ABSTRACT
A humidity sensor based on an optical fiber Mach-Zehnder interferometer (MZI) coated with a GO/MoS2@PVA composite membrane was investigated for non-contact sensing. MoS2 was used as a nanospacer to enhance the humidity-sensitive properties of GO, and the adhesion and stability of the composite membrane on the fiber surface could be increased by PVA. The proposed sensor shows a maximum sensitivity of 0.26â dB/%RH with average response and recovery times of 1.62 and 1.11â s, respectively. In non-contact sensing applications, the sensor can effectively recognize a maximum distance of 10â mm for the proximity of a human finger with a distance variation interval of 3â mm. The proposed sensor is expected to be applied in non-contact distance detection and localization or as a non-contact human-computer interaction panel.
ABSTRACT
There is an urgent need for lithium-ion batteries with high energy density to meet the increasing demand for advanced devices and ecofriendly electric vehicles. Spinel LiNi0.5Mn1.5O4 (LNMO) is the most promising cathode material for achieving high energy density due to its high operating voltage (4.75 V vs Li/Li+) and impressive capacity of 147 mAh g-1. However, the binders conventionally used are prone to high potential and oxidation at the cathode side, resulting in a loss of the ability to bond active material and conductive agent integrity. This can lead to severe capacity fading and irreversible battery failure. This study demonstrates that incorporating acrylic anhydride and methyl methacrylate into conventional acrylonitrile through solution polymerization improves the binding energy and voltage resistance. The results indicate that the triblock poly(acrylonitrile-methyl methacrylate-acrylic anhydride) (PAMA) binder has a much higher peeling strength (0.506 N cm-1) compared to its polyvinylidene fluoride (PVDF) counterpart (0.3 N cm-1), making it a more feasible strategy. When assembled with LiNi0.5Mn1.5O4, the PAMA based electrode maintains a capacity retention of 70.7% after 800 cycles at 0.1 C, which is significantly higher than the 33.9% retention of the PVDFbased electrode. This is due to the large number of polar groups, including âC≡N and âCâO, on PAMA, which are conducive to adsorbing lithium polysulfide. The S@PAMA electrode is tested and maintained a capacity value of 628.7 mAh g-1 after long-term cycling, confirming its ability to effectively suppress the shuttle effect.
ABSTRACT
Radon decay products attach to particulate matter (referred to as particle radioactivity, PR) has been shown to be potential to promote airway damage after inhalation. In this study, we investigated associations between PR with respiratory symptoms and health-related quality of life (HRQL) in patients with COPD. 141 male patients with COPD, former smokers, completed the St. George's Respiratory Questionnaire (SGRQ) after up to four 1-week seasonal assessments (N=474) of indoor (home) and ambient (central site) particulate matter ≤ 2.5⯵m in diameter (PM2.5) and black carbon (BC). Indoor PR was measured as α-activity (radiation) on PM2.5 filter samples. The ratio of indoor/ambient sulfur in PM2.5 (a ventilation surrogate) was used to estimate α-PR from indoor radon decay. SGRQ responses assessed frequent cough, phlegm, shortness of breath, wheeze, and chest attacks in the past 3 months. Multivariable linear regression with generalized estimating equations accounting for repeated measures was used to explore associations, adjusting for potential confounders. Median (IQR) indoor α-PR was 1.22 (0.62) mBq/m3. We found that there were positive associations between α-PR with cough and phlegm. The strongest associations were with estimated α-PR of indoor origin for cough (31.1â¯% increase/IQR, 95â¯%CI: 8.8â¯%, 57.8â¯%), and was suggestive for phlegm (13.0â¯% increase/IQR, 95â¯%CI: -2.5â¯%, 31.0â¯%), similar adjusting for indoor BC or PM2.5. α-PR of indoor origin was positively associated with an increase in SGRQ Symptoms score [1.2 units/IQR; 95â¯%CI: -0.3, 2.6] that did not meet conventional levels of statistical significance. Our results suggested that exposure to indoor radon decay products measured as particle radioactivity, a common indoor exposure, is associated with cough, and suggestively associated with phlegm and worse HRQL symptoms score in patients with COPD.
Subject(s)
Air Pollution, Indoor , Cough , Pulmonary Disease, Chronic Obstructive , Radon , Humans , Male , Aged , Radon/analysis , Air Pollution, Indoor/analysis , Air Pollution, Indoor/adverse effects , Middle Aged , Particulate Matter/analysis , Quality of Life , Air Pollutants, Radioactive/analysis , Surveys and QuestionnairesABSTRACT
Research on the association between dietary adherence and cancer risk is limited, particularly concerning overall cancer risk and its underlying mechanisms. Using the UK Biobank data, we prospectively investigate the associations between adherence to a Mediterranean diet (MedDiet) or a Mediterranean-Dietary Approaches to Stop Hypertension Diet Intervention for Neurodegenerative Delay diet (MINDDiet) and the risk of overall and 22 specific cancers, as well as the mediating effects of metabolites. Here we show significant negative associations of MedDiet and MINDDiet adherence with overall cancer risk. These associations remain robust across 14 and 13 specific cancers, respectively. Then, a sequential analysis, incorporating Cox regression, elastic net and gradient boost models, identify 10 metabolites associated with overall cancer risk. Mediation results indicate that these metabolites play a crucial role in the association between adherence to a MedDiet or a MINDDiet and cancer risk, independently and cumulatively. These findings deepen our understanding of the intricate connections between diet, metabolites, and cancer development.
Subject(s)
Diet, Mediterranean , Dietary Approaches To Stop Hypertension , Neoplasms , Humans , Neoplasms/prevention & control , Neoplasms/epidemiology , Male , Female , Middle Aged , Risk Factors , Aged , Prospective Studies , United Kingdom/epidemiology , Proportional Hazards Models , AdultABSTRACT
Developing high-performance composites with fast charging and superior cycle life is paramount for lithium-ion batteries (LIBs). Herein, we synthesized a double-shell carbon-coated porous structure composite with a compact surface (P-Si@rGO@C) using low-cost commercial micron-sized silicon (Si) instead of nanoscale silicon. Results reveal that the unique P-Si@rGO@C features high adaptability to volume expansion, accelerates electron/ion transmission rate, and forms a stable solid electrolyte interphase (SEI) film. This phenomenon arises from the synergistic effect of abundant internal voids and an external double-layer carbon shell with a dense surface. Specifically, the P-Si@rGO@C anode exhibits a high initial coulombic efficiency (ICE) (88.0 %), impressive rate-capability (612.1 mAh/g at 2C), and exceptional long-term cyclability (972.2 mAh/g over 500 cycles at 0.5C). Further kinetic studies elucidate the diffusion-capacitance hybrid energy storage mechanism and reveal an improved Li+ diffusion coefficient (from 3.47 × 10-11 to 2.85 × 10-9 cm2 s-1). Ex-situ characterization confirms the crystal phase change of micron-sized Si and the formation of a stable LiF-rich SEI. Theoretical calculations support these findings by demonstrating an enhancement in the adsorption ability of Si to Li+ (from -0.89 to -0.97 eV) and a reduction in the energy migration barrier (from 0.35 to 0.18 eV). Additionally, practical LixSi powder is shown to increase the ICE of full cells from 67.4 % to 87.9 %. Furthermore, a pouch cell utilizing the prelithiated P-Si@rGO@C anode paired with LiNi1/3Co1/3Mn1/3O2 (NCM111) cathode delivers a high initial reversible capacity of 7.2 mAh and 76.8 % capacity retention after 100 cycles. This work provides insights into the application of commercial silicon-aluminum alloy powder in the anode of high-energy LIBs.
ABSTRACT
Oxidative desulfurization (ODS) emerges as a critical player in enhancing efficient fuel desulfurization and promoting sustainable clean energy. Metal-organic frameworks (MOFs) show great potential as ODS catalysts because of their exceptional porosity and versatility. This study explores the use of amorphous metal-organic frameworks (aMOFs), which combine MOFs' structural advantages with unique properties of amorphous materials, to enhance catalytic efficiency in ODS. Traditional methods for synthesizing MOFs rely on solvent-thermal or solvent-free methods, each with limitations in environmental impact or scalability. To address this, we introduce a novel strategy utilizing a small quantity of benzoic acid (BA) modifier to facilitate the solvent-free, one-pot, mechanical synthesis of amorphous zirconium terephthalate (GU-2BA-3h). The resulting GU-2BA-3h demonstrates exceptional ODS performance, efficiently removing 1000 ppm of dibenzothiophene (DBT) in just 6 min at 60 °C. Amorphous GU-2BA-3h features an expanded external surface area, increased acidic sites, and exceptional stability, resulting in a high turnover frequency (19.6 h-1) and outstanding catalytic activity (53.2 mmol g-1 h-1), establishing it as a highly efficient ODS catalyst. This remarkable performance arises from the formation of dangling carboxyl groups and active metal sites due to the competitive coordination of benzoic acid with the linker. Experimental evidence confirms that these carboxyl groups and exposed Zr-OH sites interact with oxidants, generating hydroxyl radicals that effectively eliminate sulfur-containing compounds. Furthermore, the methodology exhibits universality in constructing amorphous Zr-based MOFs, and provides an eco-friendly, cost-effective route for efficient ODS catalyst production.
ABSTRACT
Background: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the degeneration of motor neurons in the brain and spinal cord with a poor prognosis. Previous studies have observed cognitive decline and changes in brain morphometry in ALS patients. However, it remains unclear whether the brain structural alterations contribute to the risk of ALS. In this study, we conducted a bidirectional two-sample Mendelian randomization (MR) and colocalization analysis to investigate this causal relationship. Methods: Summary data of genome-wide association study were obtained for ALS and the brain structures, including surface area (SA), thickness and volume of subcortical structures. Inverse-variance weighted (IVW) method was used as the main estimate approach. Sensitivity analysis was conducted detect heterogeneity and pleiotropy. Colocalization analysis was performed to calculate the posterior probability of causal variation and identify the common genes. Results: In the forward MR analysis, we found positive associations between the SA in four cortical regions (lingual, parahippocampal, pericalcarine, and middle temporal) and the risk of ALS. Additionally, decreased thickness in nine cortical regions (caudal anterior cingulate, frontal pole, fusiform, inferior temporal, lateral occipital, lateral orbitofrontal, pars orbitalis, pars triangularis, and pericalcarine) was significantly associated with a higher risk of ALS. In the reverse MR analysis, genetically predicted ALS was associated with reduced thickness in the bankssts and increased thickness in the caudal middle frontal, inferior parietal, medial orbitofrontal, and superior temporal regions. Colocalization analysis revealed the presence of shared causal variants between the two traits. Conclusion: Our results suggest that altered brain morphometry in individuals with high ALS risk may be genetically mediated. The causal associations of widespread multifocal extra-motor atrophy in frontal and temporal lobes with ALS risk support the notion of a continuum between ALS and frontotemporal dementia. These findings enhance our understanding of the cortical structural patterns in ALS and shed light on potentially viable therapeutic targets.
ABSTRACT
Thermal protective textiles are crucial for safeguarding individuals, particularly firefighters and steelworkers, against extreme heat, and for preventing burn injuries. However, traditional firefighting gear suffers from statically fixed thermal insulation properties, potentially resulting in overheating and discomfort in moderate conditions, and insufficient protection in extreme fire events. Herein, an innovative soft robotic textile is developed for dynamically adaptive thermal management, providing superior personal protection and thermal comfort across a spectrum of environmental temperatures. This unique textile features a thermoplastic polyurethane (TPU)-sealed actuation system, embedded with a low boiling point fluid for reversible phase transition, resembling an endoskeleton that triggers an expansion within the textile matrix for enhanced air gap and thermal insulation. The thermal resistance improves automatically from 0.23 to 0.48 Km2 W-1 by self-actuating under intense heat, exceeding conventional textiles by maintaining over 10 °C cooler temperatures. Additionally, the knitted substrate incorporated into the soft actuators can substantially mitigate convective heat transfer, as evidenced by the thermal resistance tests and the temperature mapping derived from numerical simulations. Moreover, it boasts significantly increased moisture permeability. The thermoadaptation and breathability of this durable all-fabric system signify considerable progress in the development of protective clothing with high comfort for dynamic and extreme temperature conditions.
ABSTRACT
A growing number of studies have implicated that gut microbiota abundance is associated with myasthenia gravis (MG). However, the causal relationship underlying the associations is still unclear. Here, we aim to investigate the causal effect of gut microbiota on MG using Mendelian randomization (MR) method. Publicly available Genome-wide association study (GWAS) summary-level data for gut microbiota and for MG were extracted. Inverse variance weighted was used as the main method to analyze causality. The robustness of the results was validated with sensitivity analyses. Our results indicated that genetically predicted increased phylum Lentisphaerae (OR = 1.319, p = 0.026), class Lentisphaerae (OR = 1.306, p = 0.044), order Victivallales (OR = 1.306, p = 0.044), order Mollicutes (OR = 1.424, p = 0.041), and genus Faecalibacterium (OR = 1.763, p = 0.002) were potentially associated with a higher risk of MG; while phylum Actinobacteria (OR = 0.602, p = 0.0124), class Gammaproteobacteria (OR = 0.587, p = 0.036), family Defluviitaleaceae (OR = 0.695, p = 0.047), family Peptococcaceae (OR = 0.698, p = 0.029), and family Family XIII (OR = 0.614, p = 0.017) were related to a lower risk of MG. The present study provides genetic evidence for the causal associations between gut microbiota and MG, thus suggesting novel insights into the gut microbiota-neuromuscular junction axis in the pathogenesis of MG.
Subject(s)
Gastrointestinal Microbiome , Myasthenia Gravis , Humans , Gastrointestinal Microbiome/genetics , Genome-Wide Association Study , Mendelian Randomization Analysis , Myasthenia Gravis/genetics , Neuromuscular JunctionABSTRACT
CONTEXT: The human TSPY1 (testis-specific protein, Y-linked 1) gene is critical for spermatogenesis and male fertility. However, there have been difficulties with studying the mechanism underlying its function, partly due to the presence of the Tspy1 pseudogene in mice. AIMS: TSPYL5 (TSPY-like 5), an autosomal homologous gene of TSPY1 showing a similar expression pattern in both human and mouse testes, is also speculated to play a role in male spermatogenesis. It is beneficial to understand the role of TSPY1 in spermatogenesis by investigating Tspyl5 functions. METHODS: Tspyl5 -knockout mice were generated to investigate the effect of TSPYL5 knockout on spermatogenesis. KEY RESULTS: Tspyl5 deficiency caused a decline in fertility and decreased the numbers of spermatogonia and spermatozoa in aged male mice. Trancriptomic detection of spermatogonia derived from aged Tspyl5 -knockout mice revealed that the Pcna -mediated DNA replication pathway was downregulated. Furthermore, Tspyl5 was proven to facilitate spermatogonia proliferation and upregulate Pcna expression by promoting the ubiquitination-degradation of the TRP53 protein. CONCLUSIONS: Our findings suggest that Tspyl5 is a positive regulator for the maintenance of the spermatogonia pool by enhancing Pcna -mediated DNA replication. IMPLICATIONS: This observation provides an important clue for further investigation of the spermatogenesis-related function of TSPY1 .
Subject(s)
Spermatogenesis , Spermatogonia , Animals , Male , Mice , Cell Cycle Proteins/genetics , Cell Proliferation , DNA Replication , Mice, Knockout , Nuclear Proteins/genetics , Spermatogenesis/genetics , Spermatogonia/metabolismABSTRACT
BACKGROUND: BMPR1A-mediated signaling transduction plays an essential role in intestinal growth. Variations of BMPR1A lead to a rare autosomal dominant inherited juvenile polyposis syndrome (JPS) with high probability of developing into colorectal cancer (CRC). Nonsense and frameshift variations, generating premature termination codons (PTCs), are the most pathogenic variants in the BMPR1A gene. OBJECTIVE: This study aimed to investigate the molecular genetic etiology in a Chinese family with three generations of CRC. METHODS: Pathogenic variants of 18 known CRC susceptibility genes were examined in a Chinese CRC family through multigene panel testing using the next-generation sequencing platform. The candidate gene variant was validated in the family members by Sanger sequencing. Potential biological functions of the gene variant were further investigated in the RKO colon cancer cell line. RESULTS: A novel nonsense variant (c.1114A > T, p.Lys372*) of BMPR1A was identified in the CRC family. This variant generated a PTC at the kinase domain and caused nonsense-mediated mRNA decay. Read-through inducing reagents G418 and PTC124 partially restored BMPR1A expression and its following signaling pathway. CONCLUSION: The identification of the novel BMPR1A variant enriched the genotype-phenotype spectrum of BMPR1A. Meanwhile, our finding also provided support for future PTC-targeting therapy for BMPR1A-mediated JPS and CRC.
Subject(s)
Bone Morphogenetic Protein Receptors, Type I , Codon, Nonsense , Pedigree , Humans , Bone Morphogenetic Protein Receptors, Type I/genetics , Male , Female , Middle Aged , Adult , Genetic Predisposition to Disease , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , Asian People/genetics , Nonsense Mediated mRNA Decay , Cell Line, Tumor , East Asian PeopleABSTRACT
Loxoprofen sodium is a chiral drug with two chiral centers. In our previous work, we found that the elimination of its four isomers showed stereospecificity in rats, while how the stereospecific behavior occurred in vivo was unclear. To clarify this issue, each single isomer of loxoprofen sodium was prepared by a chiral semi-preparative high-performance liquid chromatography (HPLC) and then administered to rats. By analysis of each isomer in rat plasma utilizing an analytical chiral HPLC, it was discovered that the chiral inversion occurred only to its (2R)-isomers, one from (1'S,2R)- to (1'S,2S)-isomer and the other from (1'R,2R)- to (1'R,2S)-isomer. The reduction of α-substituted cyclopentanone occurred only to its (1'R)-isomers, with (1'R,2R)-isomer reduced to (2'S,1'R,2R)-trans-alcohol and (1'R,2S)- to (2'S,1'R,2S)-trans-alcohol. Interestingly, both the inversion and the reduction reaction occurred to its (1'R,2R)-isomer due to the special stereo-structure with both (2R)- and (1'R)-configuration, and conversely, neither of them occurred to its (1'S,2S)-isomer, which caused the significantly different elimination rate in vivo. These new findings were meaningful for evaluation of the safety and efficacy of chiral drugs.
Subject(s)
Phenylpropionates , Sodium , Rats , Animals , Chromatography, High Pressure Liquid , Stereoisomerism , BiotransformationABSTRACT
NR0B1 is frequently activated in hepatocellular carcinoma (HCC). However, the role of NR0B1 is controversial in HCC. In this study, we observed that NR0B1 was an independent poor prognostic factor, negatively correlated with the overall survival of HCC and the relapse-free survival of patients treated with sorafenib. Meanwhile, NR0B1 promoted the proliferation, migration, and invasion of HCC cells, inhibited sorafenib-induced apoptosis, and elevated the IC50 of sorafenib in HCC cells. NR0B1 was further displayed to increase sorafenib-induced autophagic vesicles and activate Beclin1/LC3-II-dependent autophagy pathway. Finally, NR0B1 was revealed to transcriptionally suppress GSK3ß that restrains AMPK/mTOR-driven autophagy and increases BAX-mediated apoptosis. Collectively, our study uncovered that the ectopic expression of NR0B1 augmented sorafenib-resistance in HCC cells by activating autophagy and inhibiting apoptosis. Our findings supported that NR0B1 was a detrimental factor for HCC prognosis.
Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/metabolism , Sorafenib/pharmacology , Liver Neoplasms/drug therapy , Liver Neoplasms/genetics , Liver Neoplasms/metabolism , Drug Resistance, Neoplasm , Neoplasm Recurrence, Local , Apoptosis , Autophagy , Cell Proliferation , Cell Line, Tumor , DAX-1 Orphan Nuclear ReceptorABSTRACT
BACKGROUND: Azoospermia factor C (AZFc) in the male-specific region of Y-chromosome (MSY) presents wide structure variation mainly due to frequent non-allele homologous recombination, leading to significant copy number variation of the AZFc-linked coding sequences involving in spermatogenesis. A large number of studies had been conducted to investigate the association between AZFc deletions and male infertility in certain Y chromosome genetic backgrounds, however, the influence of primary AZFc duplication on spermatogenesis remained controversial and the cause of the discrepant outcomes is unknown. METHODS: In the present study, a total of 1,102 unrelated Han Chinese males without any detectable AZF deletions were recruited from 2014 to 2019, including 411 controls with normozoospermia and 691 patients with idiopathic spermatogenic failure. Using multiple paralog ratio tests (PRTs), the structure duplications were classified by the copy number of the AZFc-linked amplicons and genes. The Y-chromosome haplogroup (Y-hg) was categorized by genetyping of MSY-linked polymorphism loci. The association of primary AZFc duplication with spermatogenic phenotype was investigated in males with the same Y-hg. RESULTS: Within Y-hg O3* group, the frequency of the gr/gr duplication in patients is significantly higher than that of controls (P = 1.29×10-3 , odds ratio (OR) 7.64, 95% confidence interval (CI) 1.79-32.57). Moreover, Y-hg O3* males with the gr/gr duplication presented a significantly lower sperm production compared with non-AZFc duplicated ones (sperm concentration: P = 1.46×10-3 ; total sperm count: P = 1.82 ×10-3 ). The b2/b3 duplication were identified clustered in Y-hg Cα2*, and the significant difference in the distribution was not observed between patients with spermatogenic failure and controls. CONCLUSION: The results suggest that, in the Han Chinese population, the gr/gr duplication is a predisposing genetic factor for spermatogenic impairment in males harboring Y-hg O3* . Meanwhile, the b2/b3 duplication may be fixed on a yet-unidentified subbranch of Y-hg Cα2* without significantly deleterious effect on spermatogenesis. Our findings provide evidence that the difference in the Y-hg composition may cause the discrepancy on the association of AZFc duplication with spermatogenic failure among the studied populations.
Subject(s)
Azoospermia , Infertility, Male , Mercury , Humans , Male , Azoospermia/genetics , Case-Control Studies , DNA Copy Number Variations , Semen , Infertility, Male/genetics , Chromosomes, Human, Y/genetics , Spermatogenesis/genetics , China , Chromosome DeletionABSTRACT
Pathogenic mutations in SCN5A could result in dysfunctions of Nav1.5 and consequently lead to a wide range of inherited cardiac diseases. However, the presence of numerous SCN5A-related variants with unknown significance (VUS) and the comprehensive genotype-phenotype relationship pose challenges to precise diagnosis and genetic counseling for affected families. Here, we functionally identified two novel compound heterozygous variants (L256del and L1621F) in SCN5A in a Chinese family exhibiting complex congenital cardiac phenotypes from sudden cardiac death to overlapping syndromes including sick sinus syndrome and dilated cardiomyopathy in an autosomal recessive pattern. In silico tools predicted decreased stability and hydrophobicity of the two mutated proteins due to conformational changes. Patch-clamp electrophysiology revealed slightly decreased sodium currents, accelerated inactivation, and reduced sodium window current in the Nav1.5-L1621F channels as well as no sodium currents in the Nav1.5-L256del channels. Western blotting analysis demonstrated decreased expression levels of mutated Nav1.5 on the plasma membrane, despite enhanced compensatory expression of the total Nav1.5 expression levels. Immunofluorescence imaging showed abnormal condensed spots of the mutated channels within the cytoplasm instead of normal membrane distribution, indicating impaired trafficking. Overall, we identified the loss-of-function characteristics exhibited by the two variants, thereby providing further evidence for their pathogenic nature. Our findings not only extended the variation and phenotype spectrums of SCN5A, but also shed light on the crucial role of patch-clamp electrophysiology in the functional analysis of VUS in SCN5A, which have significant implications for the clinical diagnosis, management, and genetic counseling in affected individuals with complex cardiac phenotypes.
Subject(s)
Brugada Syndrome , Cardiomyopathy, Dilated , Heart Defects, Congenital , Humans , Cardiomyopathy, Dilated/diagnosis , Cardiomyopathy, Dilated/genetics , Sick Sinus Syndrome/diagnosis , Sick Sinus Syndrome/genetics , Pedigree , Death, Sudden, Cardiac/etiology , Mutation , Sodium/metabolism , NAV1.5 Voltage-Gated Sodium Channel/genetics , NAV1.5 Voltage-Gated Sodium Channel/metabolism , Brugada Syndrome/geneticsABSTRACT
Partial DNA duplex formation greatly impacts the quality of DNA hybridization and has been extensively studied due to its significance in many biological processes. However, traditional DNA sensing methods suffer from time-consuming amplification steps and hinder the acquisition of information about single-molecule behavior. In this work, we developed a plasmonic method to probe the hybridization process at a single base pair resolution and study the relationship between the complementarity of DNA analytes and DNA hybridization behaviors. We measured single-molecule hybridization events with Au NP-modified ssDNA probes in real time and found two hybridization adsorption events: stable and transient adsorption. The ratio of these two hybridization adsorption events was correlated with the length of the complementary sequences, distinguishing DNA analytes from different complementary sequences. By using dual incident angle excitation, we recognized different single-base complementary sequences. These results demonstrated that the plasmonic method can be applied to study partial DNA hybridization behavior and has the potential to be incorporated into the identification of similar DNA sequences, providing a sensitive and quantitative tool for DNA analysis.
Subject(s)
DNA, Single-Stranded , DNA , Base Pairing , Nucleic Acid Hybridization/methods , DNA/genetics , DNA, Single-Stranded/genetics , DNA Probes/geneticsABSTRACT
Ferroptosis has demonstrated significant potential in treating radiochemotherapy-resistant cancers, but its efficacy can be affected by recently discovered ferroptosis suppressors. In this study, we discovered that NR0B1 protects against erastin- or RSL3-induced ferroptosis in lung cancer cells. Transcriptomic analysis revealed that NR0B1 significantly interfered with the expression of 12 ferroptosis-related genes, and the expression level of NR0B1 positively correlated with that of c-JUN, NRF2, and CBS. We further revealed that NR0B1 suppression of ferroptosis depended on the activities of c-JUN, NRF2, and CBS. NR0B1 directly promoted the expression of NRF2 and c-JUN and indirectly upregulated CBS expression through enhancing NRF2 and/or c-JUN transcription. Moreover, we showed that NR0B1 depletion restrained xenograft tumor growth and facilitated RSL3-induced ferroptosis in the tumors. In conclusion, our findings uncover that NR0B1 suppresses ferroptosis by activating the c-JUN/NRF2-CBS signaling pathway in lung cancer cells, providing new evidence for the involvement of NR0B1 in drug resistance during cancer therapy.
ABSTRACT
Flavanone glucosides, such as naringin and neohesperidin, are present in specific Citrus species and manifest a chiral center at the C-2 position of their flavanone moiety. This study successfully achieved the simultaneous stereoselective separation of the C-2 diastereomers of naringin, neohesperidin and hesperidin, as well as the partial separation of narirutin using a chiral high performance liquid chromatography with ultraviolet detection method with cellulose tris(3,5-dichlorophenylcarbamate) as the stationary phase under normal-phase mode. The mobile phase comprised n-hexane and ethanol (containing 0.25% formic acid) at a proportion of 65 : 35 (v/v) with a flow rate of 0.6 mL min-1. Each single epimer of chiral flavanone glycosides was prepared using chiral semi-preparative chromatography, and the absolute configuration was then characterized by combining the experimental electronic circular dichroism detection and time-dependent density functional theory calculations. The epimer composition of each chiral flavonoid glycoside in Fructus aurantii (Zhiqiao) and Fructus aurantii immaturus (Zhishi) was determined revealing variations among herbs collected from different production regions. Additionally, the epimer composition was found to be related to the harvesting time of the herbs. Considering the safety and efficacy, the existence of epimers of different stereo-configurations should be given more attention in the quality evaluation of natural drugs.
Subject(s)
Citrus , Flavanones , Glycosides/chemistry , Citrus/chemistry , Chromatography, High Pressure Liquid/methods , Flavanones/chemistry , Flavonoids/chemistryABSTRACT
Previous studies have shown significant associations between home environmental factors and childhood eczema. However, few studies have compared how associations differ in different regions. This study investigated associations between home environmental factors and childhood eczema ever, and related symptoms including itchy rash (IR) and being awakened by itchy rash at night (awake by IR) in 4 cities located in different regions of China, based on cross-sectional investigations during 2010-2012. We used two-step analysis to explore the associations between influencing factors and eczema/related symptoms: first, group Least Absolute Shrinkage and Selection Operator (LASSO) was conducted to identify important factors among a list of candidates; then, the associations in total study population and in each city were estimated using logistic regression. We found these home environmental factors to be risk factors for eczema or related symptoms: large residence size, shared room, air cleaner at home, abnormal smell, perceived dry air, visible mold or damp stains, cooking with coal or wood, painted wall, incense, mice, new furniture during pregnancy, abnormal smell at birth, window condensation at birth and environmental tobacco smoke at birth. Environmental protective factors were rural house location and window ventilation. Associations of factors with eczema/related symptoms differed across cities. For example, air conditioning was protective for eczema in Beijing and awakening by IR in Shanghai with ORs of 0.70 (95%CI: 0.52, 0.95) and 0.33 (95%CI: 0.14, 0.81) respectively, but not significant in other cities. Our results have implications for improving home environments to reduce the risk of childhood eczema/related symptoms in different regions of China.
ABSTRACT
Nucleic acid (NA) is a widely-used biomarker for viruses. Accurate quantification of NA can provide a reliable basis for point-of-care diagnosis and treatment. Here, we propose a tilted fiber Bragg grating (TFBG)-based plasmonic fiber-optic spectral comb for fast response and ultralow limit NA detection. The TFBG is coated with a gold film which enables excitation of surface plasmon resonance (SPR), and single-stranded probe NAs with known base sequences are assembled on the gold film. To enhance sensitivity of refractive index (RI) for sensing a chosen combination of probe and target NAs around the TFBG surface, gold nanoparticles (AuNPs) are bonded to the target NA molecules as "RI-labels". The NA combination-induced aggregation of AuNPs induces significant spectral responses in the TFBG that would be below the detection threshold for the NAs in the absence of the AuNPs. The proposed TFBG-SPR NA sensor shows a fast response time of 30 s and an ultra-wide NA detection range from 1 × 10-18 mol/L to 1 × 10-7 mol/L. In the NA concentration range of 1 × 10-12 mol/L (1 pM) to 105 pM, an ultra-high sensitivity of 1.534 dB/lg(pM) is obtained. The sensor achieves an ultra-low limit of detection down to 1.0 × 10-18 mol/L (1 aM), which is more than an order of magnitude lower than the previous reports. The proposed sensor not only shows potentials in practical applications of NA detection, but also provides a new way for TFBG-SPR biochemical sensors to achieve higher RI sensitivity.