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1.
Microsyst Nanoeng ; 10: 107, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39101004

RESUMEN

With the increasing development of intelligent robots and wearable electronics, the demand for high-performance flexible energy storage devices is drastically increasing. In this study, flexible symmetric microsupercapacitors (MSCs) that could operate in a wide working voltage window were developed by combining laser-direct-writing graphene (LG) electrodes with a phosphoric acid-nonionic surfactant liquid crystal (PA-NI LC) gel electrolyte. To increase the flexibility and enhance the conformal ability of the MSC devices to anisotropic surfaces, after the interdigitated LG formed on the polyimide (PI) film surface, the devices were further transferred onto a flexible, stretchable and transparent polydimethylsiloxane (PDMS) substrate; this substrate displayed favorable flexibility and mechanical characteristics in the bending test. Furthermore, the electrochemical performances of the symmetric MSCs with various electrode widths (300, 400, 500 and 600 µm) were evaluated. The findings revealed that symmetric MSC devices could operate in a large voltage range (0-1.5 V); additionally, the device with a 300 µm electrode width (MSC-300) exhibited the largest areal capacitance of 2.3 mF cm-2 at 0.07 mA cm-2 and an areal (volumetric) energy density of 0.72 µWh cm- 2 (0.36 mWh cm- 3) at 55.07 µW cm-2 (27.54 mW cm-3), along with favorable mechanical and cycling stability. After charging for ~20 s, two MSC-300 devices connected in series could supply energy to a calculator to operate for ~130 s, showing its practical application potential as an energy storage device. Moreover, the device displayed favorable reversibility, stability and durability. After 12 months of aging in air at room temperature, its electrochemical performance was not altered, and after charging-discharging measurements for 5000 cycles at 0.07 mA cm-2, ~93.6% of the areal capacitance was still retained; these results demonstrated its practical long-term application potential as an energy storage device.

2.
Immunotherapy ; : 1-11, 2024 Aug 08.
Artículo en Inglés | MEDLINE | ID: mdl-39115961

RESUMEN

Aims: This paper was to scrutinize the toxicity mechanism of anti-programmed death 1 (anti-PD-1) therapy-caused spinal cord injury (SCI). Methods: Bone marrow transplant Rag1-/- mice were used to establish SCI model. Results: Anti-PD-1 results in SCI via CD8+ T-cells activation, while excessive activation of CD8+ T-cells further aggravated SCI. Both anti-PD-1 and the activation of CD8+ T-cells induced the expression of apoptosis-related perforin, GrB and FasL, but suppressed PI-9 level. The opposite results were observed in the effects of neuroserpin on these factors. CD8+ T-cells activation induced neurotoxicity via upregulation perforin, GrB and FasL and inhibiting PI-9. Additionally, neuroserpin suppressed CD8+ T-cells activation via perforin/GrB/PI-9/FasL pathways. Conclusion: These results may provide theoretical foundation for the clinical treatment of SCI caused by anti-PD-1.


What is this article about? In the process of treating cancer, immune checkpoint inhibitors such as anti-programmed death 1 (anti-PD-1) therapy, as a form of immunotherapy, have developed rapidly and changed the way to manage cancers significantly. However, some cancer patients who receive immune checkpoint blockade treatment suffer from severe adverse effects including spinal cord injury (SCI). This article for the first time constructed a bone marrow transplant mouse model to explore the toxicity mechanism of anti-PD-1 therapy-caused SCI.What were the results? We found that anti-PD-1 therapy can induce the activation of immune cells, while immune cell activation further promotes self-destruction of nerve cells by regulating cell death pathways.What do the results of the study mean? The mechanism of anti-PD-1 therapy-caused SCI is to activate of immune cells through regulating cell death pathways, thereby inducing self-destruction of nerve cells. These findings provide theoretical foundation for the clinical treatment of SCI caused by anti-PD-1 therapy.

3.
Cell Death Dis ; 15(8): 590, 2024 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-39138151

RESUMEN

UBE2M, a NEDD8-conjugating enzyme, is dysregulated in various human cancers and promotes tumor cell proliferation. However, its role in estrogen receptor-positive (ER+) breast cancer remains unknown. We found that UBE2M expression was significantly higher in ER+ breast cancer tissues than in ER-negative (ER-) breast cancer tissues. Higher expression of UBE2M indicated a poorer prognosis in patients with ER+ breast cancer but not in those with ER- breast cancer. Of interest, a positive feedback loop was observed between UBE2M and ERα. Specifically, ERα enhanced the HIF-1α-mediated transcription of UBE2M. In turn, UBE2M maintained ERα expression by inhibiting its ubiquitination and degradation through UBE2M-CUL3/4A-E6AP-ERα axis. Functionally, silencing of UBE2M suppressed the growth of breast cancer cells by inducing cell cycle arrest and apoptosis and improved their sensitivity to fulvestrant both in vitro and in vivo. Altogether, our findings reveal that the UBE2M-ERα feedback loop drives breast cancer progression and fulvestrant resistance, suggesting UBE2M as a viable target for endocrine therapy of ER+ breast cancer.


Asunto(s)
Neoplasias de la Mama , Resistencia a Antineoplásicos , Receptor alfa de Estrógeno , Retroalimentación Fisiológica , Enzimas Ubiquitina-Conjugadoras , Humanos , Enzimas Ubiquitina-Conjugadoras/metabolismo , Enzimas Ubiquitina-Conjugadoras/genética , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Neoplasias de la Mama/genética , Neoplasias de la Mama/tratamiento farmacológico , Femenino , Resistencia a Antineoplásicos/efectos de los fármacos , Receptor alfa de Estrógeno/metabolismo , Animales , Progresión de la Enfermedad , Ratones Desnudos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Ratones , Apoptosis/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Fulvestrant/farmacología , Ubiquitinación , Células MCF-7
4.
Hellenic J Cardiol ; 2024 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-39128706

RESUMEN

BACKGROUND: Aortic dissection remains a life-threatening condition necessitating accurate diagnosis and timely intervention. This study aimed to unravel phenotypic heterogeneity in Stanford type B aortic dissection (TBAD) patients through machine learning clustering analysis of cardiovascular CT imaging. METHODS: Electronic medical records were collected to extract demographic and clinical features of TBAD patients. Exclusion criteria ensured homogeneity and clinical relevance of the TBAD cohort. Controls were selected based on age, comorbidity status, and imaging availability. Aortic morphological parameters were extracted from CT angiography (CTA) and subjected to k-means clustering analysis to identify distinct phenotypes. RESULTS: Clustering analysis revealed three phenotypes of TBAD patients with significant correlations to population characteristics and dissection rates. This pioneering study utilized CT-based three-dimensional reconstruction to classify high-risk individuals, demonstrating the potential of machine learning in enhancing diagnostic accuracy and personalized treatment strategies. Recent advancements in machine learning have garnered attention in cardiovascular imaging, particularly in aortic dissection research. These studies leverage various imaging modalities to extract valuable features and information from cardiovascular images, paving the way for more personalized interventions. CONCLUSIONS: This study provides insights into the phenotypic heterogeneity of TBAD patients using machine learning clustering analysis of cardiovascular CT imaging. The identified phenotypes exhibit correlations with population characteristics and dissection rates, highlighting the potential of machine learning in risk stratification and personalized management of aortic dissection. Further research in this field holds promise for improving diagnostic accuracy and treatment outcomes in aortic dissection patients.

5.
Int Immunopharmacol ; 140: 112780, 2024 Aug 06.
Artículo en Inglés | MEDLINE | ID: mdl-39111148

RESUMEN

The healing of diabetic wounds has long been a significant challenge in the field of medicine. The elevated sugar levels surrounding diabetic wounds create a conducive environment for harmful bacterial growth, resulting in purulent infections that impede the healing process. Thus, the development of a biomaterial that can enhance the healing of diabetic wounds holds great importance. This study developed electrospun dressings for wound healing by combining traditional Chinese medicine and clay. The study utilized electrospinning technology to prepare polyvinyl alcohol (PVA) nanofiber membranes containing ASB and HNTs. These ASB@HNTs-PVA nanofiber membranes demonstrated rapid hemostasis, along with antibacterial and anti-inflammatory properties, facilitating the recovery of type 2 diabetic (T2D) wounds. Various analyses were conducted to assess the performance of the composite nanofiber membrane, including investigations into its biocompatibility and hemostatic abilities through antibacterial experiments, cell experiments, and mouse liver tail bleeding experiments. Western blot analysis confirmed that the composite nanofiber membrane could decrease the levels of inflammatory factors IL-1ß and TNF-α. A type 2 diabetic mouse model was utilized, with wounds artificially induced on the backs of mice. Application of the nanofiber membrane to the wounds further confirmed its anti-inflammatory effects and ability to enhance wound healing in vivo.

6.
Neurosurg Rev ; 47(1): 433, 2024 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-39141133

RESUMEN

Receptor-interacting protein kinase-3 (RIP-3) is a key component for inducing necroptosis following acute brain injury. Purpose of this study is to unveil whether serum RIP-3 levels are related to severity and clinical outcomes after human severe traumatic brain injury (sTBI). In this two-center prospective cohort study, serum RIP-3 levels were detected in 127 healthy controls coupled with 127 sTBI patients. The prognostic indicators encompassed posttraumatic 180-day mortality, overall survival and poor prognosis (defined as extended Glasgow outcome scale scores of 1-4). The prognosis associations were verified via multivariate analysis. There was a significant incremental serum RIP-3 levels in patients with sTBI, relative to the controls. RIP-3 levels of patients were independently correlated with Rotterdam Computed Tomography (CT) scores and Glasgow coma scale (GCS) scores, as well as were independently predictive of mortality, overall survival and poor prognosis. Mortality and poor prognosis were effectively predicted by serum RIP-3 levels under the receiver operating characteristic curve. Linear relationships between RIP-3 levels and their risks were verified. Mortality and poor prognosis models of serum RIP-3 levels combined with GCS and Rotterdam CT scores displayed efficient predictive abilities. The two models were graphically represented, which were of clinical stability and value by employing the calibration and decision curves. Increased serum RIP-3 levels after sTBI are closely linked to heightened trauma severity and poor prognosis, signifying that serum RIP-3 may be an encouraging biomarker for evaluating severity and predicting clinical outcome of sTBI.


Asunto(s)
Biomarcadores , Lesiones Traumáticas del Encéfalo , Proteína Serina-Treonina Quinasas de Interacción con Receptores , Humanos , Masculino , Femenino , Persona de Mediana Edad , Pronóstico , Adulto , Lesiones Traumáticas del Encéfalo/sangre , Lesiones Traumáticas del Encéfalo/mortalidad , Lesiones Traumáticas del Encéfalo/diagnóstico , Biomarcadores/sangre , Estudios Prospectivos , Proteína Serina-Treonina Quinasas de Interacción con Receptores/sangre , Anciano , Escala de Coma de Glasgow , Estudios de Cohortes , Adulto Joven
7.
Int J Nanomedicine ; 19: 6519-6546, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38957181

RESUMEN

Background: Salidroside (SAL) is the most effective component of Rhodiola rosea, a traditional Chinese medicine. Cryptotanshinone (CT) is the main fat-soluble extract of Salvia miltiorrhiza, exhibiting considerable potential for application in osteogenesis. Herein, a polycaprolactone/gelatin nanofiber membrane loaded with CT and SAL (PSGC membrane) was successfully fabricated via coaxial electrospinning and characterized. Methods and Results: This membrane capable of sustained and controlled drug release was employed in this study. Co-culturing the membrane with bone marrow mesenchymal stem cells and human umbilical vein endothelial cells revealed excellent biocompatibility and demonstrated osteogenic and angiogenic capabilities. Furthermore, drug release from the PSGC membrane activated the Wnt/ß-catenin signaling pathway and promoted osteogenic differentiation and vascularization. Evaluation of the membrane's vascularization and osteogenic capacities involved transplantation onto a rat's subcutaneous area and assessing rat cranium defects for bone regeneration, respectively. Microcomputed tomography, histological tests, immunohistochemistry, and immunofluorescence staining confirmed the membrane's outstanding angiogenic capacity two weeks post-operation, with a higher incidence of osteogenesis observed in rat cranial defects eight weeks post-surgery. Conclusion: Overall, the SAL- and CT-loaded coaxial electrospun nanofiber membrane synergistically enhances bone repair and regeneration.


Asunto(s)
Gelatina , Glucósidos , Células Endoteliales de la Vena Umbilical Humana , Células Madre Mesenquimatosas , Nanofibras , Neovascularización Fisiológica , Osteogénesis , Fenantrenos , Fenoles , Poliésteres , Ratas Sprague-Dawley , Osteogénesis/efectos de los fármacos , Animales , Nanofibras/química , Gelatina/química , Poliésteres/química , Glucósidos/química , Glucósidos/farmacología , Fenoles/química , Fenoles/farmacología , Fenantrenos/química , Fenantrenos/farmacología , Fenantrenos/farmacocinética , Fenantrenos/administración & dosificación , Humanos , Neovascularización Fisiológica/efectos de los fármacos , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Células Madre Mesenquimatosas/efectos de los fármacos , Células Madre Mesenquimatosas/citología , Ratas , Masculino , Regeneración Ósea/efectos de los fármacos , Membranas Artificiales , Técnicas de Cocultivo , Liberación de Fármacos , Diferenciación Celular/efectos de los fármacos
8.
Front Nutr ; 11: 1399251, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38957868

RESUMEN

Background: There is little research on the relationship between flavonol consumption and chronic kidney disease (CKD). This study aimed to examine the link between flavonol consumption and the risk of CKD among US adults, using data from the 2007-2008, 2009-2010 and 2017-2018 National Health and Nutrition Examination Survey (NHANES). Methods: A cross-sectional approach was used, drawing on data from three NHANES cycles. The flavonol consumption of the participants in this study was assessed using a 48 h dietary recall interview. CKD was diagnosed based on an estimated glomerular filtration rate below 60 mL/min/1.73 m2 or a urine albumin-to-creatinine ratio of 30 mg/g or higher. Results: Compared to the lowest quartile of flavonol intake (Q1), the odds ratios for CKD were 0.598 (95% CI: 0.349, 1.023) for the second quartile (Q2), 0.679 (95% CI: 0.404, 1.142) for the third quartile (Q3), and 0.628 (95% CI: 0.395, 0.998) for the fourth quartile (Q4), with a p value for trend significance of 0.190. In addition, there was a significant trend in CKD risk with isorhamnetin intake, with the odds ratios for CKD decreasing to 0.860 (95% CI: 0.546, 1.354) in the second quartile, 0.778 (95% CI: 0.515, 1.177) in the third quartile, and 0.637 (95% CI: 0.515, 1.177) in the fourth quartile (p for trend = 0.013). Conclusion: Our analysis of the NHANES data spanning 2007-2008, 2009-2010, and 2017-2018 suggests that high consumption of dietary flavonol, especially isorhamnetin, might be linked to a lower risk of CKD in US adults. These findings offer new avenues for exploring strategies for managing CKD.

9.
Microsyst Nanoeng ; 10: 104, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39050588

RESUMEN

Hydraulic technology with smaller sizes and higher reliability trends, including fault prediction and intelligent control, requires high-performance temperature and pressure-integrated sensors. Current designs rely on planar wafer- or chip-level integration, which is limited by pressure range, chip size, and low reliability. We propose a small-size temperature/high-pressure integrated sensor via the flip-chip technique. The pressure and temperature units are arranged vertically, and the sensing signals of the two units are integrated into one plane through silicon vias and gold-gold bonding, reducing the lateral size and improving the efficiency of signal transmission. The flip-chip technique ensures a reliable electrical connection. A square diaphragm with rounded corners is designed and optimised with simulation to sense high pressure based on the piezoresistive effect. The temperature sensing unit with a thin-film platinum resistor measures temperature and provides back-end high-precision compensation, which will improve the precision of the pressure unit. The integrated chip is fabricated by MEMS technology and packaged to fabricate the extremely small integrated sensor. The integrated sensor is characterised, and the pressure sensor exhibits a sensitivity and sensitivity drift of 7.97 mV/MPa and -0.19% FS in the range of 0-20 MPa and -40 to 120 °C. The linearity, hysteresis, repeatability, accuracy, basic error, and zero-time drift are 0.16% FS, 0.04% FS, 0.06% FS, 0.18% FS, ±0.23% FS and 0.04% FS, respectively. The measurement error of the temperature sensor and temperature coefficient of resistance is less than ±1 °C and 3142.997 ppm/°C, respectively. The integrated sensor has broad applicability in fault diagnosis and safety monitoring of high-end equipment such as automobile detection, industrial equipment, and oil drilling platforms.

10.
J Orthop Surg Res ; 19(1): 429, 2024 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-39054551

RESUMEN

BACKGROUND: The relationship between thyroid hormone (TH) levels in vivo and osteoarthritis (OA) remains inconclusive. This study aims to investigate the association between TH levels and OA, analyze the effect of triiodothyronine on hypertrophic chondrocyte differentiation and OA progression, and identify potential target genes of triiodothyronine in OA to evaluate its diagnostic value. METHODS: Two-sample mendelian randomization method was used to probe the causal links between hyperthyroidism and OA. Differentially expressed genes (DEGs) from two RNA-sequencing data in Gene Expression Omnibus (GSE199847 and GSE114007) and enrichment analysis of DEGs (166 commonly upregulated genes and 71 commonly downregulated genes of GSE199847 and GSE114007) was performed to analyze the effect of triiodothyronine (T3) on hypertrophic chondrocyte differentiation and OA. C28/I2 cells treated with T3 and reverse transcription and quantitative real-time polymerase chain reaction were used to validate T3 targeted genes. The diagnostic performance of target genes was assessed by the receiver operating characteristic (ROC) curve and area under the curve (AUC). RESULTS: There was a positive causal association between hyperthyroidism and OA (IVW result, OR = 1.330, 95% CI 1.136-1.557, P = 0.0004). Weighted median and Weighted mode analysis also demonstrated that hyperthyroidism had a positive causal association with OA (p < 0.05, OR > 1). Bioinformatics analysis indicated T3 can partially induce the emergence of late hypertrophic chondrocyte and promote OA through extracellular matrix organization, blood vessel development, skeletal system development and ossification. Post-T3 treatment, MAFB, C1QTNF1, COL3A1 and ANGPTL2 were significantly elevated in C28/I2 cells. ROC curves in GSE114007 showed that AUC of all above genes were ≥ 0.7. CONCLUSIONS: This study identified that hyperthyroidism has a positive causal association with OA by MR analysis. T3 induced hypertrophic chondrocytes promote OA progression by upregulating genes such as MAFB, C1QTNF1, COL3A1 and ANGPTL2, which can also serve as OA diagnosis.


Asunto(s)
Hipertiroidismo , Análisis de la Aleatorización Mendeliana , Osteoartritis , Análisis de Secuencia de ARN , Triyodotironina , Análisis de la Aleatorización Mendeliana/métodos , Osteoartritis/genética , Humanos , Hipertiroidismo/genética , Hipertiroidismo/complicaciones , Triyodotironina/sangre , Análisis de Secuencia de ARN/métodos , Condrocitos/metabolismo , Diferenciación Celular/genética , Progresión de la Enfermedad
11.
J Headache Pain ; 25(1): 117, 2024 Jul 22.
Artículo en Inglés | MEDLINE | ID: mdl-39039470

RESUMEN

INTRODUCTION: Migraine, as a complex neurological disease, brings heavy burden to patients and society. Despite the availability of established therapies, existing medications have limited efficacy. Thus, we aimed to find the drug targets that improve the prognosis of migraine. METHOD: We used Mendelian Randomization (MR) and Summary-data-based MR (SMR) analyses to study possible drug targets of migraine by summary statistics from FinnGen cohorts (nCase = 44,616, nControl = 367,565), with further replication in UK Biobank (nCase = 26,052, nControl = 487,214). Genetic instruments were obtained from eQTLGen and UKB-PPP to verify the drug targets at the gene expression and protein levels. The additional analyses including Bayesian co-localization, the heterogeneity in dependent instruments(HEIDI), Linkage Disequilibrium Score(LDSC), bidirectional MR, multivariate MR(MVMR), heterogeneity test, horizontal pleiotropy test, and Steiger filtering were implemented to consolidate the findings further. Lastly, drug prediction analysis and phenome-wide association study(PheWAS) were employed to imply the possibility of drug targets for future clinical applications. RESULT: The MR analysis of eQTL data showed that four drug targets (PROCR, GSTM4, SLC4A1, and TNFRSF10A) were significantly associated with migraine risk in both the FinnGen and UK Biobank cohorts. However, only GSTM4 exhibited consistent effect directions across the two outcomes(Discovery cohort: OR(95%CI) = 0.94(0.93-0.96); p = 2.70e - 10; Replication cohort: OR(95%CI) = 0.93(0.91-0.94); p = 4.21e - 17). Furthermore, GSTM4 passed the SMR at p < 0.05 and HEIDI test at p > 0.05 at both the gene expression and protein levels. The protein-level MR analysis revealed a strong correlation between genetically predicted GSTM4 with a lower incidence of migraine and its subtypes(Overall migraine: OR(95%CI) = 0.91(0.87-0.95); p = 6.98e-05; Migraine with aura(MA): OR(95%CI) = 0.90(0.85-0.96); p = 2.54e-03; Migraine without aura(MO): OR(95%CI) = 0.90(0.83-0.96); p = 2.87e-03), indicating a strong co-localization relationship (PPH4 = 0.86). Further analyses provided additional validation for the possibility of GSTM4 as a migraine treatment target. CONCLUSION: This study identifies GSTM4 as a potential druggable gene and promising therapeutic target for migraine.


Asunto(s)
Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Trastornos Migrañosos , Humanos , Trastornos Migrañosos/genética , Trastornos Migrañosos/tratamiento farmacológico , Análisis de la Aleatorización Mendeliana/métodos , Sitios de Carácter Cuantitativo/genética , Polimorfismo de Nucleótido Simple/genética , Glutatión Transferasa/genética , Predisposición Genética a la Enfermedad/genética , Multiómica
12.
Rev Cardiovasc Med ; 25(4): 110, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-39076556

RESUMEN

In this comprehensive review, we examine the intricate interplay between inflammation, ferroptosis, and atrial fibrillation (AF), highlighting their significant roles in AF pathophysiology and pathogenesis. Augmented inflammatory responses are pivotal to AF, potentially leading to atrial remodeling and reentry phenomena by impacting calcium channels and atrial tissue fibrosis. A strong correlation exists between inflammatory cytokines and AF, underscoring the importance of inflammatory signaling pathways, such as NOD-like receptor thermal protien domain associated protein 3 (NLRP3) inflammasome, Nuclear Factor kappa B (NF- κ B) signaling, and Tumor necrosis factor- α (TNF- α ) signaling in AF development. Ferroptosis, a non-apoptotic regulated mode of cell death, has been widely studied in relation to cardiovascular diseases including heart failure, myocardial infarction, cardiomyopathy, and reperfusion injury. The interaction between ferroptosis and inflammation is complex and mutually influential. While significant progress has been made in understanding the inflammation-AF relationship, the role of inflammation as a conduit linking ferroptosis and AF remains underexplored. The specific pathogenesis and key molecules of atrial fibrosis caused by ferroptosis are still not fully understood. Here we review the role of inflammatory signaling in ferroptosis and AF. We elucidated the association between ferroptosis and AF, aiming to unveil mechanisms for targeted inhibition of atrial cell fibrosis and to propose novel therapeutic strategies for AF. This exploration is vital for advancing our knowledge and developing more effective interventions for AF, a condition deeply intertwined with inflammatory processes and ferroptotic pathways.

13.
Biotechnol Biofuels Bioprod ; 17(1): 88, 2024 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-38918796

RESUMEN

BACKGROUND: ß-Arbutin, a hydroquinone glucoside found in pears, bearberry leaves, and various plants, exhibits antioxidant, anti-inflammatory, antimicrobial, and anticancer effects. ß-Arbutin has wide applications in the pharmaceutical and cosmetic industries. However, the limited availability of high-performance strains limits the biobased production of ß-arbutin. RESULTS: This study established the ß-arbutin biosynthetic pathway in C. glutamicum ATCC13032 by introducing codon-optimized ubiC, MNX1, and AS. Additionally, the production titer of ß-arbutin was increased by further inactivation of csm and trpE to impede the competitive metabolic pathway. Further modification of the upstream metabolic pathway and supplementation of UDP-glucose resulted in the final engineered strain, C. glutamicum AR11, which achieved a ß-arbutin production titer of 7.94 g/L in the optimized fermentation medium. CONCLUSIONS: This study represents the first successful instance of de novo ß-arbutin production in C. glutamicum, offering a chassis cell for ß-arbutin biosynthesis.

14.
Adv Sci (Weinh) ; : e2306237, 2024 Jun 23.
Artículo en Inglés | MEDLINE | ID: mdl-38922800

RESUMEN

Abdominal aortic aneurysm (AAA) is a common and potentially life-threatening condition. Chronic aortic inflammation is closely associated with the pathogenesis of AAA. Nerve injury-induced protein 1 (NINJ1) is increasingly acknowledged as a significant regulator of the inflammatory process. However, the precise involvement of NINJ1 in AAA formation remains largely unexplored. The present study finds that the expression level of NINJ1 is elevated, along with the specific expression level in macrophages within human and angiotensin II (Ang II)-induced murine AAA lesions. Furthermore, Ninj1flox/flox and Ninj1flox/floxLyz2-Cre mice on an ApoE-/- background are generated, and macrophage NINJ1 deficiency inhibits AAA formation and reduces macrophage infiltration in mice infused with Ang II. Consistently, in vitro suppressing the expression level of NINJ1 in macrophages significantly restricts macrophage adhesion and migration, while attenuating macrophage pro-inflammatory responses. Bulk RNA-sequencing and pathway analysis uncover that NINJ1 can modulate macrophage infiltration through the TLR4/NF-κB/CCR2 signaling pathway. Protein-protein interaction analysis indicates that NINJ1 can activate TLR4 by competitively binding with ANXA2, an inhibitory interacting protein of TLR4. These findings reveal that NINJ1 can modulate AAA formation by promoting macrophage infiltration and pro-inflammatory responses, highlighting the potential of NINJ1 as a therapeutic target for AAA.

15.
J Am Chem Soc ; 2024 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-38858162

RESUMEN

Understanding how life's essential homochiral biopolymers arose from racemic precursors is a challenging quest. Herein, we present a groundbreaking approach involving hierarchical chiral assembly-driven stereoselective ring-opening polymerization of ε-benzyloxycarbonyl-l/d-lysine N-carboxyanhydrides assisted by ultrasonication in an aqueous medium. This method enabled a narrow dispersity within a few minutes and the achievement of high molecular weight for polypeptides, employing a living polymerization mechanism. The polymerization of l and d enantiomers yielded predominantly right- and left-handed superhelical assemblies in a one-pot preparation, respectively. Notably, stereoselective polypeptide segments were efficiently prepared through hierarchical assembly-driven polymerization of racemic monomers in the absence of a catalyst. This research offers an innovative strategy for the convenient preparations of stereoenriched polypeptides and, more importantly, sheds light on the plausible emergence of homochiral peptides in the origin of life.

16.
Genomics ; 116(4): 110872, 2024 07.
Artículo en Inglés | MEDLINE | ID: mdl-38849017

RESUMEN

Cattle-yak is a hybrid offspring resulting from the crossbreeding of yak and cattle, and it exhibits substantial heterosis in production performance. However, male sterility in cattle-yak remains a concern. Reports suggest that noncoding RNAs are involved in the regulation of spermatogenesis. Therefore, in this study, we comprehensively compared testicular transcription profiles among cattle, yak, and cattle-yak. Numerous differentially expressed genes (DEGs), differentially expressed circRNAs (DECs), and differentially expressed miRNAs (DEMs) were identified in the intersection of two comparison groups, namely cattle versus cattle-yak and yak versus cattle-yak, with the number of DEGs, DECs, and DEMs being 4968, 360, and 59, respectively. The DEGs in cattle-yaks, cattle, and yaks were mainly associated with spermatogenesis, male gamete generation, and sexual reproduction. Concurrently, GO and KEGG analyses indicated that DEC host genes and DEM source genes were involved in the regulation of spermatogenesis. The construction of a potential competing endogenous RNA network revealed that some differentially expressed noncoding RNAs may be involved in regulating the expression of genes related to testicular spermatogenesis, including miR-423-5p, miR-449b, miR-34b/c, and miR-15b, as well as previously unreported miR-6123 and miR-1306, along with various miRNA-circRNA interaction pairs. This study serves as a valuable reference for further investigations into the mechanisms underlying male sterility in cattle-yaks.


Asunto(s)
Redes Reguladoras de Genes , MicroARNs , ARN Circular , ARN Mensajero , Testículo , Bovinos/genética , Bovinos/metabolismo , Animales , Masculino , Testículo/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , ARN Circular/genética , ARN Circular/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Espermatogénesis/genética , Transcriptoma , ARN Endógeno Competitivo
17.
Noise Health ; 26(121): 235-241, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38904829

RESUMEN

OBJECTIVE: This study aimed to analyze the effects of ward noise reduction administration on the lung function and mental health of patients with lung cancer. METHODS: A total of 195 patients who underwent lung cancer surgery in PLA Northern Theater Command Air Force Hospital from November 2020 to November 2022 were selected to be divided into a control group (routine nursing) and an observation group (routine nursing and ward noise reduction administration) in accordance with the medical record system. The general demographic data, noise level, lung function (forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC)), and complications of patients in the two groups were collected. Propensity score matching (PSM) was used to balance the baseline data of the two groups, and t-test and chi-square test were used to analyze the data. RESULTS: After PSM was conducted, 50 patients were enrolled in each group. No statistical difference was found in the baseline data, preadministration noise levels, and FEV1, FVC, FEV1/FVC, state-anxiety inventory (S-AI), and trait anxiety inventory scale (T-AI) scores between the two groups (P > 0.05). After ward noise reduction was administered, the noise level in the observation group was lower than that in the control group (P < 0.05). The FEV1, FVC, and FEV1/FVC scores of the observation group were higher than those of the control group but were not statistically significant (P > 0.05). The S-AI and T-AI scores of the observation group were lower than those of the control group (P < 0.05). No differences were found in the complications between the two groups (P > 0.05). CONCLUSION: Administering ward noise reduction in patients with lung cancer can alleviate their negative emotions, thus worthy of clinical adoption.


Asunto(s)
Neoplasias Pulmonares , Ruido , Humanos , Masculino , Femenino , Persona de Mediana Edad , Ruido/efectos adversos , Anciano , Salud Mental , Volumen Espiratorio Forzado , Capacidad Vital , Pruebas de Función Respiratoria , Adulto , Ansiedad/prevención & control , Ansiedad/etiología
18.
Vaccines (Basel) ; 12(6)2024 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-38932395

RESUMEN

Therapeutic HPV vaccines that induce potent HPV-specific cellular immunity and eliminate pre-existing infections remain elusive. Among various candidates under development, those based on DNA constructs are considered promising because of their safety profile, stability, and efficacy. However, the use of electroporation (EP) as a main delivery method for such vaccines is notorious for adverse effects like pain and potentially irreversible muscle damage. Moreover, the requirement for specialized equipment adds to the complexity and cost of clinical applications. As an alternative to EP, lipid nanoparticles (LNPs) that are already commercially available for delivering mRNA and siRNA vaccines are likely to be feasible. Here, we have compared three intramuscular delivery systems in a preclinical setting. In terms of HPV-specific cellular immune responses, mice receiving therapeutic HPV DNA vaccines encapsulated with LNP demonstrated superior outcomes when compared to EP administration, while the naked plasmid vaccine showed negligible responses, as expected. In addition, SM-102 LNP M exhibited the most promising results in delivering candidate DNA vaccines. Thus, LNP proves to be a feasible delivery method in vivo, offering improved immunogenicity over traditional approaches.

19.
Chem Soc Rev ; 53(13): 6917-6959, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38836324

RESUMEN

Electrochemical energy conversion and storage are playing an increasingly important role in shaping the sustainable future. Differential electrochemical mass spectrometry (DEMS) offers an operando and cost-effective tool to monitor the evolution of gaseous/volatile intermediates and products during these processes. It can deliver potential-, time-, mass- and space-resolved signals which facilitate the understanding of reaction kinetics. In this review, we show the latest developments and applications of DEMS in various energy-related electrochemical reactions from three distinct perspectives. (I) What is DEMS addresses the working principles and key components of DEMS, highlighting the new and distinct instrumental configurations for different applications. (II) How to use DEMS tackles practical matters including the electrochemical test protocols, quantification of both potential and mass signals, and error analysis. (III) Where to apply DEMS is the focus of this review, dealing with concrete examples and unique values of DEMS studies in both energy conversion applications (CO2 reduction, water electrolysis, carbon corrosion, N-related catalysis, electrosynthesis, fuel cells, photo-electrocatalysis and beyond) and energy storage applications (Li-ion batteries and beyond, metal-air batteries, supercapacitors and flow batteries). The recent development of DEMS-hyphenated techniques and the outlook of the DEMS technique are discussed at the end. As DEMS celebrates its 40th anniversary in 2024, we hope this review can offer electrochemistry researchers a comprehensive understanding of the latest developments of DEMS and will inspire them to tackle emerging scientific questions using DEMS.

20.
Eur Radiol ; 2024 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-38913246

RESUMEN

OBJECTIVE: To investigate the prognostic value of preoperative body composition and serum tumor markers (STM) in patients undergoing surgical treatment for colorectal cancer (CRC) and to establish the prognostic score for patients with CRC. METHODS: This study enrolled 365 patients (training set 245, validation set 120) with CRC who underwent surgical resection. The predictive value of various body composition features and STM for determining CRC prognosis were compared. A novel index score based on the independent risk factors from Cox regression for CRC patients was established and evaluated for its usefulness. RESULTS: Multivariate Cox regression showed that low skeletal muscle radiodensity (SMD) (p = 0.020), low subcutaneous fat area (SFA) (p = 0.029), high carcinoembryonic antigen (CEA) (p = 0.008), and high alpha-fetoprotein (AFP) (p = 0.039) were all independent prognostic factors for poor overall survival (OS). The multifactorial analysis indicated that high intermuscular fat area (IMFA) (p = 0.033) and high CEA (p = 0.009) were independent prognostic factors for poor disease-free survival (DFS). Based on these findings, two scoring systems for OS and DFS were established in the training datasets. CRC patients who scored higher on the new scoring systems had lower OS and DFS (both p < 0.001) as shown in the Kaplan-Meier survival curves in the training and validation datasets. CONCLUSION: In predicting the prognosis of CRC patients, SFA and SMD are superior to other body composition measurements. A scoring system based on body composition and STM can have prognostic value and clinical applicability. CLINICAL RELEVANCE STATEMENT: This scoring system, combining body composition and serum tumor markers, may help predict postoperative survival of CRC patients and help clinicians make well-informed decisions regarding the treatment of patients. KEY POINTS: Colorectal cancer prognosis can be related to body composition. High intermuscular fat area and CEA were independent prognostic factors for poor disease-free survival. This scoring system, based on body composition and tumor markers, can prognosticate for colorectal cancer patients.

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