A drug-mediated organic electrochemical transistor for robustly reusable biosensors.

Reusable point-of-care biosensors offer a cost-effective solution for serial biomarker monitoring, addressing the critical demand for tumour treatments and recurrence diagnosis. However, their realization has been limited by the contradictory requirements of robust reusability and high sensing capability to multiple interactions among transducer surface, sensing probes and target analytes. Here we propose a drug-mediated organic electrochemical transistor as a robust, reusable epidermal growth factor receptor sensor with striking sensitivity and selectivity. By electrostatically adsorbing protonated gefitinib onto poly(3,4-ethylenedioxythiophene):polystyrene sulfonate and leveraging its strong binding to the epidermal growth factor receptor target, the device operates with a unique refresh-in-sensing mechanism. It not only yields an ultralow limit-of-detection concentration down to 5.74 fg ml-1 for epidermal growth factor receptor but, more importantly, also produces an unprecedented regeneration cycle exceeding 200. We further validate the potential of our devices for easy-to-use biomedical applications by creating an 8 × 12 diagnostic drug-mediated organic electrochemical transistor array with excellent uniformity to clinical blood samples.

Thermoelectric Performance in Triplet-Ground-State Polymer Intrinsically Boosted by Enhanced Proquinoidal Characteristic.

Polymer thermoelectric materials featuring flexibility, lightness, and bio-friendliness have been paid increasing attention for waste heat recovery and energy generation. The dominant approach to optimizing the thermoelectric performance of most organic materials is chemical doping, which, however, is not always ideal for practical applications due to its tendency to involve intricate processing procedure and trigger material and device instability. The pursuit of single-component neutral thermoelectric materials without exogenous doping presents a compelling alternative. In this work, we designed and synthesized a high-spin polymer material, PBBT-TT, by simultaneously employing thieno[3,4-b]thiophene (TbT) and benzo[1,2-c:4,5-c']bis[1,2,5]thiadiazole (BBT) units with pronounced proquinoidal characteristics, and its analogue, PBBT-T. Because of the enhanced quinoidal resonance, increased spin density, and strong intermolecular antiferromagnetic coupling, PBBT-TT exhibits high intrinsic electrical conductivity and Seebeck coefficient, which showcases an outstanding power factor of 26.1 µW m-1 K-2 without doping, surpassing other neutral organic conjugated polymer and radical conductors. Notably, PBBT-TT exhibits remarkable ambient stability, retaining its initial thermoelectric performance over a 120-day period. Our finding demonstrates that modulating the intermolecular spin interactions in open-shell polymers through the introduction of strong proquinoidal units is an effective strategy for the development of doping-free, intrinsically high-performance polymer thermoelectric materials.

Quercetin activates energy expenditure to combat metabolic syndrome through modulating gut microbiota-bile acids crosstalk in mice.

Abdominal obesity-related metabolic syndrome (MetS) has emerged as a significant global public health issue that affects human health. Flavonoids, such as quercetin, have been reported to exert obvious anti-obesity and lipid-lowering effects in both humans and animal models. However, the precise underlying mechanism remains elusive. In this study, we investigated the potential roles of gut microbiota-bile acids (BAs) interactions in quercetin-induced anti-obesity effects and metabolic benefits. Oral administration of quercetin significantly enhanced energy metabolism through activating thermogenesis of brown adipose tissues (BAT) and browning of white adipose tissues (WAT), thus mitigating metabolic dysfunctions in an abdominal obesity-related MetS mouse model. Further mechanistic studies demonstrated that quercetin treatment substantially promoted the generation of non-12α-hydroxylated BAs (non-12OH BAs), particularly ursodeoxycholic acid (UDCA) and lithocholic acid (LCA), in serum via regulating the overall structure of gut microbiota and enriching Lactobacillus. High level of non-12OH BAs bind to Takeda G protein-coupled receptor 5 (TGR5) on adipocytes to stimulate thermogenesis. Remarkably, fecal microbiota transplantation (FMT) from quercetin-treated mice replicated the effects of quercetin on non-12OH BAs generation and energy expenditure, which suggested gut microbiota reshape and concomitant BAs regulation were responsible for the benefits on energy metabolism of quercetin in the MetS mouse model. Our findings not only highlighted the critical role of gut microbiota-BAs crosstalk in mediating quercetin-induced energy expenditure, but also enriched the pharmacological mechanisms of quercetin in ameliorating MetS-related diseases.

Multi-heterojunctioned plastics with high thermoelectric figure of merit.

Conjugated polymers promise inherently flexible and low-cost thermoelectrics for powering the Internet of Things from waste heat1,2. Their valuable applications, however, have been hitherto hindered by the low dimensionless figure of merit (ZT)3-6. Here we report high-ZT thermoelectric plastics, which were achieved by creating a polymeric multi-heterojunction with periodic dual-heterojunction features, where each period is composed of two polymers with a sub-ten-nanometre layered heterojunction structure and an interpenetrating bulk-heterojunction interface. This geometry produces significantly enhanced interfacial phonon-like scattering while maintaining efficient charge transport. We observed a significant suppression of thermal conductivity by over 60 per cent and an enhanced power factor when compared with individual polymers, resulting in a ZT of up to 1.28 at 368 kelvin. This polymeric thermoelectric performance surpasses that of commercial thermoelectric materials and existing flexible thermoelectric candidates. Importantly, we demonstrated the compatibility of the polymeric multi-heterojunction structure with solution coating techniques for satisfying the demand for large-area plastic thermoelectrics, which paves the way for polymeric multi-heterojunctions towards cost-effective wearable thermoelectric technologies.

Nanoscale doping of polymeric semiconductors with confined electrochemical ion implantation.

Nanoresolved doping of polymeric semiconductors can overcome scaling limitations to create highly integrated flexible electronics, but remains a fundamental challenge due to isotropic diffusion of the dopants. Here we report a general methodology for achieving nanoscale ion-implantation-like electrochemical doping of polymeric semiconductors. This approach involves confining counterion electromigration within a glassy electrolyte composed of room-temperature ionic liquids and high-glass-transition-temperature insulating polymers. By precisely adjusting the electrolyte glass transition temperature (Tg) and the operating temperature (T), we create a highly localized electric field distribution and achieve anisotropic ion migration that is nearly vertical to the nanotip electrodes. The confined doping produces an excellent resolution of 56 nm with a lateral-extended doping length down to as little as 9.3 nm. We reveal a universal exponential dependence of the doping resolution on the temperature difference (Tg - T) that can be used to depict the doping resolution for almost infinite polymeric semiconductors. Moreover, we demonstrate its implications in a range of polymer electronic devices, including a 200% performance-enhanced organic transistor and a lateral p-n diode with seamless junction widths of <100 nm. Combined with a further demonstration in the scalability of the nanoscale doping, this concept may open up new opportunities for polymer-based nanoelectronics.

Biomimetic nanocluster photoreceptors for adaptative circular polarization vision.

Nanoclusters with atomically precise structures and discrete energy levels are considered as nanoscale semiconductors for artificial intelligence. However, nanocluster electronic engineering and optoelectronic behavior have remained obscure and unexplored. Hence, we create nanocluster photoreceptors inspired by mantis shrimp visual systems to satisfy the needs of compact but multi-task vision hardware and explore the photo-induced electronic transport. Wafer-scale arrayed photoreceptors are constructed by a nanocluster-conjugated molecule heterostructure. Nanoclusters perform as an in-sensor charge reservoir to tune the conductance levels of artificial photoreceptors by a light valve mechanism. A ligand-assisted charge transfer process takes place at nanocluster interface and it features an integration of spectral-dependent visual adaptation and circular polarization recognition. This approach is further employed for developing concisely structured, multi-task, and compact artificial visual systems and provides valuable guidelines for nanocluster neuromorphic devices.

The correlation between lung ultrasound scores and outcomes of high-flow nasal cannula therapy in infants with severe pneumonia.

OBJECTIVE: The study aimed to explore the effectiveness of bedside lung ultrasound (LUS) combined with the PaO2/FiO2 (P/F) ratio in evaluating the outcomes of high-flow nasal cannula (HFNC) therapy in infants with severe pneumonia. METHODS: This retrospective study analyzed the clinical data of 150 infants diagnosed with severe pneumonia and treated with HFNC therapy at our hospital from January 2021 to December 2021. These patients were divided into two groups based on their treatment outcomes: the HFNC success group (n = 112) and the HFNC failure group (n = 38). LUS was utilized to evaluate the patients' lung conditions, and blood gas results were recorded for both groups upon admission and after 12 h of HFNC therapy. RESULTS: At admission, no significant differences were observed between the two groups in terms of age, gender, respiratory rate, partial pressure of oxygen, and partial pressure of carbon dioxide. However, the P/F ratios at admission and after 12 h of HFNC therapy were significantly lower in the HFNC failure group (193.08 ± 49.14, 228.63 ± 80.17, respectively) compared to the HFNC success group (248.51 ± 64.44, 288.93 ± 57.17, respectively) (p < 0.05). Likewise, LUS scores at admission and after 12 h were significantly higher in the failure group (18.42 ± 5.3, 18.03 ± 5.36, respectively) than in the success group (15.09 ± 4.66, 10.71 ± 3.78, respectively) (p < 0.05). Notably, in the success group, both P/F ratios and LUS scores showed significant improvement after 12 h of HFNC therapy, a trend not observed in the failure group. Multivariate regression analysis indicated that lower P/F ratios and higher LUS scores at admission and after 12 h were predictive of a greater risk of HFNC failure. ROC analysis demonstrated that an LUS score > 20.5 at admission predicted HFNC therapy failure with an AUC of 0.695, a sensitivity of 44.7%, and a specificity of 91.1%. A LUS score > 15.5 after 12 h of HFNC therapy had an AUC of 0.874, with 65.8% sensitivity and 89.3% specificity. An admission P/F ratio < 225.5 predicted HFNC therapy failure with an AUC of 0.739, 60.7% sensitivity, and 71.1% specificity, while a P/F ratio < 256.5 after 12 h of HFNC therapy had an AUC of 0.811, 74.1% sensitivity, and 73.7% specificity. CONCLUSION: Decreased LUS scores and increased P/F ratio demonstrate a strong correlation with successful HFNC treatment outcomes in infants with severe pneumonia. These findings may provide valuable support for clinicians in managing such cases.

Comparative Analysis of High-Flow Nasal Cannula Oxygen Therapy and Invasive Mechanical Ventilation in the Management of Severe Pneumonia: A Retrospective Study.

Background: Severe pneumonia continues to be a prominent cause of hospitalization and global mortality. There is ongoing debate regarding the effectiveness of different oxygen therapy modalities, particularly high-flow nasal cannula (HFNC) oxygen therapy and invasive mechanical ventilation (IMV), in the treatment of severe pneumonia. Objective: This study investigated the risk factors associated with mechanical ventilation in pediatric patients with severe pneumonia. Methods: This retrospective study included a cohort of 240 pediatric patients with severe pneumonia treated at Zhangzhou Hospital, affiliated with Fujian Medical University, from January 2019 to December 2020. Patients were categorized into two groups: the HFNC group and the IMV group. Comparative analysis was performed on general patient information, infection markers, arterial blood gas values, as well as the prevalence of underlying conditions and complications between the two groups. Multivariate logistic regression analysis was employed to identify the risk factors for invasive mechanical ventilation in children with severe pneumonia. Results: Patients in the HFNC group experienced shorter hospitalization durations, and the average age in this group was lower compared to the IMV group (P < .05). Upon admission, respiratory rate and heart rate were higher in the HFNC group compared to the IMV group (P < .05). The IMV group demonstrated higher oxygenation index (OI) and infection markers, while the pH level was lower in the IMV group than in the HFNC group (P < .05). The prevalence of underlying conditions and complications in the IMV group was significantly higher than in the HFNC group (P < .05). Basic conditions such as heart disease, prematurity, heart failure, low OI, toxic encephalopathy, and influenza virus infection were identified as risk factors for IMV. Conclusions: High-flow nasal cannula therapy has shown therapeutic efficacy in pediatric patients with severe pneumonia. However, children with underlying medical conditions may require prompt tracheal intubation and invasive mechanical ventilation.

A microRNA sponge, LINC02193, promotes neutrophil activation by upregulating ICAM1 and is correlated with ANCA-associated vasculitis.

OBJECTIVE: To investigate the pathogenic role and underlying mechanisms of lncRNAs in antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV). METHODS：: RNA-sequencing (RNA-seq) was applied to screen the expression profile of lncRNAs in peripheral leukocytes from 5 AAV patients and 5 healthy controls (HC). Candidate lncRNAs were preliminarily verified in peripheral leukocytes from 46 AAV patients and 35 HC by qRT-PCR. Then, the identified LINC02193 was further validated in peripheral neutrophils from 67 AAV patients, 45 HC and 64 disease controls. Correlation between LINC02193 levels and disease activity was analyzed. Then, a loss-of-function study was conducted to investigate the role of LINC02193 in neutrophils activation. Furthermore, bioinformatics analysis, dual luciferase reporter and RNA immunoprecipitation (RIP) assays were performed to explore the mechanism of LINC02193 regulating neutrophils activation. RESULTS: A total of 467 upregulated and 412 downregulated lncRNAs were identified in AAV patients. From top 5 upregulated lncRNAs, an elevation of LINC02193 was validated in a larger sample of AAV patients, and positively correlated with disease activity. Knockdown of LINC02193 inhibited ROS and NO production, NETs release and adhesion to endothelial cells of differentiated human promyelocytic leukaemia HL­60 cells (dHL-60), whereas overexpression of ICAM1 counteracted these effects. Mechanistic analysis demonstrated that LINC02193 acted as a miR-485-5p sponge to relieve the repressive effect of miR-485-5p on ICAM1, thus promoting ICAM1 expression. CONCLUSION: LINC02193, a novel lncRNA identified in AAV could function as competing endogenous RNAs (ceRNA) for miR-485-5p to promote ICAM1 expression and neutrophils activation, suggesting its potential as a therapeutic target of AAV.

Single-Cell RNA-Sequencing Reveals Peripheral T Helper Cells Promoting the Development of IgG4-Related Disease by Enhancing B Cell Activation and Differentiation.

Abnormal B cell differentiation plays a critical role in IgG4-related disease (IgG4-RD), but the underlying mechanism remains largely unknown. We investigated the cell landscape from three IgG4-RD retroperitoneal tissues and three control tissues using single-cell RNA-sequencing. Critical cell type or markers were further validated in the peripheral blood from the patients with IgG4-RD and healthy controls via flow cytometry as well as in the IgG4-RD and control tissue via immunofluorescence staining. The increases in B cells, plasma cells, and CD4+ T cells were found in IgG4-RD retroperitoneal tissue. Importantly, among CD4+ T cells, an increase in CD4+CXCR5-PD1hi peripheral T helper (Tph) cells with a high expression of IL-21 and TIGIT was discovered in IgG4-RD tissue, which was further validated in peripheral blood of the patients with IgG4-RD. The Tph cell and TIGIT+ Tph cell proportion were remarkably higher in active IgG4-RD patients and correlated with disease activity. Moreover, TIGIT+CD4+ cells were able to promote B cell differentiation via IL-21. Our study revealed that Tph cells are increased in IgG4-RD and probably play critical roles in B cell differentiation through TIGIT-IL-21 axis. Peripheral Tph cell and TIGIT+Tph cell are potential markers for IgG4-RD disease activity.

m6A methyltransferase KIAA1429 accelerates oral squamous cell carcinoma via regulating glycolysis and ferroptosis.

N6-methyladenosine (m6A) modification acts as the most prevalent modification on eukaryotic RNA, and its function on oral squamous cell carcinoma (OSCC) is still unclear. Here, the present research aimed to explore the novel function of m6A methyltransferase KIAA1429 in OSCC. Results illustrated that KIAA1429 up-regulated in the OSCC samples and cells. Gain/loss functional assays demonstrated that KIAA1429 repressed the ferroptosis of OSCC. Moreover, KIAA1429 positively accelerated the aerobic glycolysis of OSCC, including glucose uptake, lactate production, ATP level and ECAR. Mechanistically, KIAA1429 could install the m6A modification on the PGK1 mRNA, thereby up-regulating the methylated m6A level. Moreover, m6A reader YTHDF1 recognized the m6A modification site of PGK1 mRNA and enhanced its mRNA stability. Thus, KIAA1429 promoted the OSCC aerobic glycolysis and inhibited the ferroptosis of OSCC through YTHDF1-mediated PGK1 mRNA stability. Taken together, these findings reveal a novel insight for KIAA1429 on OSCC via m6A-dependent manner.

Effect of wet-heparinized suction on the quality of mediastinal solid tumor specimens obtained by endoscopic ultrasound-guided fine-needle aspiration: a retrospective study from a single center.

BACKGROUND: Mediastinal lesions are diagnosed sometimes by endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). Wet-heparinized suction technique has been used to improve the quality of abdominal solid tumor samples obtained by EUS-FNA. The aim of the study is to assess the effect of wet-heparinized suction on the quality of mediastinal solid tumor samples and to evaluate the safety of the method. METHODS: The medical records, EUS-FNA records, pathologic data, and follow-up data between the patients who suspected mediastinal lesions with wet-heparinized suction and conventional suction were retrospectively and comparatively analyzed. Adverse events at 48 h and 1 week after EUS-FNA were evaluated. RESULTS: Wet-heparinized suction contributed to more tissue specimens (P < 0.05), superior tissue integrity (P < 0.05), and a longer length of white tissue core (P < 0.05). In addition, the more complete the tissue bar was, the higher the rate of successful sample (P < 0.05). Moreover, the total length of the white tissue bar at the first puncture was remarkably longer in the Experimental group (P < 0.05). No significant difference in red blood cell contamination in paraffin sections was found between the two groups (P > 0.05). There was no complication after discharge in both groups. CONCLUSION: Wet-heparinized suction can improve the quality of mediastinal lesion samples obtained by EUS-FNA and increase the success rate of sampling. In addition, it will not aggravate blood contamination in paraffin sections while ensuring a safe puncture.

The functional change of the P2X7R containing the Ala348 to Thr polymorphism is associated with the pathogenesis of gout.

Our previous study has shown that ATP action on P2X7R could be the second signal to induce the onset of gouty arthritis. However, the functional changes of P2X7R single nucleotide polymorphisms (SNPs) on the effects of ATP-P2X7R-IL-1ß signaling pathway and uric acid remained unknown. We aimed to investigate the association between the functional change of P2X7R containing the Ala348 to Thr polymorphisms (rs1718119) and the pathogenesis of gout. First, 270 gout patients and 70 hyperuricemic patients (without gout attack history in recent 5 years) were recruited for genotyping. In addition, the changes of ATP-induced pore formation were assessed in HEK-293T cells overexpressing different mutants in P2RX7, and the effects on P2X7R-NLRP3-IL-1ß pathway activation were explored in P2RX7 overexpression THP-1 cells. The risk allele for gout was A at rs1718119, and the AA and AG genotypes exhibited a higher risk of gout. Furthermore, Ala348 to Thr mutants increased P2X7-dependent ethidium+ bromide uptake, upregulated IL-1ß and NLRP3 levels as compared to the wild-type. We suggest that genetic polymorphisms of P2X7R containing the Ala348 to Thr are associated with the increased risk of gout, showing an enhanced gain-of-function effect on the development of this disease.

Boosting the Thermoelectric Performance of the Doped DPP-EDOT Conjugated Polymer by Incorporating an Ionic Additive.

The thermoelectric (TE) performance of organic materials is limited by the coupling of Seebeck coefficient and electrical conductivity. Herein a new strategy is reported to boost the Seebeck coefficient of conjugated polymer without significantly reducing the electrical conductivity by incorporation of an ionic additive DPPNMe3 Br. The doped polymer PDPP-EDOT thin film exhibits high electrical conductivity up to 1377 ± 109 S cm-1 but low Seebeck coefficient below 30 µV K-1 and a maximum power factor of 59 ± 10 µW m-1 K-2 . Interestingly, incorporation of small amount (at a molar ratio of 1:30) of DPPNMe3 Br into PDPP-EDOT results in the significant enhancement of Seebeck coefficient along with the slight decrease of electrical conductivity after doping. Consequently, the power factor (PF) is boosted to 571 ± 38 µW m-1 K-2 and ZT reaches 0.28 ± 0.02 at 130 °C, which is among the highest for the reported organic TE materials. Based on the theoretical calculation, it is assumed that the enhancement of TE performance for the doped PDPP-EDOT by DPPNMe3 Br is mainly attributed to the increase of energetic disorder for PDPP-EDOT.

Iminyl-Radical-Mediated Formation of Covalent Au-N Bonds for Molecular Junctions.

The interaction between organic radicals and transition metals plays a crucial role in radical-mediated chemical reactions, functional devices, and biocatalysis. Characterizing such interactions, however, remains a long-standing challenge due to the inherently high reactivity of radical species. Here, using a scanning tunneling microscope breaking junction (STM-BJ) technique, we are able to detect the interaction mode between iminyl radicals and the gold surface at a single molecule level. We show that the free iminyl radicals generated through photochemical N-O bond homolysis of oxime esters react toward the gold electrode surface and produce covalent Au-N bonds. Intriguingly, we find that the Au-N bonding reactions lead to the formation of robust and highly conductive single-molecule junctions. These findings provide not only insights into the mechanism of iminyl-radical-involved reactions but also a facile photolysis method to create a new type of covalent electrode-molecule bonding contact for molecular devices.

The accumulation and release characteristics of heavy metals on the cultivation environment in Gracilaria litters during decay process.

Gracilaria bioremediates heavy metals (Cd, Cr, Pb, Ni, Cu, Zn, Fe, and Mn) and improves water quality in mariculture zones. However, Gracilaria litter produced during the growth and harvest process has become a critical bottleneck problem that limits the sustainable development of the Gracilaria cultivation industry. Experiments of decaying dried (dead) and frozen fresh (falling and dying) G. lemaneiformis and G. lichenosdies were carried out using the litterbag technique under laboratory-controlled and in situ conditions. The results showed that decay rates (k), decomposed time in 50 % (t50) and in 95 % (t95) varied between dried and frozen fresh Gracilaria and were different between G. lemaneiformis and G. lichenosdies. All Gracilaria samples showed an 80 %-90 % weight loss in 15-45 d. The variation in MAIs (accumulation index of metals) between the dried and frozen fresh Gracilaria litters differed significantly and provided evidence that metals could be imported or exported from litter to the environment. Based on our estimates from the 15-45 d experiment, the decay of Gracilaria can release and adsorb heavy metals. The enrichment of Fe, Pb, and Mn was more significant than the release, but the release of Cr, Zn, Cd, Pb, Cu, and Ni was more significant than the enrichment. Heavy metals in Gracilaria litters were accumulated and released simultaneously during decay. The present study simulated and underscores that Gracilaria cultivation intensely influences heavy metals recycled in marine environments It provides a theoretical basis for seaweed management for the sustainable development of the seaweed industry in the mariculture zone.

PET vascular activity score for predicting new angiographic lesions in patients with Takayasu arteritis: a Chinese cohort study.

OBJECTIVE: To investigate the ability of 18F-fluorodeoxyglucose PET/CT to predict new lesions in Takayasu arteritis. METHODS: Eighty-two Chinese patients with newly diagnosed Takayasu arteritis were recruited. Their clinical characteristics, serum biomarkers and imaging results were recorded at baseline and every visit. They were followed up for at least 2 years. New angiographic lesions were evaluated by magnetic resonance angiography. Baseline PET vascular activity scores (PETVAS) for predicting new lesions were evaluated. RESULTS: At baseline, a moderate correlation was observed between PETVAS and ESR (r = 0.74, P < 0.01) and CRP level (r = 0.69, P < 0.01). Overall, 18 (22%) patients showed new lesions on imaging during a median follow-up time of 36 months. The median time to the first occurrence of new lesions was 18 months. Compared with patients without new lesions, the patients with new lesions included more female patients (67.2% vs 94.4%, P = 0.03), patients with higher ESR values (20 vs 49, P = 0.02) and patients with active disease (62.5% vs 94.4%, P < 0.01). Multivariate Cox regression analysis revealed PETVAS was an independent risk factor for new angiographic lesions (PETVAS ≥8, hazard ratio = 7.56; 95% CI 2.20, 26.01, P < 0.01) with adjustment of age, sex, chest pain, ESR and Physician Global Assessment. Furthermore, patients with PETVAS ≥8 at baseline were more likely to experience adverse events including arterial ischaemic events during the follow-up. CONCLUSION: PETVAS showed good performance in predicting new lesions in Takayasu arteritis.

COVID-19 vaccine uptake, hesitancy and clinical effects on patients with Takayasu's arteritis: A web-based questionnaire survey from a large cohort.

Objective: This study aimed to investigate the Coronavirus disease 2019 (COVID-19) vaccination rate, reasons for vaccine hesitancy and clinical effects on patients with Takayasu's arteritis (TAK). Methods: A web-based survey was administered to a TAK cohort established by the Department of Rheumatology, Zhongshan Hospital through WeChat in April, 2022. Responses from a total of 302 patients were received. The Sinovac or Sinopharm inactivated vaccination rate, side effects, and vaccine hesitancy reasons were analyzed. In addition, disease flare, new disease onset, and changes of immune-related parameters after vaccination were analyzed in vaccinated patients. Results: Among 302 patients, 93 (30.79%) received the inactivated COVID-19 vaccination. Among the 209 unvaccinated patients, the most common reason for hesitancy were concern about side effects (136, 65.07%). Vaccinated patients had a longer disease duration (p = 0.08) and lower use of biologic agents (p < 0.001); 16 (17.20%) of the 93 vaccinated patients developed side effects, and most of them were mild; 8 (8.60%) developed disease flares or new-onset disease 12-128 days post-vaccination and 2 (2.15%) developed serious adverse effects (vision defect and cranial infarction). Immune-related parameters of 17 patients indicated decreases in IgA and IgM after vaccination (p < 0.05). Eighteen (19.35%) of the 93 vaccinated patients were diagnosed post-vaccination.These patients had a significantly higher percentage of CD19+ B cells at disease onset (p < 0.05) than the unvaccinated patients diagnosed at the same time. Conclusion: The vaccination rate was low in TAK, which was mainly caused by concerns about negative effects of vaccination on their disease. An acceptable safety profile was observed in vaccinated patients. The risk of disease flare associated with COVID-19 vaccination warrants further investigation.

Self-Doping Naphthalene Diimide Conjugated Polymers for Flexible Unipolar n-Type OTFTs.

The development of high-performance organic thin-film transistor (OTFT) materials is vital for flexible electronics. Numerous OTFTs are so far reported but obtaining high-performance and reliable OTFTs simultaneously for flexible electronics is still challenging. Herein, it is reported that self-doping in conjugated polymer enables high unipolar n-type charge mobility in flexible OTFTs, as well as good operational/ambient stability and bending resistance. New naphthalene diimide (NDI)-conjugated polymers PNDI2T-NM17 and PNDI2T-NM50 with different contents of self-doping groups on their side chains are designed and synthesized. The effects of self-doping on the electronic properties of resulting flexible OTFTs are investigated. The results reveal that the flexible OTFTs based on self-doped PNDI2T-NM17 exhibit unipolar n-type charge-carrier properties and good operational/ambient stability thanks to the appropriate doping level and intermolecular interactions. The charge mobility and on/off ratio are fourfold and four orders of magnitude higher than those of undoped model polymer, respectively. Overall, the proposed self-doping strategy is useful for rationally designing OTFT materials with high semiconducting performance and reliability.

A novel molecular mechanism of vascular fibrosis in Takayasu arteritis: macrophage-derived GPNMB promoting adventitial fibroblast extracellular matrix production in the aorta.

Takayasu arteritis (TAK) is a chronic large vessel disease characterized by aortic fibrotic thickening, which was mainly mediated by activation of aorta adventitial fibroblasts (AAFs). Our previous genetic study demonstrated that TAK-associated locus IL6 rs2069837 regulated glycoprotein non-metastatic melanoma protein B (GPNMB) expression. Thus, this study aimed to investigate the pathogenic role of GPNMB in TAK. Through pathological staining, we find that GPNMB was mainly expressed in vascular adventitia and positively correlated with adventitial extracellular matrix (ECM) expression in TAK vascular lesion. Specifically, GPNMB was increased in adventitial CD68+ macrophages, which were closely located with CD90+ adventitial fibroblasts. In in-vitro cell culture, THP-1-derived macrophages with GPNMB overexpression promoted ECM expression in AAFs. This effect was also confirmed in aortic tissue or AAFs culture with GPNMB overexpression or active GPNMB protein stimulation. Mechanistically, Co-IP assay and siRNA or inhibitor intervention demonstrated that integrin αVß1 receptor mediated GPNMB effect on AAFs, which also activated downstream Akt and Erk pathway in AAFs. Furthermore, we showed that leflunomide treatment inhibited GPNMB-mediated fibrosis in AAFs, as well as GPNMB expression in macrophages, which were also partially validated in leflunomide-treated patients. Taken together, these data indicated that macrophage-derived GPNMB promotes AAFs ECM expression via the integrin αVß1 receptor and Akt/Erk signaling pathway and leflunomide might play an anti-fibrotic role in TAK by interfering with the macrophage-derived GPNMB/AAFs axis. This study provides evidence that targeting GPNMB is a potential therapeutic strategy for treating vascular fibrosis in TAK.