Correlated Neural Activity and Encoding of Behavior across Brains of Socially Interacting Animals.

Social interactions involve complex decision-making tasks that are shaped by dynamic, mutual feedback between participants. An open question is whether and how emergent properties may arise across brains of socially interacting individuals to influence social decisions. By simultaneously performing microendoscopic calcium imaging in pairs of socially interacting mice, we find that animals exhibit interbrain correlations of neural activity in the prefrontal cortex that are dependent on ongoing social interaction. Activity synchrony arises from two neuronal populations that separately encode one's own behaviors and those of the social partner. Strikingly, interbrain correlations predict future social interactions as well as dominance relationships in a competitive context. Together, our study provides conclusive evidence for interbrain synchrony in rodents, uncovers how synchronization arises from activity at the single-cell level, and presents a role for interbrain neural activity coupling as a property of multi-animal systems in coordinating and sustaining social interactions between individuals.

Sexually Dimorphic Control of Parenting Behavior by the Medial Amygdala.

Social behaviors, including behaviors directed toward young offspring, exhibit striking sex differences. Understanding how these sexually dimorphic behaviors are regulated at the level of circuits and transcriptomes will provide insights into neural mechanisms of sex-specific behaviors. Here, we uncover a sexually dimorphic role of the medial amygdala (MeA) in governing parental and infanticidal behaviors. Contrary to traditional views, activation of GABAergic neurons in the MeA promotes parental behavior in females, while activation of this population in males differentially promotes parental versus infanticidal behavior in an activity-level-dependent manner. Through single-cell transcriptomic analysis, we found that molecular sex differences in the MeA are specifically represented in GABAergic neurons. Collectively, these results establish crucial roles for the MeA as a key node in the neural circuitry underlying pup-directed behaviors and provide important insight into the connection between sex differences across transcriptomes, cells, and circuits in regulating sexually dimorphic behavior.

Cortical regulation of helping behaviour towards others in pain.

Humans and animals exhibit various forms of prosocial helping behaviour towards others in need1-3. Although previous research has investigated how individuals may perceive others' states4,5, the neural mechanisms of how they respond to others' needs and goals with helping behaviour remain largely unknown. Here we show that mice engage in a form of helping behaviour towards other individuals experiencing physical pain and injury-they exhibit allolicking (social licking) behaviour specifically towards the injury site, which aids the recipients in coping with pain. Using microendoscopic imaging, we found that single-neuron and ensemble activity in the anterior cingulate cortex (ACC) encodes others' state of pain and that this representation is different from that of general stress in others. Furthermore, functional manipulations demonstrate a causal role of the ACC in bidirectionally controlling targeted allolicking. Notably, this behaviour is represented in a population code in the ACC that differs from that of general allogrooming, a distinct type of prosocial behaviour elicited by others' emotional stress. These findings advance our understanding of the neural coding and regulation of helping behaviour.

A LaCl3-based lithium superionic conductor compatible with lithium metal.

Inorganic superionic conductors possess high ionic conductivity and excellent thermal stability but their poor interfacial compatibility with lithium metal electrodes precludes application in all-solid-state lithium metal batteries1,2. Here we report a LaCl3-based lithium superionic conductor possessing excellent interfacial compatibility with lithium metal electrodes. In contrast to a Li3MCl6 (M = Y, In, Sc and Ho) electrolyte lattice3-6, the UCl3-type LaCl3 lattice has large, one-dimensional channels for rapid Li+ conduction, interconnected by La vacancies via Ta doping and resulting in a three-dimensional Li+ migration network. The optimized Li0.388Ta0.238La0.475Cl3 electrolyte exhibits Li+ conductivity of 3.02 mS cm-1 at 30 °C and a low activation energy of 0.197 eV. It also generates a gradient interfacial passivation layer to stabilize the Li metal electrode for long-term cycling of a Li-Li symmetric cell (1 mAh cm-2) for more than 5,000 h. When directly coupled with an uncoated LiNi0.5Co0.2Mn0.3O2 cathode and bare Li metal anode, the Li0.388Ta0.238La0.475Cl3 electrolyte enables a solid battery to run for more than 100 cycles with a cutoff voltage of 4.35 V and areal capacity of more than 1 mAh cm-2. We also demonstrate rapid Li+ conduction in lanthanide metal chlorides (LnCl3; Ln = La, Ce, Nd, Sm and Gd), suggesting that the LnCl3 solid electrolyte system could provide further developments in conductivity and utility.

Broad transcriptomic dysregulation occurs across the cerebral cortex in ASD.

Neuropsychiatric disorders classically lack defining brain pathologies, but recent work has demonstrated dysregulation at the molecular level, characterized by transcriptomic and epigenetic alterations1-3. In autism spectrum disorder (ASD), this molecular pathology involves the upregulation of microglial, astrocyte and neural-immune genes, the downregulation of synaptic genes, and attenuation of gene-expression gradients in cortex1,2,4-6. However, whether these changes are limited to cortical association regions or are more widespread remains unknown. To address this issue, we performed RNA-sequencing analysis of 725 brain samples spanning 11 cortical areas from 112 post-mortem samples from individuals with ASD and neurotypical controls. We find widespread transcriptomic changes across the cortex in ASD, exhibiting an anterior-to-posterior gradient, with the greatest differences in primary visual cortex, coincident with an attenuation of the typical transcriptomic differences between cortical regions. Single-nucleus RNA-sequencing and methylation profiling demonstrate that this robust molecular signature reflects changes in cell-type-specific gene expression, particularly affecting excitatory neurons and glia. Both rare and common ASD-associated genetic variation converge within a downregulated co-expression module involving synaptic signalling, and common variation alone is enriched within a module of upregulated protein chaperone genes. These results highlight widespread molecular changes across the cerebral cortex in ASD, extending beyond association cortex to broadly involve primary sensory regions.

Neural control of affiliative touch in prosocial interaction.

The ability to help and care for others fosters social cohesiveness and is vital to the physical and emotional well-being of social species, including humans1-3. Affiliative social touch, such as allogrooming (grooming behaviour directed towards another individual), is a major type of prosocial behaviour that provides comfort to others1-6. Affiliative touch serves to establish and strengthen social bonds between animals and can help to console distressed conspecifics. However, the neural circuits that promote prosocial affiliative touch have remained unclear. Here we show that mice exhibit affiliative allogrooming behaviour towards distressed partners, providing a consoling effect. The increase in allogrooming occurs in response to different types of stressors and can be elicited by olfactory cues from distressed individuals. Using microendoscopic calcium imaging, we find that neural activity in the medial amygdala (MeA) responds differentially to naive and distressed conspecifics and encodes allogrooming behaviour. Through intersectional functional manipulations, we establish a direct causal role of the MeA in controlling affiliative allogrooming and identify a select, tachykinin-expressing subpopulation of MeA GABAergic (γ-aminobutyric-acid-expressing) neurons that promote this behaviour through their projections to the medial preoptic area. Together, our study demonstrates that mice display prosocial comforting behaviour and reveals a neural circuit mechanism that underlies the encoding and control of affiliative touch during prosocial interactions.

Multifaceted atlases of the human brain in its infancy.

Brain atlases are spatial references for integrating, processing, and analyzing brain features gathered from different individuals, sources, and scales. Here we introduce a collection of joint surface-volume atlases that chart postnatal development of the human brain in a spatiotemporally dense manner from two weeks to two years of age. Our month-specific atlases chart normative patterns and capture key traits of early brain development and are therefore conducive to identifying aberrations from normal developmental trajectories. These atlases will enhance our understanding of early structural and functional development by facilitating the mapping of diverse features of the infant brain to a common reference frame for precise multifaceted quantification of cortical and subcortical changes.

Focal cortical dysplasia II caused by brain somatic mutation of IRS-1 is associated with ERK signaling pathway activation.

Somatic mutations have been identified in 10% to 63% of focal cortical dysplasia type II samples, primarily linked to the mTOR pathway. When the causative genetic mutations are not identified, this opens the possibility of discovering new pathogenic genes or pathways that could be contributing to the condition. In our previous study, we identified a novel candidate pathogenic somatic variant of IRS-1 c.1791dupG in the brain tissue of a child with focal cortical dysplasia type II. This study further explored the variant's role in causing type II focal cortical dysplasia through in vitro overexpression in 293T and SH-SY5Y cells and in vivo evaluation via in utero electroporation in fetal brains, assessing effects on neuronal migration, morphology, and network integrity. It was found that the mutant IRS-1 variant led to hyperactivity of p-ERK, increased cell volume, and was predominantly associated with the MAPK signaling pathway. In vivo, the IRS-1 c.1791dupG variant induced abnormal neuron migration, cytomegaly, and network hyperexcitability. Notably, the ERK inhibitor GDC-0994, rather than the mTOR inhibitor rapamycin, effectively rescued the neuronal defects. This study directly highlighted the ERK signaling pathway's role in the pathogenesis of focal cortical dysplasia II and provided a new therapeutic target for cases of focal cortical dysplasia II that are not treatable by rapamycin analogs.

Progress in RAS-targeted therapeutic strategies: From small molecule inhibitors to proteolysis targeting chimeras.

As a widely considerable target in chemical biology and pharmacological research, rat sarcoma (RAS) gene mutations play a critical driving factor in several fatal cancers. Despite the great progress of RAS subtype-specific inhibitors, rapid acquired drug resistance could limit their further clinical applications. Proteolysis targeting chimera (PROTAC) has emerged as a powerful tool to handle "undruggable" targets and exhibited significant therapeutic benefit for the combat of drug resistance. Owing to unique molecular mechanism and binding kinetics, PROTAC is expected to become a feasible strategy to break the bottleneck of classical RAS inhibitors. This review aims to discuss the current advances of RAS inhibitors and especially focus on PROTAC strategy targeting RAS mutations and their downstream effectors for relevant cancer treatment.

Exogenous Metal Cations in the Synthesis of CsPbBr3 Nanocrystals and Their Interplay with Tertiary Amines.

Current syntheses of CsPbBr3 halide perovskite nanocrystals (NCs) rely on overstoichiometric amounts of Pb2+ precursors, resulting in unreacted lead ions at the end of the process. In our synthesis scheme of CsPbBr3 NCs, we replaced excess Pb2+ with different exogenous metal cations (M) and investigated their effect on the synthesis products. These cations can be divided into two groups: group 1 delivers monodisperse CsPbBr3 cubes capped with oleate species (as for the case when Pb2+ is used in excess) and with a photoluminescence quantum yield (PLQY) as high as 90% with some cations (for example with M = In3+); group 2 yields irregularly shaped CsPbBr3 NCs with broad size distributions. In both cases, the addition of a tertiary ammonium cation (didodecylmethylammonium, DDMA+) during the synthesis, after the nucleation of the NCs, reshapes the NCs to monodisperse truncated cubes. Such NCs feature a mixed oleate/DDMA+ surface termination with PLQY values of up to 97%. For group 1 cations this happens only if the ammonium cation is directly added as a salt (DDMA-Br), while for group 2 cations this happens even if the corresponding tertiary amine (DDMA) is added, instead of DDMA-Br. This is attributed to the fact that only group 2 cations can facilitate the protonation of DDMA by the excess oleic acid present in the reaction environment. In all cases studied, the incorporation of M cations is marginal, and the reshaping of the NCs is only transient: if the reactions are run for a long time, the truncated cubes evolve to cubes.

Fast Metabolic Glycan Labeling for Click-Labeling and Imaging of Sialoglycans in Living Acute Brain Slices from Mice and Human Patients.

Living acute brain slices provide a practical platform for imaging sialylation in human brain pathology. However, the limited lifespan of acute brain slices has impeded the use of metabolic glycan labeling (MGL), which requires long-term incubation of clickable unnatural sugars such as N-azidoacetylmannosamine (ManNAz) to metabolically incorporate azides into sialoglycans. Here, we report a fast variant of MGL (fMGL), in which ManNAz-6-phosphate enables efficient azidosugar incorporation within 12 h by bypassing the bottleneck step in the sialic acid biosynthesis pathway, followed by click-labeling with fluorophores and imaging of sialoglycans in acute brain slices from mice and human patients. In the clinical samples of ganglioglioma, fMGL-based imaging reveals specific upregulation of sialylation in astrocyte-like but not neuron-like tumor cells. In addition, fMGL is integrated with click-expansion microscopy for high-resolution imaging of sialoglycans in brain slices. The fMGL strategy should find broad applications in the tissue imaging of glycans and surgical pathology.

A Multifunctional Herb-Derived Glycopeptide Hydrogel for Chronic Wound Healing.

Chronic wounds constitute an increasingly prevalent global healthcare issue, characterized by recurring bacterial infections, pronounced oxidative stress, compromised functionality of immune cells, unrelenting inflammatory reactions, and deficits in angiogenesis. In response to these multifaceted challenges, the study introduced a stimulus-responsive glycopeptide hydrogel constructed by oxidized Bletilla striata polysaccharide (OBSP), gallic acid-grafted ε-Polylysine (PLY-GA), and paeoniflorin-loaded micelles (MIC@Pae), called OBPG&MP. The hydrogel emulates the structure of glycoprotein fibers of the extracellular matrix (ECM), exhibiting exceptional injectability, self-healing, and biocompatibility. It adapts responsively to the inflammatory microenvironment of chronic wounds, sequentially releasing therapeutic agents to eradicate bacterial infection, neutralize reactive oxygen species (ROS), modulate macrophage polarization, suppress inflammation, and encourage vascular regeneration and ECM remodeling, playing a critical role across the inflammatory, proliferative, and remodeling phases of wound healing. Both in vitro and in vivo studies confirmed the efficacy of OBPG&MP hydrogel in regulating the wound microenvironment and enhancing the regeneration and remodeling of chronic wound skin tissue. This research supports the vast potential for herb-derived multifunctional hydrogels in tissue engineering and regenerative medicine.

Ultraviolet Circularly Polarized Luminescence in Chiral Perovskite Nanoplatelet-Molecular Hybrids: Direct Binding Versus Efficient Triplet Energy Transfer.

The development of ultraviolet circularly polarized light (UVCPL) sources has the potential to benefit plenty of practical applications but remains a challenge due to limitations in available material systems and a limited understanding of the excited state chirality transfer. Herein, by constructing hybrid structures of the chiral perovskite CsPbBr3 nanoplatelets and organic molecules, excited state chirality transfer is achieved, either via direct binding or triplet energy transfer, leading to efficient UVCPL emission. The underlying photophysical mechanisms of these two scenarios are clarified by comprehensive optical studies. Intriguingly, UVCPL realized via the triple energy transfer, followed by the triplet-triplet annihilation upconversion processes, demonstrates a 50-fold enhanced dissymmetry factor glum. Furthermore, stereoselective photopolymerization of diacetylene monomer is demonstrated by using such efficient UVCPL. This study provides both novel insights and a practical approach for realizing UVCPL, which can also be extended to other material systems and spectral regions, such as visible and near-infrared.

A de novo novel variant in the MT-TD gene is associated with prominent extra-neurologic manifestations.

Defects in the mitochondrial tRNA genes cause a group of highly clinically and genetically heterogeneous disorders, which poses a challenge for clinical identification and genetic diagnosis. Here, we present a pre-school boy with a novel MT-TD variant m.7560T>C at the heteroplasmy level of 76.53% in blood, 93.34% in urine sediments, and absent in the healthy mother's blood and urine. Besides convulsions, brain magnetic resonance imaging abnormalities and high plasma lactate, the boy presented with the prominent extra-neurologic phenotype including steroid-resistant nephrotic syndrome associated with focal segmental glomerulosclerosis characterized by abnormal mitochondria in podocytes, cortical blindness, and pancreatitis. To our knowledge, this is the unique case with MT-TD m.7560T>C-related multi-organ impairments, which expands the phenotypic and mutational spectrum of primary mitochondrial diseases.

All-trans retinoic acid plus low-dose rituximab vs low-dose rituximab in corticosteroid-resistant or relapsed ITP.

The study aimed to compare the efficacy and safety of all-trans retinoic acid (ATRA) plus low-dose rituximab (LD-RTX) with LD-RTX monotherapy in corticosteroid-resistant or relapsed immune thrombocytopenia (ITP) patients. Recruited patients were randomized at a ratio of 2:1 into 2 groups: 112 patients received LD-RTX plus ATRA, and 56 patients received LD-RTX monotherapy. Overall response (OR), defined as achieving a platelet count of ≥30 × 109/L confirmed on ≥2 separate occasions (≥7 days apart), at least a doubling of the baseline platelet count without any other ITP-specific treatment, and the absence of bleeding within 1 year after enrollment, was observed in more patients in the LD-RTX plus ATRA group (80%) than in the LD-RTX monotherapy group (59%) (between-group difference, 0.22; 95% CI, 0.07-0.36). Sustained response (SR), defined as maintenance of a platelet count >30 × 109/L, an absence of bleeding, and no requirement for any other ITP-specific treatment for 6 consecutive months after achievement of OR during 1 year following enrollment, was achieved by 68 (61%) patients in the combination group and 23 (41%) patients in the monotherapy group (between-group difference, 0.20; 95% CI, 0.04-0.35). The 2 most common adverse events (AEs) for the combination group were dry skin and headache or dizziness. Our findings demonstrated that ATRA plus LD-RTX significantly increased the overall and sustained response, indicating a promising treatment option for corticosteroid-resistant or relapsed adult ITP. This study is registered at www.clinicaltrials.gov as #NCT03304288.

Wide-field illumination diffuse optical tomography within a framework of single-pixel time-domain spatial frequency domain imaging.

We present a wide-field illumination time-domain (TD) diffusion optical tomography (DOT) for three-dimensional (3-D) reconstruction within a shallow region under the illuminated surface of the turbid medium. The methodological foundation is laid on the single-pixel spatial frequency domain (SFD) imaging that facilitates the adoption of the well-established time-correlated single-photon counting (TCSPC)-based TD detection and generalized pulse spectrum techniques (GPST)-based reconstruction. To ameliorate the defects of the conventional diffusion equation (DE) in the forward modeling of TD-SFD-DOT, mainly the low accuracy in the near-field region and in profiling early-photon migration, we propose a modified model employing the time-dependent δ-P1 approximation and verify its improved accuracy in comparison with both the Monte Carlo and DE-based ones. For a simplified inversion process, a modified GPST approach is extended to TD-SFD-DOT that enables the effective separation of the absorption and scattering coefficients using a steady-state equivalent strategy. Furthermore, we set up a single-pixel TD-SFD-DOT system that employs the TCSPC-based TD detection in the SFD imaging framework. For assessments of the reconstruction approach and the system performance, phantom experiments are performed for a series of scenarios. The results show the effectiveness of the proposed methodology for rapid 3-D reconstruction of the absorption and scattering coefficients within a depth range of about 5 mean free pathlengths.

Smart Hydrogel Dressing Enhances the Healing of Chronic Infectious Diabetic Wounds through Dual-Barrier Drug Delivery Action.

Chronic diabetic wounds struggle to heal due to drug-resistant bacterial infections, oxidative stress microenvironment, and immune dysfunction. At present, the disease has become a huge clinical challenge. Multifunctional hydrogels with antibacterial, antioxidant, and anti-inflammatory properties are becoming an emerging trend in the treatment of chronic wounds. However, matching different bioactive functions with the wound healing process to sequentially exert antibacterial, antioxidant, anti-inflammatory, and immunomodulatory functions remains a significant challenge. In this research, a hydrogel dressing with bactericidal and anti-inflammatory properties was synthesized by crafting a pH/ROS-responsive scaffold from phenylboronic acid-grafted hyaluronic acid (HA-PBA) and 4-arm-PEG-dopamine (4A-PEG-Dopa), employing dynamic borate ester bonds. This structure was then infused with the antimicrobial peptide (AMP) and ROS-sensitive micelle mPEG-TK-PLGA loaded with quercetin (QC). This dressing embodied a dual-barrier drug delivery mechanism, engineered for the prolonged and consistent liberation of QC. In the experiment, the hydrogel dissociated within the acidic microenvironment of diabetic wounds, thereby liberating the encapsulated micelles and AMP. Upon further dissociation, the micelles release QC due to the ROS-abundant microenvironment, which could relieve oxidative stress and encourage M2 polarization of macrophage via the Akt/STAT6 signaling pathway. Therefore, this smart delivery system, developed through our innovative approach, holds promise for treating chronic infectious diabetic wounds.

Population pharmacokinetics of long-term hydroxychloroquine therapy in patients with rheumatic diseases.

AIMS: Hydroxychloroquine (HCQ) is recommended for the long-term treatment of rheumatic diseases such as rheumatoid arthritis and systemic lupus erythematosus. Given the complex process of HCQ metabolism and individual physiological differences, the metabolic profile of HCQ after long-term administration is unknown. This study aimed to establish a population pharmacokinetic model for long-term HCQ treatment in patients with rheumatic diseases and to identify the factors influencing HCQ metabolism. METHODS: This study included 274 HCQ whole-blood trough concentration data points from 203 patients with rheumatic diseases, all of whom had taken HCQ for more than 6 months, with a median duration of 36 months. A nonlinear mixed-effects model was derived to establish a population pharmacokinetic model, and potential influencing factors were investigated. Different covariates were used to simulate the optimal dose. RESULTS: The final model describing the HCQ blood concentration-time profile was a compartmental model with first-order absorption. The estimated values for apparent clearance and volume of distribution were 16.4 L/h and 1220 L, respectively. The clearance of HCQ gradually increased with increasing dosing regimens and weight gain. Monte Carlo simulations were used to determine the optimal dosage regimens for patients with different body weights and drug durations. The simulation results revealed that an initial dose of 5 mg/kg was appropriate. CONCLUSIONS: We developed a population pharmacokinetic model for long-term HCQ therapy in patients with rheumatic diseases. HCQ clearance from whole blood increased progressively with increasing duration of drug administration.

Safety and efficacy of baricitinib in steroid-resistant or relapsed immune thrombocytopenia: An open-label pilot study.

Patients with steroid-resistant or relapsed immune thrombocytopenia (ITP) suffer increased bleeding risk and impaired quality of life. Baricitinib, an oral Janus-associated kinases (JAK) inhibitor, could alleviate both innate and adaptive immune disorders without inducing thrombocytopenia in several autoimmune diseases. Accordingly, an open-label, single-arm, phase 2 trial (NCT05446831) was initiated to explore the safety and efficacy of baricitinib in ITP. Eligible patients were adults with primary ITP who were refractory to corticosteroids and at least one subsequent treatment, and had platelet counts below 30 × 109/L at enrolment. Participants received baricitinib 4 mg daily for 6 months. The primary endpoint was durable response at the 6-month follow-up. A total of 35 patients were enrolled. Durable response was achieved in 20 patients (57.1%, 95% confidence interval, 39.9 to 74.4), and initial response in 23 (65.7%) patients. For patients responding to baricitinib, the median time to response was 12 (IQR 6-20) days, and the median peak platelet count was 94 (IQR 72-128) × 109/L. Among the 27 patients undergoing extend observation, 12 (44.4%) remained responsive for a median duration of approximately 20 weeks after baricitinib discontinuation. Adverse events were reported in 11 (31.4%) patients, including infections in 6 (17.1%) patients during the treatment period. Treatment discontinuation due to an adverse event was reported in 2 (5.7%) patients. Evidence from this pilot study suggested that baricitinib might be a novel candidate for the armamentarium of ITP-modifying agents. Future studies are warranted to validate the safety, efficacy, and optimal dosing of baricitinib in patients with ITP.

Inflammation-Responsive Mesoporous Silica Nanoparticles with Synergistic Anti-inflammatory and Joint Protection Effects for Rheumatoid Arthritis Treatment.

PURPOSE: Joint destruction is a major burden and an unsolved problem in rheumatoid arthritis (RA) patients. We designed an intra-articular mesoporous silica nanosystem (MSN-TP@PDA-GlcN) with anti-inflammatory and joint protection effects. The nanosystem was synthesized by encapsulating triptolide (TP) in mesoporous silica nanoparticles and coating it with pH-sensitive polydopamine (PDA) and glucosamine (GlcN) grafting on the PDA. The nano-drug delivery system with anti-inflammatory and joint protection effects should have good potency against RA. METHODS: A template method was used to synthesize mesoporous silica (MSN). MSN-TP@PDA-GlcN was synthesized via MSN loading with TP, coating with PDA and grafting of GlcN on PDA. The drug release behavior was tested. A cellular inflammatory model and a rat RA model were used to evaluate the effects on RA. In vivo imaging and microdialysis (MD) system were used to analyze the sustained release and pharmacokinetics in RA rats. RESULTS: TMSN-TP@PDA-GlcN was stable, had good biocompatibility, and exhibited sustained release of drugs in acidic environments. It had excellent anti-inflammatory effects in vitro and in vivo. It also effectively repaired joint destruction in vivo without causing any tissue toxicity. In vivo imaging and pharmacokinetics experiments showed that the nanosystem prolonged the residence time, lowered the Cmax value and enhanced the relative bioavailability of TP. CONCLUSIONS: These results demonstrated that MSN-TP@PDA-GlcN sustained the release of drugs in inflammatory joints and produced effective anti-inflammatory and joint protection effects on RA. This study provides a new strategy for the treatment of RA.