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1.
Adv Sci (Weinh) ; : e2402962, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38951958

RESUMO

The ultrafine cellular structure promotes the extraordinary mechanical performance of metals manufactured by laser powder-bed-fusion (L-PBF). An in-depth understanding of the mechanisms governing the thermal stability of such structures is crucial for designing reliable L-PBF components for high-temperature applications. Here, characterizations and 3D discrete dislocation dynamics simulations are performed to comprehensively understand the evolution of cellular structures in 316L stainless steel during annealing. The dominance of screw-type dislocation dipoles in the dislocation cells is reported. However, the majority of dislocations in sub-grain boundaries (SGBs) are geometrically necessary dislocations (GNDs) with varying types. The disparity in dislocation types can be attributed to the variation in local stacking fault energy (SFE) arising from chemical heterogeneity. The presence of screw-type dislocations facilitates the unpinning of dislocations from dislocation cells/SGBs, resulting in a high dislocation mobility. In contrast, the migration of SGBs with dominating edge-type GNDs requires collaborative motion of dislocations, leading to a sluggish migration rate and an enhanced thermal stability. This work emphasizes the significant role of dislocation type in the thermal stability of cellular structures. Furthermore, it sheds light on how to locally tune dislocation structures with desired dislocation types by adjusting local chemistry-dependent SFE and heat treatment.

2.
Commun Biol ; 7(1): 770, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38918569

RESUMO

Cancer is an evolutionary process shaped by selective pressure from the microenvironments. However, recent studies reveal that certain tumors undergo neutral evolution where there is no detectable fitness difference amongst the cells following malignant transformation. Here, through computational modeling, we demonstrate that negative frequency-dependent selection (or NFDS), where the immune response against cancer cells depends on the clonality of neoantigens, can lead to an immunogenic landscape that is highly similar to neutral evolution. Crucially, NFDS promotes high antigenic heterogeneity and early immune evasion in hypermutable tumors, leading to poor responses to immune checkpoint blockade (ICB) therapy. Our model also reveals that NFDS is characterized by a negative association between average clonality and total burden of neoantigens. Indeed, this unique feature of NFDS is common in the whole-exome sequencing (WES) datasets (357 tumor samples from 275 patients) from four melanoma cohorts with ICB therapy and a non-small cell lung cancer (NSCLC) WES dataset (327 tumor samples from 100 patients). Altogether, our study provides quantitative evidence supporting the theory of NFDS in cancer, explaining the high prevalence of neutral-looking tumors. These findings also highlight the critical role of frequency-dependent selection in devising more efficient and predictive immunotherapies.


Assuntos
Antígenos de Neoplasias , Imunoterapia , Evasão Tumoral , Humanos , Antígenos de Neoplasias/imunologia , Antígenos de Neoplasias/genética , Neoplasias/imunologia , Neoplasias/terapia , Neoplasias/genética , Neoplasias/tratamento farmacológico , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/terapia , Melanoma/imunologia , Melanoma/terapia , Melanoma/genética , Melanoma/tratamento farmacológico , Microambiente Tumoral/imunologia , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/terapia
3.
Fish Shellfish Immunol ; 151: 109696, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38871144

RESUMO

The hepatopancreas is the biggest digestive organ in Amphioctopus fangsiao (A. fangsiao), but also undertakes critical functions like detoxification and immune defense. Generally, pathogenic bacteria or endotoxin from the gut microbiota would be arrested and detoxified in the hepatopancreas, which could be accompanied by the inevitable immune responses. In recent years, studies related to cephalopods immune have been increasing, but the molecular mechanisms associated with the hepatopancreatic immunity are still unclear. In this study, lipopolysaccharide (LPS), a major component of the cell wall of Gram-negative bacteria, was used for imitating bacteria infection to stimulate the hepatopancreas of A. fangsiao. To investigate the immune process happened in A. fangsiao hepatopancreas, we performed transcriptome analysis of hepatopancreas tissue after LPS injection, and identified 2615 and 1943 differentially expressed genes (DEGs) at 6 and 24 h post-injection, respectively. GO and KEGG enrichment analysis showed that these DEGs were mainly involved in immune-related biological processes and signaling pathways, including ECM-receptor interaction signaling pathway, Phagosome signaling pathway, Lysosome signaling pathway, and JAK-STAT signaling pathways. The function relationships between these DEGs were further analyzed through protein-protein interaction (PPI) networks. It was found that Mtor, Mapk14 and Atm were the three top interacting DEGs under LPS stimulation. Finally, 15 hub genes involving multiple KEGG signaling pathways and PPI relationships were selected for qRT-PCR validation. In this study, for the first time we explored the molecular mechanisms associated with hepatopancreatic immunity in A. fangsiao using a PPI networks approach, and provided new insights for understanding hepatopancreatic immunity in A. fangsiao.

4.
Animals (Basel) ; 14(11)2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38891754

RESUMO

Over the years, oysters have faced recurring mass mortality issues during the summer breeding season, with Vibrio infection emerging as a significant contributing factor. Tubules of gill filaments were confirmed to be in the hematopoietic position in Crassostrea gigas, which produce hemocytes with immune defense capabilities. Additionally, the epithelial cells of oyster gills produce immune effectors to defend against pathogens. In light of this, we performed a transcriptome analysis of gill tissues obtained from C. gigas infected with Vibrio alginolyticus for 12 h and 48 h. Through this analysis, we identified 1024 differentially expressed genes (DEGs) at 12 h post-injection and 1079 DEGs at 48 h post-injection. Enrichment analysis of these DEGs revealed a significant association with immune-related Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. To further investigate the immune response, we constructed a protein-protein interaction (PPI) network using the DEGs enriched in immune-associated KEGG pathways. This network provided insights into the interactions and relationships among these genes, shedding light on the underlying mechanisms of the innate immune defense mechanism in oyster gills. To ensure the accuracy of our findings, we validated 16 key genes using quantitative RT-PCR. Overall, this study represents the first exploration of the innate immune defense mechanism in oyster gills using a PPI network approach. The findings provide valuable insights for future research on oyster pathogen control and the development of oysters with enhanced antimicrobial resistance.

5.
Molecules ; 29(11)2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38893545

RESUMO

Tetraploid oysters are artificially produced oysters that do not exist in nature. The successful breeding of 100% triploid oysters resolved the difficulties of traditional drug-induced triploids, such as the presence of drug residues and a low triploid induction rate. However, little is known concerning the biochemical composition and nutrient contents of such tetraploids. Therefore, we investigated compositional differences among diploid, triploid, and tetraploid Crassostrea gigas as well as between males and females of diploids and tetraploids. The findings indicated that glycogen, EPA, ∑PUFA, and omega-3 contents were significantly higher in triploid oysters than in diploids or tetraploids; tetraploid oysters had a significantly higher protein content, C14:0, essential amino acid, and flavor-presenting amino acid contents than diploids or triploids. For both diploid and tetraploids, females had significantly higher levels of glutamate, methionine, and phenylalanine than males but lower levels of glycine and alanine. In addition, female oysters had significantly more EPA, DHA, omega-3, and total fatty acids, a result that may be due to the fact that gonadal development in male oysters requires more energy to sustain growth, consumes greater amounts of nutrients, and accumulates more proteins. With these results, important information is provided on the production of C. gigas, as well as on the basis and backing for the genetic breeding of oysters.


Assuntos
Aminoácidos , Crassostrea , Diploide , Ácidos Graxos , Tetraploidia , Triploidia , Animais , Crassostrea/genética , Crassostrea/metabolismo , Aminoácidos/metabolismo , Ácidos Graxos/metabolismo , Ácidos Graxos/análise , Feminino , Masculino
6.
Int J Mol Sci ; 25(9)2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38731970

RESUMO

Malaria is a severe disease that presents a significant threat to human health. As resistance to current drugs continues to increase, there is an urgent need for new antimalarial medications. Aminoacyl-tRNA synthetases (aaRSs) represent promising targets for drug development. In this study, we identified Plasmodium falciparum tyrosyl-tRNA synthetase (PfTyrRS) as a potential target for antimalarial drug development through a comparative analysis of the amino acid sequences and three-dimensional structures of human and plasmodium TyrRS, with particular emphasis on differences in key amino acids at the aminoacylation site. A total of 2141 bioactive compounds were screened using a high-throughput thermal shift assay (TSA). Okanin, known as an inhibitor of LPS-induced TLR4 expression, exhibited potent inhibitory activity against PfTyrRS, while showing limited inhibition of human TyrRS. Furthermore, bio-layer interferometry (BLI) confirmed the high affinity of okanin for PfTyrRS. Molecular dynamics (MD) simulations highlighted the stable conformation of okanin within PfTyrRS and its sustained binding to the enzyme. A molecular docking analysis revealed that okanin binds to both the tyrosine and partial ATP binding sites of the enzyme, preventing substrate binding. In addition, the compound inhibited the production of Plasmodium falciparum in the blood stage and had little cytotoxicity. Thus, okanin is a promising lead compound for the treatment of malaria caused by P. falciparum.


Assuntos
Antimaláricos , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Plasmodium falciparum , Tirosina-tRNA Ligase , Plasmodium falciparum/efeitos dos fármacos , Plasmodium falciparum/enzimologia , Tirosina-tRNA Ligase/antagonistas & inibidores , Tirosina-tRNA Ligase/metabolismo , Humanos , Antimaláricos/farmacologia , Antimaláricos/química , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/química , Sítios de Ligação , Ligação Proteica , Animais , Malária Falciparum/tratamento farmacológico , Malária Falciparum/parasitologia
8.
J Pharm Anal ; 14(4): 100901, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38665223

RESUMO

The density and composition of lymphocytes infiltrating colon tumors serve as predictive factors for the clinical outcome of colon cancer. Our previous studies highlighted the potent anti-cancer properties of the principal compounds found in Garcinia yunnanensis (YTE-17), attributing these effects to the regulation of multiple signaling pathways. However, knowledge regarding the mechanism and effect of YTE-17 in the prevention of colorectal cancer is limited. In this study, we conducted isobaric tags for relative and absolute quantification (iTRAQ) analysis on intestinal epithelial cells (IECs) exposed YTE-17, both in vitro and invivo, revealing a significant inhibition of the Wnt family member 5a (Wnt5a)/c-Jun N-terminal kinase (JNK) signaling pathway. Subsequently, we elucidated the influence and mechanism of YTE-17 on the tumor microenvironment (TME), specifically focusing on macrophage-mediated T helper 17 (Th17) cell induction in a colitis-associated cancer (CAC) model with Wnt5a deletion. Additionally, we performed the single-cell RNA sequencing (scRNA-seq) on the colonic tissue from the Wnt5a-deleted CAC model to characterize the composition, lineage, and functional status of immune mesenchymal cells during different stages of colorectal cancer (CRC) progression. Remarkably, our findings demonstrate a significant reduction in M2 macrophage polarization and Th17 cell phenotype upon treatment with YTE-17, leading to the restoration of regulatory T (Treg)/Th17 cell balance in azoxymethane (AOM)/dextran sodium sulfate (DSS) model. Furthermore, we also confirmed that YTE-17 effectively inhibited the glycolysis of Th17 cells in both direct and indirect co-culture systems with M2 macrophages. Notably, our study shed light on potential mechanisms linking the non-canonical Wnt5a/JNK signaling pathway and well-established canonical ß-catenin oncogenic pathway in vivo. Specifically, we proposed that Wnt5a/JNK signaling activity in IECs promotes the development of cancer stem cells with ß-catenin activity within the TME, involving macrophages and T cells. In summary, our study undergoes the potential of YTE-17 as a preventive strategy against CRC development by addressing the imbalance with the immune microenvironment, thereby mitigating the risk of malignancies.

9.
J Orthop Translat ; 45: 168-177, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38549808

RESUMO

Background: Recently, the osteogenic potential of Adiponectin-labeled adipogenic lineage progenitors (Adipoq-lineage progenitors) in bone marrow has been observed to support bone maintenance and repair. However, little is known about the function of Schnurri-3 (SHN3, also known as HIVEP3) in other mesenchymal lineage cells, apart from its negative regulation of bone formation on osteoblasts. Method: In this study, we used single-cell RNA sequencing (scRNA-seq) profiling to demonstrate that Adipoq-lineage progenitors express higher levels of Shn3 compared to other mesenchymal cell populations in mice and humans. To investigate the role of SHN3 in Adipoq-lineage progenitors, we generated a murine model specifically harboring a Shn3-deficient allele in Adipoq-expressing cells. Information of mice body weight was collected weekly to generate body weight curve. Bone phenotype was analyzed using micro-CT and histomorphometric studies. To eliminate the role of peripheral adipose tissue on bone, we collected adipose wet weight, performed intraperitoneal glucose tolerance tests and intraperitoneal insulin tolerance tests, and conducted a fat-transplantation study. Osteoblast and osteoclast functions were assessed through toluidine blue staining and TRAP staining, respectively. We further investigated the effect of Shn3 depletion on the differentiation of Adipoq-lineage progenitors through immunostaining and in vitro differentiation assays. Finally, we evaluated whether Shn3 deficiency in Adipoq-lineage progenitors affects the fracture healing process by generating bi-cortical femoral fracture models. Results: Depletion of Shn3 in Adipoq-lineage progenitors resulted in a significant increase in trabecular bone mass and bone formation in vivo, without disrupting whole-body energy metabolism and skeletal development. Consistent with these findings, both cell-lineage tracing and functional assays revealed that Shn3 ablation effectively shifted the cell fate of Adipoq-lineage progenitors towards an osteogenic phenotype in the bone marrow. Furthermore, in vivo studies demonstrated that the lack of Shn3 in Adipoq-lineage progenitors also enhanced bone fracture healing under pathological conditions. Conclusion: Overall, our findings provide a novel strategy for targeting the osteoanabolic potential of bone marrow Adipoq-lineage progenitors as a potential treatment for bone loss-related disorders. Translational potential of this article: We have identified a novel gene target that directs the cell fate of a previously identified non-osteogenic cell population under physiological conditions. This study not only expands the therapeutic value of Shn3 ablation in treating osteoporotic or traumatic bone diseases but also provides new insights into the contribution of bone marrow Adipoq-lineage progenitors to osteogenesis. Thus, this article further supports Shn3 silencing as a valuable approach to treat osteopenia and accelerate fracture healing (see graphical abstract).

10.
Adv Sci (Weinh) ; 11(18): e2303752, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38311573

RESUMO

Loss of refreshment in nucleus pulposus (NP) cellularity leads to intervertebral disc (IVD) degeneration. Nevertheless, the cellular sequence of NP cell differentiation remains unclear, although an increasing body of literature has identified markers of NP progenitor cells (NPPCs). Notably, due to their fragility, the physical enrichment of NP-derived cells has limited conventional transcriptomic approaches in multiple studies. To overcome this limitation, a spatially resolved transcriptional atlas of the mouse IVD is generated via the 10x Genomics Visium platform dividing NP spots into two clusters. Based on this, most reported NPPC-markers, including Cathepsin K (Ctsk), are rare and predominantly located within the NP-outer subset. Cell lineage tracing further evidence that a small number of Ctsk-expressing cells generate the entire adult NP tissue. In contrast, Tie2, which has long suggested labeling NPPCs, is actually neither expressed in NP subsets nor labels NPPCs and their descendants in mouse models; consistent with this, an in situ sequencing (ISS) analysis validated the absence of Tie2 in NP tissue. Similarly, no Tie2-cre-mediated labeling of NPPCs is observed in an IVD degenerative mouse model. Altogether, in this study, the first spatial transcriptomic map of the IVD is established, thereby providing a public resource for bone biology.


Assuntos
Núcleo Pulposo , Células-Tronco , Transcriptoma , Animais , Camundongos , Núcleo Pulposo/metabolismo , Núcleo Pulposo/citologia , Células-Tronco/metabolismo , Transcriptoma/genética , Diferenciação Celular/genética , Degeneração do Disco Intervertebral/genética , Degeneração do Disco Intervertebral/metabolismo , Perfilação da Expressão Gênica/métodos , Modelos Animais de Doenças
11.
Toxicol Ind Health ; 40(4): 176-184, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38349948

RESUMO

A rapid and sensitive assessment of the toxicity of oxygenated polycyclic aromatic hydrocarbons (OPAHs), widely distributed persistent organic pollutants in the environment, is crucial for human health. In this study, using high-performance liquid chromatography, the separation and detection of four purines, xanthine (X), guanine (G), adenine (A), and hypoxanthine (HX) in cells were performed. The aim was to evaluate the cytotoxicity of three OPAHs, namely 1,4-benzoquinone (1,4-BQ), 1,2-naphthoquinone (1,2-NQ) and 9,10-phenanthrenequinone (9,10-PQ), with higher environmental concentrations, from the perspective of purine nucleotide metabolism in human skin fibroblast cells (HFF-1). The results revealed that the levels of G and A were low in HFF-1 cells, while the levels of HX and X showed a dose-response relationship with persistent organic pollutants concentration. With increased concentration of the three persistent organic pollutants, the purine metabolism in HFF-1 cells weakened, and the impact of the three persistent organic pollutants on purine metabolism in cells was in the order of 9,10-PQ > 1,4-BQ > 1,2-NQ. This study provided valuable insights into the toxic mechanisms of 1,4-BQ, 1,2-NQ and 9,10-PQ, contributing to the formulation of relevant protective measures and the safeguarding of human health.


Assuntos
Hidrocarbonetos Policíclicos Aromáticos , Humanos , Hidrocarbonetos Policíclicos Aromáticos/toxicidade , Hidrocarbonetos Policíclicos Aromáticos/análise , Poluentes Orgânicos Persistentes , Cromatografia Líquida de Alta Pressão/métodos , Purinas/análise , Fibroblastos/química
12.
Nature ; 626(7998): 411-418, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38297130

RESUMO

Ferroptosis, a form of regulated cell death that is driven by iron-dependent phospholipid peroxidation, has been implicated in multiple diseases, including cancer1-3, degenerative disorders4 and organ ischaemia-reperfusion injury (IRI)5,6. Here, using genome-wide CRISPR-Cas9 screening, we identified that the enzymes involved in distal cholesterol biosynthesis have pivotal yet opposing roles in regulating ferroptosis through dictating the level of 7-dehydrocholesterol (7-DHC)-an intermediate metabolite of distal cholesterol biosynthesis that is synthesized by sterol C5-desaturase (SC5D) and metabolized by 7-DHC reductase (DHCR7) for cholesterol synthesis. We found that the pathway components, including MSMO1, CYP51A1, EBP and SC5D, function as potential suppressors of ferroptosis, whereas DHCR7 functions as a pro-ferroptotic gene. Mechanistically, 7-DHC dictates ferroptosis surveillance by using the conjugated diene to exert its anti-phospholipid autoxidation function and shields plasma and mitochondria membranes from phospholipid autoxidation. Importantly, blocking the biosynthesis of endogenous 7-DHC by pharmacological targeting of EBP induces ferroptosis and inhibits tumour growth, whereas increasing the 7-DHC level by inhibiting DHCR7 effectively promotes cancer metastasis and attenuates the progression of kidney IRI, supporting a critical function of this axis in vivo. In conclusion, our data reveal a role of 7-DHC as a natural anti-ferroptotic metabolite and suggest that pharmacological manipulation of 7-DHC levels is a promising therapeutic strategy for cancer and IRI.


Assuntos
Desidrocolesteróis , Ferroptose , Humanos , Membrana Celular/metabolismo , Colesterol/biossíntese , Colesterol/metabolismo , Sistemas CRISPR-Cas/genética , Desidrocolesteróis/metabolismo , Genoma Humano , Nefropatias/metabolismo , Membranas Mitocondriais/metabolismo , Metástase Neoplásica , Neoplasias/metabolismo , Neoplasias/patologia , Fosfolipídeos/metabolismo , Traumatismo por Reperfusão/metabolismo
13.
Mar Environ Res ; 194: 106330, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38171258

RESUMO

Global temperatures have risen as a result of climate change, and the resulting warmer seawater will exert physiological stresses on many aquatic animals, including Apostichopus japonicus. It has been suggested that the sensitivity of aquatic poikilothermal animals to climate change is closely related to mitochondrial function. Therefore, understanding the interaction between elevated temperature and mitochondrial functioning is key to characterizing organisms' responses to heat stress. However, little is known about the mitochondrial response to heat stress in A. japonicus. In this work, we investigated the morphological and functional changes of A. japonicus mitochondria under three representative temperatures, control temperature (18 °C), aestivation temperature (25 °C) and heat stress temperature (32 °C) temperatures using transmission electron microscopy (TEM) observation of mitochondrial morphology combined with proteomics and metabolomics techniques. The results showed that the mitochondrial morphology of A. japonicus was altered, with decreases in the number of mitochondrial cristae at 25 °C and mitochondrial lysis, fracture, and vacuolization at 32 °C. Proteomic and metabolomic analyses revealed 103 differentially expressed proteins and 161 differential metabolites at 25 °C. At 32 °C, the levels of 214 proteins and 172 metabolites were significantly altered. These proteins and metabolites were involved in the tricarboxylic acid (TCA) cycle, substance transport, membrane potential homeostasis, anti-stress processes, mitochondrial autophagy, and apoptosis. Furthermore, a hypothetical network of proteins and metabolites in A. japonicus mitochondria in response to temperature changes was constructed based on proteomic and metabolomic data. These results suggest that the dynamic regulation of mitochondrial energy metabolism, resistance to oxidative stress, autophagy, apoptosis, and mitochondrial morphology in A. japonicus may play important roles in the response to elevated temperatures. In summary, this study describes the response of A. japonicus mitochondria to temperature changes from the perspectives of morphology, proteins, and metabolites, which provided a better understanding the mechanisms of mitochondrial regulation under environment stress in marine echinoderms.


Assuntos
Stichopus , Animais , Stichopus/metabolismo , Temperatura , Proteômica/métodos , Estresse Fisiológico , Mitocôndrias
14.
PhytoKeys ; 237: 153-160, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38292075

RESUMO

A new species of Orchidaceae, Phalaenopsiszhanhouana, from Xichou County, Yunnan, China, is described and illustrated. The novelty is close to P.taenialis, P.wilsonii, and P.stobartiana, but differs from them by having a distinct, fleshy anterior callus with a deeply lobed apex at the base of the labellum and lateral lobes of labellum reflexed and facing outward.

15.
J Fluoresc ; 34(1): 425-436, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37284963

RESUMO

A novel reagent named 4-(N-methyl-1,3-dioxo-benzoisoquinolin-6-yl-oxy)benzene sulfonyl chloride (MBIOBS-Cl) for the determination of estrogens in food samples by high-performance liquid chromatography (HPLC) with fluorescence detection has been developed. Estrogens could be easily labeled by MBIOBS-Cl in Na2CO3-NaHCO3 buffer solution at pH 10.0. The complete labeling reaction for estrogens could be accomplished within five minutes, the corresponding derivatives exhibited strong fluorescence with the maximum excitation and emission wavelengths at 249 nm and 443 nm, respectively. The derivatization conditions, such as the molar ratio of reagent to estrogens, derivatization time, pH, temperature, and buffers were optimized. Derivatives were sufficiently stable to be efficiently analyzed by HPLC with a reversed-phase Agilent ZORBAX 300SB-C18 column with a good baseline resolution. Excellent linear correlations were obtained for all estrogen derivatives with correlation coefficients greater than 0.9998. Ultrasonic-Assisted extraction was used to optimize the extraction of estrogens from meat samples with a recovery higher than 82%. The detection limits (LOD, S/N = 3) of the method ranged from 0.95 to 3.3 µg· kg-1. The established method, which is fast, simple, inexpensive, and environment friendly, can be successfully applied for the detection of four steroidal estrogens from meat samples with little matrix interference.


Assuntos
Estrogênios , Carne , Estrogênios/análise , Cromatografia Líquida de Alta Pressão/métodos , Carne/análise
16.
Chemistry ; 30(9): e202303708, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38088216

RESUMO

The study on structure-property relationship has been a significant focus in the field of organic molecular luminescence. In the present work, three chiral binaphthyl-based triphenylethylene (HTPE) derivatives were prepared through condensation reactions. Despite their similar structures, these compounds exhibited distinct luminescent properties. Diphenylmethane-derived HTPE displayed dual-state emissions, characterized by dual-wavelength emissions which were insensitive to the polarity of solvents. The dual emissions in solution state could be attributed to the different locally excited (LE) excitons. However, upon aggregation, two stable conformers were generated, probably leading to different emission peaks. In contrast, dibenzocycloheptadiene-derived HTPE aggregates showed only a single emission peak. Surprisingly, fluorene-derived HTPE exhibited obvious luminescence in neither solution nor aggregate states due to inherent π-π interactions. These conclusions were substantiated by X-ray analysis, spectroscopic analysis, and theory calculations. Application studies demonstrated that fluorescence on/off switches could be achieved through exposure to acetone. More importantly, trace amounts of acetone could be detected using luminescent materials in both organic and aqueous phases with a detection limit of 0.08 %. Thus, this work not only presents a strategy for designing chiral triphenylethylene fluorophores but also provides valuable information for dual wavelength emissions resulting from two stable conformations.

17.
Small Methods ; 8(3): e2301250, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38016072

RESUMO

Single-cell microRNA (miRNA) sequencing has allowed for comprehensively studying the abundance and complex networks of miRNAs, which provides insights beyond single-cell heterogeneity into the dynamic regulation of cellular events. Current benchtop-based technologies for single-cell miRNA sequencing are low throughput, limited reaction efficiency, tedious manual operations, and high reagent costs. Here, a highly multiplexed, efficient, integrated, and automated sample preparation platform is introduced for single-cell miRNA sequencing based on digital microfluidics (DMF), named Hiper-seq. The platform integrates major steps and automates the iterative operations of miRNA sequencing library construction by digital control of addressable droplets on the DMF chip. Based on the design of hydrophilic micro-structures and the capability of handling droplets of DMF, multiple single cells can be selectively isolated and subject to sample processing in a highly parallel way, thus increasing the throughput and efficiency for single-cell miRNA measurement. The nanoliter reaction volume of this platform enables a much higher miRNA detection ability and lower reagent cost compared to benchtop methods. It is further applied Hiper-seq to explore miRNAs involved in the ossification of mouse skeletal stem cells after bone fracture and discovered unreported miRNAs that regulate bone repairing.


Assuntos
MicroRNAs , Microfluídica , Animais , Camundongos , MicroRNAs/genética , Análise de Sequência com Séries de Oligonucleotídeos
18.
Abdom Radiol (NY) ; 49(3): 814-822, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38150141

RESUMO

BACKGROUND: To determine the utility of virtual-monoenergetic imaging (VMI) at low energy levels from contrast-enhanced dual-layer dual-energy (DLDE) computed tomography enterography (CTE) in the preoperative assessment of internal penetrating lesions of Crohn's disease (CD). MATERIALS AND METHODS: Thirty-eight patients with penetrating lesions of CD by surgery undergoing contrast-enhanced DLDE CTE were retrospectively included. Polyenergetic imaging (PEI) and VMIs at low energy levels [40-70 kiloelectron volts (keV)] with 10 keV intervals were reconstructed. The objective parameters of image quality [noise, signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR)] and the subjective parameter of image quality [diagnostic performance of lesions (DPL), overall image quality(OIQ)] of PEI and all VMIs at the low energy level were compared to determine the VMI on the optimal energy level. The lesion detection capability between PEI and the optimal VMI was compared. RESULTS: VMI40 was determined to be the optimal VMI among all VMIs at the low energy level for owning the best image quality. No significant difference was found in the detecting capability in penetrating lesions between VMI40 and PEI (p = 1.0), whereas a significant difference was found in the detecting capability in the bowel origin of the penetrating lesions (p = 0.004), the involved organ or structure by the fistula (p = 0.016) and the orifice of the fistula connected to the involved organ or structure ( p = 0.031) between them. CONCLUSIONS: Compared to conventional PEI, VMI40 improves the detection capability in anatomical details of penetrating lesions of CD, helping colorectal surgeons rationalizing preoperative plans of internal penetrating lesions of CD.


Assuntos
Doença de Crohn , Fístula , Imagem Radiográfica a Partir de Emissão de Duplo Fóton , Humanos , Doença de Crohn/diagnóstico por imagem , Doença de Crohn/cirurgia , Estudos Retrospectivos , Imagem Radiográfica a Partir de Emissão de Duplo Fóton/métodos , Tomografia Computadorizada por Raios X/métodos , Razão Sinal-Ruído , Interpretação de Imagem Radiográfica Assistida por Computador/métodos
19.
Micromachines (Basel) ; 14(12)2023 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-38138345

RESUMO

Micro-tools comprising difficult-to-machine materials have seen widespread application in micro-manufacturing to satisfy the demands of micro-part processing and micro-device development. Taking micro-shafts as an example, the related developmental technology, based on wire electric discharge grinding (WEDG) as the core method, is one of the key technologies used to prepare high-precision micro-shafts. To enable efficient and high-precision machining of micro-shafts with target diameters, instead of performing multiple repeated on-machine measurements and reprocessing, a geometric constraint strategy is proposed based on the previously introduced twin-mirroring-wire tangential feed electrical discharge grinding (TMTF-WEDG). This strategy encompasses the tool setting method, tangential feed distance compensation, and an equation that establishes the relationship between tangential distance and diameter variation. These components are derived from a key points analysis of the geometric constraints. The micro-shafts with diameters of 50 µm and consistencies of ±1.5 µm are repeatedly processed. A series of micro-shafts with diameters ranging from 30 µm to 120 µm achieve geometric constraints with a diameter accuracy of ±2 µm, accompanied by the complete continuous automation of the entire process. Accordingly, it can be concluded that the geometric constraint strategy is flexible and stable and can be controlled with high precision in the TMTF-WEDG process.

20.
Fish Shellfish Immunol ; 143: 109230, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37977542

RESUMO

Copper (Cu) and Cadmium (Cd), prevalent heavy metals in marine environments, have known implications in oxidative stress, immune response, and toxicity in marine organisms. Sepia esculenta, a cephalopod of significant economic value along China's eastern coastline, experiences alterations in growth, mobility, and reproduction when subjected to these heavy metals. However, the specific mechanisms resulting from heavy metal exposure in S. esculenta remain largely uncharted. In this study, we utilized transcriptome and four oxidative, immunity, and toxicity indicators to assess the toxicological mechanism in S. esculenta larvae exposed to Cu and Cd. The measurements of Superoxide Dismutase (SOD), Malondialdehyde (MDA), Glutathione S-Transferase (GST), and Metallothioneins (MTs) revealed that Cu and Cd trigger substantial oxidative stress, immune response, and metal toxicity. Further, we performed an analysis on the transcriptome data through Weighted Gene Co-expression Network Analysis (WGCNA) and Protein-Protein Interaction (PPI) network analysis. Our findings indicate that exposure methods and duration influence the type and the extent of toxicity and oxidative stress within the S. esculenta larvae. We took an innovative approach in this research by integrating WGCNA and PPI network analysis with four significant physiological indicators to closely examine the toxicity and oxidative stress profiles of S. esculenta upon exposure to Cu and Cd. This investigation is vital in decoding the toxicological, immunological, and oxidative stress mechanisms within S. esculenta when subjected to heavy metals. It provides foundational insights capable of advancing invertebrate environmental toxicology and informs S. esculenta artificial breeding practices.


Assuntos
Metais Pesados , Sepia , Animais , Cobre/toxicidade , Cádmio/toxicidade , Sepia/metabolismo , Antioxidantes/metabolismo , Redes Reguladoras de Genes , Larva/genética , Larva/metabolismo , Estresse Oxidativo , Metais Pesados/toxicidade , Imunidade
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