Bio-Inspired Screwed Conduits from the Microfluidic Rope-Coiling Effect for Microvessels and Bronchioles

Tubular microfibers have recently attracted extensive interest for applications in tissue engineering.However,the fabrication of tubular fibers with intricate hierarchical structures remains a major challenge.Here,we present a novel one-step microfluidic spinning method to generate bio-inspired screwed conduits(BSCs).Based on the microfluidic rope-coiling effect,a viscous hydrogel precursor is first curved into a helix stream in the channel,and then consecutively packed as a hollow structured stream and gelated into a screwed conduit(SC)via ionic and covalent crosslinking.By taking advantage of the excellent fluid-controlling ability of microfluidics,various tubes with diverse structures are fabricated via simple control over fluid velocities and multiple microfluidic device designs.The perfusability and permeability results,as well as the encapsulation and culture of human umbilical vein endothelial cells(HUVECs),human pulmonary alveolar epithelial cells(HPAs),and myogenic cells(C2C12),demonstrate that these SCs have good perfusability and permeability and the ability to induce the formation of functional biostructures.These features support the uniqueness and potential applications of these BSCs as biomimetic blood vessels and bronchiole tissues in combination with tissue microstructures,with likely application possibilities in biomedical engineering.

Ultrasonographic evaluation of enthesitis in patients with ankylosing spondylitis

The aim of this study was to assess sensitivity and responsiveness of power Doppler ultrasound （PDUS） in detecting enthesitis for ankylosing spondylitis （AS） patients compared to clinical examinations. Twenty AS patients initiating etanerceptunderwent clinical and PDUS examinations of six bilateral entheseal sites at baseline and after 1, 2 and 3 months of treatment. Clinical and PDUS examinations identified at least one entheseal lesion in nine （45%） and 19 （95%） patients, respectively. Furthermore, of 240 entheseal sites examined in these 20 patients, PDUS detected 123 entheseal lesions （51.3% of sites）, compared with only 47 entheseal lesions （19.6%） detected by clinical examination （P〈0.05）. The entheseal lesions found on PDUS were most commonly identified by calcification （33.3%）, tendon edema （29.2%）, abnormal blood flow （25.8%）, a thickened tendon （22.1%）, cortical irregularity （12.9%）, bony erosions （9.6%） and bursitis at the tendon insertion to the bone cortex （7.1%）. Improvements in clinical symptoms and laboratory parameters, and significant decreases in PDUS scores were observed following treatment with etanereept. Improvements in PDUS scores continued during follow-up in patients who entered remission following treatment. In conclusion, PDUS improves detection of structural and inflammatory abnormalities of the enthesis in AS compared to physical examination. In addition, PDUS may be useful inascertaining medications.

Microfluidics for Medical Additive Manufacturing

Additive manufacturing plays a vital role in the food,mechanical,pharmaceutical,and medical fields.Within these fields,medical additive manufacturing has led to especially obvious improvements in medical instruments,prostheses,implants,and so forth,based on the advantages of cost-effectiveness,customizability,and quick manufacturing.With the features of precise structural control,high throughput,and good component manipulation,microfluidic techniques present distinctive benefits in medical additive manufacturing and have been applied in the areas of drug discovery,tissue engineering,and organs on chips.Thus,a comprehensive review of microfluidic techniques for medical additive manufacturing is useful for scientists with various backgrounds.Herein,we review recent progress in the development of microfluidic techniques for medical additive manufacturing.We evaluate the distinctive benefits associated with microfluidic technologies for medical additive manufacturing with respect to the fabrication of droplet/fiber templates with different structures.Extensive applications of microfluidic techniques for medical additive manufacturing are emphasized,such as cell guidance,three-dimensional(3D)cell culture,tissue assembly,and cell-based therapy.Finally,we present challenges in and future perspectives on the development of microfluidics for medical additive manufacturing.

Microfluidic Generation of Multicomponent Soft Biomaterials

Soft biomaterials hold great potential for a plethora of biomedical applications because of their deforma-bility,biodegradability,biocompatibility,high bioactivity,and low antigenicity.Multicomponent soft bio-materials are particularly attractive as a way of accommodating components made of different materials and generating combinative functions.Microfluidic technology has emerged as an outstanding tool in generating multicomponent materials with elaborate structures and constituents,in that it can manipu-late multiphasic flows precisely on the micron scale.In recent decades,much progress has been achieved in the microfluidic fabrication of multicomponent soft biomaterials with finely defined physicochemical properties capable of controllable therapeutics delivery,three-dimensional(3D)cell culture,flexible devices and wearable electronics,and biosensing for molecules.In the paper,we summarize current pro-gress in multicomponent soft biomaterials derived from microfluidics and emphasize their applications in biomedical fields.We also provide an outlook of the remaining challenges and future trends in this field.

Effect of Jianpi Bushen formula for colon cancer patients who underwent adjuvant chemotherapy:Statistical analysis plan for a multicenter trial

Background:Patients with colon cancer who receive chemotherapy usually experience various gastrointestinal adverse reactions,including nausea,vomiting,and diarrhea,which make it challenging for them to adhere to treatment.As an effective traditional Chinese medicine,the Jianpi Bushen formula has been widely used to alleviate the side effects of chemotherapy.Objective:To evaluate the efficacy and safety of Jianpi Bushen formulae for patients who undergo chemotherapy.This statistical analysis plan(SAP)is intended to enhance the transparency and research quality of our randomized controlled trial.Methods:Our study is a multicenter,double-blind,randomized controlled clinical trial.This trial aimed to compare the completion rate of chemotherapy in colon cancer patients who are using and not using Jianpi Bushen formula.To attenuate possible selection bias in the final report,we declared the overall trial design,outcome measures,subgroup analyses,and safety measures.Also,we described the data management and statistical analysis methods in detail.Conclusion:The SAP provides more detailed information than the trial protocol for data management and statistical analysis methods.Further post-hoc analyses can be performed by referring to the SAP,and possible selection bias can be attenuated.

Expression of c-kit receptor in peripheral blood mononuclear cells in patients with systemic lupus erythematosus

Objective： To determine the expression of c-kit receptor in peripheral blood mononuclear cells （PBMCs） in patients with systemic lupus erythematosus （SLE）, and analyze the relationship between the c-kit expression level of PBMCs and clinical parameters. Methods： Peripheral blood mononuclear cells in 47 patients with SLE and 21 healthy volunteers were collected. Expression of c-kit mRNA in PBMCs were determined with reverse transcription-polymerase chain reaction （RT-PCR）. The protein of c-kit receptor （CDllT） in PBMCs was measured by flow cytometry. Results： Expression of c-kit receptor protein and mRNA in patients with active or inactive SLE （ n = 47） were significantly higher than those in controls. The c-kit receptor of PBMCs in SLE patients were significantly higher than those in healthy controls （ n = 21 ）, the c-kit receptor of PBMCs in active patients （ n = 27） were significantly higher than those in inactive patients （ n = 20） and there was no significant difference was found between patients with inactive SLE and healthy controls（ P 〉 0.05）. The c-kit receptor of PBMCs in SLE have significant association with activity index. Conclusion： Production of c-kit receptor is aberrantly increased in PBMCs in patients with SLE. C-kit receptor might be more closely related to the clinical parameters in SLE patients, which might reflect the clinical status of SLE patients.

A Pilot Study of the Therapeutic Efficacy and Mechanism of Artesunate in the MRL/lpr Murine Model of Systemic Lupus Erythematosus

Recent evidence indicates that artesunate has immunomodulatory properties that might be useful for treating autoimmune disease.In this study,we conducted a pilot study and explored the effect and mechanism of artesunate on the treatment of systemic lupus erythematosus using an MRL/lpr murine model.MRL/lpr mice were divided into control,cyclophosphamide(CTX)and artesunate treatment groups.Blood was collected to measure serum levels of creatinine,antinuclear antibody(ANA)and anti-double-stranded DNA(anti-dsDNA)antibody.Twenty-four-hour urine was collected to measure levels of proteinuria.The concentration of monocyte chemotactic protein-1(MCP-1)in serum and urine was measured.The expression of MCP-1 in kidney was detected by Western blot and immunohistochemistry assay,respectively.The expression of B cell activating factor(BAFF)in spleen was determined by real time-PCR and immunoblotting.We found that artesunate significantly increased the survival rate,body weight and blood leukocyte counts,and reduced the serum levels of ANA and anti-dsDNA antibody titer,24 h urinary protein,and serum creatinine.Our results indicated that artesunate could decrease MCP-1,major pro-inflammation cytokine,in serum,urine and kidney.We also found that the level of BAFF,the major B cell activation factor,was decreased in artesunate treated MRL/lpr mice.Its efficacy was comparable with that of CTX in this study.Taken together,we have demonstrated that artesunate can inhibit the progression of disease and reverse the pathologic lesion of lupus nephritis.

Deep3DSketch-im:rapid high-fidelity AI 3D model generation by single freehand sketches

The rise of artificial intelligence generated content(AIGC)has been remarkable in the language and image fields,but artificial intelligence(AI)generated three-dimensional(3D)models are still under-explored due to their complex nature and lack of training data.The conventional approach of creating 3D content through computer-aided design(CAD)is labor-intensive and requires expertise,making it challenging for novice users.To address this issue,we propose a sketch-based 3D modeling approach,Deep3DSketch-im,which uses a single freehand sketch for modeling.This is a challenging task due to the sparsity and ambiguity.Deep3DSketch-im uses a novel data representation called the signed distance field(SDF)to improve the sketch-to-3D model process by incorporating an implicit continuous field instead of voxel or points,and a specially designed neural network that can capture point and local features.Extensive experiments are conducted to demonstrate the effectiveness of the approach,achieving state-of-the-art(SOTA)performance on both synthetic and real datasets.Additionally,users show more satisfaction with results generated by Deep3DSketch-im,as reported in a user study.We believe that Deep3DSketch-im has the potential to revolutionize the process of 3D modeling by providing an intuitive and easy-to-use solution for novice users.

Recent advances in artificial intelligence generated content

Artificial intelligence generated content(AIGC)has been a research hotspot in the field of artificial intelligence in recent years.It is expected to replace humans in performing some of the work of content generation at a low cost and a high volume,such as music,painting,multimodal content generation,news articles,summary reports,stock commentary summaries,and even content and digital people generated in the meta-universe.AIGC provides a new technical path for the development and implementation of AI in the future.

MCP-1 and IL-4 encapsulated hydrogel particles with macrophages enrichment and polarization capabilities for systemic lupus erythematosus treatment

Macrophages play a pivotal role in systemic lupus erythematosus(SLE)therapy.Efforts have been made to develop multifunctional drug delivery systems capable of directing macrophage polarization.Here,we present a novel hyaluronic acid methacrylate(HAMA)hydrogel microparticle encapsulating multiple cytokines for SLE remission though enhancing macrophage functions.The HAMA microparticles loaded with monocyte chemotactic protein-1(MCP-1)and interleukin-4(IL-4)were fabricated by using a microfluidic technology.The released MCP-1 facilitates the aggregation of inflammatory macrophages,after which IL-4 induces the macrophage phenotype shift from inflammatory M1 to immune-protective M2,thus restoring immune balance.We have demonstrated in MRL/lpr mice that the hydrogel microparticles could improve their efficacy of intraperitoneal drug delivery,modulate immune function,and attenuate the disease symptoms.These results suggest that our proposed microparticles delivery platform has potential clinical value for treating autoimmune diseases.

Bio-inspired temporospatial catalytic cascades systems based on ultrasound-triggered multicomponent piezoelectric microparticles

Reactive oxygen species(ROS)have certain effect in cancer treatment,thus many studies have been focused on developing functional systems to generate ROS in tumor.Here,inspired by the multi-enzyme biocatalysis in organisms,novel ultrasound-triggered temporospatial catalytic cascades systems are presented based on barium titanate(BTO)and platinum(Pt)co-loaded multi-component micropar-ticles(Pt/BTO@MCMPs)to successively achieve oxygen and ROS production for tumor sonodynamic therapy.By using a customized capillary microfluidic device,the Pt/BTO@MCMPs are fabricated with Pt nanoparticles located in their core part and BTO nanocubes located in their peripheral part,alternating with blank porous hydrogel components for increasing interaction areas between the encap-sulated nanomaterials and the ambient substrates.In the microparticles,the Pt can catalyze hydrogen peroxide from the tumor microenvironment to generate O2 and H2O serving as substrates for piezoelectric catalytic reactions,contributing to additional generation of ROS under US activation.Based on the system,it is demon-strated that the Pt/BTO@MCMPs are featured with excellent biocompatibility under normal biological conditions and show desired tumor eradication properties under ultrasound irradiation in mice carrying pancreatic tumors.These results indicate that the proposed ultrasound-triggered temporospatial catalytic cascades systems are promising for clinic anti-tumor applications.

Enhanced therapeutic effects of apoptotic cell-conditioned mesenchymal stem cells in lupus-prone MRL/lpr mice

Background::Apoptotic cell-conditioned mesenchymal stem cells (AC-MSCs) exhibit stronger T cell suppressive ability via cyclooxygenase 2 (COX2)/prostaglandin E2 (PGE2);however, whether AC-MSCs exhibit enhanced therapeutic effects on systemic lupus erythematosus (SLE) remains unknown. Methods: Splenocytes from MRL/MPJ-Fas lpr (MRL /lpr) mice were cocultured with AC-MSCs, and the proportion of plasma cells was determined by flow cytometry. MSCs, AC-MSCs, COX2 knockdown MSCs, and COX2 knockdown AC-MSCs were infused into MRL/ lpr mice ( n = 10/group). Survival rates and lupus symptoms, including proteinuria, kidney injury, renal immune complex deposition, and autoantibody production, were assessed. Additionally, the number of plasma cells and serum levels of inflammatory cytokines were measured. Results::The AC-MSCs significantly inhibited plasma cells via PGE2 after 24 h coculture in vitro, whereas MSCs did not. In the MRL /lpr mice, AC-MSC treatment led to a significantly higher survival rate than phosphate-buffered saline (PBS) treatment (90% vs. 50%, p < 0.05). Moreover, AC-MSC infusion decreased urine protein levels as early as 1 week after administration (0.89 ± 0.55 mg/mL vs. 1.59 ± 0.60 mg/mL, p < 0.05, compared with PBS treatment). Administration of both MSCs and AC-MSCs reduced renal immunoglobulin G and complement C3 deposition, whereas COX2 knockdown MSCs and COX2 knockdown AC-MSCs did not. Serum anti-dsDNA antibody levels in AC-MSC-treated mice significantly decreased (0.40 ± 0.25 vs. 0.99 ± 0.58, p < 0.05), compared with PBS treatment, as well as the number of plasma cells in both the spleen ([2.14 ± 1.05] × 10^(6) vs. [8.02 ± 4.01] × 10^(6), p < 0.01) and renal-draining lymph nodes ([0.78 ± 0.68] × 10^(6) vs. [2.49 ± 1.45] × 10^(6), p < 0.05). Additionally, AC-MSCs inhibited the production of inflammatory cytokines, including interleukin-21, tumor necrosis factor-alpha, and monocyte chemoattractant protein-1. Conclusions::AC-MSCs enhanced the therapeutic effects in mice with lupus, which were partially mediated by COX2/PGE2. Therefore, AC preconditioning may be a new strategy for MSC transplantation in the treatment of SLE.

New-onset primary Sjögren's syndrome following exposure to severe acute respiratory syndrome coronavirus 2: A retrospective cohort study

Background:Understanding the clinical implications of autoimmune manifestations associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is essential to reduce its consequences. This study was aimed at determining the activities of new-onset primary Sjögren syndrome (pSS) since the emergence of SARS-CoV-2.Methods:This retrospective cohort study included data from 471 participants with dry mouths and eyes who had been attending Nanjing Drum Tower Hospital since December 2019. By April 2023, patients diagnosed with pSS were sequentially assigned to vaccinated group ( n = 24) or vaccinated and infected group based on exposure ( n = 20). Patients diagnosed with pSS within 3 months of vaccination against SARS-CoV-2 were assigned to a vaccinated group, and those who had been vaccinated and then developed pSS within 3 months of follow up after direct exposure to SARS-CoV-2 were assigned to a vaccinated and infected group. The controls comprised age- and sex-matched patients who had not been exposed to SARS-CoV-2 before December 2019 ( n = 21). We then compared data among the three groups. Results:The vaccinated and infected patients had more fever, malaise, splenomegaly, and weight loss before diagnosis and a higher European Alliance of Associations for Rheumatology Sjögren's syndrome disease activity index at the time of onset than the other two groups. Vaccinated patients had a higher frequency of anti-nuclear antibody (ANA) titers > 1:320 ( n = 12;50%) and anti-phospholipid antibodies (aPL) ( n = 7;29%) than the controls. The frequency of anti-Ro/SSA antibodies (13, 65%), ANA titers > 1:320 ( n = 16;80%), and aPLs ( n = 7;29%) ( n = 5;25%) were all significantly higher in vaccinated patients with infection than those in the controls. Higher doses of glucocorticoids, cyclosporin A, and tacrolimus were administered to the vaccinated and infected than the vaccinated and control groups ( p < 0.05, for all). Conclusions:Patients with new-onset pSS and a history of vaccination and SARS-CoV-2 infection might have more active disease. Further strengthening the assessment of people with a clear history of SARS-CoV infection and the monitoring of potential populations for autoimmune screening should not be overlooked.

The regulation of the Treg/Th 17 balance by mesenchyma stem cells in human systemic lupus erythematosus

Background and objective： Umbilical cord （UC）-derived mesenchymal stem cells （MSCs） have shown immunoregulation of various immune cells. The aim of this study was to investigate the mechanism of UC MSCs in the regulation of peripheral regulatory T cells （Treg） and T helper 17 （Th17） cells in patients with systemic lupus erythematosus （SLE）. Methods： Thirty patients with active SLE, refractory to conventional therapies, were given UC MSCs infusions. The percentages of peripheral blood CD4＋CD25＋Foxp3＋ regulatory T cells （Treg） and CD3＋CD8-1L17A＋ Th17 cells and the mean fluorescence intensities （MFI） of Foxp3 and IL- 17 were measured at I week, I month, 3 months, 6 months, and 12 months after MSCs transplantation （MSCT）. Serum cytokines, including transforming growth factor beta （TGF-β）, tumor necrosis factor alpha （TNF-α）, interleukin 6 （IL-6）, and IL-17A were detected using ELISA. Peripheral blood mononuclear cells from patients were collected and co-cultured with UC MSCs at ratios of 1：1, 10：1, and 50：1, respectively, for 72 h to detect the proportions of Treg and Th17 cells and the MFIs of Foxp3 and IL-17 were determined by flow cytometry. The cytokines in the supernatant solution were detected using ELISA. Inhibitors targeting TGF-β, IL-6, indoleamine 2,3-dioxygenase （IDO）, and prostaglandin E2 were added to the co-culture system, and the percentages of Treg and Th17 cells were observed. Results： The percentage of peripheral Treg and Foxp3 MFI increased 1 week, 1 month, and 3 months after UC MSCs transplantation, while the Th17 proportion and MFI of IL-17 decreased 3 months, 6 months, and 12 months after the treatment, along with an increase in serum TGF-β at I week, 3 months, and 12 months and a decrease in serum TNF-a beginning at I week. There were no alterations in serums IL-6 and IL-17A before or after MSCT. In vitro studies showed that the UC MSCs dose-dependently up-regulated peripheral Treg proportion in SLE patients, which was not depended on cell-cell contact. However, the down-regulation of Th17 cells was not dose-dependently and also not depended on cell-cell contact. Supernatant TGF-α and IL-6 levels significantly increased, TNF-a significantly decreased, but IL-17A had no change after the co-culture. The addition of anti-TGF-β antibody significantly abrogated the up-regulation of Treg, and the addition of PGE2 inhibitor significantly abrogated the down-regulation of Th17 cells. Both anti-lL-6 antibody and IDO inhibitor had no effects on Treg and Th17 cells. Conclusions： UC MSCs up-regulate Treg and down-regulate Th 17 cells through the regulation of TGF-β and PGE2 in lupus patients.

Transplantation of Human Bone Marrow Mesenchymal Stem Cell Ameliorates the Autoimmune Pathogenesis in MRL/lpr Mice

Recent evidence indicates that mesenchymal stem cells （MSC） possess immunosuppressive properties both in vitro and in vivo. We previously demonstrated the functional abnormality of bone marrow derived MSC in patients with systemic lupus erythematosus （SLE）. In this study, we aimed to investigate whether transplantation of human bone marrow derived MSC affects the autoimmune pathogenesis in MRL/Ipr mice. We found that human MSC from healthy donors reduced the proliferation of T lymphocytes from MRL/Ipr mice in a dose-dependent fashion. Two weeks after in vivo transfer of MSC, we detected significantly reduced serum levels of anti ds-DNA antibodies and 24 hour proteinuria in MRL/Ipr mice as compared with control groups without MSC transplantation. Moreover, flow cytometric analysis revealed markedly reduced number of CD4＋ T cells while increased Thl subpopulation in MSC group and MSC ＋ CTX group when compared with controls. Histopathological examination showed significantly reduced renal pathology in MSC-treated mice. Immunohistochemical studies further revealed reduced expression of TGF-~, FN, VEGF and the deposition of complement C3 in renal tissue after MSC and MSC ＋ CTX treatment. Taken together, we have demonstrated that transplantation of human MSC can significantly inhibit the autoimmune progression in MRL/Ipr mice. Cellular ＆ Molecular Immunology. 2008;5（6）：417-424.

MicroRNA-663 induces immune dysregulation by inhibiting TGF-β1 production in bone marrow-derived mesenchymal stem cells in patients with systemic lupus erythematosus

Mesenchymal stem cells(MSCs)are critical for immune regulation.Although several microRNAs(miRNAs)have been shown to participate in autoimmune pathogenesis by affecting lymphocyte development and function,the roles of miRNAs in MSC dysfunction in autoimmune diseases remain unclear.Here,we show that patients with systemic lupus erythematosus(SLE)display a unique miRNA signature in bone marrow-derived MSCs(BMSCs)compared with normal controls,among which miR-663 is closely associated with SLE disease activity.MiR-663 inhibits the proliferation and migration of BMSCs and impairs BMSC-mediated downregulation of follicular T helper(Tfh)cells and upregulation of regulatory T(Treg)cells by targeting transforming growth factorβ1(TGF-β1).MiR-663 overexpression weakens the therapeutic effect of BMSCs,while miR-663 inhibition improves the remission of lupus disease in MRL/lpr mice.Thus,miR-663 is a key mediator of SLE BMSC regulation and may serve as a new therapeutic target for the treatment of lupus.

CD4^(+)CD25^(+)but not CD4^(+)Foxp3^(+) T cells as a regulatory subset in primary biliary cirrhosis

Increasing evidence indicates a role for regulatory T cells(Tregs)in the immune response and in autoimmune diseases,but the role of Tregs and cytokines in autoimmune hepatic diseases remains largely unclear and controversial,especially in patients with primary biliary cirrhosis(PBC).This study was undertaken to investigate Tregs and different cytokines in the liver and peripheral blood of PBC patients.We found that these patients demonstrated a reduction of CD4^(+)CD25^(+) T cells but elevated CD4^(+)Foxp3^(+) T cells in peripheral blood mononuclear cells(PBMCs)and CD41 T cells.The percentage of CD4^(+)CD25^(+) T cells in PBMCs was negatively correlated with elevated plasma interferon(IFN)-c levels.A liver-specific analysis showed that the frequency of Foxp31 Tregs,transforming growth factor(TGF)-b1 and IFN-c were increased in PBC patients.Our findings suggest that an imbalance between CD4^(+)CD25^(+) Tregs and cytotoxic cytokines plays a crucial role in the pathogenesis of PBC while the role of Foxp3 needs further investigation.

Proteasome inhibition suppresses Th17 cell generation and ameliorates autoimmune development in experimental Sjögren’s syndrome

Immunoproteasome activation in immune cells is involved in the modulation of immune responses.Increasing evidence indicates that proteasome inhibitors show beneficial effects in treating autoimmune diseases,but it remains unclear whether proteasome inhibition is an effective approach for suppressing autoimmune development in Sjögren’s syndrome(SS).Our previous work has demonstrated a critical role for Th17 cells in the development of experimental SS(ESS)in mice.In this study,we detected high levels of low-molecular-weight protein 7(LMP7),a key subunit of the immunoproteasome,in Th17 cells from ESS mice.Moreover,treatment with bortezomib(BTZ),a proteasome inhibitor,markedly suppressed Th17 differentiation in both murine and human naive T cells in culture.Furthermore,ESS mice treated with BTZ displayed significantly higher saliva flow rates and a reduction in tissue destruction in the salivary glands compared with vehicle-treated ESS mice.Notably,BTZ-treated ESS mice showed markedly decreased Th17 cells,germinal center B cells and plasma cells in the peripheral lymphoid organs.In addition,adoptively transferred wild type naive CD4+T cells rapidly differentiated into Th17 cells and induced salivary dysfunction in IL-17-deficient mice immunized for ESS induction.However,BTZ treatment profoundly suppressed the donor T-cell-derived Th17 response and ameliorated the reduction in salivary secretion in IL-17-deficient recipient mice.Taken together,our findings demonstrate that proteasome inhibition can effectively ameliorate ESS by suppressing the Th17 response,which may contribute to the development of a novel therapeutic strategy for the treatment of SS.

SmartPaint:a co-creative drawing system based on generative adversarial networks

Artificial intelligence(AI) has played a significant role in imitating and producing large-scale designs such as e-commerce banners. However, it is less successful at creative and collaborative design outputs. Most humans express their ideas as rough sketches, and lack the professional skills to complete pleasing paintings. Existing AI approaches have failed to convert varied user sketches into artistically beautiful paintings while preserving their semantic concepts. To bridge this gap, we have developed Smart Paint, a co-creative drawing system based on generative adversarial networks(GANs), enabling a machine and a human being to collaborate in cartoon landscape painting. Smart Paint trains a GAN using triples of cartoon images, their corresponding semantic label maps, and edge detection maps. The machine can then simultaneously understand the cartoon style and semantics, along with the spatial relationships among the objects in the landscape images. The trained system receives a sketch as a semantic label map input, and automatically synthesizes its edge map for stable handling of varied sketches. It then outputs a creative and fine painting with the appropriate style corresponding to the human’s sketch. Experiments confirmed that the proposed Smart Paint system successfully generates high-quality cartoon paintings.

Bio-inspired adhesive porous particles with human MSCs encapsulation for systemic lupus erythematosus treatment

Mesenchymal stem cells(MSCs)therapy is a promising treatment for Systemic lupus erythematosus(SLE)patients.However,this method is encumbered by suboptimal phenotype of MSCs used in clinical settings,and a short in vivo persistence time.Herein,inspired by the natural microstructure of the sand tower worm nest,we proposed novel adhesive porous particles with human MSCs encapsulation via microfluidic electrospray technology for SLE treatment.The porous microparticles were formed by immediate gelation reaction between sodium alginate(ALG)and poly-D-lysine(PDL),and then sacrificed polyethylene oxide(PEO)to form the pores.The resultant microparticles could protect MSCs from immune cells while maintain their immune modulating functions,and achieve rapid exchange of nutrients from the body.In addition,owing to the electrostatic adsorption and covalent bonding between PDL and tissues,the porous microparticles could adhere to the bowel surfaces tightly after intraperitoneal injection.Through in vivo imaging system(IVIS)methods and in vivo study,it was demonstrated that the MSCs-encapsulated porous adhesive microparticles could significantly increase the cellular half-life,turn activated inflammatory macrophages into an anti-inflammatory profile,and ameliorate disease progression in MRL/lpr mice.Thus,the MSCs-encapsulated porous microparticles showed distinctive functions in chronic SLE treatment,with additional potential to be used in a variety of biomedical applications.