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BACKGROUND: Innovative attempt to explore the feasibility and accuracy of using indocyanine green fluorescence (ICGF) to identify the intersegmental plane by the target segmental veins preferential ligation during thoracoscopic segmentectomy. METHODS: A retrospective analysis was conducted on clinical data of 32 consecutive patients who underwent thoracoscopic segmentectomy with intersegmental plane identification using both ICGF and inflation-deflation method after target segmental veins prioritized blocking at Nanjing Chest Hospital from December 2022 to June 2023. Preoperative three-dimensional reconstruction was used to identify the target segment and the anatomical structure of the arteries, veins, and bronchi. After ligating the target segmental veins during surgery, the first intersegmental plane was immediately identified and marked with an electrocoagulation device using an inflation-deflation method. Subsequently, the second intersegmental plane was determined using the ICGF method. Finally, the consistency of the two intersegmental planes was evaluated. RESULTS: All the 32 patients successfully completed thoracoscopic segmentectomy without ICG-related complications and perioperative death. The average operation time was (98.59 ± 20.72) min, the average intraoperative blood loss was (45.31 ± 35.65) ml, and the average postoperative chest tube removal time was (3.5 ± 1.16) days. The average postoperative hospital stay was (4.66 ± 1.29) days, and the average tumor margin width was (26.96 ± 5.86) mm. The intersegmental plane determined by ICGF method was basically consistent with inflation-deflation method in all patients. CONCLUSION: The ICGF can safely and accurately identify the intersegmental plane by target segmental veins preferential ligation during thoracoscopic segmentectomy, which is a beneficial exploration and important supplement to the simplified thoracoscopic anatomical segmentectomy.
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Verde de Indocianina , Neoplasias Pulmonares , Neumonectomía , Humanos , Femenino , Estudios Retrospectivos , Masculino , Persona de Mediana Edad , Neumonectomía/métodos , Neoplasias Pulmonares/cirugía , Neoplasias Pulmonares/patología , Anciano , Cirugía Torácica Asistida por Video/métodos , Estudios de Factibilidad , Ligadura/métodos , Toracoscopía/métodos , Tempo Operativo , Fluorescencia , Adulto , Venas Pulmonares/cirugía , Imagenología TridimensionalRESUMEN
BACKGROUND: Trillium tschonoskii rhizome saponins (TSTT) has been significantly effective in treating traumatic injury, neurasthenia, cancer and inflammatory diseases as a folk medicine. However, the mechanism regarding to TSTT induced the neurovascular restorative after ischemia is without fully elucidated. PURPOSE: This research was constructed to study the value of TSTT in promoting endogenous repair of neurovascular and augmenting the ability of spatial study and memory retention in ischaemic rats. STUDY DESIGN: The improvement of TSTT on cerebral infraction and perfusion was observed by magnetic resonance imaging (MRI) experiments and the molecular mechanisms were further explored. METHODS: First, rats were ligated the middle cerebral artery to construct a permanent ischaemia model, subsequently intragastric injection administrated with TSTT (120, 60, 30 mg kg-1) at 6 h after operation, then once a day during next 30 days. Morris water maze was applied to observe the neurobehavioral changes. Multimodal MRI sequences were performed to monitoring brain injuries as well as cerebral blood flow. Histopathological staining was employed to evaluate the morphological changes of neurons. Transmission electron microscopy (TEM) was employed to detect the neurons, vascular structure, and synapse. Immunofluorescent staining was utilized to evaluate the endogenous repair progress. The axonal growth-inhibitors and axonal guidance cues were analyzed using western blotting. RESULTS: Contrast to the model group, TSTT declined the infarction and elevated the parenchymal volume. Notably, treated with TSTT significantly decreased the ADC (ipsilateral/contralateral). In histopathologic examination, TSTT prominently boosted amounts of cortical and striatal nerve cells and protected ultrastructure of neurovascular unit. According with results of nuclear magnetic imaging, TSTT enhanced endogenous repair progress. Especially, TSTT treatments obviously inhibited protein levels of NogoA/NgR/RhoA/ROCK2, accompanied by increased expression of Netrin/DCC and Slit2/Robo1. CONCLUSION: To sum up, our data illustrated that TSTT promoted cerebral reestablishment. The above result was in line with improving cerebral blood flow, elevated integrity of neurovascular structure, accelerating endogenous restoration and impairing the axonal growth inhibitors NogoA/NgR/RhoA/ROCK2 signaling, thereby improving poststroke learning and memory.
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In a molecule formed by two atoms, energy difference between bonding and antibonding orbitals depends on distance between the two atoms. However, exploring molecular orbitals of two natural atoms with tunable distance has remained an outstanding experimental challenge. Graphene quantum dots can be viewed as relativistic artificial atoms, thus offering a unique platform to study molecular physics. Here, through scanning tunneling microscope, we create and directly visualize the formation process of relativistic artificial molecules based on two coupled graphene quantum dots with tunable distance. Our study indicates that energy difference between the bonding and antibonding orbitals of the lowest quasibound state increases linearly with inverse distance between the two graphene quantum dots due to the relativistic nature of the artificial molecule. For quasibound states with higher orbital momenta, the coupling between these states leads to half-energy spacing of the confined states because the length of the molecular-like orbit is approximately twice that of the atomic-like orbit. Evolution from ring-like whispering-gallery modes in the artificial atoms to figure-eight orbitals in the artificial molecules is directly imaged. The ability to resolve the coupling and orbitals of the relativistic artificial molecule at the nanoscale level yields insights into the behavior of quantum-relativistic matter.
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The electrocatalytic activity of PtNi nanowires is enhanced by the co-presence of ionic liquid in carbon mesopores. Three-dimensional transmission electron microscopy tomography and surface-enhanced infrared absorption spectroscopy confirm the co-presence of PtNi nanowires and ionic liquid inside carbon mesopores even under electrochemical conditions.
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Molecular oxygen redox electrocatalysis involves oxygen reduction and evolution as core reactions in various energy conversion and environmental technology fields. Strong metal-support interactions (SMSIs) based nanomaterials are regarded as desirable and state-of-the-art heterogeneous electrocatalysts due to their exceptional physicochemical properties. Over the past decades, considerable advancements in theory and experiment have been achieved in related studies, especially in modulating the electronic structure and geometrical configuration of SMSIs to enable activity, selectivity, and stability. In this focuses on the concept of SMSI, explore their various manifestations and mechanisms of action, and summarizes recent advances in SMSIs for efficient energy conversion in oxygen redox electrocatalysis applications. Additionally, the correlation between the physicochemical properties of different metals and supports is systematically elucidated, and the potential mechanisms of the structure-activity relationships between SMSIs and catalytic performance are outlined through theoretical models. Finally, the obstacles confronting this burgeoning field are comprehensively concluded, targeted recommendations and coping strategies are proposed, and future research perspectives are outlined.
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The coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has highlighted the pivotal role of the immune response in determining the progression and severity of viral infections. In this paper, we review the most recent studies on the complicated dynamics between SARS-CoV-2 and the host immune system, highlight the importance of understanding these dynamics in developing effective treatments and formulate potent management strategies for COVID-19. We describe the activation of the host's innate immunity and the subsequent adaptive immune response following infection with SARS-CoV-2. In addition, the review emphasizes the immune evasion strategies of the SARS-CoV-2, including inhibition of interferon production and induction of cytokine storms, along with the resulting clinical outcomes. Finally, we assess the efficacy of current treatment strategies, including antiviral drugs, monoclonal antibodies, and anti-inflammatory treatments, and discuss their role in providing immunity and preventing severe disease.
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Berberine (BBR), a well-known quaternary ammonium alkaloid, is recognized for its ability to prevent and alleviate metabolic disorders because of its anti-oxidative and anti-inflammatory properties. However, the underlying mechanisms of BBR to mitigate fatty liver hemorrhagic syndrome (FLHS) through the modulation of gut microbiota and their metabolism remained unclear. The results revealed that BBR ameliorates lipid metabolism disorder in high-energy and low-protein (HELP) diet-induced FLHS laying hens, as evidenced by improved liver function and lipid deposition of the liver, reduced blood lipids, and the expression of liver lipid synthesis-related factors. Moreover, BBR alleviated HELP diet-induced barrier dysfunction, increased microbial population, and dysregulated lipid metabolism in the ileum. BBR reshaped the HELP-perturbed gut microbiota, particularly declining the abundance of Desulfovibrio_piger and elevating the abundance of Bacteroides_salanitronis_DSM_18170. Meanwhile, metabolomic profiling analysis revealed that BBR reshaped microbial metabolism and function, particularly by reducing the levels of hydrocinnamic acid, dehydroanonaine, and leucinic acid. Furthermore, fecal microbiota transplantation (FMT) experiments revealed that BBR-enriched gut microbiota alleviated hepatic lipid deposition and intestinal inflammation compared with those chicks that received a gut microbiota by HELP. Collectively, our study provided evidence that BBR effectively alleviated FLHS induced by HELP by reshaping the microbial and metabolic homeostasis within the liver-gut axis.
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Alimentación Animal , Berberina , Pollos , Microbioma Gastrointestinal , Enfermedades de las Aves de Corral , Animales , Microbioma Gastrointestinal/efectos de los fármacos , Femenino , Enfermedades de las Aves de Corral/microbiología , Enfermedades de las Aves de Corral/prevención & control , Alimentación Animal/análisis , Berberina/farmacología , Berberina/administración & dosificación , Dieta con Restricción de Proteínas/veterinaria , Metabolómica , Hígado Graso/veterinaria , Metabolismo de los Lípidos/efectos de los fármacos , Suplementos Dietéticos/análisisRESUMEN
OBJECTIVES: To observe the efficacy and safety of ginger-partitioned moxibustion combined with ringheaded thumb-tack needle stimulation in the prevention and treatment of chemotherapy-induced nausea and vomiting (CINV) in patients with malignant tumors. METHODS: Patients with malignant tumors and suffering from chemotherapy were randomly divided into control group (35 cases, 4 cases dropped off) and observation group (35 cases, 2 cases dropped off). The patients of the control group were treated by orally taking ondansetron hydrochloride tablets 8 mg/time, 3 times a day for 3 d, and those of the observation group treated by ginger-partitioned moxibustion combined with ringheaded thumb-tack needle stimulation of Zusanli(ST36), Neiguan(PC6), Tianshu(ST25), Zhongwan(CV12) and Guanyuan(CV4) once a day for a total of 3 d, based on the treatment of the control group. The patients' gastrointestinal reaction degree after the 1st , 2nd and the 3rd day of treatment were recorded. The Karnofsky performance status (KPS) score (0-100 points) was used for assessing the patients' quality of life. The TCM syndrome score (4 gradesï¼no, mild, medium and severe, i.e. 0, 2, 4 and 6 points) was given according to the patients' severity of symptoms of spleen (stomach) qi deficiency (nausea and vomiting, abdominal distension after eating, belching, loss of appetite, weakness and laziness to speak, fatigue, and loose stool). The safety of the treatment was assessed by examining the patients' blood routine, liver function and kidney function, and the adverse reactions including blisters, allergies, burns and fainting during acupuncture treatment. RESULTS: After the 2nd and 3rd day of treatment, the patients conditions of vomiting and nausea in the observation group were significantly better than those of the control group (P<0.05). The TCM syndrome score and KPS score were significantly decreased in comparison with those of pre-treatment in both groups (P<0.05), and the TCM syndrome score was obviously lower in the observation group than in the control group (P<0.05). No significant differences were found between the two groups in the KPS score after the treatment , and in the levels of white blood cells (WBC), hemoglobin (HGB), platelets (PLT), absolute neutrophil count (ANC), alanine transaminase (ALT), aspartate aminotransferase (AST), creatinine(Cr), and blood urea nitrogen (BUN). CONCLUSIONS: The use of ginger-partitioned moxibustion combined with ringheaded thumb-tack needle stimulation is safe for CINV patients, and can effectively relieve nausea and vomiting and alleviate digestive symptoms.
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Moxibustión , Náusea , Neoplasias , Vómitos , Zingiber officinale , Humanos , Masculino , Persona de Mediana Edad , Femenino , Zingiber officinale/química , Adulto , Neoplasias/terapia , Neoplasias/tratamiento farmacológico , Anciano , Náusea/terapia , Náusea/etiología , Náusea/prevención & control , Vómitos/terapia , Puntos de Acupuntura , Adulto Joven , Terapia por Acupuntura , Antineoplásicos/efectos adversos , Tracto Gastrointestinal/fisiopatologíaRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Astragaloside IV (AS), a key active ingredient obtained from Chinese herb Astragalus mongholicus Bunge, exerts potent neuroprotective and anti-inflammatory effects for treating neurodegenerative diseases. However, mechanisms of AS on improvement of ischemic brain tissue repair remain unclear. AIM OF THE STUDY: This research aims at using magnetic resonance imaging (MRI) to noninvasively determine whether AS facilitates brain tissue repair, and investigating whether AS exerts brain remodeling through adenosine monophosphate-activated protein kinase (AMPK) metabolic signaling regulating key glycolytic enzymes and energy transporters, thereby impacting microglia polarization. MATERIALS AND METHODS: Ischemic stroke model in male Sprague-Dawley rats were induced through permanent occlusion of the middle cerebral artery (MCAO). Infarct volume, the alterations of brain microstructure and nerve fibers reorganization were examined by multi-parametric MRI. The pathological damages of myelinated axons and microglia polarization surrounding infarct tissue were detected using pathological techniques. Furthermore, M1/M2 microglia polarization associated protein, glycolytic rate-limiting enzymes, energy transporters and AMPK/mammalian target of rapamycin (mTOR)/hypoxia inducible factor-1α (HIF-1α) signal were examined both in ischemic stroke rats and BV2 microglia treated with lipopolysaccharide (LPS) + interferon-γ (IFN-γ) by western blotting. RESULTS: MRI revealed that AS obviously decreased infarct volume, relieved brain microstructure damage and improved nerve fibers reorganization in ischemic stroke rats. Histological tests supported MRI findings. Notably, AS promoted microglia M2 and reduced M1 polarization, induced the AMPK activation accompanied with decreased levels of phosphorylated mTOR and HIF-1α. Moreover, AS suppressed the expression of glycolytic rate-limiting enzymes and energy transporters in ischemic stroke rats and BV2 microglia. In contrast, these beneficial effects were greatly blocked by AMPK inhibitor compound C. CONCLUSION: Overall, these results collectively suggested that AS facilitated tissue remodeling that may be partially through modulating polarization of microglia in AMPK- dependent metabolic pathways after ischemic stroke.
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Proteínas Quinasas Activadas por AMP , Microglía , Ratas Sprague-Dawley , Saponinas , Triterpenos , Animales , Triterpenos/farmacología , Triterpenos/uso terapéutico , Masculino , Saponinas/farmacología , Saponinas/uso terapéutico , Microglía/efectos de los fármacos , Proteínas Quinasas Activadas por AMP/metabolismo , Ratas , Fármacos Neuroprotectores/farmacología , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Infarto de la Arteria Cerebral Media/tratamiento farmacológico , Serina-Treonina Quinasas TOR/metabolismo , Encéfalo/efectos de los fármacos , Encéfalo/patología , Transducción de Señal/efectos de los fármacos , Modelos Animales de Enfermedad , Línea CelularRESUMEN
We propose a universal spin superconducting diode effect (SDE) induced by spin-orbit coupling (SOC) in systems with spin-triplet correlations, where the critical spin supercurrents in opposite directions are unequal. By analysis from both the Ginzburg-Landau theory and energy band analysis, we show that the spin-↑↑ and spin-↓↓ Cooper pairs possess opposite phase gradients and opposite momenta from the SOC, which leads to the spin SDE. Two superconductors with SOC, a p-wave superconductor as a toy model and a practical superconducting nanowire, are numerically studied and they both exhibit spin SDE. In addition, our theory also provides a unified picture for both spin and charge SDEs.
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Despite the observed decrease in liver fat associated with metabolic-associated fatty liver disease (MAFLD) in mice following fecal microbiota transplantation, the clinical effects and underlying mechanisms of washed microbiota transplantation (WMT), a refined method of fecal microbiota transplantation, for the treatment of MAFLD remain unclear. In this study, both patients and mice with MAFLD exhibit an altered gut microbiota composition. WMT increases the levels of beneficial bacteria, decreases the abundance of pathogenic bacteria, and reduces hepatic steatosis in MAFLD-affected patients and mice. Downregulation of the liver-homing chemokine receptor CXCR6 on ILC3s results in an atypical distribution of ILC3s in patients and mice with MAFLD, characterized by a significant reduction in ILC3s in the liver and an increase in ILC3s outside the liver. Moreover, disease severity is negatively correlated with the proportion of hepatic ILC3s. These hepatic ILC3s demonstrate a mitigating effect on hepatic steatosis through the release of IL-22. Mechanistically, WMT upregulates CXCR6 expression on ILC3s, thereby facilitating their migration to the liver of MAFLD mice via the CXCL16/CXCR6 axis, ultimately contributing to the amelioration of MAFLD. Overall, these findings highlight that WMT and targeting of liver-homing ILC3s could be promising strategies for the treatment of MAFLD.
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Quimiocina CXCL16 , Trasplante de Microbiota Fecal , Microbioma Gastrointestinal , Hígado , Receptores CXCR6 , Animales , Receptores CXCR6/metabolismo , Quimiocina CXCL16/metabolismo , Ratones , Humanos , Hígado/metabolismo , Hígado/microbiología , Linfocitos/inmunología , Linfocitos/metabolismo , Ratones Endogámicos C57BL , Masculino , Inmunidad Innata , Hígado Graso/terapia , Hígado Graso/metabolismo , Hígado Graso/microbiología , Interleucina-22 , Enfermedad del Hígado Graso no Alcohólico/terapia , Enfermedad del Hígado Graso no Alcohólico/microbiología , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Enfermedad del Hígado Graso no Alcohólico/inmunología , Interleucinas/metabolismo , FemeninoRESUMEN
Heart failure is the most costly cardiovascular disorder. New treatments are urgently needed. This study aims to evaluate the safety, pharmacokinetics, and pharmacodynamic profile of HEC95468, a soluble guanylate cyclase (sGC) stimulator, in healthy volunteers. Sixty-two, eighteen, and forty-eight participants were enrolled in the single ascending dose (SAD) study, the food effect (FE) study, and the multiple ascending dose (MAD) study, respectively. The study conforms to good clinical practice and the Declaration of Helsinki. Overall, HEC95468 was safe and tolerable; a higher proportion of HEC95468-treated participants reported mild headaches, dizziness, decreased blood pressure, increased heart rate, and gastrointestinal-related treatment-emergent adverse events (TEAEs), similar to the sGC stimulators riociguat and vericiguat. In terms of pharmacokinetic parameters, the maximum observed plasma concentration (Cmax) and the area under the concentration-time curve (AUC0-t) were dose-proportional over the dose range. Moderate accumulation was observed after multiple administrations of HEC95468. Systolic blood pressure (SBP) and diastolic blood pressure decreased, while 3',5'-cyclic guanosine monophosphate (cGMP) concentration in plasma increased and heart rate was induced. Vasoactive hormones (renin, angiotensin II, and norepinephrine) in plasma were compensatorily elevated after oral administration. These data supported further clinical trials of HEC95468 in the treatment of heart failure and pulmonary arterial hypertension. Systematic Review Registration: http://www.chinadrugtrials.org.cn, identifier CTR20210064.
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Implantación de Prótesis de Válvulas Cardíacas , Humanos , Implantación de Prótesis de Válvulas Cardíacas/métodos , Reemplazo de la Válvula Aórtica Transcatéter/métodos , Estenosis de la Válvula Aórtica/cirugía , Estenosis de la Válvula Aórtica/complicaciones , Femenino , Válvula Tricúspide/cirugía , Válvula Tricúspide/diagnóstico por imagen , Anciano , MasculinoRESUMEN
Heavy metals interact with each other in a coexisting manner to produce complex combined toxicity to organisms. At present, the toxic effects of chronic co-exposure to heavy metals hexavalent chromium [Cr(VI)] and divalent nickel [Ni(II)] on organisms are seldom studied and the related mechanisms are poorly understood. In this study, we explored the mechanism of the colon injury in mice caused by chronic exposure to Cr or/and Ni. The results showed that, compared with the control group, Cr or/and Ni chronic exposure affected the body weight of mice, and led to infiltration of inflammatory cells in the colon, decreased the number of goblet cells, fusion of intracellular mucus particles and damaged cell structure of intestinal epithelial. In the Cr or/and Ni exposure group, the activity of nitric oxide synthase (iNOS) increased, the expression levels of MUC2 were significantly down-regulated, and those of ZO-1 and Occludin were significantly up-regulated. Interestingly, factorial analysis revealed an interaction between Cr and Ni, which was manifested as antagonistic effects on iNOS activity, ZO-1 and MUC2 mRNA expression levels. Transcriptome sequencing further revealed that the expression of genes-related to inflammation, intestinal mucus and tight junctions changed obviously. Moreover, the relative contents of Cr(VI) and Ni(II) in the Cr, Ni and Cr+Ni groups all changed with in-vitro gastrointestinal ï¼IVGï¼digestion, especially in the Cr+Ni group. Our results indicated that the chronic exposure to Cr or/and Ni can lead to damage to the mice colon, and the relative content changes of Cr(VI) and Ni(II) might be the main reason for the antagonistic effect of Cr+Ni exposure on the colon damage.
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Cromo , Colon , Mucina 2 , Níquel , Animales , Cromo/toxicidad , Níquel/toxicidad , Ratones , Colon/efectos de los fármacos , Colon/patología , Mucina 2/genética , Mucina 2/metabolismo , Óxido Nítrico Sintasa de Tipo II/metabolismo , Óxido Nítrico Sintasa de Tipo II/genética , Perfilación de la Expresión Génica , Masculino , Digestión/efectos de los fármacos , Proteína de la Zonula Occludens-1/metabolismo , Proteína de la Zonula Occludens-1/genética , Transcriptoma/efectos de los fármacos , Ocludina/metabolismo , Ocludina/genética , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologíaRESUMEN
Yolk Peritonitis can lead to a rapid decline in egg production, which seriously affects the health of laying hens and the profitability of chicken farms. Escherichia coli (E. coli) is the most common cause of yolk peritonitis in laying hens. In this study, bacterial samples were collected from the ovaries and fallopian tubes of laying hens with suspected yolk peritonitis from a laying farm in Jiangsu Province, and their pathogenicity and drug resistance were investigated. Initially, morphological and biochemical detection methods were employed to isolate and identify the pathogenic bacteria. The results showed that a total of 16 strains of E. coli were isolated from laying hens with yolk peritonitis. Subsequently, the drug resistance and pathogenicity of a randomly selected E. coli strain were analyzed and predicted by genome sequencing technology, and the drug resistance of E. coli was verified by drug sensitivity test and PCR. Finally, the virulence was verified by infection experiment in mice. The study revealed that the egg-yolk peritonitis in laying hens was caused by E. coli infection, and the genome sequencing analysis revealed that the bacteria had multidrug resistance and high virulence. The drug susceptibility testing indicates that E. coli exhibited resistance to aminoglycosides, ß-lactam, macrolides, fluoroquinolones, and sulfonamides. In this study, resistance genes including KdpE, aadA5, APH(3 ")-ID, APH(6)-ID, and TEM-1 were identified, and their expression levels varied across different stages of bacterial growth. The results of virulence analysis indicated a mortality rate of 50% in mice infected with E. coli at a concentration of 2.985 × 107 CFU/mL. E. coli infection resulted in damage to various tissues and organs in mice, with the intestinal tissue structure being the most severely affected. This study provides a reference for the study of drug resistance mechanisms in E. coli and provides valuable insights into the selection of drugs for the treatment of vitelline peritonitis.
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Antibacterianos , Pollos , Infecciones por Escherichia coli , Escherichia coli , Peritonitis , Enfermedades de las Aves de Corral , Animales , Peritonitis/microbiología , Peritonitis/veterinaria , Peritonitis/tratamiento farmacológico , Escherichia coli/efectos de los fármacos , Escherichia coli/genética , Escherichia coli/fisiología , Escherichia coli/patogenicidad , Infecciones por Escherichia coli/veterinaria , Infecciones por Escherichia coli/microbiología , Enfermedades de las Aves de Corral/microbiología , Femenino , Antibacterianos/farmacología , Virulencia , Ratones , Farmacorresistencia Bacteriana , Yema de HuevoRESUMEN
Phase singularities are phase-indeterminate points where wave amplitudes are zero, which manifest as phase vertices or wavefront dislocations. In the realm of optical and electron beams, the phase singularity has been extensively explored, demonstrating a profound connection to orbital angular momentum. Direct local imaging of the impact of orbital angular momentum on phase singularities at the nanoscale, however, remains challenging. Here, we study the role of orbital angular momentum in phase singularities in graphene, particularly at the atomic level, through scanning tunneling microscopy and spectroscopy. Our experiments demonstrate that the scatterings between different orbital angular momentum states, which are induced by local rotational symmetry-breaking potentials, can generate additional phase singularities, and result in robust single-wavefront dislocations in real space. Our results pave the way for exploring the effects of orbital degree of freedom on quantum phases in quasiparticle interference processes.
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Aging skin, vulnerable to age-related defects, is poor in wound repair. Metabolic regulation in accumulated senescent cells (SnCs) with aging is essential for tissue homeostasis, and adequate ATP is important in cell activation for aged tissue repair. Strategies for ATP metabolism intervention hold prospects for therapeutic advances. Here, we found energy metabolic changes in aging skin from patients and mice. Our data show that metformin engineered EV (Met-EV) can enhance aged mouse skin repair, as well as ameliorate cellular senescence and restore cell dysfunctions. Notably, ATP metabolism was remodeled as reduced glycolysis and enhanced OXPHOS after Met-EV treatment. We show Met-EV rescue senescence-induced mitochondria dysfunctions and mitophagy suppressions, indicating the role of Met-EV in remodeling mitochondrial functions via mitophagy for adequate ATP production in aged tissue repair. Our results reveal the mechanism for SnCs rejuvenation by EV and suggest the disturbed energy metabolism, essential in age-related defects, to be a potential therapeutic target for facilitating aged tissue repair.
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Vesículas Extracelulares , Metformina , Humanos , Animales , Ratones , Anciano , Metabolismo Energético , Envejecimiento , Senescencia Celular , Adenosina TrifosfatoRESUMEN
BACKGROUND: Lupus nephritis (LN) is a complication of SLE characterised by immune dysfunction and oxidative stress (OS). Limited options exist for LN. We aimed to identify LN-related OS, highlighting the need for non-invasive diagnostic and therapeutic approaches. METHODS: LN-differentially expressed genes (DEGs) were extracted from Gene Expression Omnibus datasets (GSE32591, GSE112943 and GSE104948) and Molecular Signatures Database for OS-associated DEGs (OSEGs). Functional enrichment analysis was performed for OSEGs related to LN. Weighted gene co-expression network analysis identified hub genes related to OS-LN. These hub OSEGs were refined as biomarker candidates via least absolute shrinkage and selection operator. The predictive value was validated using receiver operating characteristic (ROC) curves and nomogram for LN prognosis. We evaluated LN immune cell infiltration using single-sample gene set enrichment analysis and CIBERSORT. Additionally, gene set enrichment analysis explored the functional enrichment of hub OSEGs in LN. RESULTS: The study identified four hub genes, namely STAT1, PRODH, TXN2 and SETX, associated with OS related to LN. These genes were validated for their diagnostic potential, and their involvement in LN pathogenesis was elucidated through ROC and nomogram. Additionally, alterations in immune cell composition in LN correlated with hub OSEG expression were observed. Immunohistochemical analysis reveals that the hub gene is most correlated with activated B cells and CD8 T cells. Finally, we uncovered that the enriched pathways of OSEGs were mainly involved in the PI3K-Akt pathway and the Janus kinase-signal transducer and activator of transcription pathway. CONCLUSION: These findings contribute to advancing our understanding of the complex interplay between OS, immune dysregulation and molecular pathways in LN, laying a foundation for the identification of potential diagnostic biomarkers and therapeutic targets.
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Lupus Eritematoso Sistémico , Nefritis Lúpica , Humanos , Nefritis Lúpica/diagnóstico , Nefritis Lúpica/genética , Fosfatidilinositol 3-Quinasas , Estrés Oxidativo/genética , Aprendizaje Automático , ADN Helicasas , ARN Helicasas , Enzimas MultifuncionalesRESUMEN
Pulmonary artery remodeling is a characteristic feature of broiler ascites syndrome (BAS). Pulmonary artery endothelial cells (PAECs) regulated by HIF-1α play a critical role in pulmonary artery remodeling, but the underlying mechanisms of HIF-1α in BAS remain unclear. In this experiment, primary PAECs were cultured in vitro and were identified by coagulation factor VIII. After hypoxia and RNA interference, the mRNA and protein expression levels of HIF-1α and VEGF were determined by qPCR and Western blotting. The transcriptome profiles of PAECs were obtained by RNA sequencing. Our results showed that the positive rate of PAECs was more than 90%, hypoxia-induced promoted the proliferation and apoptosis of PAECs, and RNA interference significantly downregulated the expression of HIF-1α, inhibited the proliferation of PAECs, and promoted the apoptosis of PAECs. In addition, transcriptome sequencing analysis indicated that HIF-1α may regulate broiler ascites syndrome by mediating COL4A, vitronectin, vWF, ITGα8, and MKP-5 in the ECM, CAMs and MAPK pathways in PAECs. These studies lay the foundation for further exploration of the mechanisms of pulmonary artery remodeling, and HIF-1α may be a potentially effective gene for the prevention and treatment of BAS.
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Pollos , Células Endoteliales , Subunidad alfa del Factor 1 Inducible por Hipoxia , Arteria Pulmonar , Interferencia de ARN , Animales , Arteria Pulmonar/metabolismo , Arteria Pulmonar/citología , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Células Endoteliales/fisiología , Células Endoteliales/metabolismo , Proliferación Celular , Proteínas Aviares/genética , Proteínas Aviares/metabolismo , Enfermedades de las Aves de Corral/genética , Ascitis/veterinaria , Ascitis/genética , Apoptosis , Células CultivadasRESUMEN
Xijiao Dihuang decoction (XDT), a famous formula, was usually used to improve the prognosis of patients with blood-heat and blood-stasis syndrome-related diseases. There were some mutual promotion and mutual assistance herb pairs in XDT. However, the exact functions of these herb pairs in the compatibility of XDT were not elucidated due to the lack of appropriate methodologies. Based on the theory of serum pharmacochemistry, a systematic method was established for the qualitative and quantitative analysis of characteristic components in the extracts and drug-containing plasma samples of XDT and its relational mutual promotion/assistance herb pairs. For qualitative analysis, 85 characteristic components were identified using the liquid chromatography with triple time-of-flight mass/mass spectrometry (LC-Triple QTOF-MS/MS) based on the mass defect filtering, product ion filtering, neutral loss filtering and isotope pattern filtering techniques. For quantitative detection, a relative quantitation assay using an extract ion chromatogram (EIC) of the full scan MS experiment was validated and employed to assess the quantity of the 85 identified compounds in the test samples of single herb, herb pairs and XDT. The results of multivariate statistical analyses indicated that both the assistant and guide herbs could improve the solubilization of active compounds from the sovereign and minister herbs in XDT in vitro, might change the trans-membrane transportation, and regulate metabolism in vivo. The methods used in present study might be also valuable for the investigation of multiple components from other classic TCM formulas for the purpose of compatibility feature study.