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Staphylococcus aureus is considered to be an extracellular pathogen. However, survival of S.aureus within host cells may cause long-term colonization and clinical failure. Current treatments have poor efficacy in clearing intracellular bacteria. Antibody-antibiotic conjugates (AACs) is a novel strategy for eliminating intracellular bacteria. Herein, we use KRM-1657 as payload of AAC for the first time, and we conjugate it with anti S. aureus antibody via a dipeptide linker (Valine-Alanine) to obtain a novel AAC (ASAK-22). The ASAK-22 exhibits good in vitro pharmacokinetic properties and inhibitory activity against intracellular MRSA, with 100 µg/mL of ASAK-22 capable of eliminating intracellular MRSA to the detection limit. Furthermore, the in vivo results demonstrate that a single administration of ASAK-22 significantly reduces the bacterial burden in the bacteremia model, which is superior to the vancomycin treatment.
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Antibacterianos , Staphylococcus aureus Resistente a Meticilina , Pruebas de Sensibilidad Microbiana , Animales , Humanos , Ratones , Antibacterianos/farmacología , Antibacterianos/química , Relación Dosis-Respuesta a Droga , Inmunoconjugados/química , Inmunoconjugados/farmacología , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Ratones Endogámicos BALB C , Estructura Molecular , Infecciones Estafilocócicas/tratamiento farmacológico , Relación Estructura-Actividad , Rifamicinas/química , Rifamicinas/farmacologíaRESUMEN
Glutathione (GSH) is an important antioxidant that is generated and degraded via the GSH cycle. Quantification of the main components in the GSH cycle is necessary to evaluate the process of GSH. In this study, a robust ultra-performance liquid chromatography-tandem mass spectrometry method for the simultaneous quantification of 10 components (GSH; γ-glutamylcysteine; cysteinyl-glycine; n-acetylcysteine; homocysteine; cysteine; cystine; methionine; glutamate; pyroglutamic acid) in GSH cycle was developed. The approach was optimized in terms of derivative, chromatographic, and spectrometric conditions as well as sample preparation. The unstable thiol groups of GSH, γ-glutamylcysteine, cysteinyl-glycine, n-acetylcysteine, cysteine, and homocysteine were derivatized by n-ethylmaleimide. The derivatized and underivatized analytes were separated on an amino column with gradient elution. The method was further validated in terms of selectivity (no interference), linearity (R2 > 0.99), precision (% relative standard deviation [RSD%] range from 0.57 to 10.33), accuracy (% relative error [RE%] range from -3.42 to 10.92), stability (RSD% < 5.68, RE% range from -2.54 to 4.40), recovery (RSD% range from 1.87 to 7.87) and matrix effect (RSD% < 5.42). The validated method was applied to compare the components in the GSH cycle between normal and oxidative stress cells, which would be helpful in clarifying the effect of oxidative stress on the GSH cycle.
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Glutatión , Espectrometría de Masas en Tándem , Espectrometría de Masas en Tándem/métodos , Glutatión/análisis , Cromatografía Líquida de Alta Presión/métodos , Humanos , Homocisteína/análisis , Cisteína/análisis , Ácido Pirrolidona Carboxílico/análisis , Ácido Pirrolidona Carboxílico/química , Ácido Pirrolidona Carboxílico/metabolismo , Dipéptidos/análisis , Acetilcisteína/análisis , Acetilcisteína/química , Cistina/análisisRESUMEN
Rhubarb is widely used in health care, but causing a great amount of rhein-containing herbal residue. Rhein with several toxicities might pollute environment, damage ecology and even hazard human health if left untreated. In this study, the degradation effects of bisulfite- (BS) and peroxymonosulfate- (PMS) based oxidation systems on rhein in rhubarb residue were compared and investigated. The effects of BS and PMS with two valence states of ferric ion (Fe) on the degradation of rhein in rhubarb residue were optimized for the selection of optimal oxidation system. The influences of reaction temperature, reaction time and initial pH on the removal of rhein under the optimal oxidation system were evaluated. The chemical profiles of rhubarb residue with and without oxidation process were compared by UPLC-QTOF-MS/MS, and the degradation effects were investigated by PLS-DA and S plot/OPLS-DA analysis. The results manifested that PMS showed relative higher efficiency than BS on the degradation of rhein. Moreover, Fe(III) promoted the degradation effect of PMS, demonstrated that Fe(III)/PMS is the optimal oxidation system to degrade rhein in rhubarb residue. Further studies indicated that the degradation of rhein by the Fe(III)/PMS oxidation system was accelerated with the prolong of reaction time and the elevation of reaction temperature, and also affected by the initial pH. More importantly, Fe(III)/PMS oxidation system could degrade rhein in rhubarb residue completely under the optimal conditions. In conclusion, Fe(III)/PMS oxidation system is a feasible method to treat rhein in rhubarb residue.
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Antraquinonas , Oxidación-Reducción , Peróxidos , Rheum , Antraquinonas/química , Rheum/química , Peróxidos/química , Espectrometría de Masas en Tándem , Sulfitos/química , Concentración de Iones de Hidrógeno , Compuestos Férricos/química , TemperaturaRESUMEN
Magnetic particle imaging (MPI) has demonstrated versatile applications in biomedicine, including tumor imaging, cell tracking, and image-guided hyperthermia. Despite these advancements, the prevalent use of clinically approved tracers has posed limitations on MPI's resolution and sensitivity. In this study, we engineered a bimagnetic core/shell nanocrystals (BMCS) tailored for MPI by optimizing the heterostructure and modulating the exchange coupling effect between the two magnetic components. The resulting BMCS exhibited remarkably heightened susceptibility and magnetization while maintaining low coercivity, thereby substantially improved both MPI resolution and sensitivity compared to conventional tracers such as VivoTrax. At an equivalent mass concentration, BMCS demonstrated a notable 5.08-fold increase in signal intensity and achieved an unprecedentedly high resolution down to 1 mm. The excellent MPI performance contributes to high resolution MPI and the sensitive detection of orthotopic colorectal cancer in mice. The design strategy employed in BMCS, centered on the exchange coupling effect, introduces an efficacious approach for the development of high performance MPI tracers.
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Evidence regarding associations of general and abdominal obesity with the risk of conventional adenomas (ADs) and serrated polyps (SPs) from Asian population is scarce. Our study aimed to investigate the independent and joint associations of general obesity assessed by body mass index (BMI) and abdominal obesity assessed by waist circumference (WC) or waist-to-hip ratio (WHR) with the risk of ADs and SPs among 25 222 participants recruited by a population-based screening program. Compared to participants with normal BMI, those with a BMI ≥28 kg/m2 had increased risk of ADs (odds ratio [OR] 1.52, 95% confidence interval [CI]: 1.36-1.70) and SPs (OR 1.69, 95% CI: 1.38-2.07). For participants with a WC ≥102 cm (≥88 cm for females), the risk of ADs (OR 1.37, 95% CI: 1.25-1.51) and SPs (OR 1.81, 95% CI: 1.52-2.16) was higher than that of the reference group. For participants with a WHR ≥0.95 (≥0.90 for females), the risk of ADs (OR 1.26, 95% CI: 1.16-1.36) and SPs (OR 1.46, 95% CI: 1.26-1.69) was higher than that of the reference group. Moreover, participants with both BMI ≥28 kg/m2 and WC ≥102 cm (≥88 cm for females) had 61% and 119% higher risk of ADs (OR 1.61, 95% CI: 1.39-1.85) and SPs (OR 2.19, 95% CI: 1.70-2.82) compared to those with both normal BMI and WC. These findings indicate that both general and abdominal obesity are associated with SPs and ADs, presenting stronger association with SPs than ADs. Moreover, the association is more evident when both obesities exist.
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Adenoma , Obesidad Abdominal , Femenino , Humanos , Obesidad Abdominal/complicaciones , Obesidad Abdominal/epidemiología , Obesidad/complicaciones , Obesidad/epidemiología , Relación Cintura-Cadera , Circunferencia de la Cintura , Índice de Masa Corporal , Asia Oriental , Adenoma/epidemiología , Adenoma/etiología , Factores de RiesgoRESUMEN
RNA-binding proteins (RBP) have emerged as essential regulators that control gene expression and modulate multiple cancer traits. T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic malignancy derived from transformation of T-cell progenitors that normally undergo discrete steps of differentiation in the thymus. The implications of essential RBP during T-cell neoplastic transformation remain largely unclear. Systematic evaluation of RBP identifies RNA helicase DHX15, which facilitates the disassembly of the spliceosome and release of lariat introns, as a T-ALL dependency factor. Functional analysis using multiple murine T-ALL models demonstrates the essential importance of DHX15 in tumor cell survival and leukemogenesis. Moreover, single-cell transcriptomics reveals that DHX15 depletion in T-cell progenitors hinders burst proliferation during the transition from doublenegative to double-positive cells (CD4-CD8- to CD4+CD8+). Mechanistically, abrogation of DHX15 perturbs RNA splicing and leads to diminished levels of SLC7A6 and SLC38A5 transcripts due to intron retention, thereby suppressing glutamine import and mTORC1 activity. We further propose a DHX15 signature modulator drug ciclopirox and demonstrate that it has prominent anti-T-ALL efficacy. Collectively, our data highlight the functional contribution of DHX15 to leukemogenesis through regulation of established oncogenic pathways. These findings also suggest a promising therapeutic approach, i.e., splicing perturbation by targeting spliceosome disassembly, may achieve considerable anti-tumor efficacy.
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Leucemia , ARN Helicasas , Humanos , Animales , Ratones , ARN Helicasas/genética , ARN Helicasas/metabolismo , Empalme del ARN , Empalmosomas/genética , Leucemia/metabolismo , Sistemas de Transporte de Aminoácidos Básicos/genética , Sistemas de Transporte de Aminoácidos Básicos/metabolismoRESUMEN
Evidence on the link between healthy lifestyle and colorectal cancer (CRC) precursors is limited. Our study aimed to examine and compare the associations of healthy lifestyle with CRC precursors in adenoma (AD)-carcinoma and serrated pathways. A total of 24 480 participants including 6309 ADs, 1343 serrated polyps (SPs), and 16 828 polyp-free controls were included. A healthy lifestyle score (HLS) was constructed based on five lifestyle factors including cigarette smoking, alcohol drinking, physical activity, diet and body weight, and categorized into least, slightly, moderately and most healthy. Multivariable logistic regressions were used to estimate odds ratio (OR) and 95% confidence interval (CI). Inverse dose-response associations between the HLS and risk of ADs were observed (OR per 1 score increment for ADs: 0.82 [95% CI 0.79-0.84]; for SPs: 0.73 [95% CI 0.69-0.78]), and the association with SPs was more evident than with ADs (OR 0.90, 95% CI 0.85-0.96). Compared to participants with the least healthy lifestyle, those with the most healthy lifestyle had 47% lower risk of ADs (OR 0.53, 95% CI 0.47-0.59) and 70% lower risk of SPs (OR 0.30, 95% CI 0.23-0.39), respectively. These inverse associations were consistent across lesion stage and anatomic subsite and not modified by any stratification factors. The risk advancement periods for the most vs the least healthy lifestyle were -9.49 years for ADs and -20.69 years for SPs. Our findings help confirm the preventive role of healthy lifestyle in colorectal carcinogenesis.
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Adenoma , Pólipos del Colon , Neoplasias Colorrectales , Adenoma/epidemiología , Adenoma/patología , Pólipos del Colon/diagnóstico , Pólipos del Colon/epidemiología , Colonoscopía , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/epidemiología , Neoplasias Colorrectales/prevención & control , Estilo de Vida Saludable , Humanos , Factores de RiesgoRESUMEN
Patients with conventional adenoma removal are recommended to undergo colonoscopy surveillance to prevent colorectal cancer (CRC). However, evidence supporting the guidelines of colonoscopy surveillance is limited, especially among the Chinese population. We investigated the association between colonoscopy adenoma findings and CRC risk among individuals aged 40 to 74 years who underwent baseline colonoscopy from 2007 to 2016 in Jiashan and Haining, Zhejiang, China; 34 382 participants were categorized into advanced adenoma, nonadvanced adenoma and no adenoma based on adenoma findings. A multivariable Cox regression model was used to estimate the hazard ratio (HR) of CRC incidence with adjustment for potential confounding factors. After a median follow-up time of 7.7 years, 113 incident cases of CRC were identified (18 occurred in 1632 participants with advanced adenoma, 16 in 3973 participants with nonadvanced adenoma and 79 in 28 777 participants with no adenoma). Compared to no adenoma group, the adjusted HR for CRC in advanced adenoma group was 4.01 (95% CI, 2.37-6.77). For nonadvanced adenomas, individuals with ≥3 adenomas showed an increased risk of CRC (HR, 3.65; 95% CI, 1.43-9.31), but no significantly increased risk of CRC was found for 1 to 2 nonadvanced adenomas, compared to those with no adenoma. Our study suggested that the risk of subsequent CRC increased in individuals with high-risk adenoma (at least one advanced adenoma or ≥3 nonadvanced adenomas), but not in those with 1 to 2 nonadvanced adenomas. These results provide the first evidence from the Chinese population for the current surveillance guidelines.
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Adenoma/cirugía , Colonoscopía , Neoplasias Colorrectales/etiología , Detección Precoz del Cáncer , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Factores de RiesgoRESUMEN
Multiplexed simultaneous detection of various cancer markers is required for accurate diagnosis and treatment of early cancer. In this work, we present a force-coded strategy for the simultaneous detection of tumor-related proteins with tunable dynamic range via magnetic sensing. The multiplexing capability of this method is achieved by designing DNA devices that can recognize different biomarkers and code them with different binding forces measured by the force-induced remnant magnetization spectroscopy, which is not influenced by the color of the light and the solution. Moreover, the force-coded assay with high sensitivity and adjustable detection range is robust, which could be used for practical biological applications such as magnetic sensing, handheld miniaturized systems, and potential in vivo diagnosis.
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Técnicas Biosensibles , Neoplasias , Biomarcadores , Técnicas Biosensibles/métodos , ADN/química , Humanos , Neoplasias/diagnóstico , ProteínasRESUMEN
Epigenetics play an essential role in colorectal neoplasia process. There is a need to determine the appropriateness of epigenetic biomarkers for early detection as well as expand our understanding of the carcinogenic process. Therefore, the aim of the study was to assess how DNA methylation pattern of GALR1 gene evolves in a sample set representing colorectal neoplastic progression. The study was designed into three phases. Firstly, Methylation status of GALR1 was assessed with genome-wide DNA methylation beadchip and pyrosequencing assays in colorectal lesions and paired normal tissues. Then, linear mixed-effects modeling analyses were applied to describe the trend of DNA methylation during the progression of colorectal neoplasia. In the third phase, quantitative RT-PCR was used to examine GALR1 expression in patients with precursor lesion and colorectal cancer. We found that significant hypermethylation of GALR1 promoter was a widely existent modification in CRCs (P < 0.001). When further examined methylation pattern of GALR1 during neoplastic progression of CRC, we found that DNA methylation level of GALR1 showed a significant stepwise increase from normal to hyperplastic polyps, to adenomas and to carcinoma samples (P < 0.001). Besides, loss of mRNA expression is a common accompaniment to adenomas and carcinomas. Public omics data analyses showed an inverse correlation between gene expression and DNA methylation (P < 0.001). Our findings indicate that epigenetic alteration of GALR1 promoter is gradually accumulated during the colorectal neoplastic progression. It can potentially be a promising biomarker used for screening and surveillance of colorectal cancer.
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Adenoma , Neoplasias Colorrectales , Receptor de Galanina Tipo 1/genética , Adenoma/diagnóstico , Adenoma/genética , Adenoma/patología , Biomarcadores de Tumor/genética , Carcinogénesis/genética , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Metilación de ADN , Epigénesis Genética , Regulación Neoplásica de la Expresión Génica , Humanos , Regiones Promotoras GenéticasRESUMEN
PURPOSE: To address the issue of local drug delivery in tumor treatment, a novel nanoparticle-hydrogel superstructure, namely semi-interpenetrating polymer networks (semi-IPNs) hydrogel composed of poly (ethylene glycol) diacrylate (PEGDA) and hyaluronic acid (HA) and incorporated with paclitaxel (PTX) loaded PLGA nanoparticles (PEGDA-HA/PLGA-PTX), was prepared by in situ UV photopolymerization for the use of local drug delivery. METHODS: Using the gelation time, swelling rate and degradation rate as indicators, the optimal proportion of Irgacure 2959 initiator and the concentration of HA was screened and obtained for preparing hydrogels. Next, paclitaxel (PTX) loaded PLGA nanoparticles (PLGA-PTX NPs) were prepared by the emulsion solvent evaporation method. RESULTS: The mass ratio of the initiator was 1%, and the best concentration of HA was 5 mg/mL in PEGDA-HA hydrogel. In vitro experiments showed that PLGA-PTX NPs had similar cytotoxicity to free PTX, and the cell uptake ratio on NCI-H460 cells was up to 96% by laser confocal microscopy and flow cytometry. The drug release of the PEGDA-HA/PLGA-PTX hydrogel local drug delivery system could last for 13 days. In vivo experiments proved that PEGDAHA/PLGA-PTX hydrogel could effectively inhibit the tumor growth without causing toxic effects in mice. CONCLUSIONS: This study demonstrated that the PEGDA-HA/PLGA-PTX hydrogel is a promising local drug delivery system in future clinical applications for tumor therapy. A photopolymerized semi-interpenetrating polymer networks-based hydrogel incorporated with paclitaxel-loaded nanoparticles was fabricated by in situ UV photopolymerization, providing a promised nanoplatform for local chemotherapy of tumors.
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Antineoplásicos Fitogénicos/administración & dosificación , Portadores de Fármacos/química , Hidrogeles/química , Neoplasias/tratamiento farmacológico , Paclitaxel/administración & dosificación , Animales , Antineoplásicos Fitogénicos/farmacocinética , Línea Celular Tumoral , Preparaciones de Acción Retardada/administración & dosificación , Preparaciones de Acción Retardada/farmacocinética , Composición de Medicamentos/métodos , Liberación de Fármacos , Humanos , Ácido Hialurónico/química , Ratones , Nanopartículas/química , Neoplasias/patología , Polietilenglicoles/química , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Pendant selenium-containing maleimide polymers with different selenium contents are synthesized via a radical copolymerization of styrene and N-butylmaleimide phenyl selenide. The polymer structures are characterized by nuclear magnetic resonance, gel permeation chromatography, Fourier transform infrared spectroscopy, ultraviolet-visible spectroscopy, and scanning electron microscopy with an energy-dispersive spectrometer, which results in the desired structures and selenium contents. The refractive indices of the polymers, which change as a function of different contents of selenium and oxidative stimuli by H2 O2 or O3 , are investigated. Finally, a photonic crystal (PC) is prepared based on the selenium-containing polymer. The visible color changes of the PC are investigated as a function of different concentrations and contact times of O3 .
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Ozono , Selenio , Maleimidas , Polimerizacion , Polímeros , Espectroscopía Infrarroja por Transformada de FourierRESUMEN
Selenium-containing monomer (p-phenylseleno) styrene (p-PhSeSt) is polymerized by reversible addition-fragmentation chain transfer polymerization. Polymer, (P(p-PhSeSt)), with controlled molecular weight and narrow molecular weight is obtained. The selenide moiety in obtained P(p-PhSeSt) can be selectively oxidized to selenoxide or selenone groups by H2 O2 or NaClO, respectively. These oxidized groups can be further reduced to selenide by Na2 S2 O4 . The structure changing of polymers during such redox cycle is characterized by nuclear magnetic resonance, X-ray photoelectron spectroscopy, and size exclusion chromatography. Properties, such as thermal performance, glass transition temperature, water contact angles, and refractive indices, of the resulting polymers are systematically investigated before and after oxidation. In addition, SiO2 inverse opal photonic crystal (IOPC) is fabricated by sacrificial polymer colloidal template method. Owing to changes of the RIs of P(p-PhSeSt) after selective oxidation, the predictable change of PC bandgap as a redox-responsive PC sensor is successfully realized, which provides new perspectives for modulating photonic crystals.
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Dióxido de Silicio , Sustancias Macromoleculares , Oxidación-Reducción , Polimerizacion , Óxidos de SelenioRESUMEN
This study was designed to provide novel insights into milk fat globule membrane (MFGM) proteins in donkey colostrum (DC) and bovine colostrum (BC) using quantitative proteomics. In total, 179 (DC) and 195 (BC) MFGM proteins were characterized, including 71 shared, 108 DC-specific, and 124 BC-specific proteins. Fifty-one shared proteins were selected as differentially expressed MFGM proteins, including 21 upregulated and 30 downregulated proteins in DC. Gene ontology analysis showed that these proteins were mainly enriched in cellular components, including the extracellular exosome, extracellular space, and plasma membrane. Additionally, they were further involved in metabolic pathways, including cholesterol metabolism, the peroxisome proliferator-activated receptor signaling pathway, and purine metabolism. Furthermore, several key protein factors with high connectivity were identified via protein-protein interaction analysis. These results provide more comprehensive knowledge of differences in the biological properties of MFGM proteins in DC and BC as well as pave the way for future studies of the nutritional and functional requirements of these important ingredients toward the development of dairy products based on multiple milk sources.
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Proteómica , Espectrometría de Masas en Tándem , Animales , Bovinos , Cromatografía Líquida de Alta Presión/veterinaria , Calostro , Equidae , Femenino , Glucolípidos , Glicoproteínas , Gotas Lipídicas , Proteínas de la Membrana , Proteínas de la Leche , Embarazo , Espectrometría de Masas en Tándem/veterinariaRESUMEN
Nonconvulsive electrotherapy (NET) defined as electrical brain stimulation administered like standard electroconvulsive therapy (ECT), but below seizure threshold, could be effective for patients with treatment-refractory depression (TRD) with fewer adverse neurocognitive outcomes. However, there is a lack of studies in Chinese patients with TRD. Thus, this study was conducted to examine the efficacy and safety of adjunctive NET for Chinese patients with TRD. Twenty TRD patients were enrolled and underwent six NET treatments. Depressive symptoms, response, and remission were assessed with the 17-item Hamilton Depression Rating Scale (HAMD-17) at baseline and after 1, 3, and 6 NET treatments. Neurocognitive function was assessed by the Wisconsin Card Sorting Test (WCST) at baseline and after the completion of six NET treatments. Mean HAMD-17 scores declined significantly from 26.2 to 10.4 (p < 0.001) after post-NET. The rates of response and remission were 60.0% (95% CI: 36.5-83.5) and 10.0% (95% CI: 0-24.4), respectively. Neurocognitive performance improved following a course of NET. No significant association was found between changes in depressive symptoms and baseline neurocognitive function. Adjunctive NET appeared to be effective for patients with TRD, without adverse neurocognitive effects. Randomized controlled studies were warranted to confirm these findings.
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Trastorno Depresivo Resistente al Tratamiento/terapia , Terapia por Estimulación Eléctrica , Adulto , Femenino , Humanos , MasculinoRESUMEN
Increasing single nucleotide polymorphisms (SNPs) have been identified to be associated with colorectal cancer (CRC). We aimed to investigate whether genetic risk scores (GRS) that aggregate information from multiple genetic variants can predict the risk of CRC in a Chinese population. Fifty candidate SNPs were selected to explore the associations with CRC in a discovery sample with 1002 CRC cases and 999 healthy controls. We modeled the significant SNPs identified by the case-control study as a multilocus weighted GRS and estimated the association of GRS with CRC. Furthermore, 300 pairs of cases and controls were included as a validation sample to confirm the finding. Area under the receiver operating characteristic curve (AUROC) was used to evaluate the predictive power of GRS in CRC. A total of seven SNPs were found to increase the risk of CRC, and two SNPs were found to be negatively associated with CRC in the discovery sample. Relative to participants with the lowest quartile of GRS, those with the highest quartile had a 2.64-fold (95% CI: 1.99-3.51) higher risk for CRC. For every 0.1 point of GRS increase, the risk of CRC increase by 11% (95% CI: 8-14%). AUROC for GRS alone were 0.59 (95% CI: 0.57-0.62) and 0.52 (95% CI: 0.46-0.58) in the discovery and validation sample, respectively. AUROC increased to 0.62 (95% CI: 0.59-0.64) and 0.71 (95% CI: 0.65-0.76) by combining environmental risk factors. Our findings support an association between GRS and risk of CRC, which provides evidence of improved prediction model for CRC in China.
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Neoplasias Colorrectales/genética , Predisposición Genética a la Enfermedad , Adulto , China/epidemiología , Neoplasias Colorrectales/patología , Femenino , Estudio de Asociación del Genoma Completo , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple/genética , Curva ROC , Medición de Riesgo , Factores de RiesgoRESUMEN
Donkey milk is an ideal substitute for human milk owing to its similar composition. Nevertheless, changes in the composition and related metabolic pathways of free fatty acids (FFA) in donkey milk between colostrum and mature milk have not been studied well. In this study, metabolomic methods based on gas chromatography tandem time-of-flight mass spectrometry (GC-TOF-MS) were used to explore and compare FFA in donkey colostrum (DC) and mature milk (DMM). A total of 24 FFA were characterized and quantified in DC and in DMM. Of these, 11 FFA differed significantly between DC and DMM, and there were 6 key differential metabolic pathways. These results demonstrated that the composition of FFA in donkey milk changed with lactation stage. The interactions and metabolic pathways were further analyzed to explore the mechanisms that altered the milk composition during lactation. Our results provide insights into the changes in milk of the nonruminant mammals during lactation. The results provide practical information for the development of donkey milk products and a foundation for future research on specific milk nutrients.
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Calostro/química , Equidae/fisiología , Ácidos Grasos no Esterificados/análisis , Metabolómica , Animales , Femenino , Cromatografía de Gases y Espectrometría de Masas , Lactancia/metabolismoRESUMEN
Donkey milk has been widely shown to be an ideal substitute for human milk because of its similar composition. However, alterations to the composition of donkey milk during lactation have not been well studied. In this study, untargeted metabolomics with ultra-high-performance liquid tandem chromatography quadrupole time-of-flight mass spectrometry were used to analyze and compare the metabolites in donkey colostrum (DC) and mature milk (DMM). Two hundred seventy metabolites were characterized in both DC and DMM. Fifty-two of the metabolites in the DC were significantly different from those in the DMM; 8 were downregulated and 44 were upregulated. This demonstrated that the composition of the donkey milk changed with lactation. Additionally, the interactions and metabolic pathways were further analyzed to explore the mechanisms that altered the milk during lactation. Our results provide comprehensive insights into the alterations in donkey milk during lactation. The results will aid in future investigations into the nutrition of donkey milk and provide practical information for the dairy industry.
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Cromatografía Liquida/veterinaria , Calostro/química , Equidae/fisiología , Espectrometría de Masas/veterinaria , Metabolómica/métodos , Animales , Cromatografía Liquida/métodos , Femenino , Lactancia , Espectrometría de Masas/métodos , EmbarazoRESUMEN
Exchange coupled bimagnetic core/shell nanoparticles are promising for emerging multiferroic and spintronic technologies compared with traditional, single-phase materials, as they deliver numerous appealing effects, such as large exchange bias, tailored coercivities, and tunable blocking temperatures. However, it remains a challenge to manipulate their magnetic properties via exchange coupling due to the lack of a straightforward method that enables the general preparation of desired composites. Here we report a robust and general one-pot approach for the synthesis of different kinds of bimagnetic core/shell nanostructures (BMCS NSs). The formation of highly crystalline and monodisperse BMCS NSs adopted a self-adaptive sequential growth, circumventing the employment of complex temperature control and elaborate seeded growth techniques. As a result of large lattice misfit, the presence of interfacial imperfections as an extra source of anisotropy induced diverse exchange coupling interactions in ferro-ferrimagnetic and ferro-antiferromagnetic systems, which had great effects on the improvement of the magnetic properties of BMCS NSs. We envision that this new strategy will open up exciting opportunities toward large-scalable production of such high-quality BMCS NSs, thereby greatly potentiating the prospective applications of nanomagnetic materials.
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Micro-/nanomotors are widely used in micro-/nanoprocessing, cargo transportation, and other microscale tasks because of their ability to move independently. Many biological hybrid motors based on bacteria have been developed. Magnetotactic bacteria (MTB) have been employed as motors in biological systems because of their good biocompatibility and magnetotactic motion in magnetic fields. However, the magnetotaxis of MTB is difficult to control due to the lack of effective methods. Herein, a strategy that enables control over the motion of MTB is presented. By depositing synthetic Fe3 O4 magnetic nanoparticles on the surface of MTB, semiartificial magnetotactic bacteria (SAMTB) are produced. The overall magnetic properties of SAMTB, including saturation magnetization, residual magnetization, and blocking temperature, are regulated in a multivariate and multilevel fashion, thus regulating the magnetic sensitivity of SAMTB. This strategy provides a feasible method to manoeuvre MTB for applications in complex fluid environments, such as magnetic drug release systems and real-time tracking systems. Furthermore, this concept and methodology provide a paradigm for controlling the mobility of micro-/nanomotors based on natural small organisms.