Publications by authors named "Qi Shen"

503 Publications

Photoactivation of TGFβ/SMAD signaling pathway ameliorates adult hippocampal neurogenesis in Alzheimer's disease model.

Stem Cell Res Ther 2021 Jun 11;12(1):345. Epub 2021 Jun 11.

MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou, 510631, China.

Background: Adult hippocampal neurogenesis (AHN) is restricted under the pathological conditions of neurodegenerative diseases, especially in Alzheimer's disease (AD). The drop of AHN reduces neural circuit plasticity, resulting in the decrease of the generation of newborn neurons in dentate gyrus (DG), which makes it difficult to recover from learning/memory dysfunction in AD, therefore, it is imperative to find a therapeutic strategy to promote neurogenesis and clarify its underlying mechanism involved.

Methods: Amyloid precursor protein/presenilin 1 (APP/PS1) mice were treated with photobiomodulation therapy (PBMT) for 0.1 mW/mm per day in the dark for 1 month (10 min for each day). The neural stem cells (NSCs) were isolated from hippocampus of APP/PS1 transgenic mice at E14, and the cells were treated with PBMT for 0.667 mW/mm in the dark (5 min for each time).

Results: In this study, photobiomodulation therapy (PBMT) is found to promote AHN in APP/PS1 mice. The latent transforming growth factor-β1 (LTGFβ1) was activated in vitro and in vivo during PBMT-induced AHN, which promoted the differentiation of hippocampal APP/PS1 NSCs into newborn neurons. In particular, behavioral experiments showed that PBMT enhanced the spatial learning/memory ability of APP/PS1 mice. Mechanistically, PBMT-stimulated reactive oxygen species (ROS) activates TGFβ/Smad signaling pathway to increase the interaction of the transcription factors Smad2/3 with Smad4 and competitively reduce the association of Smad1/5/9 with Smad4, thereby significantly upregulating the expression of doublecortin (Dcx)/neuronal class-III β-tubulin (Tuj1) and downregulating the expression of glial fibrillary acidic protein (GFAP). These in vitro effects were abrogated when eliminating ROS. Furthermore, specific inhibition of TGFβ receptor I (TGFβR I) attenuates the DNA-binding efficiency of Smad2/3 to the Dcx promotor triggered by PBMT.

Conclusion: Our study demonstrates that PBMT, as a viable therapeutic strategy, directs the adult hippocampal APP/PS1 NSCs differentiate towards neurons, which has great potential value for ameliorating the drop of AHN in Alzheimer's disease mice.
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http://dx.doi.org/10.1186/s13287-021-02399-2DOI Listing
June 2021

A snapshot of HIV-1 capsid-host interactions.

Curr Res Struct Biol 2020 19;2:222-228. Epub 2020 Oct 19.

Department of Molecular Biophysics and Biochemistry, Yale University, 266 Whitney Avenue, New Haven, CT, 06511, USA.

From cellular deposition of the HIV-1 capsid to integration of the viral genome, the capsid constitutes a primary target of a variety of host proteins that work to either promote or inhibit HIV-1 infection. Successful progression of HIV-1 infection depends on interactions between the capsid and host factors involved in stability, cellular transport, nuclear import, and genome integration. The virus must also guard its reverse-transcribing genome inside the capsid from host restriction factors that bind the capsid and suppress infection. Understanding the structure and dynamics of the capsid protein (CA) component and the assembled capsid sheds light on the molecular underpinnings of overall capsid stability, architecture, and flexibility that govern HIV-1 capsid-host interactions. The vast majority of these interactions are mediated through recognition of higher order interfaces only present in the assembled capsid lattice. Patterns formed at these interfaces serve as signposts for capsid-binders. Here we provide a graphical summary of the intricate interactions between host factors and the HIV-1 capsid while highlighting recent research. Insights into how host proteins interact with the capsid is crucial for understanding the HIV-1 replication cycle and developing antiviral therapeutics to prevent viral genome integration.
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http://dx.doi.org/10.1016/j.crstbi.2020.10.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8189282PMC
October 2020

Nanoparticles based on polymers modified with pH-sensitive molecular switch and low molecular weight heparin carrying Celastrol and ferrocene for breast cancer treatment.

Int J Biol Macromol 2021 Jun 4. Epub 2021 Jun 4.

School of Pharmacy, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai 201203, China. Electronic address:

Triple negative breast cancer (TNBC) metastasis is still one of the obstacles in clinical treatment, while highly-effective cancer drugs usually cannot be used for their hydrophobicity and comprehensive system toxicity. This study built a kind of pH-sensitive nanoparticles (PP/H NPs) constructed by poly (lactic-co-glycolic acid) modified with β-cyclodextrin (PLGA-β-CD), polyethyleneimine grafted with benzimidazole (PEI-BM) and low molecular weight heparin (LMWH) to delivery Celastrol (Cela) and ferrocene (Fc) for breast cancer therapy. PLGA-β-CD and PEI-BM were synthesized by amidation reaction, the amphipathic polymer nanoparticles with 108.37 ± 1.02 nm were self-assembled in water. After PP/H NPs treatment, the half maximal inhibitory concentration (IC) decreased by 91% compared with Cela, and ROS level was also elevated. PP/H NPs led to substantial tumor inhibiting rate (TIR, 65.86%), utilized LMWH to strengthen the anti-metastasis effect of PP/H NPs. PP/H NPs took advantage of exogenous chemotherapeutics and endogenous ROS to inhibit tumor growth, and combined with LMWH to hinder breast cancer metastasis.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.05.204DOI Listing
June 2021

Photobiomodulation therapy for hair regeneration: A synergetic activation of β-CATENIN in hair follicle stem cells by ROS and paracrine WNTs.

Stem Cell Reports 2021 Jun 20;16(6):1568-1583. Epub 2021 May 20.

MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou 510631, China; Guangdong Provincial Key Laboratory of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou 510631, China. Electronic address:

Photobiomodulation therapy (PBMT) has shown encouraging results in the treatment of hair loss. However, the mechanism by which PBMT controls cell behavior to coordinate hair cycle is unclear. Here, PBMT is found to drive quiescent hair follicle stem cell (HFSC) activation and alleviate hair follicle atrophy. Mechanistically, PBMT triggers a new hair cycle by upregulating β-CATENIN expression in HFSCs. Loss of β-Catenin (Ctnnb1) in HFSCs blocked PBMT-induced hair regeneration. Additionally, we show PBMT-induced reactive oxygen species (ROS) activate the PI3K/AKT/GSK-3β signaling pathway to inhibit proteasome degradation of β-CATENIN in HFSCs. Furthermore, PBMT promotes the expression and secretion of WNTs in skin-derived precursors (SKPs) to further activate the β-CATENIN signal in HFSCs. By contrast, eliminating ROS or inhibiting WNT secretion attenuates the activation of HFSCs triggered by PBMT. Collectively, our work suggests that PBMT promotes hair regeneration through synergetic activation of β-CATENIN in HFSCs by ROS and paracrine WNTs by SKPs.
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http://dx.doi.org/10.1016/j.stemcr.2021.04.015DOI Listing
June 2021

Photobiomodulation therapy promotes the ATP-binding cassette transporter A1-dependent cholesterol efflux in macrophage to ameliorate atherosclerosis.

J Cell Mol Med 2021 Jun 5;25(11):5238-5249. Epub 2021 May 5.

MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou, China.

Atherosclerosis is a chronic inflammatory disease related to a massive accumulation of cholesterol in the artery wall. Photobiomodulation therapy (PBMT) has been reported to possess cardioprotective effects but has no consensus on the underlying mechanisms. Here, we aimed to investigate whether PBMT could ameliorate atherosclerosis and explore the potential molecular mechanisms. The Apolipoprotein E (ApoE) mice were fed with western diet (WD) for 18 weeks and treated with PBMT once a day in the last 10 weeks. Quantification based on Oil red O-stained aortas showed that the average plaque area decreased 8.306 ± 2.012% after PBMT (P < .05). Meanwhile, we observed that high-density lipoprotein cholesterol level in WD + PBMT mice increased from 0.309 ± 0.037 to 0.472 ± 0.038 nmol/L (P < .05) compared with WD mice. The further results suggested that PBMT could promote cholesterol efflux from lipid-loaded primary peritoneal macrophages and inhibit foam cells formation via up-regulating the ATP-binding cassette transporters A1 expression. A contributing mechanism involved in activating the phosphatidylinositol 3-kinases/protein kinase C zeta/specificity protein 1 signalling cascade. Our study outlines that PBMT has a protective role on atherosclerosis by promoting macrophages cholesterol efflux and provides a new strategy for treating atherosclerosis.
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http://dx.doi.org/10.1111/jcmm.16531DOI Listing
June 2021

The safety and tolerability of alkaloids from leaves in healthy Chinese volunteers: a single-centre, randomized, double-blind, placebo-controlled phase I clinical trial.

Pharm Biol 2021 Dec;59(1):484-493

Institute of Drug Clinical Trials, West China Hospital, Sichuan University, Chengdu, People's Republic of China.

Context: Capsule of alkaloids from the leaf of (L.) R.Br. (Apocynaceae) (CALAS) is a new investigational botanical drug (No. 2011L01436) for bronchitis, post-infectious cough and asthma.

Objective: To observe the clinical safety and tolerability of CALAS.

Materials And Methods: Subjects were assigned to eight cohorts, and each received randomly CALAS or placebo in one of single ascending dose (SAD) of 8, 40, 120, 240, 360, 480, or in one of multiple ascending dose (MAD) of 40 or 120 mg, three times daily for 7 days. Each cohort contained two placebo subjects.

Results: Sixty-two enrolled volunteers completed the study and no serious adverse events and clinically significant changes in vital signs, electrocardiography, and upper abdominal Doppler ultrasonography were observed. The ratios of treatment-emergent adverse events (TEAEs) were reported in 11/46 (23.91%) of CALAS groups and 3/16 (18.75%) of the placebo group ( > 0.05), respectively, based on the results of SAD and MAD. All TEAEs were mild, transient, and disappeared without any intervention. The TEAEs possibly related to CALAS treatment were as followings: hiccups (4/46: 8%), dry mouth and nausea (3/46: 6%), increased sleep (2/46: 4%), abdominal distension (1/46: 2%), bilirubin elevated (1/46: 2%).

Discussion And Conclusions: CALAS is safe and well-tolerated with no unexpected or clinically relevant safety concerns up to a single dose of 360 mg and three times daily for 7 days up to 120 mg in healthy Chinese volunteers, supporting further Phase II studies.
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http://dx.doi.org/10.1080/13880209.2021.1893349DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8086589PMC
December 2021

Smart biomimetic metal organic frameworks based on ROS-ferroptosis-glycolysis regulation for enhanced tumor chemo-immunotherapy.

J Control Release 2021 Jun 17;334:21-33. Epub 2021 Apr 17.

School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China. Electronic address:

Antitumor immunotherapy is limited by low tumor immunogenicity and immunosuppressive microenvironment (TIME), which could be improved by "ROS-ferroptosis-glycolysis regulation" strategy. Herein, a cancer cell membrane coated metal organic framework (MOF) loading with glucose oxidase (GOx) and doxorubicin (DOX) was constructed (denoted as mFe(SS)/DG). Benefiting from the homotypic targeting of cancer cell membrane, the nanoplatform effectively accumulated in tumors. mFe(SS)/DG based on coordination between Fe and disulfide-bearing ligand scavenged GSH and downregulated glutathione peroxide 4 (GPX4) to trigger ferroptosis. GOx catalyzed glucose to generate abundant HO for enhancing Fenton reaction, resulting in excessive ROS in tumors. The ROS burst simultaneously promoted ferroptosis and inhibited glycolysis. Ferroptosis combined with DOX induced immunogenic cell death (ICD) and released tumor antigens to initiate antitumor immunity. Glycolysis repression remodeled TIME by decreasing lactate to solidify and boost the antitumor immunity. The smart biomimetic nanoplatform integrates tumor metabolism and immunity based on ROS-ferroptosis-glycolysis regulation, providing a potential anti-tumor strategy.
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http://dx.doi.org/10.1016/j.jconrel.2021.04.013DOI Listing
June 2021

Multifunctional [email protected] nanoparticles cluster synergize chemotherapy and photothermal therapy for tumor metastasis.

Nanomedicine 2021 Apr 14;34:102399. Epub 2021 Apr 14.

School of Pharmacy, Shanghai Jiao Tong University, Shanghai, China. Electronic address:

The poor drug delivery and unsatisfying therapeutic effects remain to be the primary challenges for cancer therapy. Nanosystem that combines multiple functions into a single platform is an ideal strategy. Here, a smart drug delivery nanoplatform ([email protected]/P) based on [email protected] nanoparticles, loaded with doxorubicin (DOX) and pirfenidone (PFD) was constructed. Importantly, the β-CD-DMA and PEG-DMA could be activated in the mild acidic tumor microenvironment, then the nanosystem underwent charge reversal and PFD release. PFD could inhibit cancer-associated fibroblasts (CAFs) activation and enhance tumor penetration. And the residual nanostructure [email protected] could trigger cascade amplified ROS generation to induce tumor cell death. The photothermal effect further strengthened the anti-tumor efficacy. Finally, the nanosystem showed remarkable inhibition of tumor growth (89.7%) and lung metastasis. The innovatively designed nanosystem integrating chemotherapy and photothermal effect would provide a promising strategy in breast cancer therapy.
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http://dx.doi.org/10.1016/j.nano.2021.102399DOI Listing
April 2021

Photobiomodulation Therapy Ameliorates Glutamatergic Dysfunction in Mice with Chronic Unpredictable Mild Stress-Induced Depression.

Oxid Med Cell Longev 2021 29;2021:6678276. Epub 2021 Mar 29.

MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou 510631, China.

Accumulating evidence indicates that dysfunction of the glutamatergic neurotransmission has been widely involved in the pathophysiology and treatment of depression. Photobiomodulation therapy (PBMT) has been demonstrated to regulate neuronal function both and . Herein, we aim to investigate whether the antidepressant phenotype of PBMT is associated with the improvement of glutamatergic dysfunction and to explore the mechanisms involved. Results showed that PBMT decreased extracellular glutamate levels via upregulation of glutamate transporter-1 (GLT-1) and rescued astrocyte loss in the cerebral cortex and hippocampus, which also alleviated dendritic atrophy and upregulated the expression of AMPA receptors on the postsynaptic membrane, ultimately exhibiting behaviorally significant antidepressant effects in mice exposed to chronic unpredictable mild stress (CUMS). Notably, PBMT also obtained similar antidepressant effects in a depressive mouse model subcutaneously injected with corticosterone (CORT). Evidence from mechanistic experiments demonstrated that PBMT treatment significantly increased both the GLT-1 mRNA and protein levels via the Akt/NF-B signaling pathway. NF-B-regulated transcription was in an Akt-dependent manner, while inhibition of Akt attenuated the DNA-binding efficiency of NF-B to the GLT-1 promoter. Importantly, , we further found that PKA activation was responsible for phosphorylation and surface levels of AMPA receptors induced by PBMT, which is likely to rescue excitatory synaptic transmission. Taken together, our research suggests that PBMT as a feasible therapeutic approach has great potential value to control the progression of depression.
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http://dx.doi.org/10.1155/2021/6678276DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024102PMC
June 2021

Circular RNA hsa_circ_0000700 promotes cell proliferation and migration in Esophageal Squamous Cell Carcinoma by sponging miR-1229.

J Cancer 2021 5;12(9):2610-2623. Epub 2021 Mar 5.

Department of Radiotherapy, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, Zhejiang, 310022, China.

Accumulating evidence has demonstrated that circular RNAs (circRNAs) are involved in the pathogenesis of cancer, including that of esophageal squamous cell carcinoma (ESCC). The current study aimed to investigate the role of hsa_circ_0000700 in ESCC. hsa_circ_0000700, miR-1229, and related functional gene expression was measured by RT-qPCR. To characterize the functions of hsa_circ_0000700 and miR-1229, ESCC cells were infected with hsa_circ_0000700-specific siRNA, miR-1229 mimics, and an inhibitor alone or in combination. Cell Counting Kit-8 (CCK8), colony formation, EdU, flow cytometry, and Transwell assays were employed to evaluate cell proliferation, apoptosis, and migration. Luciferase reporter and RNA immunoprecipitation assays were used to confirm the targeting relationship between hsa_circ_0000700 and miR-1229. Finally, a competing endogenous RNAs (ceRNA) network was built for hsa_circ_0000700, and miR-1229 targets were analyzed by bioinformatics. circ_0000700 expression was significantly upregulated in ESCC cell lines. Actinomycin D and RNase R treatment confirmed that circ_0000700 was more stable than its linear CDH9 mRNA form. Moreover, a cytoplasmic and nuclear fractionation assay suggested that circ_0000700 was mainly distributed in the cytoplasm of ECA-109 and TE-1 cells. , the proliferative and migratory capacities of ECA-109 and TE-1 cells were inhibited by knocking down circ_0000700 expression. Additionally, miR-1229 silencing reversed the circ_0000700-specific siRNA-induced attenuation of malignant phenotypes. Mechanistically, circ_0000700 was identified as a sponge of miR-1229 and could activate PRRG4, REEP5, and PSMB5 indirectly to promote ESCC progression. In summary, our results suggest that hsa_circ_0000700 functions as an oncogenic factor by sponging miR-1229 in ESCC.
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http://dx.doi.org/10.7150/jca.47112DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040728PMC
March 2021

Identification of a novel promoter for driving antibiotic-resistant genes to reduce the metabolic burden during protein expression and effectively select multiple integrations in Pichia Pastoris.

Appl Microbiol Biotechnol 2021 Apr 5;105(8):3211-3223. Epub 2021 Apr 5.

Key Laboratory of Bioorganic Synthesis of Zhejiang Province, College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou, 310014, People's Republic of China.

Routine approaches for the efficient expression of heterogenous proteins in Pichia pastoris include using the strong methanol-regulated alcohol oxidase (AOX1) promoter and multiple inserts of expression cassettes. To screen the transformants harboring multiple integrations, antibiotic-resistant genes such as the Streptoalloteichus hindustanus bleomycin gene are constructed into expression vectors, given that higher numbers of insertions of antibiotic-resistant genes on the expression vector confer resistance to higher concentrations of the antibiotic for transformants. The antibiotic-resistant genes are normally driven by the strong constitutive translational elongation factor 1a promoter (P). However, antibiotic-resistant proteins are necessary only for the selection process. Their production during the heterogenous protein expression process may increase the burden in cells, especially for the high-copy strains which harbor multiple copies of the expression cassette of antibiotic-resistant genes. Besides, a high concentration of the expensive antibiotic is required for the selection of multiple inserts because of the effective expression of the antibiotic-resistant gene by the TEF1 promoter. To address these limitations, we replaced the TEF1 promoter with a weaker promoter (P) derived from the potential promoter region of 2-deoxyglucose-6-phosphate phosphatase gene for driving the antibiotic-resistant gene expression. Importantly, the P has even lower activity under carbon sources (glycerol and methanol) used for the AOX1 promoter-based production of recombinant proteins compared with glucose that is usually used for the selection process. This strategy has proven to be successful in screening of transformants harboring more than 3 copies of the gene of interest by using plates containing 100 μg/ml of Zeocin. Meanwhile, levels of Zeocin resistance protein were undetectable by immunoblotting in these multiple-copy strains during expression of heterogenous proteins.Key points• P was identified as a novel glucose-regulated promoter.• The expression of antibiotic-resistant gene driven by P was suppressed during the recombinant protein expression, resulting in reducing the metabolic burden.• The transformants harboring multiple integrations were cost-effectively selected by using the P for driving antibiotic-resistant genes.
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http://dx.doi.org/10.1007/s00253-021-11195-0DOI Listing
April 2021

Downregulation of PARVA promotes metastasis by modulating integrin-linked kinase activity and regulating MAPK/ERK and MLC2 signaling in prostate cancer.

Transl Androl Urol 2021 Feb;10(2):915-928

Department of Urology, Peking University First Hospital, Beijing, China.

Background: Metastasis is the predominant cause of mortality in prostate cancer (PCa); however, the underlying mechanisms are largely uncharted. Here, we found that Parvin alpha (PARVA) is downregulated in PCa and its loss is associated with clinical metastasis. We further explored the mechanistic basis of this finding.

Methods: The mRNA expression of PARVA was identified by analysis of the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) data sets. Immunohistochemistry (IHC) analysis was performed to evaluate the PARVA expression pattern in 198 PCa tissues, and 36 metastatic lymph node tissues. The function and molecular mechanism by which PARVA affects PCa were investigated using knockdown and overexpression cell lines. The effect of PARVA in cell proliferation, migration, and invasion in PCa cells was detected by MTS assay and Transwell assay. Real-time polymerase chain reaction (PCR) and Western blot analysis were used to assess the gene expression in mRNA and protein level.

Results: The microarray data analysis indicated that PARVA was drastically downregulated in primary and metastatic PCa compared with normal and primary samples, respectively (all P<0.001). Multivariate Cox regression analysis suggested that downregulation of PARVA in PCa was an independent prognostic factor for poor biochemical recurrence (BCR)-free survival (P<0.01). IHC analysis confirmed that PARVA was frequently downregulated in metastatic and primary PCa tissues (All P<0.001). Furthermore, PARVA expression was found to be associated with Gleason score, pathological stage, extracapsular extension, and lymph node invasion (All P<0.05). Knockdown of PARVA triggered cell migration and invasion , whereas overexpression of PARVA reverted the invasive phenotypes. Mechanistic investigations identified that overexpression of PARVA repressed the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) phosphorylation via inhibiting the integrin-linked kinase (ILK) biological function. With knockdown of ILK, the downregulated MAPK/ERK phosphorylation and Myosin Light Chain 2 (MLC2) expression by PARVA overexpression were abolished, indicating that the PARVA effect on PCa is ILK/MAPK/ERK pathway dependent.

Conclusions: Our study revealed that loss of PARVA expression in PCa promotes metastasis by releasing the inhibition of ILK activity, followed by the activation of MAPK/ERK and MLC2 signaling.
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http://dx.doi.org/10.21037/tau-21-108DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947443PMC
February 2021

Ferroptosis/pyroptosis dual-inductive combinational anti-cancer therapy achieved by transferrin decorated nanoMOF.

Nanoscale Horiz 2021 04 9;6(4):348-356. Epub 2021 Mar 9.

School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China.

Non-apoptotic cell death such as ferroptosis and pyroptosis has shed new light on cancer treatment, whereas combinational therapy using both these mechanisms has not yet been fully explored. Herein, a dual-inductive nano-system to realize ferroptosis/pyroptosis mediated anti-cancer effects is presented. The nanodrug ([email protected]) is constructed with a piperlongumine (PL) loaded metal-organic framework (MOF) coated with transferrin decorated pH sensitive lipid layer. Intracellular iron was enriched with an iron-containing MOF, whose endocytosis can be further facilitated by transferrin decorated on the lipid layer, which provides a prerequisite for the occurrence of ferroptosis and pyroptosis. Piperlongumine as the ferroptosis inducer can strengthen the ferroptotic cell death, and provide HO for the dual induction system to increase ROS generation through Fenton reaction. On the basis of validation of both ferroptosis and pyroptosis, the dual-inductive nanodrug demonstrated ideal anticancer effects in the xenograft mice model, which proved that the ferroptosis/pyroptosis dual-inductive nanoplatform could be an effective and promising anticancer modality.
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http://dx.doi.org/10.1039/d0nh00674bDOI Listing
April 2021

Oleanolic acid derivative HA-20 inhibits adipogenesis in a manner involving PPARγ-FABP4/aP2 pathway.

J Mol Endocrinol 2021 Mar;66(3):245-258

State Key Laboratory of Analytical Chemistry for Life Science, Collaborative Innovation Centre of Chemistry for Life Sciences, Jiangsu Key Laboratory of Advanced Organic Materials, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, Jiangsu, China.

Obesity is a chronic disease that increases the risk of type II diabetes, heart diseases and nonalcoholic fatty liver disease. Unfortunately, to date, only a handful of drugs are approved for clinical use. This study aims at the discovery of anti-obesity agents based on naturally sourced oleanolic acid (OA) derivatives. 3T3-L1 preadipocytes were differentiated into mature adipocytes for in vitro assays, and a high-fat diet (HFD)-induced obesity mice model was established for in vivo studies. The screening of the OA derivatives was performed with 3T3-L1 cell, and resulted in a discovery of a novel compound HA-20 with a potent inhibitory activity on 3T3-L1 adipogenesis. In vitro data demonstrated that HA-20 markedly suppressed the adipogenesis in 3T3-L1 at the early stage without cytotoxicity. In vivo research using HFD mice revealed that HA-20 lowered the body weight, and possessed a lipid-lowering effect. Transcriptome analysis discovered that the mainly adipogenesis/lipogenesis genes regulated by HA-20 were Pparg, Cebpa, Fas, Acc, and Fabp4/aP2. Mechanism study revealed that HA-20 played its bioactive roles at least via downregulating PPARγ-FABP4/aP2 pathway in 3T3-L1, which was further confirmed in HFD-induced obesity mice. Our findings provided a new insight into fighting fat accumulation based on OA derivatives, and demonstrated that HA-20 may sever as a worthy leading compound for the further development of anti-obesity agents.
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http://dx.doi.org/10.1530/JME-20-0075DOI Listing
March 2021

Comparative transcriptomic analyses of normal and peloric mutant flowers in Cymbidium goeringii Rchb.f identifies differentially expressed genes associated with floral development.

Mol Biol Rep 2021 Mar 25;48(3):2123-2132. Epub 2021 Feb 25.

Institute of Horticulture, Zhejiang Academy of Agriculture Sciences, Hangzhou, Zhejiang, China.

Cymbidium geringii has high ornamental and economic importance. Its traits, including flower shape, size, and color, are highly sought by orchid breeders. Gaining insights into the molecular basis of C. geringi flower development would accelerate genetic improvement of other orchids. Methods and Results: Here, C. goeringii RNA was purified from normal and peloric mutant flowers, and cDNA libraries constructed for Illumina sequencing. We generated 329,156,782 clean reads, integrated them, and then assembled into 236,811 unigenes averaging 595 bp long. A total of 11,992 differentially expressed genes s, of which 6119 were upregulated and 5873 downregulated, were uncovered in peloric mutant flower buds relative to normal flower buds. Kyoto Encyclopedia of Genes and Genomes enrichment assessments posited that these differentially expressed genes are associated with "Photosynthesis", "Linoleic acid metabolism", as well as "Plant hormone signal transduction" cascades. The DEGs were designated to 12 remarkably enriched GO terms, and 16 cell wall associated GO terms. The expression level of 16 determined genes were verified using RT-qPCR. Conclusions: Our gene expression data may be used to study the regulatory mechanism of flower organ development in C. geringi.
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http://dx.doi.org/10.1007/s11033-021-06216-0DOI Listing
March 2021

Fate of antibiotic resistance genes and metal resistance genes during the thermophilic fermentation of solid and liquid swine manures in an ectopic fermentation system.

Ecotoxicol Environ Saf 2021 Apr 13;213:111981. Epub 2021 Feb 13.

Institute of Plant Protection and Microbiology, Zhejiang Academy of Agriculture Science, Hangzhou, Zhejiang, PR China.

Environmental pollution due to resistance genes from livestock manure has become a serious issue that needs to be resolved. However, little studies focused on the removal of resistance genes in simultaneous processing of livestock feces and urine. This study investigated the fate of antibiotic resistance genes (ARGs), metal resistance genes (MRGs), and class 1 integron-integrase gene (intI1) during thermophilic fermentation of swine manure in an ectopic fermentation system (EFS), which has been regarded as a novel system for efficiently treating both feces and urine. The abundances of MRGs and tetracycline resistance genes were 34.44-97.71% lower in the EFS. The supplementation of heavy metals significantly increased the abundance of intI1, with the enhancement effect of copper being more prominent than that of zinc. The highest abundances of resistance genes and intI1 were observed at high Cu levels (A2), indicating that Cu can increase the spreading of resistance genes through integrons. Network analysis revealed the co-occurrence of ARGs, MRGs, and intI1, and these genes potentially shared the same host bacteria. Redundancy analysis showed that the bacterial community explained most of the variations in ARGs, and environmental factors had influences on ARGs abundances by modulating the bacterial community composition. The decreased Sphingomonas, Comamonas, Acinetobacter, Lactobacillus, Bartonella, Rhizobium, and Bacteroides were mainly responsible for the reduced resistance genes. These results demonstrate that EFS can reduce resistance genes in simultaneous processing of livestock feces and urine.
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http://dx.doi.org/10.1016/j.ecoenv.2021.111981DOI Listing
April 2021

Palbociclib and cetuximab compared with placebo and cetuximab in platinum-resistant, cetuximab-naïve, human papillomavirus-unrelated recurrent or metastatic head and neck squamous cell carcinoma: A double-blind, randomized, phase 2 trial.

Oral Oncol 2021 04 8;115:105192. Epub 2021 Feb 8.

Head and Neck Oncology Division, Japanese National Cancer Center, Chiba, Japan.

Objectives: This study examined whether palbociclib and cetuximab prolonged overall survival (OS) versus placebo and cetuximab.

Materials And Methods: In this double-blind, randomized, phase 2 trial (PALATINUS), patients with platinum-resistant, cetuximab-naïve, human papillomavirus-unrelated recurrent/metastatic head and neck squamous-cell carcinoma received cetuximab and either palbociclib (arm A) or placebo (arm B). The primary endpoint was OS; 120 patients were required to have ≥80% power to detect a hazard ratio (HR) of 0.6 (median OS of 10 months in arm A and 6 months in arm B) using a one-sided, log-rank test (P = 0.10).

Results: 125 patients were randomized (arm A: 65, arm B: 60). Median follow-up was 15.9 months (IQR, 11.3-22.7). Median OS was 9.7 months in arm A and 7.8 months in arm B (HR, 0.82; 95% CI, 0.54-1.25; P = 0.18). Median progression-free survival was 3.9 months in arm A and 4.6 months in arm B (HR, 1.00; 95% CI, 0.67-1.5; P = 0.50). The most common treatment-related adverse events in arm A were rash (39 patients, 60.9%) and neutropenia (26, 40.6%; three febrile) and in arm B was rash (32, 53.3%).

Conclusion: There was no significant difference in median OS with palbociclib and cetuximab versus placebo and cetuximab.

Funding: Pfizer Inc (NCT02499120).
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http://dx.doi.org/10.1016/j.oraloncology.2021.105192DOI Listing
April 2021

Myelodysplastic syndrome with t(6;9)(p22;q34.1)/DEK-NUP214 better classified as acute myeloid leukemia? A multicenter study of 107 cases.

Mod Pathol 2021 Jun 8;34(6):1143-1152. Epub 2021 Feb 8.

Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

t(6;9)(p22;q34.1)/DEK-NUP214 is a recurrent genetic abnormality that occurs in 1-2% of patients with acute myeloid leukemia (AML), and rarely in myelodysplastic syndrome (MDS). It has been suggested by others that all myeloid neoplasms with t(6;9)/DEK-NUP214 may be considered as AML, even when blast count is <20%. In this study, we compared the clinicopathologic features of 107 patients with myeloid neoplasms harboring t(6;9)/DEK-NUP214: 33 MDS and 74 AML. Compared with patients with AML, patients with MDS were older (p = 0.10), had a lower white blood cell count (p = 0.0017), a lower blast count in the peripheral blood (p < 0.0001) and bone marrow (p < 0.0001), a higher platelet count (p = 0.022), and a lower frequency of FLT3-ITD mutation (p = 0.01). In addition, basophilia was not a common feature in the patients of this cohort. Although there was no difference in overall survival between MDS and AML patients (p = 0.18) in the entire cohort, the survival curves did show a trend toward favorable survival in MDS patients. Multivariate analyses showed that initial diagnosis of MDS vs. AML and allogeneic hematopoietic stem cell transplantation were prognostic factors for survival of patients with t(6;9)/DEK-NUP214 (p = 0.008 and p < 0.0001, respectively). Our data suggest that MDS with t(6;9)/DEK-NUP214 is prognostically not equivalent to AML with t(6;9)/DEK-NUP214. These data also show that stem cell transplantation greatly improves the survival of MDS and AML patients with myeloid neoplasms associated with t(6;9)/DEK-NUP214.
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http://dx.doi.org/10.1038/s41379-021-00741-wDOI Listing
June 2021

Effectiveness of intervention program on the change of glycaemic control in diabetes with depression patients: A meta-analysis of randomized controlled studies.

Prim Care Diabetes 2021 Jun 5;15(3):428-434. Epub 2021 Feb 5.

Department of Psychiatric, Affiliated Hospital of Guangzhou Medical University, Guangzhou, China; Guangdong Engineering Technology Research Center for Translational Medicine of Mental Disorders, Guangzhou, China. Electronic address:

Aim: The glycaemic control of diabetes with depression was inconsistent from randomized controlled studies. This meta-analysis aimed to explore the effectiveness of intervention methods in diabetes with depression.

Methods: This study systematically searched electronic databases (PubMed, EBSCO, Elsevier, Springer, Wiley, and Cochrane) for studies published up to August 17, 2020. Standardized mean difference (SMD) and 95%CI were used to evaluate the effectiveness of interventions on HbA1c. Heterogeneity was estimated using the I statistic. Begg's test was used to assess the possible publication bias among studies.

Results: Twelve studies of 2444 cases were included in this study. The overall SMD is -0.22 and 95%CI -0.33 to -0.10 in 0-6 months of intervention group. The I and P were 18.4% and 0.26. There are no publication bias tested (z = 0.37, P = 0.72).

Conclusion: Cognitive behavioral therapy and mindful self-compassion might be effective method to improve glycaemic control of diabetes with depression in 0-6 months.
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http://dx.doi.org/10.1016/j.pcd.2021.01.006DOI Listing
June 2021

Photobiomodulation Therapy for Thrombocytopenia by Upregulating Thrombopoietin Expression via the ROS-dependent Src/ERK/STAT3 Signaling Pathway.

J Thromb Haemost 2021 Jan 27. Epub 2021 Jan 27.

MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou, China.

Background: Chemotherapy-induced thrombocytopenia (CIT) can increase the risk of bleeding, which may delay or prevent the administration of anticancer treatment schedules. Photobiomodulation therapy (PBMT), a non-invasive physical treatment, has been proposed to improve thrombocytopenia; however, its underlying regulatory mechanism is not fully understood.

Objective: To further investigate the mechanism of thrombopoietin (TPO) in megakaryocytopoiesis and thrombopoiesis.

Methods: Multiple approaches such as western blotting, cell transfection, flow cytometry and animal studies were utilized to explore the effect and mechanism of PBMT on thrombopoiesis.

Results: PBMT prevented a severe drop in platelet count by increasing platelet production, and then ameliorated CIT. Mechanistically, PBMT significantly upregulated hepatic TPO expression in a thrombocytopenic mouse model, which promoted megakaryocytopoiesis and thrombopoiesis. The levels of TPO mRNA and protein increased by PBMT via the Src/ERK/STAT3 signaling pathway in hepatic cells. Furthermore, the generation of the reactive oxygen species was responsible for PBMT-induced activation of Src and its downstream target effects.

Conclusions: Our research suggests that PBMT is a promising therapeutic strategy for the treatment of CIT.
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http://dx.doi.org/10.1111/jth.15252DOI Listing
January 2021

First-in-human safety, tolerability, and pharmacokinetics of ammoxetine in healthy subjects: a randomized, double-blind, placebo-controlled phase I study.

Eur J Pharm Sci 2021 Apr 19;159:105724. Epub 2021 Jan 19.

GCP Center/ Institute of Drug Clinical Trials, West China Hospital of Sichuan University, Sichuan, China. Electronic address:

Background: Ammoxetine is a novel selective serotonin and norepinephrine reuptake inhibitor. Preclinical studies have indicated the potential utility of ammoxetine for therapy in major depressive disorder.

Purpose: To investigate the first-in-human safety, tolerability, and pharmacokinetics (PK) of ammoxetine in healthy subjects and evaluate the effect of CYP2C19 polymorphisms on metabolism of ammoxetine.

Methods: In this randomized, double-blind, placebo-controlled phase I study, healthy Chinese subjects were allocated to receive 2.5, 7.5, 15, 30, 45, 65, 100 mg ammoxetine or placebo in single-dose part and 15, 30, 45 mg ammoxetine or placebo twice daily for 8 days in multiple-dose part. Pharmacokinetic, safety and tolerability assessments were performed.

Results: A total of 134 subjects were screened and 94 were enrolled. All the ammoxetine-related adverse events (AEs) were mild and resolved spontaneously. No hepatic AEs were reported during the study. Ammoxetine was well absorbed after oral administration with T reached in 5.0-6.0 h. After single-dosing, C and AUC increased proportionally with dose, except at 65 mg. After multiple-dosing, the exposures of ammoxetine at steady state increased slightly in a more-than-dose-proportional manner over the dose range studied, probably due to the saturated elimination. Steady state was achieved 6 days after multiple-dosing was initiated. The low extent of urinary excretion of ammoxetine (< 2%) indicated it is undergoing extensive metabolism. CYP2C19 polymorphisms had minimal effect on metabolism of ammoxetine.

Conclusions: Ammoxetine has a favorable pharmacokinetic profile after oral administration and good safety properties. The PK and safety profiles of ammoxetine could enable further clinical development in patients with major depressive disorder.
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http://dx.doi.org/10.1016/j.ejps.2021.105724DOI Listing
April 2021

Porous [email protected] carbon nanowires: an ultra-high stable and large-current-density oxygen evolution electrocatalyst.

Chem Commun (Camb) 2021 Feb 21;57(14):1774-1777. Epub 2021 Jan 21.

School of Chemistry and Chemical Engineering, University of Jinan, Jinan 250022, China.

Nitrogen doped carbon functionalized CoSe nanowires ([email protected] NWs), which act as potential oxygen evolution reaction (OER) catalysts with a large current density and high stability have been reported. Owing to the collaborative optimization of electrical conductivity, free adsorption energy and binding strength of OER intermediates, the prepared [email protected] NWs exhibit an enhanced 6.61-fold catalytic activity compared to the pristine CoSe NW electrode in 1.0 M KOH solution at the overpotential of 340 mV.
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http://dx.doi.org/10.1039/d0cc07647cDOI Listing
February 2021

On-demand responsive nanoplatform mediated targeting of CAFs and down-regulating mtROS-PYK2 signaling for antitumor metastasis.

Biomater Sci 2021 Mar;9(5):1872-1885

School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China.

The desmoplastic tumor microenvironment (DTME), including overexpressed stromal cells and extracellular matrix, formed the first barrier for the accumulation and penetration of nanoparticles in tumors, which compromised the therapeutic efficacy and prognosis. In some metastatic cells, overactivity of the tricarboxylic cycle could overload the electron transport chain resulting in increased mtROS production, which triggered the mitochondria-driven tumor migration and metastasis. Hence, we developed [email protected]/NPs for down-regulating the mtROS-PYK2 pathway and remodeling the DTME to inhibit tumor growth and metastasis for the first time. TPP-RSV prodrugs were synthesized and targeted at mitochondria, resulting in the scavenging of mtROS, lower PYK2 expression, and activation of the mitochondria-driven apoptotic pathway. Pirfenidone fully remodeled the DTME through inhibiting the expression of CAFs, hyaluronan and collagen I, thereby reducing IFP, eliminating the immunosuppressive microenvironment by decreasing the expression of TGF-β, and increasing the infiltration of cytotoxic T lymphocytes. The combination therapy of different mechanisms via targeting the mtROS-PYK2 pathway and CAFs might provide deeper insights into the inhibition of malignant breast cancer growth and metastasis.
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http://dx.doi.org/10.1039/d0bm01878cDOI Listing
March 2021

Hierarchically Releasing Bio-Responsive Nanoparticles for Complete Tumor Microenvironment Modulation via TGF-β Pathway Inhibition and TAF Reduction.

ACS Appl Mater Interfaces 2021 Jan 10;13(2):2256-2268. Epub 2021 Jan 10.

School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China.

The aggressive progression of breast cancer is impacted significantly by the tumor microenvironment (TME). The current chemotherapy normally causes cytotoxicity to tumor cells, while does not effectively modulate the TME. Thus, the chemotherapy effect of breast cancer is usually dissatisfactory. In this study, a kind of hierarchically releasing bio-responsive nanoparticles (R(D)/H(S) NPs), constructed by β-cyclodextrin-grafted heparin and pH-sensitive pseudorotaxane, were investigated to enhance the breast cancer chemotherapeutic efficacy through TME modulation. Doxorubicin (DOX) and transforming growth factor-β (TGF-β) receptor inhibitor (SB431542) loaded onto R(D)/H(S) NPs were released rapidly for the respective response to low pH in endosomes/lysosomes and heparanase (HPSE) in TME. Our results showed that R(D)/H(S) NPs effectively inhibited the formation of tumor-associated fibroblasts (TAFs) and reduced TGF-β and collagen I secretion. Besides, the immunosuppressive microenvironment was effectively reversed into immunogenic, characterized by increased CD8 and CD4 T cell infiltration, which distinctly inhibited breast cancer metastasis. Therefore, R(D)/H(S) NPs remodeled the TME by downregulating TAFs, TGF-β, and collagen I; activating the immune microenvironment; and then amplifying the chemotherapeutic efficacy of DOX.
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http://dx.doi.org/10.1021/acsami.0c18545DOI Listing
January 2021

An integrated space-to-ground quantum communication network over 4,600 kilometres.

Nature 2021 01 6;589(7841):214-219. Epub 2021 Jan 6.

Jinan Institute of Quantum Technology, Shandong, China.

Quantum key distribution (QKD) has the potential to enable secure communication and information transfer. In the laboratory, the feasibility of point-to-point QKD is evident from the early proof-of-concept demonstration in the laboratory over 32 centimetres; this distance was later extended to the 100-kilometre scale with decoy-state QKD and more recently to the 500-kilometre scale with measurement-device-independent QKD. Several small-scale QKD networks have also been tested outside the laboratory. However, a global QKD network requires a practically (not just theoretically) secure and reliable QKD network that can be used by a large number of users distributed over a wide area. Quantum repeaters could in principle provide a viable option for such a global network, but they cannot be deployed using current technology. Here we demonstrate an integrated space-to-ground quantum communication network that combines a large-scale fibre network of more than 700 fibre QKD links and two high-speed satellite-to-ground free-space QKD links. Using a trusted relay structure, the fibre network on the ground covers more than 2,000 kilometres, provides practical security against the imperfections of realistic devices, and maintains long-term reliability and stability. The satellite-to-ground QKD achieves an average secret-key rate of 47.8 kilobits per second for a typical satellite pass-more than 40 times higher than achieved previously. Moreover, its channel loss is comparable to that between a geostationary satellite and the ground, making the construction of more versatile and ultralong quantum links via geosynchronous satellites feasible. Finally, by integrating the fibre and free-space QKD links, the QKD network is extended to a remote node more than 2,600 kilometres away, enabling any user in the network to communicate with any other, up to a total distance of 4,600 kilometres.
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http://dx.doi.org/10.1038/s41586-020-03093-8DOI Listing
January 2021

Dual-Responsive and Deep-Penetrating Nanomicelles for Tumor Therapy via Extracellular Matrix Degradation and Oxidative Stress.

ACS Biomater Sci Eng 2021 01 29;7(1):166-179. Epub 2020 Dec 29.

School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China.

Tumor microenvironment (TME), with complex composition, plays a vital role in the occurrence, development, and metastasis of tumors. TME becomes an important obstacle to the accessibility of nanotherapy, thus indicating the need to improve the functional design to overcome this challenge. In this study, we generate an intelligent nano-drug-delivery system ([email protected] NPs) with dual environmental response, which involves heparanase (HPSE) in TME and glutathione (GSH) in tumor cells. The nanosystem consists of a nanoskeleton formed by self-assembly of mPEG-ss-PEI and α-CD (PssP), chemotherapy drug doxorubicin (DOX) for enhancing antitumor efficacy, together with hyaluronidase (HAase), which is designed to degrade extracellular matrix to increase drug penetration, and an outer shell of heparin. Through the process of "responsive disintegration-remodeling tumor microenvironment-enhancing drug penetration-inducing oxidative stress", the semi-rotaxaneself-assembled nanomicelles were constructed to achieve the progressive function. [email protected] NPs with the size of 81.85 ± 1.85 nm exhibited satisfactory cytotoxicity (IC = 0.80 ± 0.33 μg/mL). With the disulfide bond-mediated GSH depletion and DOX-mediated reactive oxygen species (ROS) production, treatment with [email protected] NPs prominently reduced glutathione peroxidase 4 (GPX4) level and would lead to enhanced oxidative stresses. Hyaluronic acid (HA), collagen I, and α-smooth muscle actin (α-SMA) were significantly reduced for TME remodulation. Moreover, the antitumor effect in vivo implied that [email protected] NPs could inhibit tumor growth effectively and reduce tumor interstitial fluid pressure (IFP) evidently. In conclusion, [email protected] NPs improved the penetration of drugs and exhibited enhanced antitumor efficacy.
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http://dx.doi.org/10.1021/acsbiomaterials.0c01394DOI Listing
January 2021

Photobiomodulation suppresses JNK3 by activation of ERK/MKP7 to attenuate AMPA receptor endocytosis in Alzheimer's disease.

Aging Cell 2021 01 18;20(1):e13289. Epub 2020 Dec 18.

MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, South China Normal University, Guangzhou, China.

Alzheimer's disease (AD), a severe age-related neurodegenerative disorder, lacks effective therapeutic methods at present. Physical approaches such as gamma frequency light flicker that can effectively reduce amyloid load have been reported recently. Our previous research showed that a physical method named photobiomodulation (PBM) therapy rescues Aβ-induced dendritic atrophy in vitro. However, it remains to be further investigated the mechanism by which PBM affects AD-related multiple pathological features to improve learning and memory deficits. Here, we found that PBM attenuated Aβ-induced synaptic dysfunction and neuronal death through MKP7-dependent suppression of JNK3, a brain-specific JNK isoform related to neurodegeneration. The results showed PBM-attenuated amyloid load, AMPA receptor endocytosis, dendrite injury, and inflammatory responses, thereby rescuing memory deficits in APP/PS1 mice. We noted JNK3 phosphorylation was dramatically decreased after PBM treatment in vivo and in vitro. Mechanistically, PBM activated ERK, which subsequently phosphorylated and stabilized MKP7, resulting in JNK3 inactivation. Furthermore, activation of ERK/MKP7 signaling by PBM increased the level of AMPA receptor subunit GluR 1 phosphorylation and attenuated AMPA receptor endocytosis in an AD pathological model. Collectively, these data demonstrated that PBM has potential therapeutic value in reducing multiple pathological features associated with AD, which is achieved by regulating JNK3, thus providing a noninvasive, and drug-free therapeutic strategy to impede AD progression.
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http://dx.doi.org/10.1111/acel.13289DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7811840PMC
January 2021

Crystal Facet-Dependent CO Photoreduction over Porous ZnO Nanocatalysts.

ACS Appl Mater Interfaces 2020 Dec 2;12(50):56039-56048. Epub 2020 Dec 2.

CAS Key Laboratory of Nanosystem and Hierarchical Fabrication, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, China.

Crystal facet engineering provides a promising approach to tailor the performance of catalysts because of the close relationship between the photocatalytic activity and the surface atomic and electronic structures. An in-depth understanding mechanism of crystal facet-dependent CO photoreduction is still an open question. Herein, two different types of porous ZnO nanocatalysts are used as model photocatalysts for the investigation, which are, respectively, with exposed {110} and {001} facets. The porous ZnO with an exposed {110} facet exhibits superior photocatalytic activity to the one with the {001} facet. Various influencing factors have been thoroughly studied both theoretically and/or experimentally, including light harvesting (i.e., band gap), reduction capability (potential of conduction band), crystallinity, CO adsorption ability, CO activation, and charge separation. The major influencing factors are eventually figured out based on the experimental and calculation results. The product selectivity and the influence of the hole scavenger can be explained too. Our work may pave a way for directing the future rational design of efficient photocatalysts for CO reduction.
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http://dx.doi.org/10.1021/acsami.0c17596DOI Listing
December 2020

Hierarchically porous hydrangea-like InS/InO heterostructures for enhanced photocatalytic hydrogen evolution.

J Colloid Interface Sci 2021 Apr 13;587:876-882. Epub 2020 Nov 13.

School of Engineering, Edith Cowan University, 270 Joondalup Drive, Joondalup, WA, 6027, Australia. Electronic address:

Semiconductor-based photocatalytic hydrogen evolution is considered to be a promising and cost-effective approach to address the environmental issues and energy crisis. It still remains a great challenge to design highly-efficient semiconductor photocatalysts via a facile method. Herein, hierarchically porous hydrangea-like InS/InO heterostructures are successfully synthesized via a simple in situ oxidization process. The formed InS/InO heterostructures exhibit superior photocatalytic activity to the counterpart InS and InO. The boosted photocatalytic performance is ascribed to the formed heterostructures, which greatly facilitate the interfacial charge transfer. Moreover, the formation of hierarchically porous heterostructures increases the number of active sites and improves the permeability, and thus significantly promotes the photocatalytic H evolution activity. This work may provide a new insight for designing InS-based heterostructures for efficient solar light conversion.
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http://dx.doi.org/10.1016/j.jcis.2020.11.048DOI Listing
April 2021

Transformative Network Modeling of Multi-omics Data Reveals Detailed Circuits, Key Regulators, and Potential Therapeutics for Alzheimer's Disease.

Neuron 2021 01 24;109(2):257-272.e14. Epub 2020 Nov 24.

Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

To identify the molecular mechanisms and novel therapeutic targets of late-onset Alzheimer's Disease (LOAD), we performed an integrative network analysis of multi-omics profiling of four cortical areas across 364 donors with varying cognitive and neuropathological phenotypes. Our analyses revealed thousands of molecular changes and uncovered neuronal gene subnetworks as the most dysregulated in LOAD. ATP6V1A was identified as a key regulator of a top-ranked neuronal subnetwork, and its role in disease-related processes was evaluated through CRISPR-based manipulation in human induced pluripotent stem cell-derived neurons and RNAi-based knockdown in Drosophila models. Neuronal impairment and neurodegeneration caused by ATP6V1A deficit were improved by a repositioned compound, NCH-51. This study provides not only a global landscape but also detailed signaling circuits of complex molecular interactions in key brain regions affected by LOAD, and the resulting network models will serve as a blueprint for developing next-generation therapeutic agents against LOAD.
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http://dx.doi.org/10.1016/j.neuron.2020.11.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7855384PMC
January 2021