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1.
Phys Rev Lett ; 133(8): 086501, 2024 Aug 23.
Artículo en Inglés | MEDLINE | ID: mdl-39241712

RESUMEN

Moiré superlattices of layered transition metal dichalcogenides are proven to host periodic electron crystals due to strong correlation effects. These electron crystals can also be intertwined with intricate magnetic phenomena. In this Letter, we present our findings on the moiré exchange effect, resulting from the modulation of local magnetic moments by electron crystals within well-aligned WSe_{2}/WS_{2} heterobilayers. Employing polarization-resolved magneto-optical spectroscopy, we unveil a high-energy excitonic resonance near one hole per moiré unit cell (v=-1), which possesses a giant g factor several times greater than the already very large g factor of the WSe_{2} A exciton in this heterostructure. Supported by continuum model calculations, these high-energy states are found to be dark excitons brightened through Umklapp scattering from the moiré mini-Brillouin zone. When the carriers form a Mott insulating state near v=-1, the Coulomb exchange between doped carriers and excitons forms an effective magnetic field with moiré periodicity. This moiré exchange effect gives rise to the observed giant g factor for the excitonic Umklapp state.

2.
Heliyon ; 10(17): e36126, 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-39263107

RESUMEN

Unsustainable straw treatment methods detrimentally affect the environment and ecology. Aerobic fermentation (AE) and anaerobic fermentation (AN) are environmentally friendly treatments that better utilise straw resources. In this study, high-throughput sequencing was used to investigate the effects of AE and AN on nutrient content and microbial community structure during tomato straw fermentation. Nitrate nitrogen, available phosphorus, available potassium, and fulvic acid contents following AE were 1250.04 mg/kg, 80.34 %, 161.39 %, and 49.31 %, respectively, which were higher than those following AN. Ammonium nitrogen, humic acid, and humic substance levels following AN were 309.07 %, 31.18 %, and 17.38 %, respectively, which were higher than those following AE. Firmicutes (24.76 %) and Actinobacteria (12.93 %) were more abundant following AE, whereas Proteobacteria (33.82 %) and Bacteroidetes (33.82 %) exhibited higher abundance following AN. AE more effectively eliminated pathogenic bacteria (22.01%-0.26 %) and encouraged stronger interactions between dominant bacterial genera. Redundancy and Mantel test analyses revealed that electrical conductivity and temperature were the most important environmental factors affecting bacterial communities in AE and AN, respectively. AE had a stronger effect on effective nutrient release from tomato straw, implying its greater application potential as a fertiliser. Overall, our study provides a theoretical basis for the optimisation of fermentation methods and processes.

3.
Sci Rep ; 14(1): 20342, 2024 09 02.
Artículo en Inglés | MEDLINE | ID: mdl-39223272

RESUMEN

The correlation between diabetes and coronary artery disease (CAD) is well established. Insulin resistance (IR) is considered a primary contributor to elevated CAD risk in diabetic individuals. The triglyceride-glucose (TyG) index serves as a straightforward surrogate marker for insulin resistance. However, few studies have explored their correlations with myocardial infarction and CAD severity. Therefore, our study aimed to investigate the association between the TyG index and the occurrence of myocardial infarction, as well as the severity of coronary artery disease. We conducted a retrospective study involving 3865 consecutive patients who underwent coronary angiography at the First Affiliated Hospital of Zhejiang University, School of Medicine. Of these, 1724 patients were diagnosed with coronary artery disease. Demographic, biochemical, clinical, and angiographic data were gathered. A robust correlation exists between the TyG index and CAD subtypes, suggesting its potential as an independent clinical diagnostic marker. Moreover, the TyG index exhibited a significant positive correlation with disease severity, as assessed by the Gensini score. Elevated TyG index was associated with an increased predisposition to severe CAD, as indicated by the Gensini score, and myocardial infarction, even after adjusting for well-established cardiovascular risk factors.


Asunto(s)
Glucemia , Angiografía Coronaria , Enfermedad de la Arteria Coronaria , Índice de Severidad de la Enfermedad , Triglicéridos , Humanos , Masculino , Enfermedad de la Arteria Coronaria/sangre , Enfermedad de la Arteria Coronaria/diagnóstico , Triglicéridos/sangre , Persona de Mediana Edad , Glucemia/análisis , Glucemia/metabolismo , Estudios Retrospectivos , Anciano , Infarto del Miocardio/sangre , Infarto del Miocardio/diagnóstico , Infarto del Miocardio/epidemiología , Biomarcadores/sangre , Resistencia a la Insulina , Factores de Riesgo
4.
Nat Nanotechnol ; 2024 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-39251863

RESUMEN

A photonic bandgap is a range of wavelengths wherein light is forbidden from entering a photonic crystal, similar to the electronic bandgap in semiconductors. Fabricating photonic crystals with a complete photonic bandgap in the visible spectrum presents at least two important challenges: achieving a material refractive index > ~2 and a three-dimensional patterning resolution better than ~280 nm (lattice constant of 400 nm). Here we show an approach to overcome such limitations using additive manufacturing, thus realizing high-quality, high-refractive index photonic crystals with size-tunable bandgaps across the visible spectrum. We develop a titanium ion-doped resin (Ti-Nano) for high-resolution printing by two-photon polymerization lithography. After printing, the structures are heat-treated in air to induce lattice shrinkage and produce titania nanostructures. We attain three-dimensional photonic crystals with patterning resolution as high as 180 nm and refractive index of 2.4-2.6. Optical characterization reveals ~100% reflectance within the photonic crystal bandgap in the visible range. Finally, we show capabilities in defining local defects and demonstrate proof-of-principle applications in spectrally selective perfect reflectors and chiral light discriminators.

5.
BMJ Open ; 14(8): e078048, 2024 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-39209503

RESUMEN

BACKGROUND: Inadequate postoperative analgesia is associated with increased risks of various postoperative complications, longer hospital stay, decreased quality of life and higher costs. OBJECTIVES: This study aimed to investigate the risk factors for moderate-to-severe postoperative pain within the first 24 hours and 24-48 hours after major hepatobiliary pancreatic surgery. METHODS: Data of patients who underwent surgery at the Department of Hepatobiliary Surgery in Henan Provincial People's Hospital were collected from January 2018 to August 2020. Univariate and multivariate logistic regression analyses were used to identify the risk factors of postoperative pain. RESULTS: In total, 2180 patients were included in the final analysis. 183 patients (8.4%) suffered moderate-to-severe pain within 24 hours after operation. The independent risk factors associated with moderate-to-severe pain 24 hours after procedures were younger age (OR, 0.97; 95% CI 0.95 to 0.98, p<0.001), lower body mass index (BMI) (OR, 0.94; 95% CI 0.89 to 0.98, p=0.018), open surgery (OR, 0.34; 95% CI 0.22 to 0.52, p<0.001), and postoperative analgesia protocol with sufentanil (OR, 4.38; 95% CI 3.2 to 5.99, p<0.001). Postoperative hospital stay was longer in patients with inadequate analgesia (p<0.05). CONCLUSION: Age, BMI, laparoscopic surgery, and different analgesic drugs were significant predictors of postoperative pain after major hepatobiliary and pancreatic surgery. TRIAL REGISTRATION: ChiCTR2100049726.


Asunto(s)
Dolor Postoperatorio , Humanos , Masculino , Femenino , Dolor Postoperatorio/etiología , Dolor Postoperatorio/tratamiento farmacológico , Persona de Mediana Edad , Factores de Riesgo , Estudios de Casos y Controles , Anciano , China/epidemiología , Dolor Agudo/etiología , Índice de Masa Corporal , Tiempo de Internación/estadística & datos numéricos , Factores de Edad , Adulto , Sufentanilo/administración & dosificación , Sufentanilo/efectos adversos , Procedimientos Quirúrgicos del Sistema Biliar/efectos adversos , Analgésicos Opioides/uso terapéutico
6.
Nano Lett ; 24(34): 10562-10568, 2024 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-39159397

RESUMEN

MnBi2Te4 is a magnetic topological insulator with layered A-type antiferromagnetic order. It exhibits a rich layer- and magnetic-state dependent topological phase diagram; however, much about the coupling between spin, charge, and lattice remains to be explored. In this work, we report that MnBi2Te4 is an excellent acoustic phonon cavity by realizing phonon frequency combs using picosecond ultrasonics. With the generated acoustic phonon wavepackets, we demonstrate that the timing and phase of acoustic echoes can be used to detect the presence of stacking faults between van der Waals layers buried deep within the crystal. Furthermore, by implementing this nondestructive ultrafast optical measurement in conjunction with time-resolved magneto-optical Kerr effect experiments, we uncover that out-of-plane vibrations in MnBi2Te4 do not couple to the magnetic order, i.e. there is no appreciable magnetostriction. Our work points out how a well-developed technique can probe the structural defects and phonon pulse engineering in layered topological insulators.

7.
J Coll Physicians Surg Pak ; 34(8): 981-984, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39113520

RESUMEN

OBJECTIVE: To investigate the frequency of deep vein thrombosis (DVT) in patients aged over 80 years on admission after intertrochanteric femur fracture and to explore the risk factors of DVT. STUDY DESIGN: Descriptive study. Place and Duration of the Study: Department of Orthopaedics, China-Japan Friendship Hospital, Beijing, China, from 1st January 2019 to 31st December 2022. METHODOLOGY: A group of patients aged over 80 years with intertrochanteric fracture were included according to the presence or absence of DVT confirmed by ultrasonography on admission. The patients were divided into the non-DVT and DVT groups. Clinical data were retrospectively compared between the two groups and analysed by multivariate logistic regression to screen risk factors of DVT. RESULTS: A total of 130 patients meeting the inclusion criteria were enrolled, and 37 of them had DVT on admission, with a prevalence of 28.5%, including 25 (67.6%) distal peripheral DVT, 11 (29.7%) proximal central DVT, and 1 (2.7%) mixed DVT. The American Society of Anaesthesiologists (ASA) classification, Charlson comorbidity index, the serum levels of D-dimer, fibrinogen degradation products, albumin, potassium, inorganic phosphorus, and calcium showed significant differences between the two groups (p <0.1). Multivariate analysis identified increased D-dimer (>6.005 mg/L), decreased albumin (<36.45 g/L), and reduced potassium (<3.650 mmol/L) as independent factors for DVT in aged intertrochanteric fracture patients (AIFPs). CONCLUSION: A high incidence of DVT was revealed in AIFPs, and elevated D-dimer levels, reduced albumin levels, and reduced potassium concentrations were shown to be correlated to DVT. KEY WORDS: Intertrochanteric fracture, Deep vein thrombosis, Aged patients, Risk factor, Multivariate logistic regression.


Asunto(s)
Fracturas de Cadera , Trombosis de la Vena , Humanos , Trombosis de la Vena/epidemiología , Trombosis de la Vena/etiología , Femenino , Masculino , Fracturas de Cadera/epidemiología , Factores de Riesgo , Anciano de 80 o más Años , Estudios Retrospectivos , China/epidemiología , Prevalencia , Productos de Degradación de Fibrina-Fibrinógeno/análisis
8.
Exp Mol Med ; 56(8): 1869-1886, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39198543

RESUMEN

Hyperlipidemia and hypertension might play a role in cardiac fibrosis, in which a heterogeneous population of fibroblasts seems important. However, it is unknown whether CD34+ progenitor cells are involved in the pathogenesis of heart fibrosis. This study aimed to explore the mechanism of CD34+ cell differentiation in cardiac fibrosis during hyperlipidemia. Through the analysis of transcriptomes from 50,870 single cells extracted from mouse hearts and 76,851 single cells from human hearts, we have effectively demonstrated the evolving cellular landscape throughout cardiac fibrosis. Disturbances in lipid metabolism can accelerate the development of fibrosis. Through the integration of bone marrow transplantation models and lineage tracing, our study showed that hyperlipidemia can expedite the differentiation of non-bone marrow-derived CD34+ cells into fibroblasts, particularly FABP4+ fibroblasts, in response to angiotensin II. Interestingly, the partial depletion of CD34+ cells led to a notable reduction in triglycerides in the heart, mitigated fibrosis, and improved cardiac function. Furthermore, immunostaining of human heart tissue revealed colocalization of CD34+ cells and fibroblasts. Mechanistically, our investigation of single-cell RNA sequencing data through pseudotime analysis combined with in vitro cellular studies revealed the crucial role of the PPARγ/Akt/Gsk3ß pathway in orchestrating the differentiation of CD34+ cells into FABP4+ fibroblasts. Through our study, we generated valuable insights into the cellular landscape of CD34+ cell-derived cells in the hypertrophic heart with hyperlipidemia, indicating that the differentiation of non-bone marrow-derived CD34+ cells into FABP4+ fibroblasts during this process accelerates lipid accumulation and promotes heart failure via the PPARγ/Akt/Gsk3ß pathway.


Asunto(s)
Antígenos CD34 , Diferenciación Celular , Proteínas de Unión a Ácidos Grasos , Fibroblastos , Fibrosis , Metabolismo de los Lípidos , Fibroblastos/metabolismo , Fibroblastos/patología , Humanos , Ratones , Animales , Antígenos CD34/metabolismo , Proteínas de Unión a Ácidos Grasos/metabolismo , Proteínas de Unión a Ácidos Grasos/genética , Miocardio/metabolismo , Miocardio/patología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Hiperlipidemias/metabolismo , Hiperlipidemias/patología , Masculino , Transducción de Señal , PPAR gamma/metabolismo , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Modelos Animales de Enfermedad
9.
ACS Appl Bio Mater ; 7(9): 6261-6275, 2024 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-39194173

RESUMEN

The increasing complexity and difficulty of surgical procedures have led to a rise in medical errors within clinical settings in recent years. Gastrointestinal diseases, in particular, present significant medical challenges and impose substantial economic burdens, underscoring the urgent need for experiential, high-fidelity gastrointestinal surgical training tools. This study leverages patient-specific computed tomography (CT) and magnetic resonance imaging (MRI) data, combined with 3D printed manufacturing, to develop hydrogel organ models with tunable performance and tissue-mimicking softness. These properties are achieved by regulating the freeze-thaw cycles, cross-linking agents, and the concentration of incorporated antibacterial nanoparticles in DN hydrogels. Through the application of indirect 3D printing and the "sacrificial material method", we successfully fabricate organ tissues such as the stomach, intestines, and blood vessels with high precision. In ex vivo surgical training demonstrations, these tissue-like soft hydrogels provide an effective platform for preoperative simulation and surgical training in digestive surgery, accommodating various surgical procedures and accurately simulating intraoperative bleeding. The development of advanced bionic organ models with specific and tunable characteristics based on DN hydrogels is poised to significantly advance surgical training, medical device testing, and the reform of medical education.


Asunto(s)
Hidrogeles , Ensayo de Materiales , Impresión Tridimensional , Hidrogeles/química , Humanos , Alcohol Polivinílico/química , Materiales Biocompatibles/química , Tamaño de la Partícula , Ingeniería de Tejidos
10.
Neural Netw ; 179: 106620, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-39137470

RESUMEN

The recently introduced neural operator (NO) has been employed as a gain approximator in the backstepping stabilization control of first-order hyperbolic and parabolic partial differential equation (PDE) systems. Due to the global approximation ability of the DeepONet, the NO provides approximate spatial gain function with arbitrary accuracy. The closed-loop system stability can be ensured by the backstepping controller involving the approximate gain with sufficiently small error. In this paper, the NO theory is leveraged to solve the robust output regulation problem for a class of uncertain hyperbolic PDE systems under the design framework of backstepping-based regulator. The NO is trained offline on a dataset containing a sufficient number of system parameters and corresponding prior solutions of the kernel equation, so as to generate feedback gain for the robust regulator. Once the NO is trained, the kernel equation does not need to be solved ever again, for any new system parameters that do not exceed the range of the training set. Based on the internal model principle, the regulator is inherently robust to a degree of parameter uncertainty and error in approximate gain. Therefore, the tracking error can still converge to 0 if the extended regulator equations are solvable and the parameter uncertainty leads to an asymptotically stable origin. We provide a series of theory proofs and a numerical test under the approximate control and observation gains to demonstrate the robust regulation problem. It is shown that the NO is almost three orders of magnitude faster than PDE solver in generating kernel function, and the loss remains on the order of 10-4 in the test. This provides an opportunity to use the NO methodology for accelerated gain scheduling regulation for PDEs with time-varying system parameters.


Asunto(s)
Redes Neurales de la Computación , Algoritmos , Retroalimentación , Simulación por Computador , Incertidumbre
11.
Front Pharmacol ; 15: 1434136, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39185320

RESUMEN

Introduction: Overexposure to ultraviolet (UV) light is known to cause damage to the skin, leading to sunburn and photo-aging. Chemical sunscreen products may give rise to health risks including phototoxicity, photosensitivity, and photosensitivity. Natural polysaccharides have attracted considerable interests due to diverse biological activities. Methods: A novel polysaccharide isolated was purified and structurally characterized using chemical methods followed by HPLC, GLC-MS, as well as 1D and 2D NMR spectroscopy. The photoprotective effect of the EPS on UVB-induced damage was assessed in vitro using cultured keratinocytes and in vivo using C57BL/6 mouse models. Results: The average molecular weight of the EPS was 5.48 × 106 Da, composed of glucose, mannose and galactose residues at a ratio of 2:2:1. The repeating units of the EPS were →3)-ß-D-Glcp (1→3) [ß-D-Galp (1→2)-α-D-Glcp (1→2)]-α-D-Manp (1→3)-α-D-Manp (1→. In cultured keratinocytes, the EPS reduced cytotoxicity and excessive ROS production induced by UVB irradiation. The EPS also exhibits an inhibitory effect on oxidative stress, inflammation, and collagen degradation found in the photodamage in mice. 1H NMR-based metabolomics analysis for skin suggested that the EPS partly reversed the shifts of metabolic profiles of the skin in UVB-exposed mice. Conclusion: The EPS exhibits skin photoprotective effects through regulating oxidative stress both in vivo and in vitro. Our findings highlight that the EPS is a potential candidate in sunscreen formulations for an efficient solution to UVB radiation.

13.
Clin Cancer Res ; 30(18): 4201-4214, 2024 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-39024031

RESUMEN

PURPOSE: The purpose of this study was to investigate the remodeling of the multiple myeloma microenvironment after B-cell maturation antigen (BCMA)-targeted chimeric antigen receptor T (CAR-T) cell therapy. EXPERIMENTAL DESIGN: We performed single-cell RNA sequencing on paired bone marrow specimens (n = 14) from seven patients with multiple myeloma before (i.e., baseline, "day -4") and after (i.e., "day 28") lymphodepleted BCMA CAR-T cell therapy. RESULTS: Our analysis revealed heterogeneity in gene expression profiles among multiple myeloma cells, even those harboring the same cytogenetic abnormalities. The best overall responses of patients over the 15-month follow-up are positively correlated with the abundance and targeted cytotoxic activity of CD8+ effector CAR-T cells on day 28 after CAR-T cell infusion. Additionally, favorable responses are associated with attenuated immunosuppression mediated by regulatory T cells, enhanced CD8+ effector T-cell cytotoxic activity, and elevated type 1 conventional dendritic cell (DC) antigen presentation ability. DC re-clustering inferred intramedullary-originated type 3 conventional DCs with extramedullary migration. Cell-cell communication network analysis indicated that BCMA CAR-T therapy mitigates BAFF/GALECTIN/MK pathway-mediated immunosuppression and activates MIF pathway-mediated anti-multiple myeloma immunity. CONCLUSIONS: Our study sheds light on multiple myeloma microenvironment dynamics after BCMA CAR-T therapy, offering clues for predicting treatment responsivity.


Asunto(s)
Antígeno de Maduración de Linfocitos B , Inmunoterapia Adoptiva , Mieloma Múltiple , Receptores Quiméricos de Antígenos , Microambiente Tumoral , Humanos , Mieloma Múltiple/terapia , Mieloma Múltiple/inmunología , Mieloma Múltiple/patología , Antígeno de Maduración de Linfocitos B/inmunología , Antígeno de Maduración de Linfocitos B/genética , Microambiente Tumoral/inmunología , Inmunoterapia Adoptiva/métodos , Receptores Quiméricos de Antígenos/inmunología , Receptores Quiméricos de Antígenos/genética , Femenino , Depleción Linfocítica , Persona de Mediana Edad , Masculino , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/metabolismo , Anciano
14.
Opt Lett ; 49(13): 3709-3712, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38950248

RESUMEN

In the past few years, annular structured beams have been extensively studied due to their unique "doughnut" structure and characteristics such as phase and polarization vortices. Especially in the 2 µm wavelength range, they have shown promising applications in fields such as novel laser communication, optical processing, and quantum information processing. In this Letter, we observed basis vector patterns with orthogonality and completeness by finely cavity-mode tailoring with end-mirror space position in a Tm:CaYAlO4 laser. Multiple annular structured beams including azimuthally, linearly, and radially polarized beams (APB, LPB, and RPB) operated at a Q-switched mode-locking (QML) state with a typical output power of ∼18 mW around 1962 nm. Further numerical simulation proved that the multiple annular structured beams are the coherent superposition of different Hermitian Gaussian modes. Using a self-made M-Z interferometer, we have demonstrated that the obtained multiple annular beams have a vortex phase with orbital angular momentum (OAM) of l = ±1. To the best of our knowledge, this is the first observation of vector and scalar annular vortex beams in the 2 µm solid-state laser.

15.
PLoS One ; 19(7): e0307809, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39052685

RESUMEN

The airway epithelium plays a pivotal role in regulating mucosal immunity and inflammation. Epithelial barrier function, homeostasis of luminal fluid, and mucociliary clearance are major components of mucosal defense mechanisms. The epithelial sodium channel (ENaC) is one of the key players in controlling airway fluid volume and composition, and characteristic cytokines cause ENaC and barrier dysfunctions following pulmonary infections or allergic reactions. Given the limited understanding of the requisite duration and magnitude of cytokines to affect ENaC and barrier function, available treatment options for restoring normal ENaC activity are limited. Previous studies have demonstrated that distinct amino acids can modulate epithelial ion channel activities and barrier function in intestines and airways. Here, we have investigated the time- and concentration-dependent effect of representative cytokines for Th1- (IFN-γ and TNF-α), Th2- (IL-4 and IL-13), and Treg-mediated (TGF-ß1) immune responses on ENaC activity and barrier function in human bronchial epithelial cells. When cells were exposed to Th1 and Treg cytokines, ENaC activity decreased gradually while barrier function remained largely unaffected. In contrast, Th2 cytokines had an immediate and profound inhibitory effect on ENaC activity that was subsequently followed by epithelial barrier disruption. These functional changes were associated with decreased membrane protein expression of α-, ß-, and γ-ENaC, and decreased mRNA levels of ß- and γ-ENaC. A proprietary blend of amino acids was developed based on their ability to prevent Th2 cytokine-induced ENaC dysfunction. Exposure to the select amino acids reversed the inhibitory effect of IL-13 on ENaC activity by increasing mRNA levels of ß- and γ-ENaC, and protein expression of γ-ENaC. This study indicates the beneficial effect of select amino acids on ENaC activity in an in vitro setting of Th2-mediated inflammation suggesting these amino acids as a novel therapeutic approach for correcting this condition.


Asunto(s)
Aminoácidos , Bronquios , Citocinas , Células Epiteliales , Canales Epiteliales de Sodio , Canales Epiteliales de Sodio/metabolismo , Canales Epiteliales de Sodio/genética , Humanos , Bronquios/citología , Bronquios/metabolismo , Bronquios/efectos de los fármacos , Células Epiteliales/metabolismo , Células Epiteliales/efectos de los fármacos , Citocinas/metabolismo , Aminoácidos/farmacología , Células Th2/inmunología , Células Th2/metabolismo , Células Th2/efectos de los fármacos , Factor de Necrosis Tumoral alfa/metabolismo , Línea Celular , Células TH1/inmunología , Células TH1/efectos de los fármacos , Células TH1/metabolismo , Interleucina-13/metabolismo
16.
Heliyon ; 10(12): e32689, 2024 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-38994051

RESUMEN

Objective: Neuropathic pain has been considered as one of the most serious chronic pain subtypes and causes intolerable suffering to patients physically and mentally. This study aimed to verify the analgesic effect of intravenous administration of human umbilical cord mesenchymal stem cells (HUC-MSCs) upon rats with chronic constriction injury (CCI)-induced neuropathic pain and the concomitant mechanism via modulating microglia. Methods: 30 male SD rats were randomized divided into three groups (n = 10 per group): Sham + Saline group (S&S group), CCI + Saline group (C&S group) and CCI + HUC-MSCs group (C&U group). Rats were injected with either saline or HUC-MSCs via the caudal vein on the 7th day after modelling. The paw mechanical withdrawal threshold (PMWT) and thermal withdrawal latency (TWL) of the ligation side were measured before (day 0) and after (day 1, 3, 5, 7, 9, 11, 13, and 15) modelling. On day 15 after modelling, western-blotting and immunofluorescent staining were used to assess the expressive abundance of Iba-1 (a typical biomarker of activated microglia) in the ligation side of the spinal cord dorsal horn, and ultrastructural changes of the ligation of sciatic nerve were evaluated by transmission electron microscope (TEM). Results: Compared with the S&S group, PMWT and TWL in the C&S group were significantly decreased on day 5 and then persisted to day 15 after modelling (C&S vs S&S, P < 0.05), while a significant amelioration of mechanical hyperalgesia (day 13, day 15) and thermal allodynia (day 9, day 11, day 15) was observed in the C&U group (C&U vs C&S, P < 0.05). Meanwhile, the expression of Iba-1 was significantly suppressed by systemic infusion of HUC-MSCs in the C&U group according to western-blotting and immunofluorescent staining analyses (P < 0.05). With the aid of TEM detection, we intuitively noticed the efficacious reconstruction of the laminate structure of the sciatic nerve ligation, elimination of mitochondrial swelling, and formation of new myelination were noted on day 15 after modelling in the C&U group. Conclusions: Overall, intravenous administration of HUC-MSCs systemically revealed an ameliorative effect upon CCI-induced neuropathic pain in SD rats by inhibiting microglia activation in the dorsal horn of the impaired spinal cord and alleviating sciatic nerve injury. Our findings supply new references for the further development of HUC-MSCs-based cytotherapy for neuropathic pain administration.

17.
Opt Express ; 32(9): 16065-16074, 2024 Apr 22.
Artículo en Inglés | MEDLINE | ID: mdl-38859243

RESUMEN

A Kerr-lens mode-locked laser based on a Yb3+-doped disordered gadolinium scandate (Yb:GdScO3) crystal is reported for the first time, to the best of our knowledge. The crystal with the perovskite structure was grown using the Czochralski method, and its room temperature (RT) and low temperature (LT) spectra were also investigated. Due to the crystal's multisite structure (Gd3+/Sc3+ site), Yb:GdScO3 offers broad and intense polarized emission spectra in the near-infrared range (975-1075 nm). The stimulated emission cross section σSE is 0.46 × 10-20 cm2 at 1000 nm with an emission band width of 75.7 nm for E // b polarization. The continuous wave (CW) laser was operated pumped by a 976 nm fiber-coupled LD laser, resulting in a maximum output power of 8.74 W with a slope efficiency of 76.1% was obtained. Additionally, a pulses as short as 74 fs are generated at ∼1061.7 nm via Kerr-lens mode-locking. The average output power amounts to 32 mW at a pulse repetition rate of 101.4 MHz. All results indicate Yb:GdScO3 a promising candidate for 1 µm ultrashort laser.

18.
Lupus Sci Med ; 11(1)2024 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-38906550

RESUMEN

OBJECTIVE: Systemic lupus erythematosus (SLE) is a type of autoimmune disease that involves multiple organs involved as well as cytokine dysregulation. The treatment of SLE is still challenging due to the side effects of the different drugs used. Receptor-interacting protein kinase 1 (RIPK1) is a kinase involved in T cell homeostasis and autoinflammation. Although clinical trials have shown that RIPK1 inhibition exhibits significant efficacy in different autoimmune diseases, its role in SLE remains unclear. METHODS: MRL/lpr lupus-prone mice received RIPK1 inhibitor ZJU37 or vehicle intraperitoneally for 10 weeks. A BM12-induced chronic graft-versus-host-disease (cGVHD) lupus-like model was introduced in RIPK1 D138N mice or C57BL/6 mice. Nephritis, serum autoantibody levels, dysregulation of adaptive immune response and cytokines were compared in treated and untreated mice. RESULTS: ZJU37 alleviated the clinical features of the MRL/lpr mice including nephritis and anti-dsDNA antibody production. In addition, ZJU37 treatment reduced the proportion of double-negative T cells in the spleen and the cytokines of TNFα, IFN-γ, IL-6, IL-17 and IL-1ß in the serum. Moreover, RIPK1 D138N mice were able to prevent the cGVHD lupus-like model from SLE attack, manifesting as anti-dsDNA antibody production, the proliferation of germinal centre B cells, plasma cells, and T follicular helper cells as well as IgG and C3 deposits in kidneys. CONCLUSION: RIPK1 inhibition has a protective effect in the mouse model of SLE and can potentially become a new therapeutic target for SLE in humans.


Asunto(s)
Citocinas , Modelos Animales de Enfermedad , Enfermedad Injerto contra Huésped , Lupus Eritematoso Sistémico , Ratones Endogámicos C57BL , Ratones Endogámicos MRL lpr , Proteína Serina-Treonina Quinasas de Interacción con Receptores , Animales , Lupus Eritematoso Sistémico/tratamiento farmacológico , Lupus Eritematoso Sistémico/inmunología , Proteína Serina-Treonina Quinasas de Interacción con Receptores/antagonistas & inhibidores , Proteína Serina-Treonina Quinasas de Interacción con Receptores/metabolismo , Ratones , Enfermedad Injerto contra Huésped/tratamiento farmacológico , Enfermedad Injerto contra Huésped/inmunología , Citocinas/metabolismo , Femenino , Anticuerpos Antinucleares/sangre , Nefritis Lúpica/tratamiento farmacológico , Nefritis Lúpica/inmunología , Linfocitos T/inmunología , Linfocitos T/efectos de los fármacos , Bazo/inmunología , Bazo/efectos de los fármacos
19.
J Biol Chem ; 300(7): 107425, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38823639

RESUMEN

Adenosine deaminase (ADA) catalyzes the irreversible deamination of adenosine (ADO) to inosine and regulates ADO concentration. ADA ubiquitously expresses in various tissues to mediate ADO-receptor signaling. A significant increase in plasma ADA activity has been shown to be associated with the pathogenesis of type 2 diabetes mellitus. Here, we show that elevated plasma ADA activity is a compensated response to high level of ADO in type 2 diabetes mellitus and plays an essential role in the regulation of glucose homeostasis. Supplementing with more ADA, instead of inhibiting ADA, can reduce ADO levels and decrease hepatic gluconeogenesis. ADA restores a euglycemic state and recovers functional islets in db/db and high-fat streptozotocin diabetic mice. Mechanistically, ADA catabolizes ADO and increases Akt and FoxO1 phosphorylation independent of insulin action. ADA lowers blood glucose at a slower rate and longer duration compared to insulin, delaying or blocking the incidence of insulinogenic hypoglycemia shock. Finally, ADA suppresses gluconeogenesis in fasted mice and insulin-deficient diabetic mice, indicating the ADA regulating gluconeogenesis is a universal biological mechanism. Overall, these results suggest that ADA is expected to be a new therapeutic target for diabetes.


Asunto(s)
Adenosina Desaminasa , Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Gluconeogénesis , Animales , Masculino , Ratones , Adenosina/metabolismo , Adenosina Desaminasa/metabolismo , Glucemia/metabolismo , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patología , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patología , Proteína Forkhead Box O1/metabolismo , Proteína Forkhead Box O1/genética , Insulina/metabolismo , Hígado/metabolismo , Ratones Endogámicos C57BL , Fosforilación , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Proto-Oncogénicas c-akt/genética
20.
Hortic Res ; 11(6): uhae109, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38883333

RESUMEN

The economically significant genus Prunus includes fruit and nut crops that have been domesticated for shared and specific agronomic traits; however, the genomic signals of convergent and divergent selection have not been elucidated. In this study, we aimed to detect genomic signatures of convergent and divergent selection by conducting comparative population genomic analyses of the apricot-peach-plum-mei (APPM) complex, utilizing a haplotype-resolved telomere-to-telomere (T2T) genome assembly and population resequencing data. The haplotype-resolved T2T reference genome for the plum cultivar was assembled through HiFi and Hi-C reads, resulting in two haplotypes 251.25 and 251.29 Mb in size, respectively. Comparative genomics reveals a chromosomal translocation of ~1.17 Mb in the apricot genomes compared with peach, plum, and mei. Notably, the translocation involves the D locus, significantly impacting titratable acidity (TA), pH, and sugar content. Population genetic analysis detected substantial gene flow between plum and apricot, with introgression regions enriched in post-embryonic development and pollen germination processes. Comparative population genetic analyses revealed convergent selection for stress tolerance, flower development, and fruit ripening, along with divergent selection shaping specific crop, such as somatic embryogenesis in plum, pollen germination in mei, and hormone regulation in peach. Notably, selective sweeps on chromosome 7 coincide with a chromosomal collinearity from the comparative genomics, impacting key fruit-softening genes such as PG, regulated by ERF and RMA1H1. Overall, this study provides insights into the genetic diversity, evolutionary history, and domestication of the APPM complex, offering valuable implications for genetic studies and breeding programs of Prunus crops.

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