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1.
ACS Appl Bio Mater ; 5(5): 2224-2231, 2022 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-35465653

RESUMO

Semiconductor polymers have several featured advantages, such as easily tunable optical properties, high light harvesting, good photostability, etc. However, semiconductor polymers with desirable NIR-II absorbance for the applications of both NIR-II photoacoustic (PA) imaging and photothermal therapy (PTT) are still lacking. Herein, we synthesized a donor-acceptor (D-A) type semiconductor polymer PTPTQ with thiophene (TP) as the electron donor and thiadiazoloquinoxaline (TQ) as the acceptor. PTPTQ had a brushlike topological structure with two poly(ethylene glycol) (PEG) chains (2000 Da) in each repeating unit. Such an intriguing structure endowed it with high hydrophilicity, good biocompatibility, and prominent passive tumor targeting ability. PTPTQ exhibited strong absorption in 600-1800 nm and good photostability. Its photothermal conversion efficiency was determined to be about 41.36%, which rendered it excellent properties in NIR-II PA imaging and PTT. By using PTPTQ as a PTT agent, the mouse tumor models can be eradicated. Taken together, the overall properties of PTPTQ make it promising as a tumor theranostic agent.

2.
Nature ; 605(7908): 139-145, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35444279

RESUMO

Cellular transformation induces phenotypically diverse populations of tumour-infiltrating T cells1-5, and immune checkpoint blockade therapies preferentially target T cells that recognize cancer cell neoantigens6,7. Yet, how other classes of tumour-infiltrating T cells contribute to cancer immunosurveillance remains elusive. Here, in a survey of T cells in mouse and human malignancies, we identified a population of αß T cell receptor (TCR)-positive FCER1G-expressing innate-like T cells with high cytotoxic potential8 (ILTCKs). These cells were broadly reactive to unmutated self-antigens, arose from distinct thymic progenitors following early encounter with cognate antigens, and were continuously replenished by thymic progenitors during tumour progression. Notably, expansion and effector differentiation of intratumoural ILTCKs depended on interleukin-15 (IL-15) expression in cancer cells, and inducible activation of IL-15 signalling in adoptively transferred ILTCK progenitors suppressed tumour growth. Thus, the antigen receptor self-reactivity, unique ontogeny, and distinct cancer cell-sensing mechanism distinguish ILTCKs from conventional cytotoxic T cells, and define a new class of tumour-elicited immune response.


Assuntos
Imunidade Inata , Interleucina-15 , Neoplasias , Animais , Diferenciação Celular , Camundongos , Neoplasias/metabolismo , Receptores de Antígenos de Linfócitos T/metabolismo , Linfócitos T Citotóxicos/metabolismo
3.
J Immunol ; 208(9): 2196-2206, 2022 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-35418468

RESUMO

In the viral infection process, host gene function is usually reported as either defending the host or assaulting the virus. In this study, we demonstrated that zebrafish ceramide kinase-like (CERKL) mediates protection against viral infection via two distinct mechanisms: stabilization of TANK-binding kinase 1 (TBK1) through impairing K48-linked ubiquitination and degradation of spring viremia of carp virus (SVCV) P protein by dampening K63-linked ubiquitination, resulting in an improvement of the host immune response and a decline in viral activity in epithelioma papulosum cyprini (EPC) cells. On SVCV infection, ifnφ1 expression was increased or blunted by CERKL overexpression or knockdown, respectively. Subsequently, we found that CERKL localized in the cytoplasm, where it interacted with TBK1 and enhanced its stability by impeding the K48-linked polyubiquitination; meanwhile, the antiviral capacity of TBK1 was significantly potentiated by CERKL. In contrast, CERKL also interacted with and degraded SVCV P protein to disrupt its function in viral proliferation. Further mechanism analysis revealed K63-linked deubiquitination is the primary means of CERKL-mediated SVCV P protein degradation. Taken together, our study reveals a novel mechanism of fish defense against viral infection: the single gene cerkl is both a shield for the host and a spear against the virus, which strengthens resistance.


Assuntos
Carpas , Doenças dos Peixes , Infecções por Rhabdoviridae , Animais , Vírus de DNA , Fosfotransferases (Aceptor do Grupo Álcool) , Rhabdoviridae , Ubiquitinação , Proteínas Virais , Viremia , Peixe-Zebra , Proteínas de Peixe-Zebra/química , Proteínas de Peixe-Zebra/metabolismo
4.
Bioact Mater ; 16: 107-119, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35386322

RESUMO

The clinical outcomes of cancer nanovaccine have been largely impeded owing to the low antigen-specific T cell response rate and acquired resistance caused by the immunosuppressive tumor microenvironment (TME). Here, we reported a tumor acidity-responsive nanovaccine to remodel the immunosuppressive TME and expand the recruitment of tumor infiltrating lymphocytes (TILs) using hybrid micelles (HM), which encapsulated colony stimulating factor 1 receptor (CSF1-R) inhibitor BLZ-945 and indoleamine 2,3-dioxygenase (IDO) inhibitor NLG-919 in its core and displayed a model antigen ovalbumin (OVA) on its surface (denoted as BN@HM-OVA). The bioactive nanovaccine is coated with a polyethylene glycol (PEG) shell for extending nanoparticle circulation. The shell can be shed in response to the weakly acidic tumor microenvironment. The decrease in size and the increase in positive charge may cause the deep tumor penetration of drugs. We demonstrated that the bioactive nanovaccine dramatically enhance antigen presentation by dendritic cells (DCs) and drugs transportation into M1-like tumor-associated macrophages (TAMs) and tumor cells via size reduction and increasing positive charge caused by the weakly acidic TME. Such bioactive nanovaccine could remodel the immunosuppressive TME into an effector T cells favorable environment, leading to tumor growth inhibition in prophylactic and therapeutic E.G7-OVA tumor models. Furthermore, combining the bioactive nanovaccine with simultaneous anti-PD-1 antibody treatment leads to a long-term tumor inhibition, based on the optimal timing and sequence of PD-1 blockade against T cell receptor. This research provides a new strategy for the development of efficient cancer immunotherapy.

5.
Front Neurosci ; 16: 701632, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35386595

RESUMO

Due to overlapping tremor features, the medical diagnosis of Parkinson's disease (PD) and essential tremor (ET) mainly relies on the clinical experience of doctors, which often leads to misdiagnosis. Seven predictive models using machine learning algorithms including random forest (RF), eXtreme Gradient Boosting (XGBoost), support vector machine (SVM), logistic regression (LR), ridge classification (Ridge), backpropagation neural network (BP), and convolutional neural network (CNN) were evaluated and compared aiming to better differentiate between PD and ET by using accessible demographics and tremor information of the upper limbs. The tremor information including tremor acceleration and surface electromyogram (sEMG) signals were collected from 398 patients (PD = 257, ET = 141) and then were used to train the established models to separate PD and ET. The performance of the models was evaluated by indices of accuracy and area under the curve (AUC), which indicated the ensemble learning models including RF and XGBoost showed the best overall predictive ability with accuracy above 0.84 and AUC above 0.90. Furthermore, the relative importance of sex, age, four postures, and five tremor features was analyzed and ranked showing that the dominant frequency of sEMG of flexors, the average amplitude of sEMG of flexors, resting posture, and winging posture had a greater impact on the diagnosis of PD, whereas sex and age were less important. These results provide a reference for the intelligent diagnosis of PD and show promise for use in wearable tremor suppression devices.

6.
Cancer Commun (Lond) ; 2022 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-35470988

RESUMO

Dynamic and heterogeneous interaction between tumor cells and the surrounding microenvironment fuels the occurrence, progression, invasion, and metastasis of solid tumors. In this process, the tumor microenvironment (TME) fractures cellular and matrix architecture normality through biochemical and mechanical means, abetting tumorigenesis and treatment resistance. Tumor cells sense and respond to the strength, direction, and duration of mechanical cues in the TME by various mechanotransduction pathways. However, far less understood is the comprehensive perspective of the functions and mechanisms of mechanotransduction. Due to the great therapeutic difficulties brought by the mechanical changes in the TME, emerging studies have focused on targeting the adverse mechanical factors in the TME to attenuate disease rather than conventionally targeting tumor cells themselves, which has been proven to be a potential therapeutic approach. In this review, we discussed the origins and roles of mechanical factors in the TME, cell sensing, mechano-biological coupling and signal transduction, in vitro construction of the tumor mechanical microenvironment, applications and clinical significance in the TME.

7.
Redox Biol ; 52: 102304, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35413643

RESUMO

As essential regulators of mitochondrial quality control, mitochondrial dynamics and mitophagy play key roles in maintenance of metabolic health and cellular homeostasis. Here we show that knockdown of the membrane-inserted scaffolding and structural protein caveolin-1 (Cav-1) and expression of tyrosine 14 phospho-defective Cav-1 mutant (Y14F), as opposed to phospho-mimicking Y14D, altered mitochondrial morphology, and increased mitochondrial matrix mixing, mitochondrial fusion and fission dynamics as well as mitophagy in MDA-MB-231 triple negative breast cancer cells. Further, we found that interaction of Cav-1 with mitochondrial fusion/fission machinery Mitofusin 2 (Mfn2) and Dynamin related protein 1 (Drp1) was enhanced by Y14D mutant indicating Cav-1 Y14 phosphorylation prevented Mfn2 and Drp1 translocation to mitochondria. Moreover, limiting mitochondrial recruitment of Mfn2 diminished formation of the PINK1/Mfn2/Parkin complex required for initiation of mitophagy resulting in accumulation of damaged mitochondria and ROS (mtROS). Thus, these studies indicate that phospho-Cav-1 may be an important switch mechanism in cancer cell survival which could lead to novel strategies for complementing cancer therapies.


Assuntos
Caveolina 1 , Mitofagia , Caveolina 1/genética , Caveolina 1/metabolismo , Mitocôndrias/metabolismo , Dinâmica Mitocondrial/fisiologia , Proteínas Mitocondriais/genética , Proteínas Mitocondriais/metabolismo , Mitofagia/fisiologia , Espécies Reativas de Oxigênio/metabolismo
8.
Sci Transl Med ; 14(639): eabh2557, 2022 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-35385340

RESUMO

Diabetic neuropathic pain (DNP) is a common and devastating complication in patients with diabetes. The mechanisms mediating DNP are not completely elucidated, and effective treatments are lacking. A-fiber sensory neurons have been shown to mediate the development of mechanical allodynia in neuropathic pain, yet the molecular basis underlying the contribution of A-fiber neurons is still unclear. Here, we report that the orphan G protein-coupled receptor 177 (GPR177) in A-fiber neurons drives DNP via WNT5a-mediated activation of transient receptor potential vanilloid receptor-1 (TRPV1) ion channel. GPR177 is mainly expressed in large-diameter A-fiber dorsal root ganglion (DRG) neurons and required for the development of DNP in mice. Mechanistically, we found that GPR177 mediated the secretion of WNT5a from A-fiber DRG neurons into cerebrospinal fluid (CSF), which was necessary for the maintenance of DNP. Extracellular perfusion of WNT5a induced rapid currents in both TRPV1-expressing heterologous cells and nociceptive DRG neurons. Computer simulations revealed that WNT5a has the potential to bind the residues at the extracellular S5-S6 loop of TRPV1. Using a peptide able to disrupt the predicted WNT5a/TRPV1 interaction suppressed DNP- and WNT5a-induced neuropathic pain symptoms in rodents. We confirmed GPR177/WNT5A coexpression in human DRG neurons and WNT5A secretion in CSF from patients with DNP. Thus, our results reveal a role for WNT5a as an endogenous and potent TRPV1 agonist, and the GPR177-WNT5a-TRPV1 axis as a driver of DNP pathogenesis in rodents. Our findings identified a potential analgesic target that might relieve neuropathic pain in patients with diabetes.


Assuntos
Diabetes Mellitus , Neuropatias Diabéticas , Peptídeos e Proteínas de Sinalização Intracelular , Neuralgia , Receptores Acoplados a Proteínas G , Canais de Cátion TRPV , Proteína Wnt-5a , Animais , Diabetes Mellitus/metabolismo , Neuropatias Diabéticas/metabolismo , Gânglios Espinais/metabolismo , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Camundongos , Neuralgia/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Células Receptoras Sensoriais/metabolismo , Canais de Cátion TRPV/metabolismo , Proteína Wnt-5a/metabolismo
9.
Sci Rep ; 12(1): 3478, 2022 03 03.
Artigo em Inglês | MEDLINE | ID: mdl-35241713

RESUMO

Despite effective lipid reduction and corresponding benefits for cardiovascular disease prevention and treatment, statins have pleiotropic effects potentially increasing the risk of ischemic heart disease (IHD), particularly by increasing body mass index (BMI). We assessed whether the effects of genetically mimicked statins on IHD were strengthened by adjusting for BMI in men and women. We also assessed if increasing BMI was specific to statins in comparison to other major lipid-lowering treatments in current use, i.e., proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors and ezetimibe. Using univariable and multivariable Mendelian randomization (MR) we found genetically mimicked effects of statins increased BMI (0.33, 95% confidence interval (CI) 0.28 to 0.38), but genetically mimicked PCSK9 inhibitors and ezetimibe did not. Genetically mimicked effects of statins on IHD reduction in both sexes (odds ratio (OR) 0.55 per unit decrease in effect size of low-density lipoprotein cholesterol (LDL-c), 95% confidence interval (CI) 0.40 to 0.76), was largely similar after adjusting for BMI, in both men (OR 0.48, 95% CI 0.38 to 0.61) and women (OR 0.66, 95% CI 0.53 to 0.82). Compared with variations in PCSK9 and NPC1L1, only variation in HMGCR was associated with higher BMI. The effects on IHD of mimicking statins were similar after adjusting for BMI in both men and women. The BMI increase due to statins does not seem to be a concern as regards the protective effects of statins on IHD, however other factors driving BMI and the protective effects of statins could be.


Assuntos
Anticolesterolemiantes , Inibidores de Hidroximetilglutaril-CoA Redutases , Isquemia Miocárdica , Índice de Massa Corporal , LDL-Colesterol , Ezetimiba , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Masculino , Análise da Randomização Mendeliana , Isquemia Miocárdica/tratamento farmacológico , Isquemia Miocárdica/genética , Pró-Proteína Convertase 9/genética
10.
Heart Vessels ; 37(6): 1085-1096, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35320391

RESUMO

Atherosclerosis (AS) is the basic lesion underlying the occurrence and development of cerebrovascular diseases. Abnormal proliferation of vascular smooth muscle cells (VSMCs) plays a crucial role in AS. We aimed to explore the role of SNHG16 in AS and the molecular mechanism of VSMC involvement in the regulation of AS. The expression levels of SNHG16, miR-30c-5p and SDC2 were detected by qRT-PCR. CCK-8, wound healing and Transwell assays were used to assess ox-LDL-induced VSMC proliferation, migration, and invasion, respectively. Western blot analysis was used to detect SDC2 and MEK/ERK pathway-related protein levels. A dual-luciferase reporter assay confirmed the binding of SNHG16 with miR-30c-5p and miR-30c-5p with SDC2. SNHG16 and SDC2 expression was upregulated in patients with AS and ox-LDL-induced VSMCs, while miR-30c-5p was downregulated. Ox-LDL-induced VSMC proliferation and migration were increased, and the MEK/ERK signalling pathway was activated. MiR-30c-5p was targeted to SNHG16 and SDC2. Downregulating SNHG16 or upregulating miR-30c-5p inhibited ox-LDL-induced VSMC proliferation and migration and inhibited MEK/ERK signalling pathway activation. In contrast, downregulating miR-30c-5p or upregulating SDC2 reversed the effects of downregulating SNHG16 or upregulating miR-30c-5p. Furthermore, downregulating SDC2 inhibited ox-LDL-induced proliferation and migration of VSMCs and inhibited activation of the MEK/ERK signalling pathway, while upregulating lncRNA SNHG16 reversed the effects of downregulating SDC2. Downregulation of SNHG16 inhibited VSMC proliferation and migration in AS by targeting the miR-30c-5p/SDC2 axis. This study provides a possible therapeutic approach to AS.

11.
Front Immunol ; 13: 824459, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35281004

RESUMO

The consequences of systemic inflammation are a significant burden after traumatic brain injury (TBI), with almost all organs affected. This response consists of inflammation and concurrent immunosuppression after injury. One of the main immune regulatory organs, the spleen, is highly interactive with the brain. Along this brain-spleen axis, both nerve fibers as well as brain-derived circulating mediators have been shown to interact directly with splenic immune cells. One of the most significant comorbidities in TBI is acute ethanol intoxication (EI), with almost 40% of patients showing a positive blood alcohol level (BAL) upon injury. EI by itself has been shown to reduce proinflammatory mediators dose-dependently and enhance anti-inflammatory mediators in the spleen. However, how the splenic immune modulatory effect reacts to EI in TBI remains unclear. Therefore, we investigated early splenic immune responses after TBI with and without EI, using gene expression screening of cytokines and chemokines and fluorescence staining of thin spleen sections to investigate cellular mechanisms in immune cells. We found a strong FLT3/FLT3L induction 3 h after TBI, which was enhanced by EI. The FLT3L induction resulted in phosphorylation of FLT3 in CD11c+ dendritic cells, which enhanced protein synthesis, maturation process, and the immunity of dendritic cells, shown by pS6, peIF2A, MHC-II, LAMP1, and CD68 by immunostaining and TNF-α expression by in-situ hybridization. In conclusion, these data indicate that TBI induces a fast maturation and immunity of dendritic cells which is associated with FLT3/FLT3L signaling and which is enhanced by EI prior to TBI.


Assuntos
Lesões Encefálicas Traumáticas , Baço , Lesões Encefálicas Traumáticas/metabolismo , Células Dendríticas , Humanos , Inflamação , Proteínas de Membrana/genética , Tirosina Quinase 3 Semelhante a fms
12.
Gut Microbes ; 14(1): 2046246, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35259052

RESUMO

The gut microbiota was emerging as critical regulatory elements in shaping the outcome of cancer immunotherapy. However, the underlying mechanisms by which the gut commensal species enhance antitumor immunity remain largely unexplored. Here, we show that the gut microbiota from healthy individuals conferred considerable sensitivity to anti-PD-1 in the colorectal cancer (CRC) tumor-bearing mice, whereas gut microbiota from CRC patients failed to do so. By 16S rRNA gene sequencing, we identified Lactobacillus that was significantly increased in the mice with good response to anti-PD-1, and significantly correlated with anti-tumor immunity. After a series of screening, we isolated a novel Lacticaseibacillus strain, named L. paracasei sh2020. L. paracasei sh2020 showed the most notable anti-tumor immunity in the mice with gut dysbiosis. Mechanistically, the antitumor immune response elicited by L. paracasei sh2020 was dependent on CD8+ T cell. In vitro and in vivo studies revealed that L. paracasei sh2020 stimulation triggered the upregulated expression of CXCL10 in the tumors and subsequently enhanced CD8+ T cell recruitment. Meanwhile, the modulation of gut microbiota caused by L. paracasei sh2020 enhanced its antitumor effect and gut barrier function. Overall, our study offered novel insights into the mechanism by which gut microbiota shaped the outcome of cancer immunotherapy and, more importantly, the novel strain L. paracasei sh2020 might serve as an easy and effective way to promote anti-PD-1 effect in clinical practice.


Assuntos
Neoplasias Colorretais , Microbioma Gastrointestinal , Lactobacillus paracasei , Probióticos , Animais , Neoplasias Colorretais/tratamento farmacológico , Humanos , Lactobacillus paracasei/genética , Camundongos , Probióticos/farmacologia , Probióticos/uso terapêutico , RNA Ribossômico 16S/genética , Carga Tumoral
13.
Front Cell Infect Microbiol ; 12: 803242, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35295754

RESUMO

Schistosoma is a genus of parasitic trematodes that undergoes complex migration in final hosts, finally developing into adult worms, which are responsible for egg production and disease dissemination. Recent studies documented the importance of extracellular vesicles (EVs) in the regulation of host-parasite interactions. Herein, we investigated the microRNA (miRNA) profiles of EVs isolated from host plasma at different stages of Schistosoma japonicum infection (lung stage: 3 days post-infection (dpi), and liver stages: 14 and 21 dpi) to identify miRNA cargo potentially involved in the pathogenesis and immune regulation of schistosomiasis. Characterization of the isolated plasma EVs revealed their diameter to be approximately 100 nm, containing typical EV markers such as Hsp70 and Tsg101. Deep sequencing analysis indicated the presence of 811 known and 15 novel miRNAs with an increasing number of differential miRNAs from the lung stage (27 miRNAs) to the liver stages (58 and 96 miRNAs at 14 and 21 dpi, respectively) in the plasma EVs of infected mice compared to EVs isolated from the uninfected control. In total, 324 plasma EV miRNAs were shown to be co-detected among different stages of infection and the validation of selected miRNAs showed trends of abundance similar to deep sequencing analysis. For example, miR-1a-3p and miR-122-5p showed higher abundance, whereas miR-150-3p and miR-126a showed lower abundance in the plasma EVs of infected mice at 3, 14, and 21 dpi as compared to those of uninfected mice. In addition, bioinformatic analysis combined with PCR validation of the miRNA targets, particularly those associated with the immune system and parasitic infectious disease, indicated a significant increase in the expression of Gbp7and Ccr5 in contrast to the decreased expression of Fermt3, Akt1, and IL-12a. Our results suggested that the abundance of miRNA cargo of the host plasma EVs was related to the stages of Schistosoma japonicum infection. Further studies on the roles of these miRNAs may reveal the regulatory mechanism of the host-parasite interaction. Moreover, the differentially abundant miRNA cargo in host EVs associated with S. japonicum infection may also provide valuable clues for identifying novel biomarkers for schistosomiasis diagnosis.


Assuntos
Vesículas Extracelulares , MicroRNAs , Schistosoma japonicum , Esquistossomose Japônica , Animais , Vesículas Extracelulares/metabolismo , Interações Hospedeiro-Parasita , Camundongos , MicroRNAs/metabolismo , Schistosoma japonicum/genética , Esquistossomose Japônica/metabolismo , Esquistossomose Japônica/parasitologia
14.
Front Microbiol ; 13: 846543, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35308399

RESUMO

Autophagy is a crucial and conserved homeostatic mechanism for early defense against viral infections. Recent studies indicate that coronaviruses (CoVs) have evolved various strategies to evade the autophagy-lysosome pathway. In this minireview, we describe the source of double-membrane vesicles during CoV infection, which creates a microenvironment that promotes viral RNA replication and virion synthesis and protects the viral genome from detection by the host. Firstly, CoVs hijack autophagy initiation through non-structural proteins and open-reading frames, leading to the use of non-nucleated phagophores and omegasomes for autophagy-derived double-membrane vesicles. Contrastingly, membrane rearrangement by hijacking ER-associated degradation machinery to form ER-derived double-membrane vesicles independent from the typical autophagy process is another important routine for the production of double-membrane vesicles. Furthermore, we summarize the molecular mechanisms by which CoV non-structural proteins and open-reading frames are used to intercept autophagic flux and thereby evade host clearance and innate immunity. A comprehensive understanding of the above mechanisms may contribute to developing novel therapies and clinical drugs against coronavirus disease 2019 (COVID-19) in the future.

15.
Front Bioeng Biotechnol ; 10: 780211, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35356768

RESUMO

Mechanical force, being so ubiquitous that it is often taken for granted and overlooked, is now gaining the spotlight for reams of evidence corroborating their crucial roles in the living body. The bone, particularly, experiences manifold extraneous force like strain and compression, as well as intrinsic cues like fluid shear stress and physical properties of the microenvironment. Though sparkled in diversified background, long noncoding RNAs (lncRNAs) concerning the mechanotransduction process that bone undergoes are not yet detailed in a systematic way. Our principal goal in this research is to highlight the potential lncRNA-focused mechanical signaling systems which may be adapted by bone-related cells for biophysical environment response. Based on credible lists of force-sensitive mRNAs and miRNAs, we constructed a force-responsive competing endogenous RNA network for lncRNA identification. To elucidate the underlying mechanism, we then illustrated the possible crosstalk between lncRNAs and mRNAs as well as transcriptional factors and mapped lncRNAs to known signaling pathways involved in bone remodeling and mechanotransduction. Last, we developed combinative analysis between predicted and established lncRNAs, constructing a pathway-lncRNA network which suggests interactive relationships and new roles of known factors such as H19. In conclusion, our work provided a systematic quartet network analysis, uncovered candidate force-related lncRNAs, and highlighted both the upstream and downstream processes that are possibly involved. A new mode of bioinformatic analysis integrating sequencing data, literature retrieval, and computational algorithm was also introduced. Hopefully, our work would provide a moment of clarity against the multiplicity and complexity of the lncRNA world confronting mechanical input.

16.
J Hazard Mater ; 429: 128369, 2022 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-35236039

RESUMO

To properly manage nuclear wastes is critical to sustainable utilization of nuclear power and environment health. Here, we show an innovative carbiding strategy for sustainable management of radioactive graphite through digestion of carbon in H2O2. The combined action of intermolecular oxidation of graphite by MoO3 and molybdenum carbiding demonstrates success in gasifying graphite and sequestrating uranium for a simulated uranium-contaminated graphite waste. The carbiding process plays a triple role: (1) converting graphite into atomic carbon digestible in H2O2, (2) generating oxalic ligands in the presence of H2O2 to favor U-precipitation, and (3) delivering oxalic ligands to coordinate to MoVI-oxo anionic species to improve sample batching capacity. We demonstrate > 99% of uranium to be sequestrated for the simulated waste with graphite matrix completely gasifying while no detectable U-migration occurred during operation. This method has further been extended to removal of surface carbon layers for graphite monolith and thus can be used to decontaminate monolithic graphite waste with emission of a minimal amount of secondary waste. We believe this work not only provides a sustainable approach to tackle the managing issue of heavily metal contaminated graphite waste, but also indicates a promising methodology toward surface decontamination for irradiated graphite in general.


Assuntos
Grafite , Resíduos Radioativos , Radioatividade , Urânio , Carbono , Digestão , Resíduos Perigosos , Peróxido de Hidrogênio , Molibdênio , Resíduos Radioativos/análise , Resíduos Radioativos/prevenção & controle
17.
Clin Exp Hypertens ; : 1-7, 2022 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-35129024

RESUMO

OBJECTIVE: The patient of hypertension and its complication increase fast in the past years. Obesity is thought to be a risk factor for hypertension, and BMI (body mass index) is widely used to evaluate the obesity and hypertension risk. However, the abdominal obesity and visceral fat accumulation are more obvious in the East Asian population. The aim of this study was to evaluate the predictive value of fatty liver for hypertension in the Chinese population. METHOD: We compared the predictive value of BMI and fatty liver for the hypertension and its complication in 1386 patients with hypertension in Shanghai China. RESULTS: In the analysis of 1386 patients with hypertension in Shanghai China, we found that the prevalence and risk of hypertension and its complications were higher in the fatty liver group than that in the group of BMI≥24. Furthermore, the areas under the ROC curve of fatty liver for hypertension and its complications were superior to that of BMI. CONCLUSION: These results suggested that fatty liver is a more sensitive early warning for hypertension and its complication than BMI in Chinese population.

18.
J Nat Prod ; 85(4): 1180-1185, 2022 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-35179378

RESUMO

Two new guaianolide sesquiterpenes, lanicepines A (1) and B (2), possessing unusual amino acid-derived substituents at C-13, were isolated from the flowering aerial parts of Saussurea laniceps, a traditional herbal medicine also known as "snow lotus". The structures of 1 and 2 were elucidated based on spectroscopic analysis including applications of the modified Mosher's method and Marfey's method as well as ECD calculations. Lanicepine A (1) contains a dihydropyridinone moiety with a carbamoyl and a hydroxymethyl group. This substituent was considered to consist of asparagine and a C4 unit. In contrast, lanicepine B (2) has a substituent that seems to be derived from l-proline and a C4 unit. Lanicepines A (1) and B (2) and two related known sesquiterpenes isolated from the same plant material, 11ß,13-dihydrodesacylcynaropicrin (3) and 11ß,13-dihydrodesacylcynaropicrin 8-O-ß-d-glucoside (4), demonstrated inhibitory activity against IL-1ß production from LPS-stimulated microglial cells.


Assuntos
Saussurea , Sesquiterpenos , Aminoácidos/análise , Estrutura Molecular , Componentes Aéreos da Planta/química , Saussurea/química , Sesquiterpenos/química , Sesquiterpenos de Guaiano/química
19.
J Am Chem Soc ; 144(4): 1861-1871, 2022 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-35050618

RESUMO

Single clusters have attracted extensive research interest in the field of catalysis. However, achieving a highly uniform dispersion of a single-cluster catalyst is challenging. In this work, for the first time, we present a versatile strategy for uniformly dispersed polyoxometalates (POMs) in covalent organic frameworks (COFs) through confining POM cluster into the regular nanopores of COF by a covalent linkage. These COF-POM composites combine the properties of light absorption, electron transfer, and suitable catalytic active sites; as a result, they exhibit outstanding catalytic activity in artificial photosynthesis: that is, CO2 photoreduction with H2O as the electron donor. Among them, TCOF-MnMo6 achieved the highest CO yield (37.25 µmol g-1 h-1 with ca. 100% selectivity) in a gas-solid reaction system. Furthermore, a mechanism study based on density functional theory (DFT) calculations demonstrated that the photoinduced electron transfer (PET) process occurs from the COF to the POM, and then CO2 reduction and H2O oxidation occur on the POM and COF, respectively. This work developed a method for a uniform dispersion of POM single clusters into a COF, which also shows the potential of using COF-POM functional materials in the field of photocatalysis.

20.
Inorg Chem ; 61(4): 2167-2173, 2022 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-35025501

RESUMO

Photoreducing carbon dioxide (CO2) into highly valued chemicals or energy products has been recognized as one of the most promising proposals to degrade atmospheric CO2 concentration and achieve carbon neutrality. Adenine with a photosensitive amino group and aromatic nitrogen atom can strongly interact with CO2 and has been authenticated for its catalytic activity for the CO2 photoreduction reaction (CO2RR). Herein, two adenine-constructed crystalline biomimetic photocatalysts (Co2-AW and Co2-AF) were designed and synthesized to achieve CO2RR. Between them, Co2-AF displayed higher photocatalytic activity (225.8 µmol g-1 h-1) for CO2-to-HCOOH conversion than that of Co2-AW. It was found that the superior charge transfer capacity of the functional ferrocene group in Co2-AF is the primary reason to facilitate the photocatalytic performance efficiently. Additionally, this work also demonstrated the great potential of the ferrocene group as an electron donor and mediator in improving the photocatalytic activity of crystalline coordination catalysts.


Assuntos
Dióxido de Carbono
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