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The accumulation of amyloid beta (Aβ1–42) results in neurotoxicity and is strongly related to neurodegenerative disorders, especially Alzheimer's disease (AD), but the underlying molecular mechanism is still poorly understood. Therefore, there is an urgent need for researchers to discover the proteins that interact with Aβ1–42 to determine the molecular basis. Previously, we developed peptide-ligand-induced changes in the abundance of proTeinS (PACTS)-assisted thermal proteome profiling (TPP) to identify proteins that interact with peptide ligands. In the present study, we applied this technique to analyze clinical samples to identify Aβ1–42-interacting proteins. We detected 115 proteins that interact with Aβ1–42 in human frontal lobe tissue. Pathway enrichment analysis revealed that the differentially expressed proteins were involved mainly in neurodegenerative diseases. Further orthogonal validation revealed that Aβ1–42 interacted with the AD-associated protein mitogen-activated protein kinase 3 (MAPK3), and knockdown of the Aβ1–42 amyloid precursor protein (APP) inhibited the MAPK signaling pathway, suggesting potential functional roles for Aβ1–42 in interacting with MAPK3. Overall, this study demonstrated the application of the PACTS-TPP in clinical samples and provided a valuable data source for research on neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Background: Mutational inactivation of the SETDB1 histone methyltransferase is found in a subset of mesothelioma, particularly in cases with near-haploidy and TP53 mutations. However, the tumourigenic consequences of SETDB1 inactivation are poorly understood. Methods: In this study, we investigated SETDB1 tumour suppressor functions in mesothelioma and explored biologic relationships between SETDB1 and TP53. Results: Immunoblotting of early passage cultures showed that SETDB1 was undetectable in 7 of 8 near-haploid mesotheliomas whereas SETDB1 expression was retained in each of 13 near-diploid mesotheliomas. TP53 aberrations were present in 5 of 8 near-haploid mesotheliomas compared to 2 of 13 near-diploid mesotheliomas, and BAP1 inactivation was demonstrated only in near-diploid mesotheliomas, indicating that near-haploid and near-diploid mesothelioma have distinct molecular and biologic profiles. Lentiviral SETDB1 restoration in near-haploid mesotheliomas (MESO257 and MESO542) reduced cell viability, colony formation, reactive oxygen species levels, proliferative marker cyclin A expression, and inhibited growth of MESO542 xenografts. The combination of SETDB1 restoration with pemetrexed and/or cisplatin treatment additively inhibited tumour growth in vitro and in vivo. Furthermore, SETDB1 restoration upregulated TP53 expression in MESO542 and MESO257, whereas SETDB1 knockdown inhibited mutant TP53 expression in JMN1B near-haploid mesothelioma cells. Likewise, TP53 knockdown inhibited SETDB1 expression. Similarly, immunoblotting evaluations of ten near-diploid mesothelioma biopsies and analysis of TCGA expression profiles showed that SETDB1 expression levels paralleled TP53 expression. Conclusion: These findings demonstrate that SETDB1 inactivation in near-haploid mesothelioma is generally associated with complete loss of SETDB1 protein expression and dysregulates TP53 expression. Targeting SETDB1 pathways could be an effective therapeutic strategy in these often untreatable tumours. [ABSTRACT FROM AUTHOR]

The histone methyltransferase Smyd1 is essential for muscle development; however, its role in smoking-induced skeletal muscle atrophy and dysfunction has not been investigated thus far. In this study, Smyd1 was overexpressed or knocked down in C2C12 myoblasts by an adenovirus vector and cultured in differentiation medium containing 5% cigarette smoke extract (CSE) for 4 days. CSE exposure resulted in inhibition of C2C12 cell differentiation and downregulation of Smyd1 expression, whereas Smyd1 overexpression reduced the degree of inhibition of myotube differentiation caused by CSE exposure. CSE exposure activated P2RX7-mediated apoptosis and pyroptosis, caused increased intracellular reactive oxygen species (ROS) levels, and impaired mitochondrial biogenesis and increased protein degradation by downregulating PGC1α, whereas Smyd1 overexpression partially restored the altered protein levels caused by CSE exposure. Smyd1 knockdown alone produced a phenotype similar to CSE exposure, and Smyd1 knockdown during CSE exposure aggravated the degree of inhibition of myotube differentiation and the degree of activation of P2RX7. CSE exposure suppressed H3K4me2 expression, and chromatin immunoprecipitation confirmed the transcriptional regulation of P2rx7 by H3K4me2 modification. Our findings suggest that CSE exposure mediates C2C12 cell apoptosis and pyroptosis through the Smyd1-H3K4me2-P2RX7 axis, and inhibits PGC1α expression to impair mitochondrial biosynthesis and increase protein degradation by inhibiting Smyd1 expression, ultimately leading to abnormal C2C12 myoblasts differentiation and impaired myotube formation. [Display omitted] • Smyd1 is involved in CSE-induced inhibition of myoblast differentiation. • CSE exposure inhibited H3K4me2 expression and activates P2RX7-mediated death • CHIP confirmed the transcriptional regulation of P2rx7 by H3K4me2 modification. • CSE inhibited myoblast differentiation through Smyd1-H3K4me2-P2RX7 axis. • Smyd1 regulated mitochondrial biosynthesis and protein degradation through PGC1α. [ABSTRACT FROM AUTHOR]

A split G-quadruplex (G4)-programmed Cas12a platform was established, validated, and optimized. The split G4 motif was recruited as substrate for Cas12a, and the label-free sensing platform provided a concentration-dependent response towards the input target. Furthermore, exosomal surface proteins from cultured cancer cells and clinical samples were detected and profiled. [ABSTRACT FROM AUTHOR]

Bacterial surface contamination can lead to the formation of biofilms, infection by pathogens and damage the surface of materials, which can seriously endanger health and even life. However, single-system antibacterial waterborne polyurethane (WPU) cannot meet its application in the field of high antibacterial activity. Therefore, in this study, WPU was synergistically modified by lysine (Lys) and quaternary ammonium salts (QAS), and they were introduced into the WPU molecular framework by chemical bonding to form a composite system, named WKPU. The results showed that WKPU had excellent antibacterial activity against both E. coli and S. aureus compared to a single system (Lys or QAS). When the contents of both Lys and QAS were 7%, the antibacterial activity of WKPU7 was optimal, from the sum (E. coli: 8.4 mm + 8.3 mm = 16.7 mm and S. aureus: 9.7 mm + 9.5 mm = 19.2 mm) of the inhibition circles of Lys and QAS to 19.2 mm and 20.0 mm, respectively, demonstrating the net efficiency increase of 15% and 4.2%, which fully reflects the effect of "1 + 1 > 2". This highlights their great potential as antibacterial materials that could be used in highly antibacterial fields, such as medical apparatus and food packaging. [ABSTRACT FROM AUTHOR]

Deep neural networks are discovered to be non-robust when attacked by imperceptible adversarial examples, which is dangerous for it applied into medical diagnostic system that requires high reliability. However, the defense methods that have good effect in natural images may not be suitable for medical diagnostic tasks. The pre-processing methods (e.g., random resizing, compression) may lead to the loss of the small lesions feature in the medical image. Retraining the network on the augmented data set is also not practical for medical models that have already been deployed online. Accordingly, it is necessary to design an easy-to-deploy and effective defense framework for medical diagnostic tasks. In this paper, we propose a Robust and Retrain-Less Diagnostic Framework for Medical pretrained models against adversarial attack (i.e., MedRDF). It acts on the inference time of the pretrained medical model. Specifically, for each test image, MedRDF firstly creates a large number of noisy copies of it, and obtains the output labels of these copies from the pretrained medical diagnostic model. Then, based on the labels of these copies, MedRDF outputs the final robust diagnostic result by majority voting. In addition to the diagnostic result, MedRDF produces the Robust Metric (RM) as the confidence of the result. Therefore, it is convenient and reliable to utilize MedRDF to convert pretrained non-robust diagnostic models into robust ones. The experimental results on COVID-19 and DermaMNIST datasets verify the effectiveness of our MedRDF in improving the robustness of medical diagnostic models. [ABSTRACT FROM AUTHOR]

Eurycomanone (EN) is one of the representative quassinoid diterpenoids from roots of Eurycoma longifolia Jack, a natural medicine that is widely distributed in Southeast Asia. Previous studies showed that EN induces cancer cell apoptosis and exhibits anti-cancer activity, but the molecular mechanism of EN against cancer has still not been elucidated. In this study, we examined the regulatory effect of EN on autophagy to reveal the mechanism of EN-mediated colon cancer growth inhibition. First, we found that EN is able to inhibit colon cancer cell proliferation and colony formation. The angiogenesis level in cancer cells was inhibited as well. Next, the treatment of EN led to the suppression of autophagy, which was characterized by the downregulation of the LC3-II level and the formation of GFP-LC3 puncta under EN treatment in colon cancer. Moreover, we revealed that the mTOR signaling pathway was activated by EN in a time- and concentration-dependent manner. Finally, autophagy induction protected colon cancer cells from EN treatment, suggesting that autophagy improves cell survival. Taken together, our findings revealed the mechanism of EN against colon cancer through inhibiting autophagy and angiogenesis in colon cancer, supporting that the autophagy inhibitor EN could be developed to be a novel anti-cancer agent. [ABSTRACT FROM AUTHOR]

Objectives To compare the exposure data generated by using the Canadian job-exposure matrix (CANJEM) with data generated by expert assessment, for jobs held by women. Methods We selected 69 occupational agents that had been assessed by experts for each of 3403 jobs held by 998 women in a population-based case–control study of lung cancer. We then assessed the same agents among the same jobs by linking their occupation codes to CANJEM and thereby derived probability of exposure to each of the agents in each job. To create binary exposure variables, we dichotomized probability of exposure using two cutpoints: 25 and 50% (referred to as CANJEM-25% and CANJEM-50%). Using jobs as units of observation, we estimated the prevalence of exposure to each selected agent using CANJEM-25% and CANJEM-50%, and using expert assessment. Further, using expert assessment as the gold standard, for each agent, we estimated CANJEM's sensitivity, specificity, and kappa. Results CANJEM-based prevalence estimates correlated well with the prevalences assessed by the experts. When comparing CANJEM-based exposure estimates with expert-based exposure estimates, sensitivity, specificity, and kappa varied greatly among agents, and between CANJEM-25% and CANJEM-50% probability of exposure. With CANJEM-25%, the median sensitivity, specificity, and kappa values were 0.49, 0.99, and 0.46, respectively. Analogously, with CANJEM-50%, the corresponding values were 0.26, 1.00, and 0.35, respectively. For the following agents, we observed high concordance between CANJEM- and expert-based assessments (sensitivity ≥0.70 and specificity ≥0.99): fabric dust, cotton dust, synthetic fibres, cooking fumes, soldering fumes, calcium carbonate, and tin compounds. We present concordance estimates for each of 69 agents. Conclusions Concordance between CANJEM and expert assessment varied greatly by agents. Our results indicate which agents provide data that mimic best those obtained with expert assessment. [ABSTRACT FROM AUTHOR]

Complementary Labels Learning (CLL) arises in many real-world tasks such as private questions classification and online learning, which aims to alleviate the annotation cost compared with standard supervised learning. Unfortunately, most previous CLL algorithms were in a stable environment rather than an open and dynamic scenarios, where data collected from unseen augmented classes in the training process might emerge in the testing phase. In this paper, we propose a novel problem setting called Complementary Labels Learning with Augmented Classes (CLLAC), which brings the challenge that classifiers trained by complementary labels should not only be able to classify the instances from observed classes accurately, but also recognize the instance from the Augmented Classes in the testing phase. Specifically, by using unlabeled data, we propose an unbiased estimator of classification risk for CLLAC, which is guaranteed to be provably consistent. Moreover, we provide generalization error bound for proposed method which shows that the optimal parametric convergence rate is achieved for estimation error. Finally, the experimental results on several benchmark datasets verify the effectiveness of the proposed method. [ABSTRACT FROM AUTHOR]

To enlarge the linear detection range without sacrificing the sensitivity is one of the urgent problems in the development of high-performance piezoresistive flexible sensors. Inspired by a multilayer corrugated board, this study develops a new multilayer microspherical sensor in which conductive core-shell SiO 2 /Polyaniline (PANI) (PS) microspheres serve as active particles, while insulated silk fibroin (SF)/poly lactic- co -glycolic acid (PLGA) (SP) fibers are used as the support. The size of conductive microspheres attached to the insulated layer is controllable. The multiple layers of assembly endow the flexible sensor with a high sensitivity (0.071 kPa−1) and a wide linear detection (from 10 Pa to 380 kPa) simultaneously. This corrugated sensor also have a fast response time (145 ms) and an excellent durability (over 2000 cycles), and it can be used to detect human joint pressure signals and transmit encrypted information. Moreover, flexible keyboard, safety protection of machinery, as well as object position tracking can be achieved based on this sensor. Most importantly, the sensor encapsulated by biological polysaccharide kappa-carrageenan (KC) is skin-friendly and breathable, and it can be decomposed in 90 °C hot water. In conclusion, this multilayer microspherical sensor presents great potential for flexible wearable devices. We get inspiration from the multi-layer structure of corrugated board and prepare a multilayer microspherical sensor. This degradable and breathable sensor can improve the linear detection range without sacrificing the sensitivity. [Display omitted] [ABSTRACT FROM AUTHOR]

• Three hydrogen sulfide (H 2 S) production enzymes including CSE, CBS and 3-MST exist in the skin. • H 2 S regulates burn, diabetic skin wound, psoriasis, systemic sclerosis, melanoma, and pruritus. • H 2 S regulates oxidative stress, inflammation, angiogenesis and apoptosis in skin diseases. • Some ideal characteristics of H 2 S-based therapeutics for topical delivery are preferred. • Therapeutic potential of H 2 S for skin disorders will be further proposed in clinical trials. Hydrogen sulfide (H 2 S) is now recognized as a vital endogenous gasotransmitter with a variety of biological functions in different systems. Recently, studies have increasingly focused on the role of H 2 S in the skin. This review summarizes recent progress and provides perspectives on H 2 S in the treatment of dermatological diseases. Three H 2 S production enzymes, cystathionine-γ-lyase (CSE), cystathionine-β-synthase (CBS) and 3-mercaptopyruvate sulfur transferase (3-MST), are all present in the skin, and it is likely that different cell types in the skin express them differently. Previous studies have demonstrated that H 2 S protects against several dermatological diseases, such as burns, diabetic skin wounds, psoriasis, skin flap transplantation, systemic sclerosis, melanoma, and pruritus. The mechanism might be related to the regulation of oxidative stress, inflammation, angiogenesis, apoptosis, and allergic reactions. H 2 S-based therapeutics require certain characteristics for topical delivery, for example, controlled release, appropriate physicochemical properties, good storage stability, acceptable odor, and advanced delivery systems. H 2 S-induced S-sulfhydration on proteins are potential novel targets for therapeutic intervention and drug design for the skin, which may lead to the development and application of H 2 S-related drugs for dermatological diseases. [ABSTRACT FROM AUTHOR]

Convergent evidence links traditional brominated flame retardants (BFRs) exposure to weight gain, while the obesogenic potency of new BFRs (NBFRs) remain largely unknown. Aiding by luciferase-reporter gene assay, the present study revealed only pentabromoethylbenzene (PBEB), an alternative for penta-BDEs, binds with retinoid X receptor α (RXRα) but not peroxisome proliferator receptor γ (PPARγ) among the seven testing NBFRs. An apparent induction of adipogenesis in 3T3-L1 cells was observed at nanomolar of PBEB, much lower than penta-BFRs. Mechanistic research uncovered PBEB initiated the adipogenesis by demethylated CpG sites in the PPARγ promoter region. Specifically, activation RXRα by PBEB strengthened the activity of RXRα/PPARγ heterodimer, tightened the interaction between the heterodimer and PPAR response elements, and further enhanced adipogenesis. RNA sequencing combined with k -means clustering analysis exposed adenosine 5′-monophosphate (AMP)-activated protein kinase and phosphoinositide-3-kinase (PI3K)/protein kinase B (AKT) signaling as two predominant pathways that enriched in PBEB-induced lipogenesis. The obesogenic outcome was further corroborated in offspring mice when the maternal mice exposed to environmental relevant doses of PBEB. We found the male offspring exhibited adipocyte hypertrophy and increased weight gain in the epididymal white adipose tissue (eWAT). Consistent with in vitro findings, the reduction in protein phosphorylation of both AMPK and PI3K/AKT were observed within eWAT. Thus, we posited PBEB disrupts the pathways controlling adipogenesis and adipose tissue maintenance, supporting its potential as an environmental obesogen. [ABSTRACT FROM AUTHOR]

Hydrogen sulphide (H2S) is an important gasotransmitter with several physiological functions. However, the roles and the detailed mechanisms of H2S on skin wound healing are not known well. In the present study, 129S1/SvImJ mice were intraperitoneally injected with NaHS (50 μmol/kg/d) for 2 weeks. Then, a round wound of 6 mm diameter with depth into the dermis was made. The skin wound area, blood perfusion, superoxide production, malondialdehyde (MDA) levels, total antioxidant capacity (T‐AOC), expression of vascular endothelial growth factor (VEGF), dynamin‐related protein 1 (DRP1) and optic atrophy 1 (OPA1) were measured. After NaHS (50 μmol/L) pre‐administration for 4 hours, cell migration rate, DRP1, OPA1 and α–smooth muscle actin (α‐SMA) expression, superoxide production and mitochondrial membrane potential in primary skin fibroblasts were measured. Tube formation in human umbilical vein endothelial cells (HUVECs) and cell migration in human keratinocytes were also measured. The results showed that NaHS pretreatment significantly accelerated wound healing and improved blood flow in the wound after operation. NaHS increased VEGF expression in the wound and promoted tube formation in HUVECs. Meanwhile, NaHS attenuated reactive oxygen species (ROS) production, suppressed MDA level but restored T‐AOC in the wound. NaHS also promoted skin fibroblasts migration and α‐SMA expression after scratch. Moreover, NaHS alleviated ROS, increased mitochondrial membrane potential, decreased DRP1 but enhanced OPA1 expression in skin fibroblasts after scratch. NaHS also accelerated human keratinocytes migration after scratch. Taken together, exogenous H2S supplementary accelerated the skin wound healing, which might be related to oxidative stress inhibition and VEGF enhancement. [ABSTRACT FROM AUTHOR]

Astragalus membranaceus and Curcuma zedoaria, two traditional Chinese medicines, are widely used together in colorectal cancer adjuvant treatment. Many different mechanisms should be involved in the benefit effect of Astragalus membranaceus and Curcuma zedoaria. In this study, we established that the combined extract from Astragalus membranaceus and Curcuma zedoaria (HQEZ) decreased the metastasis ability in colorectal cancer cells (HCT116, a cell line of colorectal carcinoma established from Homo sapiens) in vitro, and the treatment induced the downregulation of EMT signal and decreased CXCR4 expression and the level of β-catenin. Overexpression of CXCR4 and the administration of the agonist and inhibitor to β-catenin signal pathway were used to explore the mechanism of Astragalus membranaceus and Curcuma zedoaria in colorectal cancer treatment. The data demonstrated that HQEZ increased the phosphorylation of β-catenin which related to the degradation of β-catenin, and it induced the downregulation of EMT signal and CXCR4. It meant that the influence of β-catenin should be a key event in the antimetastasis effects of Astragalus membranaceus-Curcuma zedoaria in colorectal cancer model. These findings revealed the potential effect and mechanism of Astragalus membranaceus-Curcuma zedoaria in colorectal cancer treatment and provided insight for optimization of the usage. [ABSTRACT FROM AUTHOR]

We undertake zircon U-Pb dating, Hf isotopes, and geochemical analyses of the Houtoumiao pluton in the Xilinhot microcontinent (XLMC) in the central Inner Mongolia with an aim of determining their ages, petrogenesis, and sources, which are important for understanding the late Palaeozoic tectonic evolution of the Xing’an-Mongolia Orogenic Belt. The Houtoumiao pluton consists of medium-grained granodiorite, coarse- and medium-grained syenogranite. Mafic microgranular enclaves (MMEs) are common in the Houtoumiao pluton. Zircon U-Pb dating has yielded ages of 303 ± 2 and 301 ± 2 Ma for the granodiorite, 295 ± 2 Ma for the syenogranite, and 292 ± 1 Ma for the MMEs. The granodiorite and syenogranite have features of high-K high silica content, rich in Rb, U, and Th, but low content of HFSE, belong to calc-alkaline series. The P2O5 concentration decreases with the increasing SiO2 content, suggesting I-type affinity. The MMEs, which are characterized by low SiO2, relatively high and variable TiO2, Al2O3, FeOT, MgO, CaO, Ni, and Cr contents, also have much higher total rare earth element concentrations that the REE patterns are subparallel to those of the host rocks. Zircons from the host rocks have εHf(t) values from +3.91 to +7.73 and TDM2 values of 820-1067 Ma, suggesting that the granitoids were probably dominated by remelting of juvenile crust materials. The MMEs are of εHf(t) value ranging from +6.23 to +11.04 and TDM1 values from 490 to 693 Ma, suggesting that the primary magma probably was derived from partial melting of a depleted lithospheric mantle, the mafic mineral fractional crystallization and crustal contamination occurred during the magma evolution. Combined with previous studies on the contemporaneous magma-tectonic activities in the Uliastai Continental Margin and XLMC, we suggest that the Houtoumiao pluton formed in a post-orogenic setting. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to describe time trends in response rates in case-control studies of cancer and identify study design factors that influence response rate.Methods: We reviewed 370 case-control studies of cancer published in 12 journals during indicator years in each of the last four decades. We estimated time trends of response rates and reasons for nonresponse in each of the following types of study subjects: cases, medical source controls, and population controls. We also estimated response rates according to characteristics of study context.Results: Median response rates among cases and population controls were between 75% and 80% in the 1970s. Between 1971 and 2010, study response rates declined by 0.31% per year for cases and 0.78% for population controls. Only a minority of studies reported reasons for nonparticipation; subject refusal was the most common reported reason. Studies conducted in North America had lower median response rates than studies conducted in Europe. In-person and telephone interviews elicited higher response rates than mail questionnaires.Conclusions: Response rates from case-control studies of cancer have declined, and this could threaten the validity of results derived from these studies. [ABSTRACT FROM AUTHOR]

• Targeted metabolomics and mineral element-rare earth element analysis were applied for identify the production regions of Huangguanyin oolong tea. • By PCA and SVM combined analysis of differential chemical components, forty samples were identified as 2 production regions with an identification efficiency of 88.89 %; By PCA and SVM combined analysis of differential mineral elements and differential rare earth elements, forty samples were identified as 2 production regions with an identification efficiency of 100 %. • This result has certain guiding significance for the development of the tea industry in the two production regions, and helps us to follow up the study of Huangguanyin oolong tea from different regions. Oolong tea is one of the most popular tea beverages in China. Tea cultivars, processing technology and origin of production affect the quality and price of oolong teas. To investigate the differences in Huangguanyin oolong tea from different production regions, the chemical components, mineral elements and rare earth elements of Huangguanyin oolong tea produced in Yunxiao (YX) and Wuyishan (WY) were analyzed by using spectrophotometry methods, targeted metabolomics and inductive plasma coupled mass spectrometry (ICP-MS). The results of spectrophotometry methods revealed that there were significant differences in thearubigin, tea polyphenols and water extract between Huangguanyin oolong teas from different production regions. Targeted metabolomics identified a total of 31 chemical components in Huangguanyin oolong teas from the two production regions, of which 14 chemical components were significantly different and contributed to the regional differentiation of Huangguanyin oolong tea. Yunxiao Huangguanyin had relatively higher contents of (-)-Epigallocatechin-3-O-(3-O-methylgallate) (EGCG3″Me), ornithine (Orn) and histidine (His), while Wuyishan Huangguanyin had relatively higher contents of glutamic acid (Glu), γ -aminobutyric acid (GABA), β -aminobutyric acid (β -ABA) and other components. Moreover, ICP-MS identified a total of 15 mineral elements and 15 rare earth elements in Huangguanyin oolong tea from the two production regions, of which 15 elements were significantly different between YX and WY, and contributed to the regional differentiation of Huangguanyin oolong tea. K had a relatively higher content in Yunxiao Huangguanyin, while rare earth elements had relatively higher contents in Wuyishan Huangguanyin. The classification results by the production region showed that the discrimination rate of the support vector machine (SVM) model based on the 14 different chemical components reached 88.89%, while the SVM model based on the 15 elements reached 100%. Therefore, we used targeted metabolomics and ICP-MS techniques to screen and explore the chemical components, mineral elements and rare earth elements differences among two production regions, which indicated the feasibility of Huangguanyin oolong tea classification by production regions in the study. The results will provide some reference for the distinction between the two production regions of Huangguanyin oolong tea. [ABSTRACT FROM AUTHOR]

[Display omitted] • A new gas–liquid interface polymerization at low temperature was designed to fabricate the conductive 3D meshwork. • The PANI was grown vertically along the surface of the electrospun fibers without sacrificing the 3D porous structure. • The degree of polymerization was adjusted with glycerin. High performance pressure sensing device fabricated by coating conductive polymers on flexible substrates attracts research focuses in the field of wearable devices currently. The most common method for polymerization of conductive polyaniline (PANI) in aqueous solution, generally causing problems of damage to flexible substrate, poor effect of polymerization and environmental pollution. In this study, a novel low-temperature gas–liquid interface polymerization method for PANI polymerization is developed to fabricate core–shell conductive fibrous membrane. By skillfully taking advantage of volatility of aniline monomer, layered conductive PANI grows vertically on the surface of electrospun fibers at gas–liquid interface instead of in traditional aqueous solution. The degree of PANI polymerization based on this method is controllable by glycerin, which can be analyzed by an established model. The sensor fabricated by this method demonstrates superior performance with a high sensitivity of 10.62 kPa−1, fast response time (60 ms) and subtle detection limit (5.1 Pa) compared with that prepared by traditional liquid polymerization. This breathable sensor can detect human signal detection effectively, and develop a variety of intelligent applications. In brief, this work provides a novel strategy and facile technology for developing flexible intelligent devices with conductive polymers. [ABSTRACT FROM AUTHOR]

The cast thin sections of tight oil reservoirs contain important parameters such as rock mineral composition and content, porosity, permeability and stratigraphic characteristics, which are of great significance for reservoir evaluation. The use of deep learning technology for intelligent identification of thin section images is a development trend of mineral identification. However, the difficulty of making cast thin sections, the complexity of the making process and the high cost of thin section annotation have led to a lack of cast thin section images, which cannot meet the training requirements of deep learning image recognition models. In order to increase the sample size and improve the training effect of deep learning model, we proposed a generation and annotation method of thin section images of tight oil reservoir based on deep learning, by taking Fuyu reservoir in Sanzhao Sag as the target area. Firstly, the Augmentor strategy space was used to preliminarily augment the original images while preserving the original image features to meet the requirements of the model. Secondly, the category attention mechanism was added to the original StyleGAN network to avoid the influence of the uneven number of components in thin sections on the quality of the generated images. Then, the SALM annotation module was designed to achieve semi-automatic annotation of the generated images. Finally, experiments on image sharpness, distortion, standard accuracy and annotation efficiency were designed to verify the advantages of the method in image quality and annotation efficiency. [ABSTRACT FROM AUTHOR]

• A framework for robustness evaluation of deep diagnostic models under adversarial attack has been proposed. • A novel benchmark dataset and a robustness evaluation metric are proposed to evaluate the common perturbation robustness of three representative deep diagnostic models. • Two new defense methods are designed to handle adversarial examples in deep diagnostic models, called Multi Perturbations Adversarial Training (MPAdvT) and Misclassification Aware Adversarial Training (MAAdvT) MAAdvT), respectively. • Experimental results have shown that the proposed defense method scan effectively improve the robustness of deep diagnostic models. Deep learning models (with neural networks) have been widely used in challenging tasks such as computer-aided disease diagnosis based on medical images. Recent studies have shown deep diagnostic models may not be robust in the inference process and may pose severe security concerns in clinical practice. Among all the factors that make the model not robust, the most serious one is adversarial examples. The so-called "adversarial example" is a well-designed perturbation that is not easily perceived by humans but results in a false output of deep diagnostic models with high confidence. In this paper, we evaluate the robustness of deep diagnostic models by adversarial attack. Specifically, we have performed two types of adversarial attacks to three deep diagnostic models in both single-label and multi-label classification tasks, and found that these models are not reliable when attacked by adversarial example. We have further explored how adversarial examples attack the models, by analyzing their quantitative classification results, intermediate features, discriminability of features and correlation of estimated labels for both original/clean images and those adversarial ones. We have also designed two new defense methods to handle adversarial examples in deep diagnostic models, i.e. , Multi-Perturbations Adversarial Training (MPAdvT) and Misclassification-Aware Adversarial Training (MAAdvT). The experimental results have shown that the use of defense methods can significantly improve the robustness of deep diagnostic models against adversarial attacks. [ABSTRACT FROM AUTHOR]

The development of eco-friendly reduced graphene oxide (RGO) fabric electrodes with high performance and low cost has attracted much attention. Here, a highly conductive RGO silk fabric for supercapacitors and sensors was prepared by pretreating silk fabric with ternary solvent (CaCl 2 /C 2 H 5 OH/H 2 O) and then followed by ultrasound-assisted cycle drying. Instead of using crosslinking agent, the method is eco-friendly and it can increase the load of active substance, fabricating the high-performance RGO silk fabric electrode with lower cost. The effects of different treatment methods and treatment times on the morphology and properties of the electrodes were investigated. The area capacitance can be increased by 988.31%, 375.86% and 175.76% respectively by different ways of cyclic drying, ultrasonic treatment and ternary solvent pretreatment. The electrode prepared by this method has excellent conductivity and capacitance. Impressively, it has ultrahigh capacitance retention of 148% at 10000 charge-discharge cycles and excellent electrochemical stability. Meanwhile, it also has deformation response and excellent ultraviolet performance (UPF = 2182.63). This fabricated RGO silk fabric can be used as a sensor to monitor human motion (excellent mechanical stability), and it has a great potential for application in the field of wearable electronic products. [Display omitted] • High performance RGO fabric without crosslinking agent was designed. • The effect of preparation method on RGO fabric electrode was discussed. • RGO fabric electrode has good area capacitance and ultra-high capacitance retention. • RGO fabric electrode has an ultra-high UV resistance (UPF = 2182.63). • RGO fabric electrode can be used as a flexible sensor to monitor human behavior. [ABSTRACT FROM AUTHOR]

[Display omitted] • The type of dopant atom changed the physiochemical characters of catalysts discriminately. • Surface chemical properties of catalysts determined their catalytic and anti-poisoning performances. • The support doped catalysts showed the better low temperature SO 2 resistance. • The formation of ammonium bisulfate species is inhibited on Sb/Si doping V 2 O 5 /TiO 2 catalysts surfaces. • The electronic transfer caused by formed surface sulfate species improved SCR activity of V 2 O 5 /Sb-TiO 2. The Sb/Si doped TiO 2 prepared by sol–gel method were used as supports of V 2 O 5 /TiO 2 SCR catalysts in order to improve SCR activity and SO 2 resistance. The type of dopant atoms changed catalyst physiochemical properties discriminatively. Surface chemical properties of catalysts played more important role in their catalytic performance. Simultaneous enhanced surface acidity and redox capacity leaded to the better SCR activity for V 2 O 5 /Sb-TiO 2 compared with other catalysts. The low temperature SO 2 resistance was improved for the support doped catalysts. The special electronic charge migration brought by surface sulfate species for V 2 O 5 /Sb-TiO 2 even elevated its SCR activity during SO 2 resistance test, which was due to the formation of new acid sites and enhancement of redox performance. Even though NO x conversion for V 2 O 5 /Si-TiO 2 decreased, the relative stable efficiency was kept at low temperatures with SO 2. The results proved hetero atom doping in TiO 2 by sol–gel method was a useful method to improve low temperature SO 2 resistance of catalysts. By contrast, Sb is a better choice for the development of support doped V 2 O 5 /TiO 2 SCR catalyst used in a wide temperature range. [ABSTRACT FROM AUTHOR]

Flexible sensors are becoming the focus of research because they are very vital for intelligent products, real-time data monitoring, and recording. The flat silk cocoon (FSC), as a special form of cocoon, has all the advantages of silk, which is an excellent biomass carbon-based material and a good choice for preparing flexible sensors. In this work, a flexible piezoresistive sensor was successfully prepared by encapsulating carbonized flat silk cocoons (CFSCs) using an elastic matrix polydimethylsiloxane (PDMS). The sensing performance of the material is 0.01 kPa−1, and the monitoring range can reach 680.57 kPa. It is proved that the sensor can detect human motion and has excellent durability (>800 cycles). In addition, a sensor array for a keyboard based on CFSCs was explored. The sensor has a low production cost and a simple preparation process, and it is sustainable and environmentally friendly. Thus, it may have potential applications in wearable devices and human–computer interactions. [ABSTRACT FROM AUTHOR]

A DNA framework assembled split G4 nanodevice was fabricated to realize microRNA imaging in living HeLa cells. After hybridization with the target, the separated G4 segments underwent structural transformations, which could initiate fluorescence resonance energy transfer (FRET) processes. Our design may pave a novel way to facilitate applications of the G4 motif. [ABSTRACT FROM AUTHOR]

[Display omitted] • Using PTASA to promote PTL pyrolysis for high-quality syngas was firstly proposed. • The kinetic mechanism of PTASA in the pyrolysis of PTL was revealed. • PTASA mainly decreased the activation energy of Lignin in PTL by19%. • High-quality syngas increased evidently from 0.415 to 0.523 L/g with PTASA. • Inherent minerals in PTASA could break macromolecule bonds to promote PTL pyrolysis. To improve pyrolysis syngas of Phoenix Tree's Leaves (PTL), the synergistic effect of Purified Terephthalic Acid Sludge Ash (PTASA) was comprehensively investigated. In kinetics analysis, the thermal decomposition of PTL could be divided into three pseudoreactions while PTL + PTASA was with four pseudoreactions owing to the decomposition of CaCO 3 as well as the reduction of inherent metal compounds (Co(II), Mn(III, IV), etc). Meanwhile, the reaction models for pseudoreaction 1 (P1) ∼ pseudoreaction 4 (P4) were fitted as D3, R2 and D3, and A15, respectively. The Ea (average activation energy) of PTL + PTASA during pyrolysis (200 ∼ 600 °C) was 6.2 % lower than the monopyrolysis which was mainly caused by the decrease of Ea in the decomposition of lignin. In addition, the crystal structure e.g. CaMnO 3 (ABO 3), Ca 3 Co 2 O 6 (A 3 BB'O 6), and CoO in PTASA could effectively promote the production of high-quality syngas from 41.34 % to 61.76 %. Moreover, the reaction pathways in pyrolysis of PTL + PTASA showed that the PTASA could promote the C C bond, C O bond, and C–H bond breaking of the macromolecules, e.g. anhydrosugars, N-containing compounds, and aldehydes, to produce the small molecules and release syngas. This study could provide a useful strategy for clean, valuable, and sustainable resource utilization of waste resources. [ABSTRACT FROM AUTHOR]

Mutations in isocitrate dehydrogenase (IDH) are frequently found in low-grade gliomas, secondary glioblastoma, chondrosarcoma, acute myeloid leukemias, and intrahepatic cholangiocarcinoma. However, the molecular mechanisms of how IDH2 mutations induce carcinogenesis remain unclear. Using overlapping PCR, transfection, immunoblotting, immunoprecipitation, measurements of enzyme activity, glucose, lactic acid, ATP, and reactive oxygen species (ROS), cell viability, protein degradation assays post-inhibition of the 26S proteasome (bortezomib) or HSP90 (17-AAG), and a homology model, we demonstrated that the properties of ten cancer-associated IDH2 variants (R140G/Q/W and R172S/K/M/W/G/C/P) arising from point mutations are closely related to their structure and stability. Compared with wild-type IDH2, the R172 and R140 point mutations resulted in a decrease in IDH2 activity, ROS, and lactate levels and an increase in glucose and ATP levels under normal and hypoxic conditions, indicating that mutant IDH2 increases cell dependency on mitochondrial oxidative phosphorylation, and reduces glycolysis under hypoxia. Overexpression of most of IDH2 point mutants showed anti-proliferative effects in the 293T and BV2 cell lines by inhibition of PI3K/AKT signaling and cyclin D1 expression and/or induced the expression of TNF-α and IL-6. Furthermore, bortezomib treatment resulted in dramatic degradation of IDH2 mutants, including R140G, R140Q, R140W, R172S and R172K, whereas it had little impact on the expression of WT and other mutants (R172M, R172W, R172G, R172C and R172P). In addition, targeting HSP90 minimally affected the expression of mutated IDH2 due to a lack of interaction between HSP90 and IDH2. The homology model further revealed that changes in conformation and IDH2 protein stability appeared to be associated with these point mutations. Taken together, our findings provide information important for understanding the molecular mechanisms of IDH2 mutations in tumors. [ABSTRACT FROM AUTHOR]

Summary: Development in higher organisms requires proper gene silencing, partially achieved through trimethylation of lysine 27 on histone H3 (H3K27me3). However, how the normal distribution of this modification is established and maintained and how it affects gene expression remains unclear, especially in fungi. Polycomb repressive complex 2 (PRC2) catalyses H3K27me3 to assemble transcriptionally repressed facultative heterochromatin and is crucial in animals, plants, and fungi.Here, we report on the critical role of an additional PRC2 subunit in the normal distribution of H3K27me3 occupancy and the stable maintenance of gene repression in the rice fungal pathogen Magnaporthe oryzae. P55, identified as an additional PRC2 subunit, is physically associated with core subunits of PRC2 and is required for a complete level of H3K27me3 modification.Loss of P55 caused severe global defects in the normal distribution of H3K27me3 and transcriptional reprogramming on the H3K27me3‐occupied genes. Furthermore, we found that the Sin3 histone deacetylase complex was required to sustain H3K27me3 occupancy and stably maintain gene repression by directly interacting with P55.Our results revealed a novel mechanism by which P55 and Sin3 participate in the normal distribution of facultative heterochromatic modifications and the stable maintenance of gene repression in eukaryotes. [ABSTRACT FROM AUTHOR]

Astaxanthin is a kind of keto-carotenes with various health benefits. However, its solubility and chemical stability are poor, which leads to low bio-availability. Microcapsules have been reported to improve the solubility, chemical stability, and bio-availability of lipophilic bioactives. Freeze-dried astaxanthin-loaded microcapsules were prepared by layer-by-layer assembly of tertiary emulsions with maltodextrin as the filling matrix. Tertiary emulsions were fabricated by performing chitosan and sodium alginate electrostatic deposition onto soybean lecithin stabilized emulsions. 0.9 wt% of chitosan solution, 0.3 wt% of sodium alginate solution and 20 wt% of maltodextrin were optimized as the suitable concentrations. The prepared microcapsules were powders with irregular blocky structures. The astaxanthin loading was 0.56 ± 0.05 % and the encapsulation efficiency was >90 %. A slow release of astaxanthin could be observed in microcapsules promoted by the modulating of chitosan, alginate and maltodextrin. In vitro simulated digestion displayed that the microcapsules increased the bio-accessibility of astaxanthin to 69 ± 1 %. Chitosan, alginate and maltodextrin can control the digestion of microcapsules. The coating of chitosan and sodium alginate, and the filling of maltodextrin in microcapsules improved the chemical stability of astaxanthin. The constructed microcapsules were valuable to enrich scientific knowledge about improving the application of functional ingredients. [ABSTRACT FROM AUTHOR]

Protein-protein interactions (PPIs) monitoring is critical to reveal cellular fundamental mechanism and facilitate drugs discovery. Nevertheless, the facial and robust protein 53 (p53)-murine double minute2 (MDM2) interaction detection methods remain challenging. Herein, we developed a PPIs detection platform based on CRISPR-Cas12a sensing system for the first time for p53-MDM2 interaction monitoring and inhibitors potency evaluation, designated Cas-PPIor (Cas12a-mediated PPIs detector). Inspired by the conformational-dependent consensus DNA binding ability of p53, a double stranded DNA (dsDNA) probe was designed elaborately through incorporating Cas12a activation DNA sequence into the specific p53 DNA-binding sequence. Thus, the PPI event can then be transduced into the collateral cleavage activity of Cas12a. As both the Cas12a/CRISPR RNA (crRNA) complex and p53 can bind to the same dsDNA probe in a competitive manner, the activated Cas12a mediated fluorescent readout scaled negatively with the p53 binding. Accordingly, we monitored the p53-MDM2 interaction process as well as its inhibition by a small-molecule antagonist. Based on the sequence specific binding of wild p53, our designed Cas-PPIor achieved high accuracy for differentiation of wild-type p53 cells from p53 mutation or deletion cells. Through discriminating p53 levels from cellular matrix treated with enantiomers of Nutlin-3, the assay also demonstrated reliable capability to evaluate drugs antiproliferative potency. By integrating the DNA binding ability of proteins with intrinsic flexible programmability and outstanding sensitivity of Cas12a, the proposed Cas-PPIor methodology hold great potential to enable accurate and facial PPIs monitoring and inhibitors potency evaluations. • PPIs detection platform based on CRISPR-Cas12a was developed for the first time. • The protein binding event can be detected with cleavage activity of Cas12a. • The p53-MDM2 interaction and its inhibition by antagonist was monitored. • The designed Cas-PPIor achieved high accuracy for cells in different p53 states. [ABSTRACT FROM AUTHOR]

Hair cells play key roles in hearing and balance, and hair cell loss would result in hearing loss or vestibular dysfunction. Cellular and molecular research in hair cell biology provides us a better understanding of hearing and deafness. Zebrafish, owing to their hair cell-enriched organs, have been widely applied in hair cell-related research worldwide. Similar to mammals, zebrafish have inner ear hair cells. In addition, they also have lateral line neuromast hair cells. These different types of hair cells vary in morphology and function. However, systematic analysis of their molecular characteristics remains lacking. In this study, we analyzed the GFP+ cells isolated from Tg(Brn3c:mGFP) larvae with GFP expression in all hair cells using single-cell RNA-sequencing (scRNA-seq). Three subtypes of hair cells, namely macula hair cell (MHC), crista hair cell (CHC), and neuromast hair cell (NHC), were characterized and validated by whole-mount in situ hybridization analysis of marker genes. The hair cell scRNA-seq data revealed hair cell-specific genes, including hearing loss genes that have been identified in humans and novel genes potentially involved in hair cell formation and function. Two novel genes were discovered to specifically function in NHCs and MHCs, corresponding to their specific expression in NHCs and MHCs. This study allows us to understand the specific genes in hair cell subpopulations of zebrafish, which will shed light on the genetics of both human vestibular and cochlear hair cell function. [ABSTRACT FROM AUTHOR]

The development of aerogel materials with high preparation efficiency, no pollution, and high adsorption efficiency is still an effective solution for water pollution caused by heavy metal ions. We propose a simple and efficient way to prepare composite aerogel with a porous network-like structure to adsorb copper ions. The new adsorbent (CTC) was prepared by impregnating cellulose nanofiber (CNF)/multi-walled carbon nanotubes (MWCNTs) aerogel directly into the chitosan solution. The influence of different experimental factors such as the concentration of impregnated chitosan solution, pH value, temperature, and contact time on the CTC adsorption effect was tested. The results showed that the adsorption of CTC reached equilibrium after 2 h. At 25 °C, when the pH value of the solution was four and the concentration of impregnated chitosan was 0.6 wt%, the maximum adsorption capacity was 46.05 mg g−1. CTC was expected to become a new environmentally-friendly adsorbent for copper ion adsorption due to its high adsorption efficiency and use of no toxic substances in the preparation process. [ABSTRACT FROM AUTHOR]

Myocardial ischemia or hypoxia can induce myocardial fibroblast proliferation and myocardial fibrosis. Hydrogen sulfide (H2S) is a gasotransmitter with multiple physiological functions. In our present study, primary cardiac fibroblasts were incubated with H2S donor sodium hydrosulfide (NaHS, 50 μM) for 4 h followed by hypoxia stimulation (containing 5% CO2 and 1% O2) for 4 h. Then, the preventive effects on cardiac fibroblast proliferation and the possible mechanisms were investigated. Our results showed that NaHS reduced the cardiac fibroblast number, decreased the hydroxyproline content; inhibited the EdU positive ratio; and down-regulated the expressions of α-smooth muscle actin (α-SMA), the antigen identified by monoclonal antibody Ki67 (Ki67), proliferating cell nuclear antigen (PCNA), collagen I, and collagen III, suggesting that hypoxia-induced cardiac fibroblasts proliferation was suppressed by NaHS. NaHS improved the mitochondrial membrane potential and attenuated oxidative stress, and inhibited dynamin-related protein 1 (DRP1), but enhanced optic atrophy protein 1 (OPA1) expression. NaHS down-regulated receptor interacting protein kinase 1 (RIPK1) and RIPK3 expression, suggesting that necroptosis was alleviated. NaHS increased the sirtuin 3 (SIRT3) expressions in hypoxia-induced cardiac fibroblasts. Moreover, after SIRT3 siRNA transfection, the inhibitory effects on cardiac fibroblast proliferation, oxidative stress, and necroptosis were weakened. In summary, necroptosis inhibition by exogenous H2S alleviated hypoxia-induced cardiac fibroblast proliferation via SIRT3. [ABSTRACT FROM AUTHOR]

High-performance textile electrodes exhibit considerable potential for use as electronic devices in the wearable energy field. As silk fibroin protein can be dissolved, silk fabric is pretreated with a ternary solvent (CaCl 2 /C 2 H 5 OH/H 2 O) to increase the specific surface area of the substrate and the active material loading. The area capacitance of this fabricated electrode with ternary solvent treatment (PANI@TS-silk fabric, 4091.43 mF/cm2) is 2.3 times that of an electrode prepared without ternary solvent treatment (PANI@WTS-silk fabric, 1811.43 mF/cm2) and higher than the reported area capacitance of currently used flexible electrodes prepared using pure polyaniline. The capacitance retention rate of the PANI@TS -silk fabric electrode can reach 99.54% after 3000 charge-discharge cycles. The electrode can be used as a flexible sensor with stable performance under 2000 mechanical deformation. In addition, PANI@TS-silk fabric possesses good flame retardant performance, antimicrobial properties and UV resistance. These results suggest that the prepared PANI coated silk fabric has broad potential applications to wearable textiles. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Chemotherapy resistance remains a barrier to improving the prognosis of epithelial ovarian cancer (EOC). ALKBH5 has recently been shown to be one of the RNA N6-methyladenosine (m6A) demethyltransferases associated with various cancers, but its role in cancer therapeutic resistance remains unclear. This study aimed to investigate the role of AlkB homolog 5 (ALKBH5) in cisplatin-resistant EOC. Methods: Functional assays were performed both in vitro and in vivo. RNA sequencing (RNA-seq), m6A-modified RNA immunoprecipitation sequencing (MeRIP-seq), chromatin immunoprecipitation, RNA immunoprecipitation, and luciferase reporter and actinomycin-D assays were performed to investigate RNA/RNA interaction and m6A modification of the ALKBH5-HOXA10 loop. Results: ALKBH5 was upregulated in cisplatin-resistant EOC and promoted cancer cell cisplatin resistance both in vivo and in vitro. Notably, HOXA10 formed a loop with ALKBH5 and was found to be the upstream transcription factor of ALKBH5. HOXA10 overexpression also facilitated EOC cell chemoresistance both in vivo and in vitro. Collective results of MeRIP-seq and RNA-seq showed that JAK2 is the m6A-modified gene targeted by ALKBH5. The JAK2/STAT3 signaling pathway was activated by overexpression of the ALKBH5-HOXA10 loop, resulting in EOC chemoresistance. Cell sensitivity to cisplatin was rescued by ALKBH5 and HOXA10 knockdown or inhibition of the JAK2/STAT3 signaling pathway in EOC cells overexpressing ALKBH5-HOXA10. Conclusions: The ALKBH5-HOXA10 loop jointly activates the JAK2/STAT3 signaling pathway by mediating JAK2 m6A demethylation, promoting EOC resistance to cisplatin. Thus, inhibition of the expression of the ALKBH5-HOXA10 loop may be a potential strategy to overcome cisplatin resistance in EOC. [ABSTRACT FROM AUTHOR]

Pre-eclampsia, one of the major disorders of pregnancy, is characterized by inadequate trophoblast invasion and defective trophoblast-mediated remodeling of placental vasculature. Hypoxia-inducible transcription factor (HIF)-2α plays a critical role in regulating cellular function of trophoblasts; however, its role in placental development and in the pathogenesis of pre-eclampsia remains elusive. CCK-8 assay was used to detect cell viability. Invasion assay was performed to determine the effect of HIF-2α on trophoblast function. Flow cytometry was used for detecting apoptosis and cell cycle. The mRNA and protein expressions of HIF-2α, VEGF, iNOS, and ET-1 were determined by quantitative real-time PCR and western blot techniques. The roles of HIF-2α in JEG-3 trophoblast cells were examined using siRNA technology. The presence of HIF-2α siRNA reduced the levels of cell viability after 48 h incubation, and the cell viability further reduced at 72 h. Besides, HIF-2α siRNA enhanced trophoblast apoptosis, as determined by flow cytometric measurement. Increased G1-phase and decreased S-phase cell population were induced by HIF-2α siRNA based on the determination of cell cycle distribution using propidium iodide staining. Furthermore, the invasive ability of JEG-3 trophoblasts was significantly reduced by HIF-2α siRNA. In addition, knockdown of the HIF-2α gene significantly decreased VEGF, iNOS, and ET-1 levels in JEG-3 human trophoblasts. Our findings provide preliminary evidence of the functions of HIF-2α in trophoblast biology and suggest that the downregulation of HIF-2α enhances cell apoptosis and limits trophoblast invasion. [ABSTRACT FROM AUTHOR]

[Display omitted] • In situ stability analysis of blueberry anthocyanins (BAs) by Raman spectroscopy. • Multivariate analysis explained BA degradation in aqueous solutions in bottles. • High temperature, high pH, and ultraviolet irradiation caused BA degradation. • Multi-factor perturbations exacerbated BA degradation. Blueberry anthocyanin (BA) is a functional ingredient to enhance the biological activity of food, and the stability of BA is of great interest. BA stability in aqueous solutions stored in polypropylene and glass bottles was analyzed in-situ using confocal Raman spectroscopy, and the acceptable depth of focus was optimized. The Raman characteristics of BA degradation were explained by multivariate analysis. The degradation rate of BA was significantly accelerated by heating above 65 °C for 2 h or ultraviolet irradiation (10 W) for 96 h. The first order kinetic reaction rate was accelerated with the increase of pH value and temperature and the prolongation of ultraviolet irradiation time. The synergistic effect of multiple factors promoted BA degradation. This study provides an in-situ, nondestructive method for the analysis of anthocyanin stability, which has great utility in the food industry to optimize processing, storage, and transportation measures to reduce the degradation of BA. [ABSTRACT FROM AUTHOR]

Type 1 diabetes mellitus (T1DM) is predominantly managed using insulin replacement therapy, however, pancreatic microcirculatory disturbances play a critical role in T1DM pathogenesis, necessitating alternative therapies. This study aimed to investigate the protective effects of glycine supplementation on pancreatic microcirculation in T1DM. Streptozotocin-induced T1DM and glycine-supplemented mice (n = 6 per group) were used alongside control mice. Pancreatic microcirculatory profiles were determined using a laser Doppler blood perfusion monitoring system and wavelet transform spectral analysis. The T1DM group exhibited disorganized pancreatic microcirculatory oscillation. Glycine supplementation significantly restored regular biorhythmic contraction and relaxation, improving blood distribution patterns. Further-more, glycine reversed the lower amplitudes of endothelial oscillators in T1DM mice. Ultrastructural deterioration of islet microvascular endothelial cells (IMECs) and islet microvascular pericytes, including membrane and organelle damage, collagenous fiber proliferation, and reduced edema, was substantially reversed by glycine supplementation. Additionally, glycine supplementation inhibited the production of IL-6, TNF-α, IFN-γ, pro-MMP-9, and VEGF-A in T1DM, with no significant changes in energetic metabolism observed in glycine-supplemented IMECs. A statistically significant decrease in MDA levels accompanied by an increase in SOD levels was also observed with glycine supplementation. Notably, negative correlations emerged between inflammatory cytokines and microhemodynamic profiles. These findings suggest that glycine supplementation may offer a promising therapeutic approach for protecting against pancreatic microcirculatory dysfunction in T1DM. • Pancreatic microcirculation improved with glycine supplementation in T1DM mice. • Glycine mitigates ultrastructural damage in islet microvascular cells and pericytes. • Inflammatory cytokine and microvascular mediator reduced by glycine treatment. • Energetic metabolism in IMECs remains stable after glycine supplementation. • Glycine shows potential as a therapeutic approach for T1DM. [ABSTRACT FROM AUTHOR]

Weak performance of hydrogel fabricated by a sole component limits their applications. In this study, we proposed a facile preparation of hydrogels by using three natural polymers, carboxymethyl chitosan, alginate and agarose. The fabricated carboxymethyl chitosan/sodium alginate/agarose hydrogels were further treated by divalent calcium ions to form a double crosslinked network inside. These double crosslinked hydrogels showed tunable mechanical property and the compressive strength ranged from 176 Pa to 685 Pa by varying the crosslinking degree. They also exhibited excellent swelling behavior (more than 1500%), good degradability and good biocompatibility, indicating their potential for application in wound healing, drug delivery and bone tissue engineering. [ABSTRACT FROM AUTHOR]

To test whether robot-assisted surgery can improve prognosis of small-volume thalamic hemorrhage and to provide a surgical basis for treatment of small-volume thalamic hemorrhage. This retrospective study included patients with thalamic hemorrhage and hematoma volume of 5–15 mL treated from December 2015 to December 2018. Patients were divided into an operation group and a nonoperation group. General data, types of hematoma, incidence of complications, Scandinavian Stroke Scale score, and modified Rankin Scale score were recorded and analyzed. Retrospectively, 84 cases met inclusion criteria: 35 cases in operation group and 49 cases in nonoperation group. At 90 days after onset, mortality was 11.4% in the operation group and 4.1% in the nonoperation group (P > 0.05). The Scandinavian Stroke Scale score in the operation group (43.3 ± 8.5) was higher than in the nonoperation group (36.1 ± 10.0) (P < 0.05). The modified Rankin Scale score in the operation group (2.9 ± 0.3) was lower than in the nonoperation group (3.7 ± 0.2) (P < 0.05). The incidence of pneumonia (8.6%) and renal dysfunction (14.3%) was lower in the operation group than in the nonoperation group (28.6% and 34.7%, respectively) (P < 0.05). There was no significant difference between the 2 groups in the incidence of central fever (5.7% vs. 12.2%), stress ulcer (11.4% vs. 16.3%), and ion balance disturbance (20.0% vs. 26.5%) (P > 0.05). Robot-assisted drainage of thalamic hemorrhage can improve prognosis and reduce the incidence of pneumonia and renal dysfunction. [ABSTRACT FROM AUTHOR]

Graphical abstract Abstract Ca2+/calmodulin-dependent protein kinase II (CaMKII) plays an important role in the cardiovascular system. However, the potential protective role of inhibitor 1 of protein phosphatase 1 (I1PP1), which is able to regulate CaMKII, in high glucose-induced cardiomyocytes injury remains unknown. In the present study, cardiomyocytes were transfected with I1PP1 adenovirus to inhibit protein phosphatase 1 (PP1) expression. After the cardiomyocytes were subjected to high glucose stimulation for 48 h, quantitative real-time PCR was used to detect CaMKIIδ alternative splicing. Lactate dehydrogenase (LDH) release and adenosine triphosphate (ATP) level were measured to assess cell damage and energy metabolism respectively. CaMKII activity was represented as phospholamban (PLB) phosphorylation, CaMKII phosphorylation (p-CaMKII) and oxidation (ox-CaMKII). Dihydroethidium (DHE), MitoSOX and JC-1 staining were used to assess oxidative stress and mitochondrial membrane potential. Necroptosis was evaluated by receptor interacting protein kinase 3 (RIPK3) expression, TUNEL and cleaved-caspase 3 levels. RIPK3, mixed lineage kinase domain like protein (MLKL) and dynamin-related protein 1 (DRP1) expressions were also detected. We found that high glucose disordered CaMKIIδ alternative splicing. I1PP1 over-expression suppressed PLB phosphorylation, ox-CaMKII, DRP1, RIPK3 and cleaved-caspase 3 proteins expression, decreased LDH release, attenuated necroptosis, increased ATP level, inhibited oxidative stress, and elevated mitochondrial membrane potential in high glucose-stimulated cardiomyocytes. However, there was no effect on phosphorylation of MLKL (p-MLKL), p-CaMKII, and receptor interacting protein kinase 1 (RIPK1) expression. Altogether, I1PP1 over-expression alleviated CaMKIIδ alternative splicing disorder, suppressed CaMKII oxidation, reduced reactive oxygen species (ROS) accumulation and inhibited necroptosis to attenuate high glucose-induced cardiomyocytes injury. [ABSTRACT FROM AUTHOR]

[Display omitted] • Raman spectroscopy characterize thermal degradation of edible oils during frying. • Raman spectroscopy characterize thermal degradation of edible oils during frying. • PIRs were optimized by Pearson correlation analysis combined with heat map. • Univariate models for AV of single frying oil had high correlations (0.954–0.984). • RPD of LSSVM model for AV of multi-varieties frying oils was 11.351. The health risks posed by harmful substances resulting from the thermal degradation of frying oils are of great concern. Characteristic peak intensity ratios (PIRs) screened from Raman spectra were used to characterize the thermal degradation. High correlation coefficients between PIRs and acid values (AVs) of 0.972 (linear fitting), 0.984 (logarithmic function fitting), and 0.954 (linear fitting) for fried soybean oil, canola oil, and palm oil, were obtained at the PIRs of I 1267 /I 1749 , I 1267 /I 1659 , and I 1267 /I 1749 , respectively. The highly correlated PIRs common to the three oils were determined by Pearson's correlation coefficient combined with heat maps. To accommodate both linear and nonlinear features, a global model for predicting AVs of multi-varieties frying oils was constructed using a least-squares support vector machine algorithm, and the results performed well with a root mean square error of prediction of 0.016 and a ratio of prediction to deviation of 11.351. The whole results demonstrate that Raman spectroscopy could characterize the thermal degradation and has excellent quantitative analysis ability for food control based on AV in frying oils, thus providing a new approach to quality control of frying oils. [ABSTRACT FROM AUTHOR]

After harvest at horticultural maturity, X-ray computed tomography was used for the non-destructive determination of internal defects occurring in chestnuts during storage. An image processing pipeline was established to accurately identify various types of defective chestnuts. Severely defective chestnuts, with a complete loss of eating quality, were accurately identified by their gray scale value from volume and porosity analyses. Slightly defective calcified chestnuts were classified by local voxel gray scale value analysis. Minor isolated defects in chestnuts (defects only in the kernel) were distinguished by morphological analysis. An internal pore network model was also used to effectively identify connected defective chestnuts (defects connected to the inner skin), with the type of defect being distinguished by spatial distribution morphology. Overall, X-ray computed tomography provided a new perspective for the non-destructive characterization of the three-dimensional image structure of chestnuts and provided an important concept for screening and classifying their storage lesions. [Display omitted] • X-ray computed tomography (CT) was used to identify chestnut internal defects. • Severely defective chestnuts were identified based on gray scale value and porosity. • Gray scale value of some voxels of calcified chestnut was higher than 1200. • Mildews and wormholes were distinguished by morphological analysis of CT images. • Connected defective chestnuts were classified by pore network model. [ABSTRACT FROM AUTHOR]

Dihydromyricetin (DMY) is one of the most important flavonoids in vine tea, which showed several pharmacological effects. However, information about the potential role of DMY on angiotensin II (Ang II) induced cardiac fibroblasts proliferation remains unknown. In the present study, cardiac fibroblasts isolated from neonatal Sprague-Dawley rats were pretreated with different concentrations of DMY (0–320 μM) for 4 h, or DMY (80 μM) for different time (0–24 h), followed by Ang II (100 nM) stimulation for 24 h, Then number of cardiac fibroblasts and content of hydroxyproline was measured. The level of cellular reactive oxygen species, malondialdehyde (MDA), activity of superoxide dismutase (SOD) and total antioxidant capacity (T-AOC) were also evaluated. Expression of type I, type III collagen, α-smooth muscle actin (α-SMA), p22 phox (one vital subunit of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase), SOD and thioredoxin (Trx) were detected with real time PCR or/and western blot. We found that pre-incubation with DMY (20 μM, 40 μM, 80 μM) for 4 h, 12 h or 24 h attenuated the proliferation of cardiac fibroblasts induced by Ang II. Expression of type I and type III collagen, as well as α-SMA were inhibited by DMY at both mRNA and protein level. DMY also significantly decreased cellular reactive oxygen species production and MDA level, while increased the SOD activity and T-AOC. DMY suppressed p22 phox , while enhanced antioxidant SOD and Trx expression in Ang II stimulated cardiac fibroblasts. Thus, dihydromyricetin attenuated Ang II induced cardiac fibroblasts proliferation related to inhibitory of oxidative stress. [ABSTRACT FROM AUTHOR]

[Display omitted] • Visualization of microplastics in crayfish using LCM-Raman imaging. • Microplastics were detected in the gills, intestines, and ovaries of crayfish. • Crayfish exposed to 9 mg/L of microplastics accumulated 13,000 particles in 28 days. • RPV values can quantitatively evaluate the contamination level of microplastics. Crayfish is one of the most important freshwater aquaculture species in China. The potential risks of crayfish consumption caused by environmental microplastic pollution have attracted much attention. In this study, a total of 72 crayfish samples were exposed to the microplastic concentrations of 1 mg/L, 3 mg/L, and 9 mg/L for 7, 14, and 28 days, and microplastic contamination levels in crayfish were then explored by laser confocal micro-Raman (LCM-Raman) imaging and scanning electron microscope (SEM). LCM-Raman imaging showed better performance in microplastics identification. Besides, the average percentage of the contaminated area in visualized LCM-Raman images was used to quantitatively assess contamination levels. Following 28 days of exposure to 9 mg/L microplastics, microplastic accumulation reached about 13,000 particles per crayfish. The results confirmed that LCM-Raman imaging combined with image processing technology could be used to construct a high-performance analytical strategy for the assessment of microplastic contamination in crayfish. [ABSTRACT FROM AUTHOR]

The development of field-deployable detection platform amenable for multiplexed genes testing will significantly improve the efficiency and reliability during point-of-care testing (POCT) applications. In this regard, an orthogonal CRISPR-Cas-mediated multiplexed lateral flow assay (designated as OC-MLFA) is proposed for SARS-CoV-2 genome detection. Taking the advantage of activation and cleavage preferences between Cas12a and Cas13a, orthogonal (two-independent-channel signal readout) CRISPR-Cas system is investigated. Lateral flow strips with two target lines are designed to accommodate the orthogonal CRISPR system. The interference between Cas12a and Cas13a channels can be effectively eliminated via the elaborate nucleic acids and lateral flow strips design. The high preamplification efficiency from reverse transcription recombinase polymerase amplification (RT-RPA) and Cas enzyme mediated trans -cleavage process bring the sensitivity of our OC-MLFA method to 10 copies per test (30 μL). Nasopharyngeal swab clinical samples with different cycle threshold (Ct) values according to the RT-PCR method were analyzed with the proposed OC-MLFA, during which 76 out of 76 detection accuracy was obtained. Featured with the multiplexed genes detection simultaneously in one reaction and colorimetric readout through single strip, the OC-MLFA we proposed herein ensures great accuracy and efficiency, which endows promising field-deployable POCT application feasibility. • Orthogonal CRISPR-Cas-mediated multiplexed lateral flow assay was proposed. • Lateral flow strips with two target lines were designed for SARS-CoV-2 detection. • The detection sensitivity reached 10 copies per test. • Nasopharyngeal swab clinical samples were tested with high accuracy. • The whole dual genes detection procedure can be finished within 1 h. [ABSTRACT FROM AUTHOR]

The crystal structure, elastic properties, and electronic structure of Al 4 La and Al 4 Sm intermetallics were systematically studied by both experimental (SEM, EDS, and nano-indentation) and theoretical methods (first-principle calculations). The microstructure of Al-10% La/Sm alloy exhibited a continuous reticular structure containing intermetallics with long needle-like shapes. The calculated lattice constants of Al 4 La and Al 4 Sm intermetallics were obtained through structural optimization and agreed with the results obtained by Rietveld refinement with an error of <12.6%. The difference in the calculated and experimental Young's module of Al 4 La and Al 4 Sm was less than 7.3%. Further analysis of the elastic constants indicated that Al 4 La has great plasticity and stiffness than Al 4 Sm, while Al 4 Sm showed a more anisotropic Young's modulus. Besides, Al 4 La is found to perform better than Al 4 Sm in plasticity and rigidity. [ABSTRACT FROM AUTHOR]