| 1. |
- Romero-Castillo, Laura, et al.
(author)
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Human MHC Class II and Invariant Chain Knock-in Mice Mimic Rheumatoid Arthritis with Allele Restriction in Immune Response and Arthritis Association
- 2024
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In: Advanced Science. - 2198-3844.
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Journal article (peer-reviewed)abstract
- Transgenic mice expressing human major histocompatibility complex class II (MHCII) risk alleles are widely used in autoimmune disease research, but limitations arise due to non-physiologic expression. To address this, physiologically relevant mouse models are established via knock-in technology to explore the role of MHCII in diseases like rheumatoid arthritis. The gene sequences encoding the ectodomains are replaced with the human DRB1*04:01 and 04:02 alleles, DRA, and CD74 (invariant chain) in C57BL/6N mice. The collagen type II (Col2a1) gene is modified to mimic human COL2. Importantly, DRB1*04:01 knock-in mice display physiologic expression of human MHCII also on thymic epithelial cells, in contrast to DRB1*04:01 transgenic mice. Humanization of the invariant chain enhances MHCII expression on thymic epithelial cells, increases mature B cell numbers in spleen, and improves antigen presentation. To validate its functionality, the collagen-induced arthritis (CIA) model is used, where DRB1*04:01 expression led to a higher susceptibility to arthritis, as compared with mice expressing DRB1*04:02. In addition, the humanized T cell epitope on COL2 allows autoreactive T cell-mediated arthritis development. In conclusion, the humanized knock-in mouse faithfully expresses MHCII, confirming the DRB1*04:01 alleles role in rheumatoid arthritis and being also useful for studying MHCII-associated diseases.
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| 2. |
- Xu, Zhongwei, et al.
(author)
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A subset of type-II collagen-binding antibodies prevents experimental arthritis by inhibiting FCGR3 signaling in neutrophils
- 2023
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In: Nature Communications. - 2041-1723. ; 14:1
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Journal article (peer-reviewed)abstract
- Rheumatoid arthritis (RA) involves several classes of pathogenic autoantibodies, some of which react with type-II collagen (COL2) in articular cartilage. We previously described a subset of COL2 antibodies targeting the F4 epitope (ERGLKGHRGFT) that could be regulatory. Here, using phage display, we developed recombinant antibodies against this epitope and examined the underlying mechanism of action. One of these antibodies, R69-4, protected against cartilage antibody- and collagen-induced arthritis in mice, but not autoimmune disease models independent of arthritogenic autoantibodies. R69-4 was further shown to cross-react with a large range of proteins within the inflamed synovial fluid, such as the complement protein C1q. Complexed R69-4 inhibited neutrophil FCGR3 signaling, thereby impairing downstream IL-1β secretion and neutrophil self-orchestrated recruitment. Likewise, human isotypes of R69-4 protected against arthritis with comparable efficiency. We conclude that R69-4 abrogates autoantibody-mediated arthritis mainly by hindering FCGR3 signaling, highlighting its potential clinical utility in acute RA.
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| 3. |
- Deng, Zhongwei, et al.
(author)
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Battery health evaluation using a short random segment of constant current charging
- 2022
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In: iScience. - : Elsevier BV. - 2589-0042. ; 25:5
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Journal article (peer-reviewed)abstract
- Accurately evaluating the health status of lithium-ion batteries (LIBs) is significant to enhance the safety, efficiency, and economy of LIBs deployment. However, the complex degradation processes inside the battery make it a thorny challenge. Data-driven methods are widely used to resolve the problem without exploring the complex aging mechanisms; however, random and incomplete charging-discharging processes in actual applications make the existing methods fail to work. Here, we develop three data-driven methods to estimate battery state of health (SOH) using a short random charging segment (RCS). Four types of commercial LIBs (75 cells), cycled under different temperatures and discharging rates, are employed to validate the methods. Trained on a nominal cycling condition, our models can achieve high-precision SOH estimation under other different conditions. We prove that an RCS with a 10mV voltage window can obtain an average error of less than 5%, and the error plunges as the voltage window increases.
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| 4. |
- Wang, Nan, 1988, et al.
(author)
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Tailoring the Thermal and Mechanical Properties of Graphene Film by Structural Engineering
- 2018
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In: Small. - : Wiley. - 1613-6810 .- 1613-6829. ; 14:29
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Journal article (peer-reviewed)abstract
- Due to substantial phonon scattering induced by various structural defects, the in-plane thermal conductivity (K) of graphene films (GFs) is still inferior to the commercial pyrolytic graphite sheet (PGS). Here, the problem is solved by engineering the structures of GFs in the aspects of grain size, film alignment, and thickness, and interlayer binding energy. The maximum K of GFs reaches to 3200 W m−1K−1and outperforms PGS by 60%. The superior K of GFs is strongly related to its large and intact grains, which are over four times larger than the best PGS. The large smooth features about 11 µm and good layer alignment of GFs also benefit on reducing phonon scattering induced by wrinkles/defects. In addition, the presence of substantial turbostratic-stacking graphene is found up to 37% in thin GFs. The lacking of order in turbostratic-stacking graphene leads to very weak interlayer binding energy, which can significantly decrease the phonon interfacial scattering. The GFs also demonstrate excellent flexibility and high tensile strength, which is about three times higher than PGS. Therefore, GFs with optimized structures and properties show great potentials in thermal management of form-factor-driven electronics and other high-power-driven systems.
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| 5. |
- Xu, Weidong, et al.
(author)
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Iodomethane-Mediated Organometal Halide Perovskite with Record Photoluminescence Lifetime
- 2016
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In: ACS Applied Materials and Interfaces. - : AMER CHEMICAL SOC. - 1944-8244 .- 1944-8252. ; 8:35, s. 23181-23189
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Journal article (peer-reviewed)abstract
- Organometallic lead halide perovskites are excellent light harvesters for high-efficiency photovoltaic devices. However, as the key component in these devices, a perovskite thin film with good morphology and minimal trap states is still difficult to obtain. Herein we show that by incorporating a low boiling point alkyl halide such as iodomethane (CH3I) into the precursor solution, a perovskite (CH3NH3PbI3-xClx) film with improved grain size and orientation can be easily achieved. More importantly, these films exhibit a significantly reduced amount of trap states. Record photoluminescence lifetimes of more than 4 mu s are achieved; these lifetimes are significantly longer than that of pristine CH3NH3PbI3-xClx films. Planar heterojunction solar cells incorporating these CH3I-mediated perovskites have demonstrated a dramatically increased power conversion efficiency compared to the ones using pristine CH3NH3PbI3-xClx. Photoluminescence, transient absorption, and microwave detected photoconductivity measurements all provide consistent evidence that CH3I addition increases the number of excitons generated and their diffusion length, both of which assist efficient carrier transport in the photovoltaic device. The simple incorporation of alkyl halide to enhance perovskite surface passivation introduces an important direction for future progress on high efficiency perovskite optoelectronic devices.
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| 6. |
- Xu, Zhongwei
(author)
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Beyond conventional care : developing novel therapeutic approaches to combat arthritis
- 2023
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Doctoral thesis (other academic/artistic)abstract
- Rheumatoid arthritis (RA) is an autoimmune disorder without a definitive cure. Although RA is driven by systemic autoimmunity, its most pronounced manifestation is organspecific inflammation, particularly synovitis in joints. Persistent synovitis results in progressive joint damage and deformity, ultimately compromising joint function. The etiology of RA is multifaceted, intricately intertwining genetic, environmental, and immunological elements. While autoreactive agents have traditionally been viewed as pathogenic contributors to the development of arthritis, our research, utilizing multiple experimental arthritis models, has pinpointed several pivotal autoreactive mediators, which are surprisingly regulatory. In study I, we established a cartilage antibody induced arthritis (CAIA) model. The deficiency of Fc gamma receptor (FCGR) 2B enables swift onset of CAIA within a 12-hour time frame, and overrides the resistance arising from complement C5 deficiency. Notably, our results highlight that FCGR3 is essential and sufficient for CAIA development. The role of FCGR4 remains to be further elucidated. In Study II, we engineered a range of recombinant antibodies targeting the F4 epitope on type-II collagen (COL2). One of these antibodies, denoted R69-4, not only prevented the onset of CAIA, but also effectively suppressed the established disease. Further screening revealed that R69-4 binds to numerous targets in the synovial fluid (SF), including the complement C1q. As a result, R69-4 markedly dampens FCGR3 signaling in SF neutrophils, thereby interrupting neutrophil self-orchestrated recruitment. Given this efficacy, R69-4 emerges as a promising therapeutic candidate for RA, particularly during its acute stage. In study III, we introduced mutations to the immunodominant T cell epitope of COL2. A mutation resulting in higher affinity to major histocompatibility complex class II (MHC II) confers resistance to collagen-induced arthritis (CIA). However, the absence of either FCGR2B or neutrophil cytosolic factor 1 (NCF1) disrupts this tolerance. In particular, the deficiency of NCF1 leads to a reduction of regulatory T cells (Tregs), and a decrease of autoimmune regulator (AIRE) expression in medullary thymic epithelial cells (mTECs). In Study IV, we identified a subset of autoreactive B cells that are ubiquitously present across species. These B cells target the C1 epitope on COL2. Transferring these C1 B cells effectively suppressed arthritis of recipient mice in an antigen-specific manner. We further discerned that the suppressive efficacy of C1 B cells stems from the activation of Tregs and the functional integrity of CD72. In RA patients, we noted a reduced frequency of C1 B cells, possibly attributed to their differentiation into plasma cells. Interventions that can reverse this transition may contribute to preventing the onset of RA.
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| 7. |
- Yuan, Zhongcheng, et al.
(author)
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Approximately 800-nm-Thick Pinhole-Free Perovskite Films via Facile Solvent Retarding Process for Efficient Planar Solar Cells
- 2016
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In: ACS APPLIED MATERIALS and INTERFACES. - : AMER CHEMICAL SOC. - 1944-8244 .- 1944-8252. ; 8:50, s. 34446-34454
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Journal article (peer-reviewed)abstract
- Device performance of organometal halide perovskite solar cells significantly depends on the quality and thickness of perovskite absorber films. However, conventional deposition methods often generate pinholes within similar to 300 nm-thick perovskite films, which are detrimental to the large area device manufacture. Here we demonstrated a simple solvent retarding process to deposit uniform pinhole free perovskite films with thicknesses up to similar to 800 nm. Solvent evaporation during the retarding process facilitated the components separation in the mixed halide perovskite precursors, and hence the final films exhibited pinhole free morphology and large grain sizes. In addition, the increased precursor concentration after solvent-retarding process led to thick perovskite films. Based on the uniform and thick perovskite films prepared by this convenient process, a champion device efficiency up to 16.8% was achieved. We believe that this simple deposition procedure for high quality perovskite films around micrometer thickness has a great potential in the application of large area perovskite solar cells and other optoelectronic devices.
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