Publications by authors named "Fan Xia"

529 Publications

Regional and functional division of functional elements of solid-state nanochannels for enhanced sensitivity and specificity of biosensing in complex matrices.

Nat Protoc 2021 Jul 28. Epub 2021 Jul 28.

State Key Laboratory of Biogeology and Environmental Geology, Engineering Research Center of Nano-Geomaterials of Ministry of Education, Faculty of Materials Science and Chemistry, China University of Geosciences (CUG), Wuhan, P. R. China.

Solid-state nanochannels (SSNs) provide a promising approach for biosensing due to the confinement of molecules inside, their great mechanical strength and diversified surface chemical properties; however, until now, their sensitivity and specificity have not satisfied the practical requirements of sensing applications, especially in complex matrices, i.e., media of diverse constitutions. Here, we report a protocol to achieve explicit regional and functional division of functional elements at the outer surface (FE) and inner wall (FE) of SSNs, which offers a nanochannel-based sensing platform with enhanced specificity and sensitivity. The protocol starts with the fabrication and characterization of the distribution of FE and FE. Then, the evaluation of the contributions of FE and FE to ionic gating is described; the FE mainly regulate ionic gating, and the FE can produce a synergistic effect. Finally, hydrophobic or highly charged FE are applied to ward off interference molecules, non-target molecules that may affect the ionic signal of nanochannels, which decreases false signals and helps to achieve the highly specific ionic output in complex matrices. Compared with other methods currently available, this method will contribute to the fundamental understanding of substance transport in SSNs and provide high specificity and sensitivity in SSN-based analyses. The procedure takes 3-6 d to complete.
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http://dx.doi.org/10.1038/s41596-021-00574-6DOI Listing
July 2021

Molecular mechanisms and clinical management of cancer bone metastasis.

Bone Res 2020 Jul 29;8(1):30. Epub 2020 Jul 29.

Laboratory of Aging Research and Cancer Drug Targets, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, No. 17, Block 3, Southern Renmin Road, Chengdu, 610041, Sichuan, P.R. China.

As one of the most common metastatic sites of malignancies, bone has a unique microenvironment that allows metastatic tumor cells to grow and flourish. The fenestrated capillaries in the bone, bone matrix, and bone cells, including osteoblasts and osteoclasts, together maintain the homeostasis of the bone microenvironment. In contrast, tumor-derived factors act on bone components, leading to subsequent bone resorption or excessive bone formation. The various pathways involved also provide multiple targets for therapeutic strategies against bone metastases. In this review, we summarize the current understanding of the mechanism of bone metastases. Based on the general process of bone metastases, we specifically highlight the complex crosstalk between tumor cells and the bone microenvironment and the current management of cancer bone metastases.
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http://dx.doi.org/10.1038/s41413-020-00105-1DOI Listing
July 2020

Exploring the contribution of charged species at the outer surface to the ion current signal of nanopores: a theoretical study.

Analyst 2021 Jul 23. Epub 2021 Jul 23.

State Key Laboratory of Biogeology and Environmental Geology, Engineering Research Center of Nano-Geomaterials of Ministry of Education, Faculty of Materials Science and Chemistry, China University of Geosciences, Wuhan, P. R. China.

Nanopores attached to charged species realize the artificial regulation of ion transport by the electrostatic effect in nanoconfines, produce a sensitive ion current signal and play a critical role in nanopore-based analyses. However, until now, the contribution of the charged species at the outer surface, an inherent component of nanopores, to the ion current signal has not yet been fully investigated. Here, we theoretically investigate the contribution of the charged species at the outer surface to the ion current signal of a conical nanopore. The results indicate that when the electrostatic effect at the tip of the conical nanopore is strengthened, the contribution from the charged species at the outer surface to the ionic current signal becomes stronger or even predominant compared with that of the inner walls. This effect can be further enhanced using nanopore arrays with small openings and low pore density in a low concentration electrolyte. This work focuses on the working mechanism of nanopores with a high-efficient signal conversion and promotes the performance of nanopores with a regional distribution of charged probes and targets.
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http://dx.doi.org/10.1039/d1an00826aDOI Listing
July 2021

Tertiary sulphonamide derivatives as dual acting small molecules that inhibit LSD1 and suppress tubulin polymerisation against liver cancer.

J Enzyme Inhib Med Chem 2021 Dec;36(1):1563-1572

The First Hospital of Jilin University, Changchun, China.

A series of tertiary sulphonamide derivatives were synthesised and evaluated for their antiproliferative activity against liver cancer cell lines (SNU-475, HepG-2, and Bel-7402). Among these tertiary sulphonamides, compound displayed the best anti-liver cancer activity against Bel-7402 cells with an IC value of 0.32 μM. Compound could effectively inhibit tubulin polymerisation with an IC value of 1.27 μM. Meanwhile, it selectively suppressed LSD1 with an IC value of 63 nM. It also concentration-dependently inhibited migration against Bel-7402 cells. Importantly, tertiary sulphonamide exhibited the potent antitumor activity . All these findings revealed that compound might be a tertiary sulphonamide-based dual inhibitor of tubulin polymerisation and LSD1 to treat liver cancer.
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http://dx.doi.org/10.1080/14756366.2021.1917564DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8291071PMC
December 2021

Ceria Nanozyme-Integrated Microneedles Reshape the Perifollicular Microenvironment for Androgenetic Alopecia Treatment.

ACS Nano 2021 Jul 19. Epub 2021 Jul 19.

Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.

Androgenetic alopecia (AGA) is highly prevalent in current society but lacks effective treatments. The dysregulation of the hair follicle niche induced by excessive reactive oxygen species (ROS) and insufficient vascularization in the perifollicular microenvironment is the leading cause of AGA. Herein, we designed a ceria nanozyme (CeNZ)-integrated microneedles patch (Ce-MNs) that can alleviate oxidative stress and promote angiogenesis simultaneously to reshape the perifollicular microenvironment for AGA treatment. On the basis of the excellent mechanical strength of Ce-MNs, the encapsulated CeNZs with catalase- and superoxide-mimic activities can be efficiently delivered into skin to scavenge excessive ROS. Moreover, the mechanical stimulation induced by the administration of MNs can remodel the microvasculature in the balding region. Compared with minoxidil, a widely used clinical drug for AGA treatment, Ce-MNs exhibited accelerated hair regeneration in the AGA mouse model at a lower administration frequency without inducing significant skin damage. Consequently, such a safe and perifollicular microenvironment-shaping MNs patch shows great potential for clinical AGA treatment.
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http://dx.doi.org/10.1021/acsnano.1c05272DOI Listing
July 2021

Adhesive and tough hydrogels: from structural design to applications.

J Mater Chem B 2021 Aug;9(30):5954-5966

Faculty of Materials Science and Chemistry, China University of Geosciences, Wuhan 430074, China.

In recent years, multifunctional hydrogels have garnered great interest. Usually, there is a contradiction between the toughness and interface adhesion of traditional hydrogels. In engineering and medical applications, hydrogels need to have good adhesive properties and toughness. The design of functional hydrogels with strong adhesion and high toughness is key to their application. In this review, the research progress of adhesive and tough hydrogels in recent years is outlined. Specifically, the structural design (such as integrated, layered, and gradient structures) and applications (such as cartilage repair, drug delivery, strain sensors, tissue adhesives, soft actuators, and supercapacitors) of adhesive and tough hydrogels are classified and discussed, providing new insights on their design and development.
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http://dx.doi.org/10.1039/d1tb01166aDOI Listing
August 2021

Triboelectric Nanogenerator-Based Sensor Systems for Chemical or Biological Detection.

Adv Mater 2021 Jul 9:e2008276. Epub 2021 Jul 9.

Department of Mechanical Engineering, Ulsan National Institute of Science and Technology (UNIST), 50 UNIST-gil, Ulsan, 44919, Republic of Korea.

The rapid advances in the Internet of things and wearable devices have created a massive platform for sensor systems that detect chemical or biological agents. The accelerated development of these devices in recent years has simultaneously aggravated the power supply problems. Triboelectric nanogenerators (TENGs) represent a thriving renewable energy technology with the potential to revolutionize this field. In this review, the significance of TENG-based sensor systems in chemical or biological detection from the perspective of the development of power supply for biochemical sensors is discussed. Further, a range of TENGs are classified according to their roles as power supplies and/or self-powered active sensors. The TENG powered sensor systems are further discussed on the basis of their framework and applications. The working principles and structures of different TENG-based self-powered active sensors are presented, along with the classification of the sensors based on these factors. In addition, some representative applications are introduced, and the corresponding challenges are discussed. Finally, some perspectives for the future innovations of TENG-based sensor systems for chemical/biological detection are discussed.
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http://dx.doi.org/10.1002/adma.202008276DOI Listing
July 2021

lncRNA NEAT1 aggravates sepsis-induced lung injury by regulating the miR-27a/PTEN axis.

Lab Invest 2021 Jul 8. Epub 2021 Jul 8.

NHC Key Laboratory of Pulmonary Immune-related Diseases, Guizhou Provincial People's Hospital GZU, Guiyang, P. R. China.

Sepsis is an acute inflammatory reaction and a cause of acute respiratory distress syndrome (ARDS). In the present study, we explored the roles and underlying mechanism of the lncRNA Nuclear enriched abundant transcript 1 (NEAT1) in ARDS. The expression levels of genes, proteins and pro-inflammatory cytokines in patients with ARDS, LPS-stimulated cells and septic mouse models were quantified using qPCR, western blotting and ELISA assays, respectively. The molecular targeting relationship was validated by conducting a dual-luciferase reporter assay. Cell proliferation was assessed using the Cell Counting Kit-8 (CCK-8) assay. The cell cycle phase was determined by flow cytometry assay. The expression levels of NEAT1 and pro-inflammatory cytokines were higher in patients with ARDS and septic models than in controls. Knockdown of NEAT1 significantly increased cell proliferation and cycle progression and prolonged mouse survival in vitro and in vivo. Mechanistically, miR-27a was identified as a downstream target of NEAT1 and directly inhibited PTEN expression. Further rescue experiments revealed that inhibition of miR-27a impeded the promoting effects of NEAT1 silence on cell proliferation and cycle progression, whereas inhibition of PTEN markedly weakened the inhibitory effects of NEAT1 overexpression on cell proliferation and cycle progression. Altogether, our study revealed that NEAT1 plays a promoting role in the progression of ARDS via the NEAT1/miR-27a/PTEN regulatory network, providing new insight into the pathologic mechanism behind ARDS.
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http://dx.doi.org/10.1038/s41374-021-00620-7DOI Listing
July 2021

Role of Complement Component 3 in Early Erythrolysis in the Hematoma After Experimental Intracerebral Hemorrhage.

Stroke 2021 Aug 28;52(8):2649-2660. Epub 2021 Jun 28.

Department of Neurosurgery, University of Michigan, Ann Arbor (M.W., F.X., S.W., Y.H., R.F.K., G.X.).

[Figure: see text].
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http://dx.doi.org/10.1161/STROKEAHA.121.034372DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8316397PMC
August 2021

A novel analytical strategy for discriminating antibiotic mycelial residue adulteration in feed based on ATR-IR and microscopic infrared imaging.

Spectrochim Acta A Mol Biomol Spectrosc 2021 Nov 9;261:120060. Epub 2021 Jun 9.

College of Engineering, China Agricultural University, Beijing 100083, PR China. Electronic address:

The Antibiotic mycelial residue (AMR) contains antibiotic residue, there are safety risks if it is used illegally in feed. This study investigated the feasibility of qualitative identification of AMR in protein feed and self-prepared feed based on attenuated total reflection mid-infrared spectrum (ATR-IR) and microscopic infrared imaging. Cottonseed meal (CM), soybean meal (SM), distillers dried grains with solubles (DDGS), nucleotide residue (NR), oxytetracycline residue (OR) and streptomycin sulfate residue (SR) and two self-prepared feed (broiler and pig) were used as research objects. The results showed that there were characteristic peaks at 1614 cm, 1315 cm, 779 cm, 514 cm in the ATR-IR spectra of AMR, which were related to calcium oxalate hydrate. After detection, the content of total calcium and calcium oxalate in AMR were higher than those in protein feed. ATR-IR can quickly realize the qualitative discrimination of pure material samples. The combination of ATR-IR and partial least squares discriminant analysis (PLSDA) was effective in discriminating AMR from CM and SM with a single component (the classification errors were 0), but it cannot meet the discrimination of AMR from the fermented protein feed (such as DDGS and NR, the classification errors were 0.10 and 0.12) and self-prepared feed with complex components. Compared with ATR-IR, microscopic infrared imaging was less affected by the sample complexity. Multi-component samples belong to physical mixing and will not affect the infrared spectra of each component. Therefore, microscopic infrared imaging combined with effective information extraction algorithms such as cosine similarity can distinguish OR in the fermented protein feed and self-prepared feed. The above results showed that the advantages of ATR-IR and microscopic infrared imaging were complementary, which provided a new idea for the discrimination analysis of illegal feed additives.
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http://dx.doi.org/10.1016/j.saa.2021.120060DOI Listing
November 2021

Dynamic nanoassembly-based drug delivery system (DNDDS): Learning from nature.

Adv Drug Deliv Rev 2021 Aug 15;175:113830. Epub 2021 Jun 15.

Frontiers Science Center for Transformative Molecules, School of Chemistry and Chemical Engineering, National Center of Translational Medicine, Shanghai Jiao Tong University, Shanghai 200240, China; Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China; Hangzhou Institute of Innovative Medicine, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China. Electronic address:

Dynamic nanoassembly-based drug delivery system (DNDDS) has evolved from being a mere curiosity to emerging as a promising strategy for high-performance diagnosis and/or therapy of various diseases. However, dynamic nano-bio interaction between DNDDS and biological systems remains poorly understood, which can be critical for precise spatiotemporal and functional control of DNDDS in vivo. To deepen the understanding for fine control over DNDDS, we aim to explore natural systems as the root of inspiration for researchers from various fields. This review highlights ingenious designs, nano-bio interactions, and controllable functionalities of state-of-the-art DNDDS under endogenous or exogenous stimuli, by learning from nature at the molecular, subcellular, and cellular levels. Furthermore, the assembly strategies and response mechanisms of tailor-made DNDDS based on the characteristics of various diseased microenvironments are intensively discussed. Finally, the current challenges and future perspectives of DNDDS are briefly commented.
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http://dx.doi.org/10.1016/j.addr.2021.113830DOI Listing
August 2021

MV CBCT-Based Synthetic CT Generation Using a Deep Learning Method for Rectal Cancer Adaptive Radiotherapy.

Front Oncol 2021 31;11:655325. Epub 2021 May 31.

Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.

Due to image quality limitations, online Megavoltage cone beam CT (MV CBCT), which represents real online patient anatomy, cannot be used to perform adaptive radiotherapy (ART). In this study, we used a deep learning method, the cycle-consistent adversarial network (CycleGAN), to improve the MV CBCT image quality and Hounsfield-unit (HU) accuracy for rectal cancer patients to make the generated synthetic CT (sCT) eligible for ART. Forty rectal cancer patients treated with the intensity modulated radiotherapy (IMRT) were involved in this study. The CT and MV CBCT images of 30 patients were used for model training, and the images of the remaining 10 patients were used for evaluation. Image quality, autosegmentation capability and dose calculation capability using the autoplanning technique of the generated sCT were evaluated. The mean absolute error (MAE) was reduced from 135.84 ± 41.59 HU for the CT and CBCT comparison to 52.99 ± 12.09 HU for the CT and sCT comparison. The structural similarity (SSIM) index for the CT and sCT comparison was 0.81 ± 0.03, which is a great improvement over the 0.44 ± 0.07 for the CT and CBCT comparison. The autosegmentation model performance on sCT for femoral heads was accurate and required almost no manual modification. For the CTV and bladder, although modification was needed for autocontouring, the Dice similarity coefficient (DSC) indices were high, at 0.93 and 0.94 for the CTV and bladder, respectively. For dose evaluation, the sCT-based plan has a much smaller dose deviation from the CT-based plan than that of the CBCT-based plan. The proposed method solved a key problem for rectal cancer ART realization based on MV CBCT. The generated sCT enables ART based on the actual patient anatomy at the treatment position.
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http://dx.doi.org/10.3389/fonc.2021.655325DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8201514PMC
May 2021

Two Fusarium copper radical oxidases with high activity on aryl alcohols.

Biotechnol Biofuels 2021 Jun 16;14(1):138. Epub 2021 Jun 16.

Michael Smith Laboratories, University of British Columbia, 2185 East Mall, Vancouver, BC, V6T 1Z4, Canada.

Background: Biomass valorization has been suggested as a sustainable alternative to petroleum-based energy and commodities. In this context, the copper radical oxidases (CROs) from Auxiliary Activity Family 5/Subfamily 2 (AA5_2) are attractive biocatalysts for the selective oxidation of primary alcohols to aldehydes. Originally defined by the archetypal galactose 6-oxidase from Fusarium graminearum, fungal AA5_2 members have recently been shown to comprise a wide range of specificities for aromatic, aliphatic and furan-based alcohols. This suggests a broader substrate scope of native CROs for applications. However, only 10% of the annotated AA5_2 members have been characterized to date.

Results: Here, we define two homologues from the filamentous fungi Fusarium graminearum and F. oxysporum as predominant aryl alcohol oxidases (AAOs) through recombinant production in Pichia pastoris, detailed kinetic characterization, and enzyme product analysis. Despite possessing generally similar active-site architectures to the archetypal FgrGalOx, FgrAAO and FoxAAO have weak activity on carbohydrates, but instead efficiently oxidize specific aryl alcohols. Notably, both FgrAAO and FoxAAO oxidize hydroxymethyl furfural (HMF) directly to 5-formyl-2-furoic acid (FFCA), and desymmetrize the bioproduct glycerol to the uncommon L-isomer of glyceraldehyde.

Conclusions: This work expands understanding of the catalytic diversity of CRO from AA5_2 to include unique representatives from Fusarium species that depart from the well-known galactose 6-oxidase activity of this family. Detailed enzymological analysis highlights the potential biotechnological applications of these orthologs in the production of renewable plastic polymer precursors and other chemicals.
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http://dx.doi.org/10.1186/s13068-021-01984-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8207647PMC
June 2021

A Guide to Nucleic Acid Vaccines in the Prevention and Treatment of Infectious Diseases and Cancers: From Basic Principles to Current Applications.

Front Cell Dev Biol 2021 25;9:633776. Epub 2021 May 25.

State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China.

Faced with the challenges posed by infectious diseases and cancer, nucleic acid vaccines present excellent prospects in clinical applications. Compared with traditional vaccines, nucleic acid vaccines have the characteristics of high efficiency and low cost. Therefore, nucleic acid vaccines have potential advantages in disease prevention and treatment. However, the low immunogenicity and instability of nucleic acid vaccines have limited their development. Therefore, a large number of studies have been conducted to improve their immunogenicity and stability by improving delivery methods, thereby supporting progress and development for clinical applications. This article mainly reviews the advantages, disadvantages, mechanisms, delivery methods, and clinical applications of nucleic acid vaccines.
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http://dx.doi.org/10.3389/fcell.2021.633776DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8185206PMC
May 2021

Spatial Order of Functional Modules Enabling Diverse Intracellular Performance of Fluorescent Probes.

Angew Chem Int Ed Engl 2021 Aug 2;60(33):18280-18288. Epub 2021 Jul 2.

State Key Laboratory of Biogeology and Environmental Geology, Faculty of Materials Science and Chemistry, China University of Geosciences, Wuhan, 430078, China.

To overcome a series of challenges in tumor therapy, modular-agent probes (MAPs) comprised of various functional modules have been proposed. Researchers have tried to optimize the MAPs by exploiting the new modules or increasing the numbers of module, while neglecting the configuration of various modules. Here, we focus on the different spatial arrangements of existing modules. By utilizing a tetraphenylethylene (TPE) derivative with stereochemical structure and dual modifiable end-group sites as small molecule scaffold, two MAPs with same modular agents (module T for enhancing the internalization of MAPs by tumor cells and module M for causing mitochondrial dysfunction) but different spatial arrangements (on the one side, TM-AIE, and two sides, T-AIE-M, of the molecule scaffold) are designed. T-AIE-M with larger RGD binding angle performed higher specificity, while TM-AIE characterizing longer α-helix structure displayed superior toxicity.
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http://dx.doi.org/10.1002/anie.202106195DOI Listing
August 2021

Hybridization Chain Reaction-Amplified Electrochemical DNA-Based Sensors Enable Calibration-Free Measurements of Nucleic Acids Directly in Whole Blood.

Anal Chem 2021 06 1;93(23):8354-8361. Epub 2021 Jun 1.

State Key Laboratory of Biogeology Environmental Geology, Engineering Research Center of Nano-Geomaterials of Ministry of Education, Engineering Research Center of Nano-Geomaterials of Ministry of Education, Faculty of Materials Science and Chemistry, China University of Geosciences, Wuhan 430074, China.

Hybridization chain reaction (HCR) amplification strategy has been extensively explored for the application of electrochemical DNA-based sensors. Despite the enhancement in its sensitivity using the HCR, such sensor platform exhibited significant sensor-to-sensor variations in current due to variations in probe counts and lengths. To circumvent this, we are developing here a calibration-free "O-N" approach to generate a ratiometric, unitless value that is independent of these variations. Specifically, this approach employs two types of redox reporters, denoted as "One reporter" and "N reporters", with the former attached on the capture DNA and the latter on H1 and H2 strands. By optimizing the attachment sites of these reporters onto DNA strands, we demonstrate a significantly enhanced sensitivity of such sensor platform by four orders of magnitude, achieving accurate, calibration-free measurement of nucleic acids including ctDNA directly in undiluted whole blood without the requirement to calibrate each individual sensor.
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http://dx.doi.org/10.1021/acs.analchem.1c01436DOI Listing
June 2021

Trace analysis of progesterone and 21 progestins in milk by ultra-performance liquid chromatography coupled with high-field quadrupole-orbitrap high-resolution mass spectrometry.

Food Chem 2021 Nov 15;361:130115. Epub 2021 May 15.

Institute of Quality Standards and Testing Technology for Agricultural Product, Chinese Academy of Agricultural Science, Beijing 100081, China. Electronic address:

A method for rapid screening and quantification of progesterone and progestins in milks by ultrahigh-performance liquid chromatography coupled with quadrupole-high field Orbitrap high-resolution mass spectrometry (UHPLC QE HF HRMS) was established. Milks samples were extracted by acetonitrile + hexane (80 + 20), purified by prime HLB SPE and analyzed by UHPLC QE HF HRMS. The detection limit of progesterone and 21 progestins in milk is between 0.05 µg/kg -0.3 μg /kg, the correlation coefficient of progesterone and progestins in the corresponding concentration range is more than 0.99, recoveries for milk samples are between 80.7% and 108.3% with the relative deviation is less than 15%.The method fulfils the requirements of veterinary drug residue detection validation of EU and China, and successfully applied to detecting the μg/kg level of progesterone and monitoring residual of progestins in real milk.
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http://dx.doi.org/10.1016/j.foodchem.2021.130115DOI Listing
November 2021

Zika virus induces neuronal and vascular degeneration in developing mouse retina.

Acta Neuropathol Commun 2021 05 25;9(1):97. Epub 2021 May 25.

Department of Ophthalmology and Visual Sciences, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX, 77555-0144, USA.

Zika virus (ZIKV), a mosquito-borne flavivirus, can cause severe eye disease and even blindness in newborns. However, ZIKV-induced retinal lesions have not been studied in a comprehensive way, mechanisms of ZIKV-induced retinal abnormalities are unknown, and no therapeutic intervention is available to treat or minimize the degree of vision loss in patients. Here, we developed a novel mouse model of ZIKV infection to evaluate its impact on retinal structure. ZIKV (20 plaque-forming units) was inoculated into neonatal wild type C57BL/6J mice at postnatal day (P) 0 subcutaneously. Retinas of infected mice and age-matched controls were collected at various ages, and retinal structural alterations were analyzed. We found that ZIKV induced progressive neuronal and vascular damage and retinal inflammation starting from P8. ZIKV-infected retina exhibited dramatically decreased thickness with loss of neurons, initial neovascular tufts followed by vessel dilation and degeneration, increased microglia and leukocyte recruitment and activation, degeneration of astrocyte network and gliosis. The above changes may involve inflammation and endoplasmic reticulum stress-mediated cell apoptosis and necroptosis. Moreover, we evaluated the efficacy of preclinical drugs and the safety of ZIKV vaccine candidate in this mouse model. We found that ZIKV-induced retinal abnormalities could be blocked by a selective flavivirus inhibitor NITD008 and a live-attenuated ZIKV vaccine candidate could potentially induce retinal abnormalities. Overall, we established a novel mouse model and provide a direct causative link between ZIKV and retinal lesion in vivo, which warrants further investigation of the underlying mechanisms of ZIKV-induced retinopathy and the development of effective therapeutics.
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http://dx.doi.org/10.1186/s40478-021-01195-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8147371PMC
May 2021

MRI Radiomics Signature as a Potential Biomarker for Predicting Status in Locally Advanced Rectal Cancer Patients.

Front Oncol 2021 7;11:614052. Epub 2021 May 7.

Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.

Background And Purpose: Locally advanced rectal cancer (LARC) is a heterogeneous disease with little information about status and image features. The purpose of this study was to analyze the association between T2 magnetic resonance imaging (MRI) radiomics features and status in LARC patients.

Material And Methods: Eighty-three patients with status information and T2 MRI images between 2012.05 and 2019.09 were included. Least absolute shrinkage and selection operator (LASSO) regression was performed to assess the associations between features and gene status. The patients were divided 7:3 into training and validation sets. The C-index and the average area under the receiver operator characteristic curve (AUC) were used for performance evaluation.

Results: The clinical characteristics of 83 patients in the mutant and wild-type cohorts were balanced. Forty-two (50.6%) patients had mutations, and 41 (49.4%) patients had wild-type . A total of 253 radiomics features were extracted from the T2-MRI images of LARC patients. One radiomic feature named X.LL_scaled_std, a standard deviation value of scaled wavelet-transformed low-pass channel filter, was selected from 253 features (=0.019). The radiomics-based C-index values were 0.801 (95% CI: 0.772-0.830) and 0.703 (95% CI: 0.620-0.786) in the training and validation sets, respectively.

Conclusion: Radiomics features could differentiate status in LARC patients based on T2-MRI images. Further validation in a larger dataset is necessary in the future.
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http://dx.doi.org/10.3389/fonc.2021.614052DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8138318PMC
May 2021

Modulating MnO Interface with Flexible and Self-Adhering Alkylphosphonic Layers for High-Performance Zn-MnO Batteries.

ACS Appl Mater Interfaces 2021 May 13;13(20):23724-23731. Epub 2021 May 13.

Department of Chemistry and Biochemistry, Northern Illinois University, DeKalb, Illinois 60115, United States.

Metal oxides are essential electrode materials for high-energy-density batteries, but it remains highly challenging to modulate their interfacial charge-transfer process and improve their cycling stability. Here, using MnO nanofibers as an example, we describe the application of self-assembled alkylphosphonic modification layers for significantly improved cycling stability and high-rate performance of Zn-MnO batteries. Two modifier organic molecules with the same phosphonic functional group but different alkyl tail lengths were employed and systematically compared, including butylphosphonic acid (BPA) and decylphosphonic acid (DPA). The phosphonic groups form strong interfacial covalent bonding and assist the generation of conformal and flexible coatings with few nanometers thickness on a MnO surface. The intertwined alkylphosphonic molecules in the modulation layers have interconnected phosphonic groups, which improve interfacial charge transfer of H ions for fast conversion of MnO to MnOOH without compromising electrolyte wetting. Importantly, the coating layers effectively reduce dissolutive loss of Mn from MnO during battery cycling since diffusion of both water molecules and divalent Mn cations was inhibited across the modification layers. The flexible coatings could readily adapt to the morphological changes of MnO during battery cycling and provide long-lasting protection. Overall, we identified that BPA has the optimal balance of hydrophobic-hydrophilic components and enabled modified MnO cathodes with >30% improved discharge capacity compared with unmodified MnO cathodes, together with substantially improved long-term cycling stability with >60% capacity retention for 400 cycles in aqueous ZnSO electrolytes without any Mn additive. This work provides new insights into tuning electrochemical pathways that move away from the prevailing rigid, ceramic coating-based surface modifications.
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http://dx.doi.org/10.1021/acsami.1c04097DOI Listing
May 2021

Correction to: Isoprenylated Flavonoids as Ca3.1 Low Voltage-Gated Ca Channel Inhibitors from Salvia digitaloides.

Nat Prod Bioprospect 2021 May 12. Epub 2021 May 12.

State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, and Yunnan Key Laboratory of Natural Medicinal Chemistry, Kunming, 650201, People's Republic of China.

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http://dx.doi.org/10.1007/s13659-021-00308-xDOI Listing
May 2021

PPP3CA truncating variants clustered in the regulatory domain cause early-onset refractory epilepsy.

Clin Genet 2021 Aug 1;100(2):227-233. Epub 2021 Jun 1.

Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.

PPP3CA encodes the catalytic subunit of calcineurin, a calcium-calmodulin-regulated serine-threonine phosphatase. Loss-of-function (LoF) variants in the catalytic domain have been associated with epilepsy, while gain-of-function (GoF) variants in the auto-inhibitory domain cause multiple congenital abnormalities. We herein report five new patients with de novo PPP3CA variants. Interestingly, the two frameshift variants in this study and the six truncating variants reported previously are all located within a 26-amino acid region in the regulatory domain (RD). Patients with a truncating variant had more severe earlier onset seizures compared to patients with a LoF missense variant, while autism spectrum disorder was a more frequent feature in the latter. Expression studies of a truncating variant showed apparent RNA expression from the mutant allele, but no detectable mutant protein. Our data suggest that PPP3CA truncating variants clustered in the RD, causing more severe early-onset refractory epilepsy and representing a type of variants distinct from LoF or GoF missense variants.
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http://dx.doi.org/10.1111/cge.13979DOI Listing
August 2021

Hydrocephalus Induced by Intraventricular Peroxiredoxin-2: The Role of Macrophages in the Choroid Plexus.

Biomolecules 2021 Apr 29;11(5). Epub 2021 Apr 29.

Department of Neurosurgery, University of Michigan, Ann Arbor, MI 48109, USA.

The choroid plexus (CP) is the primary source of cerebrospinal fluid in the central nervous system. Recent evidence indicates that inflammatory pathways at the CP may be involved in hydrocephalus development. Peroxiredoxin 2 (Prx2) is a major component of red blood cells. Extracellular Prx2 is proinflammatory, and its release after red blood cell lysis may contribute to hydrocephalus after intraventricular hemorrhage. This study aimed to identify alterations in CP macrophages and dendritic cells following intracerebroventricular Prx2 injection and investigate the relationship between macrophages/dendritic cells and hydrocephalus. There were two parts to this study. In the first part, adult male Sprague-Dawley rats received an intracerebroventricular injection of Prx2 or saline. In the second part, Prx2 was co-injected with clodronate liposomes or control liposomes. All animals were euthanized at 24 h after magnetic resonance imaging. Immunohistochemistry was used to evaluate macrophages in CP, magnetic resonance imaging to quantify hydrocephalus, and histology to assess ventricular wall damage. The intracerebroventricular injection of Prx2 not only increased the OX-6 positive cells, but it also altered their location in the CP and immunophenotype. Co-injecting clodronate liposomes with Prx2 decreased the number of macrophages and simultaneously attenuated Prx2-induced hydrocephalus and ventricular wall damage. These results suggest that CP macrophages play an essential role in CP inflammation-induced hydrocephalus. These macrophages may be a potential therapeutic target in post-hemorrhagic hydrocephalus.
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http://dx.doi.org/10.3390/biom11050654DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8145001PMC
April 2021

Scavenger receptor A1 participates in uptake of serovar Autumnalis strain 56606v and inflammation in mouse macrophages.

Emerg Microbes Infect 2021 Dec;10(1):939-953

Department of Medical Microbiology and Parasitology, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.

Leptospirosis, caused by pathogenic species, has emerged as a widespread zoonotic disease worldwide. Macrophages mediate the elimination of pathogens through phagocytosis and cytokine production. Scavenger receptor A1 (SR-A1), one of the critical receptors mediating this process, plays a complicated role in innate immunity. However, the role of SR-A1 in the immune response against pathogenic invasion is unknown. In the present study, we found that SR-A1 is an important nonopsonic phagocytic receptor on murine macrophages for . However, intraperitoneal injection of leptospires into WT mice presented with more apparent jaundice, subcutaneous hemorrhaging, and higher bacteria burdens in blood and tissues than that of SR-A1 mice. Exacerbated cytokine and inflammatory mediator levels were also observed in WT mice and higher recruited macrophages in the liver than those of SR-A1 mice. Our findings collectively reveal that although beneficial in the uptake of by macrophage, SR-A1 might be exploited by to modulate inflammatory activation and increase the susceptibility of infection in the host. These results provide our new insights into the innate immune response during early infection by .
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http://dx.doi.org/10.1080/22221751.2021.1925160DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8153709PMC
December 2021

Improving Image-Guided Surgical and Immunological Tumor Treatment Efficacy by Photothermal and Photodynamic Therapies Based on a Multifunctional NIR AIEgen.

Adv Mater 2021 Jun 26;33(22):e2101158. Epub 2021 Apr 26.

State Key Laboratory of Luminescent Materials and Devices, Guangdong Provincial Key Laboratory of Luminescence from Molecular Aggregates, SCUT-HKUST Joint Research Institute, South China University of Technology, Guangzhou, 510640, China.

Multimodal therapy is attracting increasing attention to improve tumor treatment efficacy, but generally requires various complicated ingredients combined within one theranostic system to achieve multiple functions. Herein, a multifunctional theranostic nanoplatform based on a single aggregation-induced-emission luminogen (AIEgen), DDTB, is designed to integrate near-infrared (NIR) fluorescence, photothermal, photodynamic, and immunological effects. Intravenously injected AIEgen-based nanoparticles can efficiently accumulate in tumors with NIR fluorescence to provide preoperative diagnosis. Most of the tumors are excised under intraoperative fluorescence navigation, whereafter, some microscopic residual tumors are completely ablated by photodynamic and photothermal therapies for maximally killing the tumor cells and tissues. Up to 90% of the survival rate can be achieved by this synergistic image-guided surgery and photodynamic and photothermal therapies. Importantly, the nanoparticles-mediated photothermal/photodynamic therapy plus programmed death-ligand 1 antibody significantly induce tumor elimination by enhancing the effect of immunotherapy. This theranostic strategy on the basis of a single AIEgen significantly improves the survival of cancer mice with maximized therapeutic outcomes, and holds great promise for clinical cancer treatment.
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http://dx.doi.org/10.1002/adma.202101158DOI Listing
June 2021

A Phosphatase-Mimetic Nano-Stabilizer of Mast Cells for Long-Term Prevention of Allergic Disease.

Adv Sci (Weinh) 2021 04 8;8(8):2004115. Epub 2021 Feb 8.

Institute of Pharmaceutics College of Pharmaceutical Sciences Zhejiang University Hangzhou Zhejiang 310058 P. R. China.

Allergic diseases are pathological immune responses with significant morbidity, which are closely associated with allergic mediators as released by allergen-stimulated mast cells (MCs). Prophylactic stabilization of MCs is regarded as a practical approach to prevent allergic diseases. However, most of the existing small molecular MC stabilizers exhibit a narrow therapeutic time window, failing to provide long-term prevention of allergic diseases. Herein, ceria nanoparticle (CeNP-) based phosphatase-mimetic nano-stabilizers (PMNSs) with a long-term therapeutic time window are developed for allergic disease prevention. By virtue of the regenerable catalytic hotspots of oxygen vacancies on the surface of CeNPs, PMNSs exhibit sustainable phosphatase-mimetic activity to dephosphorylate phosphoproteins in allergen-stimulated MCs. Consequently, PMNSs constantly modulate intracellular phospho-signaling cascades of MCs to inhibit the degranulation of allergic mediators, which prevents the initiation of allergic mediator-associated pathological responses, eventually providing protection against allergic diseases with a long-term therapeutic time window.
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http://dx.doi.org/10.1002/advs.202004115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8061383PMC
April 2021

Isoprenylated Flavonoids as Ca3.1 Low Voltage-Gated Ca Channel Inhibitors from Salvia digitaloides.

Nat Prod Bioprospect 2021 Apr 24. Epub 2021 Apr 24.

State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, and Yunnan Key Laboratory of Natural Medicinal Chemistry, Kunming, 650201, People's Republic of China.

Saldigones A-C (1, 3, 4), three new isoprenylated flavonoids with diverse flavanone, pterocarpan, and isoflavanone architectures, were characterized from the roots of Salvia digitaloides, together with a known isoprenylated flavanone (2). Notably, it's the first report of isoprenylated flavonoids from Salvia species. The structures of these isolates were elucidated by extensive spectroscopic analysis. All of the compounds were evaluated for their activities on Ca3.1 low voltage-gated Ca channel (LVGCC), of which 2 strongly and dose-dependently inhibited Ca3.1 peak current.
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http://dx.doi.org/10.1007/s13659-021-00307-yDOI Listing
April 2021

Spatiotemporal patterning of photoresponsive DNA-based hydrogels to tune local cell responses.

Nat Commun 2021 04 22;12(1):2364. Epub 2021 Apr 22.

Institute of Chemistry, Center for Nanoscience and Nanotechnology, The Hebrew University of Jerusalem, Jerusalem, Israel.

Understanding the spatiotemporal effects of surface topographies and modulated stiffness and anisotropic stresses of hydrogels on cell growth remains a biophysical challenge. Here we introduce the photolithographic patterning or two-photon laser scanning confocal microscopy patterning of a series of o-nitrobenzylphosphate ester nucleic acid-based polyacrylamide hydrogel films generating periodically-spaced circular patterned domains surrounded by continuous hydrogel matrices. The patterning processes lead to guided modulated stiffness differences between the patterned domains and the surrounding hydrogel matrices, and to the selective functionalization of sub-regions of the films with nucleic acid anchoring tethers. HeLa cells are deposited on the circularly-shaped domains functionalized with the MUC-1 aptamers. Initiation of the hybridization chain reaction by nucleic acid tethers associated with the continuous hydrogel matrix results in stress-induced ordered orthogonal shape-changes on the patterned domains, leading to ordered shapes of cell aggregates bound to the patterns.
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http://dx.doi.org/10.1038/s41467-021-22645-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8062675PMC
April 2021

Layer-by-layer assembly in nanochannels: assembly mechanism and applications.

Nanoscale 2021 Apr;13(16):7471-7497

Institute of Condensed Matter and Nanosciences - Bio and Soft Matter (IMCN/BSMA), Université catholique de Louvain, Croix du Sud 1/L7.04.02, B1348 Louvain-la-Neuve, Belgium.

Layer-by-layer (LbL) assembly is a versatile technology to construct multifunctional nanomaterials using various supporting substrates, enabled by the large selection freedom of building materials and diversity of possible driving forces. The fine regulation over the film thickness and structure provides an elegant way to tune the physical/chemical properties by mild assembly conditions (e.g. pH, ion strength). In this review, we focus on LbL in nanochannels, which exhibit a different growth mechanism compared to "open", convex substrates. The assembly mechanism in nanochannels is discussed in detail, followed by the summary of applications of LbL assemblies liberated from nanochannel templates which can be used as nanoreactors, drug carriers and transporting channels across cell membranes. For fluidic applications, robust membrane substrates are required to keep in place nanotube arrays for membrane-based separation, purification, biosensing and energy harvesting, which are also discussed. The good compatibility of LbL with crossover technologies from other fields allows researchers to further extend this technology to a broader range of research fields, which is expected to result in an increased number of applications of LbL technology in the future.
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http://dx.doi.org/10.1039/d1nr01113hDOI Listing
April 2021

Diterpenoid Alkaloids from the Aerial Parts of Aconitum flavum Hand.-Mazz.

Nat Prod Bioprospect 2021 Aug 16;11(4):421-429. Epub 2021 Apr 16.

State Key Laboratory of Phytochemistry and Plant Resources in West China and Yunnan Key Laboratory of Natural Medicinal Chemistry, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, China.

Sixteen diterpenoid alkaloids (DAs), including six aconitine-type alkaloids (5 and 9 - 13), seven 7,17-seco-aconitine-type alkaloids (1 - 4, 6 - 8), two napelline-type alkaloids (14 and 15) as well as one veatchine-type alkaloid (16), were isolated from the aerial parts of Aconitum flavum Hand.-Mazz. In which, flavumolines A - D (1 - 4) were four new ones, and flavumoline E (5) was reported as natural compound for the first time. Their chemical structures were elucidated by the analysis of extensive spectroscopic data. The inhibitory activities of these isolates on Ca3.1 low voltage-gated Ca channel, NO production in LPS-activated RAW264.7cells, five human tumor cell lines, as well as acetylcholinesterase (AChE) were tested.
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http://dx.doi.org/10.1007/s13659-021-00302-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8275754PMC
August 2021
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