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1.
Int J Mol Sci ; 25(7)2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38612392

RESUMO

The glycocalyx is a proteoglycan-glycoprotein structure lining the luminal surface of the vascular endothelium and is susceptible to damage due to blast overpressure (BOP) exposure. The glycocalyx is essential in maintaining the structural and functional integrity of the vasculature and regulation of cerebral blood flow (CBF). Assessment of alterations in the density of the glycocalyx; its components (heparan sulphate proteoglycan (HSPG/syndecan-2), heparan sulphate (HS), and chondroitin sulphate (CS)); CBF; and the effect of hypercapnia on CBF was conducted at 2-3 h, 1, 3, 14, and 28 days after a high-intensity (18.9 PSI/131 kPa peak pressure, 10.95 ms duration, and 70.26 PSI·ms/484.42 kPa·ms impulse) BOP exposure in rats. A significant reduction in the density of the glycocalyx was observed 2-3 h, 1-, and 3 days after the blast exposure. The glycocalyx recovered by 28 days after exposure and was associated with an increase in HS (14 and 28 days) and in HSPG/syndecan-2 and CS (28 days) in the frontal cortex. In separate experiments, we observed significant decreases in CBF and a diminished response to hypercapnia at all time points with some recovery at 3 days. Given the role of the glycocalyx in regulating physiological function of the cerebral vasculature, damage to the glycocalyx after BOP exposure may result in the onset of pathogenesis and progression of cerebrovascular dysfunction leading to neuropathology.


Assuntos
Proteoglicanas de Heparan Sulfato , Sindecana-2 , Animais , Ratos , Glicocálix , Hipercapnia , Circulação Cerebrovascular , Heparitina Sulfato , Sulfatos de Condroitina
2.
Nat Commun ; 15(1): 3278, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38627376

RESUMO

Distinct skyrmion phases at room temperature hosted by one material offer additional degree of freedom for the design of topology-based compact and energetically-efficient spintronic devices. The field has been extended to low-dimensional magnets with the discovery of magnetism in two-dimensional van der Waals magnets. However, creating multiple skyrmion phases in 2D magnets, especially above room temperature, remains a major challenge. Here, we report the experimental observation of mixed-type skyrmions, exhibiting both Bloch and hybrid characteristics, in a room-temperature ferromagnet Fe3GaTe2. Analysis of the magnetic intensities under varied imaging conditions coupled with complementary simulations reveal that spontaneous Bloch skyrmions exist as the magnetic ground state with the coexistence of hybrid stripes domain, on account of the interplay between the dipolar interaction and the Dzyaloshinskii-Moriya interaction. Moreover, hybrid skyrmions are created and their coexisting phases with Bloch skyrmions exhibit considerably high thermostability, enduring up to 328 K. The findings open perspectives for 2D spintronic devices incorporating distinct skyrmion phases at room temperature.

3.
Adv Mater ; : e2313411, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38469974

RESUMO

Precise manipulation of van der Waals forces within 2D atomic layers allows for exact control over electron-phonon coupling, leading to the exceptional quantum properties. However, applying this technique to diverse structures such as 3D materials is challenging. Therefore, investigating new hierarchical structures and different interlayer forces is crucial for overcoming these limitations and discovering novel physical properties. In this work, a multishelled ferromagnetic material with controllable shell numbers is developed. By strategically regulating the magnetic interactions between these shells, the magnetic properties of each shell are fine-tuned. This approach reveals distinctive magnetic characteristics including regulated magnetic domain configurations and enhanced effective fields. The nanoscale magnetic interactions between the shells are observed and analyzed, which shed light on the modified magnetic properties of each shell, enhancing the understanding and control of ferromagnetic materials. The distinctive magnetic interaction significantly boosts electromagnetic absorption at low-frequency frequencies used by fifth-generation wireless devices, outperforming ferromagnetic materials without multilayer structures by several folds. The application of magnetic interactions in materials science reveals thrilling prospects for technological and electronic innovation.

4.
Transl Cancer Res ; 13(2): 935-951, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38482409

RESUMO

Background: Breast cancer patients with positive axillary lymph nodes usually require axillary lymph node dissection (ALND), with many postoperative complications, such as lymphedema. For these patients, whether sentinel lymph node biopsy (SLNB) can replace ALND has been a research hotspot in the field of breast cancer. This study developed two risk stratification models for predicting the clinical outcomes of breast cancer patients with positive axillary lymph nodes receiving SLNB alone or ALND to determine which patients could potentially avoid ALND. Methods: A total of 21,942 breast cancer patients, including a training set (n=15,362) and a testing set (n=6,580), were enrolled in this study from Surveillance, Epidemiology, and End Results (SEER) between 2000 and 2017. The risk factors associated with breast cancer-specific survival (BCSS) and overall survival (OS) were evaluated using multivariate Cox regression analysis and then integrated into nomograms and risk stratification models examined by receiver operating characteristic (ROC) curves and calibration curves. The survival discrepancies were compared between the SLNB and ALND subgroups with different risk scores with Kaplan-Meier plots. Results: In multivariate Cox regression analyses, grade, marital status, T stage, radiotherapy and lymph node metastasis (GMTRL) were independent risk factors in breast cancer patients with both OS and BCSS status in the ALND cohort from the training set. Nomograms have been developed based on these factors to predict 3- and 5-year OS and BCSS in patients with ALND. Calibration curves and ROC curves in both the training and testing sets confirmed the excellent overall predictive performance of the nomograms. Furthermore, we developed two risk stratification models based on OS and BCSS status, revealing that patients with low GMTRL scores might avoid ALND in both OS and BCSS status [OS: hazard ratio (HR) =0.929, 95% confidence interval (CI): 0.841-1.027, P=0.150; BCSS: HR =0.953, 95% CI: 0.831-1.094, P=0.495], but patients with moderate (OS: HR =0.756, 95% CI: 0.666-0.859, P<0.001; BCSS: HR =0.643, 95% CI: 0.537-0.768, P<0.001) and high GMTRL scores could not (OS: HR =0.719, 95% CI: 0.549-0.940, P=0.014; BCSS: HR =0.731, 95% CI: 0.549-0.974, P=0.031). Conclusions: Breast cancer patients with positive nodes could be treated with SLNB alone rather than ALND without affecting prognosis based on GMTRL scores. Patients with high or moderate GMTRL scores benefited greatly from ALND, but not for patients with low GMTRL scores. This study may assist clinicians in tailoring treatments.

5.
Front Pharmacol ; 15: 1257253, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38370471

RESUMO

PARP1 is one of six enzymes required for the highly error-prone DNA repair pathway microhomology-mediated end joining (MMEJ) and needs to be inhibited when over-expressed. In order to study the PARP1 inhibitory effect of fused tetracyclic or pentacyclic dihydrodiazepinoindolone derivatives (FTPDDs) by quantitative structure-activity relationship technique, six models were established by four kinds of methods, heuristic method, gene expression programming, random forester, and support vector regression with single, double, and triple kernel function respectively. The single, double, and triple kernel functions were RBF kernel function, the integration of RBF and polynomial kernel functions, and the integration of RBF, polynomial, and linear kernel functions respectively. The problem of multi-parameter optimization introduced in the support vector regression model was solved by the particle swarm optimization algorithm. Among the models, the model established by support vector regression with triple kernel function, in which the optimal R 2 and RMSE of training set and test set were 0.9353, 0.9348 and 0.0157, 0.0288, and R2 cv of training set and test set were 0.9090 and 0.8971, shows the strongest prediction ability and robustness. The method of support vector regression with triple kernel function is a great promotion in the field of quantitative structure-activity relationship, which will contribute a lot to designing and screening new drug molecules. The information contained in the model can provide important factors that guide drug design. Based on these factors, six new FTPDDs have been designed. Using molecular docking experiments to determine the properties of new derivatives, the new drug was ultimately successfully designed.

6.
Sci Total Environ ; 912: 168834, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38036125

RESUMO

Atmosphere is an important component of the microplastics (MPs) cycle. However, studies on atmospheric MPs in peri-urban farmland ecosystems are limited. Herein, the occurrence, influencing factors and geographic sources of atmospheric MPs in peri-urban farmland ecosystems have been analyzed. The average deposition flux of atmospheric MPs was found to be 167.09 ± 92.03 item·m-2·d-1. Around 68 % MPs had particle size <1000 µm, while the main colors of MPs were black (40.71 %) and blue (20.64 %). Approximately 91 % MPs were fibers, while polyethylene terephthalate (49 %) and rayon (36.93 %) were observed as the major microplastic types. The main factors influencing the atmospheric deposition of MPs were gross domestic product (GDP), population density, air pressure, and wind direction. Deposition fluxes exhibited positive correlations with GDP, population density and air pressure, and negative correlations with wind direction. Combined with the backward trajectory model, MPs were mainly found to be originated from the southeast in September and from the northwest in October-February. The study of atmospheric MPs in farmland ecosystems in peri-urban areas is important for the protection of ecological environment, prevention of human diseases and control of MPs pollution.


Assuntos
Microplásticos , Poluentes Químicos da Água , Humanos , Pequim , Plásticos , Ecossistema , Fazendas , China , Monitoramento Ambiental
7.
Small ; : e2308192, 2023 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-38072794

RESUMO

The single-atom sites (SAs) have achieved enhanced performance toward oxygen reduction reaction (ORR) with the effective utilization of the active sites. However, the excess adsorption of the intermediates and the limited stability hinders performance improvement. Metal clusters with promising stability and weak adsorption can be used as potential substitutions, but the lack of active sites is considered undesirable for catalytic reactions. Herein, a framework of Fe nanoclusters combined with SAs on One dimensional (1D) carbon nanotubes (Fe3 C-NCNTs 90 min CC-1 ) is synthesized to confirm the synergistic atom-cluster interaction. The composite exhibits strong polarization and electron redistribution between nanocluster and SAs. The electron redistribution will significantly boost the electron transport and the desorption of the intermediates, which is confirmed by off-axis holography and DFT calculation. The electrocatalytic performance is significantly enhanced as the half-wave potential of ORR increased 75 mV and the potential of OER increased 133 mV compared with the sample without nanoclusters. Furthermore, such a bifunctional catalyst endows homemade Zn-air batteries (ZABs) with high power density and long-term stability. This work paves a facile route to design bifunctional ORR/OER electrocatalysts consisting of 0D composite structures.

8.
Molecules ; 28(21)2023 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-37959871

RESUMO

In this study, a new 3D porous PVDF-foam-imprinted membrane (PPIM) for the selective separation of artemisinin (ART) was first prepared via the dopamine adhesion of pre-synthesized MIPs into the interior of the PPIM. In the PPIM, the pre-synthesized molecularly imprinted polymers (MIPs) with artesunate (ARU) as a dummy template were uniformly loaded on the interior of the membrane, avoiding the defects of recognition site encapsulation found in the conventional membrane. This membrane also exhibited excellent flux, which is beneficial in practical separation applications. The PPIM was systematically characterized via FT-IR, SEM, pore-size distribution analysis, water contact angle test, membrane flux, and mechanical performance analysis, respectively. In the static adsorption experiment, the pseudo-second-order kinetic model better fitted the rebinding data of ART. Under dynamic conditions, the ART adsorption capacity of the PPIM could be further remarkably improved by tailoring the flow rate to 3 mL min-1. In the selective separation experiment, with artemether (ARE) as the competition substrate, the selective separation ability (α) of the PPIM towards ART/artemether (ARE) reached its peak value (3.16) within only 10 min at this flow rate, which is higher than that of porous PVDF foam non-imprinted membranes (PPNM) (ca. 1.5), showing great separation efficiency in a short time. Moreover, the PPIM can be reused five times without a significant decrease in its adsorption capacities, showing good regeneration performance. This work highlights a simple strategy for constructing new MIMs with high flux and great mechanical strength to achieve the efficient selective separation of ART and ARE in practical applications.

9.
Am J Cancer Res ; 13(10): 4492-4507, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37970368

RESUMO

Extramammary Paget's disease (EMPD) is a rare form of adenocarcinoma usually found in apocrine gland-containing cutaneous regions. EMPD affects the vulvar area most commonly, followed by the perianal area, scrotum, penis, and axillary region. In its initial form, EMPD presents as an erythematous plaque with well-defined edges, fine scaling, excoriations, exulcerations, and lichenification. Generally, a definitive diagnosis can be made through histopathological analysis. Importantly, associated malignancies should be investigated prior to treatment initiation. Photodynamic therapy (PDT) is a modern, noninvasive treatment strategy for non-oncological diseases as well as various cancers. In recent years, PDT has been widely used to treat EMPD. This present article presents a discussion of the diagnosis and treatment of EMPD as well as the usefulness of PDT in its management.

10.
Virus Evol ; 9(2): vead064, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37953976

RESUMO

Most fungal viruses are RNA viruses, and no double-stranded DNA virus that infects fungi is known to date. A recent study detected DNA polymerase genes that originated from large dsDNA viruses in the genomes of basal fungi, suggestive of the existence of dsDNA viruses capable of infecting fungi. In this study, we searched for viral infection signatures in chromosome-level genome assemblies of the arbuscular mycorrhizal fungus Rhizophagus irregularis. We identified a continuous 1.5-Mb putative viral region on a chromosome in R. irregularis strain 4401. Phylogenetic analyses revealed that the viral region is related to viruses in the family Asfarviridae of the phylum Nucleocytoviricota. This viral region was absent in the genomes of four other R. irregularis strains and had fewer signals of fungal transposable elements than the other genomic regions, suggesting a recent and single insertion of a large dsDNA viral genome in the genome of this fungal strain. We also incidentally identified viral-like sequences in the genome assembly of the sea slug Elysia marginata that are evolutionally close to the 1.5-Mb putative viral region. In conclusion, our findings provide strong evidence of the recent infection of the fungus by a dsDNA virus.

11.
Environ Microbiol ; 25(11): 2621-2635, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37543720

RESUMO

Following the discovery of Acanthamoeba polyphaga mimivirus, diverse giant viruses have been isolated. However, only a small fraction of these isolates have been completely sequenced, limiting our understanding of the genomic diversity of giant viruses. MinION is a portable and low-cost long-read sequencer that can be readily used in a laboratory. Although MinION provides highly error-prone reads that require correction through additional short-read sequencing, recent studies assembled high-quality microbial genomes only using MinION sequencing. Here, we evaluated the accuracy of MinION-only genome assemblies for giant viruses by re-sequencing a prototype marseillevirus. Assembled genomes presented over 99.98% identity to the reference genome with a few gaps, demonstrating a high accuracy of the MinION-only assembly. As a proof of concept, we de novo assembled five newly isolated viruses. Average nucleotide identities to their closest known relatives suggest that the isolates represent new species of marseillevirus, pithovirus and mimivirus. The assembly of subsampled reads demonstrated that their taxonomy and genomic composition could be analysed at the 50× sequencing coverage. We also identified a pithovirus gene whose homologues were detected only in metagenome-derived relatives. Collectively, we propose that MinION-only assembly is an effective approach to rapidly perform a genome-wide analysis of isolated giant viruses.


Assuntos
Vírus Gigantes , Vírus Gigantes/genética , Genômica , Análise de Sequência de DNA , Metagenoma , Sequenciamento de Nucleotídeos em Larga Escala
12.
J Fungi (Basel) ; 9(8)2023 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-37623603

RESUMO

Rice false smut caused by Ustilaginoidea virens is one of the most devastating fungal diseases of rice (Oryza sativa) worldwide. Prochloraz and azoxystrobin belong to the groups of demethylation inhibitors and quinone outside inhibitors, respectively, and are commonly used for controlling this disease. In this study, we analyzed the sensitivities of 100 U. virens isolates from Yunnan, Sichuan, Chongqing, and Zhejiang in Southern China to prochloraz and azoxystrobin. The ranges of EC50 for prochloraz and azoxystrobin were 0.004-0.536 and 0.020-0.510 µg/mL, with means and standard errors of 0.062 ± 0.008 and 0.120 ± 0.007 µg/mL, respectively. However, the sensitivity frequency distributions of U. virens to prochloraz and azoxystrobin indicated the emergence of subpopulations with decreased sensitivity. Therefore, the mean EC50 values of 74% and 68% of the isolates at the main peak, 0.031 ± 0.001 and 0.078 ± 0.004 µg/mL, were used as the sensitivity baselines of U. virens to prochloraz and azoxystrobin, respectively. We found significant sensitivity differences to azoxystrobin among different geographical populations and no correlation between the sensitivities of U. virens to prochloraz and azoxystrobin. Among 887 U. virens isolates, the isolate 5-3-1 from Zhejiang showed moderate resistance to prochloraz, with a resistance factor of 22.45, while no nucleotide variation in the 1986-bp upstream or 1827-bp gene regions of CYP51 from 5-3-1 was detected. Overexpression of CYP51 is probably responsible for its resistance to prochloraz. Finally, artificial inoculation showed that 5-3-1 was highly pathogenic to rice, suggesting that the resistance of U. virens to prochloraz must be monitored and managed in Zhejiang.

13.
Front Psychiatry ; 14: 1179562, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37448488

RESUMO

Background: Previous observational studies have showed that certain psychiatric disorders may be linked to breast cancer risk, there is, however, little understanding of relationships between mental disorders and a variety of breast diseases. This study aims to investigate if mental disorders influence the risks of overall breast cancer, the two subtypes of breast cancer (ER+ and ER-), breast benign tumors and breast inflammatory diseases. Methods: During our research, genome-wide association study (GWAS) data for seven psychiatric disorders (schizophrenia, major depressive disorder, bipolar disorder, post-traumatic stress disorder, panic disorder, obsessive-compulsive disorder and anorexia nervosa) from the Psychiatric Genomics Consortium (PGC) and the UK Biobank were selected, and single-nucleotide polymorphisms (SNPs) significantly linked to these mental disorders were identified as instrumental variables. GWAS data for breast diseases came from the Breast Cancer Association Consortium (BCAC) as well as the FinnGen consortium. We performed two-sample Mendelian randomization (MR) analyses and multivariable MR analyses to assess these SNPs' effects on various breast diseases. Both heterogeneity and pleiotropy were evaluated by sensitivity analyses. Results: When the GWAS data of psychiatric disorders were derived from the PGC, our research found that schizophrenia significantly increased the risks of overall breast cancer (two-sample MR: OR 1.05, 95%CI [1.03-1.07], p = 3.84 × 10-6; multivariable MR: OR 1.06, 95%CI [1.04-1.09], p = 2.34 × 10-6), ER+ (OR 1.05, 95%CI [1.02-1.07], p = 5.94 × 10-5) and ER- (two-sample MR: OR 1.04, 95%CI [1.01-1.07], p = 0.006; multivariable MR: OR 1.06, 95%CI [1.02-1.10], p = 0.001) breast cancer. Nevertheless, major depressive disorder only showed significant positive association with overall breast cancer (OR 1.12, 95%CI [1.04-1.20], p = 0.003) according to the two-sample MR analysis, but not in the multivariable MR analysis. In regards to the remainder of the mental illnesses and breast diseases, there were no significant correlations. While as for the data from the UK Biobank, schizophrenia did not significantly increase the risk of breast cancer. Conclusions: The correlation between schizophrenia and breast cancer found in this study may be false positive results caused by underlying horizontal pleiotropy, rather than a true cause-and-effect relationship. More prospective studies are still needed to be carried out to determine the definitive links between mental illnesses and breast diseases.

14.
iScience ; 26(7): 107197, 2023 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-37456831

RESUMO

Alveolar macrophages (AMs) are resident innate immune cells that play vital roles in maintaining lung physiological functions. However, the effects of aging on their dynamics, heterogeneity, and transcriptional profiles remain to be fully elucidated. Through single cell RNA sequencing (scRNA-seq), we identified CBFß as an indispensable transcription factor that ensures AM self-renewal. Intriguingly, despite transcriptome similarities of proliferating cells, AMs from aged mice exhibited reduced embryonic stem cell-like features. Aged AMs also displayed compromised DNA repair abilities, potentially leading to obstructed cell cycle progression and an elevation of senescence markers. Consistently, AMs from aged mice exhibited impaired self-renewal ability and reduced sensitivity to GM-CSF. Decreased CBFß was observed in the cytosol of AMs from aged mice. Similar senescence-like phenotypes were also found in human AMs. Taken together, these findings suggest that AMs in aged hosts demonstrate senescence-like phenotypes, potentially facilitated by the abrogated CBF ß activity.

15.
Breast Cancer Res ; 25(1): 63, 2023 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-37287069

RESUMO

BACKGROUND: Breast cancer presents as one of the top health threats to women around the world. Myeloid cells are the most abundant cells and the major immune coordinator in breast cancer tumor microenvironment (TME), target therapies that harness the anti-tumor potential of myeloid cells are currently being evaluated in clinical trials. However, the landscape and dynamic transition of myeloid cells in breast cancer TME are still largely unknown. METHODS: Myeloid cells were characterized in the single-cell data and extracted with a deconvolution algorithm to be assessed in bulk-sequencing data. We used the Shannon index to describe the diversity of infiltrating myeloid cells. A 5-gene surrogate scoring system was then constructed and evaluated to infer the myeloid cell diversity in a clinically feasible manner. RESULTS: We dissected the breast cancer infiltrating myeloid cells into 15 subgroups including macrophages, dendritic cells (DCs), and monocytes. Mac_CCL4 had the highest angiogenic activity, Mac_APOE and Mac_CXCL10 were highly active in cytokine secretion, and the DCs had upregulated antigen presentation pathways. The infiltrating myeloid diversity was calculated in the deconvoluted bulk-sequencing data, and we found that higher myeloid diversity was robustly associated with more favorable clinical outcomes, higher neoadjuvant therapy responses, and a higher rate of somatic mutations. We then used machine learning methods to perform feature selection and reduction, which generated a clinical-friendly scoring system consisting of 5 genes (C3, CD27, GFPT2, GMFG, and HLA-DPB1) that could be used to predict clinical outcomes in breast cancer patients. CONCLUSIONS: Our study explored the heterogeneity and plasticity of breast cancer infiltrating myeloid cells. By using a novel combination of bioinformatic approaches, we proposed the myeloid diversity index as a new prognostic metric and constructed a clinically practical scoring system to guide future patient evaluation and risk stratification.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/genética , Neoplasias da Mama/terapia , Células Mieloides , Macrófagos/metabolismo , Monócitos , Prognóstico , Microambiente Tumoral/genética
16.
Sci Total Environ ; 883: 163567, 2023 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-37094671

RESUMO

As the research on microplastics (MPs) has intensified, more attention has been paid to MPs deposition in the atmosphere. This study further explores and compares the characteristics, the possible sources and influencing factors of deposition of MPs in three different ecosystems: forest, agricultural and residential area in Beijing. It was found that the deposited plastics were mostly white or black fibres, with PET and RY as the main MPs types. The range of deposition fluxes was 67.06-461.02 item·m-2·d-1, with highest deposition in residential area and lowest in forest, significant differences in MPs characteristics between environments. Based on MPs composition and shape, combined with backward trajectory analysis, the main sources of MPs were found to be textiles. Deposition of MPs was found to be influenced by environmental and meteorological factors. Factors such as gross domestic product and population density had a significant impact on the deposition flux, while wind played a diluting role for atmospheric MPs. The study investigated the characteristics of MPs in different ecosystems which may help to understand the transport patterns of MPs and is of great importance for the management of MPs pollution.

17.
Sci Immunol ; 8(82): eadf0348, 2023 04 14.
Artigo em Inglês | MEDLINE | ID: mdl-36821695

RESUMO

The relationship between diabetes and coronavirus disease 2019 (COVID-19) is bidirectional: Although individuals with diabetes and high blood glucose (hyperglycemia) are predisposed to severe COVID-19, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can also cause hyperglycemia and exacerbate underlying metabolic syndrome. Therefore, interventions capable of breaking the network of SARS-CoV-2 infection, hyperglycemia, and hyperinflammation, all factors that drive COVID-19 pathophysiology, are urgently needed. Here, we show that genetic ablation or pharmacological inhibition of mitochondrial pyruvate carrier (MPC) attenuates severe disease after influenza or SARS-CoV-2 pneumonia. MPC inhibition using a second-generation insulin sensitizer, MSDC-0602K (MSDC), dampened pulmonary inflammation and promoted lung recovery while concurrently reducing blood glucose levels and hyperlipidemia after viral pneumonia in obese mice. Mechanistically, MPC inhibition enhanced mitochondrial fitness and destabilized hypoxia-inducible factor-1α, leading to dampened virus-induced inflammatory responses in both murine and human lung macrophages. We further showed that MSDC enhanced responses to nirmatrelvir (the antiviral component of Paxlovid) to provide high levels of protection against severe host disease development after SARS-CoV-2 infection and suppressed cellular inflammation in human COVID-19 lung autopsies, demonstrating its translational potential for treating severe COVID-19. Collectively, we uncover a metabolic pathway that simultaneously modulates pulmonary inflammation, tissue recovery, and host metabolic health, presenting a synergistic therapeutic strategy to treat severe COVID-19, particularly in patients with underlying metabolic disease.


Assuntos
COVID-19 , Diabetes Mellitus , Hiperglicemia , Humanos , Animais , Camundongos , Transportadores de Ácidos Monocarboxílicos , SARS-CoV-2/metabolismo , Glicemia/metabolismo , Hiperglicemia/tratamento farmacológico , Hiperglicemia/metabolismo
18.
Arch Virol ; 168(3): 80, 2023 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-36740641

RESUMO

Acanthamoeba castellanii medusavirus J1 is a giant virus that was isolated from a hot spring in Japan in 2019. Recently, a close relative of this virus, named medusavirus stheno T3, was isolated in Japan. Here, we describe their morphological, genomic, and gene content similarities and also propose to create a new family, "Mamonoviridae", a new genus, "Medusavirus", and two species, "Medusavirus medusae" and "Medusavirus sthenus", to classify these two viruses within the phylum Nucleocytoviricota.


Assuntos
Vírus Gigantes , Vírus , Filogenia , Genoma Viral , Vírus/genética , Vírus Gigantes/genética , Genômica
19.
Comput Biol Med ; 152: 106365, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36516577

RESUMO

Recently, researchers have introduced Transformer into medical image segmentation networks to encode long-range dependency, which makes up for the deficiencies of convolutional neural networks (CNNs) in global context modeling, and thus improves segmentation performance. However, in Transformer, due to the heavy computational burden of paired attention modeling between redundant visual tokens, the efficiency of Transformer needs to be further improved. Therefore, in this paper, we propose ATTransUNet, a Transformer enhanced hybrid architecture based on the adaptive token for ultrasound and histopathology image segmentation. In the encoding stage of the ATTransUNet, we introduced an Adaptive Token Extraction Module (ATEM), which can mine a few important visual tokens in the image for self-attention modeling, thus reducing the complexity of the model and improving the segmentation accuracy. In addition, in the decoding stage, we introduce a Selective Feature Reinforcement Module (SFRM) to reinforce the representation of and attention to key tissues or pathological features. The proposed ATTransUNet is evaluated on the basis of three medical image segmentation datasets. The results show that ATTransUNet achieves the best segmentation performance compared with the previous state-of-the-art models, and the proposed method is also competitive in terms of the network parameters and computation.


Assuntos
Processamento de Imagem Assistida por Computador , Redes Neurais de Computação , Ultrassonografia
20.
ACS Nano ; 16(10): 15927-15934, 2022 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-36166823

RESUMO

Studies of the diffusion dynamics of magnetic skyrmions have generated widespread interest in both fundamental physics and spintronics applications. Here we report the magnetic-field-assisted diffusion motion of skyrmions in a microstructured chiral FeGe magnet. We demonstrate the enhancement of diffusion motion of magnetic skyrmions that is manipulated and driven by an oscillatory magnetic field. Further, the directed diffusion of skyrmions is observed when an in-plane field was introduced to break the symmetry of the system. Finally, we demonstrate the application of a magnetic field can induce an arrangements transition of skyrmions assemble in microstructure, that is, from a stiff hexagonal lattice to a weak interactional isotropic state. By using a step-ascended magnetic field we finished the observation of a particle-like diffusive motion for magnetic skyrmions that transport from high-concentration regions to low-concentration regions and the diffusion flux is proportional to the concentration gradient followed Fick's law.

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