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1.
J Clin Oncol ; : JCO2301889, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38564700

RESUMO

PURPOSE: The role of neoadjuvant chemotherapy (NAC) in colon cancer remains unclear. This trial investigated whether 3 months of modified infusional fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) or capecitabine and oxaliplatin (CAPOX) as NAC could improve outcomes in patients with locally advanced colon cancer versus upfront surgery. PATIENTS AND METHODS: OPTICAL was a randomized, phase III trial in patients with clinically staged locally advanced colon cancer (T3 with extramural spread into the mesocolic fat ≥5 mm or T4). Patients were randomly assigned 1:1 to receive six preoperative cycles of mFOLFOX6 or four cycles of CAPOX, followed by surgery and adjuvant chemotherapy (NAC group), or immediate surgery and the physician's choice of adjuvant chemotherapy (upfront surgery group). The primary end point was 3-year disease-free survival (DFS) assessed in the modified intention-to-treat (mITT) population. RESULTS: Between January 2016 and April 2021, of the 752 patients enrolled, 744 patients were included in the mITT analysis (371 in the NAC group; 373 in the upfront surgery group). At a median follow-up of 48.0 months (IQR, 46.0-50.1), 3-year DFS rates were 82.1% in the NAC group and 77.5% in the upfront surgery group (stratified hazard ratio [HR], 0.74 [95% CI, 0.54 to 1.03]). The R0 resection was achieved in 98% of patients who underwent surgery in both groups. Compared with upfront surgery, NAC resulted in a 7% pathologic complete response rate (pCR), significantly lower rates of advanced tumor staging (pT3-4: 77% v 94%), lymph node metastasis (pN1-2: 31% v 46%), and potentially improved overall survival (stratified HR, 0.44 [95% CI, 0.25 to 0.77]). CONCLUSION: NAC with mFOLFOX6 or CAPOX did not show a significant DFS benefit. However, this neoadjuvant approach was safe, resulted in substantial pathologic downstaging, and appears to be a viable therapeutic option for locally advanced colon cancer.

2.
Heliyon ; 10(7): e28824, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38596142

RESUMO

Objective: This research intends to explore how variations in the SMAD4 gene impact papillary thyroid carcinoma (PTC) among patients in China. Methods: The rs10502913 and rs12968012 polymorphisms were genotyped in 405 subjects using SNP-scan high-throughput technology. Differential mRNA expression of SMAD4 was analyzed using data from TCGA and GSE33630, and protein level expression differences were analyzed using immunohistochemistry. Results: The results showed that SMAD4 mRNA expression was lower in thyroid cancer (THCA) tissues than in normal tissues. Immunohistochemical results showed that the expression level of SMAD4 in normal tissue, thyroid papillary carcinoma tissue and poorly differentiated tissue was significantly different. We found that SMAD4 mismatch variants (rs10502913 and rs12968012) were associated with PTC susceptibility. Specifically, the SMAD4-rs10502913 genotypes (GA and AA) showed a notable correlation with a lower likelihood of PTC in comprehensive and segmented studies (genotype GA: OR (95% CI) = 0.270 (0.077-0.950), p = 0.041; genotype AA: OR (95% CI) = 0.103 (0.025-0.416), p = 0.001). We categorized the immunohistochemical results according to genotype and found that rs10502913-GG protein level was expressed at the lowest level, and both GA and AA were higher than GG (GG vs. AA, P < 0.05), and rs12968012-CG protein level was expressed at the lowest level, and both GG and CC were higher than CG (GG vs. CG, P < 0.01). Conclusion: Two missense variants of SMAD4 (rs10502913 and rs12968012) are associated with reduced risk of papillary thyroid carcinoma, possibly by reducing protein expression leading to susceptibility to papillary thyroid carcinoma.

3.
Abdom Radiol (NY) ; 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38587629

RESUMO

This study aimed to compare the detection rates of 68Ga-FAPI-04 PET/CT and 18F-FDG PET/CT in colorectal cancer. A systematic search of major medical databases was conducted to identify studies up to September 2023. The primary outcome assessed was the detection rate of 68Ga-FAPI-04 PET/CT and 18F-FDG PET/CT in the primary tumor. Pooled risk ratios with a 95% CI were calculated using random-effect models to adjust for heterogeneity. Eight studies were included in the meta-analysis. 68Ga-FAPI-04 PET/CT has higher uptakes in lymph nodes, bone, and peritoneal metastasis compared with 18F-FDG PET/CT. The detection rate of 68Ga-FAPI-04 PET/CT based on lesion was better for lymph node metastasis (RR = 0.63, 95% CI 0.47-0.84, P = 0.002) and peritoneal metastasis (RR = 0.52, 95% CI 0.32-0.85, P = 0.009), both imaging modalities had essentially the same diagnostic efficacy in primary tumor (RR = 0.99, 95% CI 0.96-1.02, P = 0.49). 68Ga-FAPI-04 as a highly promising PET/CT tracer was superior to 18F-FDG PET/CT in colorectal cancer, especially in detecting lymph node metastases and peritoneal metastases.

4.
Artigo em Inglês | MEDLINE | ID: mdl-38587644

RESUMO

PURPOSE: Radiopharmaceutical therapies targeting fibroblast activation protein (FAP) have shown promising efficacy against many tumor types. But radiopharmaceuticals alone in most cases are insufficient to completely eradicate tumor cells, which can partially be attributed to the protective interplay between tumor cells and cancer-associated fibroblasts (CAFs). The C-X-C chemokine receptor type 4/C-X-C motif chemokine 12 (CXCR4/CXCL12) interaction plays an important role in orchestrating tumor cells and CAFs. We hereby investigated the feasibility and efficacy of [177Lu]Lu-DOTAGA.(SA.FAPi)2, a FAP-targeting radiopharmaceutical, in combination with AMD3100, a CXCR4 antagonist, in a preclinical murine model of triple-negative breast cancer (TNBC). METHODS: Public database was first interrogated to reveal the correlation between CAFs' scores and the prognosis of TNBC patients, as well as the expression levels of FAP and CXCR4 in normal tissues and tumors. In vitro therapeutic efficacy regarding cell proliferation, migration, and colony formation was assessed in BALB/3T3 fibroblasts and 4T1 murine breast cancer cells. In vivo therapeutic efficacy was longitudinally monitored using serial 18F-FDG, [18F]AlF-NOTA-FAPI-04, and [68Ga]Ga-DOTA-Pentixafor PET/CT scans and validated using tumor sections through immunohistochemical staining of Ki-67, α-SMA, CXCR4, and CXCL12. Intratumoral abundance of myeloid-derived suppressive cells (MDSCs) was analyzed using flow cytometry in accordance with the PET/CT schedules. Treatment toxicity was evaluated by examining major organs including heart, lung, liver, kidney, and spleen. RESULTS: CAFs' scores negatively correlated with the survival of TNBC patients (p < 0.05). The expression of CXCR4 and FAP was both significantly higher in tumors than in normal tissues. The combination of [177Lu]Lu-DOTAGA.(SA.FAPi)2 and AMD3100 significantly suppressed cell proliferation, migration, and colony formation in cell culture, and exhibited synergistic effects in 4T1 tumor models along with a decreased number of MDSCs. PET/CT imaging revealed lowest tumor accumulation of 18F-FDG and [18F]AlF-NOTA-FAPI-04 on day 13 and day 14 after treatment started, both of which gradually increased at later time points. A similar trend was observed in the IHC staining of Ki-67, α-SMA, and CXCL12. CONCLUSION: The combination of [177Lu]Lu-DOTAGA.(SA.FAPi)2 and AMD3100 is a feasible treatment against TNBC with minimal toxicity in main organs.

5.
Nat Commun ; 15(1): 3201, 2024 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-38615046

RESUMO

Yttrium iron garnet, a material possessing ultralow magnetic damping and extraordinarily long magnon diffusion length, is the most widely studied magnetic insulator in spintronics and magnonics. Field-free electrical control of perpendicular yttrium iron garnet magnetization with considerable efficiency is highly desired for excellent device performance. Here, we demonstrate such an accomplishment with a collinear spin current, whose spin polarization and propagation direction are both perpendicular to the interface. Remarkably, the field-free magnetization switching is achieved not only with a heavy-metal-free material, Permalloy, but also with a higher efficiency as compared with a typical heavy metal, Pt. Combined with the direct and inverse effect measurements, we ascribe the collinear spin current to the anomalous spin Hall effect in Permalloy. Our findings provide a new insight into spin current generation in Permalloy and open an avenue in spintronic devices.

6.
Int J Oncol ; 64(5)2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38606502

RESUMO

MicroRNAs (miRNAs) are noncoding small nucleic acids that contain ~22 nucleotides and are considered to promote the degradation or inhibit the translation of mRNA by targeting its 3'­untranslated region. However, growing evidence has revealed that nuclear miRNAs, combined with gene promoters or enhancers, are able to directly mediate gene transcription. These miRNAs exert a critical influence on cancer progression by affecting cell growth, migration and invasion. In this review, the direct regulation of gene expression by nuclear miRNAs at the transcriptional level was discussed and summarized, and their mechanisms of action in cancers were highlighted with reference to the various body systems.


Assuntos
MicroRNAs , Neoplasias , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias/genética , RNA Mensageiro
8.
ChemSusChem ; : e202400624, 2024 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-38616165

RESUMO

Glycerol oxidation-assisted water electrolysis has emerged as a cost-effective way of co-producing green hydrogen and HCOOH. Still, preparing highly selective and stable nickel-based metal electrocatalysts remains a challenge. Herein, heterostructure Ni3N/WO3 nanosheet arrays of bifunctional catalysts with large specific surface areas loaded on nickel foam (denoted as Ni3N/WO3/NF) were synthesized. This catalyst was for glycerol oxidation reaction (GOR) and hydrogen evolution reaction (HER) with excellent catalytic performance, a voltage saving of 267 mV compared to oxygen evolution reaction (OER), and a HER overpotential of 104 mV at 100 mA cm-2. The cell voltage in the assembled GOR // HER hybrid electrolysis system reaches 100 mA cm-2 at 1.50 V, 296 mV lower than the potential required for overall water splitting. This work demonstrates that replacing GOR with OER using a cost-effective and highly active Ni-based bifunctional electrocatalyst can make hybrid water electrolysis an energy-efficient, sustainable, and green strategy for hydrogen production.

9.
Diabetes Metab Syndr Obes ; 17: 1809-1818, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38650633

RESUMO

Introduction: This study aimed to investigate the association of Nicotinamide phosphoribosyl transferase (NAMPT) rs61330082 polymorphism with co-morbid hypertension (HTN) and the progression of hypertension in Chinese patients with type 2 diabetes mellitus (T2DM). Methods: A total of 453 T2DM patients were genotyped for the polymorphism of rs61330082 using SNP-scan high-throughput technology. These patients were divided into T2DM group (261 patients) and T2DM combined with hypertension group (T2MH, 192 patients). The T2MH group was further categorized into Grade I, Grade II, and Grade III based on the results of the Hypertension Grade Score. Peripheral blood plasma urea, plasma creatinine, renin-angiotensin system (RAS) indexes, and lipid biochemistry indexes were measured in patients and analyzed in relation to NAMTP polymorphisms. Results: We found that the presence of the NAMPT rs61330082-AA genotype was associated with a significantly increased risk of developing higher-grade hypertension in patients with T2MH. In addition, the A allele of the NAMPT rs61330082 gene displayed more associated in developing a higher grade of hypertension compared to the G allele. Also, the level of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-c) increased with hypertension grade in the NAMPT rs61330082-GG genotype. Conclusion: NAMPT rs61330082 polymorphism was significantly associated with the progression of hypertension grade in T2MH patients and also affected plasma creatinine and LDL-c levels.

10.
Int J Colorectal Dis ; 39(1): 38, 2024 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-38492080

RESUMO

PURPOSE: Total neoadjuvant therapy (TNT) has emerged as a therapeutic approach for locally advanced rectal cancer (LARC). However, the optimal chemotherapy cycles within TNT remain uncertain. This study aimed to evaluate and compare the prognostic efficacy of varying cycles of chemotherapy during TNT for LARC. METHODS: Patients diagnosed with LARC (T3-4N0M0/T1-4N1-2M0), who underwent TNT or chemoradiotherapy followed by total mesorectal excision (TME) between 2015 and 2020, were retrospective included. Patients were categorized into three groups based on their neoadjuvant strategy: CRT (long-course chemoradiotherapy), STNT (long-course CRT with one to three cycles of chemotherapy), and LTNT (long-course CRT with four or more cycles of chemotherapy). Propensity score matching (PSM) based on gender, age, body mass index, tumor distance from the anal verge, clinical T stage, clinical N stage, and mesorectal fascia status was employed to reduce confounding bias. Primary endpoints were disease-free survival (DFS) and metastasis-free survival (MFS). RESULTS: The study comprised 372 patients, with 73 patients in each group after PSM. Compared with CRT, both STNT and LTNT demonstrated improved DFS (5-year rate: 59.7% vs. 77.8% vs. 76.5%, p = 0.027) and MFS (5-year rate: 65.1% vs. 81.3% vs. 81.4%, p = 0.030). There was no difference in DFS or MFS between STNT and LTNT. These favorable outcomes were consistent among subgroups defined by tumor distance from the anal verge ≥ 5 cm, clinical T3 stage, clinical N positive status, or involved mesorectal fascia. CONCLUSION: Compared to CRT, both STNT and LTNT demonstrated improved DFS and MFS outcomes. Notably, survival outcomes were similar between STNT and LTNT, suggesting that chemotherapy cycles in TNT may not significantly impact survival.


Assuntos
Segunda Neoplasia Primária , Neoplasias Retais , Humanos , Terapia Neoadjuvante , Resultado do Tratamento , Estudos Retrospectivos , Pontuação de Propensão , Estadiamento de Neoplasias , Neoplasias Retais/patologia , Intervalo Livre de Doença , Quimiorradioterapia , Segunda Neoplasia Primária/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
11.
J Cancer ; 15(8): 2160-2178, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38495503

RESUMO

Background: Lung adenocarcinoma ranks as the second most widespread form of cancer globally, accompanied by a significant mortality rate. Several studies have shown that T cell exhaustion is associated with immunotherapy of tumours. Consequently, it is essential to comprehend the possible impact of T cell exhaustion on the tumor microenvironment. The purpose of this research was to create a TEX-based model that would use single-cell RNA-seq (scRNA-seq) and bulk-RNA sequencing to explore new possibilities for assessing the prognosis and immunotherapeutic response of LUAD patients. Methods: RNA-seq data from LUAD patients was downloaded from the Cancer Genome Atlas (TCGA) database and the National Center for Biotechnology Information (GEO). 10X scRNA sequencing data, as reported by Bischoff P et al., was utilized for down-sampling clustering and subgroup identification using TSNE. TEX-associated genes were identified through gene set variance analysis (GSVA) and weighted gene correlation network analysis (WGCNA). We utilized LASSO-Cox analysis to establish predicted TEX features. External validation was conducted in GSE31210 and GSE30219 cohorts. Immunotherapeutic response was assessed in IMvigor210, GSE78220, GSE35640 and GSE100797 cohorts. Furthermore, we investigated differences in mutational profiles and immune microenvironment between various risk groups. We then screened TEXRS key regulatory genes using ROC diagnostic curves and KM survival curves. Finally, we verified the differential expression of key regulatory genes through RT-qPCR. Results: Nine TEX genes were identified as highly predictive of LUAD prognosis and strongly correlated with disease outcome. Univariate and multivariate analysis revealed that patients in the low-risk group had significantly better overall survival rates compared with those in the high-risk group, highlighting the model's ability to independently predict LUAD prognosis. Our analysis revealed significant variation in the biological function, mutational landscape, and immune cell infiltration within the tumor microenvironment of both high-risk and low-risk groups. Additionally, immunotherapy was found to have a significant impact on both groups, indicating strong predictive efficacy of the model. Conclusions: The TEX model showed good predictive performance and provided a new perspective for evaluating the efficacy of preimmunization, which provides a new strategy for the future treatment of lung adenocarcinoma.

12.
Nat Commun ; 15(1): 2301, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38485746

RESUMO

Atomically precise defect engineering is essential to manipulate the properties of emerging topological quantum materials for practical quantum applications. However, this remains challenging due to the obstacles in modifying the typically complex crystal lattice with atomic precision. Here, we report the atomically precise engineering of the vacancy-localized spin-orbit polarons in a kagome magnetic Weyl semimetal Co3Sn2S2, using scanning tunneling microscope. We achieve the step-by-step repair of the selected vacancies, leading to the formation of artificial sulfur vacancies with elaborate geometry. We find that that the bound states localized around these vacancies undergo a symmetry dependent energy shift towards Fermi level with increasing vacancy size. As the vacancy size increases, the localized magnetic moments of spin-orbit polarons become tunable and eventually become itinerantly negative due to spin-orbit coupling in the kagome flat band. These findings provide a platform for engineering atomic quantum states in topological quantum materials at the atomic scale.

13.
Nature ; 628(8008): 515-521, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38509374

RESUMO

The convergence of topology and correlations represents a highly coveted realm in the pursuit of new quantum states of matter1. Introducing electron correlations to a quantum spin Hall (QSH) insulator can lead to the emergence of a fractional topological insulator and other exotic time-reversal-symmetric topological order2-8, not possible in quantum Hall and Chern insulator systems. Here we report a new dual QSH insulator within the intrinsic monolayer crystal of TaIrTe4, arising from the interplay of its single-particle topology and density-tuned electron correlations. At charge neutrality, monolayer TaIrTe4 demonstrates the QSH insulator, manifesting enhanced nonlocal transport and quantized helical edge conductance. After introducing electrons from charge neutrality, TaIrTe4 shows metallic behaviour in only a small range of charge densities but quickly goes into a new insulating state, entirely unexpected on the basis of the single-particle band structure of TaIrTe4. This insulating state could arise from a strong electronic instability near the van Hove singularities, probably leading to a charge density wave (CDW). Remarkably, within this correlated insulating gap, we observe a resurgence of the QSH state. The observation of helical edge conduction in a CDW gap could bridge spin physics and charge orders. The discovery of a dual QSH insulator introduces a new method for creating topological flat minibands through CDW superlattices, which offer a promising platform for exploring time-reversal-symmetric fractional phases and electromagnetism2-4,9,10.

14.
Sci Bull (Beijing) ; 69(7): 885-892, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38383234

RESUMO

Vortices and bound states offer an effective means of comprehending the electronic properties of superconductors. Recently, surface-dependent vortex core states have been observed in the newly discovered kagome superconductors CsV3Sb5. Although the spatial distribution of the sharp zero energy conductance peak appears similar to Majorana bound states arising from the superconducting Dirac surface states, its origin remains elusive. In this study, we present observations of tunable vortex bound states (VBSs) in two chemically-doped kagome superconductors Cs(V1-xTrx)3Sb5 (Tr = Ta or Ti), using low-temperature scanning tunneling microscopy/spectroscopy. The CsV3Sb5-derived kagome superconductors exhibit full-gap-pairing superconductivity accompanied by the absence of long-range charge orders, in contrast to pristine CsV3Sb5. Zero-energy conductance maps demonstrate a field-driven continuous reorientation transition of the vortex lattice, suggesting multiband superconductivity. The Ta-doped CsV3Sb5 displays the conventional cross-shaped spatial evolution of Caroli-de Gennes-Matricon bound states, while the Ti-doped CsV3Sb5 exhibits a sharp, non-split zero-bias conductance peak (ZBCP) that persists over a long distance across the vortex. The spatial evolution of the non-split ZBCP is robust against surface effects and external magnetic field but is related to the doping concentrations. Our study reveals the tunable VBSs in multiband chemically-doped CsV3Sb5 system and offers fresh insights into previously reported Y-shaped ZBCP in a non-quantum-limit condition at the surface of kagome superconductor.

15.
Front Oncol ; 14: 1294440, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38406803

RESUMO

Background: This study aimed to establish and validate a prognostic model based on immune-related genes (IRGPM) for predicting disease-free survival (DFS) in patients with locally advanced rectal cancer (LARC) undergoing neoadjuvant chemoradiotherapy, and to elucidate the immune profiles associated with different prognostic outcomes. Methods: Transcriptomic and clinical data were sourced from the Gene Expression Omnibus (GEO) database and the West China Hospital database. We focused on genes from the RNA immune-oncology panel. The elastic net approach was employed to pinpoint immune-related genes significantly impacting DFS. We developed the IRGPM for rectal cancer using the random forest technique. Based on the IRGPM, we calculated prognostic risk scores to categorize patients into high-risk and low-risk groups. Comparative analysis of immune characteristics between these groups was conducted. Results: In this study, 407 LARC samples were analyzed. The elastic net identified a signature of 20 immune-related genes, forming the basis of the IRGPM. Kaplan-Meier survival analysis revealed a lower 5-year DFS in the high-risk group compared to the low-risk group. The receiver operating characteristic (ROC) curve affirmed the model's robust predictive capability. Validation of the model was performed in the GSE190826 cohort and our institution's cohort. Gene expression differences between high-risk and low-risk groups predominantly related to cytokine-cytokine receptor interactions. Notably, the low-risk group exhibited higher immune scores. Further analysis indicated a greater presence of activated B cells, activated CD8 T cells, central memory CD8 T cells, macrophages, T follicular helper cells, and type 2 helper cells in the low-risk group. Additionally, immune checkpoint analysis revealed elevated PDCD1 expression in the low-risk group. Conclusions: The IRGPM, developed through random forest and elastic net methodologies, demonstrates potential in distinguishing DFS among LARC patients receiving standard treatment. Notably, the low-risk group, as defined by the IRGPM, showed enhanced activation of adaptive immune responses within the tumor microenvironment.

16.
Abdom Radiol (NY) ; 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38411692

RESUMO

BACKGROUND: To prospectively develop and validate the T2WI texture analysis model based on a node-by-node comparison for improving the diagnostic accuracy of lymph node metastasis (LNM) in rectal cancer. METHODS: A total of 381 histopathologically confirmed lymph nodes (LNs) were collected. LNs texture features were extracted from MRI-T2WI. Spearman's rank correlation coefficient and the least absolute shrinkage and selection operator were used for feature selection to construct the LN rad-score. Then the clinical risk factors and LN texture features were combined to establish combined predictive model. Model performance was assessed by the area under the receiver operating characteristic (ROC) curve (AUC). Decision curve analysis (DCA) and nomogram were used to evaluate the clinical application of the model. RESULTS: A total of 107 texture features were extracted from LN-MRI images. After selection and dimensionality reduction, the radiomics prediction model consisting of 8 texture features showed well-predictive performance in the training and validation cohorts (AUC, 0.676; 95% CI 0.582-0.771) (AUC, 0.774; 95% CI 0.648-0.899). A clinical-radiomics prediction model with the best performance was created by combining clinical and radiomics features, 0.818 (95% CI 0.742-0.893) for the training and 0.922 (95% CI 0.863-0.980) for the validation cohort. The LN Rad-score in clinical-radiomics nomogram obtained the highest classification contribution and was well calibrated. DCA demonstrated the superiority of the clinical-radiomics model. CONCLUSION: The lymph node T2WI-based texture features can help to improve the preoperative prediction of LNM.

17.
Bioact Mater ; 35: 242-258, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38333615

RESUMO

Induced pluripotent stem cells (iPSCs) can be personalized and differentiated into neural stem cells (NSCs), thereby effectively providing a source of transplanted cells for spinal cord injury (SCI). To further improve the repair efficiency of SCI, we designed a functional neural network tissue based on TrkC-modified iPSC-derived NSCs and a CBD-NT3-modified linear-ordered collagen scaffold (LOCS). We confirmed that transplantation of this tissue regenerated neurons and synapses, improved the microenvironment of the injured area, enhanced remodeling of the extracellular matrix, and promoted functional recovery of the hind limbs in a rat SCI model with complete transection. RNA sequencing and metabolomic analyses also confirmed the repair effect of this tissue from multiple perspectives and revealed its potential mechanism for treating SCI. Together, we constructed a functional neural network tissue using human iPSCs-derived NSCs as seed cells based on the interaction of receptors and ligands for the first time. This tissue can effectively improve the therapeutic effect of SCI, thus confirming the feasibility of human iPSCs-derived NSCs and LOCS for SCI repair and providing a valuable direction for SCI research.

18.
Inorg Chem ; 63(6): 3099-3106, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38299496

RESUMO

Electrochemical conversion of nitrogen into ammonia at ambient conditions as a sustainable approach has gained significant attention, but it is still extremely challenging to simultaneously obtain a high faradaic efficiency (FE) and NH3 yield. In this work, the interstitial boron-doped porous Pd nanotubes (B-Pd PNTs) are constructed by combining the self-template reduction method with boron doping. Benefiting from distinctive one-dimensional porous nanotube architectonics and the incorporation of the interstitial B atoms, the resulting B-Pd PNTs exhibit high NH3 yield (18.36 µg h-1 mgcat.-1) and FE (21.95%) in neutral conditions, outperforming the Pd/PdO PNTs (10.4 µg h-1 mgcat.-1 and 8.47%). The present study provides an attractive method to enhance the efficiency of the electroreduction of nitrogen into ammonia by incorporating interstitial boron into porous Pd-based catalysts.

19.
Nanotechnology ; 35(22)2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38387087

RESUMO

Replacing the slow oxygen evolution reaction with favorable hydrazine oxidation reaction (HzOR) is a green and efficient way to produce hydrogen. In this work, we synthesize amorphous/crystalline RhFeP metallene via phase engineering and heteroatom doping. RhFeP metallene has good catalytic activity and stability for HER and HzOR, and only an ultralow voltage of 18 mV is required to achieve 10 mA cm-2in a two-electrode hydrazine-assisted water splitting system. The superior result is mainly ascribed to the co-doping of Fe and P and the formation of amorphous/crystalline RhFeP metallene with abundant phase boundaries, thereby adjusting electronic structure and increasing active sites.

20.
Cell Signal ; 116: 111063, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38242267

RESUMO

Chronic kidney disease (CKD) often culminates in hypercalcemia, instigating severe neurological injuries that are not yet fully understood. This study unveils a mechanism, where GSK343 ameliorates CKD-induced neural damage in mice by modulating macrophage polarization through the EZH2/MST1/YAP1 signaling axis. Specifically, GSK343 downregulated the expression of histone methyltransferase EZH2 and upregulated MST1, which suppressed YAP1, promoting M2 macrophage polarization and thereby, alleviating neural injury in hypercalcemia arising from renal failure. This molecular pathway introduced herein not only sheds light on the cellular machinations behind CKD-induced neurological harm but also paves the way for potential therapeutic interventions targeting the identified axis, especially considering the M2 macrophage polarization as a potential strategy to mitigate hypercalcemia-induced neural injuries.


Assuntos
Hipercalcemia , Piridonas , Insuficiência Renal Crônica , Camundongos , Animais , Macrófagos , Indazóis/farmacologia , Insuficiência Renal Crônica/complicações
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