Tunable Negative and Positive Photoconductance in Van Der Waals Heterostructure for Image Preprocessing.

The processing of visual information occurs mainly in the retina, and the retinal preprocessing function greatly improves the transmission quality and efficiency of visual information. The artificial retina system provides a promising path to efficient image processing. Here, graphene/InSe/h-BN heterogeneous structure is proposed, which exhibits negative and positive photoconductance (NPC and PPC) effects by altering the strength of a single wavelength laser. Moreover, a modified theoretical model is presented based on the power-dependent photoconductivity effect of laser: I ph = - mP α 1 + nP α 2 ${\rm I}_{\rm ph}\,=\,-{\rm mP}^{\alpha _{1}} + {\rm nP}^{\alpha _{2}}$ , which can reveal the internal physical mechanism of negative/positive photoconductance effects. The present 2D structure design allows the field effect transistor (FET) to exhibit excellent photoelectric performance (RNPC = 1.1× 104 AW-1, RPPC = 13 AW-1) and performance stability. Especially, the retinal pretreatment process is successfully simulated based on the negative and positive photoconductive effects. Moreover, the pulse signal input improves the device responsivity by 167%, and the transmission quality and efficiency of the visual signal can also be enhanced. This work provides a new design idea and direction for the construction of artificial vision, and lay a foundation for the integration of the next generation of optoelectronic devices.

Scaffold hopping derived novel benzoxazepinone receptor-interacting protein kinase 1 (RIP1) inhibitors as anti-necroptosis agents: Anti-inflammatory effect in systemic inflammatory response syndrome (SIRS) and epilepsy.

Necroptosis is a type of regulated cell death known for its pro-inflammatory nature due to the substantial release of cellular contents. The phosphorylation of key proteins, namely RIP1, RIP3, and mixed lineage kinase domain-like protein (MLKL), plays a pivotal role in the processes associated with necroptosis. Consequently, inhibiting the phosphorylation of any of these three key protein kinases could effectively block necroptosis. Utilizing a scaffold hopping strategy, we have successfully designed and synthesized a series of novel RIP1 inhibitors with selective and anti-necrotic properties, using compound o1 as the lead compound. In comparison to o1, SY1 has demonstrated heightened antinecroptosis activity and binding affinity in vitro studies. Moreover, SY1 has exhibited superior efficacy in both in vivo studies, specifically in the context of SIRS, and pharmacokinetic assessments. Furthermore, SY1 has proven effective in significantly suppressing the central inflammatory response induced by epilepsy.

Discovery of novel 5-phenylpyrazol receptor interacting protein 1(RIP1) kinase inhibitors as anti-necroptosis agents by combining virtual screening and in vitro and in vivo experimental evaluations.

Necroptosis is one of the modes of cell death, and its occurrence and development are associated with the development of numerous diseases. To prevent the progression of necroptosis, it is crucial to inhibit the phosphorylation of three proteins: receptor-interacting protein kinase 1 (RIP1), RIP3, and mixed lineage kinase domain-like protein (MLKL). Through virtual and experimental screening approaches, we have identified 8 small molecular inhibitors with potent antinecroptotic activity and binding affinity to RIP1. Among these compounds, SY-1 demonstrated the most remarkable antinecroptotic activity (EC50 = 105.6 ± 9.6 nM) and binding affinity (RIP1 Kd = 49 nM). It effectively blocked necroptosis and impeded the formation of necrosomes by inhibiting the phosphorylations of the RIP1/RIP3/MLKL pathway triggered by TSZ (TNFα, Smac mimetic and Z-VAD-fmk). Furthermore, SY-1 exhibited a protective effect against tumor necrosis factor (TNF)-induced hypothermia in mice and significantly improved the survival rate (100 %, 30 mg/kg) of mice with systemic inflammatory response syndrome (SIRS) in a dose-dependent manner. Pharmacokinetic parameters of SY-1 were also collected in vitro and in vivo. These results strongly suggest that SY-1 and its derivatives warrant further investigation for their potential therapeutic applications.

Infrared avalanche photodiodes from bulk to 2D materials.

Avalanche photodiodes (APDs) have drawn huge interest in recent years and have been extensively used in a range of fields including the most important one-optical communication systems due to their time responses and high sensitivities. This article shows the evolution and the recent development of AIIIBV, AIIBVI, and potential alternatives to formerly mentioned-"third wave" superlattices (SL) and two-dimensional (2D) materials infrared (IR) APDs. In the beginning, the APDs fundamental operating principle is demonstrated together with progress in architecture. It is shown that the APDs evolution has moved the device's performance towards higher bandwidths, lower noise, and higher gain-bandwidth products. The material properties to reach both high gain and low excess noise for devices operating in different wavelength ranges were also considered showing the future progress and the research direction. More attention was paid to advances in AIIIBV APDs, such as AlInAsSb, which may be used in future optical communications, type-II superlattice (T2SLs, "Ga-based" and "Ga-free"), and 2D materials-based IR APDs. The latter-atomically thin 2D materials exhibit huge potential in APDs and could be considered as an alternative material to the well-known, sophisticated, and developed AIIIBV APD technologies to include single-photon detection mode. That is related to the fact that conventional bulk materials APDs' performance is restricted by reasonably high dark currents. One approach to resolve that problem seems to be implementing low-dimensional materials and structures as the APDs' active regions. The Schottky barrier and atomic level thicknesses lead to the 2D APD dark current significant suppression. What is more, APDs can operate within visible (VIS), near-infrared (NIR)/mid-wavelength infrared range (MWIR), with a responsivity ~80 A/W, external quantum efficiency ~24.8%, gain ~105 for MWIR [wavelength, λ = 4 µm, temperature, T = 10-180 K, Black Phosphorous (BP)/InSe APD]. It is believed that the 2D APD could prove themselves to be an alternative providing a viable method for device fabrication with simultaneous high-performance-sensitivity and low excess noise.

Time-series benchmarks based on frequency features for fair comparative evaluation.

Time-series prediction and imputation receive lots of attention in academic and industrial areas. Machine learning methods have been developed for specific time-series scenarios; however, it is difficult to evaluate the effectiveness of a certain method on other new cases. In the perspective of frequency features, a comprehensive benchmark for time-series prediction is designed for fair evaluation. A prediction problem generation process, composed of the finite impulse response filter-based approach and problem setting module, is adopted to generate the NCAA2022 dataset, which includes 16 prediction problems. To reduce the computational burden, the filter parameters matrix is divided into sub-matrices. The discrete Fourier transform is introduced to analyze the frequency distribution of transformed results. In addition, a baseline experiment further reflects the benchmarking capability of NCAA2022 dataset.

Simultaneous determination of 24 antiepileptic drugs and their active metabolites in human plasma by UHPLC-MS/MS.

Antiepileptic drugs (AEDs) have narrow therapeutic ranges with large individual variability. Routine therapeutic drug monitoring of AEDs was useful for dose optimization, but the common immunoassays could not meet the detection requirements of AEDs, especially for new generation AEDs. The aim of this study was to validate an ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) method for simultaneously quantification of 24 AEDs and their active metabolites in human plasma and comparison with a chemiluminescent immunoassay (Simens ADVIA Centaur). The method validation was performed according to FDA and EMEA guidelines. A one-step protein precipitation by acetonitrile followed a five-fold dilution was performed for sample pretreatment. A 5.2 min gradient separation by methanol and 10 mM ammonium acetate was used for separation at 0.6 mL/min under 45 °C. Both positive and negative electrospray ionization were used. Isotopic internal standard was used for all analytes. The inter-day (36 days) accuracy and precision of quality control samples were - 1.07-13.69% and < 6.70% for all analytes. The stability was acceptable for all analytes under routine storing conditions. A total of 436 valproic acid, 118 carbamazepine, and 65 phenobarbital samples were determined twice by each of the UHPLC-MS/MS and immunoassay. Evaluated by Bland-Altman plot, the mean overestimation of the immunoassay compared to UHPLC-MS/MS was 16.5% for valproic acid, 5.6% for carbamazepine, and 40.3% for phenobarbital.

Mitochondria associated ER membranes and cerebral ischemia: Molecular mechanisms and therapeutic strategies.

Endoplasmic reticulum (ER) and mitochondria are two important organelles that are highly dynamic in mammalian cells. The physical connection between them is mitochondria associated ER membranes (MAM). In recent years, studies on endoplasmic reticulum and mitochondria have shifted from independent division to association and comparison, especially MAM has gradually become a research hotspot. MAM connects the two organelles, not only to maintain their independent structure and function, but also to promote metabolism and signal transduction between them. This paper reviews the morphological structure and protein localization of MAM, and briefly analyzes the functions of MAM in regulating Ca2+ transport, lipid synthesis, mitochondrial fusion and fission, endoplasmic reticulum stress and oxidative stress, autophagy and inflammation. Since ER stress and mitochondrial dysfunction are important pathological events in neurological diseases including ischemic stroke, MAM is likely to play an important role in cerebral ischemia by regulating the signaling of the two organelles and the crosstalk of the two pathological events.

Trends in metabolic signaling pathways of tumor drug resistance: A scientometric analysis.

Background: Cancer chemotherapy resistance is one of the most critical obstacles in cancer therapy. Since Warburg O first observed alterations in cancer metabolism in the 1950s, people gradually found tumor metabolism pathways play a fundamental role in regulating the response to chemotherapeutic drugs, and the attempts of targeting tumor energetics have shown promising preclinical outcomes in recent years. This study aimed to summarize the knowledge structure and identify emerging trends and potential hotspots in metabolic signaling pathways of tumor drug resistance research. Methods: Publications related to metabolic signaling pathways of tumor drug resistance published from 1992 to 2022 were retrieved from the Web of Science Core Collection database. The document type was set to articles or reviews with language restriction to English. Two different scientometric software including Citespace and VOS viewer were used to conduct this scientometric analysis. Results: A total of 2,537 publications including 1,704 articles and 833 reviews were retrieved in the final analysis. The USA made the most contributions to this field. The leading institution was the University of Texas MD Anderson Cancer Center. Avan A was the most productive author, and Hanahan D was the key researcher with the most co-citations, but there is no leader in this field yet. Cancers was the most influential academic journal, and Oncology was the most popular research field. Based on keywords occurrence analysis, these selected keywords could be roughly divided into five main topics: cluster 1 (study of cancer cell apoptosis pathway); cluster 2 (study of resistance mechanisms of different cancer types); cluster 3 (study of cancer stem cells); cluster 4 (study of tumor oxidative stress and inflammation signaling pathways); and cluster 5 (study of autophagy). The keywords burst detection identified several keywords as new research hotspots, including "tumor microenvironment," "invasion," and "target". Conclusion: Tumor metabolic reprogramming of drug resistance research is advancing rapidly. This study serves as a starting point, providing a thorough overview, the development landscape, and future opportunities in this field.

Leucovorin (folinic acid) rescue for high-dose methotrexate: A review.

High-dose methotrexate (HDMTX) is active against various malignancies; it possesses serious toxicities and is associated with patient characteristics, dosage regimens, comedications, and physiological status. There are many strategies to overcome HDMTX-induced toxicities, such as hydration, alkalization, leucovorin rescue, and haemodialysis. Leucovorin rescue is a cornerstone for toxicity prevention in HDMTX treatment. However, the leucovorin dose adjustment and the existence of leucovorin overrescue are still controversial. At present, various methods for calculating leucovorin doses in different tumour types have been proposed, including empirical calculations based on MTX plasma concentration, the Bleyer nomogram, and other methods. Nonetheless, leucovorin rescue protocols differ greatly across tumour types and medical institutions. Further studies are needed to investigate the optimal dosage regimen for leucovorin rescue in various tumours using HDMTX.

Emerging applications of nano-optical sensors combined with near-infrared spectroscopy for detecting tea extract fermentation aroma under ultrasound-assisted sonication.

The current innovative work combines nano-optical sensors with near-infrared spectroscopy for rapid detection and quantification of polyphenols and investigates the potential of the nano-optical sensor based on chemo-selective colorants to detect the dynamic changes in aroma components during the fermentation of tea extract. The procedure examined the influence of different ultrasound-assisted sonication factors on the changes in the consumption rate of polyphenols during the fermentation of tea extract versus non-sonication as a control group. The results showed that the polyphenol consumption rate improved under the ultrasound conditions of 28 kHz ultrasound frequency, 24 min treatment time, and 40 W/L ultrasonic power density. The metal-organic framework based nano-optical sensors reported here have more adsorption sites for enhanced adsorption of the volatile organic compounds. The polystyrene-acrylic microstructure offered specific surface area for the reactants. Besides, the employed porous silica nanospheres with higher porosity administered improved gas enrichment effect. The nano-optical sensor exhibits good performance with a "chromatogram" for the identification of aroma components in the fermentation process of tea extract. The proposed method respectively enhanced the consumption rate of polyphenol by 35.57%, 11.34% and 16.09% under the optimized conditions. Based on the established polyphenol quantitative prediction models, this work demonstrated the feasibility of using a nano-optical sensor to perform in-situ imaging of the fermentation degree of tea extracts subjected to ultrasonic treatment.

Determination of levodopa by chromatography-based methods in biological samples: a review.

Levodopa (L-DOPA) is the most effective drug for Parkinson's disease; however, various side effects occur during therapy. L-DOPA metabolites and the high cumulative dose of L-DOPA were responsible for its side effects. It is necessary to monitor the concentration of L-DOPA and its metabolites for individualized therapy. This review focuses on L-DOPA analysis by chromatography-based methods in biological matrices. Literature published up to September 2021 was collected in the PubMed, Web of Science, and Embase by using search strategy ("levodopa" OR "L-DOPA") AND ("chromatography"). A total of 1249 articles were identified and 32 articles were included. The contents for method development and validation were summarized and analyzed. Due to the instability of catecholamines (L-DOPA, dopamine, and 3-O-methyldopa) and carbidopa, antioxidation (0.5 mg sodium metabisulfite for 100 µL sample) and environment temperature control were used alone or in combination to enhance stability. Sample was mainly pretreated by protein precipitation (0.4-0.7 M perchloric acid). Separation was usually achieved using methanol or acetonitrile:water (with formic acid) on C18 columns. Mass spectrometry, electrochemical detector, ultraviolet-visible detector and fluorescence detector were used for detection. For L-DOPA, the calibration range was 2.5-10,000 ng/mL, the matrix effect and its coefficient of variation was 85-115 and -9.0-8.5%, and the recovery was 66.8-127.0%. Without stabilization strategy, L-DOPA was stable in plasma at room temperature for 1-7 h (4-6 h for most studies), at - 70 °C to - 80 °C for 10-20 days and after 3-5 freeze-thaw cycles. With stabilization strategies, the stability of L-DOPA in plasma was significantly improved. Metabolites of L-DOPA and enzyme inhibitors (carbidopa, entacapone, tolcapone and benserazide) were all stable in biological matrix. This study might be useful for researchers to develop their methods for individualized therapy of patients with Parkinson.

Nasal metastases from neuroblastoma-a rare entity: Two case reports.

BACKGROUND: Neuroblastoma (NB) is one of the most common malignancies in children. Metastasis in NB is not uncommon. However, nasal metastases are rare. Here, we reported two pediatric cases of nasal metastases. CASE SUMMARY: Case 1 was a 3-year-old boy without a history of NB. Case 2 was a 10-year-old girl who had a history of NB for 6 years. Both of them presented with symptoms of nasal and sinus masses such as epistaxis or discharge from the nose. The radiologic imaging results revealed masses in the nasal cavity or nasopharynx in both cases and a mass in the right adrenal gland of case 1. The pathologic examination of biopsy samples of their nasal masses revealed "small round blue-cell tumor" along with abundant vascular fibrous septa. The tumor cells expressed synaptophysin, cluster of differentiation 56, chromogranin A, paired like homeobox protein 2B and a very high Ki67 index in both case but were negative for vimentin, desmin, leucocyte common antigen and cytokeratin. Myelocytomatosis viral related oncogene, neuroblastoma derived (MYCN) amplification was detected in both cases. Finally, the two cases were diagnosed as nasal metastases from NB based on the clinical and pathologic findings. The two patients affected by NB were > 18 mo old, the primary tumor location was adrenal gland, and they presented with multiple metastases. CONCLUSION: It is difficult to differentiate between metastatic NB in the nose and olfactory neuroblastoma in the absence of a history of NB. Paired like homeobox protein 2B can play an important role in the diagnosis and differential diagnosis of this disease.

A Novel NAC Transcription Factor From Eucalyptus, EgNAC141, Positively Regulates Lignin Biosynthesis and Increases Lignin Deposition.

Wood formation is a complicated process under the control of a large set of transcription factors. NAC transcription factors are considered "master switches" in this process. However, few NAC members have been cloned and characterized in Eucalyptus, which is one of the most economically important woody plants. Here, we reported an NAC transcription factor from Eucalyptus grandis, EgNAC141, which has no Arabidopsis orthologs associated with xylogenesis-related processes. EgNAC141 was predominantly expressed in lignin-rich tissues, such as the stem and xylem. Overexpression of EgNAC141 in Arabidopsis resulted in stronger lignification, larger xylem, and higher lignin content. The expression of lignin biosynthetic genes in transgenic plants was significantly higher compared with wild-type plants. The transient expression of EgNAC141 activated the expression of Arabidopsis lignin biosynthetic genes in a dual-luciferase assay. Overall, these results showed that EgNAC141 is a positive regulator of lignin biosynthesis and may help us understand the regulatory mechanism of wood formation.

Tuning the NIR photoabsorption of CuWO4-x nanodots with oxygen vacancies for CT imaging guided photothermal therapy of tumors.

A traditional CuWO4 semiconductor (Eg = 2.25 eV) shows photoabsorption in the visible range with an edge at ∼550 nm, limiting its application in near-infrared (NIR) laser-induced photothermal ablation therapy (PAT). To tune the NIR photoabsorption of CuWO4, we report a trisodium citrate-induced strategy for generating oxygen vacancies. CuWO4 and CuWO4-x nanoparticles are prepared by a facile coprecipitation-solvothermal method in the absence or presence of trisodium citrate (0.2-0.5 g) as the reducing agent. Without trisodium citrate, CuWO4 consists of aggregated particles, and its dispersion has a typical yellow-green color without NIR photoabsorption. With the addition of trisodium citrate from 0.2 to 0.5 g, CuWO4-x samples are composed of monodisperse nanodots with increased sizes from ∼2 to ∼6 nm, and the color of these dispersions becomes darker with increased NIR photoabsorption, that is, from 0.178 to 0.685 at 808 nm. As a result, the aqueous dispersion of CuWO4-x-0.5 nanodots prepared with 0.5 g trisodium citrate exhibits a high photothermal efficiency of 47.6% under 808 nm laser irradiation. Simultaneously, CuWO4-x-0.5 nanodots have high X-ray attenuation as a CT imaging agent due to the presence of a heavy metal element (W). When the CuWO4-x-0.5 dispersion is injected into the tumors of mice, the tumors can be observed by CT and thermal imaging. After 808 nm laser irradiation (1.0 W cm-2, 10 min), cancer cells in vivo can be efficiently ablated by the photothermal effects of CuWO4-x, without obvious toxicity and side effects. Therefore, CuWO4-x can act as a novel all-in-one agent for CT imaging-guided photothermal therapy of tumors.

Chitosan-mediated green synthesis and folic-acid modification of CuS quantum dots for photoacoustic imaging guided photothermal therapy of tumor.

CuS nanomaterials capped with artificial organic-molecules or polymers have been well demonstrated as efficient photothermal nanoagents for the therapy of tumor, but their biocompatibility and target ability should be improved. To address these problems, we have used chitosan (CS) as the biomacromolecule model and surface ligands to prepare CuS quantum dots (QDs) via a simple co-precipitation method. CuS-CS QDs are then conjugated with folic acid (FA). The resulting CuS-CS-FA QDs are composed of hexagonal phase nanodots with sizes of about 4 nm. FA modification process has no apparent influence on the size, phase and composition of the QDs. Furthermore, the zeta potential and infrared spectroscopy confirm the efficient conjugation of FA. CuS-CS-FA QDs exhibit strong near-infrared photoabsorption and high photothermal efficiency (47.0%). As a result of the presence of CS ligand and FA modification, CuS-CS-FA QDs have good biocompatibility and relatively high cellular uptake efficacy. When CuS-CS-FA QD dispersion is injected intravenously into the tumor-bearing mice, the photoacoustic imaging reveals that CuS-CS-FA QD can be efficiently targeted and accumulated in the tumor and reach the peak dose at 60 min. The irradiation of 1064-nm laser (1.0 W cm-2, 10 min) results in the efficient inhibition of tumor growth, without treatment-induced toxicity. Therefore, CuS-CS-FA QDs have great potential to become biocompatible multifunctional nanoagents for imaging guided therapy of tumor.

Integrated assessment of PD-L1 expression and molecular classification facilitates therapy selection and prognosis prediction in gastric cancer.

PURPOSE: Targeting the PD-1/PD-L1 pathway has emerged as a novel therapy for cancer. To identify rational candidates for anti-PD-1/PD-L1 immunotherapy in gastric cancer (GC), the abundance of PD-L1 expression was evaluated on a kind of biomarker-based molecular classification for shaping prognosis and treatment planning. METHODS: One hundred and sixty-five GCs were classified into five subgroups using immunohistochemistry (IHC) and in situ hybridization (ISH) methods, based on a panel of seven markers (MLH1, PMS2, MSH2, MSH6, E-cadherin, P53, and Epstein-Barr virus mRNA). The expression of PD-L1 in GC tissues was analyzed immunohistochemically. RESULTS: The five categories (Epstein-Barr virus positivity, microsatellite instability, aberrant E-cadherin, aberrant P53 expression, and normal P53 expression) correspond to the reported molecular subgroups for similar proportions and clinicopathologic characteristics. Survival analysis indicated that subgroups with aberrant E-cadherin expression independently predicted a worse prognosis in GC patients (HR=2.51, P=0.010). The clinical and prognostic profiles produced by this stratification in nonintestinal-type GC were distinguishable from those in intestinal-type. Although PD-L1 was not a significant prognostic factor, that more frequent presence of PD-L1-positive in microsatellite instability tumors than other subtypes (P<0.010) hinted at a prolonged clinical course. Moreover, the lowest level of PD-L1 but the highest of Her2 was observed in the group of aberrant P53, namely it was suggested that there was a negative correlation between PD-L1 and Her2 overexpression. CONCLUSION: Different molecular subtypes in GC may have a tendency to react differently to anti-PD-L1/PD-1 immunotherapy or anti-Her2 therapy. A combination of PD-L1 expression and this cost-effective classification strategy would be helpful for predicting prognosis and promoting personalized therapy in clinical practice.

Downregulation of miRNA-214 in cancer-associated fibroblasts contributes to migration and invasion of gastric cancer cells through targeting FGF9 and inducing EMT.

BACKGROUND: Cancer-associated fibroblasts (CAFs), one of the principal constituents of the tumor microenvironment, have a pivotal role in tumor progression. Dysregulation of microRNAs (miRNAs) in CAFs contributes to the tumor-promoting ability of CAFs. However, the mechanism underlying the involvement of miRNAs in CAFs of gastric cancer (GC) is not fully understood. This study aimed to explore the effects of miRNA-214 in CAFs on GC migration and invasion. METHODS: The primary CAFs and corresponding normal fibroblasts (NFs) were isolated. Cell counting kit-8, EdU cell proliferation staining and Transwell assays were used to determine the role of miRNA-214 in GC progression. Real-time polymerase chain reaction, Western blot analysis, and dual-luciferase reporter assay were performed to verify the target genes of miRNA-214. Immunofluorescence and Western blot analysis were applied to detect the expression of epithelial-mesenchymal transition (EMT) markers. Immunohistochemistry and in situ hybridization were implemented to analyze the fibroblast growth factor 9 (FGF9) and miRNA-214 expression in human GC tissues, respectively. Finally, to assess its prognostic relevance, Kaplan-Meier survival analysis was conducted. RESULTS: MiRNA-214 was significantly downregulated in CAFs of GC compared with NFs. The upregulation of miRNA-214 in CAFs inhibited GC cell migration and invasion in vitro but failed to affect proliferation. Moreover, GC cells cultured with conditioned medium from CAFs transfected with miR-214 mimic showed increased expression of E-cadherin and decreased expression of Vimentin, N-cadherin and Snail, indicating the suppression of EMT of GC cells. Furthermore, FGF9 was proved to be a direct target gene of miR-214. The expression of FGF9 was higher in CAFs than that in tumor cells not only in primary tumor but also in lymph node metastatic sites (30.0% vs 11.9%, P < 0.01 and 32.1% vs 12.3%, P < 0.01, respectively). Abnormal expression of FGF9 in CAFs of lymph node metastatic sites was significantly associated with poor prognosis in patients with GC (P < 0.05). CONCLUSIONS: This study showed that miR-214 inhibited the tumor-promoting effect of CAFs on GC through targeting FGF9 in CAFs and regulating the EMT process in GC cells, suggesting miRNA-214/FGF9 in CAFs as a potential target for therapeutic approaches in GC.

Application of the in vivo Pig-a gene mutation assay to test the potential genotoxicity of p-phenylenediamine.

Currently, it remains controversial whether p-phenylenediamine (PPD) is genotoxic. In this study, we evaluated the potential genotoxicity of PPD using the newly-developed Pig-a gene mutation assay. The results of three classical genetic toxicity tests (bacterial reverse mutation assay, mammalian cell chromosomal aberration test, and mammalian erythrocyte micronucleus test) are all positive, suggesting that PPD is potentially genotoxic. In Pig-a assay, Sprague-Dawley rats are orally administered with PPD for 28 consecutive days at three doses (12.5, 25, and 50 mg/kg/day). Our result shows that PPD (25 and 50 mg/kg/day) dose-dependently increases RETCD59- value over controls on Day 8. RETCD59- keeps increasing to the maximum on Day 15 and then decreases until Day 29. PPD also dose-dependently increase RBCCD59- value on Day 15, which keeps elevating until Day 29. The time-course of RETCD59- and RBCCD59- induced by PPD are similar with that induced by N-ethyl-N-nitrosourea (ENU) treatment for 3 days. Our data suggests that PPD has potential genotoxic effects, and the Pig-a assay is sensitive to assess mutagenicity. However, further investigation of the changes of RETCD59- and RBCCD59- induced by hair dyes containing PPD should be detected by Pig-a assay in occupational exposure population to confirm the safety of PPD usage.

Programming a crystalline shape memory polymer network with thermo- and photo-reversible bonds toward a single-component soft robot.

The need to support the two most basic functions [three-dimensional (3D)-shaped support and actuation] independently for a typical robot demands that at least two components should be used in its construction. Therefore, component assembly is unavoidable despite the ultimate dream of creating assembly-free robots. We devise a strategy that uses a programmable crystalline shape memory polymer with thermo- and photo-reversible bonds to create a single-component robot. The global 3D-shaped structural support is fabricated via a plasticity-based origami technique enabled by the thermo-reversible bonds. More critically, precisely controlled localized actuation can be programmed into the 3D origami via spatially defined reversible shape memory using the photo-reversible bonds. The overall result is that a polymer thin film can be programmed into various soft robots including a 3D crane and an elephant. Besides reversible shape memory, other types of actuation mechanisms can be potentially introduced via a similar principle. Thus, our strategy represents a general method to create single-component soft robots.

Effects of soil water and heat relationship under various snow cover during freezing-thawing periods in Songnen Plain, China.

In this study, the spatial variations of soil water and heat under bare land (BL), natural snow (NS), compacted snow (CS) and thick snow (TS) treatments were analyzed. The relationship curve between soil temperature and water content conforms to the exponential filtering model, by means of the functional form of the model, it was defined as soil water and heat relation function model. On this basis, soil water and heat function models of 10, 20, 40, 60, 100, and 140 cm were established. Finally, a spatial variation law of the relationship effect was described based on analysising of the differences between the predicted and measured results. During freezing period, the effects of external factors on soil were hindered by snow cover. As the snow increased, the accuracy of the function model gradually improved. During melting period, infiltration by snowmelt affected the relationship between the soil temperature and moisture. With the increasing of snow, the accuracy of the function models gradually decreased. The relationship effects of soil water and heat increased with increasing depth within the frozen zone. In contrast, below the frozen layer, the relationship of soil water and heat was weaker, and the function models were less accurate.