RESUMEN

Tumor cells remodel the phenotype and function of tumor microenvironment (TME) cells to favor tumor progression. Previous studies have shown that neutrophils in TME are polarized to N2 tumor-associated neutrophils (TANs) by tumor derived factors, thus promoting tumor growth and metastasis, angiogenesis, therapy resistance, and immunosuppression. Exosomes act as critical intercellular messengers in human health and diseases including cancer. So far, the biological roles of exosomes from N2 TANs in gastric cancer have not been well characterized. Herein, we represented the first report that exosomes from N2 TANs promoted gastric cancer metastasis in vitro and in vivo. We found that exosomes from N2 TANs transferred miR-4745-5p/3911 to gastric cancer cells to downregulate SLIT2 (slit guidance ligand 2) gene expression. Adenovirus-mediated overexpression of SLIT2 reversed the promotion of gastric cancer metastasis by N2 TANs derived exosomes. We further revealed that gastric cancer cells induced glucose metabolic reprogramming in neutrophils through exosomal HMGB1 (high mobility group protein B1)/NF-κB pathway, which mediated neutrophil N2 polarization and miR-4745-5p/3911 upregulation. We further employed ddPCR (droplet digital PCR) to detect the expression of miR-4745-5p/3911 in N2 TANs exosomes from human serum samples and found their increased levels in gastric cancer patients compared to healthy controls and benign gastric disease patients. Conclusively, our results indicate that N2 TANs facilitate cancer metastasis via regulation of SLIT2 in gastric cancer cells by exosomal miR-4745-5p/3911, which provides a new insight into the roles of TME cells derived exosomes in gastric cancer metastasis and offers a potential biomarker for gastric cancer diagnosis.

Asunto(s)

Exosomas , Regulación Neoplásica de la Expresión Génica , Péptidos y Proteínas de Señalización Intercelular , MicroARNs , Proteínas del Tejido Nervioso , Neutrófilos , Neoplasias Gástricas , Microambiente Tumoral , Neoplasias Gástricas/patología , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Exosomas/metabolismo , Exosomas/genética , Humanos , Neutrófilos/metabolismo , Neutrófilos/patología , MicroARNs/genética , Animales , Ratones , Proteínas del Tejido Nervioso/genética , Proteínas del Tejido Nervioso/metabolismo , Línea Celular Tumoral , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Péptidos y Proteínas de Señalización Intercelular/genética , Microambiente Tumoral/genética , Metástasis de la Neoplasia , Proteína HMGB1/metabolismo , Proteína HMGB1/genética , Masculino

RESUMEN

Background: Effective glycemic control is crucial for hospitalized patients, leading to benefits such as shorter hospital stays and reduced postoperative infection rates. While previous studies have emphasized the effectiveness of multidisciplinary collaborative stewardship for hospital-wide hyperglycemia management, patient perspectives and preferences have not been adequately considered. Objective: To identify factors influencing treatment preferences of Chinese hospitalized diabetes patients using discrete choice experiments (DCEs) and provide practical insights for the construction of a hospital-wide glycemic control programme. Methods: A face-to-face survey was conducted among diabetes patients admitted to nonendocrine departments in a tertiary hospital in Nanjing, China. The attributes and levels were determined based on DCE principles, and a conditional logit model was used to quantify patients' preferences. Results: A total of 157 respondents were analyzed. Antihyperglycemic effectiveness, healthcare providers, treatment regimen, monitoring frequency, and adverse reactions were the five attributes that significantly influenced patient preference (p < 0.05). Notably, an 80% glycemic control rate (ß = 2.009) and a multidisciplinary management team involving clinical pharmacists (ß = 1.346) had the greatest impact. Negative effects were observed for hypoglycemia (ß = -1.008), insulin pump use (ß = -0.746), and frequent glucose monitoring (ß = -0.523). Female patients exhibited higher concern for healthcare providers (ß = 1.172) compared to males. Younger and shorter-course patients prioritized antihyperglycemic effectiveness (ß = 3.330, ß = 1.510), while older patients preferred multidisciplinary management (ß = 1.186) and opposed increased monitoring frequency (ß = -0.703). Patients with higher educational backgrounds showed greater acceptance of continuous glucose monitoring (ß = 1.983), and those with higher annual income placed more emphasis on glycemic control rate. Conclusion: Treatment preferences of hospitalized diabetes patients are mainly influenced by antihyperglycemic effectiveness, adverse reactions, healthcare providers, and individual characteristics. Comprehensive consideration and an individualized therapy strategy should be given when constructing a hospital-wide glycemic control programme.

Asunto(s)

Glucemia , Diabetes Mellitus , Control Glucémico , Hospitalización , Hipoglucemiantes , Prioridad del Paciente , Humanos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Hipoglucemiantes/uso terapéutico , China , Diabetes Mellitus/terapia , Diabetes Mellitus/sangre , Glucemia/metabolismo , Adulto , Conducta de Elección , Encuestas y Cuestionarios , Hiperglucemia

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Pentatricopeptide repeat (PPR) gene family constitutes one of the largest gene families in plants, which mainly participate in RNA editing and RNA splicing of organellar RNAs, thereby affecting the organellar development. Recently, some evidence elucidated the important roles of PPR proteins in the albino process of plant leaves. However, the functions of PPR genes in the woody mangrove species have not been investigated. In this study, using a typical true mangrove Kandelia obovata, we systematically identified 298 PPR genes and characterized their general features and physicochemical properties, including evolutionary relationships, the subcellular localization, PPR motif type, the number of introns and PPR motifs, and isoelectric point, and so forth. Furthermore, we combined genome-wide association studies (GWAS) and transcriptome analysis to identify the genetic architecture and potential PPR genes associated with propagule leaves colour variations of K. obovata. As a result, we prioritized 16 PPR genes related to the albino phenotype using different strategies, including differentially expressed genes analysis and genetic diversity analysis. Further analysis discovered two genes of interest, namely Maker00002998 (PLS-type) and Maker00003187 (P-type), which were differentially expressed genes and causal genes detected by GWAS analysis. Moreover, we successfully predicted downstream target chloroplast genes (rps14, rpoC1 and rpoC2) bound by Maker00002998 PPR proteins. The experimental verification of RNA editing sites of rps14, rpoC1, and rpoC2 in our previous study and the verification of interaction between Maker00002998 and rps14 transcript using in vitro RNA pull-down assays revealed that Maker00002998 PPR protein might be involved in the post-transcriptional process of chloroplast genes. Our result provides new insights into the roles of PPR genes in the albinism mechanism of K. obovata propagule leaves.

RESUMEN

Dual inhibition of vascular endothelial growth factor and epidermal growth factor receptor (EGFR) signaling pathways offers the prospect of improving the effectiveness of EFGR-targeted therapy. In this phase 3 study (ClinicalTrial.gov: NCT04028778), 315 patients with treatment-naïve, EGFR-mutated, advanced non-small cell lung cancer (NSCLC) were randomized (1:1) to receive anlotinib or placebo plus gefitinib once daily on days 1-14 per a 3-week cycle. At the prespecified final analysis of progression-free survival (PFS), a significant improvement in PFS was observed for the anlotinib arm over the placebo arm (hazards ratio [HR] = 0.64, 95% CI, 0.48-0.80, P = 0.003). Particularly, patients with brain metastasis and those harboring EGFR amplification or high tumor mutation load gained significant more benefits in PFS from gefitinib plus anlotinib. The incidence of grade 3 or higher treatment-emergent adverse events was 49.7% of the patients receiving gefitinib plus anlotinib versus 31.0% of the patients receiving gefitinib plus placebo. Anlotinib plus gefitinib significantly improves PFS in patients with treatment-naïve, EGFR-mutated, advanced NSCLC, with a manageable safety profile.

Asunto(s)

Carcinoma de Pulmón de Células no Pequeñas , Receptores ErbB , Gefitinib , Indoles , Neoplasias Pulmonares , Mutación , Inhibidores de Proteínas Quinasas , Quinolinas , Humanos , Gefitinib/administración & dosificación , Gefitinib/efectos adversos , Gefitinib/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Quinolinas/administración & dosificación , Quinolinas/efectos adversos , Quinolinas/uso terapéutico , Indoles/administración & dosificación , Indoles/uso terapéutico , Indoles/efectos adversos , Masculino , Femenino , Receptores ErbB/genética , Receptores ErbB/antagonistas & inhibidores , Persona de Mediana Edad , Anciano , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Inhibidores de Proteínas Quinasas/efectos adversos , Inhibidores de Proteínas Quinasas/uso terapéutico , Inhibidores de Proteínas Quinasas/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Adulto , Anciano de 80 o más Años

RESUMEN

Transthiolation (also known as transthioesterification) reactions are used in the biosynthesis of acetyl coenzyme A, fatty acids and polyketides, and for post-translational modification by ubiquitin (Ub) and ubiquitin-like (Ubl) proteins1-3. For the Ub pathway, E1 enzymes catalyse transthiolation from an E1~Ub thioester to an E2~Ub thioester. Transthiolation is also required for transfer of Ub from an E2~Ub thioester to HECT (homologous to E6AP C terminus) and RBR (ring-between-ring) E3 ligases to form E3~Ub thioesters4-6. How isoenergetic transfer of thioester bonds is driven forward by enzymes in the Ub pathway remains unclear. Here we isolate mimics of transient transthiolation intermediates for E1-Ub(T)-E2 and E2-Ub(T)-E3HECT complexes (where T denotes Ub in a thioester or Ub undergoing transthiolation) using a chemical strategy with native enzymes and near-native Ub to capture and visualize a continuum of structures determined by single-particle cryo-electron microscopy. These structures and accompanying biochemical experiments illuminate conformational changes in Ub, E1, E2 and E3 that are coordinated with the chemical reactions to facilitate directional transfer of Ub from each enzyme to the next.

Asunto(s)

Microscopía por Crioelectrón , Modelos Moleculares , Ubiquitina-Proteína Ligasas , Ubiquitina , Ubiquitina/metabolismo , Ubiquitina/química , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitina-Proteína Ligasas/química , Enzimas Activadoras de Ubiquitina/metabolismo , Enzimas Activadoras de Ubiquitina/química , Enzimas Ubiquitina-Conjugadoras/metabolismo , Enzimas Ubiquitina-Conjugadoras/química , Esterificación , Procesamiento Proteico-Postraduccional

RESUMEN

Multi-Modal Entity Alignment (MMEA), aiming to discover matching entity pairs on two multi-modal knowledge graphs (MMKGs), is an essential task in knowledge graph fusion. Through mining feature information of MMKGs, entities are aligned to tackle the issue that an MMKG is incapable of effective integration. The recent attempt at neighbors and attribute fusion mainly focuses on aggregating multi-modal attributes, neglecting the structure effect with multi-modal attributes for entity alignment. This paper proposes an innovative approach, namely TriFac, to exploit embedding refinement for factorizing the original multi-modal knowledge graphs through a two-stage MMKG factorization. Notably, we propose triplet-aware graph neural networks to aggregate multi-relational features. We propose multi-modal fusion for aggregating multiple features and design three novel metrics to measure knowledge graph factorization performance on the unified factorized latent space. Empirical results indicate the effectiveness of TriFac, surpassing previous state-of-the-art models on two MMEA datasets and a power system dataset.

Asunto(s)

Algoritmos , Redes Neurales de la Computación , Minería de Datos/métodos , Humanos , Conocimiento

RESUMEN

Acute perimyocarditis is commonly preceded by viral illness and presents with non-specific complaints that can be a manifestation of serious cardiac complications such as arrhythmias and heart failure. While pericarditis is a known complication of thyrotoxicosis, termed "thyrotoxic pericarditis," concomitant new-onset perimyocarditis and Graves' disease, termed "thyro-pericarditis," has been reported. We present a case of thyro-pericarditis as the initial presentation of undiagnosed and untreated Graves' disease co-occurring with recent Coxsackievirus A and B infection. A 27-year-old male with a family history of undifferentiated hyperthyroidism presented with acute pleuritic chest pain and shortness of breath. Laboratory testing showed elevated cardiac troponin I with ST elevations and PR depressions on initial ECG. Left heart catheterization was normal, but transthoracic echocardiogram showed right ventricular systolic dysfunction and enlargement. Cardiac MRI demonstrated diffuse pericardial enhancement suggesting pericarditis. Thyroid function testing and thyroid ultrasound suggested auto-immune thyrotoxicosis. Serology noted abnormal Coxsackievirus A and B IgG antibody titers, suggesting prior infection. The patient was treated with colchicine, ibuprofen, methimazole, and metoprolol, with resolution of symptoms. Thyro-pericarditis is a rare concomitant presentation of both Graves' disease and myopericarditis, and it remains unknown whether there is an increased risk of adverse cardiac outcomes.

RESUMEN

Renal interstitial fibrosis (RIF) is a prevalent consequence of chronic renal diseases, characterized by excessive extracellular matrix (ECM) deposition. A Disintegrin and Metalloprotease 17 (ADAM17), a transmembrane metalloproteinase, plays a central role in driving renal fibrosis progression by activating Notch 1 protein and the downstream TGF-ß signaling pathway. Our study investigated potential therapeutic interventions for renal fibrosis, focusing on human umbilical cord mesenchymal stem cell-derived extracellular vesicles (hucMSC-EVs). We found that hucMSC-EVs inhibit ADAM17, thereby impeding renal fibrosis progression. Analysis of hucMSC-EVs miRNA profiles revealed significant enrichment of miR-13474, which effectively targeted and inhibited ADAM17 mRNA expression, subsequently suppressing Notch1 activation, TGF-ß signaling, and collagen deposition. Overexpression of miR-13474 enhanced hucMSC-EVs' inhibitory effect on renal fibrosis, while its downregulation abolished this protective effect. Our findings highlight the efficacy of hucMSC-EVs overexpressing miR-13474 in mitigating renal fibrosis via ADAM17 targeting. These insights offer potential therapeutic strategies for managing renal fibrosis.

Asunto(s)

Proteína ADAM17 , Vesículas Extracelulares , Fibrosis , Riñón , Células Madre Mesenquimatosas , MicroARNs , MicroARNs/genética , MicroARNs/metabolismo , Proteína ADAM17/metabolismo , Proteína ADAM17/genética , Humanos , Vesículas Extracelulares/metabolismo , Células Madre Mesenquimatosas/metabolismo , Animales , Riñón/metabolismo , Riñón/patología , Transducción de Señal , Enfermedades Renales/metabolismo , Enfermedades Renales/terapia , Enfermedades Renales/patología , Enfermedades Renales/genética , Factor de Crecimiento Transformador beta/metabolismo , Ratones

RESUMEN

Colorectal cancer (CRC) is the third most common cancer worldwide and the second most common cause of cancer death. Nanotherapies are able to selectively target the delivery of cancer therapeutics, thus improving overall antitumor efficiency and reducing conventional chemotherapy side effects. Mesoporous silica nanoparticles (MSNs) have attracted the attention of many researchers due to their remarkable advantages and biosafety. We offer insights into the recent advances of MSNs in CRC treatment and their potential clinical application value.

RESUMEN

Background: Previous research indicates that coronavirus disease 2019 (COVID-19) infection may have a role in triggering immunoglobulin A (IgA) nephropathy. However, limited research has explored the clinical implications of COVID-19 infection in individuals already diagnosed with IgA nephropathy. This study aimed to determine whether COVID-19 infection independently affects the subsequent trajectory of kidney function in IgA nephropathy patients. Methods: This was a single-center cohort study. The study included 199 patients diagnosed with IgA nephropathy. The COVID-19 infection status was determined using a combined method: a questionnaire and the Health Code application, both administered at the end of 2022 in northern China. Kidney function trajectory was assessed by the estimated glomerular filtration rate (eGFR), calculated based on serum creatinine levels measured during follow-up outpatient visits. The primary endpoint of interest was the eGFR trajectory. Results: Out of the 199 participants, 75% (n = 181) reported a confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, determined through antigen or polymerase chain reaction tests, accounting for 79% (n = 143) of the infected patients. A significant majority (98%) experienced mild to moderate symptoms. Over a median follow-up period of 10.7 months post-COVID-19 infection, notable clinical events included gross hematuria in 30 patients (16.6%), which normalized within an average of 3 days. Additionally, a 2-fold increase in proteinuria or progression to the nephrotic range was observed in 10 individuals (5.5%). No cases of acute kidney injury were noted. COVID-19 exposure was associated with an absolute change in eGFR of 2.98 mL/min/1.73 m2 per month (95% confidence interval 0.46 to 5.50). However, in a fully adjusted model, the estimated changes in eGFR slope post-COVID-19 were -0.39 mL/min/1.73 m2 per month (95% confidence interval -0.83 to 0.06, P = .088) which included the possibility of no significant effect. Notably, a higher rate of kidney function decline was primarily observed in patients with a baseline eGFR <45 mL/min/1.73 m2 [-0.56 mL/min/1.73 m2 (-1.11 to -0.01), P = .048]. In the cohort, there were few instances of severe COVID-19 cases. The absence of long-term follow-up outcomes was observed. Conclusions: Overall, mild to moderate COVID-19 infection does not appear to significantly exacerbate the subsequent decline in kidney function among IgA nephropathy patients, particularly in those with preserved baseline kidney function.

RESUMEN

OBJECTIVE: In this study, we compared the analgesic effects of intercostal nerve block (ICNB), ultrasound-guided paravertebral nerve block (PVB), and epidural block (EB) following single-port thoracoscopic lung surgery. METHOD: A total of 120 patients who underwent single-hole thoracoscopic lung surgery were randomly and equally divided into three groups: ICNB group, the PVB group, and the EB group. ICNB was performed under direct thoracoscopic visualization before the conclusion of the surgery in the ICNB group, while PVB and EB were performed after general anesthesia in the PVB and EB groups, respectively. Patient-controlled intravenous analgesia (PCIA) was used following the surgery in all the groups. The following indicators were recorded: Intraoperative sufentanil dosage, anesthesia awakening time, postoperative intubation time, nerve block operation time, postoperative visual analog scale (VAS) pain scores during resting and coughing at regular intervals of 0, 2, 4, 8, 24, and 48 h, the time until first PCIA, number of effective compressions within 24 h postoperatively, number of rescue analgesia interventions, and the side effects. RESULTS: In comparison to the ICNB group, the PVB and EB groups had a lower intraoperative sufentanil dosage, significantly shorter anesthesia awakening time, and postoperative intubation time, but longer nerve block operation time, lower VAS scores when resting and coughing within 24 h postoperatively (all p-values less than 0.05). Conversely, there were no statistically significant differences in VAS scores during resting and coughing after 24 h (all p-values greater than 0.05). Time to first PCIA, number of effective compressions and number of rescue analgesia at the 24-hour mark postoperatively were significantly better in the PVB and EB groups than that in the ICNB group (P < 0.05). However, there was a higher incidence of side effects observed in the EB group (P < 0.05). CONCLUSION: The analgesic effect of PVB and EB following single-port thoracoscopic lung surgery is better than that of ICNB. PVB causes fewer side effects and complications and is safer and more effective.

Asunto(s)

Nervios Intercostales , Bloqueo Nervioso , Dolor Postoperatorio , Ultrasonografía Intervencional , Humanos , Bloqueo Nervioso/métodos , Femenino , Masculino , Persona de Mediana Edad , Ultrasonografía Intervencional/métodos , Dolor Postoperatorio/prevención & control , Cirugía Torácica Asistida por Video/métodos , Anciano , Dimensión del Dolor , Adulto , Toracoscopía/métodos , Pulmón/cirugía

RESUMEN

We proposed a non-contact photoacoustic (PA) detection method using spectral domain optical coherence tomography (SDOCT). Two interference spectrums (A-lines) were acquired before and after the PA excitation with SDOCT. PA signal propagated within the sample causing the vibration. The vibration inner the sample introduced phase change between the acquired two A-lines. Thus, the PA signal can be detected by evaluating the difference in phase between the two A-lines. Based on the method, an OCT-PAM dual-mode imaging system was constructed. In the system, SDOCT served as the detection unit for PAM. Thus, the combination of the two imaging modalities was simplified. Another advantage of the system is that it realizes non-contact all-optic detection, which is attractive for biomedical imaging. Using the system, we imaged phantoms of carbon fibers, asparagus leaves and human hairs. Furthermore, the cortical vasculature of rat was imaged in vivo and the flow status was evaluated quantitatively.

RESUMEN

MnSO4-modified biochar (Mn-BC) was synthesized to remove berberine hydrochloride (BH) from wastewater by utilizing tea waste as raw material and MnSO4 as modifier. Brunel Emmett Taylor (BET) analysis reveals that the specific surface area (SSA) and average pore size (Dave) of Mn-BC are 1.4 and 7 times higher than those of pristine biochar apart, attributing to the dissociation effect can promote the dispersion of MnSO4 in the pores of the biochar. Meanwhile, the doping of Mn not only introduces additional oxygen-containing functional groups (OCFGs), but also modulates the π electron density. Furthermore, Response surface method (RSM) analysis reveals that Mn-BC dosage has the most significant effect on BH removal, followed by BH concentration and pH value. Kinetic and isothermal studies reveal that the BH adsorption process of Mn-BC was mainly dominated by chemical and monolayer adsorption. Meanwhile, density functional theory (DFT) calculations confirm the contribution of Mn doping to the conjugation effect in the adsorption system. Originally proposed Mn-BC is one potentially propitious material to eliminate BH from wastewater, meanwhile this also provides a newfangled conception over the sustainable utilization of tea waste resources.

RESUMEN

Mangroves perform a crucial ecological role along the tropical and subtropical coastal intertidal zone where salinity fluctuation occurs frequently. However, the differential responses of mangrove plant at the combined transcriptome and metabolome level to variable salinity are not well documented. In this study, we used Avicennia marina (Forssk.) Vierh., a pioneer species of mangrove wetlands and one of the most salt-tolerant mangroves, to investigate the differential salt tolerance mechanisms under low and high salinity using inductively coupled plasma-mass spectrometry, transcriptomic and metabolomic analysis. The results showed that HAK8 was up-regulated and transported K+ into the roots under low salinity. However, under high salinity, AKT1 and NHX2 were strongly induced, which indicated the transport of K+ and Na+ compartmentalization to maintain ion homeostasis. In addition, A. marina tolerates low salinity by up-regulating ABA signaling pathway and accumulating more mannitol, unsaturated fatty acids, amino acids' and L-ascorbic acid in the roots. Under high salinity, A. marina undergoes a more drastic metabolic network rearrangement in the roots, such as more L-ascorbic acid and oxiglutatione were up-regulated, while carbohydrates, lipids and amino acids were down-regulated in the roots, and, finally, glycolysis and TCA cycle were promoted to provide more energy to improve salt tolerance. Our findings suggest that the major salt tolerance traits in A. marina can be attributed to complex regulatory and signaling mechanisms, and show significant differences between low and high salinity.

Asunto(s)

Avicennia , Metaboloma , Raíces de Plantas , Salinidad , Tolerancia a la Sal , Plantas Tolerantes a la Sal , Transcriptoma , Avicennia/genética , Avicennia/fisiología , Avicennia/metabolismo , Plantas Tolerantes a la Sal/genética , Plantas Tolerantes a la Sal/metabolismo , Plantas Tolerantes a la Sal/fisiología , Raíces de Plantas/metabolismo , Raíces de Plantas/genética , Tolerancia a la Sal/genética , Regulación de la Expresión Génica de las Plantas

RESUMEN

The ongoing tide of spent lithium-ion batteries (LIBs) urgently calls for high-value output in efficient recycling. Recently, direct regeneration has emerged as a novel recycling strategy but fails to repair the irreversible morphology and structure damage of the highly degraded polycrystalline layered oxide materials. Here, this work carries out a solid-state upcycling study for the severely cracked LiNi1-x-yCoxMnyO2 cathodes. The specific single-crystallization process during calcination is investigated and the surface rock salt phase is recognized as the intrinsic obstacle to the crystal growth of the degraded cathodes due to sluggish diffusion in the heterogeneous grain boundary. Accordingly, this work revives the fatigue rock salt phase by restoring a layered surface and successfully reshapes severely broken cathodes into the high-performance single-crystalline particles. Benefiting from morphological and structural integrity, the upcycled single-crystalline cathode materials exhibit an enhanced capacity retention rate of 93.5% after 150 cycles at 1C compared with 61.7% of the regenerated polycrystalline materials. The performance is also beyond that of the commercial cathodes even under a high cut-off voltage (4.5 V) or high operating temperature (45 °C). This work provides scientific insights for the upcycling of the highly degraded cathodes in spent LIBs.

RESUMEN

Background: Biomaterials can improve cardiac repair combined with transplantation of bone marrow mononuclear cells (BMMNCs). In this study, we compared the phenotype and cardiac repair between human heart valve-derived scaffold (hHVS) and natural protein/polycaprolactone (NP/PCL) anchored BMNNCs. Methods and results: BMMNCs were obtained from mice five days following myocardial infarction. Subsequently, BMMNCs were separately cultured on hHVS and PCL. Proliferation and cardiomyogenic differentiation were detected in vitro. Cardiac function was measured after transplantation of cell-seeded cardiac patch on MI mice. After that, the BMMNCs were collected for mRNA sequencing after culturing on the scaffolds. Upon anchoring onto hHVS or PCL, BMMNCs exhibited an increased capacity for proliferation in vitro, however, the cells on hHVS exhibited superior cardiomyogenic differentiation ability. Moreover, both BMMNCs-seeded biomaterials effectively improved cardiac function after 4 weeks of transplantation, with reduced infarction area and restricted LV remodeling. Cell-seeded hHVS was superior to cell-seeded PCL. Conclusion: BMMNCs on hHVS showed better capacity in both cell cardiac repairing and improvement for cardiac function than on PCL. Compared with seeded onto PCL, BMMNCs on hHVS had 253 genes up regulated and 189 genes down regulated. The reason for hHVS' better performance than PCL as a scaffold for BMMNCs might be due to the fact that optimized method of decellularization let more cytokines in ECM retained.

RESUMEN

Diabetic kidney disease (DKD), a chronic kidney disease, is characterized by progressive fibrosis caused due to persistent hyperglycemia. The development of fibrosis in DKD determines the patient prognosis, but no particularly effective treatment. Here, small extracellular vesicles derived from mesenchymal stem cells (MSC-sEV) have been used to treat DKD fibrosis. Single-cell RNA sequencing was used to analyze 27,424 cells of the kidney, we have found that a novel fibrosis-associated TGF-ß1+Arg1+ macrophage subpopulation, which expanded and polarized in DKD and was noted to be profibrogenic. Additionally, Actin+Col4a5+ mesangial cells in DKD differentiated into myofibroblasts. Multilineage ligand-receptor and cell-communication analysis showed that fibrosis-associated macrophages activated the TGF-ß1/Smad2/3/YAP signal axis, which promotes mesangial fibrosis-like change and accelerates renal fibrosis niche. Subsequently, the transcriptome sequencing and LC-MS/MS analysis indicated that MSC-sEV intervention could restore the levels of the kinase ubiquitin system in DKD and attenuate renal interstitial fibrosis via delivering CK1δ/ß-TRCP to mediate YAP ubiquitination degradation in mesangial cells. Our findings demonstrate the unique cellular and molecular mechanisms of MSC-sEV in treating the DKD fibrosis niche at a single-cell level and provide a novel therapeutic strategy for renal fibrosis.

Asunto(s)

Nefropatías Diabéticas , Vesículas Extracelulares , Fibrosis , Células Madre Mesenquimatosas , Análisis de la Célula Individual , Transcriptoma , Vesículas Extracelulares/metabolismo , Células Madre Mesenquimatosas/metabolismo , Animales , Ratones , Nefropatías Diabéticas/metabolismo , Nefropatías Diabéticas/terapia , Masculino , Ratones Endogámicos C57BL , Humanos , Macrófagos/metabolismo , Transducción de Señal , Factor de Crecimiento Transformador beta1/metabolismo , Células Mesangiales/metabolismo , Riñón/patología , Riñón/metabolismo

RESUMEN

The design and construction of high strength hydrogels is a widely discussed topic in hydrogel research. In this study, we combined three toughening strategies, including dual network, oriented structure construction and nanophase doping, to develop an alginate/polyacrylamide (PAM)/modified titanium dioxide fiber (TiO2 NF@PAM) dual network composite hydrogel prepared via syringe. The effects of different preparation methods, AM/Alginate ratios, inorganic doping phases and TiO2 NF@PAM/AM ratios on the mechanical properties of composite hydrogels were investigated. The study found that the alginate hydrogel prepared by syringe exhibited superior axial orientation and achieved a tensile strength of (1091 ± 46) kPa. And the composite hydrogel doped with 0.2 wt% TiO2 NF@PAM had a tensile strength of (1006 ± 64) kPa, which was higher than that of the composite hydrogel doped with 0.2 wt% TiO2 nanoparticles (976 ± 66) kPa. The highest tensile strength (1120 ± 67) kPa and elongation at break (182 ± 8) % were achieved when the ratio of TiO2 NF@PAM/AM was 0.6 wt%. The force applied to the gel solution in the syringe affects the orientation of the polymer chains and TiO2 NF@PAM within the gel, which subsequently impacts the mechanical properties of the hydrogel. Therefore, we further investigated the mechanical properties of composite hydrogels under varying propulsion speeds, syringe diameters, and syringe lengths. It was observed that the gel solution's shear strength increased as the syringe diameter decreased. The resulting composite hydrogels were better oriented and had improved mechanical properties. The composite hydrogels' tensile strength peaked at (1117 ± 47) kPa when the syringe advance rate was between 1-7 mL/min. The mechanical properties of the hydrogels were optimal when the syringe length was 30 mm, with a maximum tensile strength of (1131 ± 67) kPa and a tensile ratio of (166 ± 5) %. This study demonstrates the viability of integrating three distinct strengthening methodologies to generate hydrogels of considerable strength. Furthermore, the Alginate/PAM/TiO2 NF@PAM composite hydrogels possess remarkable potential as adaptable, wearable sensors due to their exemplary mechanical properties, knittability, and conductivity.

RESUMEN

Schizophrenia is a severe psychological disorder. The current diagnosis mainly relies on clinical symptoms and lacks laboratory evidence, which makes it very difficult to make an accurate diagnosis especially at an early stage. Plasma protein profiles of schizophrenia patients were obtained and compared with healthy controls using 4D-DIA proteomics technology. Furthermore, 79 DEPs were identified between schizophrenia and healthy controls. GO functional analysis indicated that DEPs were predominantly associated with responses to toxic substances and platelet aggregation, suggesting the presence of metabolic and immune dysregulation in patients with schizophrenia. KEGG pathway enrichment analysis revealed that DEPs were primarily enriched in the chemokine signaling pathway and cytokine receptor interactions. A diagnostic model was ultimately established, comprising three proteins, namely, PFN1, GAPDH and ACTBL2. This model demonstrated an AUC value of 0.972, indicating its effectiveness in accurately identifying schizophrenia. PFN1, GAPDH and ACTBL2 exhibit potential as biomarkers for the early detection of schizophrenia. The findings of our studies provide novel insights into the laboratory-based diagnosis of schizophrenia.

Asunto(s)

Biomarcadores , Profilinas , Proteómica , Esquizofrenia , Esquizofrenia/metabolismo , Esquizofrenia/diagnóstico , Esquizofrenia/sangre , Humanos , Biomarcadores/sangre , Biomarcadores/metabolismo , Proteómica/métodos , Profilinas/metabolismo , Femenino , Masculino , Adulto , Estudios de Casos y Controles , Gliceraldehído-3-Fosfato Deshidrogenasa (Fosforilante)/metabolismo , Persona de Mediana Edad , Proteínas Sanguíneas/análisis , Proteoma/análisis

RESUMEN

Introduction: IgA nephropathy (IgAN) is a leading cause of end-stage renal disease. The exact pathogenesis of IgAN is not well defined, but some genetic studies have led to a novel discovery that the (immuno)proteasome probably plays an important role in IgAN. Methods: We firstly analyzed the association of variants in the UBE2L3 region with susceptibility to IgAN in 3,495 patients and 9,101 controls, and then analyzed the association between lead variant and clinical phenotypes in 1,803 patients with regular follow-up data. The blood mRNA levels of members of the ubiquitin-proteasome system including UBE2L3 were analyzed in peripheral blood mononuclear cells from 53 patients and 28 healthy controls. The associations between UBE2L3 and the expression levels of genes involved in Gd-IgA1 production were also explored. Results: The rs131654 showed the most significant association signal in UBE2L3 region (OR: 1.10, 95% CI: 1.04-1.16, p = 2.29 × 10-3), whose genotypes were also associated with the levels of Gd-IgA1 (p = 0.04). The rs131654 was observed to exert cis-eQTL effects on UBE2L3 in various tissues and cell types, particularly in immune cell types in multiple databases. The UBE2L3, LUBAC, and proteasome subunits were highly expressed in patients compared with healthy controls. High expression levels of UBE2L3 were not only associated with higher proteinuria (r = 0.34, p = 0.01) and lower eGFR (r = -0.28, p = 0.04), but also positively correlated with the gene expression of LUBAC and other proteasome subunits. Additionally, mRNA expression levels of UBE2L3 were also positively correlated with IL-6 and RELA, but negatively correlated with the expression levels of the key enzyme in the process of glycosylation including C1GALT1 and C1GALT1C1. Conclusion: In conclusion, by combined genetic association and differed expression analysis of UBE2L3, our data support a role of genetically conferred dysregulation of the (immuno)proteasome in regulating galactose-deficient IgA1 in the development of IgAN.