A 90-day subchronic exposure to heated tobacco product aerosol caused differences in intestinal inflammation and microbiome dysregulation in rats.

INTRODUCTION: Smoking is one of the most important predisposing factors of intestinal inflammatory diseases. Heated tobacco product (HTP) is a novel tobacco category that is claimed to deliver reduced chemicals to human those reported in combustible cigarette smoke (CS). However, the effect of HTP on intestine is still unknown. METHODS: In the framework of Organization for Economic Co-operation and Development guidelines 413 guidelines, Sprague-Dawley rats were exposed to HTP aerosol and CS for 13 weeks. The atmosphere was characterized and oxidative stress and inflammation of intestine were investigated after exposure. Furthermore, the faeces we performed with 16S sequencing and metabolomics analysis. RESULTS: HTP aerosol and CS led to obvious intestinal damage evidenced by increased intestinal pro-inflammatory cytokines and oxidative stress in male and female rats After HTP and CS exposure, the abundance that obviously changed were Lactobacillus and Turiciacter in male rats and Lactobacillus and Prevotella in female rats. HTP mainly induced the metabolism of amino acids and fatty acyls such as short-chain fatty acids and tryptophan, while CS involved into the main metabolism of bile acids, especially indole and derivatives. Although different metabolic pathways in the gut mediated by HTP and CS, both to inflammation and oxidative stress were ultimately induced. CONCLUSIONS: HTP aerosol and CS induced intestinal damage mediated by different gut microbiota and metabolites, while both lead to inflammation and oxidative stress. IMPLICATIONS: The concentration of various harmful components in heated tobacco product aerosol is reported lower than that of traditional cigarette smoke, however, its health risk impact on consumers remains to be studied. Our research findings indicate that heated tobacco product and cigarette smoke inhalation induced intestinal damage through different metabolic pathways mediated by gut microbiome, indicating the health risk of heated tobacco product in intestine.

Research on domain ontology construction based on the content features of online rumors.

Online rumors are widespread and difficult to identify, which bring serious harm to society and individuals. To effectively detect and govern online rumors, it is necessary to conduct in-depth semantic analysis and understand the content features of rumors. This paper proposes a TFI domain ontology construction method, which aims to achieve semantic parsing and reasoning of the rumor text content. This paper starts from the term layer, the frame layer, and the instance layer, and based on the reuse of the top-level ontology, the extraction of core literature content features, and the discovery of new concepts in the real corpus, obtains the core classes (five parent classes and 88 subclasses) of the rumor domain ontology and defines their concept hierarchy. Object properties and data properties are designed to describe relationships between entities or their features, and the instance layer is created according to the real rumor datasets. OWL language is used to encode the ontology, Protégé is used to visualize it, and SWRL rules and pellet reasoner are used to mine and verify implicit knowledge of the ontology, and judge the category of rumor text. This paper constructs a rumor domain ontology with high consistency and reliability.

Oral bacteriome and mycobiome of patients with idiopathic membranous nephropathy with different tongue coatings treated with a Chinese herbal formula.

ETHNOPHARMACOLOGICAL RELEVANCE: Moshen Fuyuan Formula (MSFY) is one of the representative Chinese medicine compound for Idiopathic membranous nephropathy (IMN), that originate from Fang Ji Huang Qi decoction in the Han dynasty. IMN is usually accompanied by different tongue coatings in traditional Chinese medicine (TCM), and tongue microorganisms are important factors affecting the formation of the tongue coating. Recently, oral microbiomes, including bacteria and fungi, have been identified as pivotal factors that contribute to disease development. However, the regulation of oral microbiomes by MSFY has not been defined. AIM OF THE STUDY: In this work, we explore the characteristics of oral bacteria and fungi in IMN patients with different tongue coatings, and clarify the therapeutic effect of MSFY based on oral microbiome. MATERIALS AND METHODS: We enrolled 24 patients with IMN, including 11 with white tongue (IMN-W) and 13 with yellow tongue (IMN-Y), and recruited an additional 10 healthy individuals. Patients with IMN were treated with the MSFY. The oral bacteriome and fungi before and after treatment were detected using full-length 16S rRNA and internal transcribed spacer gene sequencing. RESULTS: The therapeutic effect of MSFY on patients with yellow tongue coating was more significant than that on patients with white tongue coating. In terms of oral bacteriome, Campylobacter bacteria were enriched in patients with yellow tongue and could be a promising biomarker for yellow coating. Enrichment of Veillonella parvula_A may partially account for the therapeutic effect of MSFY. As for oral fungi, Malassezia globosa was enhanced in patients with IMN-W and reduced in patients with IMN-Y. Notably, it was reduced by MSFY. We also found that mycobiome-bacteriome interactions were highly complex and dynamic in patients with IMN. CONCLUSION: The regulation of the dynamic balance between oral fungi and bacteria by MSFY contributes to the treatment of IMN. This study determined the oral bacteriome and mycobiome of patients with IMN with different tongue coatings before and after MSFY treatment, which aids in promoting personalized treatment in clinical TCM and provides direction for investigating the mechanism of Chinese herbal medicines.

Gut microbiota-based discovery of Houttuyniae Herba as a novel prebiotic of Bacteroides thetaiotaomicron with anti-colitis activity.

Ulcerative colitis (UC) represents an inflammatory disease characterized by fluctuations in severity, posing substantial challenges in treatment. The gut microbiota plays a pivotal role in the pathogenesis of UC. This study sought to identify drugs specifically targeting the gut microbiota to mitigate UC. We initiated a meta-analysis on gut microbiota in UC patients to identify UC-associated bacterial strains. Subsequently, we screened 164 dietary herbal medicines in vitro to identify potential prebiotics for the UC-associated bacterium, Bacteroides thetaiotaomicron. The DSS-induced colitis mouse model was utilized to evaluate the anti-colitis efficacy of the identified dietary herbal medicine. Full-length 16 S rRNA amplicon sequencing was employed to observe changes in gut microbiota following dietary herbal medicine intervention. The relative abundance of Bacteroides was notably diminished in UC patients compared to their healthy counterparts. B. thetaiotaomicron exhibited an inverse relationship with UC symptoms, indicating its potential as an anti-colitis agent. In vitro assessments revealed that H. Herba significantly bolstered the proliferation of B. thetaiotaomicron. Further experiments showed that treating DSS-induced mice with an aqueous extract of H. Herba considerably alleviated colitis indicators such as weight loss, colon shortening, disease activity score (DAI), and systemic inflammation. Microbial analysis revealed B. thetaiotaomicron as the sole bacterium substantially augmented by H. Herba in vivo. Overall H. Herba emerges as a promising prebiotic for B. thetaiotaomicron, offering significant anti-colitis benefits. Employing a gut microbiota-centric approach proves valuable in the quest for drug discovery.This study provides a new paradigm for drug discovery that targets the gut microbiota to treat UC.

A new 4-gene-based prognostic model accurately predicts breast cancer prognosis and immunotherapy response by integrating WGCNA and bioinformatics analysis.

Background: Breast cancer (BRCA) is a common malignancy in women, and its resistance to immunotherapy is a major challenge. Abnormal expression of genes is important in the occurrence and development of BRCA and may also affect the prognosis of patients. Although many BRCA prognosis model scores have been developed, they are only applicable to a limited number of disease subtypes. Our goal is to develop a new prognostic score that is more accurate and applicable to a wider range of BRCA patients. Methods: BRCA patient data from The Cancer Genome Atlas database was used to identify breast cancer-related genes (BRGs). Differential expression analysis of BRGs was performed using the 'limma' package in R. Prognostic BRGs were identified using co-expression and univariate Cox analysis. A predictive model of four BRGs was established using Cox regression and the LASSO algorithm. Model performance was evaluated using K-M survival and receiver operating characteristic curve analysis. The predictive ability of the signature in immune microenvironment and immunotherapy was investigated. In vitro experiments validated POLQ function. Results: Our study identified a four-BRG prognostic signature that outperformed conventional clinicopathological characteristics in predicting survival outcomes in BRCA patients. The signature effectively stratified BRCA patients into high- and low-risk groups and showed potential in predicting the response to immunotherapy. Notably, significant differences were observed in immune cell abundance between the two groups. In vitro experiments demonstrated that POLQ knockdown significantly reduced the viability, proliferation, and invasion capacity of MDA-MB-231 or HCC1806 cells. Conclusion: Our 4-BRG signature has the potential as an independent biomarker for predicting prognosis and treatment response in BRCA patients, complementing existing clinicopathological characteristics.

Potential efficacy and mechanism of eight mild-natured and bitter-flavored TCMs based on gut microbiota: A review.

The mild-natured and bitter-flavored traditional Chinese medicines (MB-TCMs) are an important class of TCMs that have been widely used in clinical practice and recognized as safe long-term treatments for chronic diseases. However, as an important class of TCMs, the panorama of pharmacological effects and the mechanisms of MB-TCMs have not been systemically reviewed. Compelling studies have shown that gut microbiota can mediate the therapeutic activity of TCMs and help to elucidate the core principles of TCM medicinal theory. In this systematic review, we found that MB-TCMs commonly participated in the modulation of metabolic syndrome, intestinal inflammation, nervous system disease and cardiovascular system disease in association with promoting the growth of beneficial bacteria Bacteroides, Akkermansia, Lactobacillus, Bifidobacterium, Roseburia as well as inhibiting the proliferation of harmful bacteria Helicobacter, Enterococcus, Desulfovibrio and Escherichia-Shigella. These alterations, correspondingly, enhance the generation of protective metabolites, mainly including short-chain fatty acids (SCFAs), bile acid (BAs), 5-hydroxytryptamine (5-HT), indole and gamma-aminobutyric acid (GABA), and inhibit the generation of harmful metabolites, such as proinflammatory factors trimethylamine oxide (TAMO) and lipopolysaccharide (LPS), to further exert multiplicative effects for the maintenance of human health through several different signaling pathways. Altogether, this present review has attempted to comprehensively summarize the relationship between MB-TCMs and gut microbiota by establishing the TCMs-gut microbiota-metabolite-signaling pathway-diseases axis, which may provide new insight into the study of TCM medicinal theories and their clinical applications.

Cross-Sectional and Longitudinal Associations of Comorbidities with Knee Symptoms and Radiographic Abnormalities of Osteoarthritis.

INTRODUCTION: This study aimed to investigate the associations of comorbidities with knee symptoms and radiographic abnormalities of osteoarthritis (OA). METHODS: Participants were from the Osteoarthritis Initiative. Comorbidities were identified at baseline using the modified Charlson Comorbidity Index. For both knees, symptoms were assessed annually from baseline to 48 months using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and function scores (rescaled range 0-100), and radiographic abnormalities using the Kellgren-Lawrence (KL, 0-4) grades. The presence of significant pain and functional disability was defined as a WOMAC score of ≥ 25 and ≥ 22, respectively, and radiographic OA (ROA) as KL ≥ 2. An increase of ≥ 9 in WOMAC scores and ≥ 1 in KL grades were defined as symptomatic and radiographic progression, respectively. RESULTS: Of 3337 participants, 28% and 9% had one and ≥ 2 comorbidities, respectively. The number of comorbidities was associated with the presence of significant functional disability (odds ratios [ORs] 1.15; 1.46) and predicted the progression of both knee pain and functional disability (ORs 1.11; 1.51). For the type of comorbidities, non-OA musculoskeletal diseases were associated with the presence of ROA and significant functional disability (ORs 1.63; 1.82) and showed a trend to predict incident ROA (OR 1.84, 95% confidence interval 1.00-3.38 p = 0.051). Diabetes and kidney diseases were associated with symptomatic progression of OA (ORs 1.38; 2.72). CONCLUSIONS: Having more comorbidities, especially diabetes and kidney diseases, is associated with symptomatic progression of knee OA. Moreover, non-OA musculoskeletal diseases may be associated with the presence and onset of ROA.

Identification of Peptides of Small Extracellular Vesicles from Bone Marrow-Derived Macrophages.

Small extracellular vesicles (sEVs) are typically secreted by the exocytosis of multivesicular bodies (MVBs). These nanovesicles with a diameter of <200 nm are present in various body fluids. These sEVs regulate various biological processes such as gene transcription and translation, cell proliferation and survival, immunity and inflammation through their cargos, such as proteins, DNA, RNA, and metabolites. Currently, various techniques have been developed for sEVs isolation. Among them, the ultracentrifugation-based method is considered the gold standard and is widely used for sEVs isolation. The peptides are naturally biomacromolecules with less than 50 amino acids in length. These peptides participate in a variety of biological processes with biological activity, such as hormones, neurotransmitters, and cell growth factors. The peptidome is intended to systematically analyze endogenous peptides in specific biological samples by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Here, we introduced a protocol to isolate sEVs by differential ultracentrifugation and extracted peptidome for identification by LC-MS/MS. This method identified hundreds of sEVs-derived peptides from bone marrow-derived macrophages.

On the Asymptotic Capacity of Information-Theoretic Privacy-Preserving Epidemiological Data Collection.

The paradigm-shifting developments of cryptography and information theory have focused on the privacy of data-sharing systems, such as epidemiological studies, where agencies are collecting far more personal data than they need, causing intrusions on patients' privacy. To study the capability of the data collection while protecting privacy from an information theory perspective, we formulate a new distributed multiparty computation problem called privacy-preserving epidemiological data collection. In our setting, a data collector requires a linear combination of K users' data through a storage system consisting of N servers. Privacy needs to be protected when the users, servers, and data collector do not trust each other. For the users, any data are required to be protected from up to E colluding servers; for the servers, any more information than the desired linear combination cannot be leaked to the data collector; and for the data collector, any single server can not know anything about the coefficients of the linear combination. Our goal is to find the optimal collection rate, which is defined as the ratio of the size of the user's message to the total size of downloads from N servers to the data collector. For achievability, we propose an asymptotic capacity-achieving scheme when E

Hollow microneedle microfluidic paper-based chip for biomolecules rapid sampling and detection in interstitial fluid.

The interstitial fluid (ISF) contains rich bioinformation for disease diagnosis and healthcare monitoring. However, the efficient sampling and detection of the biomolecules in ISF is still challenging. Herein, we develop a facile but versatile ISF analysis platform by combining controllable hollow microneedles (HMNs) and elaborate microfluidic paper-based analytical devices (µPADs). The HMNs and µPADs was fixed in a bottom PDMS layer. A top PDMS layer containing a cylindrical cavity to produce negative pressure for sampling was packaged on the bottom PDMS layer. The HMNs enable efficient and swift sampling of sufficient ISF to the µPADs through one-touch finger operation without extra manipulations. The µPADs realized to simultaneously detect glucose and lactic acid in the detection area to produce chromogenic agents and analyzed by the self-programed RGB application (APP) in smartphones. The HMN microfluidic paper-based chip provides a point-of-care platform for accurate detection of biomolecules in ISF, holding great promise in the development of wearable device.

Longitudinal development of the cerebellum in human infants during the first 800 days.

Revealing early dynamic development of the normative cerebellar structures contributes to exploring cerebellum-related neurodevelopmental disorders. Here, leveraging infant-tailored cerebellar image processing techniques, we studied the dynamic volumetric developmental trajectories of cerebellum and 27 cerebellar sub-regions and their relationships with behavioral scores based on 511 high-resolution structural MRI scans during the first 800 postnatal days. The ratio of the entire cerebellum to the intracranial volume increases rapidly at first and then peaks at 13 months after birth. Both the absolute and relative volumes of most cerebellar sub-structures exhibit rapid increase at first, then the relative volumes decrease slightly after arriving at peaks (except for X lobules). Each lobule depicts larger absolute volume in males than in females. The within-subject variation of the cerebellar volumetric percentile score is generally stable. The volumetric development of several lobules (e.g., V, Crus I, and Crus II) has a significantly positive correlation with fine motor skills during the age range examined.

Trapping of a Single Microparticle Using AC Dielectrophoresis Forces in a Microfluidic Chip.

Precise trap and manipulation of individual cells is a prerequisite for single-cell analysis, which has a wide range of applications in biology, chemistry, medicine, and materials. Herein, a microfluidic trapping system with a 3D electrode based on AC dielectrophoresis (DEP) technology is proposed, which can achieve the precise trapping and release of specific microparticles. The 3D electrode consists of four rectangular stereoscopic electrodes with an acute angle near the trapping chamber. It is made of Ag-PDMS material, and is the same height as the channel, which ensures the uniform DEP force will be received in the whole channel space, ensuring a better trapping effect can be achieved. The numerical simulation was conducted in terms of electrode height, angle, and channel width. Based on the simulation results, an optimal chip structure was obtained. Then, the polystyrene particles with different diameters were used as the samples to verify the effectiveness of the designed trapping system. The findings of this research will contribute to the application of cell trapping and manipulation, as well as single-cell analysis.

Effects of arch support doses on the center of pressure and pressure distribution of running using statistical parametric mapping.

Insoles with an arch support have been used to address biomechanical risk factors of running. However, the relationship between the dose of support and running biomechanics remains unclear. The purpose of this study was to determine the effects of changing arch support doses on the center of pressure (COP) and pressure mapping using statistical parametric mapping (SPM). Nine arch support variations (3 heights * 3 widths) and a flat insole control were tested on fifteen healthy recreational runners using a 1-m Footscan pressure plate. The medial-lateral COP (COPML) coordinates and the total COP velocity (COPVtotal) were calculated throughout the entirety of stance. One-dimensional and two-dimensional SPM were performed to assess differences between the arch support and control conditions for time series of COP variables and pressure mapping at a pixel level, respectively. Two-way ANOVAs were performed to test the main effect of the arch support height and width, and their interaction on the peak values of the COPVtotal. The results showed that the COPVtotal during the forefoot contact and forefoot push off phases was increased by arch supports, while the COP medial-lateral coordinates remained unchanged. There was a dose-response effect of the arch support height on peak values of the COPVtotal, with a higher support increasing the first and third valleys but decreasing the third peak of the COPVtotal. Meanwhile, a higher arch support height shifted the peak pressure from the medial forefoot and rearfoot to the medial arch. It is concluded that changing arch support doses, primarily the height, systematically altered the COP velocities and peak plantar pressure at a pixel level during running. When assessing subtle modifications in the arch support, the COP velocity was a more sensitive variable than COP coordinates. SPM provides a high-resolution view of pressure comparisons, and is recommended for future insole/footwear investigations to better understand the underlying mechanisms and improve insole design.

Microneedle Array Encapsulated with Programmed DNA Hydrogels for Rapidly Sampling and Sensitively Sensing of Specific MicroRNA in Dermal Interstitial Fluid.

Author: Please verify that the changes made to improve the English still retain your original meaning.Detection of microRNA (miRNA) in dermal interstitial fluid (ISF) has emerged as clinically useful in health status monitoring. However, it remains a great challenge owing to the difficult sampling and low abundance. Here, we report a DNA hydrogel microneedles (MNs) array to realize rapid enrichment and sensitive detection of miRNA in ISF. The MNs' patch consists of methacrylate hyaluronic acid (MeHA) equipped with a smart DNA circuit hydrogels' system (MeHA/DNA), in which an appropriate miRNA input enables triggering a cascading toehold-mediated DNA displacement reaction to catalytically cleave cross-linking points to generate amplified fluorescence (FL) for miRNA detection. The MeHA/DNA-MNs patch with high mechanical strength can extract adequate ISF in a short time (0.97 ± 0.2 mg in 5 min) in vivo because of its supreme water affinity. Additionally, the cascading toehold-mediated DNA displacement signal amplification reaction allows for sensitive detection of the low-abundant miRNAs down to 241.56 pM. The DNA hydrogels' MNs present potential for minimally invasive personalized diagnosis and real-time health monitoring in clinical applications.

SPHERICAL TRANSFORMER FOR QUALITY ASSESSMENT OF PEDIATRIC CORTICAL SURFACES.

Brain cortical surfaces, which have an intrinsic spherical topology, are typically represented by triangular meshes and mapped onto a spherical manifold in neuroimaging analysis. Inspired by the strong capability of feature learning in Convolutional Neural Networks (CNNs), spherical CNNs have been developed accordingly and achieved many successes in cortical surface analysis. Motivated by the recent success of the transformer, in this paper, for the first of time, we extend the transformer into the spherical space and propose the spherical transformer, which can better learn contextual and structural features than spherical CNNs. We applied the spherical transformer in the important task of automatic quality assessment of infant cortical surfaces, which is a necessary procedure to identify problematic cases due to extremely low tissue contrast and strong motion effects in pediatric brain MRI studies. Experiments on 1,860 infant cortical surfaces validated its superior effectiveness and efficiency in comparison with spherical CNNs.

Using Weighted Gene Co-Expression Network Analysis to Identify Increased MND1 Expression as a Predictor of Poor Breast Cancer Survival.

Objective: We used bioinformatics analysis to identify potential biomarker genes and their relationship with breast cancer (BC). Materials and Methods: We used a weighted gene co-expression network analysis (WGCNA) to create a co-expression network based on the top 25% genes in the GSE24124, GSE33926, and GSE86166 datasets obtained from the Gene Expression Omnibus. We used the DAVID online platform to perform GO and KEGG pathway enrichment analyses and the Cytoscape CytoHubba plug-in to screen the potential genes. Then, we related the genes to prognostic values in BC using the Oncomine, GEPIA, and Kaplan-Meier Plotter databases. Findings were validated by immunohistochemical (IHC) staining in the Human Protein Atlas and the TCGA-BRCA cohort. LinkedOmics identified the interactive expressions of hub genes. We used UALCAN to evaluate the methylation levels of these hub genes. MethSurv and SurvivalMeth were used to assess the multilevel prognostic value. Finally, we assessed hub gene association with immune cell infiltration using TIMER. Results: The mRNA levels of MKI67, UBE2C, GTSE1, CCNA2, and MND1 were significantly upregulated in BC, whereas ESR1, THSD4, TFF1, AGR2, and FOXA1 were significantly downregulated. The DNA methylation signature analysis showed a better prognosis in the low-risk group. Further subgroup analyses revealed that MND1 might serve as an independent risk factor for unfavorable BC prognosis. Additionally, MND1 expression levels positively correlate with the immune infiltration statuses of CD4+ T cells, CD8+ T cells, B cells, neutrophils, dendritic cells, and macrophages. Conclusion: Our results indicate that the ten hub genes may be involved in BC's carcinogenesis, development, or metastasis, and MND1 may be a potential biomarker and therapeutic target for BC.

Path Signature Neural Network of Cortical Features for Prediction of Infant Cognitive Scores.

Studies have shown that there is a tight connection between cognition skills and brain morphology during infancy. Nonetheless, it is still a great challenge to predict individual cognitive scores using their brain morphological features, considering issues like the excessive feature dimension, small sample size and missing data. Due to the limited data, a compact but expressive feature set is desirable as it can reduce the dimension and avoid the potential overfitting issue. Therefore, we pioneer the path signature method to further explore the essential hidden dynamic patterns of longitudinal cortical features. To form a hierarchical and more informative temporal representation, in this work, a novel cortical feature based path signature neural network (CF-PSNet) is proposed with stacked differentiable temporal path signature layers for prediction of individual cognitive scores. By introducing the existence embedding in path generation, we can improve the robustness against the missing data. Benefiting from the global temporal receptive field of CF-PSNet, characteristics consisted in the existing data can be fully leveraged. Further, as there is no need for the whole brain to work for a certain cognitive ability, a top K selection module is used to select the most influential brain regions, decreasing the model size and the risk of overfitting. Extensive experiments are conducted on an in-house longitudinal infant dataset within 9 time points. By comparing with several recent algorithms, we illustrate the state-of-the-art performance of our CF-PSNet (i.e., root mean square error of 0.027 with the time latency of 518 milliseconds for each sample).

Spherical Transformer on Cortical Surfaces.

Motivated by the recent great success of attention modeling in computer vision, it is highly desired to extend the Transformer architecture from the conventional Euclidean space to non-Euclidean spaces. Given the intrinsic spherical topology of brain cortical surfaces in neuroimaging, in this study, we propose a novel Spherical Transformer, an effective general-purpose backbone using the self-attention mechanism for analysis of cortical surface data represented by triangular meshes. By mapping the cortical surface onto a sphere and splitting it uniformly into overlapping spherical surface patches, we encode the long-range dependency within each patch by the self-attention operation and formulate the cross-patch feature transmission via overlapping regions. By limiting the self-attention computation to local patches, our proposed Spherical Transformer preserves detailed contextual information and enjoys great efficiency with linear computational complexity with respect to the patch size. Moreover, to better process longitudinal cortical surfaces, which are increasingly popular in neuroimaging studies, we unprecedentedly propose the spatiotemporal self-attention operation to jointly extract the spatial context and dynamic developmental patterns within a single layer, thus further enlarging the expressive power of the generated representation. To comprehensively evaluate the performance of our Spherical Transformer, we validate it on a surface-level prediction task and a vertex-level dense prediction task, respectively, i.e., the cognition prediction and cortical thickness map development prediction, which are important in early brain development mapping. Both applications demonstrate the competitive performance of our Spherical Transformer in comparison with the state-of-the-art methods.

Programmable Polymeric Microneedles for Combined Chemotherapy and Antioxidative Treatment of Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a chronic inflammatory joint disease. Antioxidative treatment combined with chemotherapy holds great promise for RA treatment, and the ability to efficiently deliver drugs and antioxidants to the RA synovial joint is highly desired. Herein, we developed a programmable polymeric microneedle (MN) platform for transdermal delivery of methotrexate (MTX) and reactive oxygen species (ROS) scavengers for RA treatment. The biodegradable MNs made of polyvinylpyrrolidone (PVP) were incorporated with polydopamine/manganese dioxide (termed PDA@MnO2) and MTX. After insertion into skin tissue, the MNs degraded, thus enabling release of loaded MTX and PDA@MnO2. The PDA@MnO2 could be utilized as an MRI contrast agent in the RA synovial microenvironment. It also acted as a robust antioxidant to remove ROS and decrease RA inflammation, which when combined with the MTX-mediated chemotherapy led to an ideal outcome for RA treatments in a murine model. This work not only represents a valuable MN-assisted RA therapeutic agent transdermal delivery approach but also opens a new avenue for chemotherapy and antioxidative synergistic treatment of RA.