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Ulcerative colitis (UC) is a recurrent chronic mucosal inflammation disease whose most significant pathological characteristics are intestinal inflammation and damaged mucosal barrier induced by reactive oxygen/nitrogen species, abnormal immune microenvironment, and intestinal microecological imbalance. Oral probiotics are a living therapy for intestinal diseases, but their clinical application is hindered by poor bacterial biological activity and insufficient intestinal retention. Here, we developed a targeted oral formulation, functionalized probiotic Lf@MPB, with Lactobacillus fermentum (Lf) as the core and modified melanin nanoparticles (MNPs) on its surface through a click reaction of tricarboxyphenylboronic acid for synergistic therapy of UC. In vitro experiments showed that Lf@MPB not only possessed strong free radical scavenging ability, reduced cellular mitochondrial polarization, and inhibited apoptosis but also significantly enhanced the viability of Lf probiotics in simulated gastrointestinal fluid. Fluorescence imaging in vivo revealed the high accumulation of Lf@MPB at the site of intestinal inflammation in dextran sulfate sodium-induced UC mice. Moreover, in vivo results demonstrated that Lf@MPB effectively alleviated oxidative stress and inflammatory response and restored the intestinal barrier. In addition, 16S rRNA gene sequencing verified that Lf@MPB could increase the abundance and diversity of intestinal microbial communities and optimize microbial composition to inhibit the progression of UC. This work combines effective antioxidant and anti-inflammatory strategies with the oral administration of functionalized probiotics to provide a promising alternative for UC treatment.
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Colitis Ulcerosa , Melaninas , Nanopartículas , Probióticos , Animales , Humanos , Masculino , Ratones , Colitis Ulcerosa/terapia , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/patología , Sulfato de Dextran , Microbioma Gastrointestinal/efectos de los fármacos , Limosilactobacillus fermentum , Melaninas/química , Ratones Endogámicos C57BL , Nanopartículas/química , Probióticos/química , Probióticos/farmacologíaRESUMEN
Gallium nitride (GaN) nanowire, as a type of wide bandgap nanomaterial, has attracted considerable interest because of its outstanding physicochemical properties and applications in energy storage and photoelectric devices. In this study, we prepared GaN nanowires via a facile chemical vapor deposition method and investigated their nonlinear absorption responses ranging from ultraviolet to near-infrared in the z-scan technology under irradiation by picosecond laser pulses. The experiment revealed that GaN nanowires exhibit remarkable nonlinear absorption characteristics attributed to their wide bandgap and nanostructure, including saturable absorption and reverse saturable absorption. When compared to bulk GaN crystals, the nanowires provide a richer and more potent set of nonlinear optical effects. Furthermore, we conducted an analysis of the corresponding electronic transition processes associated with photon absorption. Under high peak power density laser excitation, two-photon absorption or three-photon absorption dominate, with maximum modulation depths of 73.6%, 74.9%, 63.1% and 64.3% at 266â nm, 355â nm, 532â nm, and 1064â nm, respectively, corresponding to absorption coefficients of 0.22â cm/GW, 0.28â cm/GW, 0.08â cm/GW, and 2.82 ×10-4 cm3/GW2. At lower peak energy densities, GaN nanowires demonstrate rare and excellent saturation absorption characteristics at wavelength of 355â nm due to interband transitions, while saturable absorption is also observed at 532â nm and 1064â nm due to band tail absorption. The modulation depths are 85.2%, 41.9%, and 13.7% for 355â nm, 532â nm, and 1064â nm, corresponding to saturation intensities of 3.39 GW/cm2, 5.58 GW/cm2 and 14.13 GW/cm2. This indicates that GaN nanowires can be utilized as broadband optical limiters and high-performance pulse laser modulating devices, particularly for scarce ultraviolet optical limiters, and saturable absorbers for ultraviolet and visible lasers. Furthermore, our study demonstrates the application potential of wide bandgap nanomaterials in nonlinear optical devices.
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Jinlida granule (JLD) is a Traditional Chinese Medicine (TCM) formula used for the treatment of type 2 diabetes mellitus (T2DM). However, the mechanism of JLD treatment for T2DM is not fully revealed. In this study, we explored the mechanism of JLD against T2DM by an integrative pharmacology strategy. Active components and corresponding targets were retrieved from Traditional Chinese Medicine System Pharmacology (TCMSP), SwissADME and Bioinformatics Analysis Tool for Molecular Mechanisms of Traditional Chinese Medicine Database (BATMAN-TCM) database. T2DM-related targets were obtained from Drugbank and Genecards databases. The protein-protein interaction (PPI) network was constructed and analyzed with STRING (Search Toll for the Retrieval of Interacting Genes/proteins) and Cytoscape to get the key targets. Then, Gene Ontology (GO) and Kyoto Encyclopedia of Gene and Genomes (KEGG) enrichment analyses were performed with the Database for Annotation, Visualization and Integrated Discovery (DAVID). Lastly, the binding capacities and reliability between potential active components and the targets were verified with molecular docking and molecular dynamics simulation. In total, 185 active components and 337 targets of JLD were obtained. 317 targets overlapped with T2DM-related targets. RAC-alpha serine/threonine-protein kinase (AKT1), tumor necrosis factor (TNF), interleukin-6 (IL-6), cellular tumor antigen p53 (TP53), prostaglandin G/H synthase 2 (PTGS2), Caspase-3 (CASP3) and signal transducer and activator of transcription 3 (STAT3) were identified as seven key targets by the topological analysis of the PPI network. GO and KEGG enrichment analyses showed that the effects were primarily associated with gene expression, signal transduction, apoptosis and inflammation. The pathways were mainly enriched in PI3K-AKT signaling pathway and AGE-RAGE signaling pathway in diabetic complications. Molecular docking and molecular dynamics simulation verified the good binding affinity between the key components and targets. The predicted results may provide a theoretical basis for drug screening of JLD and a new insight for the therapeutic effect of JLD on T2DM.
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Diabetes Mellitus Tipo 2 , Medicamentos Herbarios Chinos , Simulación del Acoplamiento Molecular , Mapas de Interacción de Proteínas , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/química , Humanos , Mapas de Interacción de Proteínas/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Medicina Tradicional China/métodos , Simulación de Dinámica Molecular , Biología Computacional/métodos , Ontología de Genes , Hipoglucemiantes/farmacología , Hipoglucemiantes/químicaRESUMEN
A genomic study was conducted to uncover the selection signatures in sheep that show extremely significant differences in growth traits under the same breed, age in months, nutrition level, and management practices. Hu sheep from Gansu Province and Gangba sheep from the Tibet Autonomous Region in China were selected. We collected whole-genome data from 40 sheep individuals (24 Hu sheep and 16 Gangba sheep), through whole-genome sequencing. Selection signals were analyzed using parameters such as FST, π ratio, and Tajima's D. We have identified several candidate genes that have undergone strong selection, particularly those associated with growth traits. Specifically, five growth-related genes were identified in both the Hu sheep group (HDAC1, MYH7B, LCK, ACVR1, GNAI2) and the Gangba sheep group (RBBP8, ACSL3, FBXW11, PLAT, CRB1). Additionally, in a genomic region strongly selected in both the Hu and Gangba sheep groups (Chr 22: 51,425,001-51,500,000), the growth-associated gene CYP2E1 was identified, further highlighting the genetic factors influencing growth characteristics in these breeds. This study analyzes the genetic basis for significant differences in sheep phenotypes, identifies candidate genes related to sheep growth traits, lays the foundation for molecular genetic breeding in sheep, and accelerates the genetic improvement in livestock.
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Secuenciación Completa del Genoma , Animales , Ovinos/genética , Ovinos/crecimiento & desarrollo , Secuenciación Completa del Genoma/métodos , Cruzamiento , Selección Genética , Fenotipo , Polimorfismo de Nucleótido Simple , Genoma/genéticaRESUMEN
Femtosecond optical parametric oscillators (OPOs) are widely used in ultrafast nonlinear frequency conversion and quantum information. However, conventional OPOs based on quasi-phase-matching (QPM) crystals have many parasitic non-phase-matched processes which decrease the conversion efficiency. Here, we propose nine-wave coupled equations (NWCEs) to simulate all phase-matched and non-phase-matched interactions in QPM crystals to improve conventional three-wave coupled equations (TWCEs), especially for the situation of high intensity ultrashort pulses and complexly structured crystals. We discuss how to design the poling period of QPM crystal to maximize the conversion efficiency of signal light for a given OPO system. The simulation reveals that the OPO based on chirped periodically poled lithium niobate (CPPLN) with a certain chirp rate has higher signal wave conversion efficiency than that of a PPLN, and demonstrates that NWCEs illustrate more details of the pulse evolution in the OPO cavity. Starting from a CPPLN, an aperiodically poled lithium niobate (APPLN) design is available by modifying the domain lengths of the crystal and optimizing the OPO output power via dynamical optimization algorithm. The results show that by using a properly designed APPLN crystal, a 1600â nm OPO, when pumped by a femtosecond laser with 1030â nm central wavelength, 150 femtosecond pulse duration and 5 GW/cm2 power intensity at the focus, can achieve very efficient output with a signal light conversion efficiency of 50.6%, which is higher than that of PPLN (25.2%) and CPPLN (40.2%). The scheme in this paper will provide a reference for the design of nonlinear QPM crystals of OPOs and will help to understand the complex nonlinear dynamical behavior in OPO cavities.
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Diabetic nephropathy (DN) is a serious complication in patients with diabetes, whose expansion process is closely related to oxidative stress caused by hyperglycemia. Herein, we report a chitosan-targeted dagliflozin-loaded melanin nanoparticle (CSMDNPs) that can selectively accumulate in injured kidneys, reduce blood glucose, and alleviate the oxidative stress-induced damage. CSMDNPs possess good dispersion and physiological stability, responsive release at acidic pH, and strong scavenging activities for various reactive oxygen and reactive nitrogen radicals. Moreover, in vitro experiments confirm that CSMDNPs have good biocompatibility, enable targeted uptake in NRK-52E renal tubular cells, and also well alleviate high glucose-induced oxidative stress. In the STZ-induced DN model, CSMDNPs exhibit high targeting distribution and retention in the damaged kidneys of DN mice according to photoacoustic imaging. At the end of CSMDNPs treatment, DN mice show a decrease in fasting blood glucose and a return to near-normal urine and blood indices. H&E, PAS, and masson pathological staining also indicates that CSMDNPs significantly inhibit the expansion of renal interstitium, glycogen, and collagen deposition, showing excellent therapeutic effects. In addition, melanin acts as both drug carrier and antioxidant without exogenous carrier introduction, exhibiting better biosafety and translational prospects.
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Quitosano , Diabetes Mellitus , Nefropatías Diabéticas , Humanos , Animales , Ratones , Nefropatías Diabéticas/patología , Glucemia/metabolismo , Melaninas/metabolismo , Quitosano/farmacología , Riñón , Estrés Oxidativo , Diabetes Mellitus/metabolismoRESUMEN
In this paper, the optimal solution of effective nonlinear coefficient of quasi-phase-matching (QPM) crystals for coupled third harmonic generation (CTHG) was numerically investigated. The effective nonlinear coefficient of CTHG was converted to an Ising model for optimizing domain distributions of aperiodically poled lithium niobate (APPLN) crystals with lengths as 0.5 mm and 1 mm, and fundamental wavelengths ranging from 1000â nm to 6000â nm. A method for reconstructing crystal domain poling weight curve of coupled nonlinear processes was also proposed, which demonstrated the optimal conversion ratio between two coupled nonlinear processes at each place along the crystal. In addition, by applying the semidefinite programming, the upper bound on the effective nonlinear coefficients deff for different fundamental wavelengths were calculated. The research can be extended to any coupled dual χ(2) process and will help us to understand better the dynamics of coupled nonlinear interactions based on QPM crystals.
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Ischemia/reperfusion (I/R)-induced acute kidney injury (AKI) is a serious kidney disease with high morbidity and mortality. However, there is no effective clinical treatment strategy. Herein, we developed a CD44 targeting nanoplatform based on HA-assembled melanin NPs covalently coupled with dexamethasone for I/R-induced AKI therapy by alleviating oxidative/inflammatory- induced damage. The constructed HA-MNP-DXM NPs had good dispersion, stability, and broad-spectrum scavenging capabilities against multiple reactive free radicals. Moreover, the NPs could be efficiently internalized and exhibited antioxidative, anti-inflammatory, and antiapoptotic effects in CoCl2-stimulated renal tubular epithelial NRK-52E cells. Furthermore, the I/R-induced AKI murine model was established to evaluate the in vivo performance of NPs. The results suggested the NPs could specifically target impaired kidneys upon intravenous administration according to NIR-II fluorescence imaging and showed high biosafety. Importantly, the NPs could improve renal function, alleviate oxidative stress and inflammatory reactions, inhibit apoptosis of tubular cells, and restore mitochondrial structure and function, exhibiting excellent therapeutic effects. Further therapeutic mechanism indicated the NPs maintained the cellular/mitochondrial redox balance by modulating the Nrf2 and HO-1 expression. Therefore, the NPs can be a promising therapeutic candidate for the treatment of I/R-induced AKI.
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Lesión Renal Aguda , Daño por Reperfusión , Ratones , Animales , Melaninas/metabolismo , Riñón/metabolismo , Lesión Renal Aguda/tratamiento farmacológico , Lesión Renal Aguda/metabolismo , Daño por Reperfusión/tratamiento farmacológico , Daño por Reperfusión/metabolismo , Reperfusión , Isquemia , ApoptosisRESUMEN
INTRODUCTION: Rothmund-Thomson syndrome (RTS) is a rare autosomal recessive disorder that has been reported in all ethnicities, with several identifiable pathogenic variants. There have been reported cases indicating that RTS may lead to low birth weight in fetuses, but specific data on the fetal period are lacking. Genetic testing for RTS II is currently carried out by identifying pathogenic variants in RECQL4. METHODS: In order to determine the cause, we performed whole-genome sequencing (WGS) analysis on the patient and his parents. Variants detected by WGS were confirmed by Sanger sequencing and examined in family members. RESULTS: After analyzing the WGS data, we found a heterozygous nonsense mutation c.2752G>T (p.Glu918Ter) and a novel frameshift insertion mutation c.1547dupC (p.Leu517AlafsTer23) of RECQL4, which is a known pathogenic/disease-causing variant of RTS. Further validation indicated these were compound heterozygous mutations from parents. CONCLUSION: Our study expands the mutational spectrum of the RECQL4 gene and enriches the phenotype spectrum of Chinese RTS patients. Our information can assist the patient's parents in making informed decisions regarding their future pregnancies. This case offers a new perspective for clinicians to consider whether to perform prenatal diagnosis.
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Síndrome Rothmund-Thomson , Humanos , Síndrome Rothmund-Thomson/diagnóstico , Síndrome Rothmund-Thomson/genética , Síndrome Rothmund-Thomson/patología , Mutación , Mutación del Sistema de Lectura , Fenotipo , ChinaRESUMEN
Objective: The present study is to explore the association between NQO1 gene polymorphism and coronary heart disease (CHD) risk. Methods: This research were selected 80 CHD patients as the observation group and 130 healthy people who participated in normal physical examination during the same period as the control group. NQO1 gene polymorphism was detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. In addition, we conducted a meta-analysis to summarize the results of three relevant previously published adult population studies on the association between NQO1 gene polymorphism and coronary heart disease (CHD) risk. Results: There were three genotypes (CC, CT, and TT) for NQO1 C609T polymorphism. The significant associations were found in TT genotype and T allele (all p<0.05). Specifically, People with the TT genotype have 2.06 times CHD risk as those with the CC genotype. And People with the T allele have 1.62 times CHD risk as those with the C allele. No significant association was found by any genetic models in the meta-analysis (all p >0.05). Conclusion: NQO1 gene polymorphism increased the CHD risk in a Chinese population. Combined with individual gene polymorphism, the accuracy of risk assessment for CHD can be improved and individualized health education can be provided for CHD patients by nurses.
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PURPOSE: Left ventricular (LV) dyssynchrony is believed to be associated with the prognosis of dilated cardiomyopathy (DCM) mainly assessed by echocardiography. This study sought to explore whether quantitative LV mechanical dyssynchrony by cardiovascular magnetic resonance imaging (CMR) tissue feature tracking could predict the prognosis of DCM. METHOD: Patients undergoing CMR between January 2016 and December 2017 were reviewed to identify DCM patients. Quantitative LV mechanical dyssynchrony was assessed by CMR strain analysis. The outcomes of these DCM patients were followed up. The association between LV mechanical dyssynchrony and outcomes was analyzed by Cox proportional regression analysis. RESULTS: A total of 417 patients with DCM were enrolled. At a median follow-up of 57 months, 109 patients reached endpoints: 19, sudden cardiac death; 34, heart failure death; 41, heart transplantation; 9, malignant ventricular arrhythmias; 2, LV assist devices; and 4, appropriate shocks of defibrillators. After adjustment for confounding variables, the 16-segment standard deviation of the time-to-peak radial strain (16SDTTPRS) (HR, 1.932 [95% CI: 1.079, 3.461]; P = 0.027), LV end-diastolic diameter index (HR, 1.049 [95% CI: 1.020, 1.080]; P = 0.001), NYHA classes (HR, 2.131 [95% CI: 1.597-2.844]; P < 0.001) and late gadolinium enhancement (HR, 3.219 [95% CI: 2.164, 4.787]; P < 0.001) were independently associated with composite endpoints. CONCLUSIONS: The quantitative LV mechanical dyssynchrony parameter 16SDTTPRS derived from CMR was independently associated with adverse outcomes in patients with DCM.
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Cardiomiopatía Dilatada , Disfunción Ventricular Izquierda , Humanos , Cardiomiopatía Dilatada/diagnóstico por imagen , Medios de Contraste , Gadolinio , Imagen por Resonancia Magnética , Pronóstico , Función Ventricular Izquierda , Valor Predictivo de las Pruebas , Disfunción Ventricular Izquierda/diagnóstico por imagen , Imagen por Resonancia CinemagnéticaRESUMEN
Background: Plasma cell-free RNAs (cfRNAs) can serve as noninvasive biomarkers for the diagnosis and monitoring of diseases. However, the delay in blood processing may lead to unreliable results. Therefore, an unbiased evaluation based on the whole transcriptome under different storage conditions is needed. Methods: Here, blood samples were collected in ethylenediaminetetraacetic acid tubes and processed immediately (0 hour), or stored at room temperature (RT) or 4°C for different time intervals (2, 6, and 24 hours) before plasma separation. High-throughput sequencing was applied to assess the effects of storage conditions on the transcript profiles and fragment characteristics of plasma cell-free mRNA, long noncoding RNA (lncRNA), and small RNAs. Results: More genes changed their expression levels with time when blood was stored at RT compared with those at 4°C. Cell-free mRNA and lncRNA were relatively stable in blood preserved at 4°C for 6 hours, while cell-free microRNA (miRNA) and piwi-interacting RNA (piRNA) remained stable at 4°C for 24 hours. After 24 hours, more contamination of the leukocyte-derived RNAs occurred at RT, possibly due to apoptosis. Meanwhile, significant changes were also observed regarding the characteristics of the RNA fragments, including fragment size, the proportion of intron, and the pyrimidine frequency of the fragmented 3' end. Fifteen tissue-enriched genes were detected in the plasma but not expressed in leukocytes. The expression level and fragment length of these genes gradually decreased during storage, suggesting the degradation of the cfRNA and the dilution of leukocyte-derived RNA with other tissue-derived cfRNA. Conclusions: Our results suggest that the contamination of leukocyte-derived RNA and the degradation of original cfRNA contribute to the changes in the cfRNA expression profiles and the fragment characteristics during short-term storage. The storage of blood at 4°C for 6 hours allows plasma cfRNA to remain relatively stable, which will be useful for further studies or clinical applications where adequate quantification or the fragment signature of cfRNA is required.
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Ácidos Nucleicos Libres de Células , ARN Largo no Codificante , Ácidos Nucleicos Libres de Células/genética , ARN Largo no Codificante/genética , ARN Mensajero , Recolección de Muestras de Sangre/métodos , ARN de Interacción con Piwi , Secuenciación de Nucleótidos de Alto RendimientoRESUMEN
The development of biocompatible and efficient nanoplatforms that combine diagnostic and therapeutic functions is of great importance for precise disease treatment. Melanin, an endogenous biopolymer present in living organisms, has attracted increasing attention as a versatile bioinspired functional platform owing to its unique physicochemical properties (e.g., high biocompatibility, strong chelation of metal ions, broadband light absorption, high drug binding properties) and inherent antioxidant, photoprotective, anti-inflammatory, and anti-tumor effects. In this review, the fundamental physicochemical properties and preparation methods of natural melanin and melanin-like nanoparticles were outlined. A systematical description of the recent progress of melanin and melanin-like nanoparticles in single, dual-, and tri-multimodal imaging-guided the visual administration and treatment of osteoarthritis, acute liver injury, acute kidney injury, acute lung injury, brain injury, periodontitis, iron overload, etc. Was then given. Finally, it concluded with a reasoned discussion of current challenges toward clinical translation and future striving directions. Therefore, this comprehensive review provides insight into the current status of melanin and melanin-like nanoparticles research and is expected to optimize the design of novel melanin-based therapeutic platforms and further clinical translation.
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Solid pseudopapillary neoplasm (SPN) of the pancreas is rare relatively low-grade malignant neoplasm and metastasis rarely. Surgical resection is the primary treatment option for primary and metastatic lesions of SPN, and chemotherapy is often ineffective in non-operable SPNs. SPNs are characterized by the presence of somatic CTNNB1 exon 3 mutations, leading to the activation of Wnt/ß-catenin/Cox-2 signal pathway. Here, we firstly report that a refractory liver metastatic pancreatic SPN patient after the failure of multi-line chemotherapies benefited from the Cox-2 selective inhibitor (Celecoxib) based on CTNNB1 D32V mutation detected by next-generation sequencing (NGS), achieving a more than 22-month progression-free survival without any adverse events. Our case provides a potential treatment option for liver metastatic SPN patients with CTNNB1 mutations and highlights the application of NGS for the better treatment decision making.
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Distal vaginal atresia is a rare abnormality of female reproductive tract in which the vagina is closed or absent. The distal vagina may be replaced by fibrous tissue and the condition is often not diagnosed until a girl fails to begin having periods at puberty. Although it is a congenital disorder, potential genetic causes of distal vaginal atresia are still unknown. We recruited a cohort of 39 patients with distal vaginal atresia and analyzed their phenotypic and genetic features. In addition to the complaint of distal vaginal atresia, approximately 17.9% (7/39) of the patients had other Müllerian anomalies, and 17.9% (7/39) of the patients had other structural abnormalities, including renal-tract, skeletal and cardiac anomalies. Using genome sequencing, we identified two fragment duplications on 17q12 encompassing HNF1B and LHX1, two dosage-sensitive genes with candidate pathogenic variants, in two unrelated patients. A large fragment of uniparental disomy was detected in another patient, affecting genes involved in cell morphogenesis and connective tissue development. Additionally, we reported two variants on TBX3 and AXL, leading to distal vaginal atresia in mutated mouse model, in our clinical subjects for the first time. Essential biological functions of these detected genes with pathogenic variants included regulating reproductive development and cell fate and patterning during embryogenesis. We displayed the comprehensive clinical and genetic characteristic of a cohort with distal vaginal atresia and they were highly heterogeneous both phenotypically and genetically. The duplication of 17q12 in our cohort could help to expand its phenotypic spectrum and potential contribution to the distal vaginal atresia. Our findings of pathogenic genetic variants and associated phenotypes in our cohort could provide evidence and new insight for further research attempting to reveal genetic causes of distal vaginal atresia.
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Cardiopatías Congénitas , Maduración Sexual , Ratones , Animales , Femenino , Vagina , Genitales FemeninosRESUMEN
The ability to accurately and cost-friendly monitor heavy metals in environmental solutions such as drinking or tap water is of great significance to the human health. We report a twisted fiber-based sensing mechanism that can realize highly accurate detection of Cd2+ concentration in water solution. The basic design is a twisted single-core fiber simply coated with a propylene thiourea membrane that can absorb Cd2+. Due to the twisting effect, light in the core can scatter into the cladding, yielding optical coupling and interference. We experimentally prove that both positions and amplitudes of interference dips in the sample transmission spectrum can effectively and linearly response to the change of Cd2+ concentration at the level of 10-11 mol/L. With bimodal calibration, such sensor can realize accurate and real-time monitor in a stable and nontoxic way. These excellent characteristics indicate promising potential in the field of biochemical and integrated optical sensing.
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OBJECTIVE: With advances in mobile technology, smartphone-based point-of-care testing (POCT) urinalysis hold great potential for disease screening and health management for clinicians and individual users. The purpose of this study is to evaluate the analytical performance of Hipee S2 POCT urine dipstick analyser. DESIGN: A multicentre, hospital-based, cross-sectional study. SETTING: Analytical performance of the POCT analyser was conducted at a clinical laboratory, and method comparison was performed at three clinical laboratories in China. PARTICIPANTS: Urine samples were collected from 1603 outpatients and inpatients at three hospitals, and 5 health check-up population at one of the hospitals. OUTCOME MEASURES: All tests were performed by clinical laboratory technicians. Precision, drift, carry-over, interference and method comparison of Hipee S2 were evaluated. Diagnostic accuracy of semiquantitative albumin-to-creatinine ratio (ACR) for albuminuria was carried out using quantitative ACR as the standard. RESULTS: The precision for each parameter, assessed by control materials, was acceptable. No sample carry-over or drift was observed. Ascorbate solution with 1 g/L had an inhibitory effect for the haemoglobin test. Agreement for specific gravity (SG) varied between moderate to substantial (κ values 0.496-0.687), for pH was moderate (κ values 0.423-0.569) and for other parameters varied between substantial to excellent (κ values 0.669-0.991), on comparing the Hipee S2 with laboratory analysers. The semiquantitative microalbumin and creatinine were highly correlated with the quantitative results. The sensitivity of semiquantitative ACR to detect albuminuria was 87.2%-90.7%, specificity was 70.7%-78.4%, negative predictive value was 85.3%-87.9% and positive predictive value was 73.9%-83%. CONCLUSIONS: Hipee S2 POCT urine analyser showed acceptable analytical performance as a semiquantitative method. It serves as a convenient alternate device for clinicians and individual users for urinalysis and health management. In addition, the POCT semiquantitative ACR would be useful in screening for albuminuria.
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Albuminuria , Urinálisis , Humanos , Albuminuria/diagnóstico , Creatinina , Estudios Transversales , Urinálisis/métodos , Pruebas en el Punto de Atención , Sistemas de Atención de PuntoRESUMEN
A multi-parameter dual-core fiber sensor is proposed to realize highly sensitive detection of illumination, temperature, and humidity, separately. Through partial grating etching of a one-side core, the interaction between the core and the external environment is enhanced. Then, combining the Mach-Zehnder effect of the dual core, a higher sensing sensitivity is obtained. Experimental results show the temperature sensitivity is higher than 6.1952 nm/°C. Besides, the humidity and illumination resolution can reach as accurate as 0.041 relative humidity (RH) and 0.025 light units, respectively. To have better multi-parameter sensing and demodulation, the deep learning algorithm of a one-dimensional convolutional neural network (1D-CNN) is used to reach an accuracy of 99.05% with â¼2.00 root mean square error (RMSE). We envision such an excellent multi-parameter sensor can be promising in environmental monitoring and intelligent manufacturing.
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For advanced non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations, EGFR tyrosine kinase inhibitors (TKIs) have been approved as the standard therapy and shown clinical benefits. However, the emergence of drug resistance is inevitable. Tumor heterogeneity was often observed by imaging method to evaluate the progression of primary and metastatic lesions. Tissue biopsy was also unlikely to accurately capture the complete genomic landscape from a single tissue sample. Recently, genomic characterization of circulating tumor DNA (ctDNA) offer an opportunity to reveal the clonal dynamics throughout the course of a patient's illness and provide comprehensive genomic landscape of tumors to assess tumor heterogeneity. Here, we reported a lung adenocarcinoma (LADC) with EGFR mutations who was treated with sequential EGFR TKIs. The CT image of the patient's different lesions suggested that dynamic change of tumor heterogeneity had occurred. Targeted next-generation sequencing (NGS) analysis of ctDNA revealed dynamic changes of mutational profiles between the primary and metastatic tumors to discover tumor evolution to guide treatment decision-making.