIV)" funded by the private-subsidy project for the prevention of acquired immune deficiency syndrome (AIDS) and sexually transmitted diseases to provide people living with HIV (PLWH) psychological support and counsel them about the disease and antiretroviral therapy (ART). Currently, 38 counseling nurse specialists work at 28 healthcare facilities for patient care. Of all PLWH in Korea, 71.9% received benefits from the Counseling Project. Adherence to ART medication (>95.0%), level of depression or anxiety, counseling coverage, and viral load status were monitored as common project indicators. Various specialized programs have been implemented in diverse facilities. This project has played a pivotal role in HIV care continuum and viral suppression policies, resulting in 95.9% of PLWH maintaining undetectable status (<40 copies/ml) in 2021. In this review, we present the chronology and fulfillment of this project, which will be an essential step for future planning in the context of aging and the chronic comorbid nature of HIV/AIDS., Competing Interests: No conflict of interest., (Copyright © 2023 by The Korean Society of Infectious Diseases, Korean Society for Antimicrobial Therapy, and The Korean Society for AIDS.)

Microscopic visualization of DNA molecules is a simple, intuitive, and powerful method. Nonetheless, DNA-molecule quantification methods that employ microscopic visualization have not been reported so far. In this study, a new quantitative approach is presented that enables the counting of individual DNA molecules that have been rendered visible by fluorescence microscopy. Toward this, a microfluidic device was employed that directed DNA molecules into microchannels and deposited the molecules onto a positively charged surface. This microfluidic device had a vertically tapered channel inlet structure that prevented the accumulation of excess DNA molecules in the channel inlet while creating a tapering flow, thereby ensuring the even distribution of the DNA molecules in the microchannels. The channel heights and the density of positive charges on the surface were optimized for analysis. The linearity of this method with respect to the determination of the concentration of DNA in solutions was subsequently determined. The limit of detection was 0.48 fg/μL, which corresponds to 64 molecules of 7.25 kbp DNA in 1 μL of sample. This quantitative approach was finally used to count two types of plasmids co-transformed in an E. coli cell; a measurement that is typically considered challenging with gel electrophoresis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Laser direct-writing enables micro and nanoscale patterning, and is thus widely used for cutting-edge research and industrial applications. Various nanolithography methods, such as near-field, plasmonic, and scanning-probe lithography, are gaining increasing attention because they enable fabrication of high-resolution nanopatterns that are much smaller than the wavelength of light. However, conventional methods are limited by low throughput and scalability, and tend to use electron beams or focused-ion beams to create nanostructures. In this study, we developed a procedure for massively parallel direct writing of nanoapertures using a multi-optical probe system and super-resolution near-fields. A glass micro-Fresnel zone plate array, which is an ultra-precision far-field optical system, was designed and fabricated as the multi-optical probe system. As a chalcogenide phase-change material (PCM), multiple layers of Sb 65 Se 35 were used to generate the super-resolution near-field effect. A nanoaperture was fabricated through direct laser writing on a large-area (200 × 200 mm 2 ) multi-layered PCM. A photoresist nanopattern was fabricated on an 8-inch wafer via near-field nanolithography using the developed nanoaperture and an i-line commercial exposure system. Unlike other methods, this technique allows high-throughput large-area nanolithography and overcomes the gap-control issue between the probe array and the patterning surface., Competing Interests: Conflict of interestThe authors declare no competing interests., (© The Author(s) 2022.)

Regenerative medicine requires better pre-clinical tools in order to increase the efficiency of novel therapies transitioning to the clinic. Current monolayer cell culture methods are suboptimal for effectively testing new therapies and live mouse models are expensive, time consuming and require invasive procedures. Fetal organ culture, organoids, microfluidics and culture of thick sections of adult organs all aim to fill the knowledge gap between monolayer culture and live mouse studies. Here we report on an ex vivo organ perfusion system that can support whole adult mouse organs. Ex vivo perfusion of healthy and diseased mouse organs allows for real-time analysis that provides immediate feedback and accurate data collection throughout the experiment. Having a suitable normothermic ex vivo perfusion system for mouse organs provides a tool that will help contribute to our understanding of kidney physiology and disease and can take advantage of the many mouse models of human disease that already exist. Furthermore, an ex vivo kidney perfusion system can be used for testing novel cell therapies, drug screening, drug validation and for the detection of nephrotoxic substances. Critical to the success of mouse ex vivo organ perfusion is having a suitable bioreactor to maintain the organ. Here we have focused on the mouse kidney and mathematically modeled, built and validated a bioreactor that can maintain a kidney for 7 days. The long duration of the ex vivo perfusion will help to advance studies on kidney disease and can rapidly test for new regenerative medicine therapies compared to whole animal studies.

Non-toxic InP-based nanocrystals have been developed for promising candidates for commercial optoelectronic applications and they still require further improvement on photophysical properties, compared to Cd-based quantum dots (QDs), for better device efficiency and long-term stability. It is, therefore, essential to understand the precise mechanism of carrier trapping even in the state-of-the-art InP-based QD with near-unity luminescence. Here, it is shown that using time-resolved spectroscopic measurements of systematically size-controlled InP/ZnSe/ZnS core/shell/shell QDs with the quantum yield close to one, carrier trapping decreases with increasing the energy difference between band-edge and trap states, indicating that the process follows the energy gap law, well known in molecular photochemistry for nonradiative internal conversion between two electronic states. Similar to the molecular view of the energy gap law, it is found that the energy gap between the band-edge and trap states is closely associated with ZnSe phonons that assist carrier trapping into defects in highly luminescent InP/ZnSe/ZnS QDs. These findings represent a striking departure from the generally accepted view of carrier trapping mechanism in QDs in the Marcus normal region, providing a step forward understanding how excitons in nanocrystals interact with traps, and offering valuable guidance for making highly efficient and stable InP-based QDs., (© 2021 Wiley-VCH GmbH.)

Background: Despite interest among North American orthopaedic residents to pursue rotations in resource-limited settings, little is known regarding resident motivations and impact on host surgeons., Methods: Surveys were distributed to North American orthopaedic surgeons and trainees who participated in international rotations during residency to assess motivations for participation and to orthopaedic surgeons at partnering low- and middle-income country (LMIC) institutions to assess impact of visiting trainees., Results: Responses were received from 136 North American resident rotators and 51 LMIC host surgeons and trainees. North American respondents were motivated by a desire to increase surgical capacity at the LMIC while host surgeons reported a greater impact from learning from residents than on surgical capacity. Negative aspects reported by hosts included selfishness, lack of reciprocity, racial discrimination, competition for surgical experience, and resource burdens., Conclusions: The motivations and impact of orthopaedic resident rotations in LMICs need to be aligned. Host perceptions and bidirectional educational exchange should be incorporated into partnership guidelines., Competing Interests: Declaration of competing interest Dr. Miclau has received grant funding from the Wyss Medical Foundation for activities outside the submitted work. None of the other authors have any conflicts of interest to disclose., (Copyright © 2020. Published by Elsevier Inc.)

Interest in clinical rotations in low- and middle-income countries (LMICs) has grown among high-income country (HIC) orthopaedic residents. This study addresses the following questions: (1) What motivates HIC surgical residents to rotate in LMICs? (2) What is the impact of rotations on HIC residents? (3) What are the LMIC partner perceptions of HIC collaboration?, Materials and Methods: A search strategy of multiple databases returned 3,740 unique articles pertaining to HIC surgical resident motivations for participating in rotations in LMICs or the LMIC host perspective. Data extraction was dually performed using meta-ethnography, the qualitative equivalent of meta-analysis., Results: Twenty-one studies were included in the final analysis. HIC residents were primarily motivated to rotate in LMICs by altruistic intent, with greatest impact on professional development. LMIC partners mostly valued HIC sustained investment and educational opportunities for LMIC partners. From LMIC's perspective, potential harm from collaboration arose from system-level and individual-level discordance between HIC and LMIC expectations and priorities. HIC priorities included the following: (1) adequate operative time, (2) exposure to varied pathology, and (3) mentorship. LMIC priorities included the following: (1) avoiding competition with HIC residents for surgical cases, (2) that HIC groups not undermine LMIC internal authority, (3) that HIC initiatives address local LMIC needs, and (4) that LMIC partners be included as authors on HIC research initiatives. Both HIC and LMIC partners raised ethical concerns regarding collaboration and perceived HIC residents to be underprepared for their LMIC rotation., Discussion: This study synthesizes the available literature on HIC surgical resident motivations for and impact of rotating in LMICs and the LMIC host perception of collaboration. Three improvement categories emerged: that residents (1) receive site-specific preparation before departure, (2) remain in country long enough to develop site-specific skills, and (3) cultivate flexibility and cultural humility . Specific suggestions based on synthesized data are offered for each concept and can serve as a foundation for mutually beneficial international electives in LMICs for HIC orthopaedic trainees., (Copyright © 2020 The Authors. Published by The Journal of Bone and Joint Surgery, Incorporated. All rights reserved.)

Here we demonstrate high-throughput gigapixel confocal imaging using a massively parallel optical probe array with single directional infinite scanning. For implementation of the single directional infinite scan with high lateral resolution, a parallelogram array micro-objective lens module, composed of two wafer-level microlens arrays, is proposed to generate a massively parallel optical probe array for integration into the confocal imaging system, including an objective-side telecentric relay lens with a low-magnification. To test the feasibility of the proposed system with single directional infinite scanning, we designed and constructed a confocal imaging system using a parallelogram array of multi-optical probes with a massively parallel array size of 200 × 140. The constructed system provides a full width-half maximum lateral resolution of 1.55 μm, as measured by the knife-edge detection method, and a field-of-view width of 28.0 mm with a sampling interval of 1 μm/pixel.

There exists an unmet need for locally relevant and sustainable orthopedic research in low- and middle-income countries. Partnerships between high-income countries and low- and middle-income countries can bridge gaps in resources, knowledge, infrastructure, and skill. This article presents a select list of models for high-income countries/low- and middle-income countries research partnerships including academic partnerships, international research consortia, professional society-associated working groups, and nongovernmental organization partnerships. Models that produce research with lasting legacy are those that promote mutually beneficial partnerships over individual gains., Competing Interests: Disclosure Dr D. Shearer serves on the board of SIGN Fracture Care International, a role for which he receives no financial compensation. All other authors have no relevant conflicts of interest pertinent to this article., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The recent advances in the single cell genome analysis are generating a considerable amount of novel insights into complex biological systems. However, there are still technical challenges because each cell has a single copy of DNA to be amplified in most single cell genome analytical methods. In this paper, we present a novel approach to directly visualize a genomic map on a large DNA molecule instantly stained with red and green DNA-binding fluorescent proteins without DNA amplification. For this visualization, we constructed a few types of fluorescent protein-fused DNA-binding proteins: H-NS (histone-like nucleoid-structuring protein), DNA-binding domain of BRCA1 (breast cancer 1), high mobility group-1 (HMG), and lysine tryptophan (KW) repeat motif. Because H-NS and HMG preferentially bind A/T-rich regions, we combined A/T specific binder (H-NS-mCherry and HMG-mCherry as red color) and a non-specific complementary DNA binder (BRCA1-eGFP and 2(KW)2-eGFP repeat as green color) to produce a sequence-specific two-color DNA physical map for efficient optical identification of single DNA molecules.

Focusing the femto-second (fs) laser beam on the target was the usual way to carry out a two-photon excitation (TPE) in previous photodynamic therapy (PDT) studies. However, focusing the laser deep inside the tissues of the tumor is unrealistic due to tissue scattering, so that this focusing manner seems unfit for practical TPE PDT applications. In this work, we prepared a conjugate of quantum dots (QDs) and sulfonated aluminum phthalocyanine (AlPcS) for TPE PDT, because QDs have a very high two-photon absorption cross section (TPACS) and thus QDs can be excited by an unfocused 800 nm fs laser beam with a low power density and then transfer the energy to a conjugated AlPcS via fluorescence resonance energy transfer (FRET). The FRET efficiency of the QD-AlPcS conjugate in water was as high as 90%, and the FRET process of the cellular QD-AlPcS was also observed in both KB and HeLa cells under TPE of a 800 nm fs laser. The singlet oxygen ( 1 O 2 ) products were produced by the QD-AlPcS under the TPE of the unfocused 800 nm fs laser via FRET mediated PDT. Moreover, the QD-AlPcS can effectively destroy these cancer cells under the irradiation of the 800 nm unfocused fs laser beam with a power density of 92 mW mm -2 , and particularly the killing efficiency of the TPE is comparable to that of the commonly used one-photon excitation (OPE) at visible wavelengths. These results highlight the potential of QD-AlPcS for TPE PDT with a near infrared wavelength.

We developed quantum dot-engineered M13 virus layer-by-layer hybrid composite films with incorporated fluorescence quenchers. TNT is designed to displace the quenchers and turn on the quantum dot fluorescence. TNT was detected at the sub ppb level with a high selectivity.

Many kinds of inorganic nanoparticles (NPs) including semiconductor, metal, metal oxide, and lanthanide-doped NPs have been developed for imaging and therapy applications. Their unique optical, magnetic, and electronic properties can be tailored by controlling the composition, size, shape, and structure. Interaction of such NPs with cells and/or in vivo compartments is critically determined by the surface properties, and sophisticated control over the NP surface is essential to control their fate in biological environments. We review NP surface coating strategies using the categories of small surface ligand, polymer, and lipid. Use of small ligand molecules has the advantage of maintaining the minimal hydrodynamic (HD) size. Polymers can be advantageous in NP anchoring by combining multiple affinity groups. Encapsulation of NPs in polymers, lipids or surfactants can preserve the as-synthesized NPs. NP surface properties and reaction conditions should be carefully considered to obtain a bioconjugate that maintains the physicochemical properties of NP and functionalities of the conjugated biomolecules. We highlight how the surface properties of NPs impact their interactions with cells and in vivo compartments, especially focused on the important surface design parameters such as HD size, surface charge, and targeting. Typically, maximal cellular uptake can take place in the intermediate NP size range of 40-60nm. Clearance of NPs from blood circulation is largely dependent on the degree of uptake by reticuloendothelial system when they are larger than 10nm. When the HD size is below 10nm, NPs show broad distribution over many organs. Reduction of HD size below the limit of renal barrier can achieve fast clearance of NPs. For maximal tumor accumulation, NPs should have long blood circulation time and should be large enough to prevent rapid penetration. NPs are also desired to rapidly clear out from the body after the mission before they cause toxic side effects. However, efficient clearance from the body to avoid side effects may result in the reduction in residence time required for accumulation in target tissues. Smart design of NP surface coating that can meet the conflicting demands can open a new avenue of NP applications. Surface charge and hydrophobicity need to be carefully considered for NP surface design. Positively charged NPs more adsorb on cell membranes and consequently show higher level of internalizations when compared with negatively charged or neutral NPs. NPs encounter a large variety of biomolecules in vivo, where non-specific adsorptions can potentially alter the physicochemical properties of the NPs. For optimal performance, NPs are suggested to have neutral surface charge at physiological conditions, small HD size, and minimal non-specific adsorption levels. Zwitterionic NP surface coating by small surface ligands can be a promising approach. Toxicity is one of most critical issues, where proper control of the NP surface can significantly reduce the toxicities., (Copyright © 2012 Elsevier B.V. All rights reserved.)

A challenge in using plasmonic nanostructure-drug conjugates for thermo-chemo combination cancer therapy lies in the huge size discrepancy; the size difference can critically differentiate their biodistributions and hamper the synergistic effect. Properly tuning the plasmonic wavelength for photothermal therapy typically results in the nanostructure size reaching ∼100 nm. We report a new combination cancer therapy platform that consists of relatively small 10 nm pH-responsive spherical gold nanoparticles and conjugated doxorubicins. They are designed to form aggregates in mild acidic environment such as in a tumor. The aggregates serve as a photothermal agent that can selectively exploit external light by their collective plasmon modes. Simultaneously, the conjugated doxorubicins are released. The spatiotemporal concertion is confirmed at the subcellular, cellular, and organ levels. Both agents colocalize in the cell nuclei. The conjugates accumulate in cancer cells by the rapid phagocytic actions and effective blockage of exocytosis by the increased aggregate size. They also effectively accumulate in tumors up to 17 times over the control because of the enhanced permeation and retention. The conjugates exhibit a synergistic effect enhanced by nearly an order of magnitude in cellular level. The synergistic effect is demonstrated by the remarkable reductions in both the therapeutically effective drug dosage and the photothermal laser threshold. Using an animal model, effective tumor growth suppression is demonstrated. The conjugates induce apoptosis to tumors without any noticeable damage to other organs. The synergistic effect in vivo is confirmed by qRT-PCR analysis over the thermal stress and drug-induced growth arrest.

Gold nanorod end-to-end assembly is demonstrated by the selective complexation of a bisacridinedione foldamer with Ca(2+). This setup can be applied as a chemosensor for Ca(2+) ions, as the complex shows selective red-shifting of the nanorod plasmon peak and enhancement in fluorescence from the acridinedione moieties upon exposure to Ca(2+) ., (Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Sulfonated aluminum phthalocyanines (AlPcSs), commonly used photosensitizers for photodynamic therapy of cancers (PDT), were conjugated with amine-dihydrolipoic acid-coated quantum dots (QDs) by electrostatic binding, achieving 70 AlPcSs per QD. The AlPcS-QD conjugates can utilize the intense light absorptions of conjugated QDs to indirectly excite AlPcSs producing singlet oxygen via fluorescence resonance energy transfer (FRET), demonstrating a new excitation model for PDT. The AlPcS-QD conjugates easily penetrated into human nasopharyngeal carcinoma cells and carried out the FRET in cells, with efficiency around 80%. Under the irradiation of a 532-nm laser, which is at the absorption region of QDs but not fit for the absorption of AlPcSs, the cellular AlPcS-QD conjugates can destroy most cancer cells via FRET-mediated PDT, showing the potential of this new strategy for PDT.

Potential advantages of quantum dot (QD) imaging in the second optical window (SOW) at 1,000 to 1,400 nm over the first optical window (FOW) at 700 to 900 nm have attracted much interest. QDs that emit at 800 nm (800QDs) and QDs that emit at 1,300 nm (1,300QDs) are used to investigate the imaging depths at the FOW and SOW. QD images in biologic tissues are processed binarized via global thresholding method, and the imaging depths are determined using the criteria of contrast to noise ratio and relative apparent size. Owing to the reduced scattering in the SOW, imaging depth in skin can be extended by approximately three times for 1,300QD/SOW over 800QD/FOW. In liver, excitation of 1,300QD/SOW can be shifted to longer wavelengths; thus, the imaging depth can be extended by 1.4 times. Effects of quantum yield (QY), concentration, incidence angle, polarization, and fluence rate F on imaging depth are comprehensively studied. Under F approved by the Food and Drug Administration, 1,300QDs with 50% QY can reach imaging depths of 29.7 mm in liver and 17.5 mm in skin. A time-gated excitation using 1,000 times higher F pulses can obtain the imaging depth of ≈ 5 cm. To validate our estimates, in vivo whole-body imaging experiments are performed using small-animal models.

A new multiplexed NIR in vivo imaging is showcased by using quantum dots and NaYF(4):Yb(3+),Tm(3+) nanoparticles. The 'temporal' multiplexing is demonstrated by alternating the excitation wavelengths and unmixing the emissions of different probes. Multiplexed cellular imaging and the cellular trafficking in animal models are shown.

Purpose: Researchers have been studying the mechanisms by which metastasis can be prevented via blocking the hematogenous and the lymphatic routes for a long time now. However, metastasis is still the single most challenging obstacle for successful cancer management. In a new twist that may require some retooling of this established approach, we investigated the hypothesis that tumor metastases can occur via an independent fluid-conducting system called the primo-vascular system., Procedures: The dissemination and growth of near-infrared quantum dot (NIR QD)-electroporated cancer cells in metastatic sites were investigated using in vivo multispectral imaging techniques., Results: Our results show that the NIR QD-labeled cancer cells were able to migrate through not only the blood vascular and lymphatic systems but also the primo-vascular system extending from around the tumor to inside the abdominal cavity. Furthermore, the NIR QD-labeled cancer cells, which had been seeded intraperitoneally, specifically infiltrated the primo-vascular system in the omentum and in the gonadal fat., Conclusions: These findings strongly suggest that the primo-vascular system may be an additional metastasis route, complementing the lymphatic and hematogenous routes, which facilitate the dissemination and colonization of cancer cells at secondary sites.

We report a "smart" gold nanoparticle that is designed to aggregate in mild acidic intracellular environments by its hydrolysis-susceptible citraconic amide surface. With a relatively small size of 10 nm, the "smart" gold nanoparticles can be efficiently internalized into cancerous cells. Triggered by pH change, the nanoparticle surfaces are engineered to have both positive and negative charges. Electrostatic attractions between the nanoparticles can rapidly form aggregates inside the cells, and the aggregates accumulate as the exocytosis is blocked by the increased size. Endocytosis of gold nanoparticles and the aggregation are monitored real-time by dark field optical microscopy. The pH-induced formation of aggregates shifts the absorption to far-red and near-infrared. The absorption shift to longer wavelength is used for photothermal cancer therapy as it guarantees maximal tissue penetration for potential therapeutic applications. The gold nanoparticles show selective and efficient destruction of cancerous cells with an intensity threshold of 5 W/cm(2) to induce the thermal destruction. In the intensity range 5-13 W/cm(2), the circular area of damaged cells increases linearly with the irradiation power density. This shows a new proof-of-concept for photothermal cancer therapy that exploits collective plasmon modes of metal nanoparticles.

True colors: High-quality InP and InP/ZnS quantum dots (QDs) are obtained by means of a simple one-pot method in the presence of polyethylene glycol (PEG). Rapid and size-controlled reactions lead to highly crystalline and nearly monodisperse QDs at relatively low temperatures. The particles emit from cyan blue to far-red, and are successfully used in cellular imaging (see figure).

A simple and novel electrostatic coupling method is reported, which provides a hyaluronic acid-quantum dot conjugate (HA-QD) that is colloidally stable and size-tunable from 50 to 120 nm. The HA-QDs show cancer targeting efficiency, which suggests diagnostic and imaging applications. The conjugates are also demonstrated for the fluorescence staining capability for lymphatic vessels in vitro and in vivo. Using the HA-QDs in a small animal model, lymphatic vessels are visualized real-time in vivo for days. Comprehensive cytotoxicity evaluations are made for the conjugates and the unconjugated counterpart. The HA-QDs showcase the potentials toward cancer imaging and real-time visualization of changes in lymphatic vessels such as lymphangiogenesis.