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1.
Water Res ; 261: 122060, 2024 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-39018903

RESUMO

Microplastics (MPs), discovered in oceans, lakes, and rivers, can infiltrate the food chain through ingestion by organisms, potentially posing health risks. Our research is the first to study the composition and distribution of MPs in Bosten Lake's sediment. In May, the average abundance of MPs was 0.95±0.72 particles per 10 gs, and in October, it was 0.90±0.61 particles per 10 gs. Bohu Town had the highest MP abundance, with 1.75±0.35 particles per 10 gs in spring and 2 ± 0 particles per 10 gs in autumn. In May, 53 % of the MPs were transparent, while in October, black MPs constituted 58 %. The predominant morphology was fibrous, accounting for 61 % of the total. MPs in the size range of 0.2-1 mm made up 91 % and 66 % of the total in May and October, respectively. The most common types of MPs in May were polyethylene terephthalate (PET) at 40 % and polyethylene (PE) at 26 %. In October, PET was the most prevalent at 71 %, followed by poly(ether-ether-ketone)(PEEK) at 11 %. Certain microbial taxa, such as Actinobacteriota, Pseudomonas, and Vicinamibacteraceae, associated with MP degradation or complex carbon chain breakdown, were notably enriched in sediment areas with high MP concentrations. A significant positive correlation was observed between the abundance of MPs in sediments and Actinobacteriota. Additionally, the abundance of Thiobacillus, Ca.competibacter, and other bacteria involved in soil element cycling showed a significant positive correlation with the organic matter content in the sediments. Anaerobic bacteria like Thermoanaerobacterium displayed a significant positive correlation with water depth. Our study reveals the presence, composition, and distribution of MPs in Bosten Lake's sediments, shedding light on their potential ecological impact.

2.
Huan Jing Ke Xue ; 45(7): 4279-4292, 2024 Jul 08.
Artigo em Chinês | MEDLINE | ID: mdl-39022973

RESUMO

Microbial fertilizers have the characteristics of high efficiency and environmental protection in improving saline soils, and the application of functional microbial fertilizers is of great significance for the green abatement of saline barriers and the improvement of soil quality in coastal areas. The experiment was based on moderately saline soil in the coastal area of Hebei Province, with corn as the indicator crop, on the basis of conventional chemical fertilizer application. Different microbial fertilizer treatments, namely, T1 (conventional chemical fertilizer 750 kg·hm-2 + compound microbial agent 75 kg·hm-2), T2 (conventional chemical fertilizer 750 kg·hm-2 + Bacillus megaterium 300 kg·hm-2), T3 (conventional chemical fertilizer 750 kg·hm-2 + B. mucilaginosus 300 kg·hm-2), T4 (conventional chemical fertilizer 750 kg·hm-2 + organic silicon fertilizer 600 kg·hm-2), T5 (conventional chemical fertilizer 750 kg·hm-2 + bio-organic fertilizer 600 kg·hm-2), T6 (conventional fertilizer 750 kg·hm-2 + active microalgae 15 kg·hm-2), and CK (only fertilizer 750 kg·hm-2), were used for these seven treatments, to study the effects of different microbial fertilizers on soil nutrients, salinity, bacterial community, and corn yield and economic efficiency during two critical periods (V12 stage and maturity stage) of corn. The results showed that compared with that in CK, T1 significantly increased soil total nitrogen (TN) and available phosphorus (AP) contents during the whole growth period. Over the whole reproductive period, soil organic matter (OM) at maturity increased by 10.35% over the V12 stage compared to that in CK, but there was no significant difference between treatments. Compared with that in CK, T5 and T6 significantly reduced soil total salinity and Ca2+ content during the whole growth period by an average of 14.51%-18.48% and 24.25%-25.51%. T1 significantly increased the bacterial diversity index over the whole growth period by 45.16% compared to that in CK. The dominant soil phyla were Actinobacteria, Proteobacteria, Acidobacteria, and Chloroflexi, and the dominant genera were Bacillus and Geminicoccaceae. The most abundant functions of the bacterial community in the study area were chemoheterotrophy and aerobic chemoheterotrophy, with average relative abundances of 28.89% and 27.11%, and T3 and T6 significantly improved soil N cycling function. The results of redundancy analysis (RDA) indicated that Na+, SO42-, pH, and EC were important factors driving the structure of the bacterial community, and correlation heatmaps showed that Na+, SO42-, pH, and EC were significantly and positively correlated mainly with the phylum Planctomycetota, whereas soil OM and TN were significantly and positively correlated with Cyanobacteria. Compared with that in CK, T6 increased the relative abundance of Cyanobacteria and optimized the bacterial community structure during the whole growth period. Using recommended dosages of bacterial fertilizers T1 and T6 increased maize yield by 7.31%-24.83% and economic efficiency by 9.05%-23.23%, respectively. The preliminary results of soil chemical properties and yield correlation analysis revealed that EC, AP, HCO3-, and Mg2+ were the obstacle factors limiting soil productivity in coastal areas. In conclusion, the use of the compound bacterial agent (T1) and active microalgae (T6) at the recommended dosage can significantly enhance soil nutrients, reduce salinity, and improve the structural diversity of soil bacterial communities, which not only ensures the increase in maize yield and efficiency but also realizes the efficient use of microbial fertilizers and the improvement of soil quality.


Assuntos
Bacillus megaterium , Fertilizantes , Microbiologia do Solo , Solo , Zea mays , Zea mays/crescimento & desenvolvimento , Solo/química , Bacillus megaterium/crescimento & desenvolvimento , Bacillus megaterium/metabolismo , China , Salinidade , Biomassa , Água do Mar/microbiologia , Fósforo/análise
4.
Neural Regen Res ; 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38993123

RESUMO

ABSTRACT: AAV-PHP.eB is an artificial adeno-associated virus (AAV) that crosses the blood-brain barrier and targets neurons more efficiently than other AAVs when administered systematically. While AAV-PHP.eB has been used in various disease models, its cellular tropism in cerebrovascular diseases remains unclear. In the present study, we aimed to elucidate the tropism of AAV-PHP.eB for different cell types in the brain in a mouse model of ischemic stroke and evaluate its effectiveness in mediating basic fibroblast growth factor (bFGF) gene therapy. Mice were injected intravenously with AAV-PHP.eB either 14 days prior to (pre-stroke) or 1 day following (post-stroke) transient middle cerebral artery occlusion. Notably, we observed a shift in tropism from neurons to endothelial cells with post-stroke administration of AAV-PHP.eB-mNeonGreen (mNG). This endothelial cell tropism correlated strongly with expression of the endothelial membrane receptor lymphocyte antigen 6 family member A (Ly6A). Furthermore, AAV-PHP.eB-mediated overexpression of bFGF markedly improved neurobehavioral outcomes and promoted long-term neurogenesis and angiogenesis post-ischemic stroke. Our findings underscore the significance of considering potential tropism shifts when utilizing AAV-PHP.eB-mediated gene therapy in neurological diseases and suggest a promising new strategy for bFGF gene therapy in stroke treatment.

5.
Talanta ; 278: 126537, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38996561

RESUMO

Imaging live cells under stable culture conditions is essential to investigate cell physiological activities and proliferation. To achieve this goal, typically, a specialized incubation chamber that creates desired culture conditions needs to be incorporated into a microscopy system to perform cell monitoring. However, such imaging systems are generally large and costly, hampering their wide applications. Recent advances in the field of miniaturized microscopy systems have enabled incubator cell monitoring, providing a hospitable environment for live cells. Although these systems are more cost-effective, they are usually limited in imaging modalities and spatial temporal resolution. Here, we present a dual-mode, image-enhanced, miniaturized microscopy system (termed MiniCube) for direct monitoring of live cells inside incubators. MiniCube enables both bright field imaging and fluorescence imaging with single-cell spatial resolution and sub-second temporal resolution. Moreover, this system can also perform cell monitoring inside the incubator with tunable time scales ranging from a few seconds to days. Meanwhile, automatic cell segmentation and image enhancement are realized by the proposed data analysis pipeline of this system, and the signal-to-noise ratio (SNR) of acquired data is significantly improved using a deep learning based image denoising algorithm. Image data can be acquired with 5 times lower light exposure while maintaining comparable SNR. The versatility of this miniaturized microscopy system lends itself to various applications in biology studies, providing a practical platform and method for studying live cell dynamics within the incubator.

6.
J Multidiscip Healthc ; 17: 3109-3119, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38978829

RESUMO

Purpose: This study aimed to investigate the knowledge, attitudes, and practice (KAP) of radiologists regarding artificial intelligence (AI) in medical imaging in the southeast of China. Methods: This cross-sectional study was conducted among radiologists in the Jiangsu, Zhejiang, and Fujian regions from October to December 2022. A self-administered questionnaire was used to collect demographic data and assess the KAP of participants towards AI in medical imaging. A structural equation model (SEM) was used to analyze the relationships between KAP. Results: The study included 452 valid questionnaires. The mean knowledge score was 9.01±4.87, the attitude score was 48.96±4.90, and 75.22% of participants actively engaged in AI-related practices. Having a master's degree or above (OR=1.877, P=0.024), 5-10 years of radiology experience (OR=3.481, P=0.010), AI diagnosis-related training (OR=2.915, P<0.001), and engaging in AI diagnosis-related research (OR=3.178, P<0.001) were associated with sufficient knowledge. Participants with a junior college degree (OR=2.139, P=0.028), 5-10 years of radiology experience (OR=2.462, P=0.047), and AI diagnosis-related training (OR=2.264, P<0.001) were associated with a positive attitude. Higher knowledge scores (OR=5.240, P<0.001), an associate senior professional title (OR=4.267, P=0.026), 5-10 years of radiology experience (OR=0.344, P=0.044), utilizing AI diagnosis (OR=3.643, P=0.001), and engaging in AI diagnosis-related research (OR=6.382, P<0.001) were associated with proactive practice. The SEM showed that knowledge had a direct effect on attitude (ß=0.481, P<0.001) and practice (ß=0.412, P<0.001), and attitude had a direct effect on practice (ß=0.135, P<0.001). Conclusion: Radiologists in southeastern China hold a favorable outlook on AI-assisted medical imaging, showing solid understanding and enthusiasm for its adoption, despite half lacking relevant training. There is a need for more AI diagnosis-related training, an efficient standardized AI database for medical imaging, and active promotion of AI-assisted imaging in clinical practice. Further research with larger sample sizes and more regions is necessary.

7.
Genome Biol ; 25(1): 193, 2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-39030605

RESUMO

BACKGROUND: The mitosis-to-meiosis switch during spermatogenesis requires dynamic changes in gene expression. However, the regulation of meiotic transcriptional and post-transcriptional machinery during this transition remains elusive. RESULTS: We report that methyltransferase-like protein 16 (METTL16), an N6-methyladenosine (m6A) writer, is required for mitosis-to-meiosis transition during spermatogenesis. Germline conditional knockout of Mettl16 in male mice impairs spermatogonial differentiation and meiosis initiation. Mechanistically, METTL16 interacts with splicing factors to regulate the alternative splicing of meiosis-related genes such as Stag3. Ribosome profiling reveals that the translation efficiency of many meiotic genes is dysregulated in METTL16-deficient testes. m6A-sequencing shows that ablation of METTL16 causes upregulation of the m6A-enriched transcripts and downregulation of the m6A-depleted transcripts, similar to Meioc and/or Ythdc2 mutants. Further in vivo and in vitro experiments demonstrate that the methyltransferase activity site (PP185-186AA) of METTL16 is necessary for spermatogenesis. CONCLUSIONS: Our findings support a molecular model wherein the m6A writer METTL16-mediated alternative splicing and translation efficiency regulation are required to control the mitosis-to-meiosis germ cell fate decision in mice, with implications for understanding meiosis-related male fertility disorders.


Assuntos
Adenosina , Processamento Alternativo , Meiose , Metiltransferases , Espermatogênese , Animais , Espermatogênese/genética , Masculino , Metiltransferases/metabolismo , Metiltransferases/genética , Camundongos , Adenosina/análogos & derivados , Adenosina/metabolismo , Biossíntese de Proteínas , Camundongos Knockout , Mitose , Testículo/metabolismo , Espermatogônias/metabolismo
8.
Exp Lung Res ; 50(1): 136-145, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39033404

RESUMO

Background: Macrophages constitute the main part of infiltrating immune cells in Malignant pleural mesothelioma (MPM) and abnormally high ratios of M2 macrophages are present in both pleural effusion and tissue samples of MPM patients. Whether MPM cells affect formation of M2 macrophages is poorly understood. In this study, we focused on identification of MPM-cells-derived soluble factors with M2-promoting effects. Methods: Media of malignant pleural mesothelioma cells were collected and soluble factors affecting macrophages were analyzed by mass spectrometry. TGF-ß receptor inhibitor SB431542 was used as the entry point to explore the downstream mechanism of action by qRT-PCR, WB and immunofluorescence. Results: The serum-free culture media collected from the human MPM cells Meso1 and Meso2 significantly enhanced expression of the M2 signature molecules including IL-10, TGF-ß and CD206 in the human macrophages THP-1, while the culture medium of the human MPM cells H2452 did not show such M2-promoting effects. Analysis of proteins by mass spectrometry and ELISA suggested that Leucine rich α2 glycoprotein 1(LRG1) was a potential candidate. LRG1 time- and dose-dependently increased expression of the M2 signature molecules, confirming its M2-promoting effects. Furthermore, LRG1's M2-promoting effects were reduced by the TGF-ß receptor inhibitor SB431542, and LRG1 increased phosphorylation of Smad2, indicating that M2-promoting effects of LRG1 were via the TGF-ß receptor/Smad2 signaling pathway. Conclusions: Our results provide a potential M2-promoting new member, LRG1, which contributes to the immune escape of MPM via the TGF-ß receptor/Smad2 signaling pathway.


Assuntos
Macrófagos , Mesotelioma Maligno , Humanos , Macrófagos/metabolismo , Macrófagos/efeitos dos fármacos , Mesotelioma Maligno/metabolismo , Mesotelioma Maligno/tratamento farmacológico , Glicoproteínas/metabolismo , Glicoproteínas/farmacologia , Linhagem Celular Tumoral , Neoplasias Pleurais/metabolismo , Neoplasias Pleurais/patologia , Fenótipo , Proteína Smad2/metabolismo , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Transdução de Sinais , Fator de Crescimento Transformador beta/metabolismo , Interleucina-10/metabolismo , Benzamidas , Dioxóis
9.
J Pineal Res ; 76(5): e12991, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39039850

RESUMO

Although rapid progression and a poor prognosis in influenza A virus (IAV) infection-induced acute exacerbation of chronic obstructive pulmonary disease (AECOPD) are frequently associated with metabolic energy disorders, the underlying mechanisms and rescue strategies remain unknown. We herein demonstrated that the level of resting energy expenditure increased significantly in IAV-induced AECOPD patients and that cellular energy exhaustion emerged earlier and more significantly in IAV-infected primary COPD bronchial epithelial (pDHBE) cells. The differentially expressed genes were enriched in the oxidative phosphorylation (OXPHOS) pathway; additionally, we consistently uncovered much earlier ATP exhaustion, more severe mitochondrial structural destruction and dysfunction, and OXPHOS impairment in IAV-inoculated pDHBE cells, and these changes were rescued by melatonin. The level of OMA1-dependent cleavage of OPA1 in the mitochondrial inner membrane and the shift in energy metabolism from OXPHOS to glycolysis were significantly increased in IAV-infected pDHBE cells; however, these changes were rescued by OMA1-siRNA or melatonin further treatment. Collectively, our data revealed that melatonin rescued IAV-induced cellular energy exhaustion via OMA1-OPA1-S to improve the clinical prognosis in COPD. This treatment may serve as a potential therapeutic agent for patients in which AECOPD is induced by IAV.


Assuntos
Metabolismo Energético , GTP Fosfo-Hidrolases , Vírus da Influenza A , Melatonina , Doença Pulmonar Obstrutiva Crônica , Humanos , Metabolismo Energético/efeitos dos fármacos , GTP Fosfo-Hidrolases/metabolismo , GTP Fosfo-Hidrolases/genética , Vírus da Influenza A/efeitos dos fármacos , Influenza Humana/metabolismo , Influenza Humana/tratamento farmacológico , Melatonina/farmacologia , Metaloendopeptidases , Fosforilação Oxidativa/efeitos dos fármacos , Doença Pulmonar Obstrutiva Crônica/metabolismo , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico
10.
PLoS One ; 19(7): e0306752, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38968285

RESUMO

PURPOSE: To analyze the causal relationship between 486 human serum metabolites and the active tuberculosis (ATB) in European population. METHODS: In this study, the causal relationship between human serum metabolites and the ATB was analyzed by integrating the genome-wide association study (GWAS). The 486 human serum metabolites were used as the exposure variable, three different ATB GWAS databases in the European population were set as outcome variables, and single nucleotide polymorphisms were used as instrumental variables for Mendelian Randomization. The inverse variance weighting was estimated causality, the MR-Egger intercept to estimate horizontal pleiotropy, and the combined effects of metabolites were also considered in the meta-analysis. Furthermore, the web-based MetaboAnalyst 6.0 was engaged for enrichment pathway analysis, while R (version 4.3.2) software and Review Manager 5.3 were employed for statistical analysis. RESULTS: A total of 21, 17, and 19 metabolites strongly associated with ATB were found in the three databases after preliminary screening (P < 0.05). The intersecting metabolites across these databases included tryptophan, betaine, 1-linoleoylglycerol (1-monolinolein) (1-LG), 1-eicosatrienoylglycerophosphocholine, and oleoylcarnitine. Among them, betaine (I2 = 24%, P = 0.27) and 1-LG (I2 = 0%, P = 0.62) showed the lowest heterogeneity among the different ATB databases. In addition, the metabolic pathways of phosphatidylethanolamine biosynthesis (P = 0.0068), methionine metabolism (P = 0.0089), betaine metabolism (P = 0.0205) and oxidation of branched-chain fatty acids (P = 0.0309) were also associated with ATB. CONCLUSION: Betaine and 1-LG may be biomarkers or auxiliary diagnostic tools for ATB. They may provide new guidance for medical practice in the early diagnosis and surveillance of ATB. In addition, by interfering with phosphatidylethanolamine biosynthesis, methionine metabolism, betaine metabolism, oxidation of branched-chain fatty acids, and other pathways, it is helpful to develop new anti-tuberculosis drugs and explore the virulence or pathogenesis of ATB at a deeper level, providing an effective reference for future studies.


Assuntos
Betaína , Estudo de Associação Genômica Ampla , Polimorfismo de Nucleotídeo Único , Tuberculose , Humanos , Betaína/sangue , Betaína/metabolismo , Tuberculose/genética , Tuberculose/sangue , Tuberculose/metabolismo , Europa (Continente) , População Branca/genética , Metabolômica/métodos
11.
Microbiome ; 12(1): 128, 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-39020382

RESUMO

BACKGROUND: Spring viremia of carp virus (SVCV) infects a wide range of fish species and causes high mortality rates in aquaculture. This viral infection is characterized by seasonal outbreaks that are temperature-dependent. However, the specific mechanism behind temperature-dependent SVCV infectivity and pathogenicity remains unclear. Given the high sensitivity of the composition of intestinal microbiota to temperature changes, it would be interesting to investigate if the intestinal microbiota of fish could play a role in modulating the infectivity of SVCV at different temperatures. RESULTS: Our study found that significantly higher infectivity and pathogenicity of SVCV infection in zebrafish occurred at relatively lower temperature. Comparative analysis of the intestinal microbiota in zebrafish exposed to high- and low-temperature conditions revealed that temperature influenced the abundance and diversity of the intestinal microbiota in zebrafish. A significantly higher abundance of Parabacteroides distasonis and its metabolite secondary bile acid (deoxycholic acid, DCA) was detected in the intestine of zebrafish exposed to high temperature. Both colonization of Parabacteroides distasonis and feeding of DCA to zebrafish at low temperature significantly reduced the mortality caused by SVCV. An in vitro assay demonstrated that DCA could inhibit the assembly and release of SVCV. Notably, DCA also showed an inhibitory effect on the infectious hematopoietic necrosis virus, another Rhabdoviridae member known to be more infectious at low temperature. CONCLUSIONS: This study provides evidence that temperature can be an important factor to influence the composition of intestinal microbiota in zebrafish, consequently impacting the infectivity and pathogenicity of SVCV. The findings highlight the enrichment of Parabacteroides distasonis and its derivative, DCA, in the intestines of zebrafish raised at high temperature, and they possess an important role in preventing the infection of SVCV and other Rhabdoviridae members in host fish. Video Abstract.


Assuntos
Bacteroidetes , Doenças dos Peixes , Microbioma Gastrointestinal , Infecções por Rhabdoviridae , Rhabdoviridae , Temperatura , Peixe-Zebra , Animais , Doenças dos Peixes/microbiologia , Doenças dos Peixes/virologia , Infecções por Rhabdoviridae/virologia , Rhabdoviridae/fisiologia , Rhabdoviridae/patogenicidade , Bacteroidetes/patogenicidade , Água , Vírus da Necrose Hematopoética Infecciosa/patogenicidade
12.
Artigo em Inglês | MEDLINE | ID: mdl-38871558

RESUMO

BACKGROUND: Talquetamab is a bispecific antibody targeting the multiple myeloma-associated antigen G protein-coupled receptor family C group 5 member D (GPRC5D). In the phase 1/2 MonumenTAL-1 trial (NCT03399799/NCT04634552), overall responses rates were > 71% in patients with triple-class exposed relapsed/refractory multiple myeloma (RRMM). Due to the distribution of the target antigen, a unique pattern of GPRC5D-associated adverse events (AEs) was observed, together with T-cell redirection-associated AEs. Management strategies for talquetamab-associated AEs are described. DISCUSSION: GPRC5D-associated AEs included dermatologic (rash, nonrash, and nail toxicities) and oral AEs (dysgeusia, dysphagia, and dry mouth). The incidence of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were consistent with other T-cell redirection therapies. The incidence of high-grade infections was lower than observed with B-cell maturation antigen-targeting bispecific antibodies, with less frequent use of intravenous immunoglobulin required. GPRC5D-associated AEs were mostly low grade and led to few discontinuations. Skin toxicities were managed with emollients, topical corticosteroids, and oral corticosteroids (for high-grade, persistent, or AEs that progress). Nail toxicities were commonly managed with emollients. Based on investigator experience, dose modification may be effective for controlling oral events. Observation for potential weight changes is required. Infections were managed per standard of care. CRS and ICANS were effectively managed, consistent with other trials of T-cell redirection therapies. CONCLUSION: Although talquetamab had a distinct safety profile, AEs were considered clinically manageable and mostly low grade. With appropriate education and support, health care practitioners can ensure patients with RRMM maintain quality of life and treatment adherence.

13.
Aging Cell ; : e14196, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38845183

RESUMO

Stroke is a major threat to life and health in modern society, especially in the aging population. Stroke may cause sudden death or severe sequela-like hemiplegia. Although computed tomography (CT) and magnetic resonance imaging (MRI) are standard diagnosis methods, and artificial intelligence models have been built based on these images, shortage in medical resources and the time and cost of CT/MRI imaging hamper fast detection, thus increasing the severity of stroke. Here, we developed a convolutional neural network model by integrating four networks, Xception, ResNet50, VGG19, and EfficientNetb1, to recognize stroke based on 2D facial images with a cross-validation area under curve (AUC) of 0.91 within the training set of 185 acute ischemic stroke patients and 551 age- and sex-matched controls, and AUC of 0.82 in an independent data set regardless of age and sex. The model computed stroke probability was quantitatively associated with facial features, various clinical parameters of blood clotting indicators and leukocyte counts, and, more importantly, stroke incidence in the near future. Our real-time facial image artificial intelligence model can be used to rapidly screen and prediagnose stroke before CT scanning, thus meeting the urgent need in emergency clinics, potentially translatable to routine monitoring.

14.
Artigo em Inglês | MEDLINE | ID: mdl-38848032

RESUMO

PURPOSE: In pathology images, different stains highlight different glomerular structures, so a supervised deep learning-based glomerular instance segmentation model trained on individual stains performs poorly on other stains. However, it is difficult to obtain a training set with multiple stains because the labeling of pathology images is very time-consuming and tedious. Therefore, in this paper, we proposed an unsupervised stain augmentation-based method for segmentation of glomerular instances. METHODS: In this study, we successfully realized the conversion between different staining methods such as PAS, MT and PASM by contrastive unpaired translation (CUT), thus improving the staining diversity of the training set. Moreover, we replaced the backbone of mask R-CNN with swin transformer to further improve the efficiency of feature extraction and thus achieve better performance in instance segmentation task. RESULTS: To validate the method presented in this paper, we constructed a dataset from 216 WSIs of the three stains in this study. After conducting in-depth experiments, we verified that the instance segmentation method based on stain augmentation outperforms existing methods across all metrics for PAS, PASM, and MT stains. Furthermore, ablation experiments are performed in this paper to further demonstrate the effectiveness of the proposed module. CONCLUSION: This study successfully demonstrated the potential of unsupervised stain augmentation to improve glomerular segmentation in pathology analysis. Future research could extend this approach to other complex segmentation tasks in the pathology image domain to further explore the potential of applying stain augmentation techniques in different domains of pathology image analysis.

15.
J Nanobiotechnology ; 22(1): 314, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38840113

RESUMO

Osteoporosis is the most common bone metabolic disease that affects the health of middle-aged and elderly people, which is hallmarked by imbalanced bone remodeling and a deteriorating immune microenvironment. Magnesium and calcium are pivotal matrix components that participate in the bone formation process, especially in the immune microenvironment regulation and bone remodeling stages. Nevertheless, how to potently deliver magnesium and calcium to bone tissue remains a challenge. Here, we have constructed a multifunctional nanoplatform composed of calcium-based upconversion nanoparticles and magnesium organic frameworks (CM-NH2-PAA-Ald, denoted as CMPA), which features bone-targeting and pH-responsive properties, effectively regulating the inflammatory microenvironment and promoting the coordination of osteogenic functions for treating osteoporosis. The nanoplatform can efficaciously target bone tissue and gradually degrade in response to the acidic microenvironment of osteoporosis to release magnesium and calcium ions. This study validates that CMPA possessing favorable biocompatibility can suppress inflammation and facilitate osteogenesis to treat osteoporosis. Importantly, high-throughput sequencing results demonstrate that the nanoplatform exerts a good inflammatory regulation effect through inhibition of the nuclear factor kappa-B signaling pathway, thereby normalizing the osteoporotic microenvironment. This collaborative therapeutic strategy that focuses on improving bone microenvironment and promoting osteogenesis provides new insight for the treatment of metabolic diseases such as osteoporosis.


Assuntos
Cálcio , Magnésio , Nanopartículas , Osteogênese , Osteoporose , Osteogênese/efeitos dos fármacos , Osteoporose/tratamento farmacológico , Magnésio/farmacologia , Magnésio/química , Cálcio/metabolismo , Animais , Nanopartículas/química , Camundongos , Inflamação/tratamento farmacológico , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/metabolismo , Humanos , Microambiente Celular/efeitos dos fármacos , Feminino , NF-kappa B/metabolismo
16.
World J Otorhinolaryngol Head Neck Surg ; 10(2): 113-120, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38855290

RESUMO

Objective: This cross-sectional study aimed to determine the epidemiology of olfactory and gustatory dysfunctions related to COVID-19 in China. Methods: This study was conducted by 45 tertiary Grade-A hospitals in China. Online and offline questionnaire data were obtained from patients infected with COVID-19 between December 28, 2022, and February 21, 2023. The collected information included basic demographics, medical history, smoking and drinking history, vaccination history, changes in olfactory and gustatory functions before and after infection, and other postinfection symptoms, as well as the duration and improvement status of olfactory and gustatory disorders. Results: Complete questionnaires were obtained from 35,566 subjects. The overall incidence of olfactory and taste dysfunction was 67.75%. Being female or being a cigarette smoker increased the likelihood of developing olfactory and taste dysfunction. Having received four doses of the vaccine or having good oral health or being a alcohol drinker decreased the risk of such dysfunction. Before infection, the average olfactory and taste VAS scores were 8.41 and 8.51, respectively; after infection, they decreased to 3.69 and 4.29 and recovered to 5.83 and 6.55 by the time of the survey. The median duration of dysosmia and dysgeusia was 15 and 12 days, respectively, with 0.5% of patients having symptoms lasting for more than 28 days. The overall self-reported improvement rate was 59.16%. Recovery was higher in males, never smokers, those who received two or three vaccine doses, and those that had never experienced dental health issues, or chronic accompanying symptoms. Conclusions: The incidence of dysosmia and dysgeusia following infection with the SARS-CoV-2 virus is high in China. Incidence and prognosis are influenced by several factors, including sex, SARS-CoV-2 vaccination, history of head-facial trauma, nasal and oral health status, smoking and drinking history, and the persistence of accompanying symptoms.

17.
Methods Mol Biol ; 2825: 113-124, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38913305

RESUMO

Optical genome mapping (OGM) has generated excitement following decades of research and development. Now, commercially available technical platforms have been used to compare various other cytogenetic and cytogenomic technologies, including karyotype, microarrays, and DNA sequencing, with impressive results. In this chapter, using OGM as a case study, we advocate for a new trend in future cytogenomics, emphasizing the power of machine automation to deliver higher-quality cytogenomic data. By briefly discussing OGM, along with its major advantages and limitations, we underscore the importance of karyotype-based genomic research, from both a theoretical framework and a new technology perspective. We also call for the encouragement of further technological platform development for the future of cytogenetics and cytogenomics.


Assuntos
Mapeamento Cromossômico , Genômica , Humanos , Genômica/métodos , Mapeamento Cromossômico/métodos
18.
Methods Mol Biol ; 2825: 3-37, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38913301

RESUMO

The promises of the cancer genome sequencing project, combined with various -omics technologies, have raised questions about the importance of cancer cytogenetic analyses. It is suggested that DNA sequencing provides high resolution, speed, and automation, potentially replacing cytogenetic testing. We disagree with this reductionist prediction. On the contrary, various sequencing projects have unexpectedly challenged gene theory and highlighted the importance of the genome or karyotype in organizing gene network interactions. Consequently, profiling the karyotype can be more meaningful than solely profiling gene mutations, especially in cancer where karyotype alterations mediate cellular macroevolution dominance. In this chapter, recent studies that illustrate the ultimate importance of karyotype in cancer genomics and evolution are briefly reviewed. In particular, the long-ignored non-clonal chromosome aberrations or NCCAs are linked to genome or chromosome instability, genome chaos is linked to genome reorganization under cellular crisis, and the two-phased cancer evolution reconciles the relationship between genome alteration-mediated punctuated macroevolution and gene mutation-mediated stepwise microevolution. By further synthesizing, the concept of karyotype coding is discussed in the context of information management. Altogether, we call for a new era of cancer cytogenetics and cytogenomics, where an array of technical frontiers can be explored further, which is crucial for both basic research and clinical implications in the cancer field.


Assuntos
Aberrações Cromossômicas , Genômica , Neoplasias , Humanos , Neoplasias/genética , Genômica/métodos , Análise Citogenética/métodos , Citogenética/métodos , Cariotipagem/métodos , Mutação
19.
Methods Mol Biol ; 2825: 263-280, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38913315

RESUMO

Karyotype coding, which encompasses the complete chromosome sets and their topological genomic relationships within a given species, encodes system-level information that organizes and preserves genes' function, and determines the macroevolution of cancer. This new recognition emphasizes the crucial role of karyotype characterization in cancer research. To advance this cancer cytogenetic/cytogenomic concept and its platforms, this study outlines protocols for monitoring the karyotype landscape during treatment-induced rapid drug resistance in cancer. It emphasizes four key perspectives: combinational analyses of phenotype and karyotype, a focus on the entire evolutionary process through longitudinal analysis, a comparison of whole landscape dynamics by including various types of NCCAs (including genome chaos), and the use of the same process to prioritize different genomic scales. This protocol holds promise for studying numerous evolutionary aspects of cancers, and it further enhances the power of karyotype analysis in cancer research.


Assuntos
Resistencia a Medicamentos Antineoplásicos , Cariótipo , Cariotipagem , Neoplasias , Humanos , Resistencia a Medicamentos Antineoplásicos/genética , Neoplasias/genética , Neoplasias/tratamento farmacológico , Cariotipagem/métodos , Antineoplásicos/uso terapêutico , Antineoplásicos/farmacologia , Evolução Molecular , Fenótipo
20.
Anal Chem ; 96(25): 10283-10293, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38864304

RESUMO

Single-nucleotide polymorphism (SNP) is widely used in the study of disease-related genes and in the genetic study of animal and plant strains. Therefore, SNP detection is crucial for biomedical diagnosis and treatment as well as for molecular design breeding of animals and plants. In this regard, this article describes a novel technique for detecting SNP using flap endonuclease 1 (FEN 1) as a specific recognition element and catalytic hairpin assembly (CHA) cascade reaction as a signal amplification strategy. The mutant target (MT) was hybridized with a biotin-modified upstream probe and hairpin-type downstream probe (DP) to form a specific three-base overlapping structure. Then, FEN 1 was employed for three-base overlapping structure-specific recognition, namely, the precise SNP site identification and the 5' flap of DP dissociation. After dissociation, the hybridized probes were magnetically separated by a streptavidin-biotin complex. Especially, the ability to establish such a hairpin-type DP provided a powerful tool that could be used to hide the cut sequence (CS) and avoid false-positive signals. The cleaved CS initiated the CHA reaction and allowed superior fluorescence signal generation. Owing to the high specificity of FEN 1 for single base recognition, only the MT could be distinguished from the wild-type target and mismatched DNA. Owing to the dual signal amplification, as low as 0.36 fM MT and 1% mutation abundance from the mixtures could be detected, respectively. Furthermore, it could accurately identify SNPs from human cancer cells, as well as soybean leaf genome extracts. This strategy paves the way for the development of more precise and sensitive tools for diagnosing early onset diseases as well as molecular design breeding tools.


Assuntos
Endonucleases Flap , Polimorfismo de Nucleotídeo Único , Endonucleases Flap/genética , Endonucleases Flap/metabolismo , Humanos , Técnicas de Amplificação de Ácido Nucleico/métodos , Hibridização de Ácido Nucleico
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