Fluorinated Titanium Oxide (TiO2-xFx) Nanospindles as Ultrasound-Triggered Pyroptosis Inducers to Boost Sonodynamic Immunotherapy.

Pyroptosis is an inflammatory form of programmed cell death associated with the immune system that can be induced by reactive oxygen species (ROS). As a therapeutic strategy with better penetration depth, sonodynamic therapy (SDT) is expected to induce pyroptosis of cancer cells and boost the immune response. However, it is still a limited problem to precisely adjust the structure of sonosensitizers to exhibit satisfactory sono-catalytic properties. Herein, fluorinated titanium oxide (TiO2-xFx) sonosensitizers were developed to induce pyroptosis under ultrasound (US) to boost antitumor immune responses, enabling highly effective SDT. On the one hand, the introduction of F atoms significantly reduced the adsorption energy of TiO2-xFx for oxygen and water, which is conducive to the occurrence of sono-catalytic reactions. On the other hand, the process of F replacing O increased the oxygen vacancies of the sonosensitizer and shortened the band gap, which enabled powerful ROS generation ability under US stimulation. In this case, large amounts of ROS could effectively kill cancer cells by inducing mitochondrial damage and disrupting oxidative homeostasis, leading to significant cell pyroptosis. Moreover, SDT treatment with TiO2-xFx not only suppressed tumor proliferation but also elicited robust immune memory effects and hindered tumor recurrence. This work highlighted the importance of precisely regulating the structure of sonosensitizers to achieve efficient ROS generation for inducing pyroptosis, which sets the stage for the further development of SDT-immunotherapy.

Turning Waste into Wealth: A Potent Sono-Immune Strategy Based on Microcystis.

Currently, sonodynamic therapy (SDT) has limited therapeutic outcomes and immune responses, highlighting the urgent need for enhanced strategies that can stimulate robust and long-lasting antitumor effects. Microcystis, a notorious microalga, reveals the possibility of mediating SDT owing to the presence of gas vesicles (GVs) and phycocyanin (PC). Herein, a nontoxic strain of Microcystis elabens (labeled Me) is developed as a novel agent for SDT because it generates O2 under red light (RL) illumination, while GVs and PC act as cavitation nuclei and sonosensitizers, respectively. Moreover, algal debris is released after ultrasound (US) irradiation, which primes the Toll-like receptor pathway to initiate a cascade of immune responses. This sono-immune strategy inhibits CT26 colon tumor growth largely by promoting dendritic cell (DC) maturation and cytotoxic T-cell activation. After combination with the immune checkpoint blockade (ICB), the therapeutic outcome is further amplified, accompanied by satisfactory abscopal and immune memory effects; the similar potency is proven in the "cold" 4T1 triple-negative breast tumor. In addition, Me exhibits good biosafety without significant acute or chronic toxicity. Briefly, this study turns waste into wealth by introducing sono-immunotherapy based on Microcystis that achieved encouraging therapeutic effects on cancer, which is expected to be translated into the clinic.

Gas-Amplified Metalloimmunotherapy with Dual Activation of Pyroptosis and the STING Pathway for Remodeling the Immunosuppressive Cervical Cancer Microenvironment.

The immunosuppressive microenvironment of cervical cancer significantly hampers the effectiveness of immunotherapy. Herein, PEGylated manganese-doped calcium sulfide nanoparticles (MCSP) were developed to effectively enhance the antitumor immune response of the cervical cancer through gas-amplified metalloimmunotherapy with dual activation of pyroptosis and STING pathway. The bioactive MCSP exhibited the ability to rapidly release Ca2+, Mn2+, and H2S in response to the tumor microenvironment. H2S disrupted the calcium buffer system of cancer cells by interfering with the oxidative phosphorylation pathway, leading to calcium overload-triggered pyroptosis. On the other hand, H2S-mediated mitochondrial dysfunction further promoted the release of mitochondrial DNA (mtDNA), enhancing the activation effect of Mn2+ on the cGAS-STING signaling axis and thereby activating immunosuppressed dendritic cells. The released H2S acted as an important synergist between Mn2+ and Ca2+ by modulating dual signaling mechanisms to bridge innate and adaptive immune responses. The combination of MCSP NPs and PD-1 immunotherapy achieved synergistic antitumor effects and effectively inhibited tumor growth. This study reveals the potential collaboration between H2S gas therapy and metalloimmunotherapy and provides an idea for the design of nanoimmunomodulators for rational regulation of the immunosuppressive tumor microenvironment.

Zinc-Iron Bimetallic Peroxides Modulate the Tumor Stromal Microenvironment and Enhance Cell Immunogenicity for Enhanced Breast Cancer Immunotherapy Therapy.

Immunotherapy has emerged as a potential approach for breast cancer treatment. However, the rigid stromal microenvironment and low immunogenicity of breast tumors strongly reduce sensitivity to immunotherapy. To sensitize patients to breast cancer immunotherapy, hyaluronic acid-modified zinc peroxide-iron nanocomposites (Fe-ZnO2@HA, abbreviated FZOH) were synthesized to remodel the stromal microenvironment and increase tumor immunogenicity. The constructed FZOH spontaneously generated highly oxidative hydroxyl radicals (·OH) that degrade hyaluronic acid (HA) in the tumor extracellular matrix (ECM), thereby reshaping the tumor stromal microenvironment and enhancing blood perfusion, drug penetration, and immune cell infiltration. Furthermore, FZOH not only triggers pyroptosis through the activation of the caspase-1/GSDMD-dependent pathway but also induces ferroptosis through various mechanisms, including increasing the levels of Fe2+ in the intracellular iron pool, downregulating the expression of FPN1 to inhibit iron efflux, and activating the p53 signaling pathway to cause the failure of the SLC7A11-GSH-GPX4 signaling axis. Upon treatment with FZOH, 4T1 cancer cells undergo both ferroptosis and pyroptosis, exhibiting a strong immunogenic response. The remodeling of the tumor stromal microenvironment and the immunogenic response of the cells induced by FZOH collectively compensate for the limitations of cancer immunotherapy and significantly enhance the antitumor immune response to the immune checkpoint inhibitor αPD-1. This study proposes a perspective for enhancing immune therapy for breast cancer.

FANCI serve as a prognostic biomarker correlated with immune infiltrates in skin cutaneous melanoma.

Background: As a member of tumor, Skin cutaneous melanoma (SKCM) poses a serious threat to people's health because of its strong malignancy. Unfortunately, effective treatment methods for SKCM remain lacking. FANCI plays a vital role in the occurrence and metastasis of various tumor types. However, its regulatory role in SKCM is unclear. The purpose of this study was to explore the association of FANCI with SKCM. Methods: This study investigated the expression of FANCI in GSE46517, GSE15605, and GSE114445 from the Gene Expression Omnibus database and The Cancer Genome Atlas (TCGA)-SKCM datasets using the package "limma" or "DESeq2" in R environment and also investigated the prognostic significance of FANCI by utilizing the GEPIA database. Additionally, our research made use of real-time quantitative polymerase chain reaction (RT-qPCR) and immunohistochemical (IHC) staining to verify FANCI expression between SKCM and normal tissues and developed the knockdown of FANCI in A375 and A875 cells to further analyze the function of FANCI. Finally, this study analyzed the correlation of FANCI and tumor-infiltrating immune cells by CIBERSORT, ESTIMATE, and ssGSEA algorithms. Results: The FANCI level was increasing in SKCM tissues from GSE46517, GSE15605, GSE114445, and TCGA-SKCM. However, high FANCI expression correlated with poor overall survival. The RT-qPCR and IHC confirmed the accuracy of bioinformatics. Knocking down FANCI suppresses A375 and A875 cell proliferation, migration, and invasion. FANCI could be involved in the immunological milieu of SKCM by regulating immune responses and infiltrating numerous immune cells, particularly neutrophils, CD8+ T cells, and B cells. Furthermore, patients with SKCM who have a high FANCI expression level are reported to exhibit immunosuppression, whereas those with a low FANCI expression level are more likely to experience positive outcomes from immunotherapy. Conclusions: The increased FANCI expression in SKCM can be a prognostic biomarker. Knockdown FANCI can reduce the occurrence and progression of SKCM. The FANCI expression provides a foundation for predicting the immune status and treatment of SKCM.

Comparative Analysis of the Therapeutic Effects of Fresh and Cryopreserved Human Umbilical Cord Derived Mesenchymal Stem Cells in the Treatment of Psoriasis.

Psoriasis, an inflammatory autoimmune skin disease, is characterized by scaly white or erythematous plaques, which severely influence patients' quality of life and social activities. Mesenchymal stem cells derived from the human umbilical cord (UCMSCs) represent a promising therapeutic approach for psoriasis because of its unique superiority in ethical agreeableness, abundant source, high proliferation capacity, and immunosuppression. Although cryopreservation provided multiple benefits to the cell therapy, it also greatly compromised clinical benefits of MSCs due to impaired cell functions. The current study aims to evaluate the therapeutic efficacy of cryopreserved UCMSCs in a mouse model of psoriasis as well as in patients with psoriasis. Our results showed that cryopreserved and fresh UCMSCs have comparable effects on the suppression of psoriasis-like symptoms such as thickening, erythema, and scaling, and serum IL-17 A secretion in mice model of psoriasis. Moreover, psoriatic patients injected with cryopreserved UCMSCs had a significant improvement in the Psoriasis Area and Severity Index (PASI), Physician Global Assessment (PGA), and Patient Global Assessments (PtGAs) scores compared to baseline values. Mechanically, cryopreserved UCMSCs markedly inhibit the proliferation of PHA-activated PBMCs, type 1 T helper (Th1) and type 17 T helper (Th17) cell differentiation and secretion of inflammatory cytokines including IFN-γ, TNF-a and IL-17 A in PBMCs stimulated by anti-CD3/CD28 beads. Taken together, these data indicated that cryopreserved UCMSCs exhibited great beneficial effect on psoriasis. Thus, cryopreserved UCMSCs can be systemically administered as ''off-the-shelf'' cell product for psoriasis therapy. Trial Registration ChiCTR1800019509. Registered on November 15, 2018-Retrospectively registered, http://www.chictr.org.cn/ .

Biologic and Small-Molecule Therapies for Moderate-to-Severe Psoriasis: Focus on Psoriasis Comorbidities.

Psoriasis is a systemic immune-mediated disease associated with an increased risk of comorbidities, such as psoriatic arthritis, cardiovascular disease, metabolic syndrome, inflammatory bowel disease, psychiatric disorders, and malignancy. In recent years, with the advent of biological agents, the efficacy and safety of psoriasis treatments have dramatically improved. Presently, tumor necrosis factor-α inhibitors, interleukin-17 inhibitors, interleukin-12/23 inhibitors, and interleukin-23 inhibitors are approved to treat moderate-to-severe psoriasis. Small-molecule inhibitors, such as apremilast and deucravacitinib, are also approved for the treatment of psoriasis. Although it is still unclear, systemic agents used to treat psoriasis also have a significant impact on its comorbidities by altering the systemic inflammatory state. Data from clinical trials and studies on the safety and efficacy of biologics and small-molecule inhibitors provide important information for the personalized care and treatment for patients with psoriasis. Notably, treatment with interleukin-17 inhibitors is associated with new-onset or exacerbations of inflammatory bowel disease. In addition, great caution needs to be taken when using tumor necrosis factor-α inhibitors in patients with psoriasis with concomitant congestive heart failure, multiple sclerosis, and malignancy. Apremilast may induce weight loss as an adverse effect, presenting also with some beneficial metabolic actions. A better understanding of the characteristics of biologics and small-molecule inhibitors in the treatment of psoriasis comorbidities can provide more definitive guidance for patients with distinct comorbidities.

An Autonomous Mobile Combination Disinfection System.

To address the common drawbacks of current disinfection robots, which include the potential for secondary environmental pollution, disinfection dead corners, and low efficiency, in this paper, an autonomous mobile combination disinfection system is proposed. The system utilizes ultraviolet (UV) radiation and a low-concentration hydrogen peroxide aerosol to kill pathogens. It comprises three parts: a human-computer interface, a mobile robot, and disinfection equipment. A disinfection process model with continuous and fixed-point modes was established, and the effective disinfection range, speed, and duration were quantitatively calculated. The developed prototype was tested on-site by a professional third-party testing agency. The experimental results demonstrated that the combination disinfection robot achieved a 92.95% disinfection rate of natural airborne bacteria in a room measuring 22 square meters with a height of 2.8 m in just 30 min. The disinfection efficiency is at least 25% higher compared to standalone UV lamp disinfection and also exhibits a noticeable improvement over standalone hydrogen peroxide aerosol disinfection. The system enables the environmentally friendly, rapid, efficient, and all-encompassing disinfection of natural airborne bacteria. Finally, various disinfection solutions and recommendations for different application scenarios and requirements are provided.

BP Network Model Based on SCLBOA for House Price Forecasting.

Butterfly optimization algorithm (BOA) is a new swarm intelligence algorithm mimicking the behaviors of butterflies. However, there is still much room for improvement. In order to enhance the convergence speed and accuracy of the BOA, we present an improved algorithm SCLBOA based on SIBOA, which incorporates a logical mapping and a Lévy flight mechanism. The logical chaotic map is used for population initialization, and then the Lévy flight mechanism is integrated into the SCLBOA algorithm. To evaluate the performance of the SCLBOA, we conducted many experiments on standard test functions. The simulation results suggest that the SCLBOA is capable of high-precision optimization, fast convergence, and effective global optimization, all of which show that our method outperforms other methods in solving mathematical optimization problems. Finally, the BP network is optimized according to the SCLBOA (SCLBOA-BP) to further verify the availability of the algorithm. Simulation experiments prove the practicability of this method by building a Boston housing price prediction model for training.

Abnormal lipid metabolism in epidermal Langerhans cells mediates psoriasis-like dermatitis.

Psoriasis is a chronic, inflammatory skin disease, frequently associated with dyslipidemia. Lipid disturbance in psoriasis affects both circulatory system and cutaneous tissue. Epidermal Langerhans cells (LCs) are tissue-resident DCs that maintain skin immune surveillance and mediate various cutaneous disorders, including psoriasis. However, the role of LCs in psoriasis development and their lipid metabolic alternation remains unclear. Here, we demonstrate that epidermal LCs of psoriasis patients enlarge with longer dendrites and possess elevated IL-23p19 mRNA and a higher level of neutral lipids when compared with normal LCs of healthy individuals. Accordantly, epidermal LCs from imiquimod-induced psoriasis-like dermatitis in mice display overmaturation, enhanced phagocytosis, and excessive secretion of IL-23. Remarkably, these altered immune properties in lesional LCs are tightly correlated with elevated neutral lipid levels. Moreover, the increased lipid content of psoriatic LCs might result from impaired autophagy of lipids. Bulk RNA-Seq analysis identifies dysregulated genes involved in lipid metabolism, autophagy, and immunofunctions in murine LCs. Overall, our data suggest that dysregulated lipid metabolism influences LC immunofunction, which contributes to the development of psoriasis, and therapeutic manipulation of this metabolic process might provide an effective measurement for psoriasis.

Application of Low-Intensity Laser in the Treatment of Skeletal Muscle Injury in Runners.

With the continuous improvement of people's economic level, running, as the most common sports, is not limited by sports venues and sports levels and deeply loved by people. However, during running, soft tissue resonates with the impact force, increasing the load on joints and tendons and potentially leading to sports injuries. The purpose of this article is to study the application of low-intensity laser in the treatment of muscle strain. This article analyzes running, muscle adjustment, and lower limb stiffness. On the basis of theory, 20 healthy male college students were selected as research objects in the experimental part. The subjects were allowed to run at three speeds: slow, medium, and fast. The kinematics, dynamics, and surface EMG signals of the subjects during running were collected to analyze the effect of low-intensity laser therapy on exercise muscle strain. The experimental results showed that a low-intensity laser can effectively alleviate muscle inflammation, reduce the number of cell damage, bring the mean and integral optical density of protein to the normal level significantly, and reduce the strain degree of exercise muscle. In this article, a statistical method was used to obtain the gait cycle time (P & LT; 0.01) and support cycle time (slow P < 0.01).

A Three-Stage Dynamic Assessment Framework for Industrial Control System Security Based on a Method of W-HMM.

Industrial control systems (ICS) are applied in many fields. Due to the development of cloud computing, artificial intelligence, and big data analysis inducing more cyberattacks, ICS always suffers from the risks. If the risks occur during system operations, corporate capital is endangered. It is crucial to assess the security of ICS dynamically. This paper proposes a dynamic assessment framework for industrial control system security (DAF-ICSS) based on machine learning and takes an industrial robot system as an example. The framework conducts security assessment from qualitative and quantitative perspectives, combining three assessment phases: static identification, dynamic monitoring, and security assessment. During the evaluation, we propose a weighted Hidden Markov Model (W-HMM) to dynamically establish the system's security model with the algorithm of Baum-Welch. To verify the effectiveness of DAF-ICSS, we have compared it with two assessment methods to assess industrial robot security. The comparison result shows that the proposed DAF-ICSS can provide a more accurate assessment. The assessment reflects the system's security state in a timely and intuitive manner. In addition, it can be used to analyze the security impact caused by the unknown types of ICS attacks since it infers the security state based on the explicit state of the system.

IL-17A Promotes Psoriasis-Associated Keratinocyte Proliferation through ACT1-Dependent Activation of YAP-AREG Axis.

Psoriasis is a recurrent inflammatory skin disorder characterized by epidermal hyperplasia, which is primarily driven by IL-17A. The Hippo-YAP signaling pathway plays a vital role in cell survival and tissue growth, and its target gene, AREG, has been reported to promote the development of psoriasis. However, whether IL-17A promotes keratinocyte proliferation through regulating Hippo-YAP signaling has not been explored. In this study, we show that the YAP-AREG pathway is activated in human psoriatic skin and is suppressed by IL-17A antagonist secukinumab and that imiquimod and IL-17A administration activates the YAP-AREG axis in mice epidermis. In vitro studies using HaCaT and normal human epidermal keratinocyte cells suggest that IL-17A enhances AREG expression and keratinocyte proliferation by activating Hippo-YAP signaling. Mechanistically, IL-17A stimulates the recruitment of MST1 to ACT1 in keratinocytes, which leads to reduced MST1-LATS1 interaction and YAP dephosphorylation. Together, our findings reveal a previously unknown mechanism in which IL-17A promotes keratinocyte proliferation in psoriasis, namely through activating YAP-AREG signaling.

Human umbilical cord-derived mesenchymal stem cells ameliorate psoriasis-like dermatitis by suppressing IL-17-producing γδ T cells.

Mesenchymal stem cells (MSCs) have shown great potential in treating autoimmune diseases due to their immunomodulatory capability, which has been verified in both animal experiments and clinical trials. Psoriasis is a chronic and remitting immune-related disease. Limited studies have demonstrated that MSCs might be an effective therapeutic approach for managing psoriasis, whose underlying mechanism remains to be elucidated. In our present study, human umbilical cord-derived MSCs (hUC-MSCs) were subcutaneously injected into mice with imiquimod (IMQ)-induced psoriasis-like skin inflammation to explore the feasibility of this cellular therapy. The severity of psoriasis-like dermatitis was evaluated by cumulative psoriasis area and severity index score and epidermal thickness of skin tissue sections. Flow cytometric analysis was utilized to detect T helper cells, regulatory T cells, and γδ T cells in skin-draining lymph nodes. Real-time quantitative polymerase chain reaction and enzyme-linked immunosorbent assay were used to assess the expression levels of psoriasis-related cytokines and chemokines in mouse dorsal skin lesions. We discovered that hUC-MSCs drastically diminished the severity of IMQ-induced psoriasis-like dermatitis and suppressed inflammatory cell response. Although the tail vein injection of hUC-MSCs was also effective, it was correlated with higher mortality owing to pulmonary embolism. By comparison, subcutaneous injection with two million hUC-MSCs was identified to be the optimal therapeutic strategy. Furthermore, we uncovered that hUC-MSCs might repress skin inflammation probably through inhibiting interleukin-17-producing γδ T cells. In conclusion, subcutaneous administration of hUC-MSCs might be a promising therapeutic approach for psoriasis. Our findings provide novel insights into the underpinning mechanism of hUC-MSC treatment in the management of psoriasis.

Advances in the pathogenesis of psoriasis: from keratinocyte perspective.

Psoriasis is a complex long-lasting inflammatory skin disease with high prevalence and associated comorbidity. It is characterized by epidermal hyperplasia and dermal infiltration of immune cells. Here, we review the role of keratinocytes in the pathogenesis of psoriasis, focusing on factors relevant to genetics, cytokines and receptors, metabolism, cell signaling, transcription factors, non-coding RNAs, antimicrobial peptides, and proteins with other different functions. The critical role of keratinocytes in initiating and maintaining the inflammatory state suggests the great significance of targeting keratinocytes for the treatment of psoriasis.

Does letrozole treatment have favorable effects on the lipid profile? A systematic review and meta-analysis of randomized clinical trials.

As an aromatase inhibitor, letrozole reduces estrogen levels, affecting lipid indices because of the positive role of estrogens in modulating lipoproteins and lipids. Thus, our aim was to meta-analyze data regarding letrozole administration and its effects on the traditional lipid profile. A systematic review and meta-analysis of randomized clinical trials (RCTs) were performed based on the PRISMA guidelines. Web of Science, Scopus, PubMed/Medline, and EMBASE databases were searched until February 11, 2021. From 341 potentially relevant publications, 8 RCTs were selected. All studies used 2.5 mg/d of letrozole. Total cholesterol changed significantly by -6.28 mg/dL (95% CI: -8.73, -3.84, P < 0.001) and HDL-C by -4.40 mg/dL (95% CI: -5.30 to -3.50, p < 0.001) in letrozole group when compared to the control group. Taking into account this comparison between groups, in contrast, LDL-C (WMD: -2.50 mg/dL, 95% CI: -9.94, 4.93, p = 0.510) and triglycerides (WMD: -0.89 mg/dL, 95% CI: -6.87 to 5.07, p = 0.768) did not alter. In conclusion, letrozole administration decreased the concentrations of HDL-C and tocal cholesterol, but not of triglycerides and LDL-C.

Xiao-Yin-Fang Therapy Alleviates Psoriasis-like Skin Inflammation Through Suppressing γδT17 Cell Polarization.

Psoriasis is an immune-mediated chronic inflammatory skin disease primarily mediated by the activation of interleukin (IL)-17-producing T cells. Traditional Chinese Medicine (TCM) represents one of the most effective complementary and alternative medicine (CAM) agents for psoriasis, which provides treasured sources for the development of anti-psoriasis medications. Xiao-Yin-Fang (XYF) is an empirically developed TCM formula that has been used to treat psoriasis patients in Shanghai Changhai Hospital for over three decades. Imiquimod (IMQ)-induced psoriasis-like dermatitis mouse model was utilized to investigate the therapeutic effects of XYF by the assessment of disease severity and skin thickness. Flow cytometric assay was performed to explore the influence of XYF on skin-related immunocytes, primarily T cells. And, RNA sequencing analysis was employed to determine the alternation in gene expression upon XYF therapy. We discovered that XYF alleviated psoriasis-like skin inflammation mainly through suppressing dermal and draining lymph-node IL-17-producing γδT (γδT17) cell polarization. Moreover, XYF therapy ameliorated the relapse of psoriasis-like dermatitis and prohibited dermal γδT cell reactivation. Transcriptional analysis suggested that XYF might regulate various inflammatory signaling pathways and metabolic processes. In conclusion, our results clarified the therapeutic efficacy and inner mechanism of XYF therapy in psoriasis, which might promote its clinical application in psoriasis patients and facilitate the development of novel anti-psoriasis drugs based on the bioactive components of XYF.

Assessing spatio-temporal patterns and driving force of ecosystem service value in the main urban area of Guangzhou.

Increasing human activity around the world has greatly changed the natural ecosystem and the services it provides. In the past few decades, a series of significant changes have taken place in land use/land cover (LULC) in China due to the rapid growth in population, particularly in the cities of the Zhujiang Deita. However, there have been few attempts to study the co-evolution of land use/land cover change and ecosystem service value (ESV) in the main urban area of Guangzhou. Therefore, based on Landsat TM/OLI images from 1987, 1993, 1999, 2005, 2011 and 2017, the weight vector AdaBoost (WV AdaBoost) multi-classification algorithm was utilized to extract LULC data sets, and the spatiotemporal patterns of LULC over these periods were studied. The ESV was estimated and the driving force was analysed. The effect of LULC dynamics on the ESV was evaluated. The results showed that great changes have taken place in LULC in the main urban area of Guangzhou from 1987 to 2017, of which the most significant was the large-scale expansion of the built-up area that occurred through degradation of the forest and cultivated land. The proportion of forest and cultivated land decreased from 43.12% and 34.23% to 25.88% and 12.59%, respectively. The results between periods revealed a decrease in total ESVs from 5.63 × 109 yuan in 1987 to 5.27, 4.16, 4.62, 3.76 and 4.47 × 109 yuan in 1993, 1999, 2005, 2011 and 2017, respectively. In total, ESVs decreased by 1.16 billion yuan (20.61%) from 1987 to 2017. Water supply, food production, nutrient cycling and gas regulation were the four principal ecosystem service functions that affected the total ESVs. Forest, water body and cultivated land areas played a key role in ecosystem services. Therefore, we advocate that when protecting natural ecosystems in the future land use management in Guangzhou should be prioritized.

Dysregulated Peripheral Invariant Natural Killer T Cells in Plaque Psoriasis Patients.

Background: Psoriasis is a common immune-mediated skin disease that involves T-cell-mediated immunity. Invariant natural killer T (iNKT) cells are a unique lymphocyte subpopulation that share properties and express surface markers of both NK cells and T cells. Previous reports indicate that iNKT cells regulate the development of various inflammatory diseases. IL-17 is a key cytokine in the pathogenesis of psoriasis and a key therapeutic target. Secukinumab is a fully human IgG1κ antibody that targets IL-17A, thereby antagonizing the biological effects of IL-17. Objective: To explore the expression of iNKT cells in psoriasis patients and the effect of secukinumab on them. Methods: We examined the frequencies of iNKT cells, Tregs, naïve and memory CD4+and CD8+T cells in the PBMCs as well as their cytokine production in a cohort of 40 patients with moderate-to-severe plaque psoriasis and 40 gender- and age-matched healthy controls. We further collected peripheral blood of another 15 moderate-to-severe plaque psoriasis patients who were treated with secukinumab and evaluated the proportion of iNKT cells in the PBMCs at baseline and week 12. Results: The frequencies of conventional CD4+ T cells, CD8+ T cells, and Tregs in the PBMCs were comparable between psoriasis patients and healthy controls, but the frequencies of Th17 cells, Tc1 cells and Tc17 cells were increased in psoriasis patients. The frequency of peripheral iNKT cells and CD69+ iNKT cells was significantly decreased in psoriasis patients. Both iNKT2 cells and iNKT17 cells were increased in psoriasis patients, but the ratio of iNKT2 cells vs iNKT17 cells was significantly reduced in psoriasis patients. After receiving secukinumab, the proportion of iNKT cells in the PBMCs of patients was increased, while the proportion of iNKT17 cells was decreased. Conclusion: Dysregulated iNKT cells may be involved in the pathogenesis of psoriasis and secukinumab may play a regulatory role on iNKT cells.

High-Speed Handling Robot with Bionic End-Effector for Large Glass Substrate in Clean Environment.

The development of "large display, high performance and low cost" in the FPD industry demands glass substrates to be "larger and thinner". Therefore, the requirements of handling robots are developing in the direction of large scale, high speed, and high precision. This paper presents a novel construction of a glass substrate handling robot, which has a 2.5 m/s travelling speed. It innovatively adopts bionic end-suction technology to grasp the glass substrate more firmly. The structure design is divided into the following three parts: a travel track, a robot body, and an end-effector. The manipulator can be smoothly and rapidly extended by adjusting the transmission ratio of the reducer to 1:2:1, using only one motor to drive two sections of the arm. This robot can transfer two pieces of glass substrate at one time, and improves the working efficiency. The kinematic and dynamic models of the robot are built based on the DH coordinate. Through the positioning accuracy experiment and vibration experiment of the end-effector, it is found that the robot has high precision during handling. The robots developed in this study can be used in large-scale glass substrate handling.