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Purpose: Lichen sclerosus urethral stricture disease (LS USD) is a refractory and progressive disease primarily affecting the anterior urethra in males. Various potential etiological factors, such as genetics, autoimmunity, infection, and exposure to infectious urine, have been suggested. However, the accurate etiology of LS in the male urethra remains unclear. Patients and Methods: In this study, we conducted single-cell RNA sequencing to identify the transcriptional profiles of three patients with LS USD and three patients with non-LS USD. Immunofluorescence was used to confirm the single-cell sequence results. Results: Our study revealed distinct subsets of vein endothelial cells (ECs), smooth muscle cells (SMCs), and fibroblasts (FBs) with high proportions in LS USD, contributing to the tissue microenvironment primarily involved in proinflammatory and immune responses. In particular, FBs displayed a unique subset, Fib7, which is exclusively present in LS USD, and exhibited high expression levels of SAA1 and SAA2. The accumulation of macrophages, along with the dysregulated ratios of M1/M2-like phenotype macrophages, may be engaged in the pathogenesis of LS USD. Through cell-cell communication analysis, we identified significant interactions involving CXCL8/ACKR1 and CCR7/CCL19 in LS USD. Remarkably, Fib7 exhibited exclusive communication with IL-1B macrophages through the SAA1/FPR2 receptor-ligand pair. Conclusion: Our study provides a profound understanding of the tissue microenvironment in LS USD, which may be valuable for understanding the pathogenesis of LS USD.
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Prostate cancer (PCa) rarely responds to immune-checkpoint blockade (ICB) therapies. Cancer-associated fibroblasts (CAFs) are critical components of the immunologically "cold" tumor microenvironment and are considered a promising target to enhance the immunotherapy response. In this study, we aimed to reveal the mechanisms regulating CAF plasticity to identify potential strategies to switch CAFs from pro-tumorigenic to anti-tumor phenotypes and enhance ICB efficacy in PCa. Integration of four PCa single-cell RNA-sequencing datasets defined pro-tumorigenic and anti-tumor CAFs, and RNA-seq, flow cytometry, and a PCa organoid model demonstrated the functions of two CAF subtypes. Extracellular matrix-associated CAFs (ECM-CAF) promoted collagen deposition and cancer cell progression, and lymphocyte-associated CAFs (Lym-CAF) exhibited an anti-tumor phenotype and induced the infiltration and activation of CD8+ T cells. YAP1 activity regulated the ECM-CAF phenotype, and YAP1 silencing promoted switching to Lym-CAFs. NF-κB p65 was the core transcription factor in the Lym-CAF subset, and YAP1 inhibited nuclear translocation of p65. Selective depletion of YAP1 in ECM-CAFs in vivo promoted CD8+ T-cell infiltration and activation and enhanced the therapeutic effects of anti- PD-1 treatment in PCa. Overall, this study revealed a mechanism regulating CAF identity in PCa and highlighted a therapeutic strategy for altering the CAF subtype to suppress tumor growth and increase sensitivity to ICB.
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Conventional androgen deprivation therapy (ADT) targets the androgen receptor (AR) inhibiting prostate cancer (PCa) progression; however, it can eventually lead to recurrence as castration-resistant PCa (CRPC), which has high mortality rates and lacks effective treatment modalities. The study confirms the presence of high glutathione peroxidase 4 (GPX4) expression, a key regulator of ferroptosis (i.e., iron-dependent program cell death) in CRPC cells. Therefore, inducing ferroptosis in CRPC cells might be an effective therapeutic modality for CRPC. However, nonspecific uptake of ferroptosis inducers can result in undesirable cytotoxicity in major organs. Thus, to precisely induce ferroptosis in CRPC cells, a genetic engineering strategy is proposed to embed a prostate-specific membrane antigen (PSMA)-targeting antibody fragment (gy1) in the macrophage membrane, which is then coated onto mesoporous polydopamine (MPDA) nanoparticles to produce a biomimetic nanoplatform. The results indicate that the membrane-coated nanoparticles (MNPs) exhibit high specificity and affinity toward CRPC cells. On further encapsulation with the ferroptosis inducers RSL3 and iron ions, MPDA/Fe/RSL3@M-gy1 demonstrates superior synergistic effects in highly targeted ferroptosis therapy eliciting significant therapeutic efficacy against CRPC tumor growth and bone metastasis without increased cytotoxicity. In conclusion, a new therapeutic strategy is reported for the PSMA-specific, CRPC-targeting platform for ferroptosis induction with increased efficacy and safety.
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BACKGROUND: Ultrasound-guided prostate biopsy is a reliable diagnostic procedure for prostate cancer diagnosis with minimal procedure-related trauma. However, complications, such as massive rectal bleeding may occur after the puncture. We hypothesized that using a transrectal resectoscope could help treat massive rectal bleeding after transrectal prostate punctures. AIM: To identify a simple and effective treatment for massive rectal bleeding after transrectal prostate punctures. METHODS: Patients requiring treatment for massive rectal bleeding after transrectal prostate punctures were included. A SIMAI resectoscope was inserted through the anus. Direct electrocoagulation was performed for superficial bleeding points. Part of the rectal mucosa or surface muscle layer was removed to expose deep bleeding points, followed by electrocoagulation. An electric cutting ring was used to compress and stop the bleeding for jet-like points before electrocoagulation. The fluid color in the drainage tube was monitored postoperatively for continuous bleeding. RESULTS: Eight patients were included from 2012 to 2022. None of the patients with massive rectal bleeding after the transrectal prostate punctures improved with conventional conservative and blood transfusion treatments. Two patients had an inferior artery embolism, and digital subtraction angiography was ineffective. All patients received emergency transanal prostate resection, which immediately stopped the bleeding. Four days after the procedure, the patients had recovered and were discharged. CONCLUSION: Using a transanal prostate resection instrument is a simple, safe, and effective method for treating massive rectal bleeding after transrectal prostate punctures.
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BACKGROUND: An increasing number of studies have begun to discuss the relationship between gut microbiota and diseases, yet there is currently a lack of corresponding articles describing the association between gut microbiota and hepatocellular carcinoma (HCC) and biliary tract cancer (BTC). This study aims to explore the relationship between them using Mendelian randomization (MR) analysis method. AIM: To assess the relationship between gut microbiota and HCC and BTC. METHODS: We obtained Genome-wide association study (GWAS) data for the gut microbiome from the intestinal microbiota genomic library (MiBioGen, https://mibiogen.gcc.rug.nl/). Additionally, we accessed data pertaining to HCC and BTC from the IEU open GWAS platform (https://gwas.mrcieu.ac.uk/). Our analysis employed fundamental instrumental variable analysis methods, including inverse-variance weighted, MR and Egger. To ensure the dependability of the results, we subjected the results to tests for multiple biases and heterogeneity. RESULTS: During our investigation, we discovered 11 gut microbiota linked to an increased risk to BTC and HCC. The former included the genus Eubacterium hallii group (P = 0.017), Candidatus Soleaferrea (P = 0.034), Flavonifractor (P = 0.021), Lachnospiraceae FCS020 (P = 0.034), the order Victivallales (P = 0.018), and the class Lentisphaeria (P = 0.0.18). The latter included the genus Desulfovibrio (P = 0.042), Oscillibacter (P = 0.023), the family Coriobacteriaceae (P = 0.048), the order Coriobacteriales (P = 0.048), and the class Coriobacteriia (P = 0.048). Furthermore, in BTC, we observed 2 protective gut microbiota namely the genus Dorea (P = 0.041) and Lachnospiraceae ND3007 group (P = 0.045). All results showed no evidence of multiplicity or heterogeneity. CONCLUSION: This study explores a causal link between gut microbiota and HCC and BTC. These insights may enhance the mechanistic knowledge of microbiota-related HCC and BTC pathways, potentially informing therapeutic strategies.
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In recent years, halide perovskites have attracted considerable attention for photocatalytic CO2 reduction. However, the presence of surface defects and the lack of specific catalytic sites for CO2 reduction lead to low photocatalytic performance. In this study, we demonstrate a facile method that post-treats CsPbBr3 with ZnBr2 for photocatalytic CO2 reduction. Our experimental and characterization results show that ZnBr2 has a dual role: the Br- ions in ZnBr2 passivate Br vacancies (VBr) on the CsPbBr3 surface, while Zn2+ cations act as catalytic sites for CO2 reduction. The ZnBr2-CsPbBr3 achieves a photocatalytic CO evolution rate of 57 µmol g-1 h-1, which is nearly three times higher than that of the pristine CsPbBr3. The enhanced performance over ZnBr2-CsPbBr3 is mainly due to the decreased VBr and lower reaction energy barrier for CO2 reduction. This work presents an effective method to simultaneously passivate surface defects and introduce catalytic sites, providing useful guidance for the regulation of perovskite photoelectric properties and the design of efficient photocatalysts.
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BACKGROUND: Prophylactic dose of rivaroxaban is often used in treatment of isolated calf muscle vein thrombosis (ICMVT); nevertheless, its effect is less reported. This study aims to evaluate short-term outcomes in patients with ICMVT who received prophylactic dose of rivaroxaban or warfarin therapy. METHODS: A retrospective analysis of 472 ICMVT patients who received 2 different treatment regimens was undertaken. Propensity score matching method was used to balance the confounding effect of baseline clinical data. Chi-squared test and logistic regression analysis were used to compare outcomes (venous thromboembolism events, bleeding events, complete clot resolution) according to the type of treatment regimens before and after propensity score matching. Univariate and multivariable analysis were used to investigate risk factors for incomplete clot resolution of ICMVT after propensity score matching. RESULTS: 242 ICMVT patients received prophylactic dose of rivaroxaban (rivaroxaban group, RG), and 230 received warfarin (warfarin group, WG). After propensity score matching, 156 patients were included in each group; Venous thromboembolism (VTE) events occurred in 14 (9.0%) patients in the RG and 10 (6.4%) in the WG (P = 0.395); no major bleeding events occurred in each group, and clinically relevant nonmajor bleeding events occurred in 5 (3.2%) patients in the RG and 10 (6.4%) in the WG (P = 0.186); complete clot resolution at 3 months occurred in 80 (51.3%) patients in the RG and 100 (64.1%) in the WG (P = 0.022). Logistic regression analysis showed that there were no significant differences between RG and WG in VTE events (odds ratio 1.439, 95% confidence interval 0.619-3.347, P = 0.397) and clinically relevant nonmajor bleeding events (odds ratio 0.483, 95% confidence interval 0.161-1.449, P = 0.194); it revealed that complete clot resolution rate at 3 months was different in the 2 groups (odds ratio 0.589, 95% confidence interval 0.375-0.928, P = 0.022). Treatment regimens (prophylactic dose of rivaroxaban), thrombosis (maximum diameter >7 mm), and risk factors for VTE (nonsurgery risk factors, mainly referring to active malignancy) were risk factors for incomplete clot resolution of ICMVT (P < 0.05). CONCLUSIONS: In this retrospective study with a short-term follow-up, ICMVT patients who received prophylactic dose of rivaroxaban had no significant differences in VTE and bleeding events compared to those who received warfarin therapy (the overall INR >2.0 for >50% of the time); but it was not conducive to complete clot resolution.
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Selective producing ethanol from CO2 electroreduction is highly demanded, yet the competing ethylene generation route is commonly more thermodynamically preferred. Herein, we reported an efficient CO2-to-ethanol conversion (53.5 % faradaic efficiency at -0.75â V versus reversible hydrogen electrode (vs. RHE)) over an oxide-derived nanocubic catalyst featured with abundant "embossment-like" structured grain-boundaries. The catalyst also attains a 23.2 % energy efficiency to ethanol within a flow cell reactor. In situ spectroscopy and electrochemical analysis identified that these dualphase Cu(I) and Cu(0) sites stabilized by grain-boundaries are very robust over the operating potential window, which maintains a high concentration of co-adsorbed *CO and hydroxyl (*OH) species. Theoretical calculations revealed that the presence of *OHad not only promote the easier dimerization of *CO to form *OCCO (ΔG~0.20â eV) at low overpotentials but also preferentially favor the key *CHCOH intermediate hydrogenation to *CHCHOH (ethanol pathway) while suppressing its dehydration to *CCH (ethylene pathway), which is believed to determine the remarkable ethanol selectivity. Such imperative intermediates associated with the bifurcation pathway were directly distinguished by isotope labelling in situ infrared spectroscopy. Our work promotes the understanding of bifurcating mechanism of CO2ER-to-hydrocarbons more deeply, providing a feasible strategy for the design of efficient ethanol-targeted catalysts.
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Five new B-seco-limonoids, namely toonanoronoids A-E (1-5), in conjunction with three previously reported compounds, were isolated from the EtOAc extract of the twigs and leaves of Toona ciliata var. yunnanensis. Their structures were elucidated through comprehensive spectroscopic and X-ray crystallographic analysis. The cytotoxic activities of new compounds against five human tumor cell lines (HL-60, SMMC-7721, A549, MCF-7, and SW480) were screened, Compounds 4 and 5 exerted inhibition toward two tumor cell lines (HL-60, SW-480) with IC50 values between 1.7 and 5.9 µM.
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Antineoplásicos Fitogénicos , Limoninas , Fitoquímicos , Hojas de la Planta , Toona , Humanos , Estructura Molecular , Línea Celular Tumoral , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/aislamiento & purificación , Hojas de la Planta/química , Limoninas/aislamiento & purificación , Limoninas/farmacología , Limoninas/química , Fitoquímicos/aislamiento & purificación , Fitoquímicos/farmacología , China , Toona/química , Tallos de la Planta/químicaRESUMEN
Renal cell carcinoma (RCC) is a hot tumor infiltrated by large numbers of CD8+ T cells and is highly sensitive to immunotherapy. However, tumor-associated macrophages (TAMs), mainly M2 macrophages, tend to undermine the efficacy of immunotherapy and promote the progression of RCC. Here, macrophage-derived nanosponges are fabricated by M2 macrophage membrane-coated polyï¼lactic-co-glycolic acidï¼ï¼PLGAï¼, which could chemotaxis to the CXC and CC chemokine subfamily-enriched RCC microenvironment via corresponding membrane chemokine receptors. Subsequently, the nanosponges act like cytokine decoys to adsorb and neutralize broad-spectrum immunosuppressive cytokines such as colony stimulating factor-1(CSF-1), transforming growth factor-ßï¼TGF-ßï¼, and Lnterleukin-10ï¼IL-10ï¼, thereby reversing the polarization of M2-TAMs toward the pro-inflammatory M1 phenotype, and enhancing the anti-tumor effect of CD8+ T cells. To further enhance the polarization reprogramming efficiency of TAMs, DSPE-PEG-M2pep is conjugated on the surface of macrophage-derived nanosponges for specific recognition of M2-TAMs, and the toll like receptors 7/8ï¼TLR7/8ï¼ agonist, R848, is encapsulated in these nanosponges to induce M1 polarization, which result in significant efficacy against RCC. In addition, these nanosponges exhibit undetectable biotoxicity, making them suitable for clinical applications. In summary, a promising and facile strategy is provided for immunomodulatory therapies, which are expected to be used in the treatment of tumors, autoimmune diseases, and inflammatory diseases.
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Carcinoma de Células Renales , Citocinas , Inmunoterapia , Neoplasias Renales , Macrófagos , Carcinoma de Células Renales/terapia , Carcinoma de Células Renales/inmunología , Carcinoma de Células Renales/patología , Animales , Inmunoterapia/métodos , Neoplasias Renales/terapia , Neoplasias Renales/inmunología , Neoplasias Renales/patología , Citocinas/metabolismo , Ratones , Humanos , Macrófagos/inmunología , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Macrófagos Asociados a Tumores/inmunología , Macrófagos Asociados a Tumores/efectos de los fármacos , Línea Celular Tumoral , Linfocitos T CD8-positivos/inmunología , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , Microambiente Tumoral/efectos de los fármacosRESUMEN
Efficient and stable oxygen reduction reaction (ORR) catalysts are essential for constructing reliable energy conversion and storage devices. Herein, we prepared noble metal-free FeCoNiMnV high-entropy alloy supported on nitrogen-doped carbon nanotubes (FeCoNiMnV HEA/N-CNTs) by a one-step pyrolysis at 800 °C, as certificated by a set of characterizations. The graphitization degree of the N-CHTs was optimized by tuning the pyrolysis temperature in the control groups. The resultant catalyst greatly enhanced the ORR characteristics in the alkaline media, showing the positive onset potential (Eonset) of 0.99 V and half-wave potential (E1/2) of 0.85 V. More importantly, the above FeCoNiMnV HEA/N-CNTs assembled Zn-air battery exhibited a greater open-circuit voltage (1.482 V), larger power density (185.12 mW cm-2), and outstanding cycle stability (1698 cycles, 566 h). This study provides some valuable insights on developing sustainable ORR catalysts in Zn-air batteries.
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Endosialin, also known as tumor endothelial marker 1 (TEM1) or CD248, is a single transmembrane glycoprotein with a C-type lectin-like domain. Endosialin is mainly expressed in the stroma, especially in cancer-associated fibroblasts and pericytes, in most solid tumors. Endosialin is also expressed in tumor cells of most sarcomas. Endosialin can promote tumor progression through different mechanisms, such as promoting tumor cell proliferation, adhesion and migration, stimulating tumor angiogenesis, and inducing an immunosuppressive tumor microenvironment. Thus, it is considered an ideal target for cancer treatment. Several endosialin-targeted antibodies and therapeutic strategies have been developed and have shown preliminary antitumor effects. Here, we reviewed the endosialin expression pattern in different cancer types, discussed the mechanisms by which endosialin promotes tumor progression, and summarized current therapeutic strategies targeting endosialin.
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Antígenos de Neoplasias , Neoplasias , Humanos , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Neovascularización Patológica/patología , Pericitos/metabolismo , Microambiente Tumoral , Antígenos CD/metabolismoRESUMEN
The plant genome produces an extremely large collection of long noncoding RNAs (lncRNAs) that are generally expressed in a context-specific manner and have pivotal roles in regulation of diverse biological processes. Here, we mapped the transcriptional heterogeneity of lncRNAs and their associated gene regulatory networks at single-cell resolution. We generated a comprehensive cell atlas at the whole-organism level by integrative analysis of 28 published single-cell RNA sequencing (scRNA-seq) datasets from juvenile Arabidopsis seedlings. We then provided an in-depth analysis of cell-type-related lncRNA signatures that show expression patterns consistent with canonical protein-coding gene markers. We further demonstrated that the cell-type-specific expression of lncRNAs largely explains their tissue specificity. In addition, we predicted gene regulatory networks on the basis of motif enrichment and co-expression analysis of lncRNAs and mRNAs, and we identified putative transcription factors orchestrating cell-type-specific expression of lncRNAs. The analysis results are available at the single-cell-based plant lncRNA atlas database (scPLAD; https://biobigdata.nju.edu.cn/scPLAD/). Overall, this work demonstrates the power of integrative single-cell data analysis applied to plant lncRNA biology and provides fundamental insights into lncRNA expression specificity and associated gene regulation.
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Arabidopsis , ARN Largo no Codificante , Redes Reguladoras de Genes , ARN Largo no Codificante/genética , Arabidopsis/genética , Análisis de Expresión Génica de una Sola Célula , Regulación de la Expresión GénicaRESUMEN
Pancreatic ductal adenocarcinoma (PDAC) is a highly metastatic disease refractory to all targeted and immune therapies. However, our understanding of PDAC microenvironment especially the metastatic microenvironment is very limited partly due to the inaccessibility to metastatic tumor tissues. Here, we present the single-cell transcriptomic landscape of synchronously resected PDAC primary tumors and matched liver metastases. We perform comparative analysis on both cellular composition and functional phenotype between primary and metastatic tumors. Tumor cells exhibit distinct transcriptomic profile in liver metastasis with clearly defined evolutionary routes from cancer cells in primary tumor. We also identify specific subtypes of stromal and immune cells critical to the formation of the pro-tumor microenvironment in metastatic lesions, including RGS5+ cancer-associated fibroblasts, CCL18+ lipid-associated macrophages, S100A8+ neutrophils and FOXP3+ regulatory T cells. Cellular interactome analysis further reveals that the lack of tumor-immune cell interaction in metastatic tissues contributes to the formation of the immunosuppressive microenvironment. Our study provides a comprehensive characterization of the transcriptional landscape of PDAC liver metastasis.
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Carcinoma Ductal Pancreático , Neoplasias Hepáticas , Neoplasias Pancreáticas , Humanos , Transcriptoma , Microambiente Tumoral/genética , Neoplasias Pancreáticas/genética , Neoplasias Hepáticas/genética , Carcinoma Ductal Pancreático/genética , Inmunosupresores , Neoplasias PancreáticasRESUMEN
The preoperative Gleason grade group (GG) from transrectal ultrasound-guided prostate biopsy is crucial for treatment decisions but may underestimate the postoperative GG and miss clinically significant prostate cancer (csPCa), particularly in patients with biopsy GG1. In such patients, an SUVmax of at least 12 has 100% specificity for detecting csPCa. In patients with an SUVmax of less than 12, we aimed to develop a model to improve the diagnostic accuracy of csPCa. Methods: The study retrospectively included 56 prostate cancer patients with transrectal ultrasound-guided biopsy GG1 and an SUVmax of less than 12 from 2 tertiary hospitals. All [68Ga]Ga-PSMA-HBED-CC PET scans were centrally reviewed in Xijing Hospital. A deep learning model was used to evaluate the overlap of SUVmax (size scale, 3 cm) and the level of Gleason pattern (size scale, 500 µm). A diagnostic model was developed using the PRIMARY score and SUVmax, and its discriminative performance and clinical utility were compared with other methods. The 5-fold cross-validation (repeated 1,000 times) was used for internal validation. Results: In patients with GG1 and an SUVmax of less than 12, significant prostate-specific membrane antigen (PSMA) histochemical score (H-score) H-score overlap occurred among benign gland, Gleason pattern 3, and Gleason pattern 4 lesions, causing SUVmax overlap between csPCa and non-csPCa. The model of 10 × PRIMARY score + 2 × SUVmax exhibited a higher area under the curve (AUC, 0.8359; 95% CI, 0.7233-0.9484) than that found using only the SUVmax (AUC, 0.7353; P = 0.048) or PRIMARY score (AUC, 0.7257; P = 0.009) for the cohort and a higher AUC (0.8364; 95% CI, 0.7114-0.9614) than that found using only the Prostate Imaging Reporting and Data System (PI-RADS) score of 5-4 versus 3-1 (AUC, 0.7036; P = 0.149) and the PI-RADS score of 5-3 versus 2-1 (AUC, 0.6373; P = 0.014) for a subgroup. The model reduced the misdiagnosis of the PI-RADS score of 5-4 versus 3-1 by 78.57% (11/14) and the PI-RADS score of 5-3 versus 2-1 by 77.78% (14/18). The internal validation showed that the mean 5-fold cross-validated AUC was 0.8357 (95% CI, 0.8357-0.8358). Conclusion: We preliminarily suggest that the model of 10 × PRIMARY score + 2 × SUVmax may enhance the diagnostic accuracy of csPCa in patients with biopsy GG1 and an SUVmax of less than 12 by maximizing PSMA information use, reducing the misdiagnosis of the PI-RADS score, and thereby aiding in making appropriate treatment decisions.
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Neoplasias de la Próstata , Masculino , Humanos , Neoplasias de la Próstata/patología , Próstata/patología , Estudios Retrospectivos , Imagen por Resonancia Magnética/métodos , Antígeno Prostático Específico/análisis , Biopsia Guiada por Imagen/métodosRESUMEN
Electrochemical CO2 reduction reaction (CO2 RR) provides a promising approach for sustainable chemical fuel production of carbon neutrality. Neutral and alkaline electrolytes are predominantly employed in the current electrolysis system, but with striking drawbacks of (bi)carbonate (CO3 2- /HCO3 - ) formation and crossover due to the rapid and thermodynamically favourable reaction between hydroxide (OH- ) with CO2 , resulting in low carbon utilization efficiency and short-lived catalysis. Very recently, CO2 RR in acidic media can effectively address the (bi)carbonate issue; however, the competing hydrogen evolution reaction (HER) is more kinetically favourable in acidic electrolytes, which dramatically reduces CO2 conversion efficiency. Thus, it is a big challenge to effectively suppress HER and accelerate acidic CO2 RR. In this review, we begin by summarizing the recent progress of acidic CO2 electrolysis, discussing the key factors limiting the application of acidic electrolytes. We then systematically discuss addressing strategies for acidic CO2 electrolysis, including electrolyte microenvironment modulation, alkali cations adjusting, surface/interface functionalization, nanoconfinement structural design, and novel electrolyzer exploitation. Finally, the new challenges and perspectives of acidic CO2 electrolysis are suggested. We believe this timely review can arouse researchers' attention to CO2 crossover, inspire new insights to solve the "alkalinity problem" and enable CO2 RR as a more sustainable technology.
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As a sustainable approach for N2 fixation, electrocatalytic N2 reduction reaction (N2RR) to produce ammonia (NH3) is highly desirable with a precise understanding to the structure-activity relationship of electrocatalysts. Here, firstly, we obtain a novel carbon-supported oxygen-coordinated single-Fe-atom catalyst for highly efficient production of ammonia from electrocatalytic N2RR. Based on such new type of N2RR electrocatalyst, by combining operando X-ray absorption spectra (XAS) with density function theory calculation, we reveal significantly that the as-prepared active coordination structure undergoes a potential-driven two-step restructuring, firstly from FeSAO4(OH)1a to FeSAO4(OH)1a'(OH)1b with the adsorption of another -OH on FeSA at open-circuit potential (OCP) of 0.58 VRHE, and subsequently restructuring from FeSAO4(OH)1a'(OH)1b to FeSAO3(OH)1aâ³ due to the breaking of one Fe-O bond and the dissociation of one -OH at working potentials for final electrocatalytic process of N2RR, thus revealing the first potential-induced in situ formation of the real electrocatalytic active sites to boost the conversion of N2 to NH3. Moreover, the key intermediate of Fe-NNHx was detected experimentally by both operando XAS and in situ attenuated total reflection-surface-enhanced infrared absorption spectra (ATR-SEIRAS), indicating the alternating mechanism followed by N2RR on such catalyst. The results indicate the necessity of considering the potential-induced restructuring of the active sites on all kinds of electrocatalysts for such as highly efficient ammonia production from N2RR. It also paves a new way for a precise understanding to the structure-activity relationship of a catalyst and helps the design of highly efficient catalysts.
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The present study explored whether acceptance and commitment therapy (ACT), a cognitive behavioral therapy approach, could improve the symptoms of schizophrenia spectrum disorders among patients with schizophrenia in remission. A pre- and post-treatment design with two evaluation time points was employed. Sixty outpatients with schizophrenia in remission were randomly divided into two groups: the ACT plus treatment as usual (ACT+TAU) and treatment as usual (TAU) groups. The ACT+TAU group participated in 10 group-based ACT interventions and TAU in the hospital, and the TAU group only received TAU interventions. General psycho-pathological symptoms, self-esteem, and psychological flexibility were assessed before intervention (baseline; pre-test) and after intervention (five weeks; post-test). Results indicated that, compared to the TAU group, the ACT+TAU group exhibited a more significant improvement in general psychopathological symptoms, self-esteem, cognitive fusion, and acceptance and action at post-test. ACT intervention could effectively decrease the general psycho-pathological symptoms and increase self-esteem level and psychological flexibility in people with schizophrenia in remission.
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Terapia de Aceptación y Compromiso , Terapia Cognitivo-Conductual , Esquizofrenia , Humanos , Terapia Cognitivo-Conductual/métodos , Esquizofrenia/terapia , Resultado del TratamientoRESUMEN
Specific medications to combat cerebellar ataxias, a group of debilitating movement disorders characterized by difficulty with walking, balance and coordination, are still lacking. Notably, cerebellar microglial activation appears to be a common feature in different types of ataxic patients and rodent models. However, direct evidence that cerebellar microglial activation in vivo is sufficient to induce ataxia is still lacking. Here, by employing chemogenetic approaches to manipulate cerebellar microglia selectively and directly, we found that specific chemogenetic activation of microglia in the cerebellar vermis directly leads to ataxia symptoms in wild-type mice and aggravated ataxic motor deficits in 3-acetylpyridine (3-AP) mice, a classic mouse model of cerebellar ataxia. Mechanistically, cerebellar microglial proinflammatory activation induced by either chemogenetic M3D(Gq) stimulation or 3-AP modeling hyperexcites Purkinje cells (PCs), which consequently triggers ataxia. Blockade of microglia-derived TNF-α, one of the most important proinflammatory cytokines, attenuates the hyperactivity of PCs driven by microglia. Moreover, chemogenetic inhibition of cerebellar microglial activation or suppression of cerebellar microglial activation by PLX3397 and minocycline reduces the production of proinflammatory cytokines, including TNF-α, to effectively restore the overactivation of PCs and alleviate motor deficits in 3-AP mice. These results suggest that cerebellar microglial activation may aggravate the neuroinflammatory response and subsequently induce dysfunction of PCs, which in turn triggers ataxic motor deficits. Our findings thus reveal a causal relationship between proinflammatory activation of cerebellar microglia and ataxic motor symptoms, which may offer novel evidence for therapeutic intervention for cerebellar ataxias by targeting microglia and microglia-derived inflammatory mediators.