VGLL4-TEAD1 promotes vascular smooth muscle cell differentiation from human pluripotent stem cells via TET2.

The Hippo signaling pathway plays a critical role in cardiovascular development and stem cell differentiation. Using microarray profiling, we found that the Hippo pathway components vestigial-like family member 4 (VGLL4) and TEA domain transcription factor 1 (TEAD1) were upregulated during vascular smooth muscle cell (VSMC) differentiation from H1 ESCs (H1 embryonic stem cells). To further explore the role and molecular mechanisms of VGLL4 in regulating VSMC differentiation, we generated a VGLL4-knockdown H1 ESC line (heterozygous knockout) using the CRISPR/Cas9 system and found that VGLL4 knockdown inhibited VSMC specification. In contrast, overexpression of VGLL4 using the PiggyBac transposon system facilitated VSMC differentiation. We confirmed that this effect was mediated via TEAD1 and VGLL4 interaction. In addition, bioinformatics analysis revealed that Ten-eleven-translocation 2 (TET2), a DNA dioxygenase, is a target of TEAD1, and a luciferase assay further verified that TET2 is the target of the VGLL4-TEAD1 complex. Indeed, TET2 overexpression promoted VSMC marker gene expression and countered the VGLL4 knockdown-mediated inhibitory effects on VSMC differentiation. In summary, we revealed a novel role of VGLL4 in promoting VSMC differentiation from hESCs and identified TET2 as a new target of the VGLL4-TEAD1 complex, which may demethylate VSMC marker genes and facilitate VSMC differentiation. This study provides new insights into the VGLL4-TEAD1-TET2 axis in VSMC differentiation and vascular development.

Actively Q-switched self-frequency-doubled Yb:YCOB green laser with output power of a dozen watts.

A diode laser (LD) end-pumped acousto-optic Q-switched self-frequency-doubled (SFD) Yb:YCa4O(BO3)3 (Yb:YCOB) pulsed green laser was realized for the first time (to our knowledge), with a maximum average output power of 11.6 W and an optical conversion efficiency of 30.0% from the LD to SFD lasers. The wavelength of the SFD lasers was controlled to be 507 nm for improving quantum efficiency up to 96% and reducing thermal effects. The repetition rates ranged from 20 to 500 kHz, and the maximum pulse energy was 312.0 µJ with a peak power of 4.78 kW at a repetition rate of 20 kHz. This work represents the highest output power in the SFD pulsed lasers and provides an efficient and compact way to generate high-power pulsed green lasers that should have important applications in many aspects, such as ultraviolet (UV) laser generation, laser display, and medical, military, and scientific research.

In-situ-reduced synthesis of cyano group modified g-C3N4/CaCO3 composite with highly enhanced photocatalytic activity for nicotine elimination.

Graphite carbon nitride has many excellent properties as a two-dimensional semiconductor material so that it has a wide application prospect in the field of photocatalysis. However, the traditional problems such as high recombination rate of photogenerated carriers limit its application. In this work, we introduce nitrogen deficiency into g-C3N4 to solve this problem a simple and safe in-situ reduction method. g-C3N4/CaCO3 was obtained by a simple and safe one-step calcination method with industrial-grade micron particles CaCO3. Cyano group modification was in-situ reduced during the thermal polymerization process, which would change the internal electronic structure of g-C3N4. The successful combination of g-C3N4 and CaCO3 and the introduction of cyanide have been proved by Fourier transform infrared spectroscopy and X-ray photoelectron spectrometer. The formation of the cyano group, an electron-absorbing group, promotes the effective separation of photogenic electron hole pairs and inhibits the recombination of photogenic carriers. These advantages result in the generation of more •O2- and 1O2 in the catalytic system, which increases the photocatalytic efficiency of nicotine degradation by ten times. Furthermore, the degradation process of nicotine has been studied in this work to provide a basis for the degradation of nicotine organic pollutants in the air.

High-power continuous-wave self-frequency-doubled monolithic laser.

We report a high-power self-frequency-doubled (SFD) Yb:YCa4O(BO3)3 laser by employing a simple and high-integration monolithic configuration with an oscillator length of 6 mm. By reducing the reabsorption and increasing the quantum efficiency, the continuous-wave output power of 21.6 W was obtained with an optical conversion efficiency of 19.0% at the wavelength of about 510 nm. To our knowledge, the results represent the highest output power of a SFD laser. We believe that the high-power SFD laser with a highly compact structure will have broad and promising application prospects in laser display, medical treatment, spectral analysis, scientific research, and other fields.

Self-neglect among older adults admitted to a Chinese comprehensive hospital in the COVID-19 pandemic era: a cross-sectional study.

This study aims to explore the prevalence of self-neglect and associated factors among older adults admitted to the hospital in the COVID-19 pandemic context. The cross-sectional study conducted at a Chinese comprehensive hospital between January and April 2021, 452 older adults were recruited to complete the Abrams Geriatric Self-Neglect Scale, Social Support Rate Scale, FRAIL scale, Barthel index, Patient Health Questionnaire-9, and 10-item Connor-Davidson Resilience Scale. Multivariate logistic regression was used to explore the factors associated with elder self-neglect. The results showed that the prevalence of self-neglect among our sample was 30.3%. Factors that were associated with the risk of elder self-neglect included male, having multiple children (≥4), receiving infrequent visits from children, frailty, and depression. There is a need to screen for self-neglect among older adults admitted to the hospital in the COVID-19 pandemic context. Tailored interventions are warranted to improve the quality of life of older adults.

[Characteristics and Clinical Application of Commonly Used Wound Dressings].

The pathological mechanism of wound healing is complicated and affected by multiple factors. Modern wound dressings are widely used in the clinical management of wound healing and have achieved good therapeutic effects. Clinically, wounds are often caused by different etiologies. However, there are few reviews focus on the selection of reasonable dressings for different types of wounds. This study mainly focuses on the characteristics of commonly used wound dressings and summarizes the characteristics of the most commonly used wound dressings in clinical practice and their effects. The advantages and disadvantages of pathology wounds: diabetic foot ulcers, pressure injuries, burns, and leg ulcers are reviewed. This study aims to provide references for the development and clinical selection of wound dressings for scientific researchers and first-line nursing staff who are engaged in wound dressings.

Supporting Young Students' Word Study During the COVID-19 Quarantine: ABC Scavenger Hunt.

The COVID-19 pandemic has dramatically affected U.S. schools since March 2020. K-12 schools have put in place various forms of remote learning to continue the education of students. In trying times like these, young students face unique unprecedented challenges. Often, they need parents' and/or guardians' supervision and guidance at home. How can teachers work with young students and their parents or guardians to ensure high-quality and equitable teaching and learning during the COVID-19 pandemic? More specifically, how can teachers support young students' word study from home during trying times? An ABC scavenger hunt can be a great activity to support young students' word study while bridging home and school and fostering a positive home learning environment. We share teaching tips developed by a first-grade teacher over the past several months.

Finite element analysis of fiber-optic Fabry-Perot pressure sensors based on silicon diaphragms.

Fiber-optic Fabry-Perot pressure sensors based on silicon diaphragms of different thicknesses were fabricated using surface and bulk MEMS techniques in this study. The multi-beam interference resulting from multiple reflecting mirrors with the elastic deformation of the Fabry-Perot sensor was simulated by finite element analysis. The pressure sensitivities of the sensors with different diaphragm thicknesses and the relationship between the pressure and the wavelength shift were simulated. The simulation results were in good agreement with the test results. This study provides guidance for future sensor models and parameter design.

Comparison of Measurements with Finite-Element Analysis of Silicon-Diaphragm-Based Fiber-Optic Fabry-Perot Temperature Sensors.

Silicon-diaphragm-based fiber-optic Fabry-Perot sensors with different intracavity pressures were fabricated by anodic bonding and microelectromechanical techniques. The thermal stress and thermal expansion of the Fabry-Perot (FP) sensor caused by high-temperature bonding and temperature change were simulated by finite-element analysis. The calculated thermal stress is largest in the center and edge regions of the resonance cavity, reaching from 2 to 6 MPa. The reflection spectra and temperature sensitivity of the sensors were simulated by using a two-dimensional wave-optic model in Comsol. Theoretical calculations were also made for the FP cavity without considering silicon-diaphragm deformation and thermal stress. Four sensors with intracavity pressures of 0.01, 0.03, 0.04, and 0.05 MPa were tested at low temperatures, showing a high degree of consistency with the simulation results rather than theoretical calculation, especially for high intracavity pressure. This method is expected to aid the analysis of thermal stress generated during the bonding process and to facilitate better design and control of the temperature sensitivity of the sensor.

Effect of electron avalanche breakdown on a high-purity semi-insulating 4H-SiC photoconductive semiconductor switch under intrinsic absorption.

High-power photoconductive semiconductor switching devices were fabricated from a high-purity, semi-insulating 4H-SiC wafer. A highly n-doped GaN subcontact layer was inserted between the contact metal and the high-resistivity SiC wafer. The minimum ON-state resistance of the device was less than 1 ohm when the energy of a 355 nm laser was 10.5 mJ with a bias voltage of 6 kV. The maximum device lifetime is 3151 pulses, after which the device completely fails. The failure mechanisms are determined using several analysis methods. Under a strong electric field, the failure mechanism differs for the two electrodes. Near the edge of the anode electrode, the switch is damaged due to the thermal stress caused by impact ionization. At the edge of the cathode electrode, the electrode erosion is the main reason for the failure to operate for long periods of time. These two different damage mechanisms are both important factors influencing the device performance. The electron avalanche breakdown at the edge of the anode electrode causes the formation of cracks between the electrodes, which is the root cause of the switch failure.

Reproductive Hormones and Their Receptors May Affect Lung Cancer.

BACKGROUND/AIMS: In contrast to men, women have experienced a rapid increase in lung cancer mortality. Numerous studies have found that the sex differences in lung cancer are due to reproductive hormones. Experiments in female mice with and without ovariectomy were performed to explore the possible mechanism by which sex hormones (and their receptors) influence lung cancer. METHODS: Twenty-four female C57BL/6 mice aged 56-62 days were randomly divided into the ovariectomized group and the control group. In the ovariectomized group, the bilateral ovaries were removed via the dorsal approach, while the control group underwent a sham operation with bilateral ovarian fat resection at the same sites. After 3 weeks of recovery, Lewis lung cancer cells were transplanted into these mice by subcutaneous inoculation of a tumour cell suspension to establish the ovariectomized lung cancer model. Beginning on the 6th day after subcutaneous inoculation, mouse weight and transplanted tumour volume were measured every 3 days. After 3 weeks, all the mice were killed by cervical dislocation, and we measured the tumour weight. Mouse serum and tumour tissues were removed. Then, the serum levels of E2 (oestradiol) and T (testosterone) were detected by ELISA; the protein expression levels of AR (androgen receptor), ERα (oestrogen receptor α) and ERß (oestrogen receptor ß) were detected by Western Blot and IHC (immunohistochemistry); and the mRNA expression levels of AR, ERα and ERß were detected by qRT-PCR (quantitative real-time polymerase chain reaction) in the ovariectomized and control groups. RESULTS: Compared with the control group, both mouse weight and transplanted tumour volume increased rapidly in the ovariectomized group, and the transplanted tumour weight was significantly heavier in the ovariectomized group (1.83±0.40 and 3.13±0.43, P<0.05). E2 and T serum levels decreased exponentially in the ovariectomized group, while the E2/T ratio increased compared with the control group (E2: 55.88±11.45 and 78.21±9.37; T: 0.82±0.14 and 1.46±0.16; ratio: 69.62±14.43±29.81 and 52.22±5.42; all P<0.05). The Western blot and IHC results indicated that AR, ERα and ERß protein expression levels were obviously higher in transplanted tumour and lung tissues from the ovariectomized group, with particular increases in ERß in transplanted tumour tissue and in ERα in lung tissue. The PCR results also showed markedly higher mRNA expression levels of AR, ERα and ERß in the ovariectomized group, and in particular, ERß in transplanted tumour tissue and ERα in lung tissue were significantly increased in the ovariectomized group. CONCLUSION: Ovariectomy decreased E2 and T serum levels and increased the E2/T ratio in mice, and this imbalance in the internal environment promoted the growth of transplanted tumours. Sex hormone disorder not only promoted transplanted tumour growth but also significantly reduced the protein and mRNA expression levels of sex hormone receptors. The metabolism of E2 and T may affect the growth, proliferation and metabolism of lung cancer cells, and the mechanism by which sex hormones and their receptors influence lung cancer is worthy of further research.

Tunable and selective hydrogenation of furfural to furfuryl alcohol and cyclopentanone over Pt supported on biomass-derived porous heteroatom doped carbon.

The search for and exploitation of efficient catalytic systems for selective conversion of furfural into various high value-added chemicals remains a huge challenge for green synthesis in the chemical industry. Here, novel Pt nanoparticles supported on bamboo shoot-derived porous heteroatom doped carbon materials were designed as highly active catalysts for controlled hydrogenation of furfural in aqueous media. The porous heteroatom doped carbon supported Pt catalysts were endowed with a large surface area with a hierarchical porous structure, a high content of nitrogen and oxygen functionalities, a high dispersion of the Pt nanoparticles, good water dispersibility and reaction stability. Benefiting from these features, the novel Pt catalysts displayed a high activity and controlled tunable selectivity for furfural hydrogenation to produce furfuryl alcohol and cyclopentanone in water. The product selectivity could be easily modulated by controlling the carbonization temperature of the porous heteroatom doped carbon support and the reaction conditions (temperature and H2 pressure). Under mild conditions (100 °C, 1 MPa H2), furfuryl alcohol was obtained in water with complete conversion of the furfural and an impressive furfuryl alcohol selectivity of >99% in the presence of Pt/NC-BS-500. A higher reaction temperature, in water, favored rearrangement of the furfural (FFA) with Pt/NC-BS-800 as the catalyst, which resulted in a high cyclopentanone yield of >76% at 150 °C and 3 MPa H2. The surface properties and pore structure of the heteroatom doped carbon support, adjusted using the carbonization temperature, might determine the interactions between the Pt nanoparticles, carbon support and catalytic reactants in water, which in turn could have led to a good selectivity control. The effect of different reaction temperatures and reaction times on the product selectivity was also explored. Combined with exploration of the distribution of the reaction products, a reaction mechanism for furfural reduction has been proposed.

The overshoot and phenotypic equilibrium in characterizing cancer dynamics of reversible phenotypic plasticity.

The paradigm of phenotypic plasticity indicates reversible relations of different cancer cell phenotypes, which extends the cellular hierarchy proposed by the classical cancer stem cell (CSC) theory. Since it is still questionable if the phenotypic plasticity is a crucial improvement to the hierarchical model or just a minor extension to it, it is worthwhile to explore the dynamic behavior characterizing the reversible phenotypic plasticity. In this study we compare the hierarchical model and the reversible model in predicting the cell-state dynamics observed in biological experiments. Our results show that the hierarchical model shows significant disadvantages over the reversible model in describing both long-term stability (phenotypic equilibrium) and short-term transient dynamics (overshoot) in cancer cell populations. In a very specific case in which the total growth of population due to each cell type is identical, the hierarchical model predicts neither phenotypic equilibrium nor overshoot, whereas the reversible model succeeds in predicting both of them. Even though the performance of the hierarchical model can be improved by relaxing the specific assumption, its prediction to the phenotypic equilibrium strongly depends on a precondition that may be unrealistic in biological experiments. Moreover, it still does not show as rich dynamics as the reversible model in capturing the overshoots of both CSCs and non-CSCs. By comparison, it is more likely for the reversible model to correctly predict the stability of the phenotypic mixture and various types of overshoot behavior.

Laser Ablation of 6H-SiC Single Crystals and Spectral Characterization.

Laser micromachining has proven to be a useful tool for precision processing of semiconductors. For Silicon Carbide (SiC) single crystals, ablation with ultraviolet wavelength laser could lead to the maximum absorption efficiency of incident energy. In this paper, laser ablations were performed on 6H-SiC single crystals through a 355 nm solid state laser. Different confining media were also employed to find the optimal processing condition. The surface of SiC after laser ablation was characterized by Raman spectroscopy. Amorphous silicon and nanocrystalline graphite were found to be the main compositions left. For SiC wafers ablation in air, the amorphous silicon exhibited mainly around rather than inside the ablated crater. However, the amorphous silicon showed opposite spatial distribution features for samples processing under liquid. Through analysis of the compositions left on the ablated surface, the ablation mechanism was investigated from another point of view. For liquid confined laser processing,previous studies mainly concentrate on the thickness and viscosity of the liquids, little information has been done on the reducibility of liquids. To investigate the influence of liquid reducibility, the surface morphology and oxygen content of ablation under different confining media were checked by confocal laser scanning microscopy and energy dispersive spectroscopy. Results showed that the reducibility of confining liquid also played a vital role in the ablation process under liquid. Utilizing liquids with deoxidizing ability as confining media will result in a remarkable reduction of surface oxygen content and a more regular morphology.

Arsenic suppresses cell survival via Pirh2-mediated proteasomal degradation of ΔNp63 protein.

Transcription factor p63, a member of the p53 family, shares a high degree of sequence similarity with p53. Because of transcription from two distinct promoters, the p63 gene encodes two isoforms, TAp63 and ΔNp63. Although TAp63 acts as a tumor suppressor, ΔNp63 functions as an oncogene and is often overexpressed in squamous cell carcinomas. Thus, therapeutic agents targeting ΔNp63 might be used to manage tumors that overexpress ΔNp63. Here we found that arsenic trioxide, a frontline agent for acute promyelocytic leukemia, inhibits ΔNp63 but not TAp63 expression in time- and dose-dependent manners. In addition, we found that arsenic trioxide decreases the stability of ΔNp63 protein via a proteasome-dependent pathway but has little effect on the level of ΔNp63 transcript. Furthermore, we found that arsenic trioxide activates the Pirh2 promoter and consequently induces Pirh2 expression. Consistent with this, we found that knockdown of Pirh2 inhibits, whereas ectopic expression of Pirh2 enhances, arsenic-induced degradation of ΔNp63 protein. Importantly, we found that knockdown of ΔNp63 sensitizes, whereas ectopic expression of ΔNp63 inhibits, growth suppression induced by arsenic. Together, these data suggest that arsenic degrades ΔNp63 protein at least in part via Pirh2-dependent proteolysis and that inhibition of ΔNp63 expression facilitates tumor cells to arsenic-induced death.

Glutathione Induces Keap1 S-Glutathionylation and Mitigates Oscillating Glucose-Induced ß-Cell Dysfunction by Activating Nrf2.

Glutathione (GSH), a robust endogenous antioxidant, actively participates in the modulation of the redox status of cysteine residues in proteins. Previous studies have indicated that GSH can prevent ß-cell failure and prediabetes caused by chronic oscillating glucose (OsG) administration. However, the precise mechanism underlying the protective effect is not well understood. Our current research reveals that GSH is capable of reversing the reduction in Nrf2 levels, as well as downstream genes Grx1 and HO-1, in the islet ß-cells of rats induced by chronic OsG. In vitro experiments have further demonstrated that GSH can prevent ß-cell dedifferentiation, apoptosis, and impaired insulin secretion caused by OsG. Additionally, GSH facilitates the translocation of Nrf2 into the nucleus, resulting in an upregulation of Nrf2-targeted genes such as GCLC, Grx1, HO-1, and NQO1. Notably, when the Nrf2 inhibitor ML385 is employed, the effects of GSH on OsG-treated ß-cells are abrogated. Moreover, GSH enhances the S-glutathionylation of Keap1 at Cys273 and Cys288, but not Cys151, in OsG-treated ß-cells, leading to the dissociation of Nrf2 from Keap1 and facilitating Nrf2 nuclear translocation. In conclusion, the protective role of GSH against OsG-induced ß-cell failure can be partially attributed to its capacity to enhance Keap1 S-glutathionylation, thereby activating the Nrf2 signaling pathway. These findings provide novel insights into the prevention and treatment of ß-cell failure in the context of prediabetes/diabetes, highlighting the potential of GSH.

A Bayesian benchmark concentration analysis for urinary fluoride and intelligence in adults in Guizhou, China.

Environmental fluoride exposure has been linked to numerous cases of fluorosis worldwide. Previous studies have indicated that long-term exposure to fluoride can result in intellectual damage among children. However, a comprehensive health risk assessment of fluorosis-induced intellectual damage is still pending. In this research, we utilized the Bayesian Benchmark Dose Analysis System (BBMD) to investigate the dose-response relationship between urinary fluoride (U-F) concentration and Raven scores in adults from Nayong, Guizhou, China. Our research findings indecate a dose-response relationship between the concentration of U-F and intelligence scores in adults. As the benchmark response (BMR) increased, both the benchmark concentration (BMCs) and the lower bound of the credible interval (BMCLs) increased. Specifically, BMCs for the association between U-F and IQ score were determined to be 0.18 mg/L (BMCL1 = 0.08 mg/L), 0.91 mg/L (BMCL5 = 0.40 mg/L), 1.83 mg/L (BMCL10 = 0.83 mg/L) when using BMRs of 1 %, 5 %, and 10 %. These results indicate that U-F can serve as an effective biomarker for monitoring the loss of IQ in population. We propose three interim targets for public policy in preventing interllectual harm from fluoride exposure.

CaSTH2 disables CaWRKY40 from activating pepper thermotolerance and immunity against Ralstonia solanacearum via physical interaction.

CaWRKY40 coordinately activates pepper immunity against Ralstonia solanacearum infection (RSI) and high temperature stress (HTS), forms positive feedback loops with other positive regulators and is promoted by CaWRKY27b/CaWRKY28 through physical interactions; however, whether and how it is regulated by negative regulators to function appropriately remain unclear. Herein, we provide evidence that CaWRKY40 is repressed by a SALT TOLERANCE HOMOLOG2 in pepper (CaSTH2). Our data from gene silencing and transient overexpression in pepper and epoptic overexpression in Nicotiana benthamiana plants showed that CaSTH2 acted as negative regulator in immunity against RSI and thermotolerance. Our data from BiFC, CoIP, pull down, and MST indicate that CaSTH2 interacted with CaWRKY40, by which CaWRKY40 was prevented from activating immunity or thermotolerance-related genes. It was also found that CaSTH2 repressed CaWRKY40 at least partially through blocking interaction of CaWRKY40 with CaWRKY27b/CaWRKY28, but not through directly repressing binding of CaWRKY40 to its target genes. The results of study provide new insight into the mechanisms underlying the coordination of pepper immunity and thermotolerance.

Growing Echo State Network With an Inverse-Free Weight Update Strategy.

An echo state network (ESN) draws widespread attention and is applied in many scenarios. As the most typical approach for solving the ESN, the matrix inverse operation of high computational complexity is involved. However, in the modern big data era, addressing the heavy computational burden problem is necessary. In order to reduce the computational load, an inverse-free ESN (IFESN) is proposed for the first time in this article. Besides, an incremental IFESN is constructed to attain the network topology with theoretical proof on the training error's monotone decline property. Simulations and experiments are conducted on several numerical and real-world time-series benchmarks, and corresponding results indicate that the proposed model is superior to some existing models and possesses excellent practical application potential. The source code is publicly available at https://github.com/LongJin-lab/the-supplementary-file-for-CYB-E-2021-04-0944.

Sp1-mediated miR-193b suppresses atopic dermatitis by regulating HMGB1.

Atopic dermatitis (AD) is a chronic and recurrent inflammatory skin disease. Keratinocyte dysfunction plays a central role in AD development. MicroRNA is a novel player in many inflammatory and immune skin diseases. In this study, we investigated the potential function and regulatory mechanism of miR-193b in AD. Inflamed human keratinocytes (HaCaT) were established by tumor necrosis factor (TNF)-α/interferon (IFN)-γ stimulation. Cell viability was measured using MTT assay, while the cell cycle was analyzed using flow cytometry. The cytokine levels were examined by enzyme-linked immunosorbent assay. The interaction between Sp1, miR-193b, and HMGB1 was analyzed using dual luciferase reporter and/or chromatin immunoprecipitation (ChIP) assays. Our results revealed that miR-193b upregulation enhanced the proliferation of TNF-α/IFN-γ-treated keratinocytes and repressed inflammatory injury. miR-193b negatively regulated high mobility group box 1 (HMGB1) expression by directly targeting HMGB1. Furthermore, HMGB1 knockdown promoted keratinocyte proliferation and inhibited inflammatory injury by repressing nuclear factor kappa-B (NF-κB) activation. During AD progression, HMGB1 overexpression abrogated increase of keratinocyte proliferation and repression of inflammatory injury caused by miR-193b overexpression. Moreover, transcription factor Sp1 was identified as the biological partner of the miR-193b promoter in promoting miR-193b expression. Therefore, Sp1 upregulation promotes keratinocyte proliferation and represses inflammatory injury during AD development via promoting miR-193b expression and repressing HMGB1/NF-κB activation.