Antimony Component Schottky Nanoheterojunctions as Ultrasound-Heightened Pyroptosis Initiators for Sonocatalytic Immunotherapy.

Sonocatalytic therapy (SCT) holds promise due to its exceptional penetration depth; however, the rapid recombination of electron-hole (e--h+) pairs and the complex tumor microenvironment (TME) impede its broader application. Herein, we discovered that antimony (Sb)-based nanomaterials induced pyroptosis in cancer cells. Therefore, a Schottky heterojunction containing a Sb component (Sb2Se3@Pt) was effectively designed and constructed via in-situ growth of platinum (Pt) nanoparticles (NPs) on a Sb2Se3 semiconductor with narrow bandgaps, which were utilized as US-heightened pyroptosis initiators to induce highly effective pyroptosis in cancer cells to boost SCT-immunotherapy. The biological effects of the Sb2Se3@Pt nanoheterojunction itself combined with the sonocatalytic amplification of oxidative stress significantly induced Caspase-1/GSDMD-dependent pyroptosis in cancer cells. Therefore, SCT treatment with Sb2Se3@Pt not only effectively restrained tumor proliferation but also induced potent immune memory responses and suppressed tumor recurrence. Furthermore, the integration of this innovative strategy with immune checkpoint blockade (ICB) treatment elicited a systemic immune response, effectively augmenting therapeutic effects and impeding the growth of abscopal tumors. Overall, this study provides further opportunities to explore pyroptosis-mediated SCT-immunotherapy.

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.

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.

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.

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.

Interleukin-33 alleviates psoriatic inflammation by suppressing the T helper type 17 immune response.

Psoriasis is a chronic inflammatory skin disease with unclear pathogenesis. Interleukin-33 (IL-33) is highly expressed in patients with psoriasis, but its role in psoriasis is unknown. The aim of this study was to investigate the possible role of IL-33 in the pathogenesis and treatment of psoriasis. IL-33 expression was determined using enzyme-linked immunosorbent assay, real-time fluorescent quantitative polymerase chain reaction and immunohistochemical staining. CD4+ T cells were sorted using magnetic beads and treated with or without IL-33. Imiquimod (IMQ) was used to induce psoriatic inflammation in mice. The frequency of immune cells was determined using flow cytometry. The cytokine level in mouse skin was measured using cytometric bead array. Our results showed that IL-33 was highly expressed in the lesional skin and serum of patients with moderate-to-severe plaque psoriasis. IL-33 inhibited the expression of IL-17 in CD4+ T cells of psoriasis patients. Subcutaneous injection of IL-33 alleviated the IMQ-induced psoriatic inflammation in mice, reduced tumor necrosis factor-α and IL-23 expression, and decreased the proportion of T helper type 17 (Th17) cells in the skin-draining lymph nodes in the mice. Our results suggest that IL-33 plays a protective role in the pathogenesis of psoriasis by suppressing Th17 cell differentiation and function. The potential therapeutic effect of IL-33 in treating psoriasis warrants further investigation.

Ginsenoside compound K ameliorates imiquimod-induced psoriasis-like dermatitis through inhibiting REG3A/RegIIIγ expression in keratinocytes.

BACKGROUND: Psoriasis is a chronic inflammatory skin disease characterized by keratinocyte hyperproliferation. Ginsenoside compound K (CK), a bioactive metabolite of ginseng, modulates various skin disorders with an impact on keratinocyte biology. However, the effect of Ginsenoside CK in psoriasis has not been explored. OBJECTIVE: Our aim was to investigate whether ginsenoside CK could affect the homeostasis of keratinocytes and their expression of psoriasis-associated antimicrobial protein regenerating islet-derived protein 3-alpha (REG3A) and its murine ortholog RegIIIγ. We further explored the therapeutic potential of ginsenoside CK in imiquimod (IMQ)-induced psoriasis-like dermatitis. METHODS: The effects of ginsenoside CK in cell growth and apoptosis of human keratinocytes were measured by MTT assay and flow cytometry, respectively. Bax levels were evaluated by Western blot in HaCaT cells following ginsenoside CK stimulation. REG3A levels were assessed by RT-PCR and Western blot in human keratinocytes following interleukin (IL)-36γ and ginsenoside CK co-simulation. Utilizing IMQ-induced psoriasis mouse model, the therapeutic effects of 0.1% and 1% ginsenoside CK cream were assessed by skin thicknesses and histological examinations, and RegIIIγ level in the lesional skin was detected by Western blot and immunofluorescence. RESULTS: Ginsenoside CK prohibited human keratinocyte proliferation but did not affect their apoptosis. Moreover, it inhibited IL-36γ-induced REG3A expression in HaCaT cells. Ginsenoside CK alleviated imiquimod-induced psoriasis-like hyperkeratosis and reduced RegIIIγ expression in the keratinocytes from lesional skin. CONCLUSION: Ginsenoside CK ameliorated IMQ-induced psoriasis-like dermatitis possibly through inhibiting REG3A/RegIIIγ expression in keratinocytes, which highlighted a therapeutic potential of ginsenoside CK in psoriasis.

Radius and Orientation Measurement for Cylindrical Objects by a Light Section Sensor.

In this paper, an efficient method based on a light section sensor is presented for measuring cylindrical objects' radii and orientations in a robotic application. By this method, the cylindrical objects can be measured under some special conditions, such as when the cylindrical objects are welded with others, or in the presence of interferences. Firstly, the measurement data are roughly identified and accurately screened to effectively recognize ellipses. Secondly, the data are smoothed and homogenized to eliminate the effect of laser line loss or jump and reduce the influence of the inhomogeneity of measurement data on the ellipse fitting to a minimum. Finally, the ellipse fitting is carried out to obtain the radii and orientations of the cylindrical objects. Measuring experiments and results demonstrate the effective of the proposed radius and orientation measurement method for cylindrical object.

MicroRNA-495 mimics delivery inhibits lung tumor progression.

MicroRNAs (miRNAs) can function as tumor suppressors and might provide an efficient strategy for annihilating cancer. Specific miRNAs can be reintroduced into tumor cells to elicit the tumor suppressor activities. We show that systemically delivered, synthetic miRNA mimics in complex with a novel neutral lipid emulsion are preferentially targeted to lung tumors and show therapeutic benefit in mouse models of lung cancer. The delivery was demonstrated using mimics of the tumor suppressor microRNA-495 which is found downregulated in most lung cancer. Systemic treatment of a Kras-activated autochthonous mouse model of non-small cell lung cancer (NSCLC) led to a significant decrease in tumor burden. Specifically, mice treated with microRNA-495 displayed a large reduction in tumor area compared to mice treated with a miRNA control. These findings provide direct evidence that systematically delivered synthetic miRNA mimics to the mammalian lung can inhibit tumor proliferation and support the promise of miRNAs as a targeted therapy for lung cancer in future.

Modulating the Electronic Structure of MnNi2S3 Nanoelectrodes to Activate Pyroptosis for Electrocatalytic Hydrogen-Immunotherapy.

Hydrogen (H2) therapy has demonstrated antitumor effect, but the therapeutic efficacy is restricted by the low solubility and nontarget delivery of H2. Electrolysis of H2O by electrocatalysts sustainably releases enormous amounts of H2 and inspires the precise delivery of H2 for tumor therapy. Herein, manganese-doped Ni2S3 nanoelectrodes (MnNi2S3 NEs) are designed for the electrocatalytic delivery of H2 and the activation of antitumor immunity to effectively potentiate H2-immunotherapy. Ni atoms featuring empty 3d orbitals reduce the initial energy barrier of the hydrogen evolution reaction (HER) by promoting the adsorption of H2O. Moreover, Mn atoms with different electronegativity modulate the electronic structure of Ni atoms and facilitate the desorption of the generated H2, thus enhancing the HER activity of the MnNi2S3 NEs. Based on the high HER activity, controllable delivery of H2 for electrocatalytic hydrogen therapy (EHT) is achieved in a voltage-dependent manner. Mechanistically, MnNi2S3 NE-mediated EHT induces mitochondrial dysfunction and oxidative stress, which subsequently activates pyroptosis through the typical ROS/caspase-1/GSDMD signaling pathway. Furthermore, MnNi2S3 NE-mediated EHT enhances the infiltration of CD8+ T lymphocytes into tumors and reverses the immunosuppressive microenvironment. This work demonstrates an electrocatalyst with high HER activity for synergistic gas-immunotherapy, which may spark electrocatalyst-based tumor therapy strategies.

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.

A Two-Pronged Nanostrategy of Iron Metabolism Disruption to Synergize Tumor Therapy by Triggering the Paraptosis-Apoptosis Hybrid Pathway.

Iron metabolism has emerged as a promising target for cancer therapy; however, the innate metabolic compensatory capacity of cancer cells significantly limits the effectiveness of iron metabolism therapy. Herein, bioactive gallium sulfide nanodots (GaSx), with dual functions of "reprogramming" and "interfering" iron metabolic pathways, were successfully developed for tumor iron metabolism therapy. The constructed GaSx nanodots ingeniously harness hydrogen sulfide (H2S) gas, which is released in response to the tumor microenvironment, to reprogram the inherent transferrin receptor 1 (TfR1)-ferroportin 1 (FPN1) iron metabolism axis in cancer cells. Concurrently, the gallium ions (Ga3+) derived from GaSx act as a biochemical "Trojan horse", mimicking the role of iron and displacing it from essential biomolecular binding sites, thereby influencing the fate of cancer cells. By leveraging the dual mechanisms of Ga3+-mediated iron disruption and H2S-facilitated reprogramming of iron metabolic pathways, GaSx prompted the initiation of a paraptosis-apoptosis hybrid pathway in cancer cells, leading to marked suppression of tumor proliferation. Importantly, the dysregulation of iron metabolism induced by GaSx notably increased tumor cell susceptibility to both chemotherapy and immune checkpoint blockade (ICB) therapy. This study underscores the therapeutic promise of gas-based interventions and metal ion interference strategies for the tumor metabolism treatment.

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-Nickel Bimetallic Hydroxide Nanosheets Activate the Paraptosis-Pyroptosis Positive Feedback Cycle for Enhanced Tumor Immunotherapy.

Immunotherapy holds significant promise for cancer treatment. However, the highly immunosuppressive nature of solid tumors limits its effectiveness. Herein, we developed bioactive zinc-nickel hydroxide (ZnNi(OH)4) nanosheets (NSs) that can effectively initiate the paraptosis-pyroptosis positive feedback cycle through synergistic ionic effect, thereby mitigating the immunosuppression of solid tumors and enhancing the efficacy of immunotherapy. The acid-sensitive ZnNi(OH)4 NSs releases Ni2+ and Zn2+ in the weakly acidic tumor microenvironment. The released Ni2+ alleviated pyroptosis inhibition by inducing paraptosis and inhibiting autophagic flux. Concurrently, Ni2+ triggered release of endogenous Zn2+ within the cell through a coordination competition mechanism, further amplifying zinc overload-mediated pyroptosis. Interestingly, pyroptosis-associated oxidative stress and endoplasmic reticulum stress further promote Ni2+-mediated paraptosis, forming a positive feedback loop between pyroptosis and paraptosis. This process not only effectively kills tumor cells but also stimulates a strong inflammatory response, enhancing the antitumor immune response and immunotherapy efficacy. Overall, this study proposes an effective paraptosis-pyroptosis induction strategy based on metal ions and demonstrates the effectiveness of the positive feedback loop of paraptosis-pyroptosis in potentiating immunotherapy.

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.

N6-methyladenosine modification-tuned lipid metabolism controls skin immune homeostasis via regulating neutrophil chemotaxis.

Disrupted N6-methyladenosine (m6A) modification modulates various inflammatory disorders. However, the role of m6A in regulating cutaneous inflammation remains elusive. Here, we reveal that the m6A and its methyltransferase METTL3 are down-regulated in keratinocytes in inflammatory skin diseases. Inducible deletion of Mettl3 in murine keratinocytes results in spontaneous skin inflammation and increases susceptibility to cutaneous inflammation with activation of neutrophil recruitment. Therapeutically, restoration of m6A alleviates the disease phenotypes in mice and suppresses inflammation in human biopsy specimens. We support a model in which m6A modification stabilizes the mRNA of the lipid-metabolizing enzyme ELOVL6 via the m6A reader IGF2BP3, leading to a rewiring of fatty acid metabolism with a reduction in palmitic acid accumulation and, consequently, suppressing neutrophil chemotaxis in cutaneous inflammation. Our findings highlight a previously unrecognized epithelial-intrinsic m6A modification-lipid metabolism pathway that is essential for maintaining epidermal and immune homeostasis and lay the basis for potential therapeutic targeting of m6A modulators to attenuate inflammatory skin diseases.

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.

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/ .