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1.
Chem Commun (Camb) ; 2023 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-36722415

RESUMO

A novel responsive hydrogel exhibiting self-reinforcement and self-healing capacity was developed based on the hydrophobic aggregation of strained 1,2-dithiolane rings. Oligomerization of 1,2-dithiolane within hydrophobic domains under UV irradiation not only reinforced the hydrogel but also maintained its dynamic cross-linked nature by converting the intraring dynamic S-S bond to an outer one.

2.
Mol Med ; 29(1): 2, 2023 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-36604627

RESUMO

Atherosclerosis (AS), leading to gradual occlusion of the arterial lumen, refers to the accumulation of lipids and inflammatory debris in the arterial wall. Despite therapeutic advances over past decades including intervention or surgery, atherosclerosis is still the most common cause of cardiovascular diseases and the main mechanism of death and disability worldwide. Vascular smooth muscle cells (VSMCs) play an imperative role in the occurrence of atherosclerosis and throughout the whole stages. In the past, there was a lack of comprehensive understanding of VSMCs, but the development of identification technology, including in vivo single-cell sequencing technology and lineage tracing with the CreERT2-loxP system, suggests that VSMCs have remarkable plasticity and reevaluates well-established concepts about the contribution of VSMCs. Transcription factors, a kind of protein molecule that specifically recognizes and binds DNA upstream promoter regions or distal enhancer DNA elements, play a key role in the transcription initiation of the coding genes and are necessary for RNA polymerase to bind gene promoters. In this review, we highlight that, except for environmental factors, VSMC genes are transcriptionally regulated through complex interactions of multiple conserved cis-regulatory elements and transcription factors. In addition, through a series of transcription-related regulatory processes, VSMCs could undergo phenotypic transformation, proliferation, migration, calcification and apoptosis. Finally, enhancing or inhibiting transcription factors can regulate the development of atherosclerotic lesions, and the downstream molecular mechanism of transcriptional regulation has also been widely studied.


Assuntos
Aterosclerose , Músculo Liso Vascular , Humanos , Músculo Liso Vascular/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Proliferação de Células/genética , Aterosclerose/metabolismo , Regulação da Expressão Gênica , Miócitos de Músculo Liso/metabolismo , Células Cultivadas , Fenótipo
4.
Dev Cell ; 2023 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-36696903

RESUMO

Chromothripsis is a catastrophic event of chromosomal instability that involves intensive fragmentation and rearrangements within localized chromosomal regions. However, its cause remains unclear. Here, we show that reduction and inactivation of Ran GTPase-activating protein 1 (RanGAP1) commonly occur in human osteosarcoma, which is associated with a high rate of chromothripsis. In rapidly expanding mouse osteoprogenitors, RanGAP1 deficiency causes chromothripsis in chr1q, instant inactivation of Rb1 and degradation of p53, consequent failure in DNA damage repair, and ultrafast osteosarcoma tumorigenesis. During mitosis, RanGAP1 anchors to the kinetochore, where it recruits PP1-γ to counteract the activity of the spindle-assembly checkpoint (SAC) and prevents TOP2A degradation, thus safeguarding chromatid decatenation. Loss of RanGAP1 causes SAC hyperactivation and chromatid decatenation failure. These findings demonstrate that RanGAP1 maintains mitotic chromosome integrity and that RanGAP1 loss drives tumorigenesis through its direct effects on SAC and decatenation and secondary effects on DNA damage surveillance.

5.
Patterns (N Y) ; 4(1): 100658, 2023 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-36699735

RESUMO

Metagenomic analysis has been explored for disease diagnosis and biomarker discovery. Low sample sizes, high dimensionality, and sparsity of metagenomic data challenge metagenomic investigations. Here, an unsupervised microbial embedding, grouping, and mapping algorithm (MEGMA) was developed to transform metagenomic data into individualized multichannel microbiome 2D representation by manifold learning and clustering of microbial profiles (e.g., composition, abundance, hierarchy, and taxonomy). These 2D representations enable enhanced disease prediction by established ConvNet-based AggMapNet models, outperforming the commonly used machine learning and deep learning models in metagenomic benchmark datasets. These 2D representations combined with AggMapNet explainable module robustly identified more reliable and replicable disease-prediction microbes (biomarkers). Employing the MEGMA-AggMapNet pipeline for biomarker identification from 5 disease datasets, 84% of the identified biomarkers have been described in over 74 distinct works as important for these diseases. Moreover, the method also discovered highly consistent sets of biomarkers in cross-cohort colorectal cancer (CRC) patients and microbial shifts in different CRC stages.

6.
J Affect Disord ; 324: 334-340, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36608848

RESUMO

The differential structural covariance of nucleus accumbens (NAcc), playing a vital role in etiology and treatment, remains unclear in depression. We aimed to investigate whether structural covariance of NAcc was altered and how it was modulated by illness duration and severity of symptom measured with Hamilton Depression scale (HAMD). T1-weighted anatomical images of never-treated first-episode patients with depression (n = 195) and matched healthy controls (HCs, n = 78) were acquired. Gray matter volumes were calculated using voxel-based morphometry analysis for each subject. Then, we explored abnormal structural covariance of NAcc and how the abnormality was modulated by illness duration and severity of symptom. Patients with depression exhibited altered structural covariance of NAcc connected to key brain regions in reward system including the medial orbitofrontal cortex, amygdala, insula, parahippocampa gyrus, precuneus, thalamus, hippocampus and cerebellum. In addition, the structural covariance of the NAcc was distinctly modulated by illness duration and the severity of symptom in patients with depression. What is more, the structural covariance of the NAcc connected to hippocampus was modulated by these two factors at the same time. These results elucidate altered structural covariance of the NAcc and its distinct modulation of illness duration and severity of symptom.


Assuntos
Depressão , Núcleo Accumbens , Humanos , Núcleo Accumbens/diagnóstico por imagem , Depressão/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Encéfalo , Substância Cinzenta/diagnóstico por imagem
7.
Am J Transplant ; 2023 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-36695693

RESUMO

Acute rejection (AR) is an important factor that leads to poor prognosis after liver transplantation (LT). Macrophage M1-polarization is an important mechanism in AR development. MicroRNAs play vital roles in disease regulation; however, their effects on macrophages and AR remain unclear. In this study, rat models of AR were established following LT, and macrophages and peripheral blood mononuclear cells were isolated from rats and humans, respectively. We found miR-449a expression to be significantly reduced in macrophages and peripheral blood mononuclear cells. Overexpression of miR-449a not only inhibited the M1-polarization of macrophages in vitro but also improved the AR of transplant in vivo. The mechanism involved inhibiting the noncanonical nuclear factor-kappaB (NF-κB) pathway. We identified procollagen-lysine1,2-oxoglutarate5-dioxygenase 1 (PLOD1) as a target gene of miR-449a, which could reverse miR-449a's inhibition of macrophage M1-polarization, amelioration of AR, and inhibition of the NF-κB pathway. Overall, miR-449a inhibited the NF-κB pathway in macrophages through PLOD1 and also inhibited the M1-polarization of macrophages, thus attenuating AR after LT. In conclusion, miR-449a and PLOD1 may be new targets for the prevention and mitigation of AR.

8.
Chem Biodivers ; 2023 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-36696143

RESUMO

Shawurenine C (1a) and D (1b), a new pair of regioisomeric C19-diterpenoid alkaloids, and five known C19-diterpenoid alkaloids (2-6) were isolated from the aerial part of Delphinium shawurense W. T. Wang. The chemical structures of new compounds were established based on spectroscopic analyses: HR-ESI-MS, and 1D, 2D NMR spectroscopic data. The anti-inflammatory and cytotoxic activities of these diterpenoid alkaloids were also evaluated.

9.
Water Sci Technol ; 87(2): 492-507, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36706295

RESUMO

In this study, magnetic biochar (Fe-BC) was synthesized from phoenix tree leaves and FeSO4·7H2O by impregnation-pyrolysis method, and was used to activate H2O2 to degrade Cu-EDTA. The effects of preparation parameters on the degradation of Cu-EDTA by Fe-BC/H2O2 system were investigated by degradation experiments and characterization methods (SEM, BET, FTIR, XRD and XPS). The results showed that the magnetic biochar prepared under the pyrolysis temperature of 400 °C, pyrolysis time of 3 h and iron content of 3 wt% had the best catalytic activity. Within 120 min, the breaking efficiency of Cu-EDTA binding, precipitation efficiency of Cu2+ and removal efficiency of TOC could reach 78.48, 71.65 and 46.54% at the conditions of adding 1.0 g/L magnetic biochar and 25 mM H2O2 and the iron dissolution was only 0.32 mg/L. The characterization results and comparison experiments demonstrated that the catalytic effect of magnetic biochar not only depends on the transfer of electrons to H2O2 by the loaded iron oxides, but also the active oxygen functional groups (OFGs) and persistent free radicals (PFRs) contained on the surface can transfer electrons to H2O2 or even dissolved oxygen to produce an amount of hydroxyl radicals (·OH) and superoxide anion radicals (O2·-).


Assuntos
Peróxido de Hidrogênio , Ferro , Ácido Edético , Peróxido de Hidrogênio/química , Ferro/química , Carvão Vegetal/química , Oxigênio , Fenômenos Magnéticos
11.
Cell Rep ; 42(1): 112002, 2023 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-36662617

RESUMO

Type I interferon (IFN-I) signaling is central to inducing antiviral innate immunity. However, the mechanisms for IFN-I signaling self-regulation are still largely unknown. Here, we report that RNA virus-infected macrophages with UBE2M deficiency produced decreased IFN-I expression in a RIG-I-dependent manner, causing an aggravated viral infection. Mechanistically, UBE2M inhibits RIG-I degradation by preventing the interaction of RIG-I and E3 ligase STUB1, resulting in antiviral IFN-I signaling activation. Simultaneously, IFN-I signaling-activated STAT1 facilitates the transcription of Trim21, leading to increased UBE2M degradation and blunted antiviral immunity. Translationally, oral administration of milk-derived extracellular vesicles containing RING domain-truncated TRIM21 (TRIM21-ΔRING) lacking E3 ligase activity efficiently transfers TRIM21-ΔRING into macrophages. TRIM21-ΔRING suppresses UBE2M degradation by competitively binding to UBE2M with TRIM21, thereby enhancing antiviral immunity. Overall, we reveal a negative feedback loop of IFN-I signaling and develop a reagent to improve innate immunity against RNA viruses.

12.
Adipocyte ; 2023 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-36654490

RESUMO

High-fat diet (HFD) can cause obesity, inducing dysregulation of the visceral adipose tissue (VAT). This study aimed to explore potential biological pathways and hub genes involved in obese VAT, and for that, bioinformatic analysis of multiple datasets was performed. METHODS: The expression profiles (GSE30247, GSE167311 and GSE79434) were downloaded from Gene Expression Omnibus. Overlapping differentially expressed genes (ODEGs) between normal diet and HFD groups in GSE30247 and GSE167311 were selected to run protein-protein interaction network, GO and KEGG analysis. The hub genes in ODEGs were screened by Cytoscape software and further verified in GSE79434 and obese mouse model. RESULTS: 747 ODEGs (599 up-regulated and 148 down-regulated) were screened, and the GO and KEGG analysis showed that the up-regulated ODEGs were significantly enriched in inflammatory response and extracellular matrix receptor interaction pathways. On the other hand, the down-regulated ODEGs were involved in metabolic pathways; However, there were none significant KEGG pathways. Furthermore, six hub genes, Mki67, Rac2, Itgb2, Emr1, Tyrobp, and Csf1r were acquired. These pathways and genes were verified in GSE79434 and VAT of obese mice. CONCLUSION: This study revealed that HFD induced VAT expansion, inflammation, and fibrosis, and the hub genes could be used as therapeutic biomarkers in obesity.

13.
Small ; : e2206360, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36587962

RESUMO

Dual-ion batteries (DIBs) with Co/Ni-free cathodes especially graphite cathodes are very attractive energy storage systems in the long run because of the cost effectiveness and sustainability. However, graphite cathodes severely suffer from poor structural stability during anions storage at high potentials owing to the oxidative decomposition of electrolytes and volume expansion. This work proposes an artificial cathode/electrolyte interphase (CEI) strategy by implanting polyphosphoric acid (PPA) nanofilms tightly on natural graphite (NG) particles via interfacial hydrogen bonding. The electrochemical results show that the PPA-modified graphite cathodes possess enhanced charge-discharge reversibility, accelerated electrode reaction kinetic, decreased resistance, decelerated self-discharge, and prolonged cycling life. Through post-analyses on the cycled graphite cathodes, the improved performance is mainly attributed to the PPA-based CEI, which effectively mitigates the electrolyte decomposition and protects the graphitic structure. More interestingly, the hydrogen bonding interactions between poly(vinyldifluoride) (PVDF) binder and PPA as validated through density functional theory calculations and practical experiments can increase the contact sites of PVDF chains on NG@PPA particles. Meanwhile, the cross-linking effect of PPA can enhance the mechanical strength of PVDF, thus the long life of NG@PPA cathode is also correlated with the improved mechanical stability of the entire electrode.

14.
Med Image Anal ; 85: 102753, 2023 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-36682152

RESUMO

Pancreatic cancer is a malignant tumor, and its high recurrence rate after surgery is related to the lymph node metastasis status. In clinical practice, a preoperative imaging prediction method is necessary for prognosis assessment and treatment decision; however, there are two major challenges: insufficient data and difficulty in discriminative feature extraction. This paper proposed a deep learning model to predict lymph node metastasis in pancreatic cancer using multiphase CT, where a dual-transformation with contrastive learning framework is developed to overcome the challenges in fine-grained prediction with small sample sizes. Specifically, we designed a novel dynamic surface projection method to transform 3D data into 2D images for effectively using the 3D information, preserving the spatial correlation of the original texture information and reducing computational resources. Then, this dynamic surface projection was combined with the spiral transformation to establish a dual-transformation method for enhancing the diversity and complementarity of the dataset. A dual-transformation-based data augmentation method was also developed to produce numerous 2D-transformed images to alleviate the effect of insufficient samples. Finally, the dual-transformation-guided contrastive learning scheme based on intra-space-transformation consistency and inter-class specificity was designed to mine additional supervised information, thereby extracting more discriminative features. Extensive experiments have shown the promising performance of the proposed model for predicting lymph node metastasis in pancreatic cancer. Our dual-transformation with contrastive learning scheme was further confirmed on an external public dataset, representing a potential paradigm for the fine-grained classification of oncological images with small sample sizes. The code will be released at https://github.com/SJTUBME-QianLab/Dual-transformation.

15.
J Am Coll Emerg Physicians Open ; 4(1): e12879, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36618778
16.
Dev Neurorehabil ; : 1-18, 2023 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-36659872

RESUMO

Children with cerebral palsy (CP) are faced with long-term dysfunction. The International Classification of Functioning, Disability and Health for Children and Youth (ICF-CY) has been proposed but the complicated procedure limits the feasibility of clinical application and the exploration of health degrees. This study was aimed to establish a Mokken scale based on the ICF-CY for CP, and then to estimate psychometric properties through the derived Rasch model. 150 children with CP were assessed by the categories of "b" and "d" components in the core set. The binarized data was screened by the Mokken scale analysis and utilized for generating a reliable Rasch model. The validity of the final model was checked by the correlation between person ability, Gross Motor Function Classification System (GMFCS) and total scores. Using the Mokken scale to guide Rasch modeling, we can parameterize the properties of ICF-CY and realize the simple assessment of person abilities for children with CP.

17.
Plant Cell ; 2023 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-36648110

RESUMO

In Arabidopsis thaliana, female gametophyte (FG) development is accompanied by the formation and expansion of the large vacuole in the FG; this is essential for FG expansion, nuclear polar localization, and cell fate determination. Arabidopsis VACUOLELESS GAMETOPHYTES (VLG) facilitates vesicular fusion to form large vacuole in the FG, but the regulation of VLG remains largely unknown. Here we found that gain-of-function mutation of BRASSINOSTEROID INSENSITIVE2 (BIN2) (bin2-1) increases VLG abundance to induce the vacuole formation at stage FG1, and leads to abortion of FG. Loss-of-function mutation of BIN2 and its homologs (bin2-3 bil1 bil2) reduced VLG abundance and mimicked vlg/VLG phenotypes. Knocking down VLG in bin2-1 decreased the ratio of aberrant vacuole formation at stage FG1, whereas FG1-specific overexpression of VLG mimicked the bin2-1 phenotype. VLG partially rescued the bin2-3 bil1 bil2 phenotype, demonstrating that VLG acts downstream of BIN2. Mutation of VLG residues that are phosphorylated by BIN2 altered VLG stability and a phosphorylation mimic of VLG causes similar defects as did bin2-1. Therefore, BIN2 may function by interacting with and phosphorylating VLG in the FG to enhance its stability and abundance, thus facilitating vacuole formation. Our findings provide mechanistic insight into how the BIN2-VLG module regulates the spatiotemporal formation of the large vacuole in FG development.

18.
BMC Sports Sci Med Rehabil ; 15(1): 6, 2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36631910

RESUMO

BACKGROUND: In the postpandemic era, wearing protective masks in public places will still be an important means of blocking popular viruses in the future. The purpose of this study was to explore whether sports performance was affected by mask wearing and exercise duration during 15-min treadmill running at a speed of 75% maximal aerobic speed. METHODS: Thirty-six males were randomly divided into mask and nonmask groups. The kinematic and kinetic data were obtained at four time points (RN0-1 min, RN5-6 min, RN9-10 min, and RN14-15 min) during running. Two-way mixed ANOVA was applied to examine the effects between groups and times with Bonferroni post hoc comparison and independent samples t-test. RESULTS: The results showed that there was no difference between mask and nonmask group during running (p > 0.05). As running time increased, hip joint ROM, hip joint flexion/extension max, and ankle joint plantarflexion max angles increased; knee joint flexion min and ankle joint dorsiflexion max angles decreased; average peak vertical ground reaction forces (PVGRF) increased after 9 min-running (p < 0.05). CONCLUSIONS: Wearing a medical protective mask does not affect the joint angle and touchdown PVGRF of lower extremities during treadmill running while affected by running time and changed after 9 min-treadmill running. Future studies will examine the effects of wearing masks during the pandemic on muscle activation and blood biochemical values during exercise. TRIAL REGISTRATION NO: ChiCTR2000040535 (date of registration on December 1, 2020). Prospectively registered in the Chinese Clinical Trial Registry.

19.
Ophthalmol Ther ; 2023 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-36609829

RESUMO

INTRODUCTION: Myopia is recognized as a progressive eye disease. The aim of this study was to evaluate the frequency and associated factors of clinically significant axial length (AL) shortening among myopic children following repeated low-level red light (RLRL) therapy. METHODS: The clinical data that were collected for the myopic children aged 3-17 years who received an RLRL therapy delivered by home-use desktop light device that emitted light at 650 nm for at least 1 year, were reviewed. The clinical data included AL, spherical equivalent refraction (SER), and visual acuity measured at baseline and follow-up. The primary outcomes were frequency of AL shortening of > 0.05 mm, > 0.10 mm, and > 0.20 mm per year, and associated factors of AL shortening per year. RESULTS: A total of 434 myopic children with at least 12 months of follow-up data were included. The mean age of participants was 9.7 (2.6) years with SER of -3.74 (2.60) diopters. There were 115 (26.50%), 76 (17.51%), and 20 (4.61%) children with AL shortening based on cutoffs of 0.05 mm/year, 0.10 mm/year, and 0.20 mm/year, respectively. In the multivariable model, AL shortening was significantly associated with older baseline age, female gender, and longer baseline AL or greater spherical equivalent refraction (all P < 0.05). Among AL shortened eyes, the mean AL difference (standard deviation, SD) was -0.142 (0.094) mm/year. Greater AL shortening was observed among children who were younger and had longer baseline AL (all P < 0.05). CONCLUSIONS: More than a quarter of children had AL shortening > 0.05 mm following RLRL therapy, and the overall mean AL change was -0.142 mm/year. Further studies should explore the mechanisms underlying AL shortening.

20.
Small ; : e2207044, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36642802

RESUMO

Precise design of low-cost, efficient and definite electrocatalysts is the key to sustainable renewable energy. Herein, this work develops a targeted-anchored and subsequent spontaneous-redox strategy to synthesize nickel-iron layered double hydroxide (LDH) nanosheets anchored with monodispersed platinum (Pt) sites (Pt@LDH). Intermediate metal-organic frameworks (MOF)/LDH heterostructure not only provides numerous confine points to guarantee the stability of Pt sites, but also excites the spontaneous reduction for PtII . Electronic structure, charge transfer ability and reaction kinetics of Pt@LDH can be effectively facilitated by the monodispersed Pt moieties. As a result, the optimized Pt@LDH that with the 5% ultra-low content Pt exhibits the significant increment in electrochemical water splitting performance in alkaline media, which only afford low overpotentials of 58 mV at 10 mA cm-2 for hydrogen evolution reaction (HER) and 239 mV at 10 mA cm-2 for oxygen evolution reaction (OER), respectively. In a real device, Pt@LDH can drive an overall water-splitting at low cell voltage of 1.49 V at 10 mA cm-2 , which can be superior to most reported similar LDH-based catalysts. Moreover, the versatility of the method is extended to other MOF precursors and noble metals for the design of ultrathin LDH supported monodispersed noble metal electrocatalysts promoting research interest in material design.

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