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Hydrogen sulfide is a vital signaling molecule which holds a pivotal position in numerous biological functions. In this research, two novel "OFF-ON" fluorescence probes named YNO and TNO were designed based on the nitroso recognition group to detect H2S. Both YNO and TNO performed outstanding response rate and linear relationship between the fluorescence intensity and the concentration of H2S. YNO possessed larger Stokes shift and longer emission wavelength. TNO had lower limit of detection. In addition, YNO was successful applied to sense endogenous and exogenous H2S and target endoplasmic reticulum (ER) in Hela cells.
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Background: Alterations in metabolites and metabolic pathways are thought to be important triggers of idiopathic pulmonary fibrosis (IPF), but our lack of a comprehensive understanding of this process has hampered the development of IPF-targeted drugs. Methods: To fully understand the metabolic profile of IPF, C57BL/6 J male mice were injected intratracheally with bleomycin so that it could be used to construct a mouse model of IPF, and lung tissues from 28-day and control IPF mice were analyzed by pathology and immunohistochemistry. In addition, serum metabolites from IPF mice were examined using LC-ESI-MS/MS, and the differential metabolites were analyzed for KEGG metabolic pathways and screened for biomarkers using machine learning algorithms. Results: In total, the levels of 1465 metabolites were detected, of which 104 metabolites were significantly altered after IPF formation. In IPF mouse serum, 52% of metabolite expression was downregulated, with lipids (e.g., GP, FA) and organic acids and their derivatives together accounting for more than 70% of the downregulated differentially expressed metabolites. In contrast, FA and oxidised lipids together accounted for 60% of the up-regulated differentially expressed metabolites. KEGG pathway enrichment analyses of differential metabolites were mainly enriched in the biosynthesis of unsaturated fatty acids, pentose phosphate pathway, and alanine, aspartate, and glutamate metabolism. Seven metabolites were screened by machine learning LASSO models and evaluated as ideal diagnostic tools by receiver operating characteristic curves (ROCs). Discussion: In conclusion, the serum metabolic disorders found to be associated with pulmonary fibrosis formation will help to deepen our understanding of the pathogenesis of pulmonary fibrosis.
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Solar carbon dioxide (CO2) reduction provides an attractive alternative to producing sustainable chemicals and fuel. However, the construction of a highly active photocatalyst was challenging because of the rapid charge recombination and sluggish surface CO2 reduction. Herein, a unique Co-N4Cl2 single site was fabricated by loading Co species into the 2,2'-bipyridine and triazine-containing covalent organic framework (COF) for CO2 conversion into syngas under visible light irradiation. The resulting champion catalyst TPy-COF-Co enabled a record-high CO production rate of 426 mmol g-1 h-1, associated with the unprecedented turnover number (TON) and turnover frequency (TOF) of 2095 and 1607 h-1, respectively. The catalyst also exhibited favorable recycling performance and widely adjustable syngas production (CO/H2 ratio: 1.8:1-1:16). A systematical investigation including operando synchrotron X-ray absorption fine structure (XAFS) spectroscopy, in-situ attenuated total reflection surface-enhanced infrared absorption spectroscopy (ATR-SEIRAS), and theoretical calculation indicated that the triazine-based COF framework promoted the charge transfer towards the single Co-N4Cl2 sites that greatly promoted the CO2 activation by lowering the energy barrier of *COOH generation, facilitating the CO2 transformation. This work highlights the great potential of the molecular regulation of COF-derived single-atom catalysts to boost CO2 photoreduction efficiency.
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Paclitaxel, a microtubule-stabilizing chemotherapy drug, can cause severe paclitaxel-induced peripheral neuropathic pain (PIPNP). The roles of transient receptor potential (TRP) ion channel vanilloid 1 (TRPV1, a nociceptor and heat sensor) and melastatin 8 (TRPM8, a cold sensor) in PIPNP remain controversial. In this study, Western blotting, immunofluorescence staining, and calcium imaging revealed that the expression and functional activity of TRPV1 were upregulated in rat dorsal root ganglion (DRG) neurons in PIPNP. Behavioral assessments using the von Frey and brush tests demonstrated that mechanical hyperalgesia in PIPNP was significantly inhibited by intraperitoneal or intrathecal administration of the TRPV1 antagonist capsazepine, indicating that TRPV1 played a key role in PIPNP. Conversely, the expression of TRPM8 protein decreased and its channel activity was reduced in DRG neurons. Furthermore, activation of TRPM8 via topical application of menthol or intrathecal injection of WS-12 attenuated the mechanical pain. Mechanistically, the TRPV1 activity triggered by capsaicin (a TRPV1 agonist) was reduced after menthol application in cultured DRG neurons, especially in the paclitaxel-treated group. These findings showed that upregulation of TRPV1 and inhibition of TRPM8 are involved in the generation of PIPNP, and they suggested that inhibition of TRPV1 function in DRG neurons via activation of TRPM8 might underlie the analgesic effects of menthol.
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Gânglios Espinais , Neuralgia , Paclitaxel , Ratos Sprague-Dawley , Canais de Cátion TRPM , Canais de Cátion TRPV , Animais , Paclitaxel/efeitos adversos , Paclitaxel/farmacologia , Canais de Cátion TRPM/metabolismo , Canais de Cátion TRPV/metabolismo , Gânglios Espinais/metabolismo , Gânglios Espinais/efeitos dos fármacos , Ratos , Neuralgia/metabolismo , Neuralgia/tratamento farmacológico , Neuralgia/induzido quimicamente , Masculino , Hiperalgesia/metabolismo , Hiperalgesia/induzido quimicamente , Hiperalgesia/tratamento farmacológico , Capsaicina/farmacologia , Capsaicina/análogos & derivados , Neurônios/metabolismo , Neurônios/efeitos dos fármacosRESUMO
This study aimed to explore the expression, function, and mechanisms of TBC1D10B in colon cancer, as well as its potential applications in the diagnosis and treatment of the disease.The expression levels of TBC1D10B in colon cancer were assessed by analyzing the TCGA and CCLE databases. Immunohistochemistry analysis was conducted using tumor and adjacent non-tumor tissues from 68 colon cancer patients. Lentiviral infection techniques were employed to silence and overexpress TBC1D10B in colon cancer cells. The effects on cell proliferation, migration, and invasion were evaluated using CCK-8, EDU, wound healing, and Transwell invasion assays. Additionally, GSEA enrichment analysis was used to explore the association of TBC1D10B with biological pathways related to colon cancer. TBC1D10B was significantly upregulated in colon cancer and closely associated with patient prognosis. Silencing of TBC1D10B notably inhibited proliferation, migration, and invasion of colon cancer cells and promoted apoptosis. Conversely, overexpression of TBC1D10B enhanced these cellular functions. GSEA analysis revealed that TBC1D10B is enriched in the AKT/PI3K/mTOR signaling pathway and highly correlated with PAK4. The high expression of TBC1D10B in colon cancer is associated with poor prognosis. It influences cancer progression by regulating the proliferation, migration, and invasion capabilities of colon cancer cells, potentially acting through the AKT/PI3K/mTOR signaling pathway. These findings provide new targets and therapeutic strategies for the treatment of colon cancer.
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Apoptose , Movimento Celular , Proliferação de Células , Neoplasias do Colo , Proteínas Ativadoras de GTPase , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Transdução de Sinais , Serina-Treonina Quinases TOR , Quinases Ativadas por p21 , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Apoptose/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Neoplasias do Colo/genética , Neoplasias do Colo/patologia , Neoplasias do Colo/metabolismo , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Proteínas Ativadoras de GTPase/metabolismo , Proteínas Ativadoras de GTPase/genética , Quinases Ativadas por p21/metabolismo , Quinases Ativadas por p21/genética , Fosfatidilinositol 3-Quinases/metabolismo , Fosfatidilinositol 3-Quinases/genética , Prognóstico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Serina-Treonina Quinases TOR/metabolismo , Serina-Treonina Quinases TOR/genéticaRESUMO
Ulcerative colitis (UC) is a chronic recurrent inflammatory disease affecting the rectum and colon. Numerous epidemiological studies have identified smoking as a protective factor for UC. Dysbiosis of intestinal microbiota and release of inflammatory factors are well-established characteristics associated with UC. Therefore, we have observed that nicotine exhibits the potential to ameliorate colitis symptoms in UC mice. Additionally, it exerts a regulatory effect on colonic microbiota dysbiosis by promoting the growth of beneficial bacteria while suppressing harmful bacteria. Combined in vivo and in vitro investigations demonstrate that nicotine primarily impedes the assembly of NLRP3, subsequently inhibiting downstream IL-1ß secretion.
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Sulfato de Dextrana , Microbioma Gastrointestinal , Proteína 3 que Contém Domínio de Pirina da Família NLR , Nicotina , Animais , Microbioma Gastrointestinal/efeitos dos fármacos , Proteína 3 que Contém Domínio de Pirina da Família NLR/antagonistas & inibidores , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Nicotina/farmacologia , Camundongos , Colite/tratamento farmacológico , Colite/induzido quimicamente , Camundongos Endogâmicos C57BL , Interleucina-1beta/metabolismo , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Estrutura Molecular , Masculino , Disbiose/tratamento farmacológico , HumanosRESUMO
Ajaniaflavida, a new species from western Sichuan and eastern Xizang, China, is described and illustrated. It is readily assigned to A.sect.Ajania owing to its straw-colored, glossy involucres and marginally whitish scarious phyllaries. Within the section, it is distinct in being a shrub of 1-2 m in height, and in having creamy yellow florets. It is superficially similar to A.ramosa in A.sect.Phaeoscyphus, but can easily be distinguished by, among other characters, the plant height, color of the florets and margins of the phyllaries. In addition, we provide a distribution map of the new species.
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The eukaryotic translation initiation factor eIF4E can regulate cellular translation via phosphorylation on serine 209. In a recent study, by two rounds of TMT relative quantitative proteomics, we found that phosphorylated eIF4E (p-eIF4E) favors the translation of selected mRNAs, and the encoded proteins are mainly involved in ECM-receptor, focal adhesion, and PI3K-Akt signaling. The current paper is focused on the relationship between p-eIF4E and the downstream host cell proteins, and their presumed effect on efficient entry of PEDV. We found that the depletion of membrane-residential factor TSPAN3, CD63, and ITGB2 significantly inhibited viral invasion of PEDV, and reduced the entry of pseudotyped particles PEDV-pp, SARS-CoV-pp, and SARS-CoV-2-pp. The specific antibodies of TSPAN3, CD63, and ITGB2 blocked the adsorption of PEDV into host cells. Moreover, we detected that eIF4E phosphorylation was increased at 1 h after PEDV infection, in accordance with the expression of TSPAN3, CD63, and ITGB2. Similar trends appeared in the intestines of piglets in the early stage of PEDV challenge. Compared with Vero cells, S209A-Vero cells in which eIF4E cannot be phosphorylated showed a decrease of invading PEDV virions. MNK kinase inhibitor blocked PEDV invasion, as well as reduced the accumulation of TSPAN3, CD63, and ITGB2. Further study showed that the ERK-MNK pathway was responsible for the regulation of PEDV-induced early phosphorylation of eIF4E. This paper demonstrates for the first time the connections among p-eIF4E stimulation and membrane-residential host factors. Our findings also enrich the understanding of the biological function of phosphorylated eIF4E during the viral life cycle.IMPORTANCEThe eukaryotic translation initiation factor eIF4E can regulate cellular translation via phosphorylation. In our previous study, several host factors susceptible to a high level of p-eIF4E were found to be conducive to viral infection by coronavirus PEDV. The current paper is focused on cell membrane-residential factors, which are involved in signal pathways that are sensitive to phosphorylated eIF4E. We found that the ERK-MNK pathway was activated, which resulted in the stimulation of phosphorylation of eIF4E in early PEDV infection. Phospho-eIF4E promoted the viral invasion of PEDV by upregulating the expression of host factors TSPAN3, CD63, and ITGB2 at the translation level rather than at the transcription level. Moreover, TSPAN3, CD63, or ITGB2 facilitates the efficient entry of coronavirus SARS-CoV, SARS-CoV-2, and HCoV-OC43. Our findings broaden our insights into the dynamic phosphorylation of eIF4E during the viral life cycle, and provide further evidence that phosphorylated eIF4E regulates selective translation of host mRNA.
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Membrana Celular , Fator de Iniciação 4E em Eucariotos , Vírus da Diarreia Epidêmica Suína , Biossíntese de Proteínas , Internalização do Vírus , Animais , Membrana Celular/química , Membrana Celular/genética , Membrana Celular/metabolismo , Membrana Celular/virologia , Chlorocebus aethiops , Fator de Iniciação 4E em Eucariotos/química , Fator de Iniciação 4E em Eucariotos/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Cadeias beta de Integrinas/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Fosforilação , Vírus da Diarreia Epidêmica Suína/fisiologia , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteômica , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Suínos , Tetraspaninas/metabolismo , Células VeroRESUMO
Tumor metastasis is a key factor affecting the life of patients with malignant tumors. For the past hundred years, scientists have focused on how to kill cancer cells and inhibit their metastasis in vivo, but few breakthroughs have been made. Here we hypothesized a novel mode for cancer metastasis. We show that the phagocytosis of apoptotic tumor cells by macrophages leads to their polarization into the M2 phenotype, and that the expression of stem cell related as well as drug resistance related genes was induced. Therefore, it appears that M2 macrophages have "defected" and have been transformed into the initial "metastatic cancer cells", and thus are the source, at least in part, of the distal tissue tumor metastasis. This assumption is supported by the presence of fused cells with characteristics of both macrophage and tumor cell observed in the peripheral blood and ascites of patients with ovarian cancer. By eliminating the expression of CD206 in M2 macrophages using siRNA, we show that the growth and metastasis of tumors was suppressed using both in vitro cell line and with experimental in vivo mouse models. In summary, we show that M2 macrophages in the blood circulation underwent a "change of loyalty" to become "cancer cells" that transformed into distal tissue metastasis, which could be suppressed by the knockdown of CD206 expression.
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AIM: The liver is an important metabolic organ that governs glucolipid metabolism, and its dysfunction may cause non-alcoholic fatty liver disease, type 2 diabetes mellitus, dyslipidaemia, etc. We aimed to systematic investigate the key factors related to hepatic glucose metabolism, which may be beneficial for understanding the underlying pathogenic mechanisms for obesity and diabetes mellitus. MATERIALS AND METHODS: Oral glucose tolerance test (OGTT) phenotypes and liver transcriptomes of BXD mice under chow and high-fat diet conditions were collected from GeneNetwork. QTL mapping was conducted to pinpoint genomic regions associated with glucose homeostasis. Candidate genes were further nominated using a multi-criteria approach and validated to confirm their functional relevance in vitro. RESULTS: Our results demonstrated that plasma glucose levels in OGTT were significantly affected by both diet and genetic background, with six genetic regulating loci were mapped on chromosomes 1, 4, and 7. Moreover, TEAD1, MYO7A and NDUFC2 were identified as the candidate genes. Functionally, siRNA-mediated TEAD1, MYO7A and NDUFC2 knockdown significantly decreased the glucose uptake and inhibited the transcription of genes related to insulin and glucose metabolism pathways. CONCLUSIONS: Our study contributes novel insights to the understanding of hepatic glucose metabolism, demonstrating the impact of TEAD1, MYO7A and NDUFC2 on mitochondrial function in the liver and their regulatory role in maintaining in glucose homeostasis.
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Diabetes Mellitus Tipo 2 , Resistência à Insulina , Hepatopatia Gordurosa não Alcoólica , Animais , Camundongos , Diabetes Mellitus Tipo 2/complicações , Dieta Hiperlipídica , Glucose/metabolismo , Resistência à Insulina/fisiologia , Fígado/metabolismo , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/metabolismoRESUMO
Ligularialushuiensis, a new species from northwestern Yunnan, China, is described and illustrated. It was tentatively placed in L.sect.Ligulariaser.Ligularia on the basis of the pinnate-palmate leaf venation, racemose synflorescence and pappus which is as long as tubular corolla. Within the series, it appeared somewhat close to both L.lamarum and L.pseudolamarum. However, L.lushuiensis can be easily distinguished from the latter two species by, among other characters, the leaf margin, bract size, involucre shape and size, and number and width of ray florets. Morphologically, L.lushuiensis is also superficially similar to L.secunda but differs readily by having distally shortly yellowish and brownish puberulent stems, palmately-pinnately veined leaves regularly dentate at margin, scarious, brown and larger bracts, and larger ray laminae. In addition, a distribution map and a diagnostic key to Chinese species of L.ser.Ligularia are also provided.
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BACKGROUND: In clinical practice, stem cell transplantation has become an effective method for treating spinal cord nerve injury. Up to now, there has been no report on teratoma caused by transplanted stem cell's abnormal differentiation in the clinic, especially in the analysis of imaging manifestations. Therefore, this article aims to analyze the PET/CT imaging manifestations of teratoma caused by stem cell transplantation to improve the imaging diagnosing capability. CASE PRESENTATION: A patient with a spinal cord injury who had received a stem cell transplant was examined by PET/CT on September 10th, 2020. The PET/CT images of the lesion showed irregular mixed low density on the right side of the erector spinae muscle area at the level of the cervical 3-5 vertebral body, with a maximum cross-section of 9.1×3.9 cm. The 18F-FDG metabolism of the lesion was increased, and the maximum standard uptake value (SUVmax) was 10.7. The boundary was unclear with the third cervical vertebra and cervical 3 and 4-level vertebral plates. Based on the patient's medical history, the lesion was diagnosed as an abnormal proliferative tumor, which was consistent with the pathological examination results. CONCLUSION: To date, there have been no clinical reports on teratomas caused by stem cell transplantation for spinal cord injury at home or abroad. This case report enhances the knowledge of the diagnosis and treatment methods of this type of disease and confirms the diagnostic value of PET/CT examination.
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Traumatismos da Medula Espinal , Teratoma , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Compostos Radiofarmacêuticos , Tomografia Computadorizada por Raios X/métodos , Teratoma/diagnóstico por imagem , Teratoma/cirurgia , Traumatismos da Medula Espinal/diagnóstico por imagem , Traumatismos da Medula Espinal/cirurgia , Transplante de Células-Tronco , Vértebras Cervicais/diagnóstico por imagem , Vértebras Cervicais/cirurgiaRESUMO
Autophagy generally functions as a cellular surveillance mechanism to combat invading viruses, but viruses have evolved various strategies to block autophagic degradation and even subvert it to promote viral propagation. White spot syndrome virus (WSSV) is the most highly pathogenic crustacean virus, but little is currently known about whether crustacean viruses such as WSSV can subvert autophagic degradation for escape. Here, we show that even though WSSV proliferation triggers the accumulation of autophagosomes, autophagic degradation is blocked in the crustacean species red claw crayfish. Interestingly, the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex including CqSNAP29, CqVAMP7, and the novel autophagosome SNARE protein CqSyx12 is required for autophagic flux to restrict WSSV replication, as revealed by gene silencing experiments. Simultaneously, the expressed WSSV tegument protein VP26, which likely localizes on autophagic membrane mediated by its transmembrane region, binds the Qb-SNARE domain of CqSNAP29 to competitively inhibit the binding of CqSyx12-Qa-SNARE with CqSNAP29-Qb-SNARE; this in turn disrupts the assembly of the CqSyx12-SNAP29-VAMP7 SNARE complex, which is indispensable for the proposed fusion of autophagosomes and lysosomes. Consequently, the autophagic degradation of WSSV is likely suppressed by the expressed VP26 protein in vivo in crayfish, thus probably protecting WSSV components from degradation via the autophagosome-lysosome pathway, resulting in evasion by WSSV. Collectively, these findings highlight how a DNA virus can subvert autophagic degradation by impairing the assembly of the SNARE complex to achieve evasion, paving the way for understanding host-DNA virus interactions from an evolutionary point of view, from crustaceans to mammals.IMPORTANCEWhite spot syndrome virus (WSSV) is one of the largest animal DNA viruses in terms of its genome size and has caused huge economic losses in the farming of crustaceans such as shrimp and crayfish. Detailed knowledge of WSSV-host interactions is still lacking, particularly regarding viral escape from host immune clearance. Intriguingly, we found that the presence of WSSV-VP26 might inhibit the autophagic degradation of WSSV in vivo in the crustacean species red claw crayfish. Importantly, this study is the first to show that viral protein VP26 functions as a core factor to benefit WSSV escape by disrupting the assembly of the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex, which is necessary for the proposed fusion of autophagosomes with lysosomes for subsequent degradation. These findings highlight a novel mechanism of DNA virus evasion by blocking SNARE complex assembly and identify viral VP26 as a key candidate for anti-WSSV targeting.
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Astacoidea , Autofagia , Vírus da Síndrome da Mancha Branca 1 , Animais , Astacoidea/metabolismo , Autofagossomos/metabolismo , Proteínas Qb-SNARE/metabolismo , Proteínas SNARE/genética , Proteínas SNARE/metabolismo , Proteínas de Ligação a Fator Solúvel Sensível a N-Etilmaleimida , Vírus da Síndrome da Mancha Branca 1/fisiologiaRESUMO
Photocatalytic overall water splitting into hydrogen and oxygen is desirable for long-term renewable, sustainable and clean fuel production on earth. Metal sulfides are considered as ideal hydrogen-evolved photocatalysts, but their component homogeneity and typical sulfur instability cause an inert oxygen production, which remains a huge obstacle to overall water-splitting. Here, a distortion-evoked cation-site oxygen doping of ZnIn2S4 (D-O-ZIS) creates significant electronegativity differences between adjacent atomic sites, with S1 sites being electron-rich and S2 sites being electron-deficient in the local structure of S1-S2-O sites. The strong charge redistribution character activates stable oxygen reactions at S2 sites and avoids the common issue of sulfur instability in metal sulfide photocatalysis, while S1 sites favor the adsorption/desorption of hydrogen. Consequently, an overall water-splitting reaction has been realized in D-O-ZIS with a remarkable solar-to-hydrogen conversion efficiency of 0.57%, accompanying a ~ 91% retention rate after 120 h photocatalytic test. In this work, we inspire an universal design from electronegativity differences perspective to activate and stabilize metal sulfide photocatalysts for efficient overall water-splitting.
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Spin-polarized two-dimensional (2D) materials with large and tunable spin-splitting energy promise the field of 2D spintronics. While graphene has been a canonical 2D material, its spin properties and tunability are limited. Here, this work demonstrates the emergence of robust spin-polarization in graphene with large and tunable spin-splitting energy of up to 132 meV at zero applied magnetic fields. The spin polarization is induced through a magnetic exchange interaction between graphene and the underlying ferrimagnetic oxide insulating layer, Tm3 Fe5 O12 , as confirmed by its X-ray magnetic circular dichroism (XMCD). The spin-splitting energies are directly measured and visualized by the shift in their Landau-fan diagram mapped by analyzing the measured Shubnikov-de-Haas (SdH) oscillations as a function of applied electric fields, showing consistent fit with the first-principles and machine learning calculations. Further, the observed spin-splitting energies can be tuned over a broad range between 98 and 166 meV by field cooling. The methods and results are applicable to other 2D (magnetic) materials and heterostructures, and offer great potential for developing next-generation spin logic and memory devices.
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BACKGROUND:At present,it is found that both Chinese medicine for activating blood circulation and removing blood stasis and platelet-rich plasma technology can repair damaged blood vessels,promote vascular regeneration,rebuild blood supply in the femoral head,restore normal blood supply,and further promote osteogenesis.Both of them have certain advantages in early intervention of steroid-induced necrosis of femoral head.It can also further understand the mechanism of blood activating and stasis removing herbs and platelet-rich plasma technology in improving steroid-induced necrosis of the femoral head,and provide new ideas for future treatment. OBJECTIVE:To review the research progress of the mechanism of the combination of blood activating and blood stasis removing herbs and platelet-rich plasma technology on steroid-induced necrosis of the femoral head according to the related literature at home and abroad. METHODS:PubMed,Web of Science,Metstr,CNKI and WanFang databases were searched for relevant articles."Traditional Chinese medicine,signal pathways,steroid induced necrosis of femoral head,vascular endothelial growth factor,platelet rich plasma"were used as the Chinese and English search terms separately.The time limit for searching the literature was from January 2000 to July 2022,and 75 related articles were finally included. RESULTS AND CONCLUSION:Both Chinese medicine for activating blood circulation and removing blood stasis and platelet-rich plasma technology have certain advantages in intervening the early stage of steroid-induced necrosis of femoral head.For traditional Chinese medicine,both single and compound drugs can effectively alleviate the further development of steroid-induced necrosis of the femoral head.The specific mechanism is as follows:(1)The traditional Chinese medicine for activating blood circulation and removing blood stasis has a significant anticoagulation effect,which can antagonize the abnormal(hypercoagulable)state of blood caused by hormone drugs,and further restore the normal blood supply in the femoral head.(2)Traditional Chinese medicine for activating blood circulation and removing blood stasis can repair damaged vascular endothelium,regenerate blood vessels and remodel blood supply in the femoral head by activating vascular endothelial growth factor.(3)The traditional Chinese medicine of promoting blood circulation and removing blood stasis has the obvious effect of removing blood stasis,which can reduce the accumulation of fat cells in the bone marrow cavity and relieve the pressure in the femoral head.(4)Traditional Chinese medicine for promoting blood circulation and removing blood stasis can regulate relevant signal pathways,maintain bone metabolism,promote the differentiation and balance of osteoblasts and osteoclasts,and effectively reduce steroid-induced necrosis of the femoral head.In addition,platelet-rich plasma contains a large amount of high concentration of cell growth factor,which plays a positive role in osteogenesis and vascular regeneration,and can also improve the abnormal state of the blood.Traditional Chinese medicine for activating blood circulation and removing blood stasis combined with platelet-rich plasma technology can play their biological roles,and the intervention effect is more significant.
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The electrosynthesis of hydrogen peroxide (H2 O2 ) via two-electron (2e- ) oxygen (O2 ) reduction reaction (ORR) has great potential to replace the traditional energy-intensive anthraquinone process, but the design of low-cost and highly active and selective catalysts is greatly challenging for the long-term H2 O2 production under industrial relevant current density, especially under neutral electrolytes. To address this issue, this work constructed a carboxylated hexagonal boron nitride/graphene (h-BN/G) heterojunction on the commercial activated carbon through the coupling of B, N co-doping with surface oxygen groups functionalization. The champion catalyst exhibited a high 2e- ORR selectivity (>95 %), production rate (up to 13.4â mol g-1 h-1 ), and Faradaic efficiency (FE, >95 %). The long-term H2 O2 production under the high current density of 100â mA cm-2 caused the cumulative concentration as high as 2.1â wt %. The combination of in situ Raman spectra and theoretical calculation indicated that the carboxylated h-BN/G configuration promotes the adsorption of O2 and the stabilization of the key intermediates, allowing a low energy barrier for the rate-determining step of HOOH* release from the active site and thus improving the 2e- ORR performance. The fast dye degradation by using this electrochemical synthesized H2 O2 further illustrated the promising practical application.
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Background: Although surgical methods are the most effective treatments for colon adenocarcinoma (COAD), the cure rates remain low, and recurrence rates remain high. Furthermore, platelet adhesion-related genes are gaining attention as potential regulators of tumorigenesis. Therefore, identifying the mechanisms responsible for the regulation of these genes in patients with COAD has become important. The present study aims to investigate the underlying mechanisms of platelet adhesion-related genes in COAD patients. Methods: The present study was an experimental study. Initially, the effects of platelet number and related genomic alteration on survival were explored using real-world data and the cBioPortal database, respectively. Then, the differentially expressed platelet adhesion-related genes of COAD were analyzed using the TCGA database, and patients were further classified by employing the non-negative matrix factorization (NMF) analysis method. Afterward, some of the clinical and expression characteristics were analyzed between clusters. Finally, least absolute shrinkage and selection operator regression analysis was used to establish the prognostic nomogram. All data analyses were performed using the R package. Results: High platelet counts are associated with worse survival in real-world patients, and alternations to platelet adhesion-related genes have resulted in poorer prognoses, based on online data. Based on platelet adhesion-related genes, patients with COAD were classified into two clusters by NMF-based clustering analysis. Cluster2 had a better overall survival, when compared to Cluster1. The gene copy number and enrichment analysis results revealed that two pathways were differentially enriched. In addition, the differentially expressed genes between these two clusters were enriched for POU6F1 in the transcription factor signaling pathway, and for MATN3 in the ceRNA network. Finally, a prognostic nomogram, which included the ALOX12 and ACTG1 genes, was established based on the platelet adhesion-related genes, with a concordance (C) index of 0.879 (0.848-0.910). Conclusion: The mRNA expression-based NMF was used to reveal the potential role of platelet adhesion-related genes in COAD. The series of experiments revealed the feasibility of targeting platelet adhesion-associated gene therapy.
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BACKGROUND: Several proteins in the tripartite-motif (TRIM) family are associated with the development of colorectal cancer (CRC), but research on the role of TRIM69 was lacking. The present study examined the correlation between TRIM69 expression and colon adenocarcinoma (COAD). METHODS: mRNA sequencing data for COAD patients was extracted from The Cancer Genome Atlas to analyze correlations between TRIM69 expression and patients' clinical features as well as survival. Potential associations with immune cells and chemosensitivity also were predicted using various algorithms in the TIMER, Limma, clusterProfiler, GeneMANIA, and Gene Set Cancer Analysis platforms. Subsequently, polymerase chain reaction analysis and immunohistochemical staining were used to detect TRIM69 expression in COAD tissue samples from real-world patients. RESULTS: TRIM69 expression was lower in COAD tissues than in normal tissues and correlated with the pathologic stage and metastasis (M category). Additionally, TRIM69 was found to be involved in several immune-related pathways, notably the NOD-like signaling pathway. These results suggest that high TRIM69 expression has the potential to enhance tumor sensitivity to 5-fluorouracil and programmed cell death protein 1 (PD-1) blockers. CONCLUSIONS: From our findings that TRIM69 expression was significantly reduced in COAD compared with non-cancer tissues and associated with pathologic stage and metastasis, we conclude that increasing TRIM69 expression and/or activity may help to improve therapeutic outcomes. Accordingly, TRIM69 represents a potentially valuable marker of metastasis and target for adjuvant therapy in COAD.
Assuntos
Adenocarcinoma , Neoplasias do Colo , Humanos , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/genética , Fluoruracila/uso terapêutico , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/genética , Receptor de Morte Celular Programada 1 , Algoritmos , Proteínas com Motivo Tripartido/genética , Ubiquitina-Proteína Ligases/genéticaRESUMO
Background: There is an unmet need for accurate non-invasive methods to diagnose non-alcoholic steatohepatitis (NASH). Since impedance-based measurements of body composition are simple, repeatable and have a strong association with non-alcoholic fatty liver disease (NAFLD) severity, we aimed to develop a novel and fully automatic machine learning algorithm, consisting of a deep neural network based on impedance-based measurements of body composition to identify NASH [the bioeLectrical impEdance Analysis foR Nash (LEARN) algorithm]. Methods: A total of 1,259 consecutive subjects with suspected NAFLD were screened from six medical centers across China, of which 766 patients with biopsy-proven NAFLD were included in final analysis. These patients were randomly subdivided into the training and validation groups, in a ratio of 4:1. The LEARN algorithm was developed in the training group to identify NASH, and subsequently, tested in the validation group. Results: The LEARN algorithm utilizing impedance-based measurements of body composition along with age, sex, pre-existing hypertension and diabetes, was able to predict the likelihood of having NASH. This algorithm showed good discriminatory ability for identifying NASH in both the training and validation groups [area under the receiver operating characteristics (AUROC): 0.81, 95% CI: 0.77-0.84 and AUROC: 0.80, 95% CI: 0.73-0.87, respectively]. This algorithm also performed better than serum cytokeratin-18 neoepitope M30 (CK-18 M30) level or other non-invasive NASH scores (including HAIR, ION, NICE) for identifying NASH (P value <0.001). Additionally, the LEARN algorithm performed well in identifying NASH in different patient subgroups, as well as in subjects with partial missing body composition data. Conclusions: The LEARN algorithm, utilizing simple easily obtained measures, provides a fully automated, simple, non-invasive method for identifying NASH.