Visible light-driven photodynamic therapy for hypertrophic scars with MOF armored microneedles patch.

Photodynamic therapy (PDT) is widely used for the treatment of hypertrophic scars in clinical practice. However, the low transdermal delivery of photosensitizers in scar tissue and protective autophagy induced by Photodynamic therapy greatly reduces the therapeutic efficiency. Therefore, it is necessary to deal with these difficulties for overcoming obstacles in Photodynamic therapy treatment. In this study, a photosensitizer with photocatalytic performance was designed and synthesized using innovative MOFs (metal-organic frameworks). Additionally, the MOFs, together with an autophagy inhibitor chloroquine (CQ), was loaded in a high mechanical strength microneedle patch (MNP) for transdermal delivery. With these functionalized MNP, photosensitizers and chloroquine were delivered deep inside hypertrophic scars. Inhibition of autophagy increases the levels of reactive oxygen species (ROS) under high-intensity visible-light irradiation. Multiprong approaches have been used to remove obstacles in Photodynamic therapy and successfully enhance its anti-scarring effect. In vitro experiments indicated that the combined treatment increased the toxicity of hypertrophic scar fibroblasts (HSFs), downregulated the level of collagen type I expression as well as transforming growth factor-ß1 (TGF-ß1)expression, decreased the autophagy marker protein LC3II/I ratio, increased the expression of P62. In vivo experiments showed that the MNP had good puncture performance, and significant therapeutic effects were observed in the rabbit ear scar model. These results indicate that functionalized MNP has high potential clinical value.

Microglia sustain anterior cingulate cortex neuronal hyperactivity in nicotine-induced pain.

BACKGROUND: Long-term smoking is a risk factor for chronic pain, and chronic nicotine exposure induces pain-like effects in rodents. The anterior cingulate cortex (ACC) has been demonstrated to be associated with pain and substance abuse. This study aims to investigate whether ACC microglia are altered in response to chronic nicotine exposure and their interaction with ACC neurons and subsequent nicotine-induced allodynia in mice. METHODS: We utilized a mouse model that was fed nicotine water for 28 days. Brain slices of the ACC were collected for morphological analysis to evaluate the impacts of chronic nicotine on microglia. In vivo calcium imaging and whole-cell patch clamp were used to record the excitability of ACC glutamatergic neurons. RESULTS: Compared to the vehicle control, the branch endpoints and the length of ACC microglial processes decreased in nicotine-treated mice, coinciding with the hyperactivity of glutamatergic neurons in the ACC. Inhibition of ACC glutamatergic neurons alleviated nicotine-induced allodynia and reduced microglial activation. On the other hand, reactive microglia sustain ACC neuronal excitability in response to chronic nicotine, and pharmacological inhibition of microglia by minocycline or liposome-clodronate reduces nicotine-induced allodynia. The neuron-microglia interaction in chronic nicotine-induced allodynia is mediated by increased expression of neuronal CX3CL1, which activates microglia by acting on CX3CR1 receptors on microglial cells. CONCLUSION: Together, these findings underlie a critical role of ACC microglia in the maintenance of ACC neuronal hyperactivity and resulting nociceptive hypersensitivity in chronic nicotine-treated mice.

Inhibition of H3N2 Influenza Virus Induced Apoptosis by Selenium Nanoparticles with Chitosan through ROS-Mediated Signaling Pathways.

In recent years, nanotechnology has received more and more attention in the antiviral field. Among them, selenium nanoparticles (SeNPs) have received a lot of attention. Chitosan, as a substance with antiviral effect, is limited by water solubility, low bioavailability, and poor stability. In this study, the combination of SeNPs with chitosan (Se@CS) showed less toxic and good anti-H3N2 infection effect. CCK-8 and RT-PCR showed that Se@CS effectively prevented H3N2 infection of MDCK cells by inhibiting viral replication and preventing cell fragmentation and cell aggregation. In addition, Se@CS can inhibit the excessive production of ROS and the change of mitochondrial membrane potential. More importantly, Se@CS can inhibit the late apoptosis of cells caused by virus, which may be related to the inhibition of apoptotic proteins in the ROS/JNK apoptotic signaling pathway. Finally, Se@CS was also found to inhibit H3N2-induced inflammation and alleviate infection. These results prove that Se@CS is a promising inhibitor for controlling influenza H3N2 virus infection.

Up-regulation of HCN2 channels in a thalamocortical circuit mediates allodynia in mice.

Chronic pain is a significant problem that afflicts individuals and society, and for which the current clinical treatment is inadequate. In addition, the neural circuit and molecular mechanisms subserving chronic pain remain largely uncharacterized. Herein we identified enhanced activity of a glutamatergic neuronal circuit that encompasses projections from the ventral posterolateral nucleus (VPLGlu) to the glutamatergic neurons of the hindlimb primary somatosensory cortex (S1HLGlu), driving allodynia in mouse models of chronic pain. Optogenetic inhibition of this VPLGlu→S1HLGlu circuit reversed allodynia, whereas the enhancement of its activity provoked hyperalgesia in control mice. In addition, we found that the expression and function of the HCN2 (hyperpolarization-activated cyclic nucleotide-gated channel 2) were increased in VPLGlu neurons under conditions of chronic pain. Using in vivo calcium imaging, we demonstrated that downregulation of HCN2 channels in the VPLGlu neurons abrogated the rise in S1HLGlu neuronal activity while alleviating allodynia in mice with chronic pain. With these data, we propose that dysfunction in HCN2 channels in the VPLGlu→S1HLGlu thalamocortical circuit and their upregulation occupy essential roles in the development of chronic pain.

Elasticity of Slide-Ring Gels.

Slide-ring gels are polymer networks with cross-links that can slide along the chains. In contrast to conventional unentangled networks with cross-links fixed along the chains, the slide-ring networks are strain-softening and distribute tension much more uniformly between their strands due to the so-called "pulley effect". The sliding of cross-links also reduces the elastic modulus in comparison with the modulus of conventional networks with the same number density of cross-links and elastic strands. We develop a single-chain model to account for the redistribution of monomers between network strands of a primary chain. This model takes into account both the pulley effect and fluctuations in the number of monomers per network strand. The pulley effect leads to modulus reduction and uniform tension redistribution between network strands, while fluctuations in the number of strand monomers dominate the strain-softening, the magnitude of which decreases upon network swelling and increases upon deswelling.

Inhibition of H1N1 by Picochlorum sp. 122 via AKT and p53 signaling pathways.

Influenza viruses cause a severe threat to global health, which can lead to annual epidemics and cause pandemics occasionally. However, the number of anti-influenza therapeutic agents is very limited. Polysaccharides, extracted from Picochlorum sp. (PPE), seaweed Polysaccharides, have exhibited antiviral activity and were expected to be used for influenza treatment. In our research, the capability of PPE to inhibit H1N1 infection was proved in MDCK cells. PPE could make MDCK cells avoid being infected with H1N1 and inhibited nuclear fragmentation and condensation of chromatin. PPE evidently inhibited the generation of reactive oxygen species in MDCK cells. Mechanism study revealed that PPE prevented MDCK cells from H1N1 infection through induction of apoptosis by stimulating AKT signaling pathway and suppressing p-p53 signaling pathway. In conclusion, PPE turns out to act as a prospective antiviral drug for H1N1 influenza.

An enriched environment improves long-term functional outcomes in mice after intracerebral hemorrhage by mechanisms that involve the Nrf2/BDNF/glutaminase pathway.

Post-stroke depression exacerbates neurologic deficits and quality of life. Depression after ischemic stroke is known to some extent. However, depression after intracerebral hemorrhage (ICH) is relatively unknown. Increasing evidence shows that exposure to an enriched environment (EE) after cerebral ischemia/reperfusion injury has neuroprotective effects in animal models, but its impact after ICH is unknown. In this study, we investigated the effect of EE on long-term functional outcomes in mice subjected to collagenase-induced striatal ICH. Mice were subjected to ICH with the standard environment (SE) or ICH with EE for 6 h/day (8:00 am-2:00 pm). Depressive, anxiety-like behaviors and cognitive tests were evaluated on day 28 with the sucrose preference test, tail suspension test, forced swim test, light-dark transition experiment, morris water maze, and novel object recognition test. Exposure to EE improved neurologic function, attenuated depressive and anxiety-like behaviors, and promoted spatial learning and memory. These changes were associated with increased expression of transcription factor Nrf2 and brain-derived neurotrophic factor (BDNF) and inhibited glutaminase activity in the perihematomal tissue. However, EE did not change the above behavioral outcomes in Nrf2-/- mice on day 28. Furthermore, exposure to EE did not increase BDNF expression compared to exposure to SE in Nrf2-/- mice on day 28 after ICH. These findings indicate that EE improves long-term outcomes in sensorimotor, emotional, and cognitive behavior after ICH and that the underlying mechanism involves the Nrf2/BDNF/glutaminase pathway.

Two-dimensional power allocation scheme for NOMA-based underwater visible light communication systems.

In this work, a two-dimensional power allocation scheme combining fractional transmit power allocation (FTPA) and the sine cosine algorithm (SCA) is proposed for non-orthogonal multiple access (NOMA)-based underwater visible light communication (UVLC) systems. Considering the proposed power allocation scheme, a downlink NOMA-based UVLC system using blue-light-emitting diodes in the deep-sea environment is set up to evaluate the influence of the FTPA coefficient and SCA on system communication performance. The simulation results demonstrate that the two-dimensional power allocation scheme can effectively reduce the impact of user pairing on system performance and improve the system transmission rate compared with the conventional power allocation scheme.

Ebselen inhibits enterovirus A71-induced apoptosis through reactive oxygen species-mediated signaling pathway.

BACKGROUND: Enterovirus A71 (EV-A71)is a prevalent infection in severe hand, foot and mouth disease HFMD and can induce acute central nervous system seizures. The three EV-A71 vaccines now circulating in the market are produced for a single subtype. While EV-A71 is constantly evolving and the vaccine's efficacy is gradually reducing, no specialized anti-EV-A71 medication has yet been developed. Therefore, it is crucial to consistently develop new anti-EV-A71 medications. METHOD: Ebselen, an organoselenium molecule with glutathione oxidase-like activity, is resistant to a range of viruses. In this investigation, we used the Cell counting kit-8 (CCK-8 kit) assay in a Vero cell model to confirm the effectiveness of ebselen against EV-A71 infection. Later, to examine ebselen's anti-EV-A71 mechanism, we measured the apoptosis level of cells in different treatment groups through Annexin V, JC-1, and cell cycle assays, as well as the intracellular reactive oxygen species (ROS) concentration. Ebselen may have an impact on the apoptotic signaling pathway caused by EV-A71 infection, according to the results of a caspase-3 activity experiment. RESULT: The results showed that Ebselen protected cell damage from ROS generation, decreased the frequency of EV-A71-induced apoptosis, and inhibited caspase-3-mediated apoptosis by lowering caspase-3 activity. CONCLUSION: To summarize, ebselen is a promising anti-EV-A71 medication.

Effect and mechanism of apelin on lipopolysaccharide induced acute pulmonary vascular endothelial barrier dysfunction.

Vascular endothelial barrier dysfunction is the most prominent manifestation and important cause of mortality in infectious acute lung injury (ALI). Exogenous apelin is effective in ameliorating lipopolysaccharide (LPS)-induced inflammatory response in ALI lungs, reducing exudation of lung tissue and decreasing mortality. This study set out to investigate the association between apelin and Friend leukemia integration-1 (Fli-1) in the prevention and treatment of ALI, and to elucidate the molecular mechanism by which apelin protects the permeability of the vascular endothelial barrier. At the vivo functional level, lung wet/dry weight ratio was used to detect whole lung permeability, evans blue assay and dual fluorescent protein tracking assay were used to detect lung vascular endothelial permeability, HE staining to observe the inflammatory status of lung tissue, and immunofluorescence staining for VE-cadherin expression levels in blood vessels. The changes in inflammatory factors in bronchoalveolar lavage fluid (BALF) were detected by ELASA. Western blot was used to detect the expression level of proteins. qRT-PCR was performed to detect changes in mRNA expression of Fli-1 and adherent junction-related proteins. The correlation analysis of Fli-1 with vascular endothelial permeability and SRC showed that Fli-1 participated in the process of ALI. After preventive and therapeutic treatment of ALI mice with exogenous apelin, Fli-1, APJ, VE-cadherin, phosphorylated-VE-cadherin (p-VE-cadherin) and ß-catenin were up-regulated, while SRC, phosphorylated-SRC (p-SRC), VEGF and VEGF-R were down-regulated, which indicated that the stability of vascular endothelial barrier was enhanced. With the use of Fli-1 inhibitor irinotecan, the protective effect of apelin was weakened in various functional indexes, genes and proteins. The lung was maintained at the level of the injury. Our research shows that Fli-1 is involved in the LPS-induced ALI process. The molecular mechanism for apelin in preventing endothelial barrier dysfunction in ALI is through up-regulating Fli-1, thus regulating adherens junction-related proteins, and finally recovering the endothelial barrier function.

Cip2a induces arginine biosynthesis and promotes tumor progression in non-small cell lung cancer.

Cancerous inhibitor of protein phosphatase 2A (Cip2a) is an oncoprotein, playing important roles in tumor progression. However, the underlying mechanisms by which Cip2a promotes tumor aggressiveness in NSCLC remain to be further investigated. In this study, we found that Cip2a expression is elevated in NSCLC and correlates with poor prognosis. Knockdown of Cip2a significantly reduced the ability of cell proliferation, invasion, and metastasis of NSCLC both in vitro and in vivo. Furthermore, we found that Cip2a promotes tumor progression partly by inducing arginine biosynthesis, and knockdown of Cip2a exhibited a significantly increased sensitivity to arginine deprivation and mTOR inhibition. In addition, we found that p53 mutants in NSCLC cells increased Cip2a expression by inhibiting the activity of wild-type p53. Our findings provide new insights into the mechanisms of Cip2a in promoting tumor progression and suggest that Cip2a represents a potential therapeutic target for treating NSCLC.

Angiotensin Type 2 Receptor Pharmacological Agonist Relieves Neurocognitive Deficits via Reducing Neuroinflammation and Microglial Engulfment of Dendritic Spines.

Mechanically ventilated patients suffering critical illness are at high risk of developing neurocognitive impairments. Angiotensin type 2 receptor (AGTR2) has been demonstrated to be anti-inflammatory and neuroprotective. The present study thus aimed to investigate whether AGTR2 can alleviate cerebral dysfunction in mice subjected to cochallenge with lipopolysaccharide (LPS) and mechanical ventilation (MV), and to reveal the underlying mechanism. We utilized a mice model that received a single injection of LPS (1 mg/kg, intraperitoneally) followed 2 h later by MV (10 ml/kg, lasting for 2 h). Pretreatment with the AGTR2 pharmacological agonist C21 (0.03, 0.3, and 3 mg/kg, intraperitoneally, once daily, lasting for 10 days). Locomotor activity and behavioral deficits were evaluated 24 h post-MV by open-field and fear-condition tests. Brain hippocampus and prefrontal cortex tissues were collected for immunofluorescence staining and western blotting to evaluate the resulting impacts on microglia, including morphological traits, functional markers, synaptic engulfment, superoxide production, and signaling molecules. Compared with vehicle-control, pre-administrated C21 reduced the branch endpoints and length of microglia processes in a dose-dependent manner in mice subjected to LPS/MV. The neuroprotective effect of AGTR2 was behaviorally confirmed by the improvement of memory decline in LPS/MV-treated mice following C21 pretreatment. In addition to morphological alterations, C21 reduced microglial functional markers and reduced microglial-dendrite contact and microglial engulfment of synaptic protein markers. In terms of the underlying molecular mechanism, AGTR2 stimulation by C21 leads to activation of protein phosphatase 2A, which subsequently mitigates microglial PKCδ and NF-κB activation, and inhibites NOX2-derived ROS production. The AGTR2 agonist C21 alleviates behavioral deficits in those mice subjected to LPS/MV, via mechanisms that involve reactive microglia and abnormal synaptic plasticity in NOX2-derived ROS and the PKCδ-NFκB pathway.

Intradermal delivery of an angiotensin II receptor blocker using a personalized microneedle patch for treatment of hypertrophic scars.

High-quality postoperative rehabilitation is the focus of most patients currently, and hypertrophic scar (HS) greatly reduces the patient's quality of life due to the symptom of severe itching. Traditional HS therapies are associated with limitations, such as poor drug delivery efficiency for topical administration and severe pain for intralesional injection. In this study, we developed a personalized microneedle patch system for minimally invasive and effective treatment of HSs. The microneedle patches were personalized designed and fabricated with 3D printing in order to adapt to individual HS. The optimized microneedle patches were composed of dissolving gelatin and starch and loaded with losartan. Losartan, as a drug class of angiotensin II receptor blockers (ARBs), can effectively inhibit the proliferation and migration of hypertrophic scar fibroblasts (HSFs) and downregulate the gene expression related to scar formation in HSFs. The dissolving microneedle patches exhibited strong mechanical strength, effectively penetrated the stratum corneum of HSs and increased the losartan delivery into HSs upon dissolution of gelatin and starch. Together, the losartan-loaded microneedle patches effectively inhibited the formation of HSs in rabbit ears with reduced scar elevation index (SEI), and decreased fibrosis and collagen deposition in HSs. This personalized microneedle patch system increases the drug delivery efficiency into HSs with minimal invasion, and opens a new window for personalized management and treatment of skin diseases.

Thalamocortical circuits drive remifentanil-induced postoperative hyperalgesia.

Remifentanil-induced hyperalgesia (RIH) is a severe but common postoperative clinical problem with elusive underlying neural mechanisms. Here, we discovered that glutamatergic neurons in the thalamic ventral posterolateral nucleus (VPLGlu) exhibited significantly elevated burst firing accompanied by upregulation of Cav3.1 T-type calcium channel expression and function in RIH model mice. In addition, we identified a glutamatergic neuronal thalamocortical circuit in the VPL projecting to hindlimb primary somatosensory cortex glutamatergic neurons (S1HLGlu) that mediated RIH. In vivo calcium imaging and multi-tetrode recordings revealed heightened S1HLGlu neuronal activity during RIH. Moreover, preoperative suppression of Cav3.1-dependent burst firing in VPLGlu neurons or chemogenetic inhibition of VPLGlu neuronal terminals in the S1HL abolished the increased S1HLGlu neuronal excitability while alleviating RIH. Our findings suggest that remifentanil induces postoperative hyperalgesia by upregulating T-type calcium channel-dependent burst firing in VPLGlu neurons to activate S1HLGlu neurons, thus revealing an ion channel-mediated neural circuit basis for RIH that can guide analgesic development.

Two-Dimensional Mg2 Si Nanosheet-Enabled Sustained Hydrogen Generation for Improved Repair and Regeneration of Deeply Burned Skin.

Molecular hydrogen holds a high potential for wound healing owing to its anti-inflammatory effect and high biosafety, but commonly used hydrogen administration routes hardly achieve the sustained supply of high-dosage hydrogen, limiting hydrogen therapy efficacy. Here, two-dimensional Mg2 Si nanosheet (MSN) is exploited as a super-persistent hydrogen-releasing nanomaterial with high biocompatibility, and the incorporation of MSN into the chitosan/hyaluronic acid hydrogel (MSN@CS/HA) is developed as a dressing to repair deeply burned skin. The MSN@CS/HA hydrogel dressing can continuously generate hydrogen molecules for about 1 week in the physiological conditions in support of local, long-term, and plentiful hydrogen supply and remarkably promotes the healing and regeneration of deep second-degree and third-degree burn wounds without visible scar and toxic side effect. Mechanistically, a sustained supply of hydrogen molecules induces anti-inflammatory M2 macrophage polarization in time by enhancing CCL2 (chemokine C-C motif ligand 2) expression to promote angiogenesis and reduce fibrosis and also enhances the proliferation and migration capability of skin cells directly and indirectly by locally scavenging overexpressed reactive oxygen species, synergistically favoring wound repair. The proposed synthesis method, therapeutic strategy, and mechanisms will open a window for synthesizing a variety of MSene nanomaterials and developing their various proangiogenesis applications besides wound healing.

Paeoniflorin drives the immunomodulatory effects of mesenchymal stem cells by regulating Th1/Th2 cytokines in oral lichen planus.

Lichen planus (LP) is a chronic inflammatory disease. Oral lichen planus (OLP) mainly appears as oral mucosal reticular or ulcerative lesions with an unknown etiology. We aimed to explore the immunomodulatory effect of paeoniflorin (PF) in mesenchymal stem cells (MSCs) and the potential involvement of Th1/Th2 cytokines in OLP. The effects of paeoniflorin on the proliferation and migration of MSCs were detected by Cell Counting Kit-8 (CCK8) and Transwell assays. MSCs were subjected to osteogenic, adipogenic and neurogenic induction followed by Alizarin red, oil red O, real-time PCR and immunofluorescence assays. We found that paeoniflorin promoted the proliferation, migration and multilineage differentiation of MSCs from OLP lesions (OLP-MSCs) in vitro. Paeoniflorin pretreatment increased the inhibitory effect of OLP-MSCs on peripheral blood mononuclear cells. Furthermore, paeoniflorin-pretreated OLP-MSCs simultaneously decreased Th1 cytokine levels and increased Th2 cytokine levels in T lymphocyte cocultures. Finally, paeoniflorin-pretreated OLP-MSCs also promoted the Th1/Th2 balance both in vitro and in the serum of mice that received skin allografts. In conclusion, paeoniflorin enhanced MSC immunomodulation and changed the inflammatory microenvironment via T lymphocytes, suggesting that the improvement of OLP-MSCs is a promising therapeutic approach for OLP.

Integrated visible light communication and positioning CDMA system employing modified ZCZ and Walsh code.

In this paper, an integrated visible light communication and positioning (VLCP) code division multiple access (CDMA) system is proposed for recovering original user data and obtaining positioning information simultaneously. A generalized modification method for balanced bipolar code set is presented, which can be applied to VLCP-CDMA system with intensity modulation. Both modified bipolar code sets, zero correlation zone (ZCZ) code set and Walsh code set, are employed and evaluated in VLCP-CDMA systems. When considering synchronous and quasi-synchronous (QS) systems, it is demonstrated that the modified ZCZ code set with ideal zero correlation zone properties performs better communication and positioning performance than the modified Walsh code set by system simulations and experiments. As a result, a bit error rate (BER) of 1.8×10-3 and an average positioning error of 1.50 cm are successfully obtained by adopting modified ZCZ code set in a 4-user real-time VLCP-CDMA system. It will offer a promising solution to meet both communication and positioning requirements of future intelligent systems.

Integrative genomic analysis facilitates precision strategies for glioblastoma treatment.

Glioblastoma (GBM) is the most common form of malignant primary brain tumor with a dismal prognosis. Currently, the standard treatments for GBM rarely achieve satisfactory results, which means that current treatments are not individualized and precise enough. In this study, a multiomics-based GBM classification was established and three subclasses (GPA, GPB, and GPC) were identified, which have different molecular features both in bulk samples and at single-cell resolution. A robust GBM poor prognostic signature (GPS) score model was then developed using machine learning method, manifesting an excellent ability to predict the survival of GBM. NVP-BEZ235, GDC-0980, dasatinib and XL765 were ultimately identified to have subclass-specific efficacy targeting patients with a high risk of poor prognosis. Furthermore, the GBM classification and GPS score model could be considered as potential biomarkers for immunotherapy response. In summary, an integrative genomic analysis was conducted to advance individual-based therapies in GBM.

Hybrid multi-user access scheme for a visible light communication system.

A hybrid multi-user access scheme based on orthogonal frequency-division multiple access and non-orthogonal multiple access (OFDMA-NOMA) is proposed for visible light communication (VLC) systems with a bandwidth-constrained channel. In the scheme, a novel user resource allocation method is used, to the best of our knowledge, to reduce the unfairness among different users caused by the high-frequency fading characteristic of VLC systems. Furthermore, the particle swarm optimization (PSO) is introduced to satisfy the transmitting power requirements of each user and to improve system performance. Simulation results show that, under the same VLC system conditions, the OFDMA-NOMA scheme with PSO has significant improvements in terms of user capacity and transmission rates compared to the purely NOMA scheme and the OFDMA scheme.

NIR-photocatalytic regulation of arthritic synovial microenvironment.

Synovial microenvironment (SME) plays a vital role in the formation of synovial pannus and the induction of cartilage destruction in arthritis. In this work, a concept of the photocatalytic regulation of SME is proposed for arthritis treatment, and monodispersive hydrogen-doped titanium dioxide nanorods with a rutile single-crystal structure are developed by a full-solution method to achieve near infrared-photocatalytic generation of hydrogen molecules and simultaneous depletion of overexpressed lactic acid (LA) for realizing SME regulation in a collagen-induced mouse model of rheumatoid arthritis. Mechanistically, locally generated hydrogen molecules scavenge overexpressed reactive oxygen species to mediate the anti-inflammatory polarization of macrophages, while the simultaneous photocatalytic depletion of overexpressed LA inhibits the inflammatory/invasive phenotypes of synoviocytes and macrophages and ameliorates the abnormal proliferation of synoviocytes, thereby remarkably preventing the synovial pannus formation and cartilage destruction. The proposed catalysis-mediated SME regulation strategy will open a window to realize facile and efficient arthritis treatment.