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1.
IEEE Trans Image Process ; 33: 2950-2965, 2024.
Article in English | MEDLINE | ID: mdl-38598374

ABSTRACT

Few-shot image generation aims to generate images of high quality and great diversity with limited data. However, it is difficult for modern GANs to avoid overfitting when trained on only a few images. The discriminator can easily remember all the training samples and guide the generator to replicate them, leading to severe diversity degradation. Several methods have been proposed to relieve overfitting by adapting GANs pre-trained on large source domains to target domains using limited real samples. This work presents masked discrimination to realize few-shot GAN adaptation, which is the first feature-level augmentation method for generative tasks. Random masks are applied to features extracted by the discriminator from input images. We aim to encourage the discriminator to judge various images that share partially common features with training samples as realistic. Correspondingly, the generator is guided to generate diverse images instead of replicating training samples. In addition, we employ a cross-domain consistency loss for the discriminator to keep relative distances between generated samples in its feature space. It strengthens global image discrimination and guides adapted GANs to preserve more information learned from source domains for higher image quality, resulting in better cross-domain correspondence. The effectiveness of our approach is demonstrated both qualitatively and quantitatively with higher quality and greater diversity on a series of few-shot image generation tasks than prior methods.

2.
Signal Transduct Target Ther ; 9(1): 95, 2024 Apr 24.
Article in English | MEDLINE | ID: mdl-38653979

ABSTRACT

Bietti crystalline corneoretinal dystrophy is an inherited retinal disease caused by mutations in CYP4V2, which results in blindness in the working-age population, and there is currently no available treatment. Here, we report the results of the first-in-human clinical trial (NCT04722107) of gene therapy for Bietti crystalline corneoretinal dystrophy, including 12 participants who were followed up for 180-365 days. This open-label, single-arm exploratory trial aimed to assess the safety and efficacy of a recombinant adeno-associated-virus-serotype-2/8 vector encoding the human CYP4V2 protein (rAAV2/8-hCYP4V2). Participants received a single unilateral subretinal injection of 7.5 × 1010 vector genomes of rAAV2/8-hCYP4V2. Overall, 73 treatment-emergent adverse events were reported, with the majority (98.6%) being of mild or moderate intensity and considered to be procedure- or corticosteroid-related; no treatment-related serious adverse events or local/systemic immune toxicities were observed. Compared with that measured at baseline, 77.8% of the treated eyes showed improvement in best-corrected visual acuity (BCVA) on day 180, with a mean ± standard deviation increase of 9.0 ± 10.8 letters in the 9 eyes analyzed (p = 0.021). By day 365, 80% of the treated eyes showed an increase in BCVA, with a mean increase of 11.0 ± 10.6 letters in the 5 eyes assessed (p = 0.125). Importantly, the patients' improvement observed using multifocal electroretinogram, microperimetry, and Visual Function Questionnaire-25 further supported the beneficial effects of the treatment. We conclude that the favorable safety profile and visual improvements identified in this trial encourage the continued development of rAAV2/8-hCYP4V2 (named ZVS101e).


Subject(s)
Corneal Dystrophies, Hereditary , Cytochrome P450 Family 4 , Dependovirus , Genetic Therapy , Retinal Diseases , Humans , Male , Female , Middle Aged , Adult , Corneal Dystrophies, Hereditary/genetics , Corneal Dystrophies, Hereditary/therapy , Corneal Dystrophies, Hereditary/pathology , Dependovirus/genetics , Cytochrome P450 Family 4/genetics , Genetic Vectors/genetics , Visual Acuity
3.
Micromachines (Basel) ; 15(4)2024 Apr 17.
Article in English | MEDLINE | ID: mdl-38675349

ABSTRACT

Retroreflective gratings serve as fundamental optical elements in nanophotonics, with polarization-independent diffraction efficiency being one of the critical parameters for assessing their performance. In the far-infrared spectral range, traditional retroreflective gratings typically refer to metal echelette gratings, but their diffraction efficiency cannot approach 100% due to metal absorption. In the visible and near-infrared spectral ranges, metal echelette gratings have gradually been replaced by all-dielectric metasurfaces because dielectric materials exhibit negligible absorption at specific wavelengths. However, there is still a lack of relevant research in the far-infrared range, mainly due to the weak control capability of the existing devices over the polarization-independent phase. Here, we propose a kind of all-dielectric retroreflective metasurface composed of asymmetric pillars and freely tunable aperiodic multilayer films. The pillar structure can achieve polarization insensitivity, and the insufficient modulation capability of the dielectric materials can be compensated for by aperiodic Ge/ZnS films. The designed metasurface achieves the diffraction efficiency by RCWA, with the maximum larger than 99% and the overall reaching 95% (9.3-9.6 µm). We have provided detailed explanations of the design methodology and fabrication process. Our work lays the groundwork for further exploration and application of far-infrared lasers.

4.
Opt Express ; 31(25): 41339-41350, 2023 Dec 04.
Article in English | MEDLINE | ID: mdl-38087535

ABSTRACT

Multilayer metagratings have strong wavefront manipulation capabilities and find important applications in beam splitters. Traditional methods rely on the phase gradient design of generalized Snell's law, which can achieve highly efficient beam splitters with uniform energy distribution. However, designing arbitrary energy distributions in different channels under two orthogonal polarizations remains a challenge because it requires more complex structures to modulate the energy flow. In this work, we employed a hybrid evolutionary particle swarm optimization (HEPSO) from the combination of particle swarm optimization (PSO) and genetic algorithm (GA) which has a strong ability to find the optimal structures that satisfy the specific energy flow distributions. We used the crossover and mutation operators of GA to improve the global search capabilities, and the velocity updating formula of PSO to replace the selection operator of GA to avoid local optimization. Using this approach, we successfully designed a uniform beam splitter with an efficiency of over 90% and two beam splitters with arbitrary energy distributions, achieving an average error of about 0.5%. The optimal and average efficiencies obtained from running 10 optimizations are 2.2% and 4% higher than those obtained using PSO alone with 30 populations and 75 iterations. We envision that the proposed method can also provide an idea for other photonics design problems.

5.
Nanomaterials (Basel) ; 13(19)2023 Sep 23.
Article in English | MEDLINE | ID: mdl-37836265

ABSTRACT

On-chip multi-dimensional detection systems integrating pixelated polarization and spectral filter arrays are the latest trend in optical detection instruments, showing broad application potential for diagnostic medical imaging and remote sensing. However, thin-film or microstructure-based filter arrays typically have a trade-off between the detection dimension, optical efficiency, and spectral resolution. Here, we demonstrate novel on-chip integrated polarization spectral detection filter arrays consisting of metasurfaces and multilayer films. The metasurfaces with two nanopillars in one supercell are designed to modulate the Jones matrix for polarization selection. The angle of diffraction of the metasurfaces and the optical Fabry-Perot (FP) cavities determine the spectrum's center wavelength. The polarization spectral filter arrays are placed on top of the CMOS sensor; each array corresponds to one pixel, resulting in high spectral resolution and optical efficiency in the selected polarization state. To verify the methodology, we designed nine-channel polarized spectral filter arrays in a wavelength range of 1350 nm to 1550 nm for transverse electric (TE) linear polarization. The array has a 10 nm balanced spectral resolution and average peak transmission efficiency of over 75%, which is maintained by utilizing lossless dielectric material. The proposed array can be fabricated using overlay e-beam lithography, and the process is CMOS-compatible. The proposed array enables broader applications of in situ on-chip polarization spectral detection with high efficiency and spectral resolution, as well as in vivo imaging systems.

6.
Light Sci Appl ; 12(1): 229, 2023 Sep 15.
Article in English | MEDLINE | ID: mdl-37714831

ABSTRACT

Exceptional point (EP) is a special degeneracy of non-Hermitian systems. One-dimensional transmission systems operating at EPs are widely studied and applied to chiral conversion and sensing. Lately, two-dimensional systems at EPs have been exploited for their exotic scattering features, yet so far been limited to only the non-visible waveband. Here, we report a universal paradigm for achieving a high-efficiency EP in the visible by leveraging interlayer loss to accurately control the interplay between the lossy structure and scattering lightwaves. A bilayer framework is demonstrated to reflect back the incident light from the left side ( | r-1 | >0.999) and absorb the incident light from the right side ( | r+1 | < 10-4). As a proof of concept, a bilayer metasurface is demonstrated to reflect and absorb the incident light with experimental efficiencies of 88% and 85%, respectively, at 532 nm. Our results open the way for a new class of nanoscale devices and power up new opportunities for EP physics.

7.
Front Psychol ; 14: 1207453, 2023.
Article in English | MEDLINE | ID: mdl-37614493

ABSTRACT

Introduction: The investigation of trust vulnerability is important to the understanding of the potential mechanisms of trust formation and erosion. However, more effective exploration of trust vulnerability has been hindered due to the lack of consideration of risk sources and types of information. Methods: This study extended the investigation of asymmetry to both social and natural risk under experiential and descriptive decisions. Using the trust game as the decision-making paradigm and money as the subject matter, the research employed experimental methods to examine how people perceive and make decisions after being positively and negatively affected by natural and social risks. A total of 286 college students were participated in our study. Study 1 (n = 138) and Study 2 (n = 148) explored asymmetry in experiential and descriptive decision separately. Results: The findings indicated that when considering experiential information, negative information had a greater effect in reducing trust compared to the enhancing effect of positive information (t = -1.95, p = 0.050). Moreover, the study revealed that negative information had a stronger negative impact in the context of social risks rather than natural risks (t = -3.26, p = 0.002), suggesting that trust is vulnerable both internally and externally. Conversely, when considering descriptive information, the effect of both positive and negative information on trust was symmetrical, and the impact of negative information was less significant compared to that of natural risks, indicating that trust has a certain level of resilience (t = 2.25, p = 0.028). Discussion: The study emphasizes the importance of refining risk sources and information characteristics in complex scenarios in order to improve understanding of trust enhancement and repair.

8.
Opt Express ; 31(9): 14027-14036, 2023 Apr 24.
Article in English | MEDLINE | ID: mdl-37157275

ABSTRACT

Pixelated filter arrays of Fabry-Perot (FP) cavities are widely integrated with photodetectors to achieve a WYSIWYG ("what you see is what you get") on-chip spectral measurements. However, FP-filter-based spectral sensors typically have a trade-off between their spectral resolution and working bandwidth due to design limitations of conventional metal or dielectric multilayer microcavities. Here, we propose a new idea of integrated color filter arrays (CFAs) consisting of multilayer metal-dielectric-mirror FP microcavities that, enable a hyperspectral resolution over an extended visible bandwidth (∼300 nm). By introducing another two dielectric layers on the metallic film, the broadband reflectance of the FP-cavity mirror was greatly enhanced, accompanied by as-flat-as-possible reflection-phase dispersion. This resulted in balanced spectral resolution (∼10 nm) and spectral bandwidth from 450 nm to 750 nm. In the experiment, we used a one-step rapid manufacturing process by using grayscale e-beam lithography. A 16-channel (4 × 4) CFA was fabricated and demonstrated on-chip spectral imaging with a CMOS sensor and an impressive identification capability. Our results provide an attractive method for developing high-performance spectral sensors and have potential commercial applications by extending the utility of low-cost manufacturing process.

9.
Appl Opt ; 62(7): B19-B24, 2023 Mar 01.
Article in English | MEDLINE | ID: mdl-37132882

ABSTRACT

Diffractive optical elements (DOEs) play an important role in modern optical applications such as spectral and imaging systems, but it is challenging to balance the diffraction efficiency with the working bandwidth. The core issue is controlling the broadband dispersion of all phase units to achieve achromatic 2π-phase modulation in the broadband domain. Here, we demonstrate broadband DOEs utilizing multilayer subwavelength structures with different materials, making it possible to freely control the phase and phase dispersion of the structural units on a much larger scale than monolayer structures. The desired dispersion-control abilities arose due to a dispersion-cooperation mechanism and vertical mode-coupling effects between the top and bottom layers. An infrared design comprised of two vertically concatenated T i O 2 and Si nanoantennas separated by a S i O 2 dielectric spacer layer was demonstrated. It showed an average efficiency of over 70% in the three-octave bandwidth. This work shows enormous value for broadband optical systems with DOEs such as spectral imaging and augmented reality.

10.
Nanomaterials (Basel) ; 13(7)2023 Mar 30.
Article in English | MEDLINE | ID: mdl-37049327

ABSTRACT

Meta-optics based on metasurfaces that interact strongly with light has been an active area of research in recent years. The development of meta-optics has always been driven by human's pursuits of the ultimate miniaturization of optical elements, on-demand design and control of light beams, and processing hidden modalities of light. Underpinned by meta-optical physics, meta-optical devices have produced potentially disruptive applications in light manipulation and ultra-light optics. Among them, optical metalens are most fundamental and prominent meta-devices, owing to their powerful abilities in advanced imaging and image processing, and their novel functionalities in light manipulation. This review focuses on recent advances in the fundamentals and applications of the field defined by excavating new optical physics and breaking the limitations of light manipulation. In addition, we have deeply explored the metalenses and metalens-based devices with novel functionalities, and their applications in computational imaging and image processing. We also provide an outlook on this active field in the end.

11.
Int J Ophthalmol ; 16(3): 427-433, 2023.
Article in English | MEDLINE | ID: mdl-36935788

ABSTRACT

AIM: To investigate the risk and protective factors associated with the retinal nerve fiber layer defect (RNFLD) in a Chinese adult population. METHODS: This study was a cross-sectional population-based investigation including employees and retirees of a coal mining company in Kailuan City, Hebei Province. All the study participants underwent a comprehensive systemic and ophthalmic examination. RNFLD was diagnosed on fundus photographs. Binary logistic regression was used to investigate the risk and protective factors associated with the RNFLD. RESULTS: The community-based study included 14 440 participants. There were 10 473 participants in our study, including 7120 males (68.0%) and 3353 females (32.0%). The age range was 45-108y, averaging 59.56±8.66y. Totally 568 participants had RNFLD and the prevalence rate was 5.42%. A higher prevalence of RNFLD was associated with older age [P<0.001, odds ratio (OR): 1.032; 95% confidence interval (CI): 1.018-1.046], longer axial length (P=0.010, OR: 1.190; 95%CI: 1.042-1.359), hypertension (P=0.007, OR: 0.639; 95%CI: 0.460-0.887), and diabetes mellitus (P=0.019, OR: 0.684; 95%CI: 0.499-0.939). The protective factors of RNFLD were visual acuity (P=0.038, OR: 0.617; 95%CI: 0.391-0.975), and central anterior chamber depth (P=0.046, OR: 0.595; 95%CI: 0.358-0.990). CONCLUSION: In our cross-sectional community-based study, with an age range of 45-108y, RNFLD is associated with older age, longer axial length, hypertension, and diabetes mellitus. The protective factors of RNFLD are visual acuity and central anterior chamber depth. These can help to predict and evaluate RNFLD related diseases and identify high-risk populations early.

12.
Ecotoxicol Environ Saf ; 251: 114518, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36640576

ABSTRACT

Dental fluorosis (DF) is a widely prevalent disease caused by excessive fluoride with limited awareness of its underlying pathogenesis. Here, a pilot population study was conducted to explore the pathogenesis of DF from the perspective of intestinal microbiome changes, and verified it in animal experiments combining intestinal microbiome and metabolomics. A total of 23 children were recruited in 2017 in China and divided into DF (n = 9) and control (n = 14) groups (DFG and CG, respectively). The SD rat model was established by drinking water containing sodium fluoride (NaF). Gut microbiome profiles of children and rats were analyzed by16S rDNA V3-V4 sequencing, and the intestinal metabolomics analysis of rats was performed by LC-MS methods. The 16 S rDNA sequencing revealed that the gut microbiome composition was significantly perturbed in children in DFG compared to that in CG. Acidobacteria and Thermi were specifically observed in DFG and CG, respectively. Besides, 15 fecal microbiotas were significantly altered at the genus level in DFG. Furthermore, only the expression of annotated genes for pentose and glucuronate interconversion pathway was significant lower in DFG than that in CG (P = 0.04). Notably, in NaF-treated rats, we also observed the changes of some key components of pentose and glucuronate interconversion pathway at the level of microorganisms and metabolites. Our findings suggested that the occurrence of DF is closely related to the alteration of intestinal microorganisms and metabolites annotated in the pentose and glucuronate interconversion pathway.


Subject(s)
Fluorosis, Dental , Rats , Animals , Fluorosis, Dental/genetics , Fluorosis, Dental/epidemiology , Rats, Sprague-Dawley , Metabolomics/methods , Fluorides , Sodium Fluoride
14.
ACS Nanosci Au ; 2(5): 396-403, 2022 Oct 19.
Article in English | MEDLINE | ID: mdl-36281252

ABSTRACT

Information processing by traditional, serial electronic processors consumes an ever-increasing part of the global electricity supply. An alternative, highly energy efficient, parallel computing paradigm is network-based biocomputation (NBC). In NBC a given combinatorial problem is encoded into a nanofabricated, modular network. Parallel exploration of the network by a very large number of independent molecular-motor-propelled protein filaments solves the encoded problem. Here we demonstrate a significant scale-up of this technology by solving four instances of Exact Cover, a nondeterministic polynomial time (NP) complete problem with applications in resource scheduling. The difficulty of the largest instances solved here is 128 times greater in comparison to the current state of the art for NBC.

15.
BMC Cancer ; 22(1): 863, 2022 Aug 08.
Article in English | MEDLINE | ID: mdl-35941565

ABSTRACT

BACKGROUND: There is no clear consensus on the benefits of adjuvant chemotherapy for tumor-node-metastasis (TNM) stage T1 (T1N0M0) breast cancer (BC). Our study investigated the effects of adjuvant chemotherapy on T1N0M0 BC patients. METHODS: Seventy-five thousand one hundred thirty-nine patients diagnosed with T1N0M0 BC were selected from the Surveillance, Epidemiology, and End Results (SEER) database. Multivariate Cox analyses were performed to investigate the effects of adjuvant chemotherapy on T1a, T1b, and T1cN0M0 BC, including various tumor grades, and four molecular subtypes. Propensity score matching (PSM) was used to eliminate confounding factors and further compare the results between adjuvant chemotherapy and no adjuvant chemotherapy. Additionally, 545 T1N0M0 BC patients treated at the Northern Jiangsu People's Hospital were included as an independent external validation cohort. Univariate and multivariate Cox analyses were used to confirm the effects of adjuvant chemotherapy in T1a, T1b, and T1cN0M0 BC. Survival curves for the different tumor grades and molecular subtypes were plotted using the Kaplan-Meier method. RESULTS: Adjuvant chemotherapy demonstrated a statistically significant improvement in overall survival (OS) in T1b and T1c BC, but not in T1a BC. Within T1b BC, adjuvant chemotherapy was found to have effects on grade III, and hormone receptor + (HoR +)/human epidermal growth factor receptor 2 + (HER2 +), HoR-/HER2 + , and HoR-/HER2- molecular subtypes, respectively. Adjuvant chemotherapy was beneficial to OS for grade II/III and T1c BC. Identical results were obtained after PSM. We also obtained similar results with external validation cohort, except that adjuvant chemotherapy made a difference in grade II and T1b BC of the external validation dataset. CONCLUSIONS: Partial T1N0M0 BC patients with grade III T1bN0M0, patients with tumor grade II and III T1cN0M0, and excluding those with HoR + /HER2- subtype tumors, could obtain OS benefits from adjuvant chemotherapy.


Subject(s)
Breast Neoplasms , Breast Neoplasms/drug therapy , Breast Neoplasms/epidemiology , Breast Neoplasms/pathology , Chemotherapy, Adjuvant/methods , Cohort Studies , Female , Humans , Neoplasm Staging , Prognosis , Propensity Score , Receptor, ErbB-2/metabolism
16.
PLoS One ; 17(3): e0266088, 2022.
Article in English | MEDLINE | ID: mdl-35353844

ABSTRACT

Compound screening by in silico approaches has advantages in identifying high-activity leading compounds and can predict the safety of the drug. A key challenge is that the number of observations of drug activity and toxicity accumulation varies by target in different datasets, some of which are more understudied than others. Owing to an overall insufficiency and imbalance of drug data, it is hard to accurately predict drug activity and toxicity of multiple tasks by the existing models. To solve this problem, this paper proposed a two-stage transfer learning workflow to develop a novel prediction model, which can accurately predict drug activity and toxicity of the targets with insufficient observations. We built a balanced dataset based on the Tox21 dataset and developed a drug activity and toxicity prediction model based on Siamese networks and graph convolution to produce multitasking output. We also took advantage of transfer learning from data-rich targets to data-poor targets. We showed greater accuracy in predicting the activity and toxicity of compounds to targets with rich data and poor data. In Tox21, a relatively rich dataset, the prediction model accuracy for classification tasks was 0.877 AUROC. In the other five unbalanced datasets, we also found that transfer learning strategies brought the accuracy of models to a higher level in understudied targets. Our models can overcome the imbalance in target data and predict the compound activity and toxicity of understudied targets to help prioritize upcoming biological experiments.


Subject(s)
Workflow
17.
Int J Environ Health Res ; 32(5): 952-962, 2022 May.
Article in English | MEDLINE | ID: mdl-32866029

ABSTRACT

The nasopharynx is a key niche of the upper respiratory tract which contains many commensal bacteria and potential pathogens. Dysbiosis of the nasopharyngeal (NP) microbiota is associated with a variety of respiratory diseases. Little is known about NP flora in healthy youth, nor about its relationship with environmental factors. We characterized NP microbiota using the 16S rRNA gene sequencing method, and compared microbial composition from subjects sampled in Spring and Fall when exposed to different environmental factors. Results showed that beta diversity was significantly different. Phyla Acidobacteria, Gemmatimonadetes, and genus Symbiobacterium were positively associated with PM2.5. Genera Streptococcus, Prevotella, and [Prevotella] were positively correlated with temperature (T). Ozone (O3) was associated with these floras for exposure that occurred 30 days prior to collection. These preliminary data suggest that the change in environmental factors between spring and fall can influence the composition of the NP microbiota, characterized by a significant correlation to specific taxa. These changes in NP microbiota might be a potential risk factor for respiratory disease.


Subject(s)
Microbiota , Adolescent , Bacteria/genetics , Humans , Nasopharynx/microbiology , RNA, Ribosomal, 16S/genetics
18.
Int J Environ Health Res ; 32(1): 232-241, 2022 Jan.
Article in English | MEDLINE | ID: mdl-32281876

ABSTRACT

To assess the association between fluoride exposure and children's behavioural outcomes, we recruited 325 resident school-age children (7-13 years old) lived in Tongxu County of Henan Province in China. We measured urinary fluoride (UF) concentrations using the ion-selective electrode method. Children's behavioural outcomes were assessed by Conners' Parent Rating Scale-Revised, including conduct problems, learning problems, psychosomatic problems, impulsive-hyperactive, anxiety, and ADHD index. It turned out that each 1.0 mg/L increment in UF concentration corresponded with an elevation in the psychosomatic problem score of 4.01 (95% CI: 2.74, 5.28) and a 97% (OR = 1.97, 95% CI: 1.19, 3.27) increase in the prevalence of psychosomatic problems after adjusting for potential influencing factors. The sensitivity analysis results were consistent with those observed in our preliminary analysis. Our study suggests that fluoride exposure is positively related to the behavioural problem in school-age children, psychosomatic problem in particular.


Subject(s)
Fluorides , Schools , Adolescent , Child , China/epidemiology , Fluorides/analysis , Humans , Pilot Projects
19.
Sci Total Environ ; 806(Pt 3): 150685, 2022 Feb 01.
Article in English | MEDLINE | ID: mdl-34600986

ABSTRACT

Livestock farms are recognized as the main sources of antibiotic resistance genes (ARGs) and antibiotic-resistant bacteria (ARB) with potential implications for human health. In this study, we systematically analyzed microbiome composition, distribution of ARGs and mobile genetic elements (MGEs) in the oropharynx and gut of workers in cattle farms and surrounding villagers, cattle feces and farm air, and the relationship of microbial communities among farm air, cattle feces and farmworkers (oropharynx and gut). Exposure to the farm environment may have remodeled farmworkers' oropharynx and gut microbiota, with reduced microbial diversity (P < 0.05) and enrichment of some opportunistic pathogenic bacteria like Shigella, Streptococcus, and Neisseria in the oropharynx. Meanwhile, compared with villagers, ARG abundance in oropharynx of farmworkers increased significantly (P < 0.05), but, no significant difference in gut (P > 0.05). Microbial composition and ARG profile in farmworkers might be influenced by working time and work type, ARG abundance in farmworkers' gut was positively correlated with working time (P < 0.01), and higher ARG abundance was found in the oropharynx of drovers. The network analysis revealed that 4 MGEs (tnpA-01, tnpA-04, Tp614, and IS613), 5 phyla (e.g. Bacteroidetes, Fusobacteria, and TM7), and 6 genera were significantly associated with 37 ARGs (ρ > 0.6, P < 0.01). Overall, our results indicated that farm exposure may have affected the microbial composition and increased ARG abundance of farmworkers. Transmission of some ARGs may have occurred among the environment, animals and humans via host bacteria, which might pose a potential threat to human health.


Subject(s)
Anti-Bacterial Agents , Microbiota , Angiotensin Receptor Antagonists , Angiotensin-Converting Enzyme Inhibitors , Animals , Anti-Bacterial Agents/pharmacology , Cattle , Drug Resistance, Microbial , Farms , Genes, Bacterial , Oropharynx
20.
Ecotoxicol Environ Saf ; 223: 112612, 2021 Oct 15.
Article in English | MEDLINE | ID: mdl-34371455

ABSTRACT

Excessive fluoride exposure and epigenetic change can induce numerous adverse health outcomes, but the role of epigenetics underneath the harmful health effects induced by fluoride exposure is unclear. In such gap, we evaluated the associations between fluoride exposure and genome-wide DNA methylation, and identified that novel candidate genes associated with fluoride exposure. A total of 931 school-age children (8-12 years) in Tongxu County of Henan Province (China) were recruited in 2017. Urinary fluoride (UF) concentrations were measured using the national standardized ion selective electrode method. Participants were divided into a high fluoride-exposure group (HFG) and control group (CG) according to the UF concentrations. Candidate differentially methylated regions (DMRs) were screened by Infinium-Methylation EPIC BeadChip of DNA samples collected from 16 participants (eight each from each group). Differentially methylated genes (DMGs) containing DMRs associated with skeletal and neuronal development influenced by fluoride exposure were confirmed using MethylTarget™ technology from 100 participants (fifty each from each group). DMGs were verified by quantitative methylation specific PCR from 815 participants. Serum levels of hormones were measured by auto biochemical analyzer. The mediation analysis of methylation in the effect of fluoride exposure on hormone levels was also performed. A total of 237 differentially methylated sites (DMSs) and 212 DMRs were found in different fluoride-exposure groups in the epigenome-wide phase. Methylation of the target sequences of neuronatin (NNAT), calcitonin-related polypeptide alpha (CALCA) and methylenetetrahydrofolate dehydrogenase 1 showed significant difference between the HFG and CG. Each 0.06% (95% CI: -0.11%, -0.01%) decreased in NNAT methylation status correlated with each increase of 1.0 mg/L in UF concentration in 815 school-age children using QMSP. Also, each 1.88% (95% CI: 0.04%, 3.72%) increase in CALCA methylation status correlated with each increase of 1.0 mg/L in UF concentration. The mediating effect of NNAT methylation was found in alterations of ACTH levels influenced by fluoride exposure, with a ß value of 11.7% (95% CI: 3.4%, 33.4%). In conclusion, long-term fluoride exposure affected the methylation pattern of genomic DNA. NNAT and CALCA as DMGs might be susceptible to fluoride exposure in school-age children.


Subject(s)
DNA Methylation , Fluorides , Child , Epigenesis, Genetic , Epigenome , Fluorides/toxicity , Humans , Schools
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