MiR-383-5p inhibits the proliferation and migration of lung adenocarcinoma cells by targeting SHMT2.

Purpose: To explore the effects of miR-383-5p and serine hydroxymethyltransferase 2 (SHMT2) on the proliferation and migration of lung adenocarcinoma cells. Methods: SHMT2 expression in lung adenocarcinoma and normal tissues was investigated using The Cancer Genome Atlas database. Immunohistochemical analysis was performed to confirm SHMT2 expression in lung adenocarcinoma and adjacent normal lung tissues. Bioinformatics analysis and luciferase reporter assays were used to analyze the relationship between miR-383-5p and SHMT2 expression. The protein expression levels of SHMT2, vimentin, N-cadherin, E-cadherin, Bcl-2, and cyclinD1 were analyzed using western blotting. The reverse transcription-quantitative polymerase chain reaction was used to detect SHMT2 knockdown efficiency, miR-383-5p overexpression, and inhibition efficiency. The proliferative ability of cells was detected using the Cell Counting Kit-8 assay. The Transwell assay was used to detect the migration ability of cells. Results: SHMT2 expression was significantly increased in patients with lung adenocarcinoma compared to that in control patients; the higher the SHMT2 expression the worse the outcomes were in patients with lung adenocarcinoma. SHMT2 knockdown inhibited the proliferation, migration, and epithelial-mesenchymal transition of lung adenocarcinoma A549 and H1299 cells. MiR-383-5p directly targeted and downregulated SHMT2 in A549 and H1299 cells. The effects of miRNA-383-5p on the proliferation and migration of these cells differed from those of SHMT2. Exogenous overexpression of SHMT2 reversed the miR-383-5p-induced proliferation and migration inhibition in A549 and H1299 cells. Conclusion: MiR-383-5p inhibits the proliferation and migration of lung adenocarcinoma cells by targeting and downregulating SHMT2.

Combination of epidrugs with immune checkpoint inhibitors in cancer immunotherapy: From theory to therapy.

Immunotherapy based on immune checkpoint inhibitors (ICIs) has revolutionized treatment strategies in multiple types of cancer. However, the resistance and relapse as associated with the extreme complexity of cancer-immunity interactions remain a major challenge to be resolved. Owing to the epigenome plasticity of cancer and immune cells, a growing body of evidence has been presented indicating that epigenetic treatments have the potential to overcome current limitations of immunotherapy, thus providing a rationalefor the combination of ICIs with epigenetic agents (epidrugs). In this review, we first make an overview about the epigenetic regulations in tumor biology and immunodevelopment. Subsequently, a diverse array of inhibitory agents under investigations targeted epigenetic modulators (Azacitidine, Decitabine, Vorinostat, Romidepsin, Belinostat, Panobinostat, Tazemetostat, Enasidenib and Ivosidenib, etc.) and immune checkpoints (Atezolizmab, Avelumab, Cemiplimab, Durvalumb, Ipilimumab, Nivolumab and Pembrolizmab, etc.) to increase anticancer responses were described and the potential mechanisms were further discussed. Finally, we summarize the findings of clinical trials and provide a perspective for future clinical studies directed at investigating the combination of epidrugs with ICIs as a treatment for cancer.

Delivery of miR-3529-3p using MnO2 -SiO2 -APTES nanoparticles combined with phototherapy suppresses lung adenocarcinoma progression by targeting HIGD1A.

BACKGROUND: The present study aimed to investigate the function of miR-3529-3p in lung adenocarcinoma and MnO2 -SiO2 -APTES (MSA) as a promising multifunctional delivery agent for lung adenocarcinoma therapy. METHODS: Expression levels of miR-3529-3p were evaluated in lung carcinoma cells and tissues by qRT-PCR. The effects of miR-3529-3p on apoptosis, proliferation, metastasis and neovascularization were assessed by CCK-8, FACS, transwell and wound healing assays, tube formation and xenografts experiments. Luciferase reporter assays, western blot, qRT-PCR and mitochondrial complex assay were used to determine the targeting relationship between miR-3529-3p and hypoxia-inducible gene domain family member 1A (HIGD1A). MSA was fabricated using MnO2 nanoflowers, and its heating curves, temperature curves, IC50, and delivery efficiency were examined. The hypoxia and reactive oxygen species (ROS) production was investigated by nitro reductase probing, DCFH-DA staining and FACS. RESULTS: MiR-3529-3p expression was reduced in lung carcinoma tissues and cells. Transfection of miR-3529-3p could promote apoptosis and suppress cell proliferation, migration and angiogenesis. As a target of miR-3529-3p, HIGD1A expression was downregulated, through which miR-3529-3p could disrupt the activities of complexes III and IV of the respiratory chain. The multifunctional nanoparticle MSA could not only efficiently deliver miR-3529-3p into cells, but also enhance the antitumor function of miR-3529-3p. The underlying mechanism may be that MSA alleviates hypoxia and has synergistic effects in cellular ROS promotion with miR-3529-3p. CONCLUSIONS: Our results establish the antioncogenic role of miR-3529-3p, and demonstrate that miR-3529-3p delivered by MSA has enhanced tumor suppressive effects, probably through elevating ROS production and thermogenesis.

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.

A Novel Way to Fill Green Gap of GaN-Based LEDs by Pinning Defects in Nanorod Array.

Nanorod array and planar green-emission InGaN/GaN multi-quantum well (MQW) LEDs were fabricated by lithography, nano-imprinting, and top-down etching technology. The defect-pinning effect of the nanostructure was found for the first time. The ratio of the bright regions to the global area in the panchromatic CL images of green MQW samples increased from 30% to about 90% after nano-fabrication. The overall luminous performance significantly improved. Throughout temperature-dependent photoluminescence (TDPL) and time-resolved PL (TRPL) measurements, the migration and recombination of carriers in the MQWs of green LEDs were analyzed. It was proved that nanostructures can effectively prevent carriers from being captured by surrounding nonradiative recombination centers. The overall PL integral intensity can be enhanced to above 18 times. A much lower carrier lifetime (decreasing from 91.4 to 40.2 ns) and a higher internal quantum efficiency (IQE) (increasing from 16.9% to 40.7%) were achieved. Some disputes on the defect influence were also discussed and clarified.

Synergistic effects of fluid shear stress and adhesion morphology on the apoptosis and osteogenesis of mesenchymal stem cells.

Mechanical microenvironments, such as characteristics defining mechanical environments and fluid flow play an important role in steering the fate of mesenchymal stem cells (MSCs). However, the synergistic effect of adhesion morphology and fluid flow on the biological behavior of MSCs is seldom investigated. In this article, 0.5 or 0.8 Pa fluid shear stress (FSS) was applied to the MSCs on micropatterned substrates, and the apoptosis and osteogenic differentiation of MSCs were measured by double fluorescent staining. Results showed that the cellular adhesion patterns with low circularity and large area are beneficial to the osteogenic differentiation of individual MSCs. Meanwhile, FSS facilitated osteogenic differentiation of MSCs, as shown by the expression of alkaline phosphatase, osteocalcin, and collagen I. In addition, nuclear transfer of Yes-associated protein, a transcriptional regulator in MSCs, was enhanced after being exposed to FSS. These results demonstrated the synergistic effects of FSS and adhesion morphology in directing the fate of MSCs, and these effects may be adopted to design bio-functional substrates for cell transplantation in tissue engineering.

Finite element analysis on mechanical state on the osteoclasts under gradient fluid shear stress.

Mechanical loading, such as fluid shear stress (FSS), is regarded as the main factor that regulates the biological responses of bone cells. Our previous studies have demonstrated that the RAW264.7 osteoclast precursors migrate toward the low-FSS region under the gradient FSS field by a cone-and-plate flow chamber, in which the FSS in the outer region is larger than that in the inner region along the radial direction. Whether the FSS distribution on a cell depends on the gradient direction of FSS field should be clarified to explain this experimental observation. In this study, the finite element models of the discretely distributed or closely packed cells adherent on the bottom plate in a cone-and-plate flow chamber were constructed, and cells were regarded as compressible isotropic Hookean solid. Results showed that the average FSS of each discretely distributed cell at the quarter sector far from the center (SFC) was about 0.1% greater than that at the quarter sector near the center (SNC). In the bands with different orientations for a cell, the relative difference between the average FSS in the SFC and the SNC becomes smaller with increased band height. For the hexagonal closely packed cells, the relative value of SFC and SNC increases with increasing cell spacing. The difference between the local wall FSS in the SFC and the SNC may activate mechanosensitive ion channels and further regulate the migration of osteoclast precursors toward the low-FSS region under the gradient FSS field.

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.

Polymer-Assisted Space-Confined Strategy for the Foot-Scale Synthesis of Flexible Metal-Organic Framework-Based Composite Films.

At the gas-liquid interface, the confined synthesis of metal-organic framework (MOF) films has been extensively developed by spreading an ultrathin oil layer on the aqueous surface as a reactor. However, this interface is susceptible to various disturbances and incapable of synthesizing large-area crystalline MOF films. Herein, we developed a polymer-assisted space-confined strategy to synthesize large-area films by blending poly(methyl methacrylate) (PMMA) into the oil layer, which improved the stability of the gas-liquid interface and the self-shrinkage of the oil layer on the water surface. Meanwhile, the as-synthesized MOFs as a quasi-solid substrate immobilized the edge of the oil layer, which maintained a large spreading area. Thanks to this synergistic effect, we synthesized the freestanding MOF-based film with a foot-level (0.66 ft) lateral dimension, which is the largest size reported so far. Besides, due to the phase separation of the two components, the MOF-PMMA composite film combined the conductivity of MOFs (1.13 S/m) with the flexibility of PMMA and exhibited excellent mechanical properties. More importantly, this strategy could be extended to the preparation of other MOFs, coordination polymers (CPs), and even inorganic material composite films, bringing light to the design and large-scale synthesis of various composite films for practical applications.

Unconventional Thermoelectric Materials for Energy Harvesting and Sensing Applications.

Heat is an abundant but often wasted source of energy. Thus, harvesting just a portion of this tremendous amount of energy holds significant promise for a more sustainable society. While traditional solid-state inorganic semiconductors have dominated the research stage on thermal-to-electrical energy conversion, carbon-based semiconductors have recently attracted a great deal of attention as potential thermoelectric materials for low-temperature energy harvesting, primarily driven by the high abundance of their atomic elements, ease of processing/manufacturing, and intrinsically low thermal conductivity. This quest for new materials has resulted in the discovery of several new kinds of thermoelectric materials and concepts capable of converting a heat flux into an electrical current by means of various types of particles transporting the electric charge: (i) electrons, (ii) ions, and (iii) redox molecules. This has contributed to expanding the applications envisaged for thermoelectric materials far beyond simple conversion of heat into electricity. This is the motivation behind this review. This work is divided in three sections. In the first section, we present the basic principle of the thermoelectric effects when the particles transporting the electric charge are electrons, ions, and redox molecules and describe the conceptual differences between the three thermodiffusion phenomena. In the second section, we review the efforts made on developing devices exploiting these three effects and give a thorough understanding of what limits their performance. In the third section, we review the state-of-the-art thermoelectric materials investigated so far and provide a comprehensive understanding of what limits charge and energy transport in each of these classes of materials.

Great future or greedy venture: Precision medicine needs philosophy.

INTRODUCTION: Over the past decade, we have witnessed the initiation and implementation of precision medicine (PM), a discipline that promises to individualize and personalize medical management and treatment, rendering them ultimately more precise and effective. Despite of the continuing advances and numerous clinical applications, the potential of PM remains highly controversial, sparking heated debates about its future. METHOD: The present article reviews the philosophical issues and practical challenges that are critical to the feasibility and implementation of PM. OUTCOME: The explanation and argument about the relations between PM and computability, uncertainty as well as complexity, show that key foundational assumptions of PM might not be fully validated. CONCLUSION: The present analysis suggests that our current understanding of PM is probably oversimplified and too superficial. More efforts are needed to realize the hope that PM has elicited, rather than make the term just as a hype.

When graphene meets white graphene - recent advances in the construction of graphene and h-BN heterostructures.

2D heterostructures have very recently witnessed a boom in scientific and technological activities owing to the customized spatial orientation and tailored physical properties. A large amount of 2D heterostructures have been constructed on the basis of the combination of mechanical exfoliation and located transfer method, opening wide possibilities for designing novel hybrid systems with tuned structures, properties, and applications. Among the as-developed 2D heterostructures, in-plane graphene and h-BN heterostructures have drawn the most attention in the past few decades. The controllable synthesis, the investigation of properties, and the expansion of applications have been widely explored. Herein, the fabrication of graphene and h-BN heterostructures is mainly focused on. Then, the spatial configurations for the heterostructures are systematically probed to identify the highly related unique features. Moreover, as a most promising approach for the scaled production of 2D materials, the in situ CVD fabrication of the heterostructures is summarized, demonstrating a significant potential in the controllability of size, morphology, and quality. Further, the recent applications of the 2D heterostructures are discussed. Finally, the concerns and challenges are fully elucidated and a bright future has been envisioned.

A Critical Review on Black Phosphorus-Based Photocatalytic CO2 Reduction Application.

Energy shortages and greenhouse effects are two unavoidable problems that need to be solved. Photocatalytically converting CO2 into a series of valuable chemicals is considered to be an effective means of solving the above dilemmas. Among these photocatalysts, the utilization of black phosphorus for CO2 photocatalytic reduction deserves a lightspot not only for its excellent catalytic activity through different reaction routes, but also on account of the great preponderance of this relatively cheap catalyst. Herein, this review offers a summary of the recent advances in synthesis, structure, properties, and application for CO2 photocatalytic reduction. In detail, the review starts from the basic principle of CO2 photocatalytic reduction. In the following section, the synthesis, structure, and properties, as well as CO2 photocatalytic reduction process of black phosphorus-based photocatalyst are discussed. In addition, some possible influencing factors and reaction mechanism are also summarized. Finally, a summary and the possible future perspectives of black phosphorus-based photocatalyst for CO2 reduction are established.

miR-4293 upregulates lncRNA WFDC21P by suppressing mRNA-decapping enzyme 2 to promote lung carcinoma proliferation.

Non-coding RNAs (ncRNAs) involve in diverse biological processes by post-transcriptional regulation of gene expression. Emerging evidence shows that miRNA-4293 plays a significant role in the development of non-small cell lung cancer. However, the oncogenic functions of miR-4293 have not been studied. Our results demonstrated that miR-4293 expression is markedly enhanced in lung carcinoma tissue and cells. Moreover, miR-4293 promotes tumor cell proliferation and metastasis but suppresses apoptosis. Mechanistic investigations identified mRNA-decapping enzyme 2 (DCP2) as a target of miR-4293 and its expression is suppressed by miR-4293. DCP2 can directly or indirectly bind to WFDC21P and downregulates its expression. Consequently, miR-4293 can further promote WFDC21P expression by regulating DCP2. With a positive correlation to miR-4293 expression, WFDC21P also plays an oncogenic role in lung carcinoma. Furthermore, knockdown of WFDC21P results in functional attenuation of miR-4293 on tumor promotion. In vivo xenograft growth is also promoted by both miR-4293 and WFDC21P. Overall, our results establish oncogenic roles for both miR-4293 and WFDC21P and demonstrate that interactions between miRNAs and lncRNAs through DCP2 are important in the regulation of carcinoma pathogenesis. These results provided a valuable theoretical basis for the discovery of lung carcinoma therapeutic targets and diagnostic markers based on miR-4293 and WFDC21P.

The effects of dynamic daylight-like light on the rhythm, cognition, and mood of irregular shift workers in closed environment.

Shift workers are mostly suffered from the disruption of circadian rhythm and health problems. In this study, we designed proper light environment to maintain stable circadian rhythm, cognitive performance, and mood status of shift workers. We used five-channel light-emitting diodes to build up the dynamic daylight-like light environment. The illuminance, correlated color temperature, and circadian action factor of light were tunable in the ranges of 226 to 678 lx, 2680 to 7314 K, and 0.32 to 0.96 throughout the day (5:30 to 19:40). During the nighttime, these parameters maintained about 200 lx, 2700 K, and 0.32, respectively. In this light environment, three subjects had engaged in shift work for 38 consecutive days. We measured plasma melatonin, activity counts, continuous performance tests, and visual analogue scale on mood to assess the rhythm, cognitive performance, and mood of subjects. After 38-day shift work, the subjects' peak melatonin concentration increased significantly. Their physiological and behavioral rhythms maintained stable. Their cognitive performance improved significantly after night work, compared with that before night work. Their mood status had no significant change during the 38-day shift work. These results indicated that the light environment was beneficial to maintain circadian rhythm, cognitive performance and mood status during long-term shift work in closed environment.

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.

Continuous orientated growth of scaled single-crystal 2D monolayer films.

Single-crystal 2D materials have attracted a boom of scientific and technological activities. Recently, chemical vapor deposition (CVD) shows great promise for the synthesis of high-quality 2D materials owing to high controllability, high scalability and ultra-low cost. Two types of strategies have been developed: one is single-seed method, which focuses on the ultimate control of the density of nucleation into only one nucleus and the other is a multi-seed approach, which concentrates on the precise engineering of orientation of nuclei into a uniform alignment. Currently, the latter is recognized as a more effective method to meet the demand of industrial production, whereas the oriented domains can seamlessly merge into a continuous single-crystal film in a short time. In this review, we present the detailed cases of growing the representative monocrystalline 2D materials via the single-seed CVD method as well as show its advantages and disadvantages in shaping 2D materials. Then, other typical 2D materials (including graphene, h-BN, and TMDs) are given in terms of the unique feature under the guideline of the multi-seed growth approach. Furthermore, the growth mechanism for the 2D single crystals is presented and the following application in electronics, optics and antioxidation coatings are also discussed. Finally, we outline the current challenges, and a bright development in the future of the continuous orientated growth of scaled 2D crystals should be envisioned.

Chitin binding protein from the kuruma shrimp Marsupenaeus japonicus facilitates the clearance of Vibrio anguillarum.

Peritrophic membrane (PM) refers to a vital physical barrier enabling shrimp to resist pathogen invasion. It primarily consists of chitin and proteins, mostly chitin-binding protein (CBP). CBPs have been identified from microorganisms to higher organisms. In the present study, a CBP, designated MjCBP, was reported from Marsupenaeus japonicus. The open reading frame of MjCBP was 1854 bp, encoding a protein with 618 amino acids (MH544098). To be specific, the theoretical pI and molecular mass of mature MjCBP reached 5.43 and 66064.00 Da, respectively. MjCBP consisted of seven type Ⅱ chitin-binding domains (ChtB D2), which was up-regulated after being challenged with Vibrio anguillarum and then agglutinating several bacteria. In addition, MjCBP and the first chitin-binding domain (CBD1) could bind to several Gram-positive and Gram-negative bacteria via the binding process to lipopolysaccharides and peptidoglycans, whereas CBD1 was not capable of agglutinating bacteria. Moreover, the anterior and posterior segments of CBD1 were synthesized in vitro, and the posterior segment could bind to lipopolysaccharides. However, both segments fail to agglutinate bacteria. Furthermore, MjCBP and CBD1 facilitated the clearance of V. anguillarum in vivo, and the silencing of MjCBP via RNA interference reduced the ability of bacterial clearance. As revealed from the mentioned results, MjCBP acts as an opsonin or pattern recognition receptor to achieve antibacterial immune response in shrimp.

High Thermoelectric Performance in n-Type Perylene Bisimide Induced by the Soret Effect.

Low-cost, non-toxic, abundant organic thermoelectric materials are currently under investigation for use as potential alternatives for the production of electricity from waste heat. While organic conductors reach electrical conductivities as high as their inorganic counterparts, they suffer from an overall low thermoelectric figure of merit (ZT) due to their small Seebeck coefficient. Moreover, the lack of efficient n-type organic materials still represents a major challenge when trying to fabricate efficient organic thermoelectric modules. Here, a novel strategy is proposed both to increase the Seebeck coefficient and achieve the highest thermoelectric efficiency for n-type organic thermoelectrics to date. An organic mixed ion-electron n-type conductor based on highly crystalline and reduced perylene bisimide is developed. Quasi-frozen ionic carriers yield a large ionic Seebeck coefficient of -3021 µV K-1 , while the electronic carriers dominate the electrical conductivity which is as high as 0.18 S cm-1 at 60% relative humidity. The overall power factor is remarkably high (165 µW m-1 K-2 ), with a ZT = 0.23 at room temperature. The resulting single leg thermoelectric generators display a high quasi-constant power output. This work paves the way for the design and development of efficient organic thermoelectrics by the rational control of the mobility of the electronic and ionic carriers.