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Controlled charge flows are fundamental to many areas of science and technology, serving as carriers of energy and information, as probes of material properties and dynamics1 and as a means of revealing2,3 or even inducing4,5 broken symmetries. Emerging methods for light-based current control5-16 offer particularly promising routes beyond the speed and adaptability limitations of conventional voltage-driven systems. However, optical generation and manipulation of currents at nanometre spatial scales remains a basic challenge and a crucial step towards scalable optoelectronic systems for microelectronics and information science. Here we introduce vectorial optoelectronic metasurfaces in which ultrafast light pulses induce local directional charge flows around symmetry-broken plasmonic nanostructures, with tunable responses and arbitrary patterning down to subdiffractive nanometre scales. Local symmetries and vectorial currents are revealed by polarization-dependent and wavelength-sensitive electrical readout and terahertz (THz) emission, whereas spatially tailored global currents are demonstrated in the direct generation of elusive broadband THz vector beams17. We show that, in graphene, a detailed interplay between electrodynamic, thermodynamic and hydrodynamic degrees of freedom gives rise to rapidly evolving nanoscale driving forces and charge flows under the extremely spatially and temporally localized excitation. These results set the stage for versatile patterning and optical control over nanoscale currents in materials diagnostics, THz spectroscopies, nanomagnetism and ultrafast information processing.
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Behçet's disease (BD) is a chronic vasculitis characterized by systemic immune aberrations. However, a comprehensive understanding of immune disturbances in BD and how they contribute to BD pathogenesis is lacking. Here, we performed single-cell and bulk RNA sequencing to profile peripheral blood mononuclear cells (PBMCs) and isolated monocytes from BD patients and healthy donors. We observed prominent expansion and transcriptional changes in monocytes in PBMCs from BD patients. Deciphering the monocyte heterogeneity revealed the accumulation of C1q-high (C1qhi) monocytes in BD. Pseudotime inference indicated that BD monocytes markedly shifted their differentiation toward inflammation-accompanied and C1qhi monocyte-ended trajectory. Further experiments showed that C1qhi monocytes enhanced phagocytosis and proinflammatory cytokine secretion, and multiplatform analyses revealed the significant clinical relevance of this subtype. Mechanistically, C1qhi monocytes were induced by activated interferon-γ (IFN-γ) signaling in BD patients and were decreased by tofacitinib treatment. Our study illustrates the BD immune landscape and the unrecognized contribution of C1qhi monocytes to BD hyperinflammation, showing their potential as therapeutic targets and clinical assessment indexes.
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Síndrome de Behçet , Complemento C1q , Monocitos , Síndrome de Behçet/genética , Síndrome de Behçet/inmunología , Complemento C1q/genética , Complemento C1q/inmunología , Humanos , Monocitos/inmunología , RNA-Seq , Análisis de la Célula IndividualRESUMEN
We present an on-chip filter with a broad tailorable working wavelength and a single-mode operation. This is realized through the application of topological photonic crystal nanobeam filters employing synthesis parameter dimensions. By introducing the translation of air holes as a new synthetic parameter dimension, we obtained nanobeams with tunable Zak phases. Leveraging the bulk-edge correspondence, we identify the existence of topological cavity modes and establish a correlation between the cavity's interface morphology and working wavelength. Through experiments, we demonstrate filters with adjustable filtering wavelengths ranging from 1301 to 1570 nm. Our work illustrates the use of the synthetic translation dimension in the design of on-chip filters, and it holds potential for applications in other devices such as microcavities.
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Cellular senescence (CS), a state of permanent growth arrest, is intertwined with tumorigenesis. Due to the absence of specific markers, characterizing senescence levels and senescence-related phenotypes across cancer types remain unexplored. Here, we defined computational metrics of senescence levels as CS scores to delineate CS landscape across 33 cancer types and 29 normal tissues and explored CS-associated phenotypes by integrating multiplatform data from ~20 000 patients and ~212 000 single-cell profiles. CS scores showed cancer type-specific associations with genomic and immune characteristics and significantly predicted immunotherapy responses and patient prognosis in multiple cancers. Single-cell CS quantification revealed intra-tumor heterogeneity and activated immune microenvironment in senescent prostate cancer. Using machine learning algorithms, we identified three CS genes as potential prognostic predictors in prostate cancer and verified them by immunohistochemical assays in 72 patients. Our study provides a comprehensive framework for evaluating senescence levels and clinical relevance, gaining insights into CS roles in cancer- and senescence-related biomarker discovery.
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Neoplasias de la Próstata , Microambiente Tumoral , Senescencia Celular/genética , Genómica , Humanos , Inmunoterapia , Masculino , Neoplasias de la Próstata/genética , Microambiente Tumoral/genéticaRESUMEN
Lenses with a tunable focus are highly desirable but remain a challenge. Here, we demonstrate a microwave varifocal meta-lens based on the Alvarez lens principle, consisting of two mechanically movable tri-layer metasurface phase plates with reversed cubic spatial profiles. The manufactured multilayer Alvarez meta-lens enables microwave beam collimation/focusing at frequencies centered at 7.5 GHz, and shows one octave focal length tunability when transversely translating the phase plates by 8 cm. The measurements reveal a gain enhancement up to 15 dB, 3-dB beam width down to 3.5∘, and relatively broad 3-dB bandwidth of 3 GHz. These advantageous characteristics, along with its simplicity, compactness, and lightweightness, make the demonstrated flat Alvarez meta-lens suitable for deployment in many microwave systems.
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STUDY QUESTION: Are there associations of age at menarche (AAM) with health-related outcomes in East Asians? SUMMARY ANSWER: AAM is associated with osteoporosis, Type 2 diabetes (T2D), glaucoma, and uterine fibroids, as demonstrated through observational studies, polygenic risk scores, genetic correlations, and Mendelian randomization (MR), with additional findings indicating a causal effect of BMI and T2D on earlier AAM. WHAT IS KNOWN ALREADY: Puberty timing is linked to adult disease risk, but research predominantly focuses on European populations, with limited studies in other groups. STUDY DESIGN, SIZE, DURATION: We performed an AAM genome-wide association study (GWAS) with 57 890 Han Taiwanese females and examined the association between AAM and 154 disease outcomes using the Taiwanese database. Additionally, we examined genetic correlations between AAM and 113 diseases and 67 phenotypes using Japanese GWAS summary statistics. PARTICIPANTS/MATERIALS, SETTING, METHODS: We performed AAM GWAS and gene-based GWAS studies to obtain summary statistics and identify potential AAM-related genes. We applied phenotype, polygenic risk scores, and genetic correlation analyses of AAM to explore health-related outcomes, using multivariate regression and linkage disequilibrium score regression analyses. We also explored potential bidirectional causal relationships between AAM and related outcomes through univariable and multivariable MR analyses. MAIN RESULTS AND THE ROLE OF CHANCE: Fifteen lead single-nucleotide polymorphisms and 24 distinct genes were associated with AAM in Taiwan. AAM was genetically associated with later menarche and menopause, greater height, increased osteoporosis risk, but lower BMI, and reduced risks of T2D, glaucoma, and uterine fibroids in East Asians. Bidirectional MR analyses indicated that higher BMI/T2D causally leads to earlier AAM. LIMITATIONS, REASONS FOR CAUTION: Our findings were specific to Han Taiwanese individuals, with genetic correlation analyses conducted in East Asians. Further research in other ethnic groups is necessary. WIDER IMPLICATIONS OF THE FINDINGS: Our study provides insights into the genetic architecture of AAM and its health-related outcomes in East Asians, highlighting causal links between BMI/T2D and earlier AAM, which may suggest potential prevention strategies for early puberty. STUDY FUNDING/COMPETING INTEREST(S): The work was supported by China Medical University, Taiwan (CMU110-S-17, CMU110-S-24, CMU110-MF-49, CMU111-SR-158, CMU111-MF-105, CMU111-MF-21, CMU111-S-35, CMU112-SR-30, and CMU112-MF-101), the China Medical University Hospital, Taiwan (DMR-111-062, DMR-111-153, DMR-112-042, DMR-113-038, and DMR-113-103), and the Ministry of Science and Technology, Taiwan (MOST 111-2314-B-039-063-MY3, MOST 111-2314-B-039-064-MY3, MOST 111-2410-H-039-002-MY3, and NSTC 112-2813-C-039-036-B). The funders had no influence on the data collection, analyses, or conclusions of the study. No conflict of interests to declare. TRIAL REGISTRATION NUMBER: N/A.
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Diabetes Mellitus Tipo 2 , Estudio de Asociación del Genoma Completo , Menarquia , Adolescente , Adulto , Niño , Femenino , Humanos , Persona de Mediana Edad , Factores de Edad , Índice de Masa Corporal , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/epidemiología , Pueblos del Este de Asia , Menarquia/genética , Análisis de la Aleatorización Mendeliana , Herencia Multifactorial , Osteoporosis/genética , Polimorfismo de Nucleótido Simple , Taiwán/epidemiologíaRESUMEN
Water contamination irritated by Cd(II) brings about severe damage to the ecosystem and to human health. The decontamination of Cd(II) by the adsorption method is a promising technology. Here, we construct aminomethylpyridine-functionalized polyamidoamine (PAMAM) dendrimer/apple residue biosorbents (AP-G1.0-AMP and AP-G2.0-AMP) for adsorbing Cd(II) from aqueous solution. The adsorption behaviors of the biosorbents for Cd(II) were comprehensively evaluated. The maximum adsorption capacities of AP-G1.0-AMP and AP-G2.0-AMP for Cd(II) are 1.40 and 1.44 mmol·g-1 at pH 6. The adsorption process for Cd(II) is swift and can reach equilibrium after 120 min. The film diffusion process dominates the adsorption kinetics, and a pseudo-second-order model is appropriate to depict this process. The uptake of Cd(II) can be promoted by increasing concentration and temperature. The adsorption isotherm follows the Langmuir model with a chemisorption mechanism. The biosorbents also display satisfied adsorption for Cd(II) in real aqueous media. The adsorption mechanism indicates that C-N, NâC, C-O, CONH, N-H, and O-H groups participate in the adsorption for Cd(II). The biosorbents display a good regeneration property and can be reused with practical value. The as-prepared biosorbents show great potential for removing Cd(II) from water solutions with remarkable significance.
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Cellulose nanocrystals (CNCs) have garnered significant attention as a modifiable substrate because of their exceptional performances, including remarkable degradability, high tensile strength, high elastic modulus, and biocompatibility. In this article, the successful adsorption of phytic acid (PA) onto the surface of cellulose nanocrystals @polydopamine (CNC@PDA) was achieved. Taking inspiration from mussels, a dopamine self-polymerization reaction was employed to coat the surface of CNCs with PDA. Utilizing Pickering emulsion, the CNC@PDA-PA nanomaterial was obtained by grafting PA onto CNC@PDA. An environmentally friendly hydrogel was prepared through various reversible interactions using poly(acrylic acid) (PAA) and Fe3+ as raw materials with the assistance of CNC@PDA-PA. By multiple hydrogen bonding and metal-ligand coordination, nanocomposite hydrogels exhibit remarkable mechanical properties (the tensile strength and strain were 1.82 MPa and 442.1%, respectively) in addition to spectacular healing abilities (96.6% after 5 h). The study aimed to develop an innovative approach for fabricating nanocomposite hydrogels with exceptional self-healing capabilities.
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OBJECTIVE: This study investigated the relationship of serum homocysteine (Hcy) and cystatin C (Cys C) levels with the prognosis of patients with heart failure with preserved ejection fraction (HFpEF). METHODS: A total of 178 patients with HFpEF who were admitted to our hospital between December 2019 and November 2020 were included. Patients were grouped based on their serum Hcy and Cys C levels: high Hcy level, normal Hcy level, high Cys C level, and normal Cys C level. Cardiac function, ventricular remodeling indices, and prognosis were compared among patients in these groups. Additionally, the predictive value of serum Hcy and Cys C levels for adverse cardiovascular events in HFpEF patients was analyzed. RESULTS: Patients' mean age in the high Hcy level, normal Hcy level, high Cys C level, and normal Cys C level groups was 69.21 ± 4.17,67.74 ± 4.28,69.95 ± 4.98, and 67.06 ± 4.13 years old, respectively. The high Hcy level group exhibited a lower proportion of class II cardiac function according to the New York Heart Association (NYHA) classification and a higher proportion of class IV cardiac function than the normal Hcy level group, with statistically significant differences. Similarly, the high Cys C level group had a lower proportion of class II cardiac function and a higher proportion of class IV cardiac function compared with the normal Cys C level group, with statistically significant differences. Left ventricular end-diastolic internal diameter (LVEDD), left ventricular end-systolic internal diameter (LVESD), and left ventricular mass index (LVMI) were significantly higher in both the high Hcy level and high Cys C level groups compared with the normal group, with statistically significant differences. The rates of all-cause mortality and class I endpoint events were significantly higher in the high Hcy level and high Cys C level groups than in the normal group. Multifactorial logistic regression analysis demonstrated that adverse cardiovascular events were significantly associated with cardiac function class, LVEDD, LVESD, LVMI, Hcy, and Cys C in patients with HFpEF. The area under the curve (AUC) values for Hcy and Cys C, determined using receiver operating characteristic (ROC) curve analysis, were 0.778 (optimal critical value, 25.38) and 0.681 (optimal critical value, 1.56), respectively, for predicting adverse cardiovascular events. Both Hcy and Cys C serum levels were positively correlated with LVEDD, LVESD, LVMI, and NYHA classification. CONCLUSION: Serum levels of Hcy and Cys C were closely associated with cardiac function, ventricular remodeling indices, and prognosis in patients with HFpEF. These levels may serve as valuable indices for assessing HFpEF patients' health status and prognosis, providing important insights into their potential role as biomarkers for HFpEF management and prognosis.
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Biomarcadores , Cistatina C , Insuficiencia Cardíaca , Homocisteína , Valor Predictivo de las Pruebas , Volumen Sistólico , Función Ventricular Izquierda , Humanos , Homocisteína/sangre , Cistatina C/sangre , Masculino , Femenino , Insuficiencia Cardíaca/sangre , Insuficiencia Cardíaca/fisiopatología , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/mortalidad , Biomarcadores/sangre , Anciano , Pronóstico , Persona de Mediana Edad , Medición de Riesgo , Estudios Retrospectivos , Remodelación Ventricular , Factores de RiesgoRESUMEN
INTRODUCTION: This study aimed to identify risk factors affecting outcomes in pediatric patients requiring emergent peritoneal dialysis (PD) for all causes, focusing on survival rates, kidney function recovery, PD duration, complications, and quality of life. METHODS: A retrospective review was conducted on medical records of pediatric patients who received emergent bedside PD in the intensive care unit from January 2010 to February 2023. Thirty-four catheters were placed, with demographic, preoperative, and procedural data collected. MedCalc® Statistical Software was used for analysis with a significance level set at p < 0.05. Prophylactic antibiotics were administered prior to surgery, and catheters were placed using a consistent technique by a single team of pediatric surgeons. RESULTS: The median age at catheter placement was 39 days (range 2-2,286), and the median body weight was 3.53 kg (range 1.2-48.8). The majority were male (64.7%), with 17.6% preterm. The most common indication for PD was acute kidney injury (AKI) (88.2%), followed by hyperammonemia, metabolic acidosis, and abdominal compartment syndrome. The median waiting period for PD placement was 1 day, and the median duration of PD was 7 days. Complications included dialysate leakage (22.8%) and catheter obstruction leading to PD discontinuation (31.4%). The mortality rate was high at 71.4%. CONCLUSION: It is advisable to advocate for the early initiation of PD in pediatric patients following cardiac surgery. AKI is a significant risk factor for mortality, while prematurity increases the risk of dialysate leakage. Omentectomy and the method of catheter exit did not significantly affect outcomes. The study's limitations highlight the need for larger prospective studies to better understand and improve emergent PD management in this vulnerable population.
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Diálisis Peritoneal , Humanos , Diálisis Peritoneal/métodos , Diálisis Peritoneal/efectos adversos , Masculino , Femenino , Estudios Retrospectivos , Lactante , Preescolar , Niño , Recién Nacido , Unidades de Cuidados Intensivos , Lesión Renal Aguda/terapia , Lesión Renal Aguda/etiología , Lesión Renal Aguda/mortalidad , Factores de Riesgo , Calidad de Vida , Resultado del TratamientoRESUMEN
AIMS: The mechanisms underlying ageing-induced vascular remodelling remain unclear. This study investigates the role and underlying mechanisms of the cytoplasmic deacetylase sirtuin 2 (SIRT2) in ageing-induced vascular remodelling. METHODS AND RESULTS: Transcriptome and quantitative real-time PCR data were used to analyse sirtuin expression. Young and old wild-type and Sirt2 knockout mice were used to explore vascular function and pathological remodelling. RNA-seq, histochemical staining, and biochemical assays were used to evaluate the effects of Sirt2 knockout on the vascular transcriptome and pathological remodelling and explore the underlying biochemical mechanisms. Among the sirtuins, SIRT2 had the highest levels in human and mouse aortas. Sirtuin 2 activity was reduced in aged aortas, and loss of SIRT2 accelerated vascular ageing. In old mice, SIRT2 deficiency aggravated ageing-induced arterial stiffness and constriction-relaxation dysfunction, accompanied by aortic remodelling (thickened vascular medial layers, breakage of elastin fibres, collagen deposition, and inflammation). Transcriptome and biochemical analyses revealed that the ageing-controlling protein p66Shc and metabolism of mitochondrial reactive oxygen species (mROS) contributed to SIRT2 function in vascular ageing. Sirtuin 2 repressed p66Shc activation and mROS production by deacetylating p66Shc at lysine 81. Elimination of reactive oxygen species by MnTBAP repressed the SIRT2 deficiency-mediated aggravation of vascular remodelling and dysfunction in angiotensin II-challenged and aged mice. The SIRT2 coexpression module in aortas was reduced with ageing across species and was a significant predictor of age-related aortic diseases in humans. CONCLUSION: The deacetylase SIRT2 is a response to ageing that delays vascular ageing, and the cytoplasm-mitochondria axis (SIRT2-p66Shc-mROS) is important for vascular ageing. Therefore, SIRT2 may serve as a potential therapeutic target for vascular rejuvenation.
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Sirtuina 2 , Remodelación Vascular , Ratones , Humanos , Animales , Anciano , Sirtuina 2/metabolismo , Proteína Transformadora 1 que Contiene Dominios de Homología 2 de Src , Especies Reactivas de Oxígeno/metabolismo , Envejecimiento , Ratones NoqueadosRESUMEN
Nowadays, stretchable self-healing hydrogels designed by biomass-based materials have gathered remarkable attention in numerous frontier fields such as wound healing, health monitoring issues, and electronic skin. In this study, soy protein isolate (SPI), a common plant protein, was cross-linked to nanoparticles (SPI NPs) by Genipin, (Gen) which was attracted from the native Geniposide. Oil-in-water (O/W) Pickering emulsion was formed by SPI NPs wrapping the linseed oil, and further implanted into poly(acrylic acid)/guar gum (PAA/GG)-based self-healing hydrogels by multiple reversible weak interactions. With the addition of Pickering emulsion, the hydrogels have achieved a remarkable self-healing ability (self-healing efficiency could reach 91.6% within 10 h) and mechanical properties (tensile strength of 0.89 MPa and strain of 853.2%). Therefore, these hydrogels with good reliable durability have outstanding application prospects in sustainable materials.
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Nanopartículas , Proteínas de Soja , Hidrogeles , EmulsionesRESUMEN
A visible-light metal-free photocatalytic regioselective and enantioselective alkene halofunctionalization reaction under mild conditions is reported. Various terminal and internal alkenes were transformed to their α-halogenated and α,ß-dibrominated derivatives in good to excellent yields within reaction time as short as 5 min. Water can be used as the "green" nucleophile and solvent in the halohydroxylation and halo-oxidation reactions. Different types of products can be obtained by adjusting the reaction conditions. In addition, sunlight is proved to produce products with similar yields, representing a practical example of solar synthesis and providing an opportunity for solar energy utilization.
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BACKGROUND: Vesicoureteral junction (VUJ) obstruction after Deflux® subureteral injection for vesicoureteral reflux (VUR) is rare and minimally invasive management has not been reported. This work investigated the patients who underwent Deflux® injection for VUR and identified those with subsequent VUJ obstruction. METHODS: Medical records of matched patients from October 2003 to March 2022 were reviewed, and parameters were retrospectively studied. All patients underwent Deflux® injection. The injection was performed under general anesthesia using the same manner. For patients complicated with VUJ obstruction, the symptoms, signs, management, images, renal ultrasounds, Tc-99m dimercaptosuccinic acid renal scintigraphy, histology of VUJ region, and outcomes were documented and reported. VUJ stenosis was diagnosed by performing renal ultrasound and magnetic resonance imaging. RESULTS: Totally 407 patients (554 ureterorenal units) received Dx/HA injections for VUR. VUJ obstruction was found in three patients (four ureterorenal units). Originally, three were grade V VUR, and one was grade IV. The repeated injection was not a risk factor for VUJ obstruction. The overall incidence of VUJ obstruction post-Dx/HA injection was 0.7% by ureter. The incidences were 0%, 0.75%, and 2.25% for grade I-III, IV, and V VUR, respectively. After the initial conversion case of pneumovesicoscopic ureteral reimplantation, the procedure was performed smoothly and successfully in the two following cases. CONCLUSIONS: Pneumovesicoscopic ureteral reimplantation offers an alternative for VUJ obstruction following Dx/HA injection for VUR. Fibrosis and foreign-body reaction may influence the feasibility. High-grade VUR and young age of injection were related to VUJ obstruction.
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Uréter , Reflujo Vesicoureteral , Humanos , Estudios Retrospectivos , Vejiga Urinaria , Reflujo Vesicoureteral/etiología , Reflujo Vesicoureteral/cirugíaRESUMEN
Our previous study has shown that p66Shc plays an important role in the process of myocardial regeneration in newborn mice, and p66Shc deficiency leads to weakened myocardial regeneration in newborn mice. This study aims to explore the role of p66Shc protein in myocardial injury repair after myocardial infarction in adult mice, in order to provide a new target for the treatment of myocardial injury after myocardial infarction. Mouse myocardial infarction models of adult wild-type (WT) and p66Shc knockout (KO) were constructed by anterior descending branch ligation. The survival rate and heart-to-body weight ratio of two models were compared and analyzed. Masson's staining was used to identify scar area of injured myocardial tissue, and myocyte area was determined by wheat germ agglutinin (WGA) staining. TUNEL staining was used to detect the cardiomyocyte apoptosis. The protein expression of brain natriuretic peptide (BNP), a common marker of myocardial hypertrophy, was detected by Western blotting. The results showed that there was no significant difference in survival rate, myocardial scar area, myocyte apoptosis, and heart weight to body weight ratio between the WT and p66ShcKO mice after myocardial infarction surgery. Whereas the protein expression level of BNP in the p66ShcKO mice was significantly down-regulated compared with that in the WT mice. These results suggest that, unlike in neonatal mice, the deletion of p66Shc has no significant effect on myocardial injury repair after myocardial infarction in adult mice.
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Infarto del Miocardio , Estrés Oxidativo , Animales , Ratones , Peso Corporal , Cicatriz/metabolismo , Ratones Noqueados , Infarto del Miocardio/genética , Proteínas Adaptadoras de la Señalización Shc/metabolismo , Proteína Transformadora 1 que Contiene Dominios de Homología 2 de Src/genética , Proteína Transformadora 1 que Contiene Dominios de Homología 2 de Src/metabolismoRESUMEN
The traditional Chinese medicine(TCM) enterprises have accumulated a large amount of product quality review(PQR) data. Mining these data can reveal the hidden knowledge in production and helps improve pharmaceutical manufacturing technology. However, there are few studies involving the mining of PQR data and thus enterprises lack the guidance to analyze the data. This study proposed a method to mine the PQR data, which consisted of 4 functional modules: data collection and preprocessing, risk classification of variables, risk evaluation by batches, and the regression analysis of quality. Further, we carried out a case study of the formulation process of a TCM product to illustrate the method. In the case study, the data of 398 batches of products during 2019-2021 were collected, which contained 65 process variables. The risks of variables were classified according to the process performance index. The risk of each batch was analyzed through short-term and long-term evaluation, and the critical variables with the strongest impact on the product quality were identified by partial least square regression. The results showed that 1 variable and 13 batches were of high risk, and the critical process variable was the quality of the intermediates. The proposed method enables enterprises to comprehensively mine the PQR data and helps to enhance the process understanding and improve the quality control.
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Medicamentos Herbarios Chinos , Medicina Tradicional China , Minería de Datos/métodos , Control de Calidad , Tecnología FarmacéuticaRESUMEN
Cardiovascular diseases are a serious threat to human health, especially in the elderly. Vascular aging makes people more susceptible to cardiovascular diseases due to significant dysfunction or senescence of vascular cells and maladaptation of vascular structure and function; moreover, vascular aging is currently viewed as a modifiable cardiovascular risk factor. To emphasize the relationship between senescent cells and vascular aging, we first summarize the roles of senescent vascular cells (endothelial cells, smooth muscle cells and immune cells) in the vascular aging process and inducers that contribute to cellular senescence. Then, we present potential strategies for directly targeting senescent cells (senotherapy) or preventively targeting senescence inducers (senoprevention) to delay vascular aging and the development of age-related vascular diseases. Finally, based on recent research, we note some important questions that still need to be addressed in the future.
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Enfermedades Cardiovasculares , Células Endoteliales , Anciano , Envejecimiento , Enfermedades Cardiovasculares/etiología , Senescencia Celular , Humanos , Miocitos del Músculo LisoRESUMEN
RATIONALE: Maintaining iron homeostasis is essential for proper cardiac function. Both iron deficiency and iron overload are associated with cardiomyopathy and heart failure via complex mechanisms. Although ferritin plays a central role in iron metabolism by storing excess cellular iron, the molecular function of ferritin in cardiomyocytes remains unknown. OBJECTIVE: To characterize the functional role of Fth (ferritin H) in mediating cardiac iron homeostasis and heart disease. METHODS AND RESULTS: Mice expressing a conditional Fth knockout allele were crossed with 2 distinct Cre recombinase-expressing mouse lines, resulting in offspring that lack Fth expression specifically in myocytes (MCK-Cre) or cardiomyocytes (Myh6-Cre). Mice lacking Fth in cardiomyocytes had decreased cardiac iron levels and increased oxidative stress, resulting in mild cardiac injury upon aging. However, feeding these mice a high-iron diet caused severe cardiac injury and hypertrophic cardiomyopathy, with molecular features typical of ferroptosis, including reduced glutathione (GSH) levels and increased lipid peroxidation. Ferrostatin-1, a specific inhibitor of ferroptosis, rescued this phenotype, supporting the notion that ferroptosis plays a pathophysiological role in the heart. Finally, we found that Fth-deficient cardiomyocytes have reduced expression of the ferroptosis regulator Slc7a11, and overexpressing Slc7a11 selectively in cardiomyocytes increased GSH levels and prevented cardiac ferroptosis. CONCLUSIONS: Our findings provide compelling evidence that ferritin plays a major role in protecting against cardiac ferroptosis and subsequent heart failure, thereby providing a possible new therapeutic target for patients at risk of developing cardiomyopathy.
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Sistema de Transporte de Aminoácidos y+/metabolismo , Apoferritinas/deficiencia , Cardiomiopatías/etiología , Ferroptosis/fisiología , Hierro/metabolismo , Miocardio/metabolismo , Envejecimiento , Alelos , Animales , Apoferritinas/efectos adversos , Apoferritinas/genética , Cardiomiopatías/metabolismo , Cardiomiopatías/prevención & control , Cardiomiopatía Hipertrófica/etiología , Cardiomiopatía Hipertrófica/prevención & control , Cruzamientos Genéticos , Ciclohexilaminas/administración & dosificación , Glutatión/metabolismo , Insuficiencia Cardíaca/etiología , Homeostasis , Hipertrofia Ventricular Izquierda/etiología , Deficiencias de Hierro , Sobrecarga de Hierro , Hierro de la Dieta/efectos adversos , Peroxidación de Lípido , Masculino , Ratones , Ratones Transgénicos , Miocitos Cardíacos/metabolismo , Estrés Oxidativo , Fenilendiaminas/administración & dosificación , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Multiple morphological abnormalities of the sperm flagella (MMAF) is a characteristic form of severe asthenozoospermia and closely related to male infertility. However, it is not sure whether intracytoplasmic sperm injection (ICSI) allows MMAF patients reproductive success. The present study reported the first case of successful intracytoplasmic sperm injection-embryo transfer (ICSI-ET) in Chinese brothers with a novel compound heterozygous mutation of FSIP2 (fibrous sheath interacting protein 2), a newly identified MMAF-related genes. The proband and his brother were referred for MMAF because of their abnormal sperm flagellum. Through whole-exome sequencing in the genetic analyses of the proband, his brother and parents showed that the proband and his brother carry a novel compound heterozygous FSIP2 mutation (c.1750T>A and c.13600A>G), which will lead to abnormal expression of FSIP2 and loss of its function. Considering that these brothers had the MMAF phenotype, we recommended ICSI treatment. The successful outcome of ICSI indicated that a lose-function mutation of FSIP2 might not have any effect on ICSI, although the latest report showed a failed outcome of ICSI in a patient with FSIP2 mutation. This study provides new knowledge to understand the effect of MMAF caused by FSIP2 mutation on ICSI outcome.
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Infertilidad Masculina , Inyecciones de Esperma Intracitoplasmáticas , China , Transferencia de Embrión , Humanos , Infertilidad Masculina/genética , Infertilidad Masculina/terapia , Masculino , Mutación , Hermanos , Cola del Espermatozoide , EspermatozoidesRESUMEN
BACKGROUND: One-handed backhand (OB) and two-handed backhand (TB) styles are commonly used in tennis, but only TB generates loadings on the non-dominant arm and a greater extension torque on the rear leg, leading to a greater axial torque involving rotation of the hip and trunk. The current study investigated whether those effects can further affect bone area (BA), bone mineral content (BMC) and density (BMD) in postmenopausal recreational tennis players. METHODS: BA, BMC and BMD of the lumbar spine, hip and distal radius were assessed using dual-energy X-ray absorptiometry in TB, OB, and swimmers' group as a control (SG) (all participants self-reported for at least 5 years of exercise history, n = 14 per group). Muscular strength was assessed with a hand dynamometer. Among these three groups, the BA, BMC and BMD of distal radius and muscle strength were assessed using one-way ANOVA, and those of the lumbar region and the hip joint were tested by one-way ANCOVA. RESULTS: TB showed higher BMC and BMD for both lumbar spine and femoral neck than SG (all, p < 0.05). Both OB and TB showed greater BMD inter-trochanter than SG (both, p < 0.05). OB demonstrated greater inter-arm differences in the distal radius, which involved 1/3 distal for BMC and mid-distal radius for BMD compared to the TB and SG (all, p < 0.05). In addition, greater inter-arm asymmetry of grip strength was found in OB compared to TB and SG (both, p < 0.05). CONCLUSION: For postmenopausal women, performing two-handed backhand strokes, leads to higher BMC and BMD in the non-dominant arm, the lumbar region, and hips, indicating potential benefit to maintain bone health and strength. Whether this result leads to reducing the risk of osteoporosis needs to be investigated in further research.