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The prevalence of environmental problems and the increasing risk of human exposure to environmental pollutants have become a global concern. The increasing environmental pollution is one of the main reasons for the rising incidence of most neurological-related diseases in recent years. However, the ethical constraints of direct human research and the racial limitations of animal models have slowed the progress of research in this area. The purpose of this study is to review the neurotoxicity of different environmental pollutants on the brain using brain organoids as a new model and to conclude that brain organoids may play a key role in assessing the mechanisms by which environmental pollutants affect neurogenesis and cause neurological pathogenesis. To accurately determine the negative effects of environmental pollutants on the nervous system, self-organizing brain organoids that are highly similar to the developing brain have become a new model system for studying the effects of environmental pollutants on human brain development and disease. This study uses brain organoids as a model to summarize the neurotoxicity of different environmental pollutants on the nervous system, including structural changes in brain organoids, inhibition of neuronal differentiation and migration, impairment of mitochondrial function, damage to cellular cilia, and influence on signaling pathways. In conclusion, exposure to environmental pollutants may cause different neurotoxicity to the nervous system. Therefore, it is crucial to understand how to use brain organoids to ameliorate neurological disorders caused by environmental pollution., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Prevalent Gene Regulatory Network (GRN) construction methods rely on generalized correlation analysis. However, in biological systems, regulation is essentially a causal relationship that cannot be adequately captured solely through correlation. Therefore, it is more reasonable to infer GRNs from a causal perspective. Existing causal discovery algorithms typically rely on Directed Acyclic Graphs (DAGs) to model causal relationships, but it often requires traversing the entire network, which result in computational demands skyrocketing as the number of nodes grows and make causal discovery algorithms only suitable for small networks with one or two hundred nodes or fewer. In this study, we propose the SLIVER (cauSaL dIscovery Via dimEnsionality Reduction) algorithm which integrates causal structural equation model and graph decomposition. SLIVER introduces a set of factor nodes, serving as abstractions of different functional modules to integrate the regulatory relationships between genes based on their respective functions or pathways, thus reducing the GRN to the product of two low-dimensional matrices. Subsequently, we employ the structural causal model (SCM) to learn the GRN within the gene node space, enforce the DAG constraint in the low-dimensional space, and guide each factor to aggregate various functions through cosine similarity. We evaluate the performance of the SLIVER algorithm on 12 real single cell transcriptomic datasets, and demonstrate it outperforms other 12 widely used methods both in GRN inference performance and computational resource usage. The analysis of the gene information integrated by factor nodes also demonstrate the biological explanation of factor nodes in GRNs. We apply it to scRNA-seq of Type 2 diabetes mellitus to capture the transcriptional regulatory structural changes of β cells under high insulin demand., Competing Interests: Declaration of competing interest None Declared., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Detecting oriented objects along with estimating their rotation information is one crucial step for image analysis, especially for remote sensing images. Despite that many methods proposed recently have achieved remarkable performance, most of them directly learn to predict object directions under the supervision of only one (e.g., the rotation angle) or a few (e.g., several coordinates) groundtruth (GT) values individually. Oriented object detection would be more accurate and robust if extra constraints, with respect to proposal and rotation information regression, are adopted for joint supervision during training. To this end, we propose a mechanism that simultaneously learns the regression of horizontal proposals, oriented proposals, and rotation angles of objects in a consistent manner, via naive geometric computing, as one additional steady constraint. An oriented center prior guided label assignment strategy is proposed for further enhancing the quality of proposals, yielding better performance. Extensive experiments on six datasets demonstrate the model equipped with our idea significantly outperforms the baseline by a large margin and several new state-of-the-art results are achieved without any extra computational burden during inference. Our proposed idea is simple and intuitive that can be readily implemented. Source codes are publicly available at: https://github.com/wangWilson/CGCDet.git.

Nanoparticles (NPs) are generally defined as very small particles in the size range of 1-100 nm. Due to the rapid development of modern society, many new materials have been developed. The widespread use of NPs in medical applications, the food industry and the textile industry has led to an increase in NPs in the environment and the possibility of human contact, which poses a serious threat to human health. The nervous system plays a leading role in maintaining the integrity and unity of the body and maintaining a harmonious balance with the external environment. Therefore, based on two categories of organic and inorganic NPs, this paper systematically summarizes the toxic effects and mechanisms of NPs released into the nervous system. The results showed that exposure to NPs may damage the nervous system, decrease learning and cognitive ability, and affect embryonic development. Finally, a remediation scheme for NPs entering the body via the environment is also introduced. This scheme aims to reduce the neurotoxicity caused by NPs by supplementing NPs with a combination of antioxidant and anti-inflammatory compounds. The results provide a valuable reference for future research in this field., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Single-image rain streaks' removal has attracted great attention in recent years. However, due to the highly visual similarity between the rain streaks and the line pattern image edges, the over-smoothing of image edges or residual rain streaks' phenomenon may unexpectedly occur in the deraining results. To overcome this problem, we propose a direction and residual awareness network within the curriculum learning paradigm for the rain streaks' removal. Specifically, we present a statistical analysis of the rain streaks on large-scale real rainy images and figure out that rain streaks in local patches possess principal directionality. This motivates us to design a direction-aware network for rain streaks' modeling, in which the principal directionality property endows us with the discriminative representation ability of better differing rain streaks from image edges. On the other hand, for image modeling, we are motivated by the iterative regularization in classical image processing and unfold it into a novel residual-aware block (RAB) to explicitly model the relationship between the image and the residual. The RAB adaptively learns balance parameters to selectively emphasize informative image features and better suppress the rain streaks. Finally, we formulate the rain streaks' removal problem into the curriculum learning paradigm which progressively learns the directionality of the rain streaks, rain streaks' appearance, and the image layer in a coarse-to-fine, easy-to-hard guidance manner. Solid experiments on extensive simulated and real benchmarks demonstrate the visual and quantitative improvement of the proposed method over the state-of-the-art methods.

Background and Objectives: Proteinuria is a common complication after the application of bevacizumab therapy in patients with metastatic colorectal cancer, and severe proteinuria can lead to discontinuation of the drug. There is a lack of sophisticated means to predict bevacizumab-induced proteinuria, so the present study aims to predict bevacizumab-induced proteinuria using peripheral venous blood samples., Methods: A total of 122 subjects were enrolled and underwent pre-treatment plasma markers, and we followed them for six months with proteinuria as the endpoint event. We then analyzed the clinical features and plasma markers for grade ≥ 2 proteinuria occurrence using machine learning to construct a model with predictive utility., Results: One hundred sixteen subjects were included in the statistical analysis. We found that high baseline systolic blood pressure, low baseline HGF, high baseline ET1, high baseline MMP2, and high baseline ACE1 were risk factors for the development of grade ≥ 2 proteinuria in patients with metastatic colorectal cancer who received bevacizumab. Then, we constructed a support vector machine model with a sensitivity of 0.889, a specificity of 0.918, a precision of 0.615, and an F1 score of 0.727., Conclusion: We constructed a machine learning model for predicting grade ≥ 2 bevacizumab-induced proteinuria, which may provide proteinuria risk assessment for applying bevacizumab in patients with metastatic colorectal cancer., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Lossy image compression is a fundamental technology in media transmission and storage. Variable-rate approaches have recently gained much attention to avoid the usage of a set of different models for compressing images at different rates. During the media sharing, multiple re-encodings with different rates would be inevitably executed. However, existing Variational Autoencoder (VAE)-based approaches would be readily corrupted in such circumstances, resulting in the occurrence of strong artifacts and the destruction of image fidelity. Based on the theoretical findings of preserving image fidelity via invertible transformation, we aim to tackle the issue of high-fidelity fine variable-rate image compression and thus propose the Invertible Continuous Codec (I2C). We implement the I2C in a mathematical invertible manner with the core Invertible Activation Transformation (IAT) module. I2C is constructed upon a single-rate Invertible Neural Network (INN) based model and the quality level (QLevel) would be fed into the IAT to generate scaling and bias tensors. Extensive experiments demonstrate that the proposed I2C method outperforms state-of-the-art variable-rate image compression methods by a large margin, especially after multiple continuous re-encodings with different rates, while having the ability to obtain a very fine variable-rate control without any performance compromise.

Wavefront aberration describes the deviation of a wavefront in an imaging system from a desired perfect shape, such as a plane or a sphere, which may be caused by a variety of factors, such as imperfections in optical equipment, atmospheric turbulence, and the physical properties of imaging subjects and medium. Measuring the wavefront aberration of an imaging system is a crucial part of modern optics and optical engineering, with a variety of applications such as adaptive optics, optical testing, microscopy, laser system design, and ophthalmology. While there are dedicated wavefront sensors that aim to measure the phase of light, they often exhibit some drawbacks, such as higher cost and limited spatial resolution compared to regular intensity measurement. In this paper, we introduce a lightweight and practical learning-based method, named LWNet, to recover the wavefront aberration for an imaging system from a single intensity measurement. Specifically, LWNet takes a measured point spread function (PSF) as input and recovers the wavefront aberration with a two-stage network. The first stage network estimates an initial wavefront aberration via supervised learning, and the second stage network further optimizes the wavefront aberration via self-supervised learning by enforcing the statistical priors and physical constraints of wavefront aberrations via Zernike decomposition. For supervised learning, we created a synthetic PSF-wavefront aberration dataset via ray tracing of 88 lenses. Experimental results show that even trained with simulated data, LWNet works well for wavefront aberration estimation of real imaging systems and consistently outperforms prior learning-based methods.

The complex tumor structure and microenvironment such as abnormal tumor vasculature, dense tumor matrix, and elevated interstitial fluid pressure greatly hinder the penetration and retention of therapeutic agents in solid tumors. The development of an advanced method for robust penetration and retention of therapeutic agents in tumors is of great significance for efficient tumor treatments. In this work, we demonstrated that magnetotactic bacteria AMB-1 with hypoxic metabolism characteristics can actively penetrate the tumor to selectively colonize deep hypoxic regions, which emerge as a promising intelligent drug carrier. Furthermore, AMB-1 presents intrinsic second near-infrared (NIR-II) photothermal performance that can efficiently convert a 1064 nm laser into heat for tumor thermal ablation. We believe that our investigations not only develop a novel bacteria-based photothermal agent but also provide useful insights for the development of advanced tumor microbial therapies., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Text generation is a key component of many natural language tasks. Motivated by the success of generative adversarial networks (GANs) for image generation, many text-specific GANs have been proposed. However, due to the discrete nature of text, these text GANs often use reinforcement learning (RL) or continuous relaxations to calculate gradients during learning, leading to high-variance or biased estimation. Furthermore, the existing text GANs often suffer from mode collapse (i.e., they have limited generative diversity). To tackle these problems, we propose a new text GAN model named text feature GAN (TFGAN), where adversarial learning is performed in a continuous text feature space. In the adversarial game, GPT2 provides the "true" features, while the generator of TFGAN learns from them. TFGAN is trained by maximum likelihood estimation on text space and adversarial learning on text feature space, effectively combining them into a single objective, while alleviating mode collapse. TFGAN achieves appealing performance in text generation tasks, and it can also be used as a flexible framework for learning text representations.

Background: Emerging evidence has demonstrated the benefits of greenness exposure on human health, while conflicts remain unsolved in issue of adverse birth outcomes., Methods: Utilizing data from project ELEFANT spanning the years 2011 to 2021, we assessed residential greenness using the NDVI from MODIS data and residential PM 2.5 exposure level from CHAP data. Our primary concerns were PTD, LBW, LGA, and SGA. Cox proportional hazard regression model was used to examine the association of residential greenness and air pollution exposure with risk of adverse birth outcomes. We performed mediation and modification effect analyses between greenness and air pollutant., Results: We identified 61,762 mother‑neonatal pairs in final analysis. For per 10 μg/m 3 increase in PM 2.5 concentration during entire pregnancy was associated with 19.8 % and 20.7 % increased risk of PTD and LGA. In contrast, we identified that an 0.1 unit increment in NDVI were associated with 24 %, 43 %, 26.5 %, and 39.5 % lower risk for PTD, LBW, LGA, and SGA, respectively. According to mediation analysis, NDVI mediated 7.70 % and 7.89 % of the associations between PM 2.5 and PTD and LGA. Residential greenness could reduce the risk of PTD among mothers under 35 years old, living in rural areas, primigravidae and primiparity.., Conclusions: In summary, our results highlighted the potential of residential greenness to mitigate the risk of adverse birth outcomes, while also pointing to the adverse impact of PM 2.5 on increased risk of multiple adverse birth outcomes (PTD and LGA). The significant mediation effect of NDVI emphasizes its potential as an important protective factor of PM 2.5 exposure. Additionally, the identification of susceptible subgroups can inform targeted interventions to reduce adverse birth outcomes related to air pollution and lack of green spaces. Further research and understanding of these associations can contribute to better public health strategies aimed at promoting healthier pregnancies and birth outcomes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

As an emerging type of pollutant, microplastics have become a global environmental problem. Approximately, a fifth of the global burden of type 2 diabetes can be attributed to air particulate pollution. However, scientific knowledge remains limited about the effects of airborne nanoplastics (NPs) exposure on metabolic diseases. In this experiment, a whole-body exposure system was used to simulate the real atmospheric environment, and three exposure concentrations combined with the actual environmental concentration were selected to explore the effects of airborne NPs on metabolic diseases. Based on histological analyses, metabolic studies, gene expression, metabolites, and molecular signaling analyses, mice exposed to airborne NPs were observed to show a phenotype of systemic inflammation and complete insulin resistance featuring excessive drinking and eating, weight loss, elevated blood glucose, and decreased triglyceride levels. After airborne NPs exposure, mice were intolerant to glucose and tolerant to insulin. In addition, airborne NPs exposure could result in long-term irreversible hyperglycemia. Together, the research findings provide a strong basis for understanding the hazards of airborne nanopollution on metabolic disorders.

Cognitive impairments are a core symptom of schizophrenia. Although low-intensity repetitive transcranial magnetic stimulation (rTMS) also has cognitive improving effect like the commonly used high-intensity rTMS, it has not been applied in schizophrenia yet. To fill this gap, inpatients with schizophrenia were randomized to receive 20 sessions of daily adjunctive active low-intensity rTMS in 4 weeks, or sham treatment. At baseline, 4 weeks, and 6 months, the Positive and Negative Syndrome Scale (PANSS) was used to assess psychotic symptom severity, while the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and the Stroop Color and Word Test (SCWT) were used to assess cognitive functions. Compared to the sixty-nine patients receiving sham treatment, those fifty-nine patients receiving active rTMS performed better in all cognitive domains at post-treatment with small to large effect sizes. This superiority of active rTMS over sham treatment remained significant at 6-month follow-up, with small to large effect sizes, except for visuospatial function and delayed memory. The reduction in PANSS scores were not correlated with cognitive improvements. Our findings provide evidence for using low-intensity rTMS to ameliorate cognitive impairments in schizophrenia. More research are needed to determine the optimal intensity for each domain of cognitive functions., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Metastasis is one of the leading causes of cancer-related deaths. A comprehensive comparison of the differences between primary and metastatic cancers within the same organ can aid in understanding the growth mechanisms of cancer cells at metastatic sites, thereby helping to develop more effective targeted treatment strategies. Primary liver cancer is one of the most common types of cancer, and the liver is also one of the main metastatic sites. In this paper, we utilize single-cell RNA-Seq data to compare primary liver cancer and colorectal liver metastases from multiple perspectives, including cell types and proportions, activity of various cell types, cell-cell communication, mRNA expression differences within the same types of cells, key factors associated with cell proliferation, etc. Our analysis results show the following: (i) Compared to primary tissue, metastatic tissue contains more cytotoxic T cells and exhausted T cells, and it retains some specific characteristics of the primary site. (ii) Cells of the same type exhibit functional differences between primary and metastatic cancers, with metastatic cancer cells showing lower metabolism levels and immune cells exhibiting stronger immune activity. (iii) Interactions between monocytes and hepato-associated cells are strong in primary cancer, while depleted T cells frequently communicate with hepatocytes in metastatic cancer. (iv) Proliferation-related genes in primary and metastatic cancers are mainly involved in cell energy supply and basic metabolism activity, respectively.

Objective: To investigate the efficacy of roxadustat in hemodialysis patients with erythropoietin (EPO) hypo-responsive anemia., Materials and Methods: This retrospective study included 55 hemodialysis patients with erythropoietin hypo-responsive anemia at the First Affiliated Hospital of Chongqing Medical University from January to December 2020. We observed their hemoglobin (Hb) changes, inflammatory factors, and adverse reactions before and after 12 weeks of roxadustat treatment., Results: Among the 55 patients, the average age was 60.75 ± 13.96 years old, and the median dialysis age was 48 months. All patients were taken off EPO and switched to roxadustat during the follow-up period. Compared with baseline, patients' Hb was significantly increased (90.64 ± 20.01 g/L, 98.52 ± 15.89 g/L, 104.34 ± 19.15 g/L, and 107.02 ± 20.54 g/L, respectively) (p < 0.05). At 12 weeks of roxadustat treatment, 34 patients (61.82%) met the target Hb levels (100 - 130 g/L). The multivariate logistic analysis showed that Hb response positively correlated with the Hb level before roxadustat treatment (p = 0.046), while responding well to roxadustat negatively correlated with blood platelet-to-lymphocyte ratio (PLR) and duration of dialysis (p = 0.029 and p = 0.046) in patients with EPO hypo-responsive anemia., Conclusion: Roxadustat could effectively improve anemia; the PLR and dialysis age were independent predictors of roxadustat efficacy in dialysis patients with EPO hypo-responsive anemia.

Nanoplastics can be easily absorbed into the human body through inhalation, ingestion, and skin contact due to their physicochemical property. Despite the numerous studies postulating the potential adverse effects of environmental exposure to nanoplastics on neurodevelopment, the effects of nanoplastics and their regulatory mechanisms have not been specifically elucidated. We focused on the toxic effects of nanoplastics on brain developmental processes by investigating their interactions with brain organoids. Our findings indicated that nanoplastics exposure caused cellular dysfunction and structural disorders. Nanoplastics adversely affected critical cells in brain organoids, resulting in the reduction of neural precursor cells and neuronal cells. The expression of neural cadherin was also inhibited, which might lead to impaired axonal extension and formation of synaptic connections. In addition, transcriptome sequencing was performed to study the effects of different concentrations of nanoplastics on the signaling pathway. The qRT-PCR analysis confirmed that nanoplastics exposure resulted in decreased expression of several genes related to the Wnt signaling pathway, suggesting that nanoplastics may adversely affect embryonic brain growth through the suppression of the expression of these genes. Our research findings shed light on the deleterious effects of nanoplastics on embryonic brain development and have significant implications for the field of environmental toxicology., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Liqun Chen reports financial support was provided by National Key Research and Development Program of China. Liqun Chen reports financial support was provided by National Natural Science Foundation of China., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Asini Corii Colla (ACC) and Taurus Corii Colla (TCC) are well-known for their high nutritional value, especially for medicinal purposes. However, the aforementioned are also potential candidates for adulteration because of their low yield and high price. A UPLC-MS/MS approach based on the specific peptide was proposed to detect adulterated gelatin with possible mixed animal species. To explore the antioxidant activity, the peptides were separated to evaluate their effect on ·OH radical and DPPH· scavenging activity, together with PI3K-AKT pathway activation. The results showed that the peptides had excellent DPPH· and ·OH radical scavenging effects, and could alleviate H 2 O 2 -induced oxidative stress by promoting the phosphorylation of PI3K and AKT. According to the results of MALDI-TOF/MS, the shared mass-to-charge ratio ( m/z ) 1466, 1744 and 2382 may serve as a material basis for the antioxidant activity of both ACC and TCC, and contribute to their traditional tonic effects.

Calcium oxalate kidney stone has become an urgent issue due to its high incidence and recurrence rate. Thus, it is necessary to explore for mechanisms of calcium oxalate stones formation. Previous studies demonstrated that oxalate crystals could induce the activation of nucleotide‑binding domain and leucine‑rich repeat‑containing family pyrin domain‑containing 3 (NLRP3) inflammasome and change the renal tubular epithelium adhesion. However, the type and molecular mechanism of NLRP3 inflammasome‑mediated calcium oxalate stones formation still need to be further investigated. In the present study, it was confirmed that the NLRP3‑gasdermin D (GSDMD) signaling was involved in oxalate‑induced cell injury in vitro and in vivo . Inhibition of reactive oxygen species production could effectively prevent the NLRP3 inflammasome formation in oxalate‑treated HK‑2 cells. NLRP3 gene silence could inhibit the DNA damage and cellular membrane injury of HK‑2 cells treated with oxalate. The ultrastructural changes of several organelles and particular structures, similar to typical cell pyroptosis, were observed in oxalate‑stimulated HK‑2 cells. NLRP3 gene silence could antagonize the oxalate‑induced injury and ultrastructure changes. Additionally, NSA (GSDMD inhibitor) could prevent the oxalate‑induced injury of membrane integrity in HK‑2 cells. Moreover, oxalate crystals were significantly decreased in GSDMD ‑/‑ mice compared with wild‑type mice with glyoxylic acid. Together, NLRP3‑GSDMD pathway was involved in the oxalate‑induced pyroptotic injury in HK‑2 cells. GSDMD and its cleavage form GSDMD‑N played an important role in the oxalate‑induced renal cell injury and oxalate calcium crystals formation in vitro and in vivo . This provided a new target for prevention and treatment of oxalate nephropathy and oxalate calcium stones.

Target-responsive aptamer hydrogels are increasingly used in the field of analytical sensing with different morphologies developed by various strategies. Herein, we developed a DNA hydrogel film combined with capillary self-driven action for the specific detection of the tumor marker EpCAM and further introduced Exo I for signal amplification. EpCAM aptamer was used as a crosslinking agent to construct the DNA hydrogel film. When EpCAM was present, it competed for binding with the EpCAM aptamer, resulting in a permeability change of the DNA hydrogel film attached to one end of the capillary, and leading to different solution flow rates through the capillaries that can be utilized for the quantitative detection of EpCAM. This method did not require any instrument and was easy to use. The distance the solution travelled through the capillary was quantified as the concentration of EpCAM, and only a small amount of DNA hydrogel was required for each detection. The detection limit of EpCAM was as low as 0.018 ng mL -1 , while offering the advantages of good stability and specificity, and showing great potential in point-of-care testing.

Background: Sarcopenia is a complication of asthma, and asthmatics with sarcopenia are at an increased risk of poor prognosis. Anti-inflammatory intervention promising as an effective measure to prevent sarcopenia among patients with asthma. Diet is an important way to regulate inflammation throughout the body. The dietary inflammatory index (DII) is an index that assesses an individual's overall dietary inflammatory potential. The relationship between DII and sarcopenia among patients with asthma is not clear., Objective: To examine the correlation between DII and the sarcopenia among individuals with asthma., Methods: The National Health and Nutrition Examination Survey (NHANES) was the data source utilized in this study, spanning two time periods from 1999 to 2006 and 2011 to 2018. The study encompassed 3,389 participants in total. DII was calculated using the results of the participants' 24-h dietary recall interviews. Patients were categorized into three groups based on the DII tertile: T1 group ( n  = 1,130), T2 group ( n  = 1,129), and T3 group ( n  = 1,130). Logistic regression analysis, taking into account the NHANES recommended weights, was performed to assess the relationship between DII and sarcopenia., Results: After full adjustment, there was a significant positive correlation between DII levels and the risk of sarcopenia in asthmatic patients (OR: 1.27, 95% CI: 1.13-1.42, p  < 0.001). Compared with T1 group, T3 group had higher risk of sarcopenia (T2: OR: 1.39, 95%CI: 0.88-2.18, p  = 0.157; T3: OR: 2.37, 95%CI: 1.47-3.83, p  < 0.001)., Conclusion: There was a significant positive correlation between DII and the risk of sarcopenia., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Lin, Su, Chen and Cai.)

Glioma stem cells (GSCs) are thought to be responsible for the initiation and progression of glioblastoma (GBM). GBM presents highly invasive growth with a very high recurrence rate, so it has become a clinical problem to be solved urgently. RNAseq demonstrates that thrombospondin 1 (THBS1) acts not only in the angiogenic core of glioma but also with a high degree of invasiveness and infiltration. Nevertheless, defects in the signaling pathway research lead to a poor prognosis in glioma patients. To investigate the relevant molecular mechanism and signal pathway of glioma stem cell behavior mediated by THBS1, U251 astroglioma cells and GSCs were taken as model cells for in vitro experiments. The biological effects of THBS1 on glioma proliferation, migration, and adhesion were evaluated using Cell Counting Kit-8(CCK8) assays, EdU incorporation assays, migration assays, Transwell assays, Western blotting, and RNAseq. We found that the knockout of the THBS1 gene by CRISPR/Cas9 promoted proliferation and migration in U251 cells and GSCs, as well as influencing cell cycle progression by regulating the TNF/MAPK/NF-κB and TGF-β/Smad signaling pathways. Moreover, U251 cells and GSCs showed different responses to THBS1 knockout, suggesting specific and potential targets for GSCs in signaling pathways mediated by THBS1., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2023. Published by Elsevier Inc.)

Blood glucose monitoring has become the weakest point in the overall management of diabetes in China. Long-term monitoring of blood glucose levels in diabetic patients has become an important means of controlling the development of diabetes and its complications, so that technological innovations in blood glucose testing methods have far-reaching implications for accurate blood glucose testing. This article discusses the basic principles of minimally invasive and non-invasive blood glucose testing assays, including urine glucose assays, tear assays, methods of extravasation of tissue fluid, and optical detection methods, etc., focuses on the advantages of minimally invasive and non-invasive blood glucose testing methods and the latest relevant results, and summarizes the current problems of various testing methods and prospects for future development trends.

As an indispensable strategy for tumor treatment, surgery may cause two major challenges: tumor recurrence and wound infection. Here, a thermoelectric therapeutic strategy is provided as either an independent cancer therapy or surgical adjuvant treatment. Bi 0.5 Sb 1.5 Te 3 (BST) and Bi 2 Te 2.8 Se 0.2 (BTS) nanoplates composed of Z-scheme thermoelectric heterojunction (BST/BTS) are fabricated via a two-step hydrothermal processes. The contact between BST and BTS constructs an interfacial electric field due to Fermi energy level rearrangement, guiding electrons in the conductive band (CB) of BTS combine with the holes in the valance band (VB) of BST, leaving stronger reduction/oxidation potentials of electrons and holes in the CB of BST and the VB of BTS. Moreover, under a mild temperature gradient, another self-built-in electric field is formed facilitating the migration of electrons and holes to their surfaces. Based on the PEGylated BST/BTS heterojunction, a novel thermoelectric therapy platform is developed through intravenous injection of BST/BTS and external cooling of the tumors. This thermoelectric strategy is also proved effective for combination cancer therapy with β-elemene. Moreover, the combination of heterojunction and hydrogel is administrated on the wound after surgery, achieving efficient residual tumor treatment and antibacterial effects., (© 2022 Wiley-VCH GmbH.)

Tumor hypoxia is a great physiological barrier for tumor treatment. The development of efficient detection and treatment methods for tumor hypoxia has great scientific and clinical significance. In this work, we investigated the potential of magnetotactic bacteria AMB-1 for magnetic resonance imaging (MRI)-guided magnetic hyperthermia treatment of hypoxic tumors. Our investigations reveal that AMB-1 bacteria can selectively migrate to the hypoxic regions of solid tumors due to their anaerobic characteristics, showing active deep tumor penetrability. Moreover, AMB-1 bacteria exhibit high MRI contrast and magnetic heating performances because of the excellent magnetic performance of their magnetosomes. In vivo studies demonstrate that AMB-1 can not only generate T 2 -weighted contrast signals in tumor tissue, but also efficiently ablate hypoxic solid tumors through the magnetic hyperthermia effect. We believe that this novel microbial therapy can be a potential weapon for hypoxic tumor treatment.

In the long process of human evolution, the Intestinal Bacteria has become intimately related to human health, producing many metabolites in the intestines that can affect cardiovascular disease. Today, the incidence of cardiovascular disease is rising, its treatment is becoming increasingly important, and new therapeutic targets are needed. Here we describe the effects of trimethylamine oxide (TMAO), lipid metabolism, phenolic compounds, indole sulfate (IS), oleuropein (OL), and hydroxytyrosol (HT) on atherosclerosis, heart failure, hypertension, and other cardiovascular diseases, as well as their mechanism of action. This study provides new ideas, new methods, and new directions for the treatment of cardiovascular disease.

The rapid recombination of electron-hole pairs and limited substrates are the most critical factors astricting the effect of catalytic therapy. Thus, two-dimensional interplanar heterojunction (BiOCl/Bi 2 O 3 ) that prolongs the lifetime of excited electrons and holes and extends the selectivity of substrates under ultrasound irradiation is prepared to facilitate high-performance cancer therapy. An edge modification displacing marginal BiOCl to Bi 2 O 3 is proposed to construct the interplanar heterojunction, promoting ultrathin nanosheets exfoliation due to the enhanced edge affinity with H 2 O. The spontaneously aligning Fermi levels mediate a built-in electric field-guided Z-scheme interplanar heterojunction, retard electron-hole pairs recombination, and improve redox potentials. Hence, these high-powered electrons and holes are capable of catalyzing diverse and stable substrates, such as the reduction reactions, O 2 → ·O 2 - and CO 2 → CO, and oxidation reactions, GSH → GSSG and H 2 O → ·OH. The Z-scheme interplanar heterojunction with the extending substrates selectivity completely breaks the tumor microenvironment limitation, exhibiting high anticancer activity.

Hydrogels have blossomed as superstars in various fields, owing to their prospective applications in tissue engineering, soft electronics and sensors, flexible energy storage, and biomedicines. Two-dimensional (2D) nanomaterials, especially 2D mono-elemental nanosheets (Xenes) exhibit high aspect ratio morphology, good biocompatibility, metallic conductivity, and tunable electrochemical properties. These fascinating characteristics endow numerous tunable application-specific properties for the construction of Xene-based hydrogels. Hierarchical multifunctional hydrogels can be prepared according to the application requirements and can be effectively tuned by different stimulation to complete specific tasks in a spatiotemporal sequence. In this review, the synthesis mechanism, properties, and emerging applications of Xene hydrogels are summarized, followed by a discussion on expanding the performance and application range of both hydrogels and Xenes., Competing Interests: The authors declare no competing interests., (© 2022 The Author(s).)

Background: The diverse manifestations of tuberculosis (TB) in chronic kidney disease (CKD) patients can cause difficulty in diagnosis, delayed treatment, even death. Therefore, this study investigated the clinical characteristics and the risk factors for mortality in CKD patients with TB., Methods: This retrospective study included 167 patients diagnosed with active TB at two tertiary medical centers in Chongqing within six years. Clinical characteristics and outcomes of anti-TB treatment in patients with and without CKD were collected, and the predictive mortality values of variables were analyzed., Results: Of the 167 patients, 66.7% (44/66) hemodialysis (HD), 41.1% (21/51) pre-HD, and 32.0% (16/50) non-CKD patients had extrapulmonary TB. The pleura and lymph node were the common sites in CKD patients. Clinical presentations of cough and hemoptysis in CKD patients were less common than those in non-CKD patients, 13.7% (16/117) of CKD patients even not having any clinical symptoms. The positive rates of tuberculin skin test, TB-polymerase chain reaction and acid-fast bacilli in sputum in HD patients were lower than those in pre-HD and non-CKD patients ( p <0.05). CKD patients were more prone to gastrointestinal and neurological side effects during anti-TB treatment. The mortality rates of non-CKD, pre-HD and HD patients was 6.1%, 31.9% and 37.3%, respectively. Multivariate Cox analysis revealed that age≥40 years (HR: 5.871; p =0.019), hypoalbuminemia (HR:2.879; p =0.004), CKD stage 4-5 (HR:4.719; p =0.018) and HD (HR:6.13; p =0.005) were associated with mortality., Discussion: CKD patients with TB have atypical clinical manifestations and high mortality. Age, hypoalbuminemia, CKD stage 4-5, and HD were independent predictors of mortality., Competing Interests: The authors report no conflicts of interest in this work., (© 2022 Xiao et al.)

Spontaneous bursts in neuronal networks with propagation involving a large number of synchronously firing neurons are considered to be a crucial feature of these networks both in vivo and in vitro . Recently, learning has been shown to improve the association and synchronization of spontaneous events in neuronal networks by promoting the firing of spontaneous bursts. However, little is known about the relationship between the learning phase and spontaneous bursts. By combining high-resolution measurement with a 4,096-channel complementary metal-oxide-semiconductor (CMOS) microelectrode array (MEA) and graph theory, we studied how the learning phase influenced the initiation of spontaneous bursts in cultured networks of rat cortical neurons in vitro . We found that a small number of selected populations carried most of the stimulus information and contributed to learning. Moreover, several new burst propagation patterns appeared in spontaneous firing after learning. Importantly, these "learning populations" had more hubs in the functional network that governed the initiation of spontaneous burst activity. These results suggest that changes in the functional structure of learning populations may be the key mechanism underlying increased bursts after learning. Our findings could increase understanding of the important role that synaptic plasticity plays in the regulation of spontaneous activity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Jia, Shao, Hu, Shi, Fan, Chen, Wang, Chen, Qiao and Li.)

Cancer therapies based on energy conversion, such as photothermal therapy (PTT, light-to-thermal energy conversion) and photodynamic therapy (PDT, light-to-chemical energy conversion) have attracted extensive attention in preclinical research. However, the PTT-related hyperthermia damage to surrounding tissues and shallow penetration of PDT-applied light prevent further advanced clinical practices. Here, we developed a thermoelectric therapy (TET) based on thermoelectric materials constructed p-n heterojunction (SrTiO 3 /Cu 2 Se nanoplates) on the principle of light-thermal-electricity-chemical energy conversion. Upon irradiation and natural cooling-induced the temperature gradient (35-45 o C), a self-build-in electric field was constructed and thereby facilitated charges separation in bulk SrTiO 3 and Cu 2 Se. Importantly, the contact between SrTiO 3 (n type) and Cu 2 Se (p type) constructed another interfacial electric field, further guiding the separated charges to re-locate onto the surfaces of SrTiO 3 and Cu 2 Se. The formation of two electric fields minimized probability of charges recombination. Of note, high-performance superoxide radicals and hydroxyl radicals' generation from O 2 and H 2 O under catalyzation by separated electrons and holes, led to intracellular ROS burst and cancer cells apoptosis without apparent damage to surrounding tissues. Construction of bulk and interfacial electric fields in heterojunction for improving charges separation and transfer is also expected to provide a robust strategy for diverse applications., Competing Interests: The authors declare no conflict of interest., (© 2022 The Authors.)

Objective: To explore the effects of self-care plus forecasting nursing on the treatment outcomes and emotions in nasopharyngeal carcinoma patients undergoing radiotherapy., Methods: Eighty nasopharyngeal carcinoma patients after radiotherapy admitted to our hospital from February 2020 to August 2021 were selected. The patients were allocated into an observation group ( n  = 40) and an experimental group ( n  = 40) according to different nursing protocols. The observation group received traditional nursing intervention, whereas the experimental group received self-care plus forecasting nursing intervention. The levels of the indexes (quality of life, score on the Zung Self-Rating Anxiety Scale (SAS), score on the Zung Self-Rating Depression Scale (SDS), and adverse reaction) were compared between the two groups., Results: The score of the experimental group for the quality of life was significantly higher than that of the observation group ( P < 0.05); the SAS and SDS scores of the experimental group after nursing intervention were significantly lower than those of the observation group ( P < 0.05); the incidence of adverse reactions in the experimental group during radiotherapy was significantly lower than that of the observation group ( P < 0.05)., Conclusion: The self-care plus forecasting nursing intervention is effective in postradiotherapy patients with nasopharyngeal carcinoma. The technique is proved effective to improve the quality of life, reduce anxiety and depression, and decrease the incidence of adverse reactions in patients during treatment. These features make the technique worthy of a wider clinical application., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Liqun Chen et al.)

With the rapid development of nanotechnology and nanoscience, nanosafety assessment has raised public concern. Although many studies have illustrated that nanomaterials could lead to genotoxicity, the early alterations of DNA methylation with nanomaterials under low-dose exposure have not been completely clear. In this study, we investigated the potential effect and molecular mechanism of AgNPs on the alternation of DNA methylation fingerprints in HEK293T cells under sublethal exposure. Intriguingly, silver nanoparticle treatment increased 5-mC level and changed methylation-related enzyme contents. Mechanistically, we scrutinized the changes in the molecular signaling and biological functions by means of MeDIP-Seq and RNA-seq. Our results revealed that AgNPs might undermine a number of vital regulatory networks including the metabolic processes, biological regulation and other cellular processes. More specifically at the DNA methylation fingerprints, there were 12 up-regulated and simultaneous hypomethylated genes, and 22 down-regulated and concomitant hypermethylated genes in HEK293T cells responding to AgNPs. Notably, these genes were primarily involved in lipid metabolism and ion metabolism. Together, these responsive genes might be used as early sensitive indicators for the variations of early epigenetic integrity through changing the DNA methylation fingerprints, as reflective of biological risk and toxicity of silver nanoparticles under realistic exposure scenarios., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Chen, Sheng, Wang, Zhang, Qi and Chen.)

Objective: To explore the differential efficacy of chemoradiotherapy combined with adoptive immunotherapy and radiochemotherapy alone in patients with non-small-cell lung cancer (NSCLC)., Methods: Qualified randomized controlled trial (randomized controlled trial, RCT), or nonrandomized concurrent controlled trial (NRCCT), published in various databases, including PubMed, EMBASE, Chinese journal full-text database, Medline, Cochrane database, and VIP Chinese database, and the Revman5. 0 software performed the data analysis., Results: We found the significantly different curative effect between the experimental and control groups (OR = 1.94, 95% CI (1.46, 2.58), P < 0.001, I 2 = 0%, Z = 4.59), effect of adoptive immunotherapy on the progression of disease (OR = 1.80, 95% CI (1.38, 2.35), P < 0.001, I 2 = 0%, Z = 4.33), adoptive immunotherapy on overall survival (OR = 2.19, 95% CI (1.60, 2.99), P < 0.001, I 2 = 0%, Z = 4.91), and adverse effects of adoptive immunotherapy (OR = 1.76, 95% CI (1.25, 2.48), P = 0.001, I 2 = 0%, Z = 3.26)., Conclusion: Adoptive immunotherapy combined with microradiotherapy can decrease the recurrence of NSCLC and improve patient survival, as well as early patients can be benefited more significantly from immunotherapy., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Zhiming Fan et al.)

Organ size is an important agronomic trait. Small peptides function in various stages of plant growth, but their regulatory mechanisms in organ growth remain poorly understood. Here, we characterize a novel small peptide, AtZSP1, which positively regulates organ size in Arabidopsis. Loss-of-function mutant atzsp1-1 exhibited small organs, whereas AtZSP1 overexpression plants (p35S:AtZSP1#1) produced larger organs. Differentially expressed genes in the shoots of atzsp1-1 and p35S:AtZSP1#1 were enriched in the cytokinin pathway. Further analysis on shoots of atzsp1-1 showed that endogenous cytokinin levels were significantly reduced, consistent with reduced expression of the cytokinin response genes ARR5/6/7 and a decrease in pARR5:GUS activity. By contrast, cytokinin levels were elevated in p35S:AtZSP1#1. These results indicate that AtZSP1 affects shoot size via changes in cytokinin levels. AtZSP1 is ubiquitously expressed and encodes a 57-amino acid endomembrane-associated protein that is highly conserved among plant species. AtZSP1 interacts with ROCK1 at the endomembrane. Genetic analysis confirmed that the small organs and low cytokinin levels in atzsp1-1 shoots are partially suppressed by the rock1-4 mutation, suggesting that AtZSP1 may function in a common pathway with ROCK1 to antagonistically regulate organ growth. Our study identified an unknown small peptide, AtZSP1, and defined its function in regulating organ size in Arabidopsis., (© 2022 The Authors. New Phytologist © 2022 New Phytologist Foundation.)

As the market size of the cosmetics industry increases, the safety and effectiveness of new products face higher requirements. The marine environment selects for species of micro-organisms with metabolic pathways and adaptation mechanisms different from those of terrestrial organisms, resulting in their natural products exhibiting unique structures, high diversity, and significant biological activities. Natural products are usually safe and non-polluting. Therefore, considerable effort has been devoted to searching for cosmetic ingredients that are effective, safe, and natural for marine micro-organisms. However, marine micro-organisms can be difficult, or impossible, to culture because of their special environmental requirements. Metagenomics technology can help to solve this problem. Moreover, using marine species to produce more green and environmentally friendly products through biotransformation has become a new choice for cosmetic manufacturers. In this study, the natural products of marine micro-organisms are reviewed and evaluated with respect to various cosmetic applications., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ding, Wu and Chen.)

Restriction of pollen germination before the pollen grain is pollinated to stigma is essential for successful fertilization in angiosperms. However, the mechanisms underlying the process remain poorly understood. Here, we report functional characterization of the MAPKKK kinases, MAP3Kε1 and MAP3Kε2, involve in control of pollen germination in Arabidopsis. The two genes were expressed in different tissues with higher expression levels in the tricellular pollen grains. The map3kε1 map3kε2 double mutation caused abnormal callose accumulation, increasing level of JA and precocious pollen germination, resulting in significantly reduced seed set. Furthermore, the map3kε1 map3kε2 double mutations obviously upregulated the expression levels of genes in JA biosynthesis and signaling. The MAP3Kε1/2 interacted with MOB1A/1B which shared homology with the core components of Hippo singling pathway in yeast. The Arabidopsis mob1a mob1b mutant also exhibited a similar phenotype of precocious pollen germination to that in map3kε1 map3kε2 mutants. Taken together, these results suggested that the MAP3Kεs interacted with MOB1s and played important role in restriction of the precocious pollen germination, possibly through crosstalk with JA signaling and influencing callose accumulation in Arabidopsis.

Background: Hypertension is a chronic disease affecting middle-aged and elderly patients worldwide. Self-management behavior plays a critical role in maintaining blood pressure. Roy adaptation model (RAM), which was proposed by Roy in 1970, has been used to guide hypertension nursing to improve self-management behavior of elderly patients. In the study, to explore the effect of nursing based on the RAM on the self-management behavior of elderly hypertensive patients., Methods: A total of 120 elderly hypertensive patients admitted from June 2020 to March 2021 were selected and randomly divided into a control group and observation group based on odd and even numbers of the admission order, with 60 cases in each group. The control group received routine nursing measures while the observation group was given nursing based on the RAM. The self-management behavior, medication compliance, quality of life, and blood pressure control effect were compared between the two groups., Results: The scores of the self-efficacy and self-management behaviors of the observation group and the total score of the scale were higher than those of the control group (P<0.05); the observation group patients' medication compliance score was 6.57±1.47, which was higher than that of the control group (4.90±2.16) (P<0.01); physiological function, physical pain, energy, social function, emotional function, mental health scores, and total scores of the SF-36 scale in the observation group were all higher than those of the control group (P<0.05), while comparison of the general health status dimension scores showed no statistically significant difference; the systolic blood pressure and diastolic blood pressure of the observation group were respectively lower than those of the control group (P<0.05); The blood pressure control compliance rate of the observation group was 85.4%, which was higher than that of the control group 64.6% (P<0.05)., Conclusions: Nursing intervention based on Roy's adaptation model can better enhance the self-efficacy and self-management ability of elderly hypertensive patients, have a positive effect on promoting healthy behavior changes and improving the quality of life, improve medication compliance, and achieve better blood pressure control effects., Trial Registration: Chinese Clinical Trial Registry ChiCTR2100052466.

Background: Young females tend to overestimate their weight status, which might induce unhealthy weight loss intentions and behaviours. This study aimed to examine weight perception measured by visual and verbal descriptions and its correlation with weight loss intentions among female nursing students., Methods: A cross-sectional survey was conducted among 600 female nursing students from four medical colleges in Shanghai, China. The participants rated perceptions of their weight by selecting a silhouette from the female Photographic Figure Rating Scale (PFRS) and one of the following verbal descriptions: "very underweight", "slightly underweight", "normal", "overweight" or "obese". Weight loss intentions were measured using the question "How often do you want to lose weight?". Body mass index (BMI) was calculated from self-reported height and weight. Data were analysed using univariate and ordinal logistic regression analyses., Results: The accuracy of weight perceptions measured by verbal descriptions and visual descriptions was 44.50% and 55%, respectively. In females with underweight BMI ( n = 135), 88.15% and 49.63% accurately classified their weight using visual descriptions and verbal descriptions, respectively. These females were more likely to overestimate (53.83% vs. 14.50%) and less likely to underestimate (1.67% vs. 30.50%) their weight when using verbal descriptions than when using visual descriptions. For verbal descriptions, weight overestimation was associated with weight loss intentions (odds ratio, 1.80; 95% confidence interval, 1.25-2.60). However, for visual descriptions, the two variables were not associated., Conclusions: A mismatch occurred between weight perceptions measured by the two methods and BMI status among female nursing students. Compared with verbal descriptions, visual descriptions had higher weight perception accuracy. However, weight overestimation measured by verbal descriptions was more likely to be associated with stronger intentions to lose weight than that of visual descriptions. These findings suggest that methodological discrepancies should be taken into account when measuring weight perception in future studies.

Because of resistance to bio-macromolecular adhesion, antifouling hydrogels have attracted great attention in biomedical field. But traditional antifouling hydrogels made by hydrophilic polymers are always poor of mechanical properties. Herein, a new hybrid ionic-covalent cross-linked double network (DN) hydrogel was prepared by a simple one-pot method based on sodium alginate and the zwitterionic material carboxybetaine acrylamide (CBAA). The DN hydrogel has good mechanical properties, including high elastic modulus (0.28 MPa), high tensile strength (0.69 MPa), as well as good self-recovery capability. More importantly, the DN hydrogel is highly resistance to the adsorption of non-specific protein, cells, bacteria and algae, exhibiting an outstanding antifouling property. The in vitro and in vivo experiments prove that the DN hydrogel is highly biocompatible. This study provides a new strategy for the preparation of antifouling DN hydrogels with good mechanical properties for different needs, such as tissue scaffolds, wound dressings, implantable devices, and other fields., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

We report compounds 5 (CG416) and 6 (CG428) as two first-in-class tropomyosin receptor kinase (TRK) degraders that target the intracellular kinase domain of TRK. Degraders 5 and 6 reduced levels of the tropomyosin 3 (TPM3)-TRKA fusion protein in KM12 colorectal carcinoma cells and inhibited downstream PLCγ1 signaling at sub-nanomolar concentrations. Both degraders also degraded human wild-type TRKA with similar potency. Interestingly, both degraders, especially 6 , showed selectivity for the degradation of endogenous TPM3-TRKA over ectopically expressed ATP/GTP binding protein-like 4 (AGBL4)-TRKB or ETS variant transcription factor 6 (ETV6)-TRKC fusion proteins in KM12 cells. Global proteomic profiling assays demonstrated that 5 is highly selective for the intended target. TPM3-TRKA protein degradation induced by 5 and 6 was further confirmed to be mediated through cereblon and the ubiquitin-proteasome system. Compared with the parental TRK kinase inhibitor, both degraders exhibited higher potency for inhibiting growth of KM12 cells. Moreover, both 5 and 6 showed good plasma exposure levels in mice. Therefore, 5 and 6 are valuable chemical tool compounds for investigating the in vivo function of TRK fusion during tumorigenesis. Our study also paves the way for pharmacological degradation of TRK.

With advances in modern medicine, diverse tumor therapies have been developed. However, because of a lack of effective methods, the delivery of drugs or micromolecules in the human body has many limitations. Biomaterials are natural or synthetic functional materials that are prone to contact or interact with living systems. Therefore, the application of biomaterials provides innovative anti-tumor strategies, especially in tumor targeting, chemotherapy sensitization, tumor immunotherapy. The combination of biomaterials and drugs provides a promising strategy to overcome the biological barriers of drug delivery. Nanomaterials can target specific tumor sites to enhance the efficiency of tumor therapies and decrease the toxicity of drug through passive targeting, active targeting and direct targeting. Additionally, biomaterials can be used to enhance the sensitivity of tumor cells to chemotherapy drugs. Furthermore, modifiable biomaterials can induce effective anti-tumor immune response. Currently, the developmental trend of biomaterial for drug delivery is motivated by the combination and diversification of different therapies. With interdisciplinary development, a variety of anti-tumor strategies will emerge in an endless stream to bring great hope for tumor therapy. In this review, we will discuss the anti-tumor strategies based on nanoparticles and injectable scaffolds., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objective: To develop a method for the rapid isolation of rat RPE cells with high yield and maintain its epithelial state in modified culture system., Methods: The eyeballs were incubated with dispase. The retina was isolated with RPE attached and cut into several pieces. Following a brief incubation in growth medium, large RPE sheets can be harvested rapidly. RPE cells were divided into four groups and cultured for several weeks, that is, (1) in cell culture dishes with 10% FBS containing medium (CC dish-FBS), (2) in petri dishes with 10% FBS containing medium (Petri dish-FBS), (3) in cell culture dishes with N2 and B27 containing medium (CC dish-N2B27), and (4) in petri dishes with N2 and B27 containing medium (Petri dish-N2B27). Morphological and biological characteristics were investigated using light microscopy, Q-PCR, and western blot., Results: The retina would curl inwardly during the growth medium incubation period, releasing RPE sheets in the medium. Compared with low density group (5,000 cells/cm 2 ), RPE cells plated at high density (15,000 cells/cm 2 ) can maintain RPE morphology for a more extended period. Meanwhile, plating RPE cells at low density significantly reduced the expression of RPE cell type-specific genes (RPE65, CRALBP, and bestrophin) and increased the expression of EMT-related genes (N-cadherin, fibronectin, and α -SMA), in comparison with the samples from the high density group. The petri dish culture condition reduced cell adhesion and thus inhibited RPE cell proliferation. As compared with other culture conditions, RPE cells in the petri dish-N2B27 condition could maintain RPE phenotype with increased expression of RPE-specific genes and decreased expression of EMT-related genes. The AKT/mTOR pathway was also decreased in petri dish-N2B27 condition., Conclusion: The current study provided an alternative method for easy isolation of RPE cells with high yield and maintenance of its epithelial morphology in the petri dish-N2B27 condition., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2020 Hui Lou et al.)

Objective: To assess oral health knowledge, beliefs and practices among community-dwelling older adults in Shanghai, China., Background: China is ageing faster than other developing countries. Four National Oral Health Surveys have been carried out in China between 1983 and 2015, focused on clinical oral examinations., Materials and Methods: A cross-sectional study was conducted among 983 participants aged 60-93 years old, drawn from two community health service centres of Pudong New Area in Shanghai. Data were collected using a Chinese language questionnaire of oral health knowledge, beliefs and practices based on the Knowledge, Attitudes (beliefs) and Practices (KAP) model. The scale ranges were knowledge 0-19, beliefs 0-17 and practices 0-55, where a higher score indicated a more accurate perception. Multivariate analysis explored the related factors using IBM SPSS Statistics version 22.0., Results: Mean (SD) scores of this questionnaire were oral health knowledge 13.0 (3.6), beliefs 13.0 (3.2) and practices 31.2 (11.2). Geographic location, age group, employment status, education and monthly household income showed significant statistical association with these scores (P < .001). Only three sociodemographic variables (education, age group and employment status) remained significant after further multiple regression analysis (P < .001)., Conclusions: The level of oral health knowledge, beliefs and practices among older adults in Shanghai, China, was not high. Younger and working individuals with higher level of education showed good oral health knowledge, beliefs and practices. Community-based oral health strategies are needed to increase oral health knowledge, in particular of oral daily cleaning, and improve beliefs and practices in regular dental visits., (© 2020 Gerodontology Association and John Wiley & Sons Ltd.)

A rapid PCR technology was developed to differentiate Cervus antlers species and adulteration based on the difference in mitochondrial genome. Three specifically designed primer sets were confirmed to have high inter-species specificity and good intra-species stability. Limits of detection were estimated to be 1 ng of genomes for reindeer and 10 ng for the other species. Especially, when the mixture of Cervus antlers and reindeer or sambar was assayed, these primer sets still exhibited strong capability of differentiation but not the conventional COI barcoding. By using the newly developed approach, five batches out of fourteen commercial Cervus antler products were identified to be fake products made from reindeer antlers. It has shown its good potential to be extensively applied in the identification of counterfeits or adulterates of Cornu Chinese medicines for their pulverized and processed form, and even the traditional Chinese patent medicines composed of these species.

BRAF is among the most frequently mutated oncogenes in human cancers. Multiple small molecule BRAF kinase inhibitors have been approved for treating melanoma carrying BRAF-V600 mutations. However, the benefits of BRAF kinase inhibitors are generally short-lived. Small molecule-mediated targeted protein degradation has recently emerged as a novel pharmaceutical strategy to remove disease proteins through hijacking the cellular ubiquitin proteasome system (UPS). In this study, we developed thalidomide-based heterobifunctional compounds that induced selective degradation of BRAF-V600E, but not the wild-type BRAF. Downregulation of BRAF-V600E suppressed the MEK/ERK kinase cascade in melanoma cells and impaired cell growth in culture. Abolishing the interaction between degraders and cereblon or blocking the UPS significantly impaired the activities of these degraders, validating a mechanistic role of UPS in mediating targeted degradation of BRAF-V600E. These findings highlight a new approach to modulate the functions of oncogenic BRAF mutants and provide a framework to treat BRAF-dependent human cancers.

Introduction: CRISPR/CAS9 systems, which can be utilized in vitro biological experiments, have recently captured much attention for their important roles and benefits. However, full realization of the potential of CRISPR/CAS9 approaches requires addressing many challenges and side effects. The expression of genes and potential side effects of CRISPR/CAS9 in human cells remains to be elucidated. The aim of our study was to explore the effect of CRISPR/CAS9 on gene expression in 293T cells., Methods: A Cas9-expressing PX458 plasmid and Cas9-deactivated PX458-T2A plasmid were used to study the role of CRISPR/CAS9 on regulating gene expression in 293T cells. Gene expression in 293T cells after transfection of the PX458 plasmid or PX458-T2A plasmid was detected by RNA sequencing and correlative statistical analysis. Differential gene expression in both PX458 transfected 293T cells and PX458-T2A transfected 293T cells compared with normal 293T cells was detected using quantitative reverse transcription polymerase chain reaction (RT qPCR). The mRNA and protein levels were measured using reverse transcription PCR and Western blot. Co-IP assay combined with shotgun LC-MS/MS were used to investigate the differences of NGFR-interaction proteins between PX458 transfected 293T cells and PX458-T2A transfected 293T cells., Results: In this study, we observed that PX458 plasmid transfection and Cas9 expression can affect the expression of different genes, including FOSB (FBJ murine osteosarcoma viral oncogene homolog B), IL-11 (Interleukin-11), MMP1 (matrix metalloproteinase), CYP2D6 (CytochromeP4502D6), and NGFR (matrix metalloproteinase 1). Downregulation of NGFR after PX458 transfection was confirmed by RT qPCR and western blot analysis. NGFR expression was significantly lower in PX458 transfected 293T cells than in normal 293T cells and PX458-T2A transfected 293T cells. The co-IP dilutions analyzed by shotgun LC-MS/MS showed a total of 183 proteins interact with NGFR in PX458 transfected 293T cells while 221 proteins interact with NGFR were identified in PX458-T2A transfected 293T cells using the MASCOT engine., Conclusions: Cas9 expression by transfection of the PX458 plasmid was negatively correlated with the NGFR mRNA level and NGFR protein expression in 293T cells, while PX458-T2A, in which Cas9 is deactivated, did not affect NGFR expression. The decrease in NGFR expression also affects the amount of proteins that interact with NGFR. These results suggest that the effect of Cas9 on NGFR expression and the expression of other genes should be noticed when developing cell-based studies and therapies utilizing CRISPR/CAS9 systems., Competing Interests: All authors, including Liqun Chen, Huilian Zhang Linteng Zhang, Wenbo Li, Fengtian Fan, Xiaoyun Wu, Xueling Wu, Jun Lin, declare that they have no competing interests., (© Biomedical Engineering Society 2019.)