Giant pyroelectricity in nanomembranes.

Pyroelectricity describes the generation of electricity by temporal temperature change in polar materials1-3. When free-standing pyroelectric materials approach the 2D crystalline limit, how pyroelectricity behaves remained largely unknown. Here, using three model pyroelectric materials whose bonding characters along the out-of-plane direction vary from van der Waals (In2Se3), quasi-van der Waals (CsBiNb2O7) to ionic/covalent (ZnO), we experimentally show the dimensionality effect on pyroelectricity and the relation between lattice dynamics and pyroelectricity. We find that, for all three materials, when the thickness of free-standing sheets becomes small, their pyroelectric coefficients increase rapidly. We show that the material with chemical bonds along the out-of-plane direction exhibits the greatest dimensionality effect. Experimental observations evidence the possible influence of changed phonon dynamics in crystals with reduced thickness on their pyroelectricity. Our findings should stimulate fundamental study on pyroelectricity in ultra-thin materials and inspire technological development for potential pyroelectric applications in thermal imaging and energy harvesting.

CRISPR/dCas9-Mediated Specific Molecular Assembly Facilitates Genotyping of Mutant Circulating Tumor DNA.

Breakthroughs in circulating tumor DNA (ctDNA) analysis are critical in tumor liquid biopsies but remain a technical challenge due to the double-stranded structure, extremely low abundance, and short half-life of ctDNA. Here, we report an electrochemical CRISPR/dCas9 sensor (E-dCas9) for sensitive and specific detection of ctDNA at a single-nucleotide resolution. The E-dCas9 design harnesses the specific capture and unzipping of target ctDNA by dCas9 to introduce a complementary reporter probe for specific molecular assembly and signal amplification. By efficient homogeneous assembly and interfacial click reaction, the assay demonstrates superior sensitivity (up to 2.86 fM) in detecting single-base mutant ctDNA and a broad dynamic range spanning 6 orders of magnitude. The sensor is also capable of measuring 10 fg/µL of a mutated target in excess of wild-type ones (1 ng/µL), equivalent to probing 0.001% of the mutation relative to the wild type. In addition, our sensor can monitor the dynamic expression of cellular genomic DNA and allows accurate analysis of blood samples from patients with nonsmall cell lung cancer, suggesting the potential of E-dCas9 as a promising tool in ctDNA-based cancer diagnosis.

The Arabidopsis Nodulin Homeobox Factor AtNDX Interacts with AtRING1A/B and Negatively Regulates Abscisic Acid Signaling.

The phytohormone abscisic acid (ABA) and the Polycomb group proteins have key roles in regulating plant growth and development; however, their interplay and underlying mechanisms are not fully understood. Here, we identified an Arabidopsis (Arabidopsis thaliana) nodulin homeobox (AtNDX) protein as a negative regulator in the ABA signaling pathway. AtNDX mutants are hypersensitive to ABA, as measured by inhibition of seed germination and root growth, and the expression of AtNDX is downregulated by ABA. AtNDX interacts with the Polycomb Repressive Complex1 (PRC1) core components AtRING1A and AtRING1B in vitro and in vivo, and together, they negatively regulate the expression levels of some ABA-responsive genes. We identified ABA-INSENSITIVE (ABI4) as a direct target of AtNDX. AtNDX directly binds the downstream region of ABI4 and deleting this region increases the ABA sensitivity of primary root growth. Furthermore, ABI4 mutations rescue the ABA-hypersensitive phenotypes of ndx mutants and ABI4-overexpressing plants are hypersensitive to ABA in primary root growth. Thus, our work reveals the critical functions of AtNDX and PRC1 in some ABA-mediated processes and their regulation of ABI4.

More light components and less light damage on rats' eyes: evidence for the photobiomodulation and spectral opponency.

The blue-light hazard (BLH) has raised concerns with the increasing applications of white light-emitting diodes (LEDs). Many researchers believed that the shorter wavelength or more light components generally resulted in more severe retinal damage. In this study, based on the conventional phosphor-coated white LED, we added azure (484 nm), cyan (511 nm), and red (664 nm) light to fabricate the low-hazard light source. The low-hazard light sources and conventional white LED illuminated 68 Sprague-Dawley (SD) rats for 7 days. Before and after light exposure, we measured the retinal function, thickness of retinal layers, and fundus photographs. The expression levels of autophagy-related proteins and the activities of oxidation-related biochemical indicators were also measured to investigate the mechanisms of damaging or protecting the retina. With the same correlated color temperature (CCT), the low-hazard light source results in significantly less damage on the retinal function and photoreceptors, even if it has two times illuminance and blue-light hazard-weighted irradiance ([Formula: see text]) than conventional white LED. The results illustrated that [Formula: see text] proposed by IEC 62471 could not exactly evaluate the light damage on rats' retinas. We also figured out that more light components could result in less light damage, which provided evidence for the photobiomodulation (PBM) and spectral opponency on light damage.

circRNA circRIMS Downregulates miR-505 through Methylation to Suppress Cell Proliferation in Endometrial Cancer.

It is known that the circular RNA (circRNA) molecule circRIMS is overexpressed in gastric cancer and plays an oncogenic role. However, its role in other cancers is unknown. In this study, we analyzed its role in endometrial cancer (EC). EC and paired non-tumor tissue samples were collected from a total of 63 EC patients and subjected to total RNA isolations and reverse transcription quantitative polymerase chain reaction (RT-qPCR) to analyze the differential expression of circRIMS and miR-505. Overexpression of circRIMS and miR-505 was reached in EC cells and their interaction was analyzed using RT-qPCRs. The role of circRIMS in regulating miR-505 methylation was analyzed by methylation-specific RT-qPCR. Bromodeoxyuridine (BrdU) assay was performed to analyze the roles of circRIMS and miR-505 in regulating cell proliferation. circRIMS was upregulated in EC, while miR-505 was downregulated in EC. circRIMS and miR-505 were inversely correlated across both EC and non-tumor tissues. In EC cells, circRIMS overexpression decreased miR-505 expression and increased miR-505 gene methylation. BrdU assay showed that circRIMS overexpression increased cell proliferation and reduced the inhibitory effects of miR-505 overexpression on cell proliferation. circRIMS may downregulate miR-505 through methylation to increase cell proliferation.

TIM-1 promotes proliferation and metastasis, and inhibits apoptosis, in cervical cancer through the PI3K/AKT/p53 pathway.

BACKGROUND: T-cell immunoglobulin mucin-1 (TIM-1) has been reported to be associated with the biological behavior of several malignant tumors; however, it is not clear whether it has a role in cervical cancer (CC). METHODS: TIM-1 expression in cervical epithelial tumor tissues and cells was detected by immunohistochemistry or real-time quantitative-PCR and western blotting. CC cells from cell lines expressing low levels of TIM-1 were infected with lentiviral vectors encoding TIM-1. Changes in the malignant behavior of CC cells were assessed by CCK-8, wound healing, Transwell migration and invasion assays, and flow cytometry in vitro; while a xenograft tumor model was established to analyze the effects of TIM-1 on tumor growth in vivo. Changes in the levels of proteins related to the cell cycle, apoptosis, and Epithelial-mesenchymal transition (EMT) were determined by western blotting. RESULTS: TIM-1 expression was higher in CC tissues, than in high grade squamous intraepithelial lesion, low grade squamous intraepithelial lesion, or normal cervical tissues, and was also expressed in three CC cell lines. In HeLa and SiHa cells overexpressing TIM-1, proliferation, invasion, and migration increased, while whereas apoptosis was inhibited. Furthermore, TIM-1 downregulated the expression of p53, BAX, and E-cadherin, and increased cyclin D1, Bcl-2, Snail1, N-cadherin, vimentin, MMP-2, and VEGF. PI3K, p-AKT, and mTOR protein levels also increased, while total AKT protein levels remained unchanged. CONCLUSIONS: Our study indicated that TIM-1 overexpression promoted cell migration and invasion, and inhibited cell apoptosis in CC through modulation of the PI3K/AKT/p53 and PI3K/AKT/mTOR signaling pathways, and may be a candidate diagnostic biomarker of this disease.

Enhanced light extraction efficiency of an LED package by a surface-mounted amorphous photonic structure.

In this study, we propose a low-cost, simple and feasible post-processing approach to improve the light extraction efficiency (LEE) of LED packages. Amorphous photonic structures (APSs) with only short-range order are fabricated from anodic aluminum oxide (AAO) and transferred to intermediate polymer stamp (IPS) by nanoimprint technology. The IPS with APSs is directly mounted onto the surface of an LED package, where the LEE is achieved as 94.6%. The scanning electron microscope (SEM) images of AAO templates and imprinted IPS are analyzed by radial distribution function and diameter histogram. The far-field patterns of APS-mounted LED packages are measured in electroluminescence (EL). The three-dimensional finite-difference time-domain (3D-FDTD) calculations of transmittance of APSs confirm that they improve the light extraction above the critical angle. Two-dimensional Fourier power spectra from SEM images of APSs are also calculated. The LEE enhancement is attributed to that the APSs have short-range order on a length scale comparable to emission wavelength of LED. We provide novel multistage simulations in a simplified FDTD model for the LED package. Finally, we discuss the influence of the morphology of APSs on the LEE of the APS mounted LEDs.

Investigation on many-body effects in micro-LEDs under ultra-high injection levels.

Micro-LEDs can work under an extremely high injection level and are widely used in high-brightness micro-displays and visible light communication. With the increase of carrier concentration, many-body effects gradually become important factors affecting devices' characteristics. Considering the effects of carrier scattering, bandgap renormalization, and Coulomb enhancement (CE), changes in the electroluminescence spectra of micro-LEDs are analyzed as the current density increases from 49.2 to 358.2 kA/cm2, the latter representing an ultra-high injection level. Affected by plasma screening, CE decreases below about 150 kA/cm2. After that, polarization screening dominates and effectively alleviates the spatial separation of electrons and holes, which results in CE increases to the maximum injection level of 358.2 kA/cm2. It is established that CE promotes radiative recombination processes. Different from the traditional phenomenon of "efficiency droop", the enhanced attraction between carriers leads to an abnormal increase of external quantum efficiency at high current density.

A Reconfigurable Remotely Epitaxial VO2 Electrical Heterostructure.

The reconfigurability of the electrical heterostructure featured with external variables, such as temperature, voltage, and strain, enabled electronic/optical phase transition in functional layers has great potential for future photonics, computing, and adaptive circuits. VO2 has been regarded as an archetypal phase transition building block with superior metal-insulator transition characteristics. However, the reconfigurable VO2-based heterostructure and the associated devices are rare due to the fundamental challenge in integrating high-quality VO2 in technologically important substrates. In this report, for the first time, we show the remote epitaxy of VO2 and the demonstration of a vertical diode device in a graphene/epitaxial VO2/single-crystalline BN/graphite structure with VO2 as a reconfigurable phase-change material and hexagonal boron nitride (h-BN) as an insulating layer. By diffraction and electrical transport studies, we show that the remote epitaxial VO2 films exhibit higher structural and electrical quality than direct epitaxial ones. By high-resolution transmission electron microscopy and Cs-corrected scanning transmission electron microscopy, we show that a graphene buffered substrate leads to a less strained VO2 film than the bare substrate. In the reconfigurable diode, we find that the Fermi level change and spectral weight shift along with the metal-insulator transition of VO2 could modify the transport characteristics. The work suggests the feasibility of developing a single-crystalline VO2-based reconfigurable heterostructure with arbitrary substrates and sheds light on designing novel adaptive photonics and electrical devices and circuits.

Redox-Mediated Endocytosis of a Receptor-Like Kinase during Distal Stem Cell Differentiation Depends on Its Tumor Necrosis Factor Receptor Domain.

Cellular redox status plays critical roles in cell division and differentiation, but the underlying mechanism is unclear. Here we explored the effect of redox status on stem cell identity in distal stem cells (DSCs) of Arabidopsis (Arabidopsis thaliana) roots. Treatment with the reductive reagent glutathione and the oxidative reagent H2O2 inhibited DSC differentiation, as did endogenously altering reactive oxygen species production via various mutations. This suggests that both highly reductive and oxidative environments inhibit specification of stem cell identity. In our observations of mutant components of the CLAVATA3/ENDOSPERM SURROUNDING REGION 40 (CLE40)-ARABIDOPSIS CRINKLY4 (ACR4)/CLAVATA1 (CLV1)-WUSCHEL RELATED HOMEOBOX5 (WOX5) module, both reductive and oxidative reagents influenced DSC differentiation in wox5-1 and clv1-1, but not in acr4-2 or cle40 mutant plants. The stability of the receptor-like kinase ACR4 is modulated by redox status through endocytosis in root tips. ACR4 with multiple Cys mutations in the tumor necrosis factor receptor (TNFR) extracellular domain failed to undergo endocytosis. ACR4 with a complete deletion of the TNFR domain was localized directly to endosomes, bypassing the plasma membrane. Both mutations affected DSC differentiation, but not seed filling. Conversely, the intracellular domain of the ACR4 protein is partially required for seed filling, but not for DSC differentiation. Our study uncovers an important biological role of the TNFR domain in redox-mediated endocytosis of ACR4 in root DSC differentiation.

In Vivo Photoacoustic/Single-Photon Emission Computed Tomography Imaging for Dynamic Monitoring of Aggregation-Enhanced Photothermal Nanoagents.

Emerging nanomedical strategy is to construct a nanoagent that affords not only diagnostic and therapeutic functions but also imaging-guided treatment. It is crucial to understand the in vivo biological processes of nanoagents for improving theranostic function and biosafety. Herein, we report a multimodal photoacoustic/single-photon emission computed tomography (SPECT) imaging technique to dynamically monitor the in vivo behaviors of nanoagents. Near-infrared cypate-induced silk fibroin nanoassembly was chosen as the nanoagent object due to their promise in biocompatibility and aggregation-enhanced photothermal effect. This unique effect makes the nanoagents useful for the integration of photoacoustic imaging and photothermal therapy. Moreover, the nanoagents are also labeled with the radionuclides (99mTc) to render SPECT imaging. Multimodal photoacoustic/SPECT imaging provides real time, noninvasive, sensitive, and whole-body 3D information about nanoagents' distribution in vivo. These results highlight the significance of visualizing the in vivo behaviors of nanoagents and locating the tumor in vivo, substantially benefiting the better treatment planning.

Better ILP models for haplotype assembly.

BACKGROUND: The haplotype assembly problem for diploid is to find a pair of haplotypes from a given set of aligned Single Nucleotide Polymorphism (SNP) fragments (reads). It has many applications in association studies, drug design, and genetic research. Since this problem is computationally hard, both heuristic and exact algorithms have been designed for it. Although exact algorithms are much slower, they are still of great interest because they usually output significantly better solutions than heuristic algorithms in terms of popular measures such as the Minimum Error Correction (MEC) score, the number of switch errors, and the QAN50 score. Exact algorithms are also valuable because they can be used to witness how good a heuristic algorithm is. The best known exact algorithm is based on integer linear programming (ILP) and it is known that ILP can also be used to improve the output quality of every heuristic algorithm with a little decline in speed. Therefore, faster ILP models for the problem are highly demanded. RESULTS: As in previous studies, we consider not only the general case of the problem but also its all-heterozygous case where we assume that if a column of the input read matrix contains at least one 0 and one 1, then it corresponds to a heterozygous SNP site. For both cases, we design new ILP models for the haplotype assembly problem which aim at minimizing the MEC score. The new models are theoretically better because they contain significantly fewer constraints. More importantly, our experimental results show that for both simulated and real datasets, the new model for the all-heterozygous (respectively, general) case can usually be solved via CPLEX (an ILP solver) at least 5 times (respectively, twice) faster than the previous bests. Indeed, the running time can sometimes be 41 times better. CONCLUSIONS: This paper proposes a new ILP model for the haplotype assembly problem and its all-heterozygous case, respectively. Experiments with both real and simulated datasets show that the new models can be solved within much shorter time by CPLEX than the previous bests. We believe that the models can be used to improve heuristic algorithms as well.

Dual-Hole Excitons Activated Photoelectrolysis in Neutral Solution.

II-VI semiconductors exhibit unique behaviors that can generate dual-holes ("heavy and light"), but the application in photocatalysis is still missing. Herein, an empirical utilization of light/heavy holes in a hybrid metal cluster-2D semiconductor nanoplatelets is reported. This hybrid material can boost the hole-transfer at the surface and suppress the recombination. Different roles are enacted by light-holes and heavy-holes, in which the light-holes with higher energy and mobility can facilitate the slow kinetics of water oxidation and further reduce the onset voltage, while the massive heavy-holes can increase the resulting photocurrent by about five times, achieving a photocurrent of 2 mA cm-2 at 1.23 V versus RHE under AM 1.5 G illumination in nonsacrificial neutral solution. These strategies can be the solutions for photoelectrolysis and be beneficial for sustainable development in solar conversion.

Investigation on strain relaxation distribution in GaN-based µLEDs by Kelvin probe force microscopy and micro-photoluminescence.

GaN/InGaN multi-quantum-wells (MQWs) micron light emitting diodes (µLEDs) with the size ranging from 10 to 300 µm are fabricated. Effects of strain relaxation on the performance of µLEDs have been investigated both experimentally and numerically. Kelvin probe force microscopy (KPFM) and micro-photoluminescence (µPL) are used to characterize the strained area on micron pillars. Strain relaxation and reducing polarization field in MQWs almost affects the whole mesa for 10 µm LEDs and about 4% area around the lateral for 300 µm LEDs. It makes a great contribution to high performance for smaller size µLEDs. Moreover, an indirect nanoscale strain measurement for µLEDs are provided.

ABA-mediated ROS in mitochondria regulate root meristem activity by controlling PLETHORA expression in Arabidopsis.

Although research has determined that reactive oxygen species (ROS) function as signaling molecules in plant development, the molecular mechanism by which ROS regulate plant growth is not well known. An aba overly sensitive mutant, abo8-1, which is defective in a pentatricopeptide repeat (PPR) protein responsible for the splicing of NAD4 intron 3 in mitochondrial complex I, accumulates more ROS in root tips than the wild type, and the ROS accumulation is further enhanced by ABA treatment. The ABO8 mutation reduces root meristem activity, which can be enhanced by ABA treatment and reversibly recovered by addition of certain concentrations of the reducing agent GSH. As indicated by low ProDR5:GUS expression, auxin accumulation/signaling was reduced in abo8-1. We also found that ABA inhibits the expression of PLETHORA1 (PLT1) and PLT2, and that root growth is more sensitive to ABA in the plt1 and plt2 mutants than in the wild type. The expression of PLT1 and PLT2 is significantly reduced in the abo8-1 mutant. Overexpression of PLT2 in an inducible system can largely rescue root apical meristem (RAM)-defective phenotype of abo8-1 with and without ABA treatment. These results suggest that ABA-promoted ROS in the mitochondria of root tips are important retrograde signals that regulate root meristem activity by controlling auxin accumulation/signaling and PLT expression in Arabidopsis.

Photon Transport in One-Dimensional Incommensurately Epitaxial CsPbX3 Arrays.

One-dimensional nanoscale epitaxial arrays serve as a great model in studying fundamental physics and for emerging applications. With an increasing focus laid on the Cs-based inorganic halide perovskite out of its outstanding material stability, we have applied vapor phase epitaxy to grow well aligned horizontal CsPbX3 (X: Cl, Br, or I or their mixed) nanowire arrays in large scale on mica substrate. The as-grown nanowire features a triangular prism morphology with typical length ranging from a few tens of micrometers to a few millimeters. Structural analysis reveals that the wire arrays follow the symmetry of mica substrate through incommensurate epitaxy, paving a way for a universally applicable method to grow a broad family of halide perovskite materials. The unique photon transport in the one-dimensional structure has been studied in the all-inorganic Cs-based perovskite wires via temperature dependent and spatially resolved photoluminescence. Epitaxy of well oriented wire arrays in halide perovskite would be a promising direction for enabling the circuit-level applications of halide perovskite in high-performance electro-optics and optoelectronics.

ARF2 coordinates with PLETHORAs and PINs to orchestrate ABA-mediated root meristem activity in Arabidopsis .

Multiple hormones, including abscisic acid (ABA) and auxin, regulate cell division and differentiation of Arabidopsis root meristems. AUXIN RESPONSE FACTOR 2 (ARF2) functions as a negative regulator of ABA responses, as seed germination and primary root growth of arf2 mutants are hypersensitive to ABA. In this study, we found that ABA treatment reduced the expression levels of the PIN-FORMEDs (PIN) auxin efflux carriers, PIN1, PIN3, PIN4, and PIN7, to a greater extent in the root meristems of arf2-101 mutant than in the wild type. Also, arf2-101 pin1 and arf2-101 pin4 double mutants show less ABA-induced inhibition of root meristem activity than the arf2-101 mutants. Furthermore, ARF2 positively mediates the transcripts of transcription factor PLETHORA 1 (PLT1) gene but negatively mediates PLT2 at protein level in root meristems. Using a dexamethasone (DEX)-inducible transgenic line, Pro35S:PLT2-GR, we showed that PLT2 greatly promotes cell division and completely inhibits cell differentiation in root meristems of the arf2-101 mutant once PLT2 is induced by DEX, which can be partially reversed by ABA treatment, suggesting that ABA regulates root meristem activity in both ARF2-dependent and independent pathways. Our results uncover a complex regulatory architecture in which ARF2 coordinates with PLTs and PINs to orchestrate ABA-mediated regulation of root meristem activity in Arabidopsis.

Fabrication, characterization and applications of flexible vertical InGaN micro-light emitting diode arrays.

Flexible vertical InGaN micro-light emitting diode (micro-LED) arrays have been fabricated and characterized for potential applications in flexible micro-displays and visible light communication. The LED epitaxial layers were transferred from initial sapphire substrates to flexible AuSn substrates by metal bonding and laser lift off techniques. The current versus voltage characteristics of flexible micro-LEDs degraded after bending the devices, but the electroluminescence spectra show little shift even under a very small bending radius 3 mm. The high thermal conductivity of flexible metal substrates enables high thermal saturation current density and high light output power of the flexible micro-LEDs, benefiting the potential applications in flexible high-brightness micro-displays and high-speed visible light communication. We have achieved ~40 MHz modulation bandwidth and 120 Mbit/s data transmission speed for a typical flexible micro-LED.

A novel compound heterozygosity in Southern China: IVS-II-5 (G > C) and IVS-II-672 (A > C).

ß-Thalassemia (ß-thal) is a common hereditary anemia due to decreased or absent synthesis of the ß-globin chains. Here, we report a patient found to be a novel compound heterozygote for the rare IVS-II-5 (G > C) (NG_000007.3: g.71044G > C) and IVS-II-672 (A > C) (NG_000007.3: g.71711A > C) mutations, which may be silent mutations that are associated with consistent residual output of ß chains, normal red blood cell (RBC) indices and normal or borderline Hb A2 levels.

[Analysis of the phenotype-genotype relationship of hemoglobin Q-Thailand in Guangxi].

OBJECTIVE: To investigate the hematological and molecular characteristics of hemoglobin Q-Thailand in Guangxi, so as to provide reference data for hemoglobinopathy screening. METHODS: A total of 51088 samples were screened by capillary electrophoresis. Samples suspected with Hb Q-Thailand were processed with blood cell count and DNA sequencing. Gap-PCR and PCR-reverse dot blotting were used for the detection of common mutations of alpha and beta thalassemia. RESULTS: The carrier rate of Hb Q-Thailand in Guangxi was 0.06%. The hematological phenotype index(HGB, MCV, MCH, Hb Q-Thailand, Hb A2, Hb QA2) of 28 Hb Q-Thailand heterozygous samples were (125.60±22.30) g/L, (78.22±4.81) fl, (25.79±2.14) pg, (27.37±2.72)%, (1.89±0.22)%, (0.69±0.16)%, respectively, and of 2 Hb Q-Thailand heterozygous combined with beta-thalassemia samples were (125.00±18.39) g/L, (69.65±5.02) fl, (22.00±0.0) pg, (14.80±0.71)%, (4.45±0.07)%, (0.95±0.71)%, respectively. A statistical difference was found in hematological phenotype index between the two groups except HGB (P<0.05). CONCLUSION: In Guangxi, the detected Hb Q-Thailands were mainly heterozygous. Part of Hb Q-Thailand heterozygotes had normal red blood cell parameters, but can still be detected by hemoglobin electrophoresis. When combined with other types of thalassemia, these heterozygotes may still exhibit reduced MCV and MCH or various degrees of anemia.