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1.
Front Oncol ; 14: 1328146, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39169945

RESUMO

Pancreatic tumors are small in size, diverse in shape, and have low contrast and high texture similarity with surrounding tissue. As a result, the segmentation model is easily confused by complex and changeable background information, leading to inaccurate positioning of small targets and false positives and false negatives. Therefore, we design a cascaded pancreatic tumor segmentation algorithm. In the first stage, we use a general multi-scale U-Net to segment the pancreas, and we exploit a multi-scale segmentation network based on non-local localization and focusing modules to segment pancreatic tumors in the second stage. The non-local localization module learns channel and spatial position information, searches for the approximate area where the pancreatic tumor is located from a global perspective, and obtains the initial segmentation results. The focusing module conducts context exploration based on foreground features (or background features), detects and removes false positive (or false negative) interference, and obtains more accurate segmentation results based on the initial segmentation. In addition, we design a new loss function to alleviate the insensitivity to small targets. Experimental results show that the proposed algorithm can more accurately locate pancreatic tumors of different sizes, and the Dice coefficient outperforms the existing state-of-the-art segmentation model. The code will be available at https://github.com/HeyJGJu/Pancreatic-Tumor-SEG.

2.
Adv Colloid Interface Sci ; 332: 103271, 2024 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-39146581

RESUMO

With the rapid development of information and communication industries, the usage of electromagnetic waves has caused the hazard of human health and misfunction of devices. The adsorption and shielding of electromagnetic waves have been achieved in various materials. The unique adjustable spatial structure makes metal-organic frameworks (MOFs) promising for electromagnetic shielding and adsorbing. As MOFs research advances, various large-scale MOF-based materials have been developed. For instance, MOFs spatial structure has been expanded from 2D to 3D to load more ligands. Progress in synthetic methods for MOFs and their derivatives is advancing, with priority on large-scale preparation and green synthesis. This review summarizes the methods for synthesizing MOFs and their derivatives, and explores the effects of MOFs spatial structure on electromagnetic interference (EMI) shielding and electromagnetic wave absorption capabilities. At the same time, detailed examples are used to focus on the applications of five different MOFs composites in electromagnetic shielding and electromagnetic wave absorption. Finally, the current challenges and prospects of MOFs in the electromagnetic field are introduced, providing a useful reference for the preparation and design of MOFs and their composites for electromagnetic wave processing applications.

3.
Environ Sci Technol ; 58(33): 14629-14640, 2024 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-39102579

RESUMO

Graphene quantum dots (GQDs) are used in diverse fields from chemistry-related materials to biomedicines, thus causing their substantial release into the environment. Appropriate visual function is crucial for facilitating the decision-making process within the nervous system. Given the direct interaction of eyes with the environment and even nanoparticles, herein, GQDs, sulfonic acid-doped GQDs (S-GQDs), and amino-functionalized GQDs (A-GQDs) were employed to understand the potential optic neurotoxicity disruption mechanism by GQDs. The negatively charged GQDs and S-GQDs disturbed the response to light stimulation and impaired the structure of the retinal nuclear layer of zebrafish larvae, causing vision disorder and retinal degeneration. Albeit with sublethal concentrations, a considerably reduced expression of the retinal vascular sprouting factor sirt1 through increased DNA methylation damaged the blood-retina barrier. Importantly, the regulatory effect on vision function was influenced by negatively charged GQDs and S-GQDs but not positively charged A-GQDs. Moreover, cluster analysis and computational simulation studies indicated that binding affinities between GQDs and the DNMT1-ligand binding might be the dominant determinant of the vision function response. The previously unknown pathway of blood-retinal barrier interference offers opportunities to investigate the biological consequences of GQD-based nanomaterials, guiding innovation in the industry toward environmental sustainability.


Assuntos
Metilação de DNA , Grafite , Pontos Quânticos , Pontos Quânticos/química , Pontos Quânticos/toxicidade , Grafite/química , Animais , Degeneração Retiniana , Barreira Hematorretiniana/metabolismo , Peixe-Zebra
4.
Colloids Surf B Biointerfaces ; 243: 114126, 2024 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-39106631

RESUMO

Presently, the non-biodegradable polypropylene (PP) patches frequently used for hernia repair can cause fibrous tissue growth and adhesions. This study created a Janus Patch with anti-adhesion and antimicrobial properties to improve hernia repair while promoting tissue repair. The biologically active 4arm-PLGA-BLPD was initially synthesized through the modification of 4arm-PLGA with lysine, followed by the fabrication of a Janus patch using a layer-by-layer electrostatic spinning technique. This patch consisted of three layers: a repair layer composed of 4arm-PLGA-BLPD/PCL fiber membrane, a mechanical layer of 4arm-PLGA/PCL fiber membrane, and an antimicrobial layer of EMO-4arm-PLGA/PCL fiber membrane loaded with Emodin (EMO). The results showed that Janus patch exhibited notable tensile strength and elongation at break, enabling it to offer enhanced mechanical reinforcement for abdominal wall defects. In addition, it slowly releases lysine for repair and inhibits bacterial growth with EMO. In vivo experiments demonstrated that the patch effectively induced neovascularization, reduced collagen ac-cumulation, and stabilized the expression of relevant proteins through the up-regulation of MMP1 and MMP9. This facilitated successful repair of the abdominal wall defect model and prevented adhesions. In summary, the Janus patch offers both practical application and theoretical insight for hernia repair.

5.
J Gastroenterol ; 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-39145797

RESUMO

BACKGROUND: Pancreatic fibrosis is the main pathological feature of chronic pancreatitis. There is a lack of medications that effectively alleviate or reverse pancreatic fibrosis and thus cure chronic pancreatitis. METHODS: We screened drugs that could alleviate pancreatic fibrosis from 80 traditional Chinese medicine monomers and verified their efficacy and mechanisms. RESULTS: We preliminarily identified corynoline as an antifibrotic candidate by drug screening among 80 compounds. In vitro, corynoline dose-dependently reduces collagen I synthesis in pancreatic stellate cells induced by TGF-ß1 and inhibits its activation. Furthermore, we found that corynoline could alleviate the morphological disruption, such as acinar cell atrophy, collagen deposition etc., as well as reduced pancreatic weight in mice with chronic pancreatitis. We further validated the antifibrotic effect of corynoline in mRNA and protein levels. We also found that corynoline could inhibit NF-κB signaling pathway in vitro and in vivo. Next, we identified PSMA2 as the binding protein of corynoline by Lip-SMap and validated it using DARTS. Moreover, the siRNA of PSMA2 disrupts the anti-fibrotic effect of corynoline. CONCLUSION: In conclusion, corynoline is a promising agent for the treatment of pancreatic fibrosis and chronic pancreatitis.

6.
Ecotoxicol Environ Saf ; 283: 116859, 2024 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-39137466

RESUMO

The developmental toxicity and human health risks of triazole fungicides (TFs) have attracted worldwide attention due to the ability to enter the human body in a variety of ways. Nevertheless, the specific mechanism by which TFs exert remains incompletely understood. Given that retinoic acid (RA) signaling pathway are closely related to development, this study aimed to screen and identify developmentally disabled chemicals in commonly used TFs and to reveal the potential effects of TFs on developmental retardation through the RA signaling pathway in mouse embryonic stem cells (mESCs). Specifically, six typical TFs (myclobutanil, tebuconazole, hexaconazole, propiconazole, difenoconazole, and flusilazole) were exposed through the construction of an embryoid bodies (EBs)-based in vitro global differentiation models. Our results clarified that various TFs disturbed lineage commitment during early embryonic development. Crucially, the activation of RA signaling pathway, which alters the expression of key genes and interferes the transport and metabolism of retinol, may be responsible for this effect. Furthermore, molecular docking, molecular dynamics simulations, and experiments using a retinoic acid receptor α inhibitor provide evidence supporting the potential modulatory role of the retinoic acid signaling pathway in developmental injury. The current study offers new insights into the TFs involved in the RA signaling pathway that interfere with the differentiation process of mESCs, which is crucial for understanding the impact of TFs on pregnancy and early development.

7.
J Proteome Res ; 2024 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-39129220

RESUMO

In this study, we utilized the Olink Cardiovascular III panel to compare the expression levels of 92 cardiovascular-related proteins between patients with dilated cardiomyopathy combined with heart failure (DCM-HF) (n = 20) and healthy normal people (Normal) (n = 18). The top five most significant proteins, including SPP1, IGFBP7, F11R, CHI3L1, and Plaur, were selected by Olink proteomics. These proteins were further validated using ELISA in plasma samples collected from an additional cohort. ELISA validation confirmed significant increases in SPP1, IGFBP7, F11R, CHI3L1, and Plaur in DCM-HF patients compared to healthy controls. GO and KEGG analysis indicated that NT-pro BNP, SPP1, IGFBP7, F11R, CHI3L1, Plaur, BLM hydrolase, CSTB, Gal-4, CCL15, CDH5, SR-PSOX, and CCL2 were associated with DCM-HF. Correlation analysis revealed that these 13 differentially expressed proteins have strong correlations with clinical indicators such as LVEF and NT-pro BNP, etc. Additionally, in the GEO-DCM data sets, the combined diagnostic value of these five core proteins AUC values of 0.959, 0.773, and 0.803, respectively indicating the predictive value of the five core proteins for DCM-HF. Our findings suggest that these proteins may be useful biomarkers for the diagnosis and prediction of DCM-HF, and further research is prompted to explore their potential as therapeutic targets.

8.
Nanoscale ; 2024 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-39129530

RESUMO

Bismuth produces different types of ordered superstructures on the InAs(100) surface, depending on the growth procedure and coverage. The (2 × 1) phase forms at completion of one Bi monolayer and consists of a uniformly oriented array of parallel lines of Bi dimers. Scanning tunneling and core level spectroscopies demonstrate its metallic character, in contrast with the semiconducting properties expected on the basis of the electron counting principle. The weak electronic coupling among neighboring lines gives rise to quasi one-dimensional Bi-derived bands with open contours at the Fermi level. Spin- and angle-resolved photoelectron spectroscopy reveals a giant Rashba splitting of these bands, in good agreement with ab initio electronic structure calculations. The very high density of the dimer lines, the metallic and quasi one-dimensional band dispersion and the Rashba-like spin texture make the Bi/InAs(100)-(2 × 1) phase an intriguing system, where novel transport regimes can be studied.

9.
Materials (Basel) ; 17(15)2024 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-39124334

RESUMO

The In-Bi-Sn low-temperature solder alloys are regarded as potential candidates for cryogenic and space exploration applications. This study investigates the variations in the mechanical properties and microstructures of two different compositions: In15wt%Bi35wt%Sn and In30wt%Bi20wt%Sn, after exposure to a low-temperature environment (-20 °C) for 10 months. An increase in the ultimate tensile strength was observed across all the tested samples and a decrease in elongation to failure was observed in In30wt%Bi20wt%Sn. Changes in the microstructure were identified through scanning electron microscopy (SEM) and electron backscatter diffraction (EBSD). The impact of this low-temperature environment is described, considering the varying proportions and compositions of the three phases (BiIn2(Sn), γ-InSn4(Bi), and ß-In3Sn(Bi)) present within the alloys and their contribution to the mechanical properties.

10.
ACS Omega ; 9(25): 27492-27498, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38947779

RESUMO

Diamond nanopillar arrays can enhance the fluorescence collection of diamond color centers, playing a crucial role in quantum communication and quantum sensing. In this paper, the preparation of diamond nanopillar arrays was realized by the processes of polystyrene (PS) sphere array film preparation, PS sphere etching shrinkage control, tilted magnetron sputtering of copper film, and oxygen plasma etching. Closely aligned PS sphere array films were prepared on the diamond surface by the gas-liquid interfacial method, and the effects of ethanol and dodecamethylacrylic acid solutions on the formation of the array films were discussed. Controllable reduction of PS sphere diameter is realized by the oxygen plasma etching process, and the changes of the PS sphere array film under the influence of etching power, bias power, and etching time are discussed. Copper antietching films were prepared at the top of arrayed PS spheres by the tilted magnetron sputtering method, and the antietching effect of copper films with different thicknesses was explored. Diamond nanopillar arrays were prepared by oxygen plasma etching, and the effects of etching under different process parameters were discussed. The prepared diamond nanopillars were in hexagonal close-rowed arrays with a spacing of 800 nm and an average diameter of 404 nm, and the spacing, diameter, and height could be parametrically regulated. Raman spectroscopy and photoluminescence spectroscopy detection revealed that the prepared diamond nanopillar array still maintains polycrystalline diamond properties, with only a small amount of the graphite phase appearing. Moreover, the prepared diamond nanopillar array can enhance the photoluminescence of diamond color centers by approximately 2 times. The fabrication method of diamond nanopillar array structures described in this article lays the foundation for quantum sensing technology based on diamond nanostructures.

11.
Obstet Gynecol Int ; 2024: 1810634, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38957414

RESUMO

Aim: To explore the potential factors that influence the presentation and recovery of postoperative chylous ascites (CA) in gynecological malignancies. Methods: We reported two cases of postoperative CA following gynecological surgery and reviewed the clinical features of 140 patients from 16 relevant papers. Patients' clinicopathological characteristics, surgical approach, and management were summarized. The onset and resolution times of postoperative CA in different groups were analyzed separately. Results: The two patients in our report had recovery after conservative treatments. According to the literature review, the median time of onset of postoperative CA was 5 days (range, 0-75 days) after surgery. The median resolution time was 9 days (range, 2-90 days). Among patients, 87.14% of them had lymphadenectomy during gynecological surgeries, while 92.86% of the patients had resolution after conservative treatments. Conclusions: Lymphadenectomy during surgery may be relevant to the postoperative CA. Conservative management could be the initial choice for postoperative CA treatment.

12.
Int Immunopharmacol ; 138: 112574, 2024 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-38971104

RESUMO

BACKGROUND: Ischemic cardiomyopathy (IC) is primarily due to long-term ischemia/hypoxia of the coronary arteries, leading to impaired cardiac contractile or diastolic function. A new form of cell death induced by copper, called "cuproptosis" is related to the development and progression of multiple diseases. The cuproptosis-related gene (CuGs) plays an important role in acute myocardial infarction, while the specific mechanisms of CuGs in ischemic cardiomyopathy remain unclear. METHODS: The expressions of CuGs and their immune characteristics were analyzed with the IC datasets obtained from the Gene Expression Omnibus, namely GSE5406 and GSE57338, identifying core genes associated with IC development. By comparing RF, SVM, GLM and XGB models, the optimal machine learning model was selected. The expression of marker genes was validated based on the GSE57345, GSE48166 and GSE42955 datasets. Construct a CeRNA network based on core genes. Therapeutic chemiacals targeting core genes were acquired using the CTD database, and molecular docking was performed using Autodock vina software. By ligating the left anterior descending (LAD) coronary artery, an IC mouse model is established, and core genes were experimentally validated using Western blot (WB) and immunohistochemistry (IHC) methods. RESULTS: We identified 14 CuGs closely associated with the onset of IC. The SVM model exhibited superior discriminative power (AUC = 0.914), with core genes being DLST, ATP7B, FDX1, SLC31A1 and DLAT. Core genes were validated on the GSE42955, GSE48166 and GSE57345 datasets, showing excellent performance (AUC = 0.943, AUC = 0.800, and AUC = 0.932). The CeRNA network consists of 218 nodes and 264 lines, including 5 core diagnostic genes, 52 miRNAs, and 161 lncRNAs. Chemicals predictions indicated 8 chemicals have therapeutic effects on the core diagnostic genes, with benzo(a)pyrene molecular docking showing the highest affinity (-11.3 kcal/mol). Compared to the normal group, the IC group,which was established by LAD ligation, showed a significant decrease in LVEF as indicated by cardiac ultrasound, and increased fibrosis as shown by MASSON staining, WB results suggest increased expression of DLST and ATP7B, and decreased expression of FDX1, SLC31A1 and DLAT in the myocardial ischemic area (p < 0.05), which was also confirmed by IHC in tissue sections. CONCLUSION: In summary, this study comprehensively revealed that DLST, ATP7B, FDX1, SLC31A1 and DLAT could be identified as potential immunological biomarkers in IC, and validated through an IC mouse model, providing valuable insights for future research into the mechanisms of CuGs and its diagnostic value to IC.


Assuntos
Apoptose , Biologia Computacional , Isquemia Miocárdica , Animais , Humanos , Masculino , Camundongos , Cardiomiopatias/genética , Cardiomiopatias/imunologia , Bases de Dados Genéticas , Modelos Animais de Doenças , Redes Reguladoras de Genes , Camundongos Endogâmicos C57BL , Simulação de Acoplamento Molecular , Isquemia Miocárdica/genética , Isquemia Miocárdica/imunologia , Cobre
13.
Environ Sci Ecotechnol ; 21: 100438, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39036799

RESUMO

Ethane, the second most abundant gaseous hydrocarbon in vast anoxic environments, is an overlooked greenhouse gas. Microbial anaerobic oxidation of ethane can be driven by available electron acceptors such as sulfate and nitrate. However, despite nitrite being a more thermodynamically feasible electron acceptor than sulfate or nitrate, little is known about nitrite-driven anaerobic ethane oxidation. In this study, a microbial culture capable of nitrite-driven anaerobic ethane oxidation was enriched through the long-term operation of a nitrite-and-ethane-fed bioreactor. During continuous operation, the nitrite removal rate and the theoretical ethane oxidation rate remained stable at approximately 25.0 mg NO2 -N L-1 d-1 and 11.48 mg C2H6 L-1 d-1, respectively. Batch tests demonstrated that ethane is essential for nitrite removal in this microbial culture. Metabolic function analysis revealed that a species affiliated with a novel genus within the family Rhodocyclaceae, designated as 'Candidatus Alkanivoras nitrosoreducens', may perform the nitrite-driven anaerobic ethane oxidation. In the proposed metabolic model, despite the absence of known genes for ethane conversion to ethyl-succinate and succinate-CoA ligase, 'Ca. A. nitrosoreducens' encodes a prospective fumarate addition pathway for anaerobic ethane oxidation and a complete denitrification pathway for nitrite reduction to nitrogen. These findings advance our understanding of nitrite-driven anaerobic ethane oxidation, highlighting the previously overlooked impact of anaerobic ethane oxidation in natural ecosystems.

14.
Brain Behav ; 14(7): e3600, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38988142

RESUMO

OBJECTIVE: In this study, multimodal magnetic resonance imaging (MRI) imaging was used to deeply analyze the changes of hippocampal subfields perfusion and function in patients with type 2 diabetes mellitus (T2DM), aiming to provide image basis for the diagnosis of hippocampal-related nerve injury in patients with T2DM. METHODS: We recruited 35 patients with T2DM and 40 healthy control subjects (HCs). They underwent resting-state functional MRI (rs-fMRI), arterial spin labeling (ASL) scans, and a series of cognitive tests. Then, we compared the differences of two groups in the cerebral blood flow (CBF) value, amplitude of low-frequency fluctuation (ALFF) value, and regional homogeneity (ReHo) value of the bilateral hippocampus subfields. RESULTS: The CBF values of cornu ammonis area 1 (CA1), dentate gyrus (DG), and subiculum in the right hippocampus of T2DM group were significantly lower than those of HCs. The ALFF values of left hippocampal CA3, subiculum, and bilateral hippocampus amygdala transition area (HATA) were higher than those of HCs in T2DM group. The ReHo values of CA3, DG, subiculum, and HATA in the left hippocampus of T2DM group were higher than those of HCs. In the T2DM group, HbAc1 and FINS were negatively correlated with imaging characteristics in some hippocampal subregions. CONCLUSION: This study indicates that T2DM patients had decreased perfusion in the CA1, DG, and subiculum of the right hippocampus, and the right hippocampus subiculum was associated with chronic hyperglycemia. Additionally, we observed an increase in spontaneous neural activity within the left hippocampal CA3, subiculum, and bilateral HATA regions, as well as an enhanced local neural coordination in the left hippocampal CA3, DG, HATA, and subiculum among patients with type 2 diabetes, which may reflect an adaptive compensation for cognitive decline. However, this compensation may decline with the exacerbation of metabolic disorders.


Assuntos
Circulação Cerebrovascular , Diabetes Mellitus Tipo 2 , Hipocampo , Imageamento por Ressonância Magnética , Humanos , Diabetes Mellitus Tipo 2/fisiopatologia , Diabetes Mellitus Tipo 2/diagnóstico por imagem , Masculino , Feminino , Hipocampo/diagnóstico por imagem , Hipocampo/fisiopatologia , Circulação Cerebrovascular/fisiologia , Pessoa de Meia-Idade , Adulto , Descanso/fisiologia , Disfunção Cognitiva/fisiopatologia , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/diagnóstico por imagem
15.
mBio ; 15(6): e0033924, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38988221

RESUMO

The emergence of oxacillin-susceptible methicillin-resistant Staphylococcus aureus (OS-MRSA) has imposed further challenges to the clinical management of MRSA infections. When exposed to ß-lactam antibiotics, these strains can easily acquire reduced ß-lactam susceptibility through chromosomal mutations, including those in RNA polymerase (RNAP) genes such as rpoBC, which may then lead to treatment failure. Despite the increasing prevalence of such strains and the apparent challenges they pose for diagnosis and treatment, there is limited information available on the actual mechanisms underlying such chromosomal mutation-related transitions to reduced ß-lactam susceptibility, as it does not directly associate with the expression of mecA. This study investigated the cellular physiology and metabolism of six missense mutants with reduced oxacillin susceptibility, each carrying respective mutations on RpoBH929P, RpoBQ645H, RpoCG950R, RpoCG498D, RpiAA64E, and FruBA211E, using capillary electrophoresis-mass spectrometry-based metabolomics analysis. Our results showed that rpoBC mutations caused RNAP transcription dysfunction, leading to an intracellular accumulation of ribonucleotides. These mutations also led to the accumulation of UDP-Glc/Gal and UDP-GlcNAc, which are precursors of UTP-associated peptidoglycan and wall teichoic acid. Excessive amounts of building blocks then contributed to the cell wall thickening of mutant strains, as observed in transmission electron microscopy, and ultimately resulted in decreased susceptibility to ß-lactam in OS-MRSA. IMPORTANCE: The emergence of oxacillin-susceptible methicillin-resistant Staphylococcus aureus (OS-MRSA) strains has created new challenges for treating MRSA infections. These strains can become resistant to ß-lactam antibiotics through chromosomal mutations, including those in the RNA polymerase (RNAP) genes such as rpoBC, leading to treatment failure. This study investigated the mechanisms underlying reduced ß-lactam susceptibility in four rpoBC mutants of OS-MRSA. The results showed that rpoBC mutations caused RNAP transcription dysfunction, leading to an intracellular accumulation of ribonucleotides and precursors of peptidoglycan as well as wall teichoic acid. This, in turn, caused thickening of the cell wall and ultimately resulted in decreased susceptibility to ß-lactam in OS-MRSA. These findings provide insights into the mechanisms of antibiotic resistance in OS-MRSA and highlight the importance of continued research in developing effective treatments to combat antibiotic resistance.


Assuntos
Antibacterianos , RNA Polimerases Dirigidas por DNA , Staphylococcus aureus Resistente à Meticilina , Testes de Sensibilidade Microbiana , Oxacilina , Staphylococcus aureus Resistente à Meticilina/genética , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/enzimologia , Oxacilina/farmacologia , RNA Polimerases Dirigidas por DNA/genética , RNA Polimerases Dirigidas por DNA/metabolismo , Antibacterianos/farmacologia , beta-Lactamas/farmacologia , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Mutação de Sentido Incorreto , Parede Celular/efeitos dos fármacos , Parede Celular/metabolismo , Parede Celular/genética , Humanos , Mutação , Metabolômica
16.
Sci Rep ; 14(1): 16225, 2024 07 13.
Artigo em Inglês | MEDLINE | ID: mdl-39003336

RESUMO

In response to the escalating global threat of antimicrobial resistance, our laboratory has established a phagemid packaging system for the generation of CRISPR-Cas13a-antimicrobial capsids targeting methicillin-resistant Staphylococcus aureus (MRSA). However, a significant challenge arose during the packaging process: the unintentional production of wild-type phages alongside the antimicrobial capsids. To address this issue, the phagemid packaging system was optimized by strategically incorporated silent mutations. This approach effectively minimized contamination risks without compromising packaging efficiency. The study identified the indispensable role of phage packaging genes, particularly terL-terS, in efficient phagemid packaging. Additionally, the elimination of homologous sequences between the phagemid and wild-type phage genome was crucial in preventing wild-type phage contamination. The optimized phagemid-LSAB(mosaic) demonstrated sequence-specific killing, efficiently eliminating MRSA strains carrying target antibiotic-resistant genes. While acknowledging the need for further exploration across bacterial species and in vivo validation, this refined phagemid packaging system offers a valuable advancement in the development of CRISPR-Cas13a-based antimicrobials, shedding light on potential solutions in the ongoing battle against bacterial infections.


Assuntos
Sistemas CRISPR-Cas , Capsídeo , Staphylococcus aureus Resistente à Meticilina , Mutação , Staphylococcus aureus Resistente à Meticilina/genética , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Capsídeo/metabolismo , Antibacterianos/farmacologia , Bacteriófagos/genética
17.
Insect Sci ; 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38831720

RESUMO

N6-methyladenosine (m6A) is the most prevalent modification in cellular RNA which orchestrates diverse physiological and pathological processes during stress response. However, the differential m6A modifications that cope with herbivore stress in resistant and susceptible crop varieties remain unclear. Here, we found that rice stem borer (RSB) larvae grew better on indica rice (e.g., MH63, IR64, Nanjing 11) than on japonica rice varieties (e.g., Nipponbare, Zhonghua 11, Xiushui 11). Then, transcriptome-wide m6A profiling of representative resistant (Nipponbare) and susceptible (MH63) rice varieties were performed using a nanopore direct RNA sequencing approach, to reveal variety-specific m6A modifications against RSB. Upon RSB infestation, m6A methylation occurred in actively expressed genes in Nipponbare and MH63, but the number of methylation sites decreased across rice chromosomes. Integrative analysis showed that m6A methylation levels were closely associated with transcriptional regulation. Genes involved in herbivorous resistance related to mitogen-activated protein kinase, jasmonic acid (JA), and terpenoid biosynthesis pathways, as well as JA-mediated trypsin protease inhibitors, were heavily methylated by m6A, and their expression was more pronounced in RSB-infested Nipponbare than in RSB-infested MH63, which may have contributed to RSB resistance in Nipponbare. Therefore, dynamics of m6A modifications act as the main regulatory strategy for expression of genes involved in plant-insect interactions, which is attributed to differential responses of resistant and susceptible rice varieties to RSB infestation. These findings could contribute to developing molecular breeding strategies for controlling herbivorous pests.

18.
Gynecol Oncol ; 188: 27-34, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38901080

RESUMO

OBJECTIVE: Given the low incidence of venous thromboembolism (VTE) in endometrial cancer patients undergoing minimally invasive surgery, coupled with the existing uncertainties within guidelines regarding pharmacologic thromboprophylaxis in this area, there is an urgent need for a comprehensive literature review. This review aims to evaluate the necessity of pharmacologic VTE prophylaxis in these patients. METHODS: PubMed, Embase, Cochrane Central Register of Controlled Trials, International Clinical Trials Registry Platform, and ClinicalTrials.gov were systematically searched from inception to March 10, 2024. The analysis was performed using R version 4.2.3. RESULTS: Seven studies involving 3931 endometrial cancer patients were included in the analysis. Meta-analysis results revealed that within 30 days postoperatively, the incidence of VTE was 0.51% (5 out of 990) in the pharmacologic prophylaxis group and 0.70% (7 out of 995) in the mechanical prophylaxis group, with a relative risk (RR) of 1.14 (95% CI 0.19-6.95), indicating no significant difference between the groups. Additionally, within the same timeframe, the incidence of VTE was 0.37% (4 out of 1083) in the extended pharmacologic prophylaxis group and 1.14% (4 out of 352) in the non-extended pharmacologic prophylaxis group, yielding an RR of 0.41 (95% CI 0.11-1.54), again showing no significant difference between the groups. CONCLUSIONS: Our study indicates that routine pharmacological VTE prophylaxis may not be imperative for endometrial cancer patients undergoing minimally invasive surgery, as mechanical prophylaxis alone seems to be efficacious. However, it is crucial to acknowledge that a subset of high-risk patients may derive benefit from pharmacological prophylaxis or even extended regimens. Nonetheless, the absence of a validated risk prediction model for identifying such patients underscores the need for further research in this area. PROTOCOL REGISTRATION: CRD 42024516595.

19.
Sci Rep ; 14(1): 14155, 2024 06 19.
Artigo em Inglês | MEDLINE | ID: mdl-38898215

RESUMO

Coronary atherosclerotic heart disease (CAD) is among the most prevalent chronic diseases globally. Circadian rhythm disruption (CRD) is closely associated with the progression of various diseases. However, the precise role of CRD in the development of CAD remains to be elucidated. The Circadian rhythm disruption score (CRDscore) was employed to quantitatively assess the level of CRD in CAD samples. Our investigation revealed a significant association between high CRDscore and adverse prognosis in CAD patients, along with a substantial correlation with CAD progression. Remarkably distinct CRDscore distributions were also identified among various subtypes. In summary, we have pioneered the revelation of the relationship between CRD and CAD at the single-cell level and established reliable markers for the development, treatment, and prognosis of CAD. A deeper understanding of these mechanisms may offer new possibilities for incorporating "the therapy of coronary heart disease based circadian rhythm" into personalized medical treatment regimens.


Assuntos
Ritmo Circadiano , Humanos , Ritmo Circadiano/fisiologia , Masculino , Feminino , Pessoa de Meia-Idade , Isquemia Miocárdica , Prognóstico , Doença da Artéria Coronariana , Idoso , Biomarcadores , Progressão da Doença
20.
Sensors (Basel) ; 24(12)2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38931666

RESUMO

The numerical aperture of the spectrometer is crucial for weak signal detection. The transmission lens-based configuration has more optimization variations, and the grating can work approximately in the Littrow condition; thus, it is easier to acquire high numerical aperture (NA). However, designing a large aperture focusing lens remains challenging, and thus, ultra-high NA spectrometers are still difficult to acquire. In this paper, we propose a method of setting image plane tilt ahead directly when designing the large aperture focusing lens to simplify the high NA spectrometer design. By analyzing the accurate demands of the focusing lens, it can be concluded that a focusing lens with image plane tilt has much weaker demand for achromatism, and other monochromatic aberration can also be reduced, which is helpful to increase the NA. An NA0.5 fiber optic spectrometer design is given to demonstrate the proposed method. The design results show that the NA can achieve 0.5 using four lenses of two materials, and the MTF is higher than 0.5 when the spectral dispersion length is 12.5 mm and the pixel size is 25 µm, and thus, the spectral resolution can achieve 6.5 nm when the spectral sampling ratio is 2:1. The proposed method can provide reference for applications when appropriate materials are limited and high sensitivity is necessary.

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