Organic High-Temperature Synaptic Phototransistors for Energy-Efficient Neuromorphic Computing.

Organic optoelectronic synaptic devices that can reliably operate in high-temperature environments (i.e., beyond 121°C) or remain stable after high-temperature treatments have significant potential in biomedical electronics and bionic robotic engineering. However, it is challenging to acquire this type of organic devices considering the thermal instability of conventional organic materials and the degradation of photoresponse mechanisms at high temperatures. Here, high-temperature synaptic phototransistors (HTSPs) based on thermally stable semiconductor polymer blends as the photosensitive layer are developed, successfully simulating fundamental optical-modulated synaptic characteristics at a wide operating temperature range from room temperature to 220°C. Robust optoelectronic performance can be observed in HTSPs even after experiencing 750 h of the double 85 testing due to the enhanced operational reliability. Using HTSPs, Morse-code optical decoding scheme and the visual object recognition capability are also verified at elevated temperatures. Furthermore, flexible HTSPs are fabricated, demonstrating an ultralow power consumption of 12.3 aJ per synaptic event at a low operating voltage of -0.05 mV. Overall, the conundrum of achieving reliable optical-modulated neuromorphic applications while balancing low power consumption can be effectively addressed. This research opens up a simple but effective avenue for the development of high-temperature and energy-efficient wearable optoelectronic devices in neuromorphic computing applications.

Energy effective utilization of circulating fluidized bed fly ash to prepare silicon-aluminum composite aerogel and gypsum.

To reduce the cost of Si-Al aerogels preparation, circulating fluidized bed fly ash (CFA) was developed to be as the alternative to synthetic precursors. High energy consumption of alkali-melting and secondary wastes production were the major challenges. Here, a technique characterized by effective energy consumption and non-secondary waste was developed to convert CFA into Si-Al aerogel. The process consists two stages, preparation of Si-Al sol by sintering of CFA and Na2CO3 followed by sulfuric acid leaching, and synthesis of Si-Al aerogel by so-gel with trimethyl chlorosilane modification and ambient pressure drying. The optimization results of proportion and sintering temperature showed that the optimal temperature of sintering of Na2CO3 and CFA with the mass ratio of 0.7 was 750 °C, 100 °C lower than that of most other waste aluminosilicate materials. CaSO4·0.5H2O which meet building gypsum requirement was obtained by specifying the drying temperature of acid-leached residue at 126 °C for 2 h. The modification procedure was explored to obtain Si-Al aerogel with a large specific surface area of 857 m2/g and hydrophobic angle of 139.3°. Thermal and mechanical properties tests indicated that the Si-Al aerogels and gypsum produced from CFA exhibited promising thermal insulation and the potential application in construction.

[Keloid nomogram prediction model based on weighted gene co-expression network analysis and machine learning].

Keloids are benign skin tumors resulting from the excessive proliferation of connective tissue in wound skin. Precise prediction of keloid risk in trauma patients and timely early diagnosis are of paramount importance for in-depth keloid management and control of its progression. This study analyzed four keloid datasets in the high-throughput gene expression omnibus (GEO) database, identified diagnostic markers for keloids, and established a nomogram prediction model. Initially, 37 core protein-encoding genes were selected through weighted gene co-expression network analysis (WGCNA), differential expression analysis, and the centrality algorithm of the protein-protein interaction network. Subsequently, two machine learning algorithms including the least absolute shrinkage and selection operator (LASSO) and the support vector machine-recursive feature elimination (SVM-RFE) were used to further screen out four diagnostic markers with the highest predictive power for keloids, which included hepatocyte growth factor (HGF), syndecan-4 (SDC4), ectonucleotide pyrophosphatase/phosphodiesterase 2 (ENPP2), and Rho family guanosine triphophatase 3 (RND3). Potential biological pathways involved were explored through gene set enrichment analysis (GSEA) of single-gene. Finally, univariate and multivariate logistic regression analyses of diagnostic markers were performed, and a nomogram prediction model was constructed. Internal and external validations revealed that the calibration curve of this model closely approximates the ideal curve, the decision curve is superior to other strategies, and the area under the receiver operating characteristic curve is higher than the control model (with optimal cutoff value of 0.588). This indicates that the model possesses high calibration, clinical benefit rate, and predictive power, and is promising to provide effective early means for clinical diagnosis.

Nuclear-targeted carbon quantum dot mediated CRISPR/Cas9 delivery for fluorescence visualization and efficient editing.

Nuclear targeted delivery has great potential in improving the efficiency of non-viral carrier mediated genome editing. However, direct and efficient delivery of CRISPR/Cas9 plasmid into the nucleus remains a challenge. In this study, a nuclear targeted gene delivery platform based on fluorescent carbon quantum dots (CQDs) was developed. Polyethylenimine (PEI) and polyethylene glycol (PEG) synergistically passivated the surface of CQDs, providing an excitation-independent green-emitting fluorescent CQDs-PEI-PEG conjugate (CQDs-PP) with an ultra-small size and positive surface charge. Here we show that CQDs-PP could bind CRISPR/Cas9 plasmid to form a nano-complex by electrostatic attraction, which can bypass lysosomes and enter the nucleus by passive diffusion, and thereby improve the transfection efficiency. Also, CQDs-PP could deliver CRISPR/Cas9 plasmid into HeLa cells, resulting in the insertion/deletion mutation of the target EFHD1 gene. More importantly, CQDs-PP exhibited a considerably higher gene editing efficiency as well as comparable or lower cytotoxicity relative to Lipo2000 and PEI-passivated CQDs-PEI (CQDs-P). Thus, the nuclear-targeted CQDs-PP is expected to constitute an efficient CRISPR/Cas9 delivery carrier in vitro with imaging-trackable ability.

The adsorption mechanisms of oriental plane tree biochar toward bisphenol S: A combined thermodynamic evidence, spectroscopic analysis and theoretical calculations.

Garden pruning waste is becoming a problem that intensifies the garbage siege. It is of great significance to purify polluted water using biochar prepared from garden pruning waste. Herein, the interaction mechanism between BPS and oriental plane tree biochar (TBC) with different surface functional groups was investigated by adsorption experiments, spectroscopic analysis and theoretical calculations. Adsorption kinetics and isotherm of BPS on TBC can be satisfactorily fitted into pseudo-second-order kinetic and Langmuir models, respectively. A rapid adsorption kinetic toward BPS was achieved by TBC in 15 min. As compared with TBC prepared at low temperature (300 °C) (LTBC), the maximum adsorption capacity of TBC prepared at high temperature (600 °C) (HTBC) can be significantly improved from 46.7 mg g-1 to 72.9 mg g-1. Besides, the microstructure and surface functional groups of HTBC were characterized using SEM, BET-N2, and XPS analysis. According to density functional theory (DFT) theoretical calculations, the higher adsorption energy of HTBC for BPS was mainly attributed to π-π interaction rather than hydrogen bonding, which was further supported by the analysis of FTIR and Raman spectra as well as the adsorption thermodynamic parameters. These findings suggested that by improving π-π interaction through high pyrolysis temperature, BPS could be removed and adsorbed by biochar with high efficacy, cost-efficiency, easy availability, and carbon-negative in nature, contributing to global carbon neutrality.

Carbon quantum Dot@Silver nanocomposite-based fluorescent imaging of intracellular superoxide anion.

Silver nanoparticle (Ag NP)-coated carbon quantum dot (CQD) core-shell-structured nanocomposites (CQD@Ag NCs) were developed for fluorescent imaging of intracellular superoxide anion (O2•-). The morphology of CQD@Ag NCs was investigated by transmission electron microscopy, and the composition was characterized by X-ray diffraction and X-ray photoelectron spectroscopy. CQDs display blue fluorescence with excitation/emission maxima at 360/440 nm, and the fluorescence was quenched by Ag NPs in CQD@Ag NCs. In the presence of O2•-, Ag NPs were oxide-etched and the fluorescence of CQDs was recovered. A linearity between the relative fluorescence intensity and O2•- solution concentration within the range 0.6 to 1.6 µM was found, with a detection limit of 0.3 µM. Due to their high sensitivity, selectivity, and low cytotoxicity, the as-synthesized CQD@Ag NCs have been successfully applied for imaging of O2•- in MCF-7 cells during the whole process of autophagy induced by serum starvation. In our perception, the developed method provides a cost-effective, sensitive, and selective tool in bioimaging and monitoring of intracellular O2•- changes, and is promising for potential biological applications. Graphical abstract Illustration of the synthesis of carbon quantum Dot@Silver nanocomposites (CQD@Ag NCs), and CQD@Ag NCs as a "turn-on" nanoprobe for fluorescent imaging of intracellular superoxide anion.

Downregulation of miR­141 deactivates hepatic stellate cells by targeting the PTEN/AKT/mTOR pathway.

The activation of hepatic stellate cells (HSCs) caused by stimulating factors or fibrogenic cytokines is the critical stage of liver fibrosis. Recent studies have demonstrated the influence of microRNAs (miRNAs or miRs) on HSC activation and transformation; however, the function and underlying mechanisms of miRNAs in HSC activation have not yet been completely clarified. In the present study, transforming growth factor ß1 (TGF­ß1) was used to treat human HSC lines (HSC­T6 and LX2 cells) to simulate the activation of HSCs in vivo and whether the expression of miRNAs in HSCs was affected by TGF­ß1 treatment was examined using a miRNA microarray. It was observed that miR­141 was one of the most upregulated miRNAs during HSC activation. Functional analyses revealed that miR­141 knockdown suppressed the viability of HSCs and inhibited the expression levels of pro­fibrotic markers. In addition, phosphatase and tensin homolog (PTEN), a well­known suppressor of the AKT/mammalian target of rapamycin (mTOR) pathway, was found to be directly targeted by miR­141 in HSCs. More importantly, the knockdown of PTEN markedly reversed the suppressive effects of miR­141 inhibition on the viability of and the expression levels of pro­fibrotic markers during HSC activation. Finally, it was observed that the downregulation of miR­141 blocked the TGF­ß1­induced activation of the AKT/mTOR pathway in HSCs. On the whole, the findings of the present study indicate that miR­141 inhibition suppresses HSC activation via the AKT/mTOR pathway by targeting PTEN, highlighting that miR­141 may serve as a novel therapeutic target for liver fibrosis.

MiR-873, as a suppressor in cervical cancer, inhibits cells proliferation, invasion and migration via negatively regulating ULBP2.

BACKGROUND: Cervical cancer (CC) remains a large burden in the developing countries. The tumor inhibitory role of miR-873 has been verified in a variety of cancers, however, whether miR-873 has a suppressive effect on CC remains unclear. OBJECTIVE: The purpose of this study was to investigate the functional role of miR-873 in CC, as well as explore the underlying molecular mechanism. METHODS: The prognostic values of miR-873 were assessed by Kaplan-Meier methods and cox regression models using the data which were downloaded from TCGA database. The expression of miR-873 was measured by RT-qPCR. Cell counting Kit-8, clone formation, and Transwell assays were used to assess the cell viability and metastasis, appropriately. The targeting relationship between miR-873 and ULBP2 was predicted by biological software and confirmed by dual luciferase reporter assay. Rescue assays were conducted to investigate whether miR-873 affects the phenotype of CC cells via regulating ULBP2. RESULTS: We observed that miR-873 was low-expressed in CC. Up-regulation of miR-873 notably restrained the proliferation, invasion and migration of C33a cells. Meanwhile, down-regulation of miR-873 in SiHa cells presented the opposite outcomes. ULBP2 was forecasted and certified as a target of miR-873. The results of rescue assays showed that overexpression of ULBP2 could restore the proliferation and motility of CC cells that inhibited by miR-873. CONCLUSION: MiR-873 suppressed the CC cells proliferation, invasion and migration via negatively regulating ULBP2, suggesting that miR-873 could serve as a valuable therapeutic target for CC therapy.

Existence of Ligands within Sol-Gel-Derived ZnO Films and Their Effect on Perovskite Solar Cells.

The sol-gel (SG) method has been well-documented as one useful way to produce ZnO films as an excellent electron transport material (ETM) for efficient perovskite solar cells (PSCs). Generally, the precursor films containing zinc acetate dihydrate and a stabilizing ligand monoethanolamine (EA) were annealed to obtain ZnO films. A noteworthy issue is the commonly reported annealing temperature (Ta) in a wide range of 150-600 °C. In this work, we investigated the effect of the annealing temperature on the film composition and first confirmed the co-existence of acetate and EA species when Ta is below 380 °C. EA still survived within the ZnO films when Ta was between 380 and 450 °C. When Ta was over 450 °C, pure ZnO films can be obtained. The presence of ligands also remarkably altered the work function of the corresponding ZnO samples, thereby resulting in the remarkably different effects on the efficiency and stability of PSCs with the ZnO samples as ETMs. This work affords a clearer understanding of ZnO films prepared by the SG method at molecular insights, promoting their application in photoelectric fields.

Ran1 is essential for parental macronuclear import of apoptosis-inducing factor and programmed nuclear death in Tetrahymena thermophila.

During programmed nuclear death (PND), apoptosis-inducing factor (AIF) translocates from mitochondria to the parental macronucleus (MAC) in Tetrahymena thermophila. In the degenerating parental MAC, AIF induces chromatin condensation and large-scale DNA fragmentation in a caspase-independent manner. However, the regulation of AIF nuclear translocation and molecular mechanism of PND are less clear. In this study, we demonstrated that the asymmetric distribution of nuclear GDP-bound Ran1-mimetic mutant Ran1T25N and cytoplasmic GTP-bound Ran1-mimetic mutant Ran1Q70L exists across the parental macronuclear-cytoplasmic barrier during PND. Knockdown of RAN1 led to defects in PND progression and failure of parental macronuclear accumulation of AIF. Moreover, AIF parental macronuclear import occurred in Ran1T25N mutants, while it was inhibited in Ran1Q70L mutants. Importantly, artificial accumulation of AIF in the parental MAC rescued PND progression defects in RAN1 knockdown mutants. These data suggest that Ran1 is essential for parental macronuclear import of AIF and PND in T. thermophila.

Development and validation of a HPLC-MS/MS method with electrospray ionization for quantitation of potassium oxonate in human plasma: Application to a pharmacokinetic study.

A rapid, sensitive and specific HPLC-MS/MS method was developed and validated for the quantification of potassium oxonate (Oxo) in human plasma using [(13)C(2),(15)N(3)]-Oxo as an internal standard (IS). The target substance was separated from human plasma using the solid-phase extraction method. Chromatography separation was performed on a Waters:Atlantis dC(18) column (150×4.6 mm, 5.0 µm) with a mobile phase consisting of H(2)O with 0.1% formic acid in acetonitrile (90:10, v/v). The mass spectrometer works with electrospray ionization and multiple reaction monitoring in its negative ion mode, using target ions at [M-H](-) m/z 111.9 for Oxo and [M-H](-) m/z 117.0 for the IS. The mean standard curve was linear (r=0.9991) over the concentration range of 2.0-200.0 ng/ml and had good back-calculated accuracy and precision. The intra- and inter-day precision were <6.33% and the accuracy was >99.38%. The extraction recovery was >60.26%. The lower limit of quantification achieved with this method was 2.0 ng/ml. This assay method was demonstrated to be accurate, sensitive and simple and was successfully applied to a pharmacokinetic study following single oral administration of a 40-mg S-1 capsule in 12 tumor patients.

Subcellular localization and role of Ran1 in Tetrahymena thermophila amitotic macronucleus.

Amitosis, a direct method of cell division is common in ciliated protozoan, fungi and some animal and plant cells. During amitosis, intranuclear microtubules are reorganized into specified arrays which assist in separation of nucleus, despite lack of a bipolar spindle. However, the regulation of amitosis is not understood. Here, we focused on the localization and role of mitotic spindle assembly regulator: Ran GTPase (Ran1) in macronuclear amitosis in binucleated protozoan Tetrahymena thermophila. HA-tagged Ran1 was localized in the macronucleus throughout the cell cycle of Tetrahymena during vegetative growth, and the accessory factor binding domains of Ran1 contributed to its macronuclear localization. Incomplete somatic knockout of RAN1 resulted in aberrant intramacronuclear microtubule array formation, missegregation of macronuclear chromosomes and ultimately blocked macronuclei proliferation. When the Ran1 cycle was perturbed by overexpression of Ran1T25N (GDP-bound Ran1-mimetic) or Ran1Q70L (GTP-bound Ran1-mimetic), intramacronuclear microtubule assembly was inhibited or multi-micronucleate cells formed. These results suggest that Ran GTPase pathway is involved in assembly of a specialized intramacronuclear microtubule network and coordinates amitotic progression in Tetrahymena.

Simple, sensitive and rapid HPLC-MS/MS method for the determination of cepharanthine in human plasma.

A rapid, sensitive and specific method for the determination of cepharanthine in human plasma using high performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS) was described. Cepharanthine and the internal standard (I.S.), telmisartan, were extracted from human plasma by methanol to precipitate the protein. A centrifuged upper layer was then evaporated and reconstituted with 100µL methanol. Chromatographic separation was performed on an AGILENT XDB-C(8) column (150mm×2.1mm, 5.0µm, Agilent, USA) using a gradient mobile phase with 1mmol/L ammonium acetate in water with 0.05% formic acid and methanol. Detection and quantitation was performed by MS/MS using electrospray ionization (ESI) and multiple reaction monitoring (MRM) in the positive ion mode. The most intense [M+H](+) MRM transition of cepharanthine at m/z 607.3→365.3 was used for quantitation and the transition at m/z 515.5→276.4 was used to monitor telmisartan. The calibration curve was linear within the concentration range of 0.5-200.0ng/mL (r=0.9994). The limit of quantification (LOQ) was 0.5ng/mL. The extraction recovery was above 81.1%. The accuracy was higher than 92.3%. The intra- and inter-day precisions were less than 9.66%. The method was accurate, sensitive and simple and was successfully applied to a pharmacokinetic study after single intravenous administration of 50mg cepharanthine in 12 healthy Chinese volunteers.

Effects of clozapine administration on body weight, glucose tolerance, blood glucose concentrations, plasma lipids, and insulin in male C57BL/6 mice: A parallel controlled study.

BACKGROUND: Clozapine has been associated with metabolic adverse events (AEs) (eg, elevated body weight, blood glucose concentrations, cholesterol, triglycerides [TG]), all of which have deleterious effects on health and medication compliance. However, little focus has been directed toward finding a suitable experimental model to study the metabolic AEs associated with clozapine. OBJECTIVE: The aim of this study was to assess the effects of clozapine administration for 28 days on body weight, glucose tolerance, blood glucose concentrations, plasma lipids, and insulin in C57BL/6 mice. METHODS: C57BL/6 mice were grouped and treated with clozapine 2 or 10 mg/kg or vehicle intraperitoneally QD for 28 days. Body weight was assessed on days 0 (baseline), 7, 14, 21, and 28, and glucose tolerance, blood glucose concentrations, insulin (calculated by insulin resistance index [IRI]), and plasma lipids (including total cholesterol, TG, high-density lipoprotein cholesterol [HDL-C], and low-density lipoprotein cholesterol) were assessed on day 29. RESULTS: Sixty 10-week-old, male C57BL/6 mice were included in the study and were divided into 3 groups (20 mice per group). The body weight significantly decreased in the clozapine 10-mg-treated group on days 14, 21, and 28 compared with the vehicle group (mean [SD] body weight: 21.61 [1.05] vs 22.79 [1.11], 22.53 [1.05] vs 24.17 [1.24], and 22.21 [1.07] vs 24.99 [1.39] g, respectively; all, P < 0.05). In the clozapine 10-mg/kg group, blood glucose concentrations significantly increased 0, 30, 60, and 120 minutes after glucose administration compared with the vehicle group (mean [SD]: 6.67 [1.25], 25.34 [5.85], 12.68 [3.39], and 7.52 [1.45] mmol/L, respectively, vs 4.61 [0.78], 21.54 [6.55], 11.46 [3.46], and 6.55 [1.42] mmol/L, respectively; all P < 0.05). The clozapine 10-mg/kg group also had significant increases in plasma insulin concentrations compared with the vehicle group (12.70 [5.27] vs 7.62 [4.54] µIU/mL; P < 0.05) and IRI (3.01 [1.26] vs 1.51 [0.96]; P < 0.05). Plasma HDL-C concentration also significantly decreased in the clozapine 10-mg/kg group compared with the vehicle group (1.23 [0.25] vs 1.47 [0.16]; P < 0.05). CONCLUSION: Clozapine 10 mg/kg was associated with significant decreases in body weight and significant increases in fasting blood glucose and glucose tolerance in these male C57BL/6 mice.