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Magnetic miniature robotic systems have attracted broad research interest because of their precise maneuverability in confined spaces and adaptability to diverse environments, holding significant promise for applications in both industrial infrastructures and biomedical fields. However, the predominant construction methodology involves the preprogramming of magnetic components into the system's structure. While this approach allows for intricate shape transformations, it exhibits limited flexibility in terms of reconfiguration and presents challenges when adapting to diverse materials, combining, and decoupling multiple functionalities. Here, we propose a construction strategy that facilitates the on-demand assembly of magnetic components, integrating ferrofluid droplets with the system's structural body. This approach enables the creation of complex solid-droplet robotic systems across a spectrum of length scales, ranging from 0.8 mm to 1.5 cm. It offers a diverse selection of materials and structural configurations, akin to assembling components like building blocks, thus allowing for the seamless integration of various functionalities. Moreover, it incorporates decoupling mechanisms to enable selective control over multiple functions, leveraging the fluidity, fission/fusion, and magneto-responsiveness properties inherent in the ferrofluid. Various solid-droplet systems have validated the feasibility of this strategy. This study advances the complexity and functionality achievable in small-scale magnetic robots, augmenting their potential for future biomedical and other applications.
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The development of single-cell ribonucleic acid (RNA) sequencing (scRNA-seq) technology has led to great opportunities for the identification of heterogeneous cell types in complex tissues. Clustering algorithms are of great importance to effectively identify different cell types. In addition, the definition of the distance between each two cells is a critical step for most clustering algorithms. In this study, we found that different distance measures have considerably different effects on clustering algorithms. Moreover, there is no specific distance measure that is applicable to all datasets. In this study, we introduce a new single-cell clustering method called SD-h, which generates an applicable distance measure for different kinds of datasets by optimally synthesizing commonly used distance measures. Then, hierarchical clustering is performed based on the new distance measure for more accurate cell-type clustering. SD-h was tested on nine frequently used scRNA-seq datasets and it showed great superiority over almost all the compared leading single-cell clustering algorithms.
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Algoritmos , ARN , Análisis por Conglomerados , Consenso , Análisis de Secuencia de ARN/métodosRESUMEN
Thanks to the advancements in bioinformatics, drugs, and other interventions that modulate microbes to treat diseases have been emerging continuously. In recent years, an increasing number of databases related to traditional Chinese medicine (TCM) or gut microbes have been established. However, a database combining the two has not yet been developed. To accelerate TCM research and address the traditional medicine and micro ecological system connection between short board, we have developed the most comprehensive micro-ecological database of TCM. This initiative includes the standardization of the following advantages: (1) A repeatable process achieved through the standardization of a retrieval strategy to identify literature. This involved identifying 419 experiment articles from PubMed and six authoritative databases; (2) High-quality data integration achieved through double-entry extraction of literature, mitigating uncertainties associated with natural language extraction; (3) Implementation of a similar strategy aiding in the prediction of mechanisms of action. Leveraging drug similarity, target entity similarity, and known drug-target entity association, our platform enables the prediction of the effects of a new herb or acupoint formulas using the existing data. In total, MicrobeTCM includes 171 diseases, 725 microbes, 1468 herb-formulas, 1032 herbs, 15780 chemical compositions, 35 acupoint-formulas, and 77 acupoints. For further exploration, please visit https://www.microbetcm.com.
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Medicina Tradicional China , Microbiota , Medicina Tradicional , Biología Computacional , Bases de Datos FactualesRESUMEN
A 3-year-old female patient with no significant medical history presented to her pediatrician with foamy urine. Initial testing revealed moderate proteinuria on qualitative testing, although she was incidentally noted to have severe hypertension (240/200 mmHg). Physical examination of the carotid and femoral areas revealed significant systolic vascular murmurs. Labs showed elevated serum creatinine, hypokalemia, metabolic alkalosis, elevated renin and aldosterone and hypercalciuria. Echocardiography identified ventricular hypertrophy. Computed tomography (CT) of the abdomen and magnetic resonance angiography of the head showed multiple tortuous or interrupted arteries and multiple calcifications in the renal sinus area. B-mode ultrasonography suggested thickening of the carotid and femoral artery walls, with numerous spotted calcifications. Genetic testing revealed that ABCC6 had a complex heterozygous mutation (exon 24: c.3340C > T and intron 30: c.4404-1G > A). Our panel of experts reviewed the evaluation of this patient with hypertension, proteinuria, hypercalciuria, and vascular abnormalities as well as the diagnosis and appropriate management of a rare disease.
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Hipertensión , Hipopotasemia , Femenino , Humanos , Preescolar , Hipercalciuria/complicaciones , Hipercalciuria/diagnóstico , Hipercalciuria/genética , Hipertensión/complicaciones , Hipertensión/diagnóstico , Hipopotasemia/genética , Pruebas Genéticas , Proteinuria/etiología , Proteinuria/genéticaRESUMEN
BACKGROUND: Irisin, as a myokine, plays a protective role against cardiovascular disease, including myocardial infarction, atherosclerosis and hypertension. However, whether irisin attenuates salt-sensitive hypertension and the related underlying mechanisms is unknown. METHODS: Male Dahl salt-resistant (DSR) and Dahl salt-sensitive (DSS) (12 weeks) rats were fed a high salt diet (8% NaCl) with or without irisin treatment by intraperitoneal injection for 8 weeks. RESULTS: Compared with DSR rats, DSS rats showed higher systolic blood pressure (SBP), impaired natriuresis and diuresis and renal dysfunction. In addition, it was accompanied by downregulation of renal p-AMPKα and upregulation of renal RAC1 and nuclear mineralocorticoid receptor (MR). Irisin intervention could significantly up-regulated renal p-AMPKα level and down-regulated renal RAC1-MR signal, thereby improving renal sodium excretion and renal function, and ultimately reducing blood pressure in DSS rats. Ex vivo treatment with irisin reduced the expression of RAC1 and nuclear MR in primary renal distal convoluted tubule cells from DSS rats and the effects of irisin were abolished by cotreatment of compound C (AMPK inhibitor), indicating that the regulation of RAC1-MR signals by irisin depended on the activation of AMPK. CONCLUSIONS: Irisin administration lowered salt-sensitive hypertension through regulating RAC1-MR signaling via activation of AMPK, which may be a promising therapeutic approach for salt-sensitive hypertension.
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Proteínas Quinasas Activadas por AMP , Presión Sanguínea , Fibronectinas , Hipertensión , Riñón , Ratas Endogámicas Dahl , Transducción de Señal , Proteína de Unión al GTP rac1 , Animales , Masculino , Ratas , Proteínas Quinasas Activadas por AMP/metabolismo , Presión Sanguínea/efectos de los fármacos , Fibronectinas/metabolismo , Hipertensión/metabolismo , Hipertensión/fisiopatología , Hipertensión/tratamiento farmacológico , Riñón/efectos de los fármacos , Riñón/metabolismo , Proteína de Unión al GTP rac1/metabolismo , Receptores de Mineralocorticoides/metabolismo , Transducción de Señal/efectos de los fármacos , Cloruro de Sodio DietéticoRESUMEN
BACKGROUND: Gestational diabetes can lead to increased blood pressure in offspring, accompanied by impaired renal sodium excretion function and vasoconstriction and diastole dysfunction. However, there are few studies on whether it is accompanied by increased sympathetic nerve activity. METHODS: Pregnant C57BL/6 mice were intraperitoneally injected with streptozotocin (35 mg/kg) or citrate buffer at day 0 of gestation. The mice of control mother offspring (CMO) and diabetic mother offspring (DMO) at 16 weeks of age were infused with vehicle (artificial cerebrospinal fluid, aCSF, 0.4 µL/h) or tempol (1 mmol/L, 0.4 µL/h) into the bilateral paraventricular nucleus (PVN) of mice for 4 weeks, respectively. RESULTS: Compared with CMO group, SBP and peripheral sympathetic nerve activity (increased heart rate, LF/HF and plasma norepinephrine and decreased SDNN and RMSSD) were increased in DMO group, which was accompanied by increased angiotensin II type-1 receptor (AT1R) expression and function in PVN. The increase in AT1R expression levels was attributed to a decrease in the methylation level of the AT1R promoter region, resulting in an increase in AT1R mRNA levels in PVN of DMO. Moreover, compared with CMO group, the levels of oxidative stress were increased and DNMT1 expression was decreased in PVN of DMO. Bilateral PVN infusion of tempol attenuated oxidative stress increased the level of DNMT1 expression and the binding of DNMT1 to the AT1R promoter region, which reduced mRNA and protein expression level of AT1R, heart rate and SBP in DMO, but not in CMO. CONCLUSIONS: The present study provides evidence for overactive sympathetic nervous systems in the pathogenesis of gestational diabetes-induced hypertension in offspring. Central antioxidant intervention in the PVN may be an important treatment strategy for fetal-programmed hypertension.
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Diabetes Mellitus Experimental , Diabetes Gestacional , Hipertensión , Ratones Endogámicos C57BL , Sistema Nervioso Simpático , Animales , Embarazo , Sistema Nervioso Simpático/fisiopatología , Femenino , Ratones , Diabetes Gestacional/fisiopatología , Hipertensión/fisiopatología , Hipertensión/etiología , Diabetes Mellitus Experimental/fisiopatología , Diabetes Mellitus Experimental/complicaciones , Óxidos N-Cíclicos/farmacología , Efectos Tardíos de la Exposición Prenatal/fisiopatología , Marcadores de Spin , Núcleo Hipotalámico Paraventricular/metabolismo , Núcleo Hipotalámico Paraventricular/fisiopatología , Presión Sanguínea/fisiología , Receptor de Angiotensina Tipo 1/genética , Masculino , Frecuencia Cardíaca/fisiología , Estrés OxidativoRESUMEN
Primary nocturnal enuresis (PNE) is a disease characterized by involuntary urination during sleep after the age of five, causing inconvenience and psychological burden to children and their families. The onset of PNE is related to many factors, and in recent years, delayed central nervous system maturation has been considered one of the important causes of PNE. Previous studies have demonstrated functional changes in multiple brain regions in children with PNE. However, these studies either focused on changes in local brain regions or the functional connection (FC) between specific brain regions, and there is currently a lack of research on the whole brain FC in children with PNE. This study analyzed functional connectivity density (FCD) across the entire brain based on voxels and comprehensively evaluated the global FCD (gFCD), local FCD (lFCD), and long-range FCD (lrFCD). Decreased gFCD and lFCD were found in the left temporal lobe and the right posterior cerebellum in the children with PNE compared with the HC. The FCD values in these regions were negatively correlated with the scores of hyperactivity/impulsivity in the children with PNE. This study may help to reveal the neural mechanisms underlying the onset of PNE in children from a new perspective.
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Primary nocturnal enuresis (PNE) is a common childhood disorder with abnormal sleep or arousal. The corpus callosum (CC) continues to develop into adulthood and plays an important role in sleep arousal. This study aimed to evaluate the microstructure of the CC in children with PNE. Diffusion tensor imaging (DTI) indices were extracted throughout the CC and its seven subregions were compared between the children with PNE and healthy children (HC). The correlation between abnormal DTI indices of the CC and cognitive condition was also tested. Compared to HC, decreased fiber number (NF) (F = 8.492, PFDR = 0.032) and fractional anisotropy (FA) value (F = 8.442, PFDR = 0.040) were found in the posterior midbody of the CC, increased RD was found in the posterior midbody (F = 6.888, PFDR = 0.040) and isthmus (F = 7.967, PFDR = 0.040) in children with PNE. The reduction of FA value was more obvious in boys than girls with PNE. In children with PNE, there was a significant positive correlation between the NF of the posterior midbody and full IQ (r = 0.322, P = 0.025) and between the FA value and the general knowledge memory (r = 0.293, P = 0.043). This study provides imaging evidence for abnormalities in the microstructure of the CC in children with PNE, especially in male PNE, which might affect the children's cognitive performance.
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In this study, the mesoporous material NCNT was prepared by treating carbon nanotubes (CNT) with hydrazine and subsequently loaded with Cu-Fe layered double hydroxide (CuFeLDH) to create a multiphase catalyst (CuFeLDH-NCNT). Its application as a multiphase catalyst was investigated in an ultrasound-assisted Fenton process for ciprofloxacin (CIP) degradation in aqueous solution. In addition, the impacts of catalyst dosage, ultrasonic power, H2O2 dosage, and beginning pH on CIP removal efficiency were carefully evaluated to maximize the removal efficiency of CIP. The findings indicated that the elimination rate of the initial CIP concentration of 20 mg/L surpassed 94.66% after a mere 100 min, while the TOC degradation rate was 70.4%. The high removal rate was due to the synergistic action between the nanoparticles, H2O2, and ultrasonography. The degradation intermediates of CIP were examined, and putative degradation pathways and mechanisms were postulated.
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Peróxido de Hidrógeno , Nanotubos de Carbono , Ultrasonografía , Ciprofloxacina , HidróxidosRESUMEN
BACKGROUND: Advances in single-cell RNA-seq technology have led to great opportunities for the quantitative characterization of cell types, and many clustering algorithms have been developed based on single-cell gene expression. However, we found that different data preprocessing methods show quite different effects on clustering algorithms. Moreover, there is no specific preprocessing method that is applicable to all clustering algorithms, and even for the same clustering algorithm, the best preprocessing method depends on the input data. RESULTS: We designed a graph-based algorithm, SC3-e, specifically for discriminating the best data preprocessing method for SC3, which is currently the most widely used clustering algorithm for single cell clustering. When tested on eight frequently used single-cell RNA-seq data sets, SC3-e always accurately selects the best data preprocessing method for SC3 and therefore greatly enhances the clustering performance of SC3. CONCLUSION: The SC3-e algorithm is practically powerful for discriminating the best data preprocessing method, and therefore largely enhances the performance of cell-type clustering of SC3. It is expected to play a crucial role in the related studies of single-cell clustering, such as the studies of human complex diseases and discoveries of new cell types.
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RNA-Seq/métodos , Algoritmos , Análisis por Conglomerados , Expresión Génica , Humanos , Análisis de Secuencia de ARNRESUMEN
A new terbium (III) luminescent compound {[Tb2(PDC)2(ox)(H2O)4](H2O)2}n was synthesized by the self-assembly of Tb3+ ions with 3,5-pyridinedicarboxylate (PDC) and oxalate (ox) ligands and characterized by fluorescence spectroscopy and single-crystal X-ray diffraction. The density functional theory (DFT) and high-level correlated ab initio wave function methods with Spin-Orbit Coupling correction (CASSCF/SO and CAS-NEVPT2/SOC) were successfully applied to predict the absorption and emission spectra of this strongly correlated lanthanide system in excellent agreement with the experimental results.
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OBJECTIVE: This study aimed to investigate the effectiveness and safety of a method combining double-balloon catheter for cervical ripening and intravenous drip of oxytocin on the induction of term labor, providing the reference for clinical safety. METHODS: A total of 120 pregnant women with a gestation between 37+0 and 41+6 weeks, indications of labor induction, singleton pregnancy with cephalic presentation were enrolled. The patients were divided into the research group receiving cervical dilation balloon combined with intravenous drip of oxytocin and the control group receiving an intravenous drip of oxytocin at a concentration of 0.5% for labor induction (n = 60 for each). The effectiveness and safety of labor induction were evaluated by the rates of successful cervical ripening promotion and labor induction, as well as the vaginal delivery rate, induced labor time, total duration of labor, the total amount of postpartum hemorrhage within 24 h after giving birth, the incidences of postpartum hemorrhage, cervical laceration, puerperal infection and neonatal outcomes. RESULTS: There was no statistical difference in the basal demographic and clinical characteristics, including ages, gestational weeks, delivery times and Bishop scores at admission between two groups. The rate of successful cervical ripening promotion (research vs. control = 90.00% vs. 55.00%), the rate of successful induction (95.00% vs. 40.00%), the vaginal delivery rate (93.33% vs. 63.33%), the induced labor time (15.03 ± 5.40 vs. 30.68 ± 10.82 h), and the total duration of labor (8.12 ± 2.65 vs. 15.01 ± 6.06 h) were significantly different between two groups (all P < 0.05). There was no significant difference in the total amount of postpartum hemorrhage, incidences of postpartum hemorrhage, cervical laceration, puerperal infection as well as the neonatal outcomes, including neonatal weight, neonatal asphyxia and incidence of meconium aspiration syndrome between two groups. CONCLUSIONS: Compared to labor induction of oxytocin, the method combining double-balloon catheter for cervical ripening and intravenous drip of oxytocin for the induction of term labor has a higher vaginal delivery rate, shorter total duration of labor, and does not increase the incidences of postpartum hemorrhage and neonatal infection, which is a more effective and safer method for induction of term labor.
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Cateterismo , Dilatación , Trabajo de Parto Inducido/métodos , Oxitócicos/administración & dosificación , Oxitocina/administración & dosificación , Administración Intravaginal , Adulto , Cateterismo/métodos , Maduración Cervical , Parto Obstétrico , Femenino , Humanos , Infusiones Intravenosas , Inicio del Trabajo de Parto , Oxitocina/farmacología , Hemorragia Posparto/tratamiento farmacológico , Embarazo , Nacimiento a Término , Factores de Tiempo , Enfermedades del Cuello del Útero/etiologíaRESUMEN
An unprecedented Tf2NH-catalyzed formal [3 + 2] cycloaddition of ynamides with dioxazoles was developed to construct various polysubstituted 4-aminooxazoles. This approach features a metal-free catalytic bimolecular assembly of oxazole motifs, a low-cost catalyst, exceptionally mild reaction conditions, a very short reaction time, a broad substrate scope, and high efficiency. This metal-free protocol may find applications in pharmaceutical-oriented synthesis.
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A ruthenium-catalyzed intermolecular [3 + 2] cycloaddition of 2H-azirines and activated alkynes is reported, which provides polysubstituted pyrroles in moderate to good yields. This approach features a C-N bond cleavage of 2H-azirines by a ruthenium catalyst. The results of this study would provide a complementary method to synthesize polysubstituted pyrroles from the known 2H-azirine approaches and advance 2H-azirine chemistry.
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2H-azirines can serve as three-atom synthons by C-C bond cleavage, however, it involves a high energy barrier under thermal conditions (>50.0â kcal mol(-1) ). Reported is a ruthenium-catalyzed [3+2+2] cycloaddition reaction of 2H-azirines with diynes, thus leading to the formation of fused azepine skeletons. This approach features an unprecedented metal-catalyzed C-C bond cleavage of 2H-azirines at room temperature, and the challenging construction of aza-seven-membered rings from diynes. The results of this study provide a new reaction pattern for constructing nitrogen-containing seven-membered rings and may find applications in the synthesis of other complex heterocycles.
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The root of Prismatomeris connata has been used in China for centuries as the medicinal herb "Huang Gen" (HG), but its phytochemicals or active ingredients are not well understood. In this study, we performed chemical analysis of the ethyl acetate fraction of a HG ethanol extract. We thus isolated seven new tetrahydroanthraquinones, prisconnatanones C-I (compounds 1-7) from the root of P. connata and identified their structures using spectroscopic analyses. Their absolute configurations were established by both modified Mosher's and Mo2OAc4 methods, and ORD techniques. Their cytotoxicity was tested in a panel of human lung tumor cells (H1229, HTB179, A549 and H520 cell lines). Prisconnatanone I (7) showed the highest activity, with an IC50 value ranging from 2.7 µM to 3.9 µM in the suppression of tumor cell growth, and the others with chelated phenolic hydroxyls exhibited relatively lower activity (IC50: 8-20 µM). In conclusion, these data suggest that some of the natural tetrahydroanthraquinones in HG are bioactive, and hydroxylation at C-1 significantly increases the cytotoxicity of these compounds against lung tumor cell growth.
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Antraquinonas/farmacología , Antineoplásicos Fitogénicos/farmacología , Neoplasias Pulmonares/tratamiento farmacológico , Extractos Vegetales/farmacología , Rubiaceae/química , Antraquinonas/química , Antraquinonas/aislamiento & purificación , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Cristalografía por Rayos X , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Concentración 50 Inhibidora , Modelos Moleculares , Conformación Molecular , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificaciónRESUMEN
The direct C-H annulation of anilines or related compounds with internal alkynes provides straightforward access to 2,3-disubstituted indole products. However, this transformation proceeds with poor regioselectivity in the synthesis of unsymmetrically 2,3-diaryl substituted indoles. Herein, we report the rhodium(III)-catalyzed C-H annulation of nitrones with symmetrical diaryl alkynes as an alternative method to prepare 2,3-diaryl-substituted N-unprotected indoles with two different aryl groups. One of the aryl substituents is derived from N=C-aryl ring of the nitrone and the other from the alkyne substrate, thus providing the indole products with exclusive regioselectivity.
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NIS-mediated iodocyclization of N-sulfonyl propargylamides for the synthesis of various oxazolidines and iodoalkylidenedihydrooxazoles via a 5-exo-dig process is developed. The resulting iodoalkylidenedihydrooxazoles can be further transformed into the corresponding oxazoles in the presence of dioxygen.
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Oxazoles/química , Oxazoles/síntesis química , Oxígeno/química , Pargilina/análogos & derivados , Pargilina/química , Succinimidas/química , Catálisis , Cristalografía por Rayos X , Ciclización , Estructura Molecular , Oxidación-ReducciónRESUMEN
The DABCO-catalyzed reaction of propargyl alcohols with methyl 2-perfluoroalkynoate to give trifluoromethylated furans in up to 98% yield under mild conditions has been developed. The established allene-enol and control experiments indicate that the reaction should proceed through a Michael addition and Claisen rearrangement/cyclization process.
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BACKGROUND: There is currently no grading standard for the degree of clinical and bowel morphological changes. The objective of this study was to define clinical and bowel morphological classifications and investigate the possible relationship with the characteristics of patients with incarcerated groin hernias. MATERIAL AND METHODS: We retrospectively studied 195 patients who underwent emergency hernia repair with simultaneous bowel resection between January 1992 and January 2012. We classified the degree of clinical and bowel morphological changes into 3 grades based on the incarceration time, intestinal morphology after damage, hernia sac integrity, degree of inflammation, and the presence/absence of bacterial growth, peritonitis signs, mechanical obstruction, cellulitis, and systemic shock. We also recorded patient characteristics and analyzed their relationships with these degrees according to our grading system. RESULTS: We identified 134, 42, and 19 cases of Grades I, II, and III of clinical and bowel morphological changes, respectively. Pearson's chi-squared tests revealed that advanced age (P=0.001), presence of comorbid disease (P=0.002), and high American Society of Anesthesiologists (ASA) score (P=0.017) were related to the degree. Morbidity and mortality also showed significant relationships with the degree (P<0.001, P=0.005, respectively), especially with regard to post-operative infection. CONCLUSIONS: The proposed 3-stage classifications of clinical and bowel morphological changes can be used to objectively reflect the degree of bowel damage. Greater levels of the changes were associated with higher incidences of complications and increased mortality, especially for older patients with comorbid diseases and poor ASA scores. Urgent surgery should be performed to avoid bowel damage exacerbation.