Publications by authors named "Jiajia Zhou"

140 Publications

Wetting Dynamics in an Angular Channel.

Langmuir 2021 Sep 19. Epub 2021 Sep 19.

Center of Soft Matter Physics and its Applications, Beihang University, Beijing 100191, China.

We analyze the dynamics of liquid filling in a thin, slightly inflated rectangular channel driven by capillary forces. We show that although the amount of liquid in the channel increases in time following the classical Lucas-Washburn law, ∝ , the prefactor is very sensitive to the deformation of the channel because the filling takes place by the growth of two parts, the bulk part (where the cross section is completely filled by the liquid), and the finger part (where the cross section is partially filled). We calculate the time dependence of accounting for the coupling between the two parts and show that the prefactor for the filling can be reduced significantly by a slight deformation of the rectangular channel, e.g., the prefactor is reduced 50% for a strain of 0.1%. This offers an explanation for the large deviation on the value of the prefactor reported previously.
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http://dx.doi.org/10.1021/acs.langmuir.1c01755DOI Listing
September 2021

Biofabrication of a Low Modulus Bioelectroprobe for Neurons to Grow Into.

Materials (Basel) 2021 Aug 21;14(16). Epub 2021 Aug 21.

State Key Laboratory for Manufacturing System Engineering, Xi'an Jiaotong University, Xi'an 710054, China.

Implantable nerve electrodes, as a bridge between the brain and external devices, have been widely used in areas such as brain function exploration, neurological disease treatment and human-computer interaction. However, the mechanical properties mismatch between the electrode material and the brain tissue seriously affects the stability of electrode signal acquisition and the effectiveness of long-term service in vivo. In this study, a modified neuroelectrode was developed with conductive biomaterials. The electrode has good biocompatibility and a gradient microstructure suitable for cell growth. Compared with metal electrodes, bioelectrodes not only greatly reduced the elastic modulus (<10 kpa) but also increased the conductivity of the electrode by 200 times. Through acute electrophysiological analysis and a 12-week chronic in vivo experiment, the bioelectrode clearly recorded the rat's brain electrical signals, effectively avoided the generation of glial scars and induced neurons to move closer to the electrode. The new conductive biomaterial electrodes developed in this research make long-term implantation of cortical nerve electrodes possible.
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http://dx.doi.org/10.3390/ma14164718DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8400188PMC
August 2021

Preselectable Optical Fingerprints of Heterogeneous Upconversion Nanoparticles.

Nano Lett 2021 Sep 18;21(18):7659-7668. Epub 2021 Aug 18.

Institute for Biomedical Materials and Devices (IBMD), Faculty of Science, University of Technology Sydney, Sydney, New South Wales 2007, Australia.

The control in optical uniformity of single nanoparticles and tuning their diversity in multiple dimensions, dot to dot, holds the key to unlocking nanoscale applications. Here we report that the entire lifetime profile of the single upconversion nanoparticle (τ profile) can be resolved by confocal, wide-field, and super-resolution microscopy techniques. The advances in both spatial and temporal resolutions push the limit of optical multiplexing from microscale to nanoscale. We further demonstrate that the time-domain optical fingerprints can be created by utilizing nanophotonic upconversion schemes, including interfacial energy migration, concentration dependency, energy transfer, and isolation of surface quenchers. We exemplify that three multiple dimensions, including the excitation wavelength, emission color, and τ profile, can be built into the nanoscale derivative τ-dots. Creating a vast library of individually preselectable nanotags opens up a new horizon for diverse applications, spanning from sub-diffraction-limit data storage to high-throughput single-molecule digital assays and super-resolution imaging.
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http://dx.doi.org/10.1021/acs.nanolett.1c02404DOI Listing
September 2021

Ultrahigh energy-dissipation elastomers by precisely tailoring the relaxation of confined polymer fluids.

Nat Commun 2021 Jun 14;12(1):3610. Epub 2021 Jun 14.

Key Laboratory of Bioinspired Smart Interfacial Science and Technology of Ministry of Education, School of Chemistry, Beihang University, Beijing, P. R. China.

Energy-dissipation elastomers relying on their viscoelastic behavior of chain segments in the glass transition region can effectively suppress vibrations and noises in various fields, yet the operating frequency of those elastomers is difficult to control precisely and its range is narrow. Here, we report a synergistic strategy for constructing polymer-fluid-gels that provide controllable ultrahigh energy dissipation over a broad frequency range, which is difficult by traditional means. This is realized by precisely tailoring the relaxation of confined polymer fluids in the elastic networks. The symbiosis of this combination involves: elastic networks forming an elastic matrix that displays reversible deformation and polymer fluids reptating back and forth to dissipate mechanical energy. Using prototypical poly (n-butyl acrylate) elastomers, we demonstrate that the polymer-fluid-gels exhibit a controllable ultrahigh energy-dissipation property (loss factor larger than 0.5) with a broad frequency range (10 ~ 10 Hz). Energy absorption of the polymer-fluid-gels is over 200 times higher than that of commercial damping materials under the same dynamic stress. Moreover, their modulus is quasi-stable in the operating frequency range.
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http://dx.doi.org/10.1038/s41467-021-23984-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8203694PMC
June 2021

Stable and Highly Efficient Antibody-Nanoparticles Conjugation.

Bioconjug Chem 2021 06 19;32(6):1146-1155. Epub 2021 May 19.

Institute for Biomedical Materials and Devices (IBMD), School of Mathematical and Physical Sciences, Faculty of Science, University of Technology Sydney, Sydney, New South Wales 2007, Australia.

Functional ligands and polymers have frequently been used to yield target-specific bio-nanoconjugates. Herein, we provide a systematic insight into the effect of the chain length of poly(oligo (ethylene glycol) methyl ether acrylate) (POEGMEA) containing polyethylene glycol on the colloidal stability and antibody-conjugation efficiency of nanoparticles. We employed Reversible Addition-Fragmentation Chain Transfer (RAFT) to design diblock copolymers composed of 7 monoacryloxyethyl phosphate (MAEP) units and 6, 13, 35, or 55 OEGMEA units. We find that when the POEGMEA chain is short, the polymer cannot effectively stabilize the nanoparticles, and when the POEGMEA chain is long, the nanoparticles cannot be efficiently conjugated to antibody. In other words, the majority of the carboxylic groups in larger POEGMEA chains are inaccessible to further chemical modification. We demonstrate that the polymer containing 13 OEGMEA units can effectively bind up to 64% of the antibody molecules, while the binding efficiency drops to 50% and 0% for the polymer containing 35 and 55 OEGMEA units. Moreover, flow cytometry assay statistically shows that about 9% of the coupled antibody retained its activity to recognize B220 biomarkers on the B cells. This work suggests a library of stabile, specific, and bioactive lanthanide-doped nanoconjugates for flow cytometry and mass cytometry application.
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http://dx.doi.org/10.1021/acs.bioconjchem.1c00192DOI Listing
June 2021

Correction to: Dexmedetomidine attenuates myocardial ischemia-reperfusion injury in vitro by inhibiting NLRP3 Inflammasome activation.

BMC Anesthesiol 2021 May 10;21(1):141. Epub 2021 May 10.

Shandong Provincial Medicine and Health Key Laboratory of Clinical Anesthesia, School of Anesthesiology, Weifang Medical University, No. 7166, Baotong West Street, Weicheng District, Weifang, 261021, China.

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http://dx.doi.org/10.1186/s12871-021-01356-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8111707PMC
May 2021

LIMIT is an immunogenic lncRNA in cancer immunity and immunotherapy.

Nat Cell Biol 2021 05 6;23(5):526-537. Epub 2021 May 6.

Department of Surgery, University of Michigan, Ann Arbor, MI, USA.

Major histocompatibility complex-I (MHC-I) presents tumour antigens to CD8 T cells and triggers anti-tumour immunity. Humans may have 30,000-60,000 long noncoding RNAs (lncRNAs). However, it remains poorly understood whether lncRNAs affect tumour immunity. Here, we identify a lncRNA, lncRNA inducing MHC-I and immunogenicity of tumour (LIMIT), in humans and mice. We found that IFNγ stimulated LIMIT, LIMIT cis-activated the guanylate-binding protein (GBP) gene cluster and GBPs disrupted the association between HSP90 and heat shock factor-1 (HSF1), thereby resulting in HSF1 activation and transcription of MHC-I machinery, but not PD-L1. RNA-guided CRISPR activation of LIMIT boosted GBPs and MHC-I, and potentiated tumour immunogenicity and checkpoint therapy. Silencing LIMIT, GBPs and/or HSF1 diminished MHC-I, impaired antitumour immunity and blunted immunotherapy efficacy. Clinically, LIMIT, GBP- and HSF1-signalling transcripts and proteins correlated with MHC-I, tumour-infiltrating T cells and checkpoint blockade response in patients with cancer. Together, we demonstrate that LIMIT is a cancer immunogenic lncRNA and the LIMIT-GBP-HSF1 axis may be targetable for cancer immunotherapy.
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http://dx.doi.org/10.1038/s41556-021-00672-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8122078PMC
May 2021

Microchannel and Nanofiber Array Morphology Enhanced Rapid Superspreading on Animals' Corneas.

Adv Mater 2021 Jun 23;33(23):e2007152. Epub 2021 Apr 23.

Key Laboratory of Bioinspired Smart Interfacial Science, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing, 100190, China.

The dynamic spreading phenomenon of liquids is vital for both understanding wetting mechanisms and visual reaction time-related applications. However, how to control and accelerate the spreading process is still an enormous challenge. Here, a unique microchannel and nanofiber array morphology enhanced rapid superspreading (RSS) effect on animals' corneas with a superspreading time (ST) of 830 ms is found, and the respective roles of the nanofiber array and the microchannel in the RSS effect are explicitly demonstrated. Specifically, the superspreading is induced by in-/out-of-plane nanocapillary forces among the nanofiber array; the microchannel is responsible for tremendously speeding up the superspreading process. Inspired by the RSS strategy, not only is an RSS surface fabricated with an ST of only 450 ms, which is, respectively, more than 26 and 1.8 times faster than conventional superamphiphilic surfaces and animal's corneas and can be applied as RSS surfaces on video monitors to record clear videos, but also it is demonstrated that the RSS effect has tremendous potential as advanced ophthalmic material surfaces to enhance its biocompatibility for clear vision.
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http://dx.doi.org/10.1002/adma.202007152DOI Listing
June 2021

Super-spreading on superamphiphilic micro-organized nanochannel anodic aluminum oxide surfaces for heat dissipation.

iScience 2021 Apr 19;24(4):102334. Epub 2021 Mar 19.

Key Laboratory of Bio-inspired Smart Interfacial Science and Technology of Ministry of Education, School of Chemistry, Beihang University, Beijing 100191, P. R. China.

Nature-inspired superamphiphilic surfaces have drawn tremendous attention owing to its extreme liquid-loving behaviors. Herein, a micro-organized nano-channel (Mo-Na) superamphiphilic anodic aluminum oxide (AAO) surface with long-lasting superamphiphilic property is prepared by a facile one-step anodization method with controllable temperature change. Analysis of dynamic wetting behaviors on superamphiphilic Mo-Na AAO surfaces for various liquids reveals that the spreading factor is in negative correlation with the surface tension and liquid polarity. Detailed observation of the three-phase contact line shows a micro-scale capillary film on superamphiphilic Mo-Na AAO surfaces, which results from the horizontal component of the capillary force. Taking advantage of the superamphiphilic property, water droplets can spread completely on these Mo-Na AAO surfaces within a short time, which can be applied for efficient heat dissipation. Moreover, the unique AAO surface with Mo-Na structures also offers an effective template for future efforts in AAO-based composite devices.
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http://dx.doi.org/10.1016/j.isci.2021.102334DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8027538PMC
April 2021

Dexmedetomidine attenuates myocardial ischemia-reperfusion injury in vitro by inhibiting NLRP3 Inflammasome activation.

BMC Anesthesiol 2021 04 6;21(1):104. Epub 2021 Apr 6.

Shandong Provincial Medicine and Health Key Laboratory of Clinical Anesthesia, School of Anesthesiology, Weifang Medical University, No. 7166, Baotong West Street, Weicheng District, Weifang, 261021, China.

Background: Myocardial ischemia-reperfusion injury (MIRI) is the most common cause of death worldwide. The NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome plays an important role in the inflammatory response to MIRI. Dexmedetomidine (DEX), a specific agonist of α2-adrenergic receptor, is commonly used for sedation and analgesia in anesthesia and critically ill patients. Several studies have shown that dexmedetomidine has a strong anti-inflammatory effect in many diseases. Here, we investigated whether dexmedetomidine protects against MIRI by inhibiting the activation of the NLRP3 inflammasome in vitro.

Methods: We established an MIRI model in cardiomyocytes (CMs) alone and in coculture with cardiac fibroblasts (CFs) by hypoxia/reoxygenation (H/R) in vitro. The cells were treated with dexmedetomidine with or without MCC950 (a potent selective NLRP3 inhibitor). The beating rate and cell viability of cardiomyocytes, NLRP3 localization, the expression of inflammatory cytokines and NLRP3 inflammasome-related proteins, and the expression of apoptosis-related proteins, including Bcl2 and BAX, were determined.

Results: Dexmedetomidine treatment increased the beating rates and viability of cardiomyocytes cocultured with cardiac fibroblasts. The expression of the NLRP3 protein was significantly upregulated in cardiac fibroblasts but not in cardiomyocytes after H/R and was significantly attenuated by dexmedetomidine treatment. Expression of the inflammatory cytokines IL-1β, IL-18 and TNF-α was significantly increased in cardiac fibroblasts after H/R and was attenuated by dexmedetomidine treatment. NLRP3 inflammasome activation induced the increased expression of cleaved caspase1, mature IL-1β and IL-18, while dexmedetomidine suppressed H/R-induced NLRP3 inflammasome activation in cardiac fibroblasts. In addition, dexmedetomidine reduced the expression of Bcl2 and BAX in cocultured cardiomyocytes by suppressing H/R-induced NLRP3 inflammasome activation in cardiac fibroblasts.

Conclusion: Dexmedetomidine treatment can suppress H/R-induced NLRP3 inflammasome activation in cardiac fibroblasts, thereby alleviating MIRI by inhibiting the inflammatory response.
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http://dx.doi.org/10.1186/s12871-021-01334-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8022424PMC
April 2021

The ubiquitin ligase MDM2 sustains STAT5 stability to control T cell-mediated antitumor immunity.

Nat Immunol 2021 04 25;22(4):460-470. Epub 2021 Mar 25.

Department of Surgery, University of Michigan Rogel Cancer Center, University of Michigan School of Medicine, Ann Arbor, MI, USA.

Targeting the p53-MDM2 pathway to reactivate tumor p53 is a chemotherapeutic approach. However, the involvement of this pathway in CD8 T cell-mediated antitumor immunity is unknown. Here, we report that mice with MDM2 deficiency in T cells exhibit accelerated tumor progression and a decrease in tumor-infiltrating CD8 T cell survival and function. Mechanistically, MDM2 competes with c-Cbl for STAT5 binding, reduces c-Cbl-mediated STAT5 degradation and enhances STAT5 stability in tumor-infiltrating CD8 T cells. Targeting the p53-MDM2 interaction with a pharmacological agent, APG-115, augmented MDM2 in T cells, thereby stabilizing STAT5, boosting T cell immunity and synergizing with cancer immunotherapy. Unexpectedly, these effects of APG-115 were dependent on p53 and MDM2 in T cells. Clinically, MDM2 abundance correlated with T cell function and interferon-γ signature in patients with cancer. Thus, the p53-MDM2 pathway controls T cell immunity, and targeting this pathway may treat patients with cancer regardless of tumor p53 status.
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http://dx.doi.org/10.1038/s41590-021-00888-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8026726PMC
April 2021

Networking State of Ytterbium Ions Probing the Origin of Luminescence Quenching and Activation in Nanocrystals.

Adv Sci (Weinh) 2021 Mar 29;8(6):2003325. Epub 2021 Jan 29.

Beijing National Laboratory for Molecular Sciences State Key Laboratory of Rare Earth Materials Chemistry and Applications PKU-HKU Joint Laboratory in Rare Earth Materials and Bioinorganic Chemistry College of Chemistry and Molecular Engineering Peking University Beijing 100871 China.

At the organic-inorganic interface of nanocrystals, electron-phonon coupling plays an important but intricate role in determining the diverse properties of nanomaterials. Here, it is reported that highly doping of Yb ions within the nanocrystal host can form an energy-migration network. The networking state Yb shows both distinct Stark splitting peak ratios and lifetime dynamics, which allows quantitative investigations of quenching and thermal activation of luminescence, as the high-dimensional spectroscopy signatures can be correlated to the attaching and de-attaching status of surface molecules. By in-situ surface characterizations, it is proved that the Yb-O coordination associated with coordinated water molecules has significantly contributed to this reversible effect. Moreover, using this approach, the prime quencher -OH can be switched to -CH in the wet-chemistry annealing process, resulting in the electron-phonon coupling probability change. This study provides the molecular level insights and dynamics of the surface dark layer of luminescent nanocrystals.
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http://dx.doi.org/10.1002/advs.202003325DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7967042PMC
March 2021

High dose expression of heme oxigenase-1 induces retinal degeneration through ER stress-related DDIT3.

Mol Neurodegener 2021 03 10;16(1):16. Epub 2021 Mar 10.

Laboratory of Developmental Cell Biology and Disease, School of Ophthalmology and Optometry and Eye Hospital, and State Key Laboratory of Ophthalmology, Optometry and Vision Science, Wenzhou Medical University, Wenzhou, China.

Background: Oxidative stress is a common cause of neurodegeneration and plays a central role in retinal degenerative diseases. Heme oxygenase-1 (HMOX1) is a redox-regulated enzyme that is induced in neurodegenerative diseases and acts against oxidative stress but can also promote cell death, a phenomenon that is still unexplained in molecular terms. Here, we test whether HMOX1 has opposing effects during retinal degeneration and investigate the molecular mechanisms behind its pro-apoptotic role.

Methods: Basal and induced levels of HMOX1 in retinas are examined during light-induced retinal degeneration in mice. Light damage-independent HMOX1 induction at two different expression levels is achieved by intraocular injection of different doses of an adeno-associated virus vector expressing HMOX1. Activation of Müller glial cells, retinal morphology and photoreceptor cell death are examined using hematoxylin-eosin staining, TUNEL assays, immunostaining and retinal function are evaluated with electroretinograms. Downstream gene expression of HMOX1 is analyzed by RNA-seq, qPCR examination and western blotting. The role of one of these genes, the pro-apoptotic DNA damage inducible transcript 3 (Ddit3), is analyzed in a line of knockout mice.

Results: Light-induced retinal degeneration leads to photoreceptor degeneration and concomitant HMOX1 induction. HMOX1 expression at low levels before light exposure prevents photoreceptor degeneration but expression at high levels directly induces photoreceptor degeneration even without light stress. Photoreceptor degeneration following high level expression of HMOX1 is associated with a mislocalization of rhodopsin in photoreceptors and an increase in the expression of DDIT3. Genetic deletion of Ddit3 in knockout mice prevents photoreceptor cell degeneration normally resulting from high level HMOX1 expression.

Conclusion: The results reveal that the expression levels determine whether HMOX1 is protective or deleterious in the retina. Furthermore, in contrast to the protective low dose of HMOX1, the deleterious high dose is associated with induction of DDIT3 and endoplasmic reticulum stress as manifested, for instance, in rhodopsin mislocalization. Hence, future applications of HMOX1 or its regulated targets in gene therapy approaches should carefully consider expression levels in order to avoid potentially devastating effects.
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http://dx.doi.org/10.1186/s13024-021-00437-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7944639PMC
March 2021

Triplet Fusion Upconversion with Oxygen Resistance in Aqueous Media.

Anal Chem 2021 03 5;93(10):4641-4646. Epub 2021 Mar 5.

Institute for Biomedical Materials and Devices, Faculty of Science, University of Technology Sydney, Sydney, New South Wales 2007, Australia.

Triplet fusion upconversion (also called triplet-triplet annihilation, TTA) arouses much attention due to its potential in the fields of biological imaging, optogenetics, and light harvesting. However, oxygen quenching remains a challenge ahead, restricting its applications in aqueous media. Previous efforts to realize aqueous TTA with oxygen resistance have been focused on core-shell structures and self-assembly, but tedious processes and complicated chemical modification are required. Here, we report a direct and efficient strategy to realize aqueous TTA by controlling the ionic equilibrium of the TTA dyad. We find that the ionized organic dyad in physiological buffers and electrolyte-based media shows a natural aerotolerance without any complicated structure engineering. In particular, the upconversion intensity of this aqueous TTA in Tris buffer under an air-saturated condition is more than twice that under the deaerated condition. We further demonstrate the TTA system for potential applications in pH and temperature sensing with reversible and sensitive performance. We anticipate this facile approach will inspire the development of practical aqueous TTA and broad applications in biological science.
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http://dx.doi.org/10.1021/acs.analchem.1c00096DOI Listing
March 2021

Loss of Optineurin Drives Cancer Immune Evasion via Palmitoylation-Dependent IFNGR1 Lysosomal Sorting and Degradation.

Cancer Discov 2021 Jul 24;11(7):1826-1843. Epub 2021 Feb 24.

Department of Surgery, University of Michigan School of Medicine, Ann Arbor, Michigan.

Mutations in IFN and MHC signaling genes endow immunotherapy resistance. Patients with colorectal cancer infrequently exhibit IFN and MHC signaling gene mutations and are generally resistant to immunotherapy. In exploring the integrity of IFN and MHC signaling in colorectal cancer, we found that optineurin was a shared node between the two pathways and predicted colorectal cancer patient outcome. Loss of optineurin occurs in early-stage human colorectal cancer. Immunologically, optineurin deficiency was shown to attenuate IFNGR1 and MHC-I expression, impair T-cell immunity, and diminish immunotherapy efficacy in murine cancer models and patients with cancer. Mechanistically, we observed that IFNGR1 was -palmitoylated on Cys122, and AP3D1 bound with and sorted palmitoylated IFNGR1 to lysosome for degradation. Unexpectedly, optineurin interacted with AP3D1 to prevent palmitoylated IFNGR1 lysosomal sorting and degradation, thereby maintaining IFNγ and MHC-I signaling integrity. Furthermore, pharmacologically targeting IFNGR1 palmitoylation stabilized IFNGR1, augmented tumor immunity, and sensitized checkpoint therapy. Thus, loss of optineurin drives immune evasion and intrinsic immunotherapy resistance in colorectal cancer. SIGNIFICANCE: Loss of optineurin impairs the integrity of both IFNγ and MHC-I signaling pathways via palmitoylation-dependent IFNGR1 lysosomal sorting and degradation, thereby driving immune evasion and intrinsic immunotherapy resistance in colorectal cancer. Our work suggests that pharmacologically targeting IFNGR1 palmitoylation can stabilize IFNGR1, enhance T-cell immunity, and sensitize checkpoint therapy in colorectal cancer...
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http://dx.doi.org/10.1158/2159-8290.CD-20-1571DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8292167PMC
July 2021

Quantitatively Monitoring Mitochondrial Thermal Dynamics by Upconversion Nanoparticles.

Nano Lett 2021 02 6;21(4):1651-1658. Epub 2021 Feb 6.

Institute for Biomedical Materials & Devices (IBMD), Faculty of Science, University of Technology Sydney, Sydney, NSW 2007, Australia.

Temperature dynamics reflect the physiological conditions of cells and organisms. Mitochondria regulate the temperature dynamics in living cells as they oxidize the respiratory substrates and synthesize ATP, with heat being released as a byproduct of active metabolism. Here, we report an upconversion nanoparticle-based thermometer that allows the thermal dynamics monitoring of mitochondria in living cells. We demonstrate that the upconversion nanothermometers can efficiently target mitochondria, and the temperature-responsive feature is independent of probe concentration and medium conditions. The relative sensing sensitivity of 3.2% K in HeLa cells allows us to measure the mitochondrial temperature difference through the stimulations of high glucose, lipid, Ca shock, and the inhibitor of oxidative phosphorylation. Moreover, cells display distinct response time and thermodynamic profiles under different stimulations, which highlight the potential applications of this thermometer to study vital processes related to mitochondrial metabolism pathways and interactions between organelles.
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http://dx.doi.org/10.1021/acs.nanolett.0c04281DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7908016PMC
February 2021

Stanniocalcin 1 is a phagocytosis checkpoint driving tumor immune resistance.

Cancer Cell 2021 Apr 28;39(4):480-493.e6. Epub 2021 Jan 28.

Department of Surgery, University of Michigan School of Medicine, Ann Arbor, MI, USA; Center of Excellence for Cancer Immunology and Immunotherapy, University of Michigan Rogel Cancer Center, University of Michigan School of Medicine, Ann Arbor, MI, USA; Department of Pathology, University of Michigan School of Medicine, Ann Arbor, MI, USA; Graduate Program in Immunology, University of Michigan School of Medicine, Ann Arbor, MI, USA; Graduate Program in Cancer Biology, University of Michigan School of Medicine, Ann Arbor, MI, USA. Electronic address:

Immunotherapy induces durable clinical responses in a fraction of patients with cancer. However, therapeutic resistance poses a major challenge to current immunotherapies. Here, we identify that expression of tumor stanniocalcin 1 (STC1) correlates with immunotherapy efficacy and is negatively associated with patient survival across diverse cancer types. Gain- and loss-of-function experiments demonstrate that tumor STC1 supports tumor progression and enables tumor resistance to checkpoint blockade in murine tumor models. Mechanistically, tumor STC1 interacts with calreticulin (CRT), an "eat-me" signal, and minimizes CRT membrane exposure, thereby abrogating membrane CRT-directed phagocytosis by antigen-presenting cells (APCs), including macrophages and dendritic cells. Consequently, this impairs APC capacity of antigen presentation and T cell activation. Thus, tumor STC1 inhibits APC phagocytosis and contributes to tumor immune evasion and immunotherapy resistance. We suggest that STC1 is a previously unappreciated phagocytosis checkpoint and targeting STC1 and its interaction with CRT may sensitize to cancer immunotherapy.
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http://dx.doi.org/10.1016/j.ccell.2020.12.023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044011PMC
April 2021

Modeling Elastically Mediated Liquid-Liquid Phase Separation.

Phys Rev Lett 2020 Dec;125(26):268001

CAS Key Laboratory of Theoretical Physics, Institute of Theoretical Physics, Chinese Academy of Sciences, Beijing 100190, China.

We propose a continuum theory of the liquid-liquid phase separation in an elastic network, where phase-separated microscopic droplets rich in one fluid component can form as an interplay of fluids mixing, droplet nucleation, network deformation, thermodynamic fluctuation, etc. We find that the size of the phase-separated droplets decreases with the shear modulus of the elastic network in the form of ∝[modulus]^{-1/3} and the number density of the droplet increases almost linearly with the shear modulus ∝[modulus], which are verified by the experimental observations. Phase diagrams in the space of (fluid constitution, mixture interaction, network modulus) are provided, which can help to understand similar phase separations in biological cells and also to guide fabrications of synthetic cells with desired phase properties.
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http://dx.doi.org/10.1103/PhysRevLett.125.268001DOI Listing
December 2020

Wetting equilibrium in a rectangular channel.

Soft Matter 2021 Apr 8;17(13):3594-3602. Epub 2021 Jan 8.

State Key Laboratory of Hydroscience and Engineering, Tsinghua University, Beijing 100084, China.

When a capillary channel with corners is wetted by a fluid, there are regions where the fluid fills the whole cross-section and regions where only the corners are filled by the fluid. The fluid fraction of the partially-filled region, s*, is an important quantity related to the capillary pressure. We calculate the value of s* for channels with a cross-section slightly deviated from a rectangle: the height is larger in the center than those on the two short sides. We find that a small change in the cross-section geometry leads to a huge change of s*. This result is consistent with experimental observations.
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http://dx.doi.org/10.1039/d0sm01727bDOI Listing
April 2021

Liver metastasis restrains immunotherapy efficacy via macrophage-mediated T cell elimination.

Nat Med 2021 01 4;27(1):152-164. Epub 2021 Jan 4.

Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA.

Metastasis is the primary cause of cancer mortality, and cancer frequently metastasizes to the liver. It is not clear whether liver immune tolerance mechanisms contribute to cancer outcomes. We report that liver metastases diminish immunotherapy efficacy systemically in patients and preclinical models. Patients with liver metastases derive limited benefit from immunotherapy independent of other established biomarkers of response. In multiple mouse models, we show that liver metastases siphon activated CD8 T cells from systemic circulation. Within the liver, activated antigen-specific FasCD8 T cells undergo apoptosis following their interaction with FasLCD11bF4/80 monocyte-derived macrophages. Consequently, liver metastases create a systemic immune desert in preclinical models. Similarly, patients with liver metastases have reduced peripheral T cell numbers and diminished tumoral T cell diversity and function. In preclinical models, liver-directed radiotherapy eliminates immunosuppressive hepatic macrophages, increases hepatic T cell survival and reduces hepatic siphoning of T cells. Thus, liver metastases co-opt host peripheral tolerance mechanisms to cause acquired immunotherapy resistance through CD8 T cell deletion, and the combination of liver-directed radiotherapy and immunotherapy could promote systemic antitumor immunity.
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http://dx.doi.org/10.1038/s41591-020-1131-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8095049PMC
January 2021

Low threshold lasing emissions from a single upconversion nanocrystal.

Nat Commun 2020 Dec 1;11(1):6156. Epub 2020 Dec 1.

Institute for Biomedical Materials and Devices (IBMD), Faculty of Science, University of Technology Sydney, Sydney, NSW, 2007, Australia.

Cross-relaxation among neighboring emitters normally causes self-quenching and limits the brightness of luminescence. However, in nanomaterials, cross-relaxation could be well-controlled and employed for increasing the luminescence efficiency at specific wavelengths. Here we report that cross-relaxation can modulate both the brightness of single upconversion nanoparticles and the threshold to reach population inversion, and both are critical factors in producing the ultra-low threshold lasing emissions in a micro cavity laser. By homogenously coating a 5-μm cavity with a single layer of nanoparticles, we demonstrate that doping Tm ions at 2% can facilitate the electron accumulation at the intermediate state of H level and efficiently decrease the lasing threshold by more than one order of magnitude. As a result, we demonstrate up-converted lasing emissions with an ultralow threshold of continuous-wave excitation of ~150 W/cm achieved at room temperature. A single nanoparticle can lase with a full width at half-maximum as narrow as ~0.45 nm.
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http://dx.doi.org/10.1038/s41467-020-19797-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7708641PMC
December 2020

Accelerated strategy for the MLEM algorithm.

J Xray Sci Technol 2021 ;29(1):135-149

School of Science, Beijing Jiaotong University, Beijing, China.

Background: A statistical method called maximum likelihood expectation maximization (MLEM) is quite attractive, especially in PET/SPECT. However, the convergence rate of the iterative scheme of MLEM is quite slow.

Objective: This study aims to develop and test a new method to speed up the convergence rate of the MLEM algorithm.

Methods: We introduce a relaxation parameter in the conventional MLEM iterative formula and propose the relaxation strategy on the condition that the spectral radius of the derived iterative matrix from the iterative scheme with the accelerated parameter reaches a minimum value.

Results: Experiments with Shepp-Logan phantom and an annual tree image demonstrate that the new computational strategy effectively accelerates computation time while maintains reasonable image quality.

Conclusions: The proposed new computational method involving the relaxation strategy has a faster convergence speed than the original method.
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http://dx.doi.org/10.3233/XST-200749DOI Listing
January 2021

Nanorods with multidimensional optical information beyond the diffraction limit.

Nat Commun 2020 Nov 27;11(1):6047. Epub 2020 Nov 27.

Institute for Biomedical Materials & Devices (IBMD), Faculty of Science, University of Technology Sydney, Ultimo, NSW, 2007, Australia.

Precise design and fabrication of heterogeneous nanostructures will enable nanoscale devices to integrate multiple desirable functionalities. But due to the diffraction limit (~200 nm), the optical uniformity and diversity within the heterogeneous functional nanostructures are hardly controlled and characterized. Here, we report a set of heterogeneous nanorods; each optically active section has its unique nonlinear response to donut-shaped illumination, so that one can discern each section with super-resolution. To achieve this, we first realize an approach of highly controlled epitaxial growth and produce a range of heterogeneous structures. Each section along the nanorod structure displays tunable upconversion emissions, in four optical dimensions, including color, lifetime, excitation wavelength, and power dependency. Moreover, we demonstrate a 210 nm single nanorod as an extremely small polychromatic light source for the on-demand generation of RGB photonic emissions. This work benchmarks our ability toward the full control of sub-diffraction-limit optical diversities of single heterogeneous nanoparticles.
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http://dx.doi.org/10.1038/s41467-020-19952-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7695702PMC
November 2020

Upconversion nanoparticles coated with molecularly imprinted polymers for specific sensing.

Dalton Trans 2020 Dec 17;49(47):17200-17206. Epub 2020 Nov 17.

State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, P. R. China.

The development of fluorescent sensors based on lanthanide-doped luminescent nanoparticles has increased their application in biomarker detection. Lanthanide-doped upconversion nanoparticles (UCNPs) have been explored as one of the most promising sensors owing to their merits such as excellent photostability, zero background auto-fluorescence, and reduced side effects of near-infrared triggered treatments. However, traditional upconversion luminescence assay based on direct Fluorescence Resonance Energy Transfer (FRET) between the target molecules and surface of UCNPs encounters low detection accuracy due to superficial adsorption interactions. In this work, we use a molecularly imprinting technique to achieve the specific interaction between UCNPs and molecules for accurate sensing. We demonstrate this by synthesizing a nanostructure with a molecularly imprinted polymer at the surface of UCNPs, in which the imprinted cavities can specifically capture the target molecule of rhodamine B. The upconversion signal changes in relation to the molecule concentration due to FRET. Quantitative analysis shows that the fluorescence-quenching rate is consistent with the Stern-Volmer equation, resulting in a limit of detection of 6.27 μg mL. Our fluorescence sensing approach integrates the advantages of both nonlinear upconversion and molecular imprinting technologies, showing great potential for the detection of specific molecules.
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http://dx.doi.org/10.1039/d0dt03555fDOI Listing
December 2020

Comparative Analysis of Skeletal Muscle Transcriptional Signatures Associated With Aerobic Exercise Capacity or Response to Training in Humans and Rats.

Front Endocrinol (Lausanne) 2020 26;11:591476. Epub 2020 Oct 26.

Molecular and Cellular Exercise Physiology, Department of Physiology and Pharmacology, Biomedicum. Karolinska Institute, Stockholm, Sweden.

Increasing exercise capacity promotes healthy aging and is strongly associated with lower mortality rates. In this study, we analyzed skeletal muscle transcriptomics coupled to exercise performance in humans and rats to dissect the inherent and response components of aerobic exercise capacity. Using rat models selected for intrinsic and acquired aerobic capacity, we determined that the high aerobic capacity muscle transcriptome is associated with pathways for tissue oxygenation and vascularization. Conversely, the low capacity muscle transcriptome indicated immune response and metabolic dysfunction. Low response to training was associated with an inflammatory signature and revealed a potential link to circadian rhythm. Next, we applied bioinformatics tools to predict potential secreted factors (myokines). The predicted secretome profile for exercise capacity highlighted circulatory factors involved in lipid metabolism and the exercise response secretome was associated with extracellular matrix remodelling. Lastly, we utilized human muscle mitochondrial respiration and transcriptomics data to explore molecular mediators of exercise capacity and response across species. Human transcriptome comparison highlighted epigenetic mechanisms linked to exercise capacity and the damage repair for response. Overall, our findings from this cross-species transcriptome analysis of exercise capacity and response establish a foundation for future studies on the mechanisms that link exercise and health.
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http://dx.doi.org/10.3389/fendo.2020.591476DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7649134PMC
June 2021

Interfacial Interactions During In Situ Polymer Imbibition in Nanopores.

Phys Rev Lett 2020 Sep;125(12):127802

Max Planck Institute for Polymer Research, 55128 Mainz, Germany.

Using in situ nanodielectric spectroscopy we demonstrate that the imbibition kinetics of cis-1,4-polyisoprene in native alumina nanopores proceeds in two time regimes both with higher effective viscosity than bulk. This finding is discussed by a microscopic picture that considers the competition from an increasing number of chains entering the pores and a decreasing number of fluctuating chain ends. The latter is a direct manifestation of increasing adsorption sites during flow. At the same time, the longest normal mode is somewhat longer than in bulk. This could reflect an increasing density of topological constraints of chains entering the pores with the longer loops formed by other chains.
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http://dx.doi.org/10.1103/PhysRevLett.125.127802DOI Listing
September 2020

Bioinspired Anti-Plateau-Rayleigh-Instability on Dual Parallel Fibers.

Adv Mater 2020 Nov 5;32(45):e2003453. Epub 2020 Oct 5.

Key Laboratory of Bio-Inspired Smart Interfacial Science and Technology of Ministry of Education, School of Chemistry, Beijing Advanced Innovation Center for Biomedical Engineering, International Research Institute for Multidisciplinary Science, Beihang University, No. 37, Xueyuan Road, Haidian District, Beijing, 100191, P.R. China.

The Plateau-Rayleigh instability (PRI) is a well-known phenomenon where a liquid column always breaks up into droplets to achieve the minimization of surface energy. It normally leads to the non-uniformity of a liquid film, which, however, is unfavorable for the fluid coating process. So far, strategies to overcome this instability rely on either the surfactants, UV/high-temp curing treatments, or specific chemical reactions, which suffer from both limited liquid composition and complicated experimental conditions. Natural mulberry silk, a typical composite fiber, is produced by silkworms through a similar fluidic coating process, but exhibits a remarkably uniform and smooth surface. Drawing inspiration, it is revealed that the unique dual parallel fibers are capable of overcoming the PRI during the fluid coating process. Such anti-PRI ability is attributable to the changes in the Laplace pressure difference caused by the alternative asymmetry of the liquid film, as has been demonstrated by both a force analysis on the irregular liquid film and theoretical simulation according to the stability of the liquid on parallel fibers in the fluid coating process. The strategy is applicable for preparing various smooth functional coatings on fibers, which offers new perspectives for fluid coating and microfluidic technologies.
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http://dx.doi.org/10.1002/adma.202003453DOI Listing
November 2020

An Optimized Fibril Network Morphology Enables High-Efficiency and Ambient-Stable Polymer Solar Cells.

Adv Sci (Weinh) 2020 Sep 26;7(18):2001986. Epub 2020 Jul 26.

School of Chemistry Beihang University Beijing 100191 P. R. China.

Morphological stability is crucially important for the long-term stability of polymer solar cells (PSCs). Many high-efficiency PSCs suffer from metastable morphology, resulting in severe device degradation. Here, a series of copolymers is developed by manipulating the content of chlorinated benzodithiophene-4,8-dione (T1-Cl) via a random copolymerization approach. It is found that all the copolymers can self-assemble into a fibril nanostructure in films. By altering the T1-Cl content, the polymer crystallinity and fibril width can be effectively controlled. When blended with several nonfullerene acceptors, such as TTPTT-4F, O-INIC3, EH-INIC3, and Y6, the optimized fibril interpenetrating morphology can not only favor charge transport, but also inhibit the unfavorable molecular diffusion and aggregation in active layers, leading to excellent morphological stability. The work demonstrates the importance of optimization of fibril network morphology in realizing high-efficiency and ambient-stable PSCs, and also provides new insights into the effect of chemical structure on the fibril network morphology and photovoltaic performance of PSCs.
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http://dx.doi.org/10.1002/advs.202001986DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7509652PMC
September 2020

Advances and challenges for fluorescence nanothermometry.

Nat Methods 2020 10 28;17(10):967-980. Epub 2020 Sep 28.

Institute for Biomedical Materials & Devices (IBMD), Faculty of Science, University of Technology Sydney, Sydney, Australia.

Fluorescent nanothermometers can probe changes in local temperature in living cells and in vivo and reveal fundamental insights into biological properties. This field has attracted global efforts in developing both temperature-responsive materials and detection procedures to achieve sub-degree temperature resolution in biosystems. Recent generations of nanothermometers show superior performance to earlier ones and also offer multifunctionality, enabling state-of-the-art functional imaging with improved spatial, temporal and temperature resolutions for monitoring the metabolism of intracellular organelles and internal organs. Although progress in this field has been rapid, it has not been without controversy, as recent studies have shown possible biased sensing during fluorescence-based detection. Here, we introduce the design principles and advances in fluorescence nanothermometry, highlight application achievements, discuss scenarios that may lead to biased sensing, analyze the challenges ahead in terms of both fundamental issues and practical implementations, and point to new directions for improving this interdisciplinary field.
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http://dx.doi.org/10.1038/s41592-020-0957-yDOI Listing
October 2020

Colorectal Tumor Microenvironment-Activated Bio-Decomposable and Metabolizable Cu [email protected] Nanocomposites for Synergistic Oncotherapy.

Adv Mater 2020 Oct 18;32(43):e2004647. Epub 2020 Sep 18.

State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, P. R. China.

Rational design of tumor microenvironment (TME)-activated nanocomposites provides an innovative strategy to construct responsive oncotherapy. In colorectal cancer (CRC), the specific physiological features are the overexpressed endogenous H S and slightly acidic microenvironment. Here, a core-shell Cu [email protected] nanostructure for CRC "turn-on" therapy is reported. With CaCO responsive to pH decomposition and Cu O responsive to H S sulfuration, Cu [email protected] can be triggered "on" into the therapeutic mode by the colorectal TME. When the CaCO shell decomposes and releases calcium in acidic colorectal TME, the loss of protection from the CaCO shell exposes the Cu O core to be sulfuretted by H S to form metabolizable Cu S nanocrystals that gain remarkably strong near-infrared absorption. After modifying hyaluronic acid, Cu [email protected] can achieve synergistic CRC-targeted and TME-triggered photothermal/photodynamic/chemodynamic/calcium-overload-mediated therapy. Moreover, it is found that the generation of hyperthermia and oxidative stress from Cu [email protected] nanocomposites can efficiently reprogram the macrophages from the M2 phenotype to the M1 phenotype and initiate a vaccine-like immune effect after primary tumor removal, which further induces an immune-favorable TME and intense immune responses for anti-CD47 antibody to simultaneously inhibit CRC distant metastasis and recurrence by immunotherapy.
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http://dx.doi.org/10.1002/adma.202004647DOI Listing
October 2020
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