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BACKGROUND: Microvascular complications are the major outcome of type 2 diabetes progression, and the underlying mechanism remains to be determined. METHODS: High-throughput RNA sequencing was performed using human monocyte samples from controls and diabetes. The transgenic mice expressing human CTSD (cathepsin D) in the monocytes was constructed using CD68 promoter. In vivo 2-photon imaging, behavioral tests, immunofluorescence, transmission electron microscopy, Western blot analysis, vascular leakage assay, and single-cell RNA sequencing were performed to clarify the phenotype and elucidate the molecular mechanism. RESULTS: Monocytes expressed high-level CTSD in patients with type 2 diabetes. The transgenic mice expressing human CTSD in the monocytes showed increased brain microvascular permeability resembling the diabetic microvascular phenotype, accompanied by cognitive deficit. Mechanistically, the monocytes release nonenzymatic pro-CTSD to upregulate caveolin expression in brain endothelium triggering caveolae-mediated transcytosis, without affecting the paracellular route of brain microvasculature. The circulating pro-CTSD activated the caveolae-mediated transcytosis in brain endothelial cells via its binding with low-density LRP1 (lipoprotein receptor-related protein 1). Importantly, genetic ablation of CTSD in the monocytes exhibited a protective effect against the diabetes-enhanced brain microvascular transcytosis and the diabetes-induced cognitive impairment. CONCLUSIONS: These findings uncover the novel role of circulatory pro-CTSD from monocytes in the pathogenesis of cerebral microvascular lesions in diabetes. The circulatory pro-CTSD is a potential target for the intervention of microvascular complications in diabetes.
Subject(s)
Cathepsin D , Diabetes Mellitus, Type 2 , Monocytes , Animals , Humans , Mice , Brain/metabolism , Cathepsin D/metabolism , Cathepsin D/pharmacology , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/genetics , Diabetes Mellitus, Type 2/metabolism , Endothelial Cells/metabolism , Endothelium, Vascular/metabolism , Enzyme Precursors , Mice, Transgenic , Monocytes/metabolism , Transcytosis/physiologyABSTRACT
ConspectusZinc oxide (ZnO) is a multipurpose material and finds its applications in various fields such as rubber manufacturing, medicine, food additives, electronics, etc. It has also been intensively studied in photocatalysis due to its wide band gap and environmental compatibility. Recently, heterogeneous catalysts with supported ZnOx species have attracted more and more attention for the dehydrogenation of propane (PDH) and isobutane (iBDH) present in shale/natural gas. The olefins formed in these reactions are key building blocks of the chemical industry. These reactions are also of academic importance for understanding the fundamentals of the selective activation of C-H bonds. Differently structured ZnOx species supported on zeolites, SiO2, and Al2O3 have been reported to be active for nonoxidative dehydrogenation reactions. However, the structure-activity-selectivity relationships for these catalysts remain elusive. The main difficulty stems from the preparation of catalysts containing only one kind of well-defined ZnOx species.In this Account, we describe the studies on PDH and iBDH over differently structured ZnOx species and highlight our approaches to develop catalysts with controllable ZnOx speciation relevant to their performance. Several methods, including (i) the in situ reaction of gas-phase metallic Zn atoms with OH groups on the surface of supports, (ii) one-pot hydrothermal synthesis, and (iii) impregnation/anchoring methods, have been developed/used for the tailored preparation of supported ZnOx species. The first method allows precise control of the molecular structure of ZnOx through the nature of the defective OH groups on the supports. Using this method, a series of ZnOx species ranging from isolated, binuclear to nanosized ZnOx have been successfully generated on different SiO2-based or ZrO2-based supports as demonstrated by complementary ex/in situ characterization techniques. Based on kinetic studies and detailed characterization results, the intrinsic activity (Zn-related turnover frequency) of ZnOx was found to depend on its speciation. It increases with an increasing number of Zn atoms in a ZnmOn cluster from 1 to a few atoms (less than 10) and then decreases strongly for ZnOx nanoparticles. The latter promote the formation of undesired C1-C2 hydrocarbons and coke, resulting in lower propene selectivity in comparison with the catalysts containing only ZnOx species ranging from isolated to subnanometer ZnmOn clusters. In addition, the strategy for improving the thermal stability of ZnOx species and the consequences of mass-transport limitations for DH reactions were also elucidated. The results obtained allowed us to establish the fundamentals for the targeted preparation of well-structured ZnOx species and the relationships between their structures and the DH performance. This knowledge may inspire further studies in the field of C-H bond activation and other reactions, in which ZnOx species act as catalytically active sites or promoters, such as the dehydroaromatization of light alkanes and the hydrogenation of CO2 to methanol.
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Early identification of safe and efficacious disease targets is crucial to alleviating the tremendous cost of drug discovery projects. However, existing experimental methods for identifying new targets are generally labor-intensive and failure-prone. On the other hand, computational approaches, especially machine learning-based frameworks, have shown remarkable application potential in drug discovery. In this work, we propose Progeni, a novel machine learning-based framework for target identification. In addition to fully exploiting the known heterogeneous biological networks from various sources, Progeni integrates literature evidence about the relations between biological entities to construct a probabilistic knowledge graph. Graph neural networks are then employed in Progeni to learn the feature embeddings of biological entities to facilitate the identification of biologically relevant target candidates. A comprehensive evaluation of Progeni demonstrated its superior predictive power over the baseline methods on the target identification task. In addition, our extensive tests showed that Progeni exhibited high robustness to the negative effect of exposure bias, a common phenomenon in recommendation systems, and effectively identified new targets that can be strongly supported by the literature. Moreover, our wet lab experiments successfully validated the biological significance of the top target candidates predicted by Progeni for melanoma and colorectal cancer. All these results suggested that Progeni can identify biologically effective targets and thus provide a powerful and useful tool for advancing the drug discovery process.
Subject(s)
Computational Biology , Drug Discovery , Machine Learning , Neural Networks, Computer , Humans , Computational Biology/methods , Drug Discovery/methods , Algorithms , Melanoma , Probability , Colorectal NeoplasmsABSTRACT
Covalent organic frameworks (COFs) have recently seen significant advancements. Large quantities of structurally & functionally oriented COFs with a wide range of applications, such as gas adsorption, catalysis, separation, and drug delivery, have been explored. Recent achievements in this field are primarily focused on advancing synthetic methodologies, with catalysts playing a crucial role in achieving highly crystalline COF materials, particularly those featuring novel linkages and chemistry. A series of reviews have already been published over the last decade, covering the fundamentals, synthesis, and applications of COFs. However, despite the pivotal role that catalysts and auxiliaries play in forming COF materials and adjusting their properties (e.g., crystallinity, porosity, stability, and morphology), limited attention has been devoted to these essential components. In this Critical Review, we mainly focus on the state-of-the-art progress of catalysts and auxiliaries applied to the synthesis of COFs. The catalysts include four categories: acid catalysts, base catalysts, transition-metal catalysts, and other catalysts. The auxiliaries, such as modulators, oxygen, and surfactants, are discussed as well. This is then followed by the description of several specific applications derived from the utilization of catalysts and auxiliaries. Lastly, a perspective on the major challenges and opportunities associated with catalysts and auxiliaries is provided.
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Photosynthesis of H2O2 from seawater represents a promising pathway to acquire H2O2, but it is still restricted by the lack of a highly active photocatalyst. In this work, we propose a convenient strategy of regulating the number of benzene rings to boost the catalytic activity of materials. This is demonstrated by ECUT-COF-31 with adding two benzene rings as the connector, which can result in 1.7-fold enhancement in the H2O2 production rate relative to ECUT-COF-30 with just one benzene ring as the connector. The reason for enhancement is mainly due to the release of *OOH from the surface of catalyst and the final formation of H2O2 being easier in ECUT-COF-31 than in ECUT-COF-30. Moreover, ECUT-COF-31 provides a stable photogeneration of H2O2 for 70 h, and a theoretically remarkable H2O2 production of 58.7 mmol per day from seawater using one gram of photocatalyst, while the cost of the used raw material is as low as 0.24 $/g.
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Homochiral MOF membranes offer a promising route to efficient chiral separation, but their fabrication remains challenging. Here, we report for the first time the design and preparation of homochiral polycrystalline MOF-808 membranes for the first time. The membrane exhibits a high integrity and thin membrane thickness. Achieving homochirality through chiral amino acid postsynthetic modification, MOF-808 membranes demonstrate remarkable solvent stability. Notably, they successfully separated racemic naproxen enantiomers, achieving enantiomeric excess (ee) values of up to â¼95.0%. This work paves the way for turning achiral polycrystalline MOF membranes into high-performance chiral membranes for enantioselective separation.
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The transformation of carbon dioxide (CO2) into functional materials has garnered considerable worldwide interest. Metal-organic frameworks (MOFs), as a distinctive class of materials, have made great contributions to CO2 capture and conversion. However, facile conversion of CO2 to stable porous MOFs for CO2 utilization remains unexplored. Herein, we present a facile methodology of using CO2 to synthesize stable zirconium-based MOFs. Two zirconium-based MOFs CO2-Zr-DEP and CO2-Zr-DEDP with face-centered cubic topology were obtained via a sequential desilylation-carboxylation-coordination reaction. The MOFs exhibit excellent crystallinity, as verified through powder X-ray diffraction and high-resolution transmission electron microscopy analyses. They also have notable porosity with high surface area (SBET up to 3688 m2 g-1) and good CO2 adsorption capacity (up to 12.5 wt %). The resulting MOFs have abundant alkyne functional moieties, confirmed through 13C cross-polarization/magic angle spinning nuclear magnetic resonance and Fourier transform infrared spectra. Leveraging the catalytic prowess of Ag(I) in diverse CO2-involved reactions, we incorporated Ag(I) into zirconium-based MOFs, capitalizing on their interactions with carbon-carbon π-bonds of alkynes, thereby forming a heterogeneous catalyst. This catalyst demonstrates outstanding efficiency in catalyzing the conversion of CO2 and propargylic alcohols into cyclic carbonates, achieving >99% yield at room temperature and atmospheric pressure conditions. Thus, this work provides a dual CO2 utilization strategy, encompassing the synthesis of CO2-based MOFs (20-24 wt % from CO2) and their subsequent application in CO2 capture and conversion processes. This approach significantly enhances overall CO2 utilization.
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Inverted p-i-n perovskite solar cells (PSCs) are easy to process but need improved interface characteristics with reduced energy loss to prevent efficiency drops when increasing the active photovoltaic area. Here, we report a series of poly ferrocenyl molecules that can modulate the perovskite surface enabling the construction of small- and large-area PSCs. We found that the perovskite-ferrocenyl interaction forms a hybrid complex with enhanced surface coordination strength and activated electronic states, leading to lower interfacial nonradiative recombination and charge transport resistance losses. The resulting PSCs achieve an enhanced efficiency of up to 26.08% for small-area devices and 24.51% for large-area devices (1.0208 cm2). Moreover, the large-area PSCs maintain >92% of the initial efficiency after 2000 h of continuous operation at the maximum power point under 1-sun illumination and 65 °C.
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BACKGROUND: The prognosis for patients with pancreatic ductal adenocarcinoma (PDAC) is poor. Secondary brain metastasis (Br-M) occurs in less than 1% of patients. Clinical characteristics and molecular alterations have not been characterized in this rare patients' subset. MATERIALS AND METHODS: The Foundry software platform was used to retrospectively query electronic health records for patients with Br-M secondary to PDAC from 2005 to 2023; clinical, molecular, and overall survival (OS) data were analyzed. RESULTS: Br-M was diagnosed in 44 patients with PDAC. Median follow-up was 78 months; median OS from initial PDAC diagnosis was 47 months. Median duration from PDAC diagnosis to Br-M detection was 24 months; median OS from Br-M diagnosis was 3 months. At Br-M diagnosis, 82% (nâ =â 36) of patients had elevated CA19-9. Lung was the most common preexisting metastatic location (71%) with Br-M, followed by liver (66%). Br-M were most frequently observed in the frontal lobe (34%, nâ =â 15), cerebellar region (23%, nâ =â 10), and leptomeninges (18%, nâ =â 8). KRAS mutations were detected in 94.1% (nâ =â 16) of patients who had molecular data available (nâ =â 17) with KRASG12V being the most frequent subtype 47% (nâ =â 8); KRASG12D in 29% (nâ =â 5); KRASG12R in 18% (nâ =â 3). Patients who underwent Br-M surgical resection (nâ =â 5) had median OS of 8.6 months, while median OS following stereotactic radiosurgery only (nâ =â 11) or whole-brain radiation only (nâ =â 20) was 3.3 and 2.8 months, respectively. CONCLUSION: Br-M is a late PDAC complication, resulting in an extremely poor prognosis especially in leptomeningeal disease. KRAS was mutated in 94.1% of the patients and the KRASG12V subtype was prevalent.
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A few-mode erbium-doped waveguide amplifier (FM-EDWA) with a confined Er3+ doped ring structure is proposed to equalize the differential modal gain (DMG). The FM-EDWA amplifying three spatial modes (LP01, LP11a and LP11b) is optimized by genetic algorithm and fabricated using precise lithography overlay alignment technology. We observe gain values of over 14â dB for all modes with DMG of 0.73â dB at 1529â nm pumped only with LP01 for the power of 200â mW. Furthermore, a flat gain of more than 10â dB is demonstrated across 1525-1565â nm, with a sufficiently low DMG of less than 1.3â dB.
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We propose a strip loaded amplifier employing SU-8 as the loaded waveguide and nanoparticles (NPs)-polymethyl methacrylate (PMMA) as the cladding layer. By leveraging the undoped SU-8 loaded waveguide, the polymer waveguide amplifier accomplished remarkably low transmission losses, reaching as low as 1.8â dB/cm at 1530â nm. We prepared NPs-PMMA nanocomposite by utilizing NaLu0.1Y0.7F4: Er3+, Yb3+ @NaLuF4 core-shell nanoparticles, which exhibited a significantly enhanced lifetime of 6.15â ms. An internal net gain of up to 17.7â dB was achieved on a strip loaded waveguide with a length as short as 0.5â cm when the on-chip pump power was 77â mW. Signal enhancement (SE) was measured at different wavelengths, revealing that the strip loaded waveguide exhibited broadband SE ranging from 1510â nm to 1570â nm, covering the C-band. To the best of our knowledge, this work has achieved the highest gain results reported thus far on a polymer matrix and provides an efficient method for optical amplification in passive devices on silicon and Si3N4 platforms, leveraging the ease of integration of polymer materials with diverse photonic platforms.
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OBJECTIVE: This study investigates the association between a new insulin resistance indicator, the triglyceride-glucose (TyG) index, and the risk of macrosomia. DESIGN: This is a prospective cohort study. METHODS: This study included 1332 women who delivered at Peking University International Hospital between October 2017 and August 2019. Participants were divided equally into three groups based on the TyG index. Logistic regression and restricted cubic spline (RCS) analyses were used to evaluate the relationship between the TyG index and macrosomia and conducted subgroup analyses. The TyG index's ability to predict macrosomia was assessed using the receiver operating characteristic (ROC) curve. RESULTS: Multivariable logistic regression analysis revealed that the TyG index is an independent risk factor for macrosomia (Odds ratio [OR] 1.84, 95% confidence interval [CI] 1.02-3.30, p < .05). RCS analysis indicates that the risk of macrosomia increases with the rise of the TyG index (p for nonlinearity <.001) when the TyG index is >6.53. Subgroup analysis showed a synergistic additive interaction between the TyG index and gestational diabetes mellitus (GDM) of macrosomia. The area under the ROC curve for the predictive model was 0.733 (95% CI 0.684, 0.781), with a sensitivity of 76.4% and specificity of 66.9%. Incorporating the TyG index alongside traditional risk factors notably enhances macrosomia prediction (p < .05). CONCLUSIONS: The TyG index independently predicts macrosomia, and exhibits an additive interaction with GDM in its occurrence. Integrating the TyG index with traditional risk factors improves the prediction of macrosomia. TRIAL REGISTRY: Clinical trials. gov [NCT02966405].
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Phosphor-in-glass-film (PiG-F) has been extensively investigated, showing great potential for use in laser lighting technique. Thickness is apparently a key parameter for PiG-F, affecting the heat dissipation, absorption, and reabsorption, thus determining the luminous efficacy and luminescence saturation threshold (LST). Conventional studies suggest that thinner films often have lower thermal load than that of the thicker ones. Unexpectedly, we found that the Lu3Al5O12:Ce (LuAG:Ce)-based PiG-F with a moderate thickness (78â µm) yielded the optimal LST of 31.9â W (14.2â W·mm-2, rather than 28.0â W (12.3â W·mm-2) for the thinnest one (56â µm). This unexpected result was further verified by thermal simulations. With the high saturation threshold together with a high luminous efficacy (â¼296â lm·W-1), an ultrahigh luminous flux of 7178â lm with a luminous exitance of 2930â lm·mm-2 was thus attained. We believe the new, to the best of our knowledge, findings in this study will substantially impact the design principles of phosphors for laser lighting.
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BACKGROUND: Adult head and neck rhabdomyosarcoma (HNRMS) is an exceptionally rare malignancy, and there is a paucity of data and research dedicated to understanding its characteristics and management in adult populations. This study aimed to assess the outcomes and identify survival predictors in adult HNRMS. METHODS: We retrospectively evaluated 42 adult patients (> 16 years) with HNRMS who received radiotherapy (RT)-based treatment at our institute between 2008 and 2022. We analysed the clinical characteristics and prognosis of these patients, including the locoregional recurrence-free survival (LRFS), progression-free survival (PFS), and overall survival (OS), using the Kaplan-Meier method. The chi-square and Fisher's exact tests were used to analyse differences between groups for dichotomous and categorical variables, respectively. Survival rates were calculated using the Kaplan-Meier method. Prognostic variables were assessed through univariate Cox analyses. RESULTS: The median patient age was 28 years (range, 16-82 years). Alveolar RMS was the most common histological type, observed in 21 patients (50.0%), followed by embryonal in 16 patients (38.1%). The anatomic sites of origin were orbital in one (2.4%), parameningeal in 26 (61.9%), and non-orbital/non-parameningeal in 15 (35.7%) patients. Nineteen patients (45.2%) had regional lymph node metastasis, and five patients (11.9%) presented with distant metastatic disease. Distant metastasis (n = 17) was the primary cause of treatment failure. At a median follow-up of 47.0 months, the 5-year LRFS, PFS, and OS rates were 69.0%, 39.7%, and 41.0%, respectively. Univariate analysis revealed that tumour size, lymph node involvement, and the local treatment pattern (surgery and RT vs. RT alone) were significant predictors of survival. CONCLUSIONS: The main failure pattern in patients with HNRMS receiving RT-based treatment was distant metastasis. Tumour size > 5 cm and lymph node involvement were predictors of worse LRFS. Multimodality local treatment, combining surgery and RT, is effective and provides survival benefits.
Subject(s)
Head , Rhabdomyosarcoma , Adult , Humans , Adolescent , Young Adult , Middle Aged , Aged , Aged, 80 and over , Retrospective Studies , Neck , Rhabdomyosarcoma/radiotherapy , Combined Modality TherapyABSTRACT
BACKGROUND: The Global Diet Quality Score (GDQS) is a simple and practical dietary metric associated with a number of chronic diseases. The GDQS included various foods related to blood pressure, especially diverse plant-based foods that have shown to lower blood pressure. However, studies on the role of the GDQS in reducing the risk of new-onset hypertension and whether its performance differs from that of other dietary metrics are lacking. OBJECTIVE: We aimed to examine the association between the GDQS and new-onset hypertension and to compare its performance with that of other dietary patterns, including the Plant-based Diet Index (PDI), alternate Mediterranean diet (aMED) score, Alternative Healthy Eating Index-2010, and Dietary Approaches to Stop Hypertension (DASH) score in Chinese adults. METHODS: We included a total of 12,002 participants (5644 males and 6358 females) aged >18 y from the China Health and Nutrition Survey (1997-2015). Dietary intake was estimated using average food intakes from 3 consecutive 24-h dietary recalls. Multivariable relative risks (RRs) were computed for hypertension using modified Poisson regression models. RESULTS: With ≤18 y of follow-up (mean 8.7± 5.4 y), we ascertained 4232 incident cases of hypertension. Compared with participants with a low GDQS score (<15), the multivariable-adjusted RR of hypertension was 0.72 [95% confidence interval (CI): 0.62, 0.83] among participants with a high score (≥23). A 25% increment in the GDQS was associated with a 30% (RR, 0.70; 95% CI: 0.64, 0.76) lower risk of new-onset hypertension, which was comparable with the RRs of new-onset hypertension associated with every 25% increment in the PDI (RR, 0.84; 95% CI: 0.76, 0.93), DASH score (RR, 0.84; 95% CI: 0.78, 0.91), and aMED score (RR, 0.89; 95% CI: 0.84, 0.93). CONCLUSION: A higher GDQS was associated with a lower risk of new-onset hypertension, with comparable associations of new-onset hypertension with PDI, DASH, and aMED scores in Chinese adults.
Subject(s)
Diet, Mediterranean , Dietary Approaches To Stop Hypertension , Hypertension , Adult , Male , Female , Humans , Cohort Studies , Diet , Hypertension/epidemiology , Hypertension/etiology , Diet, HealthyABSTRACT
INTRODUCTION: Renal fibrosis (RF), being the most important pathological change in the progression of CKD, is currently assessed by the evaluation of a biopsy. This present study aimed to apply a novel functional MRI (fMRI) protocol named amide proton transfer (APT) weighting to evaluate RF noninvasively. METHODS: Male Sprague-Dawley (SD) rats were initially subjected to bilateral kidney ischemia/reperfusion injury (IRI), unilateral ureteral obstruction, and sham operation, respectively. All rats underwent APT mapping on the 7th and 14th days after operation. Besides, 26 patients underwent renal biopsy at the Nephrology Department of Shanghai Tongji Hospital between July 2022 and May 2023. Patients underwent APT and apparent diffusion coefficient (ADC) mappings within 1 week before biopsy. MRI results of both patients and rats were calculated by comparing with gold standard histology for fibrosis assessment. RESULTS: In animal models, the cortical APT (cAPT) and medullary APT (mAPT) values were positively correlated with the degree of RF. Compared to the sham group, IRI group showed significantly increased cAPT and mAPT values on the 7th and 14th days after surgery, but no group differences were found in ADC values. Similar results were found in human patients. Cortical/medullary APT values were significantly increased in patients with moderate-to-severe fibrosis than in patients with mild fibrosis. ROC curve analysis indicated that APT value displayed a better diagnostic value for RF. Furthermore, combination of cADC and cAPT improved fibrosis detection by imaging variables alone (p < 0.1). CONCLUSION: APT values had better diagnostic capability at early stage of RF compared to ADC values, and the addition of APT imaging to conventional ADC will significantly improve the diagnostic performance for predicting kidney fibrosis.
Subject(s)
Fibrosis , Kidney , Magnetic Resonance Imaging , Rats, Sprague-Dawley , Male , Animals , Fibrosis/diagnostic imaging , Humans , Rats , Middle Aged , Kidney/diagnostic imaging , Kidney/pathology , Magnetic Resonance Imaging/methods , Reperfusion Injury/diagnostic imaging , Female , Adult , Amides , Protons , Kidney Diseases/diagnostic imaging , Kidney Diseases/pathology , Kidney Diseases/diagnosis , Aged , Renal Insufficiency, Chronic/diagnostic imaging , Renal Insufficiency, Chronic/pathology , Ureteral Obstruction/diagnostic imaging , Disease Models, AnimalABSTRACT
A critical constraint impeding the utilization of Mn-based oxide catalysts in NH3 selective catalytic reduction (NH3-SCR) is their inadequate resistance to water and sulfur. This vulnerability primarily arises from the propensity of SO2 to bind to the acidic site in manganese oxide, resulting in the formation of metal sulfate and leading to the irreversible deactivation of the catalyst. Therefore, gaining a comprehensive understanding of the detrimental impact of SO2 on the acidic sites and elucidating the underlying mechanism of this toxicity are of paramount importance for the effective application of Mn-based catalysts in NH3-SCR. Herein, we strategically modulate the acidity of the manganese oxide catalyst surface through the incorporation of Ce and Nb. Comprehensive analyses, including thermogravimetry, NH3 temperature-programmed desorption, in situ diffused reflectance infrared Fourier transform spectroscopy, and density functional theory calculations, reveal that SO2 exhibits a propensity for adsorption at strongly acidic sites. This mechanistic understanding underscores the pivotal role of surface acidity in governing the sulfur resistance of manganese oxide.
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OBJECTIVE: Here, we explored the phenotype and function of MAIT cells in the peripheral blood of patients with HSP. METHODS: Blood samples from HSP patients and HDs were assessed by flow cytometry and single-cell RNA sequencing to analyze the proportion, phenotype, and function of MAIT cells. Th-cytokines in the serum of HSP patients were analyzed by CBA. IgA in cocultured supernatant was detected by CBA to analyze antibody production by B cells. RESULTS: The percentage of MAIT cells in HSP patients was significantly reduced compared with that in HDs. Genes related to T cell activation and effector were up-regulated in HSP MAIT cells, indicating a more activated phenotype. In addition, HSP MAIT cells displayed a Th2-like profile with the capacity to produce more IL-4 and IL-5, and IL-4 was correlated with IgA levels in the serum of HSP patients. Furthermore, CD40L was up-regulated in HSP MAIT cells, and CD40L+ MAIT cells showed an increased ability to produce IL-4 and to enhance IgA production by B cells. CONCLUSION: Our data demonstrate that MAIT cells in HSP patients exhibit an activated phenotype. The enhanced IL-4 production and CD40L expression of MAIT cells in HSP patients could take part in the pathogenesis of HSP.
Subject(s)
IgA Vasculitis , Mucosal-Associated Invariant T Cells , Humans , Antibody Formation , CD40 Ligand , Immunoglobulin A , Interleukin-4ABSTRACT
The effective coupling of photoinduced alcohol oxidation and water reduction may economically produce hydrogen (H2) from water, which is of great significance in solving the current energy crisis. This study discloses that decatungstate (DT) and especially Ni2+ions-doped DTs are active for the photoreaction of benzyl alcohol with H2O, and under 48 h of violet light illumination, the best 1%Ni-DT yields ca. 86.1% benzoic acid and a 4.65 h-1 H2 generation efficiency (turnover frequency, TOF). Also, 1%Ni-DT is efficient for the photoredox coupling reaction of aliphatic and especially aromatic primary/secondary alcohols with water. A series of characterizations support that the doubled-reduced H2DT produced from the photoreaction plays a key role in water reduction to H2, which is accelerated by the doped Ni2+. In particular, it and the derived Ni3+ may construct a Z-type catalyst for water overall splitting, thereby hoisting the acid yield and H2 amount in the later stage of the photoreaction.
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Lymph node tuberculosis is particularly common in regions with a high tuberculosis burden, and it has a great risk of rupture. This study aims to investigate the utility of ultrasound multimodal imaging in predicting the rupture of cervical tuberculous lymphadenitis (CTL). 128 patients with unruptured CTL confirmed by pathology or laboratory tests were included. Various ultrasonic image features, including long-to-short-axis ratio (L/S), margin, internal echotexture, coarse calcification, Color Doppler Flow Imaging (CDFI), perinodal echogenicity, elastography score, and non-enhanced area proportion in contrast-enhanced ultrasound (CEUS), were analyzed to determine their predictive value for CTL rupture within a one-year follow-up period. As a result, L/S (P < 0.001), margin (P < 0.001), internal echotexture (P < 0.001), coarse calcification (P < 0.001), perinodal echogenicity (P < 0.001), and the area of non-enhancement in CEUS (P < 0.001) were identified as significant imaging features for predicting CTL rupture. The prognostic prediction showed a sensitivity of 89.29%, specificity of 100%, accuracy of 95.31%, respectively. Imaging findings such as L/S < 2, unclear margin, heterogeneous internal echotexture, perinodal echogenicity changed, and non-enhancement area in CEUS > 1/2, are indicative of CTL rupture, while coarse calcification in the lymph nodes is associated with a favorable prognosis.