Publications by authors named "Jue Wang"

1,258 Publications

  • Page 1 of 1

Salvia-Nelumbinis naturalis improves lipid metabolism of NAFLD by regulating the SIRT1/AMPK signaling pathway.

BMC Complement Med Ther 2022 Aug 9;22(1):213. Epub 2022 Aug 9.

Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China.

Background: Salvia-Nelumbinis naturalis (SNN), the extract of Chinese herbal medicine, has shown effects on NAFLD. This study aims to explore the underlying mechanism of SNN for regulating the lipid metabolism disorder in NAFLD based on the SIRT1/AMPK signaling pathway.

Methods: Male C57BL/6J mice fed with a high-fat diet (HFD) were used to establish the NAFLD model. Dynamic changes of mice including body weight, liver weight, serological biochemical indexes, liver histopathological changes, and protein level of AMPK and SIRT1 were monitored. After18 weeks, SNN treatment was administrated to the NAFLD mice for another 4 weeks. Besides the aforementioned indices, TC and TG of liver tissues were also measured. Western blot and quantitative RT-PCR were used to detect the expression and/or activation of SIRT1 and AMPK, as well as the molecules associated with lipid synthesis and β-oxidation. Furthermore, AML12 cells with lipid accumulation induced by fatty acids were treated with LZG and EX527 (SIRT1 inhibitor) or Compound C (AMPK inhibitor ) to confirm the potential pharmacological mechanism.

Results: Dynamic observation found the mice induced by HFD with gradually increased body and liver weight, elevated serum cholesterol, hepatic lipid accumulation, and liver injury. After 16 weeks, these indicators have shown obvious changes. Additionally, the hepatic level of SIRT1 and AMPK activation was identified gradually decreased with NAFLD progress. The mice with SNN administration had lower body weight, liver weight, and serum level of LDL-c and ALT than those of the NAFLD model. Hepatosteatosis and hepatic TG content in the liver tissues of the SNN group were significantly reduced. When compared with control mice, the NAFLD mice had significantly decreased hepatic expression of SIRT1, p-AMPK, p-ACC, ACOX1, and increased total Acetylated-lysine, SUV39H2, and SREBP-1c. The administration of SNN reversed the expression of these molecules. In vitro experiments showed the effect of SNN in ameliorating hepatosteatosis and regulating the expression of lipid metabolism-related genes in AML12 cells, which were diminished by EX527 or Compound C co-incubation.

Conclusions: Taken together, the SIRT1/AMPK signaling pathway, involved in hepatic lipid synthesis and degradation, plays a pivotal role in the pathogenesis of NAFLD development. The regulation of SIRT1/AMPK signaling greatly contributes to the underlying therapeutic mechanism of SNN for NAFLD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12906-022-03697-9DOI Listing
August 2022

Exosome-transported Long Non-coding Ribonucleic Acid H19 Induces Blood-brain Barrier Disruption in Cerebral Ischemic Stroke Via the H19/micro Ribonucleic Acid-18a/Vascular Endothelial Growth factor Axis.

Neuroscience 2022 Aug 2. Epub 2022 Aug 2.

Department of Neurology, Shengjing Hospital of China Medical University, China. Electronic address:

Long non-coding RNA H19 (lncRNA H19) is transcribed from the H19 gene. We previously reported the role of lncRNA H19 in the pathogenesis of cerebral ischemic stroke. The present study aimed to elucidate the relationship between lncRNA H19 and blood-brain barrier breakdown induced by cerebral ischemic stroke. We observed that plasma levels of lncRNA H19 were positively associated with the extent of blood-brain barrier damage. In cellular co-culture models, neurons expressed and transported lncRNA H19 to astrocytes via exosomes and contributed to an increase in endothelium permeability induced by oxygen-glucose deprivation. Inhibition of neuronal exosomal lncRNA H19 regulated astrocytic microRNA (miR)-18a and vascular endothelial growth factor (VEGF) expression. Further, lncRNA H19 induced a decrease in tight junction proteins expression via the lncRNA H19/miR-18a/VEGF axis. This study highlights the transportation of lncRNA H19 by exosomes and the relationship between lncRNA H19 and blood-brain barrier breakdown.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.neuroscience.2022.07.028DOI Listing
August 2022

Wumei Pill Ameliorates AOM/DSS-Induced Colitis-Associated Colon Cancer through Inhibition of Inflammation and Oxidative Stress by Regulating S-Adenosylhomocysteine Hydrolase- (AHCY-) Mediated Hedgehog Signaling in Mice.

Oxid Med Cell Longev 2022 26;2022:4061713. Epub 2022 Jul 26.

School of Pharmacy, Nantong University, 19 Qixiu Road, Nantong, Jiangsu Province 226001, China.

Wumei Pill (WMP) is a traditional Chinese herbal formulation and widely used to treat digestive system diseases in clinical. S-Adenosylhomocysteine hydrolase (AHCY) can catalyze the hydrolysis of S-adenosylhomocysteine to adenosine and homocysteine in living organisms, and its abnormal expression is linked to the pathogenesis of many diseases including colorectal cancer (CRC). A previous study reported that WMP could prevent CRC in mice; however, the underlying mechanisms especially the roles of AHCY in WMP-induced anti-CRC remain largely unknown. Here, we investigated the regulatory roles and potential mechanisms of AHCY in WMP-induced anti-CRC. WMP notably alleviated the azoxymethane/dextran sulfate sodium- (AOM/DSS-) induced colitis-associated colon cancer (CAC) in mice. Besides, WMP inhibited the inflammation and oxidative stress in AOM/DSS-induced CAC mice. AHCY was high expression in clinical samples of colon cancer compared to the adjacent tissues. WMP inhibited the AHCY expression in AOM/DSS-induced CAC mice. An study found that AHCY overexpression induced cell proliferation, colony formation, invasion, and tumor angiogenesis, whereas its knockdown impaired its oncogenic function. AHCY overexpression enhanced, while its knockdown weakened the inflammation and oxidative stress in colon cancer cells. Interestingly, WMP potently suppressed the hedgehog (Hh) signaling in AOM/DSS-induced CAC mice. A further study showed that AHCY overexpression activated the Hh signaling while AHCY knockdown inactivated the Hh signaling. Moreover, activation of the Hh signaling reversed the effect of AHCY silencing on inflammation and oxidative stress . In conclusion, WMP alleviated the AOM/DSS-induced CAC through inhibition of inflammation and oxidative stress by regulating AHCY-mediated hedgehog signaling in mice. These findings uncovered a potential molecular mechanism underlying the anti-CAC effect of WMP and suggested WMP as a promising therapeutic candidate for CRC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2022/4061713DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9345734PMC
August 2022

LcERF19, an AP2/ERF transcription factor from , positively regulates geranial and neral biosynthesis.

Hortic Res 2022 22;9:uhac093. Epub 2022 Apr 22.

State Key Laboratory of Tree Genetics and Breeding, Chinese Academy of Forestry, Beijing, 100091, China.

The APETALA2/ETHYLENE RESPONSE FACTOR (AP2/ERF) transcription factors (TFs) are involved in the regulation of specialized terpenoid biosynthesis. However, the AP2/ERF TFs in have not been characterized and their role in the biosynthesis of terpenoids is unknown. Here, 174 LcAP2/ERF TFs were identified in and categorized into four subfamilies: 27 AP2, 7 RAV, 1 Soloist, and 139 ERF. Transcriptomic and qRT-PCR assays both showed that the expression levels of were similar to that of terpene synthase in the pericarp, which is related to the synthesis of geranial and neral in . was further shown to encode a nuclear-localized protein and its expression was strongly induced by jasmonate. Yeast one-hybrid and dual-luciferase assays showed that LcERF19 associated with GCC box elements of the promoter and promoted its activity. Transient overexpression of in and overexpression of in tomato resulted in a significant increase in geranial and neral. Our findings show that LcERF19 enhances geranial and neral biosynthesis through activation of expression, which provides a strategy to improve the flavor of tomato and other fruits.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/hr/uhac093DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9327096PMC
April 2022

A Cellulose-Type Carrier for Intimate Coupling Photocatalysis and Biodegradation.

Polymers (Basel) 2022 Jul 24;14(15). Epub 2022 Jul 24.

Guangxi Key Laboratory of Clean Pulp & Papermaking and Pollution Control, Nanning 530004, China.

Intimate coupling photocatalysis and biodegradation treatment technology is an emerging technology in the treatment of refractory organic matter, and the carrier plays an important role in this technology. In this paper, sugarcane cellulose was used as the basic skeleton, absorbent cotton was used as a reinforcing agent, anhydrous sodium sulfate was used as a pore-forming agent to prepare a cellulose porous support with good photocatalytic performance, and nano-TiO was loaded onto it by a low-temperature bonding method. The results showed that the optimal preparation conditions of cellulose carriers were: cellulose mass fraction 1.0%; absorbent cotton 0.6 g; and NaSO 60 g. The SEM, EDS and XPS characterization further indicated that the nano-TiO was uniformly loaded onto the cellulose support. The degradation experiments of Rhodamine B showed that the nano-TiO-loaded composite supports had good photocatalytic performance. The degradation rate of 1,2,4-trichlorobenzene was more than 92% after 6 cycles, and the experiment of adhering a large number of microorganisms on the carriers before and after the reaction showed that the cellulose-based carriers obtained the required photocatalytic performance and stability, which is a good cellulose porous carrier.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/polym14152998DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9332189PMC
July 2022

Zinc in Cognitive Impairment and Aging.

Biomolecules 2022 07 18;12(7). Epub 2022 Jul 18.

Department of Neurology, Shengjing Hospital of China Medical University, 36 Sanhao St., Shenyang 110004, China.

Zinc, an essential micronutrient for life, was first discovered in 1869 and later found to be indispensable for the normal development of plants and for the normal growth of rats and birds. Zinc plays an important role in many physiological and pathological processes in normal mammalian brain development, especially in the development of the central nervous system. Zinc deficiency can lead to neurodegenerative diseases, mental abnormalities, sleep disorders, tumors, vascular diseases, and other pathological conditions, which can cause cognitive impairment and premature aging. This study aimed to review the important effects of zinc and zinc-associated proteins in cognitive impairment and aging, to reveal its molecular mechanism, and to highlight potential interventions for zinc-associated aging and cognitive impairments.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/biom12071000DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9312494PMC
July 2022

High Prevalence and Overexpression of Fosfomycin-Resistant Gene X in From China.

Front Microbiol 2022 8;13:900185. Epub 2022 Jul 8.

Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China.

i are one of the main causes of gastrointestinal tract infections in the healthcare system and can develop resistance to fosfomycin through plasmid or chromosomally encoded fosfomycin resistance genes. To investigate the mechanisms of fosfomycin resistance, a total of 4,414 clinical isolates of non-replicated clinical enterococci collected from 62 hospitals in 26 provinces or cities in China were tested. Antibiotic susceptibility testing, detection of fosfomycin resistance genes, and cloning of the X gene were done. The PFGE, MLST, qRT-PCR, and next genome sequencing were carried out. The results revealed that the fosfomycin-resistant rate of enterococci was 3.5% (153/4,414), and the major resistance mechanism was X (101/153) and B (52/153) genes. The X gene could increase 4- fold fosfomycin MIC in BM4105RF transformants, and the results of PFGE showed the 101 carrying X were grouped into 48 pulse types. The multilocus sequence typing identified ST555 as the vast majority of STs, mostly distributed in Shanghai, China. Furthermore, the X gene expression was strongly related to the fosfomycin-resistant levels of . The present study was the first to describe the high prevalence presence of the X gene in from China.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fmicb.2022.900185DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9304900PMC
July 2022

Aberrant visual-related networks in familial cortical myoclonic tremor with epilepsy.

Parkinsonism Relat Disord 2022 Jul 19;101:105-110. Epub 2022 Jul 19.

Department of Neurology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China. Electronic address:

Introduction: In familial cortical myoclonic tremor with epilepsy, photic stimulation can trigger visual symptoms and induce a photoparoxysmal response, or photosensitivity, on electroencephalography. However, the mechanism is poorly understood. In this study, we aimed to explore the neuroimaging changes related to visual symptoms and photosensitivity in genetically confirmed familial cortical myoclonic tremor with epilepsy type 1.

Methods: Resting-state functional magnetic resonance imaging and electroencephalography data were collected from 31 patients carrying the heterozygous pathogenic intronic pentanucleotide (TTTCA)n insertion in the sterile alpha motif domain-containing 12 gene and from 52 age- and sex-matched healthy controls.

Results: (1) Both regional homogeneity and degree centrality values in the bilateral calcarine sulcus were significantly increased in patients compared with healthy controls. (2) When the calcarine sulcus area with increased regional homogeneity was taken as a seed, increased functional connectivity values were observed in the right precentral gyrus, while decreased functional connectivity values were observed in the right superior frontal gyrus and right inferior parietal lobule. (3) Independent component analysis showed increased connectivity in the left calcarine sulcus inside the medial visual network. (4) Correlation analysis revealed a significant positive correlation between regional homogeneity values and frequency of seizure, and photoparoxysmal response grades were positively correlated with the severity of cortical tremor and duration of epilepsy.

Conclusion: These findings provide strong evidence for the interpretation of visual symptoms and photosensitivity in familial cortical myoclonic tremor with epilepsy. We speculate that functional changes in the primary visual cortex may be an imaging biomarker for the disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.parkreldis.2022.07.001DOI Listing
July 2022

Scaffolding protein functional sites using deep learning.

Science 2022 07 21;377(6604):387-394. Epub 2022 Jul 21.

Department of Biochemistry, University of Washington, Seattle, WA 98105, USA.

The binding and catalytic functions of proteins are generally mediated by a small number of functional residues held in place by the overall protein structure. Here, we describe deep learning approaches for scaffolding such functional sites without needing to prespecify the fold or secondary structure of the scaffold. The first approach, "constrained hallucination," optimizes sequences such that their predicted structures contain the desired functional site. The second approach, "inpainting," starts from the functional site and fills in additional sequence and structure to create a viable protein scaffold in a single forward pass through a specifically trained RoseTTAFold network. We use these two methods to design candidate immunogens, receptor traps, metalloproteins, enzymes, and protein-binding proteins and validate the designs using a combination of in silico and experimental tests.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1126/science.abn2100DOI Listing
July 2022

Phonon signatures for polaron formation in an anharmonic semiconductor.

Proc Natl Acad Sci U S A 2022 Jul 21;119(30):e2122436119. Epub 2022 Jul 21.

Department of Chemistry, Columbia University, New York, NY 10027.

Mechanistic studies on lead halide perovskites (LHPs) in recent years have suggested charge carrier screening as partially responsible for long carrier diffusion lengths and lifetimes that are key to superior optoelectronic properties. These findings have led to the ferroelectric large polaron proposal, which attributes efficient charge carrier screening to the extended ordering of dipoles from symmetry-breaking unit cells that undergo local structural distortion and break inversion symmetry. It remains an open question whether this proposal applies in general to semiconductors with LHP-like anharmonic and dynamically disordered phonons. Here, we study electron-phonon coupling in BiOSe, a semiconductor which bears resemblance to LHPs in ionic bonding, spin-orbit coupling, band transport with long carrier diffusion lengths and lifetimes, and phonon disorder as revealed by temperature-dependent Raman spectroscopy. Using coherent phonon spectroscopy, we show the strong coupling of an anharmonic phonon mode at 1.50 THz to photo-excited charge carriers, while the Raman excitation of this mode is symmetry-forbidden in the ground-state. Density functional theory calculations show that this mode, originating from the A phonon of out-of-plane Bi/Se motion, gains oscillator strength from symmetry-lowering in polaron formation. Specifically, lattice distortion upon ultrafast charge localization results in extended ordering of symmetry-breaking unit cells and a planar polaron wavefunction, namely a two-dimensional polaron in a three-dimensional lattice. This study provides experimental and theoretical insights into charge interaction with anharmonic phonons in BiOSe and suggests ferroelectric polaron formation may be a general principle for efficient charge carrier screening and for defect-tolerant semiconductors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1073/pnas.2122436119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9335324PMC
July 2022

Perturbation of biological processes with small molecule kinase inhibitors.

Curr Opin Chem Biol 2022 Jul 16;70:102185. Epub 2022 Jul 16.

Beijing National Laboratory for Molecular Sciences, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, Department of Chemical Biology, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China; Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China; Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China; Institute for Cancer Research, Shenzhen Bay Laboratory, Shenzhen, China. Electronic address:

The reversible phosphorylation of substrates mediated by kinases and phosphatases affects their subcellular localization, catalytic activity, and/or interaction with other molecules. It is essential for signal transduction and the regulation of nearly all cellular processes, such as proliferation, apoptosis, metabolism, motility, and differentiation. Small molecule kinase inhibitors (SMKIs) have served as critical chemical probes to reveal the biological functions and mechanisms of kinases and their potential as therapeutic targets. In this review, we focused on a few novel SMKIs and their recent application in biological and preclinical studies to showcase how highly selective and potent SMKIs can be developed and utilized to propel the investigations on kinases and the biology behind.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cbpa.2022.102185DOI Listing
July 2022

Extract of (Roxb.) Moon [Apocynaceae] Suppresses Hepatocellular Carcinoma by Inhibiting Angiogenesis.

Front Pharmacol 2022 30;13:900128. Epub 2022 Jun 30.

Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

The extract of (Roxb.) Moon [Apocynaceae] (MTE) has shown a significant anti-cancer effect on hepatocellular carcinoma (HCC), but its mechanism remains unclear. In this study, we used transcriptomics methods to investigate the underlying mechanism of MTE against HCC. Both MHCC97H and HepG2 cell lines were treated with MTE. The cell viability and migration were measured using the cell counting kit-8 assay and transwell assay. RNA-sequencing was used to identify differentially expressed genes (DEGs) between HepG2 cells treated with and without MTE. The expression levels of selected DEGs-vascular endothelial growth factor-A (VEGFA), platelet-derived growth factor receptor-β (PDGFRB), and von Willebrand factor (VWF)-were verified by RT-PCR and Western blot. The effect of conditioned medium from HCC cells with MTE treatment (CM-MTE) on blood vessels was observed by tube formation assay of HUVECs and chick chorioallantoic membrane (CAM) assay. A mouse model of HCC patient-derived tumor xenograft (PDX) was established and treated with MTE. The effect of MTE on the growth and angiogenesis of HCC-PDX was analyzed. The results demonstrated that MTE inhibited the viability and migration of HCC cells. RNA-seq showed that MTE treatment downregulated multiple genes associated with metabolism and angiogenesis. The expression levels of VEGFA, VWF, PDGFB, and PDGFRB in HCC cells were significantly suppressed by MTE. Meanwhile, MTE effectively inhibited the tube-forming capability of HUVECs and the angiogenesis of chick CAM. experiments revealed that the extract reduced tumor volume, inhibited the proliferation of HCC cells, and expanded the necrotic area of the tumor. Immunohistochemical results showed that the expression levels of CD31, PDGFB, VEGF, VWF, and PDGFRB in the HCC-PDX tumor tissues were all downregulated by MTE in a dose-dependent manner. Taken together, MTE could inhibit angiogenesis by repressing the expression of VEGF, VWF, PDGF, and PDGFRB in HCC cells, a mechanism that may enable MTE to counter HCC development.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphar.2022.900128DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9279733PMC
June 2022

Bioinformatics Analysis for Constructing a Six-Immune-Related Long Noncoding RNA Signature as a Prognostic Model of Hepatocellular Carcinoma.

Biomed Res Int 2022 7;2022:2093437. Epub 2022 Jul 7.

Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021 Guangxi Province, China.

The present study was aimed at identifying the potential prognostic biomarkers of the immune-related long noncoding RNA (IRL) signature for patients with hepatocellular carcinoma (HCC). RNA-sequencing data and clinical information about HCC were obtained from The Cancer Genome Atlas. The IRLs were determined with regard to the coexpression of immune-related genes and differentially expressed lncRNAs. The survival IRLs were obtained using the univariate Cox analysis. Subsequently, the prognosis model was constructed via the multivariate Cox analysis. Subsequently, functional annotation was conducted using Gene Set Enrichment Analysis (GSEA) and principal component analysis (PCA). In total, 341 IRLs were identified, and 6 IRLs were found to have a highly significant association with the prognosis of patients with HCC. The immune prognosis model was constructed with these 6 IRLs (AC099850.4, negative regulator of antiviral response, AL031985.3, PRRT3-antisense RNA1, AL365203.2, and long intergenic nonprotein coding RNA 1224) using the multivariate Cox regression analysis. In addition, immune-related prognosis signatures were confirmed as an independent prognostic factor. The association between prognostic signatures and immune infiltration indicated that the 6 lncRNAs could reflect the immune status of the tumor. Collectively, the present study demonstrates that six-lncRNA signatures may be potential biomarkers to predict the prognosis of patients with HCC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2022/2093437DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9283041PMC
July 2022

Cellulose-based thermosensitive supramolecular hydrogel for phenol removal from polluted water.

Environ Res 2022 Jul 14;214(Pt 2):113863. Epub 2022 Jul 14.

Jiangsu Co-Innovation Center of Efficient Processing and Utilization of Forest Resources, International Innovation Center for Forest Chemicals and Materials, College of Materials Science and Engineering, Nanjing Forestry University, Nanjing, Jiangsu, 210037, China; Higher Institution Centre of Excellence (HICoE), Institute of Tropical Aquaculture and Fisheries (AKUATROP), Universiti Malaysia Terengganu, 21030, Kuala Nerus, Terengganu, Malaysia; Sustainability Cluster, School of Engineering, University of Petroleum & Energy Studies, Dehradun, Uttarakhand, 248007, India. Electronic address:

Pollution of phenolic effluent from spice and plastics factories has become increasingly serious. Thus, developing a green and highly efficient adsorbent to remove phenolic compounds from wastewater is of urgent need. In this study, cellulose graft copolymer was synthesized through grafting 4-vinylpyridine monomer and polyethylene glycol methacrylate to a molecular skeleton of cellulose by free radical polymerization. The supramolecular hydrogel was successfully synthesized by physical cross-linking of cellulose graft copolymer and α-cyclodextrin. These supramolecular hydrogels were thoroughly characterized and the adsorption performance (adsorption isotherms and adsorption kinetics) of phenol on the supramolecular hydrogel were investigated in batch operation. The supramolecular hydrogel not only exhibited excellent adsorption of phenol, but also demonstrated increased mechanical strength due to the introduction of a modified cellulose base material. The adsorption kinetics of phenol on the supramolecular hydrogel followed a quasi-second-order reaction, with a correlation coefficient of 0.9909. The adsorption isotherm conformed to the Langmuir adsorption isotherm, and the maximum adsorption capacity of phenol can reach 80.71 mg g, which was 2-3 times higher than traditional carbon-based materials. The results demonstrate the great promise of the waste-derived supramolecular hydrogel to be used as an efficient adsorbent in wastewater treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.envres.2022.113863DOI Listing
July 2022

Update on the research and development of magnesium-based biodegradable implants and their clinical translation in orthopaedics.

Biomater Transl 2021 28;2(3):188-196. Epub 2021 Sep 28.

Musculoskeletal Research Laboratory of Department of Orthopaedics & Traumatology and The Chinese University of Hong Kong Shenzhen-Hong Kong Innovation and Technology Institute (Futian), The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China.

Biodegradable magnesium (Mg) or its alloys are desirable materials for development into new-generation internal fixation devices or implants with high biocompatibility, adequate mechanical modulus, and osteopromotive properties, which may overcome some of the drawbacks of the existing permanent orthopaedic implants with regard to stress-shielding of bone and beam-hardening effects on radiographic images. This review summarises the current research status of Mg-based orthopaedic implants in animals and clinical trials. First, detailed information of animal studies including bone fracture repair and anterior cruciate ligament reconstruction with the use of Mg-based orthopaedic devices is introduced. Second, the repair mechanisms of the Mg-based orthopaedic implants are also reviewed. Afterwards, reports of recent clinical cases treated using Mg-based implants in orthopaedics are summarised. Finally, the challenges and the strategies of the use of Mg-based orthopaedic implants are discussed. Taken together, the collected efforts in basic research, translational work, and clinical applications of Mg-based orthopaedic implants over the last decades greatly contribute to the development of a new generation of biodegradable metals used for the design of innovative implants for better treatment of orthopaedic conditions in patients with challenging skeletal disorders or injuries.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.12336/biomatertransl.2021.03.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9255812PMC
September 2021

Directed evolution of the genetically encoded zinc(II) FRET sensor ZapCY1.

Biochim Biophys Acta Gen Subj 2022 Oct 12;1866(10):130201. Epub 2022 Jul 12.

State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, PR China. Electronic address:

Zinc(II) ions (Zn) play an essential role in living systems, with their delicate concentration balance differing among the various intracellular organelles. The spatiotemporal distribution and homeostasis of Zn can be monitored through photoluminescence imaging using zinc sensors. Among such biosensors, genetically encoded fluorescent sensor proteins are attractive tools owing to their subcellular localization advantage and high biocompatibility. However, the limited fluorescent properties of these proteins, such as their insufficient quantum yield and dynamic range, restrict their practical use. In this study, we developed an expression-screening-directed evolution system and used it to improve ZapCY1, a genetically encoded fluorescence resonance energy transfer (FRET) sensor. After four rounds of directed evolution, the FRET dynamic range of the modified sensor (designated ZapTV-EH) was increased by 1.5-1.7-fold. With its enhanced signal-to-noise ratio and ability to detect a wide Zn concentration range, ZapTV-EH proves to be a better visualization tool for monitoring Zn at the subcellular level. Combined with the simplified subcloning and expression steps and sufficient mutant libraries, this directed evolution system may provide a more simple and efficient way to develop and optimize genetically encoded FRET sensors through high-throughput screening.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bbagen.2022.130201DOI Listing
October 2022

Investigating the association between the socioeconomic environment of the service area and fast food visitation: A context-based crystal growth approach.

Health Place 2022 Jul 11;76:102855. Epub 2022 Jul 11.

Department of Geography, Geomatics and Environment, University of Toronto Mississauga, 3359 Mississauga Road, Mississauga, ON, L5L 1C6, Canada. Electronic address:

Fast food consumption is one of the major causes of rising obesity rates. Fast food consumers are mostly residents located in the service area-the fast food outlet's surrounding area. Conventional buffer approaches may exhibit bias in measuring service areas by ignoring the local community's detailed spatial configuration and transportation preferences. This study uses fast food outlets and their visits provided by a mobile phone-based dataset named SafeGraph and applies a novel context-based crystal growth algorithm (CG) to delineate improved service areas of fast food outlets in Chicago. We also explore how socioeconomic variables in service areas by CG and buffer-based approaches are related to visits to fast food outlets. Results show that compared to conventional buffers, CG produces improved service areas as it excludes inaccessible barriers and adjusts the accessible areas by transportation preferences. Further, the model using service areas of public transport users by CG yields the best performance. Additionally, the rate of single-mother households and the number of other fast food outlets nearby are positively related to fast food visits in all models. Findings acknowledge the advantages of CG and help make policy interventions to reduce fast food consumption.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.healthplace.2022.102855DOI Listing
July 2022

Efficacy and safety of multi-kinase inhibitors in patients with radioiodine-refractory differentiated thyroid cancer: a systematic review and meta-analysis of clinical trials.

Expert Rev Anticancer Ther 2022 Jul 20:1-10. Epub 2022 Jul 20.

Department of Oncology, Hangzhou Hospital of Traditional Chinese Medicine Affiliated to Zhejiang Chinese Medical University, Hangzhou, Zhejiang province, China.

Objectives: Radioiodine-refractory differentiated thyroid cancer (RAI-rDTC) has frequently been associated with poor prognosis. We conducted a meta-analysis of published randomized controlled trials to evaluate multi-kinase inhibitors' efficacy and safety profile treatment.

Methods: A comprehensive search was conducted using PubMed, Embase, Cochrane, and Medline databases. The quality of literature and trial risk of bias was assessed using the Cochrane risk of bias tool, while the results of progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were evaluated using RevMan5.3 software.

Results: Treatment with MKIs significantly improved PFS and OS, but AEs were significantly higher than those in the control group (). The studies demonstrated the median PFS (HR 0.30, 95% CI: 0.18-0.50, ) and OS (HR 0.70, 95% CI: 0.57-0.88, ) in RAI-rDTC patients treated with MKIs, and the median PFS of papillary thyroid carcinoma (HR0.28, 95% CI: 0.22-0.37, ) along with follicular thyroid carcinoma (HR0.14, 95%CI 0.09-0.24, ) were extended.

Conclusion: MKIs significantly prolonged PFS and OS in patients with RAI-rDTC (). Our recommendation is to use MKIs carefully in patients after evaluating their health status to maximize treatment benefits and minimize adverse effects.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/14737140.2022.2102000DOI Listing
July 2022

Identification of a novel heterozygous missense TP63 variant in a Chinese pedigree with split-hand/foot malformation.

BMC Med Genomics 2022 07 13;15(1):157. Epub 2022 Jul 13.

Department of Obstetrics and Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu, China.

Background: Tumor protein p63 is an important transcription factor regulating epithelial morphogenesis. Variants associated with the TP63 gene are known to cause multiple disorders. In this study, we determined the genetic cause of split-hand/foot malformation in a Chinese pedigree.

Methods: For this study, we have recruited a Chinese family and collected samples from affected and normal individuals of the family (three affected and two normal). Whole exome sequencing was performed to detect the underlying genetic defect in this family. The potential variant was validated using the Sanger sequencing approach.

Results: Using whole-exome and Sanger sequencing, we identified a novel heterozygous pathogenic missense variant in TP63 (NM_003722.5: c.921G > T; p.Met307Ile). This variant resulted in the substitution of methionine with isoleucine. Structural analysis suggested a resulting change in the structure of a key functional domain of the p63 protein.

Conclusion: This novel missense variant expands the TP63 variant spectrum and provides a basis for genetic counseling and prenatal diagnosis of families with split-hand/foot malformation or other TP63-related diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12920-022-01311-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9281006PMC
July 2022

Vitamin B and folate decrease inflammation and fibrosis in NASH by preventing Syntaxin 17 homocysteinylation.

J Hepatol 2022 Jul 9. Epub 2022 Jul 9.

Laboratory of Hormonal Regulation, Cardiovascular and Metabolic Disorders, Duke-NUS Medical School, Singapore 169857; Duke Molecular Physiology Institute, Duke University School of Medicine, 300 N Duke St, Durham, NC 27701, USA; Endocrinology, Diabetes, and Metabolism Division, Duke University School of Medicine, 300 N Duke St, Durham, NC 27701, USA. Electronic address:

Background And Aims: The relationship between hyperhomocysteinemia (HHcy) and non-alcoholic steatohepatitis (NASH) is poorly understood.

Methods: We examined the effects of HHcy on NASH progression, metabolism, and autophagy in dietary and genetic mouse models, patients, and primates. We employed vitamin B (B) and folate (Fol) to reverse NASH features in mice and cell culture.

Results: Serum homocysteine (Hcy) correlated with hepatic inflammation and fibrosis in NASH. Elevated hepatic Hcy induced and exacerbated NASH. Gene expression of hepatic Hcy-metabolizing enzymes was down-regulated in NASH. Surprisingly, we found increased homocysteinylation (Hcy-lation) and ubiquitination of multiple hepatic proteins in NASH including the key autophagosome/lysosome fusion protein, Syntaxin 17 (Stx17). This protein was Hcy-lated and ubiquitinated, and its degradation led to autophagy block. Genetic manipulation of Stx17 revealed its critical role in regulating autophagy, inflammation and fibrosis during HHcy. Remarkably, dietary B/Fol, which promotes enzymatic conversion of homocysteine to methionine, decreased HHcy and hepatic Hcy-lated protein levels, restored Stx17 expression and autophagy, stimulated β-oxidation of fatty acids, and improved hepatic histology in mice with pre-established NASH.

Conclusions: HHcy plays a key role in the pathogenesis of NASH via Stx17 homocysteinylation. B/folate also may represent a novel first-line therapy for NASH.

Lay Summary: The roles of high serum homocysteine levels (HHcy) and intrahepatic homocysteine on the development of non-alcoholic seatohepatitis (NASH) are not known. We found HHcy increased with NASH severity and showed that homocysteinylation of the key autophagy protein STX17 led to autophagy block during NASH and NASH progression. Vitmains B and folate supplementation restored autophagy and reduced NASH progression and could be a new first-line therapy for NASH.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jhep.2022.06.033DOI Listing
July 2022

Discrimination of Lonicerae Japonicae Flos according to species, growth mode, processing method, and geographical origin with ultra-high performance liquid chromatography analysis and chemical pattern recognition.

J Pharm Biomed Anal 2022 Jul 5;219:114924. Epub 2022 Jul 5.

NMPA Key Laboratory for Quality Research and Evaluation of Traditional Chinese Medicine, Shenzhen Institute for Drug Control, Shenzhen, Guangdong 518057, China; Shenzhen Key Laboratory of Drug Quality Standard Research, Shenzhen Institute for Drug Control, Shenzhen, Guangdong 518057, China; School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, China. Electronic address:

Lonicerae japonicae flos (LJF, Lonicera japonica Thunb.) is often confused and/or adulterated with Lonicerae flos (LF, Lonicera macrantha (D.Don) Spreng.). Ecological conditions and processing methods strongly influenced the safety and efficacy of LJF. For the strict quality control of LJF, a rapid and feasible strategy for identification and classification of LJF by species, growth mode, processing method and geographical origin, based on chromatographic profiles and pattern recognition analysis, in 119 batches of Lonicera samples was systematically established. Firstly, comprehensive analysis of the chemical compositions of LJF was achieved using ultra-high performance liquid chromatography (UHPLC). Next, unsupervised principal component analysis showed that the influence of species, growth mode, processing method and geographical origin displayed a decreasing trend. Subsequently, classification models for authentication of LJF samples were established by linear discriminant analysis (LDA) with good classification abilities. Finally, sweroside and secoxyloganin could be considered as markers associated of cultivated and wild LJF, respectively, while 3-O-caffeoylquinic acid and 3,5-Di-O-caffeoylquinic acid could be regarded as markers for LF. Consequently, the findings suggest that UHPLC profiles combined with pattern recognition analysis is precise and feasible strategy for the discrimination and quality control of LJF.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jpba.2022.114924DOI Listing
July 2022

ARG-Mask RCNN: An Infrared Insulator Fault-Detection Network Based on Improved Mask RCNN.

Sensors (Basel) 2022 Jun 22;22(13). Epub 2022 Jun 22.

School of Information Science and Engineering, Dalian Polytechnic University, Dalian 116039, China.

Traditional power equipment defect-detection relies on manual verification, which places a high demand on the verifier's experience, as well as a high workload and low efficiency, which can lead to false detection and missed detection. The Mask of the regions with CNN features (Mask RCNN) deep learning model is used to provide a defect-detection approach based on the Mask RCNN of Attention, Rotation, Genetic algorithm (ARG-Mask RCNN), which employs infrared imaging as the data source to assess the features of damaged insulators. For the backbone network of Mask RCNN, the structure of Residual Network 101 (ResNet101) is improved and the attention mechanism is added, which makes the model more alert to small targets and can quickly identify the location of small targets, improve the loss function, integrate the rotation mechanism into the loss function formula, and generate an anchor frame where a rotation angle is used to accurately locate the fault location. The initial hyperparameters of the network are improved, and the Genetic Algorithm Combined with Gradient Descent (GA-GD) algorithm is used to optimize the model hyperparameters, so that the model training results are as close to the global best as possible. The experimental results show that the average accuracy of the insulator fault-detection method proposed in this paper is as high as 98%, and the number of frames per second (FPS) is 5.75, which provides a guarantee of the safe, stable, and reliable operation of our country's power system.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/s22134720DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9268765PMC
June 2022

Description of the novel HLA-A allele, HLA-A*02:937 in a Chinese individual.

HLA 2022 Jul 7. Epub 2022 Jul 7.

Clinical Transfusion Research Center, Institute of Blood Transfusion, CAMS & PUMC, Chengdu, China.

HLA-A*02:937 has one nucleotide change compared with HLA-A*02:07:01:01 in codon 182 of exon 3 (ACG>GCG).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/tan.14735DOI Listing
July 2022

Sirtuin 1 in Chronic Kidney Disease and Therapeutic Potential of Targeting Sirtuin 1.

Front Endocrinol (Lausanne) 2022 20;13:917773. Epub 2022 Jun 20.

Division of Nephrology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

The incidence and prevalence of chronic kidney disease (CKD) continue to increase worldwide remaining as a major public health burden. CKD eventually progresses to end-stage kidney failure and patients with CKD have high morbidity and mortality. Sirtuin 1 (SIRT1), a NAD+-dependent deacetylases, has significant renal protective effects through its regulation of fibrosis, apoptosis, and senescence, oxidative stress, inflammation and aging process. The renal protective effects of Sirt1 have been described in many kidney diseases such as diabetic kidney disease and HIV-related kidney disease. SIRT1 also has protective effects against vascular calcification and therefore could be developed as a therapy for both CKD and CKD complications. In this narrative review, we will give an overview of the recent progress on the role of SIRT1 and its downstream pathways in CKD. We will also discuss potential therapeutic approach by activating SIRT1-related pathway in patients with CKD. The purpose is to hope to provide some insights on the future direction of the research in the field of SIRT1 for CKD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fendo.2022.917773DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9251114PMC
June 2022

Mitochondrial fission induces immunoescape in solid tumors through decreasing MHC-I surface expression.

Nat Commun 2022 Jul 6;13(1):3882. Epub 2022 Jul 6.

Department of Oral and Maxillofacial Surgery, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, Guangzhou, 510120, China.

Mitochondrial dynamics can regulate Major Histocompatibility Complex (MHC)-I antigen expression by cancer cells and their immunogenicity in mice and in patients with malignancies. A crucial role in the mitochondrial fragmentation connection with immunogenicity is played by the IRE1α-XBP-1s axis. XBP-1s is a transcription factor for aminopeptidase TPP2, which inhibits MHC-I complex cell surface expression likely by degrading tumor antigen peptides. Mitochondrial fission inhibition with Mdivi-1 upregulates MHC-I expression on cancer cells and enhances the efficacy of adoptive T cell therapy in patient-derived tumor models. Therefore mitochondrial fission inhibition might provide an approach to enhance the efficacy of T cell-based immunotherapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-022-31417-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9259736PMC
July 2022

A Modified Technique in Rhinoplasty: A Septal Extension Graft Complex using Septal Cartilage, Ethmoid Bone, and Auricular Cartilage.

Aesthet Surg J 2022 Jul 4. Epub 2022 Jul 4.

Face and Neck Aesthetic and Plastic Surgery Center, Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Background: Due to the small and weak septal cartilage of Asians, it's a challenge to obtain ideal tip projection and nose lengthening by septal extension graft using only septal cartilage.

Objectives: This study was aim to introduce a septal extension graft complex using nasal septal cartilage and the perpendicular plate of ethmoid (PPE) bone as well as bilateral auricular cartilage, and examine its effectiveness in terms of morphological and mechanical support.

Methods: Septal cartilage was harvested under an endoscope according to standard techniques. Two pieces of PPE were placed on either side of the "L" strut, served as two spreader grafts. A double-layer of auricular cartilage was fixed as columellar strut grafts. Three-dimensional facial scanning was used to examine the change of three parameters. Nasal tip resistance was evaluated by a digital Newton meter.

Results: A total of 25 patients were followed up over a mean postoperative duration of 25.9 months. The analysis showed significant differences in both contour parameters and nasal resistance; nasal length (41.4±4.0 vs 46.2±3.4 mm, p<0.05) and nasal tip projection (21.3±3.2 vs 24.4±2.7 mm, p<0.05) appeared to increase postoperatively, while nasolabial angle (117.6±5.9° vs 109.5±5.3°, p<0.05) showed a significant decrease after surgery. The resistance of the nasal tip also increased significantly (p < 0.05) at the displacement of 1mm, 2mm, and 3mm. All patients were satisfied with the aesthetic results, and no serious complications occur.

Conclusions: This kind of modified SEG technique can effectively adjust nasal morphology for short-nose East Asians.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/asj/sjac185DOI Listing
July 2022

Intimately coupled photocatalysis and functional bacterial system enhance degradation of 1,2,3- and 1,3,5-trichlorobenzene.

J Environ Manage 2022 Sep 28;318:115595. Epub 2022 Jun 28.

Guangxi Bossco Environmental Protection Technology Co., Ltd., Nanning, 530007, China. Electronic address:

Intimate coupling of photocatalysis and biodegradation (ICPB) is considered a promising approach for the degradation of recalcitrant organic compounds. In this work, using Trichoderma with benzene degradation ability coupled with activated sludge as a biological source and sugarcane bagasse cellulose composite as a carrier, the ICPB system showed excellent degradation and mineralization of trichlorobenzene under visible light induction. The biofilm inside the ICPB carrier can degrade and mineralize the photocatalytic products. ICPB increased the degradation efficiency of 1,2,3-TCB and 1,3,5-TCB by 12.43% and 4.67%, respectively, compared to photocatalysis alone. The biofilms inside the ICPB carriers can mineralize photocatalytic products, which increases the mineralization efficiency by 18.74%. According to the analysis of intermediates, the degradation of 1,2,3-TCB in this coupled system involved stepwise dechlorination and ring opening. The biofilm in ICPB carrier evolved to be enriched in Cutaneotrichosporon, Trichoderma, Apiotrichum, Zoogloea, Dechloromonas, Flavihumibacter and Cupriavidus, which are known for biodegradable aromatic hydrocarbon and halogenate. Novel microbial seeds supplemented with Trichoderma-based ICPB seem to provide a new potential strategy for effective degradation and mineralization of TCB.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jenvman.2022.115595DOI Listing
September 2022

Continuous Interstitial Glucose Measurement for Flap Venous Occlusion Monitoring in a Diabetic Model.

J Craniofac Surg 2022 Jun 28. Epub 2022 Jun 28.

Head and Neck Plastic and Cosmetic Surgery Center, Plastic Surgery Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.

Abstract: Glucose has been used in the monitoring of transplanted flaps. However, few studies have focused on the effect of diabetes on the decrease in flap glucose levels. The purpose of this study was to evaluate the application of continuous interstitial glucose monitoring to detect flap venous occlusion in a diabetic rat model. The flap interstitial glucose level was measured by transcutaneous sensors in the bilateral vertical rectus abdominis myocutaneous flaps of each rat. interstitial glucose values in the bilateral flaps were recorded every 5 minutes after the venous occlusion of 1 flap. Forty-one rats were divided into the control group (n = 13), diabetic group (n = 15, established by the intraperitoneal injection of streptozotocin), and insulin-treated diabetic group (n = 13, systemic glucose well controlled by insulin before surgery). Results indicated that flap interstitial glucose decreased to the lowest level in all flaps with venous occlusion. The time from venous occlusionto the lowest interstitial glucose level was significantlylongerinthe diabetic group than the control group (120.8 ± 5.7 minutes versus 56.5 ± 6.7 min-minutes, P < 0.001), but was similar in the insulin-treated diabetic and control groups (56.5 ± 6.7 minutes versus 56.0 ± 6.6 minutes, P = 0.876). The change in interstitial glucose in both the diabetic and insulin-treated diabetic groups began with a plateau period or a slow decline before decreasing for 49.0 ± 6.4 minutes and 24.4 ± 4.3 min-minutes, respectively. in a diabetic rat model, impaired glucose metabolism prolongs the required monitoring time and dulls the reaction of flap interstitial glucose to venous congestion. Insulin restores the prolonged monitoring time, but not the reaction of flap interstitial glucose. Therefore, care is needed during application of the technique in diabetic patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/SCS.0000000000008657DOI Listing
June 2022

Walking Dead Tumor Cells for Targeted Drug Delivery Against Lung Metastasis of Triple-Negative Breast Cancer.

Adv Mater 2022 Jun 27:e2205462. Epub 2022 Jun 27.

State Key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.

Lung metastasis is challenging in patients with triple-negative breast cancer (TNBC). Surgery is always not available due to the dissemination of metastatic foci and most drugs are powerless because of poor retention at metastatic sites. TNBC cells generate an inflamed microenvironment and overexpress adhesive molecules to promote invasion and colonization. Herein, "walking dead" TNBC cells are developed through conjugating anti-PD-1 (programmed death protein 1 inhibitor) and doxorubicin (DOX)-loaded liposomes onto cell corpses for temporal chemo-immunotherapy against lung metastasis. The walking dead TNBC cells maintain plenary tumor antigens to conduct vaccination effects. Anti-PD-1 antibodies are conjugated to cell corpses via reduction-activated linker, and DOX-loaded liposomes are attached by maleimide-thiol coupling. This anchor strategy enables rapid release of anti-PD-1 upon reduction conditions while long-lasting release of DOX at inflamed metastatic sites. The walking dead TNBC cells improve pulmonary accumulation and local retention of drugs, reprogram the lung microenvironment through damage-associated molecular patterns (DAMPs) and PD-1 blockade, and prolong overall survival of lung metastatic 4T1 and EMT6-bearing mice. Taking advantage of the walking dead TNBC cells for pulmonary preferred delivery of chemotherapeutics and checkpoint inhibitors, this study suggests an alternative treatment option of chemo-immunotherapy to augment the efficacy against lung metastasis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/adma.202205462DOI Listing
June 2022

Boosting Fast Adversarial Training With Learnable Adversarial Initialization.

IEEE Trans Image Process 2022 1;31:4417-4430. Epub 2022 Jul 1.

Adversarial training (AT) has been demonstrated to be effective in improving model robustness by leveraging adversarial examples for training. However, most AT methods are in face of expensive time and computational cost for calculating gradients at multiple steps in generating adversarial examples. To boost training efficiency, fast gradient sign method (FGSM) is adopted in fast AT methods by calculating gradient only once. Unfortunately, the robustness is far from satisfactory. One reason may arise from the initialization fashion. Existing fast AT generally uses a random sample-agnostic initialization, which facilitates the efficiency yet hinders a further robustness improvement. Up to now, the initialization in fast AT is still not extensively explored. In this paper, focusing on image classification, we boost fast AT with a sample-dependent adversarial initialization, i.e., an output from a generative network conditioned on a benign image and its gradient information from the target network. As the generative network and the target network are optimized jointly in the training phase, the former can adaptively generate an effective initialization with respect to the latter, which motivates gradually improved robustness. Experimental evaluations on four benchmark databases demonstrate the superiority of our proposed method over state-of-the-art fast AT methods, as well as comparable robustness to advanced multi-step AT methods. The code is released at https://github.com//jiaxiaojunQAQ//FGSM-SDI.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1109/TIP.2022.3184255DOI Listing
July 2022
-->