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1.
Drug Resist Updat ; 73: 101052, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38262246

RESUMO

AIMS: This investigation aims to elucidate the mechanism underlying sorafenib-induced ferroptosis in hepatocellular carcinoma (HCC). METHODS: The role of dual specificity phosphatase 4 (DUSP4) in sorafenib-treated HCC was investigated using comprehensive assessments both in vitro and in vivo, including Western blotting, qRT-PCR, cell viability assay, lipid reactive oxygen species (ROS) assay, immunohistochemistry, and xenograft tumor mouse model. Additionally, label-free quantitative proteomics was employed to identify potential proteins associated with DUSP4. RESULTS: Our study revealed that suppression of DUSP4 expression heightens the susceptibility of HCC cells to ferroptosis inducers, specifically sorafenib and erastin, in both in vitro and in vivo settings. Furthermore, we identified DUSP4-mediated regulation of key ferroptosis-related markers, such as ferritin light chain (FTL) and ferritin heavy chain 1 (FTH1). Notably, label-free quantitative proteomics unveiled the phosphorylation of threonine residue T148 on YTH Domain Containing 1 (YTHDC1) by DUSP4. Further investigations unraveled that YTHDC1, functioning as an mRNA nuclear export regulator, is a direct target of DUSP4, orchestrating the subcellular localization of FTL and FTH1 mRNAs. Significantly, our study highlights a strong correlation between elevated DUSP4 expression and sorafenib resistance in HCC. CONCLUSIONS: Our findings introduce DUSP4 as a negative regulator of sorafenib-induced ferroptosis. This discovery opens new avenues for the development of ferroptosis-based therapeutic strategies tailored for HCC treatment.


Assuntos
Carcinoma Hepatocelular , Fosfatases de Especificidade Dupla , Ferroptose , Neoplasias Hepáticas , Animais , Humanos , Camundongos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Linhagem Celular Tumoral , Ferroptose/genética , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Monoéster Fosfórico Hidrolases/uso terapêutico , Sorafenibe/farmacologia , Sorafenibe/uso terapêutico , Fosfatases de Especificidade Dupla/genética , Fosfatases de Especificidade Dupla/metabolismo , Fosfatases da Proteína Quinase Ativada por Mitógeno/genética , Fosfatases da Proteína Quinase Ativada por Mitógeno/metabolismo
2.
Oncologist ; 29(10): e1302-e1314, 2024 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-39110901

RESUMO

Endocervical adenocarcinoma (ECA) is reported increasingly often in young women, and this aggressive disease lacks effective methods of targeted therapy. Since mismatch repair deficiency (dMMR) is an important biomarker for predicting response to immune checkpoint inhibitors, it is important to investigate the clinicopathological features and immune microenvironment of dMMR ECAs. We assessed 617 ECAs from representative tissue microarray sections, gathered clinicopathologic information, reviewed histological characteristics, and performed immunohistochemical staining for MMR, programmed cell death 1 (PD-L1), and other immune markers. Of 617 ECA samples, 20 (3.2%) cases had dMMR. Among them, loss of MMR-related proteins expression was observed in 17/562 (3.0%) human papilloma virus-associated (HPVA) adenocarcinoma and 3/55 (5.5%) non-HPV-associated (NHPVA) adenocarcinoma. In NHPVA cohort, dMMR status was observed in 3 (3/14, 15.0%) patients with clear cells. dMMR ECAs had a higher tendency to have a family history of cancer, larger tumor size, p16 negative, HPV E6/E7 mRNA in situ hybridization (HPV E6/E7 RNAscope) negative, and lower ki-67 index. Among the morphological variables evaluated, poor differentiation, necrosis, stromal tumor-infiltrating lymphocytes, peritumoral lymphocytes, and lymphoid follicles were easily recognized in the dMMR ECAs. In addition, dMMR ECAs had higher CD3+, CD8+, CD38+, CD68+ and PD-1+ immune cells. A relatively high prevalence of PD-L1 expression was observed in dMMR ECAs. dMMR ECAs were significantly more likely to present with a tumor-infiltrating lymphocytes -high/PD-L1-positive status. In conclusion, dMMR ECAs have some specific morphological features and a critical impact on the immune microenvironment, which may provide insights into improving responses to immunotherapy-included comprehensive treatment for ECAs in the future.


Assuntos
Adenocarcinoma , Reparo de Erro de Pareamento de DNA , Neoplasias do Colo do Útero , Humanos , Feminino , Neoplasias do Colo do Útero/imunologia , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/virologia , Adulto , Pessoa de Meia-Idade , Adenocarcinoma/imunologia , Adenocarcinoma/genética , Adenocarcinoma/patologia , Adenocarcinoma/virologia , Microambiente Tumoral/imunologia , Idoso , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Linfócitos do Interstício Tumoral/imunologia , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Adulto Jovem , Neoplasias Encefálicas , Síndromes Neoplásicas Hereditárias , Neoplasias Colorretais
3.
BMC Med ; 22(1): 282, 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38972973

RESUMO

BACKGROUND: The advances in deep learning-based pathological image analysis have invoked tremendous insights into cancer prognostication. Still, lack of interpretability remains a significant barrier to clinical application. METHODS: We established an integrative prognostic neural network for intrahepatic cholangiocarcinoma (iCCA), towards a comprehensive evaluation of both architectural and fine-grained information from whole-slide images. Then, leveraging on multi-modal data, we conducted extensive interrogative approaches to the models, to extract and visualize the morphological features that most correlated with clinical outcome and underlying molecular alterations. RESULTS: The models were developed and optimized on 373 iCCA patients from our center and demonstrated consistent accuracy and robustness on both internal (n = 213) and external (n = 168) cohorts. The occlusion sensitivity map revealed that the distribution of tertiary lymphoid structures, the geometric traits of the invasive margin, the relative composition of tumor parenchyma and stroma, the extent of necrosis, the presence of the disseminated foci, and the tumor-adjacent micro-vessels were the determining architectural features that impacted on prognosis. Quantifiable morphological vector extracted by CellProfiler demonstrated that tumor nuclei from high-risk patients exhibited significant larger size, more distorted shape, with less prominent nuclear envelope and textural contrast. The multi-omics data (n = 187) further revealed key molecular alterations left morphological imprints that could be attended by the network, including glycolysis, hypoxia, apical junction, mTORC1 signaling, and immune infiltration. CONCLUSIONS: We proposed an interpretable deep-learning framework to gain insights into the biological behavior of iCCA. Most of the significant morphological prognosticators perceived by the network are comprehensible to human minds.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Aprendizado Profundo , Humanos , Colangiocarcinoma/patologia , Prognóstico , Neoplasias dos Ductos Biliares/patologia , Masculino , Feminino , Pessoa de Meia-Idade , Processamento de Imagem Assistida por Computador/métodos , Idoso
4.
Cereb Cortex ; 33(7): 3773-3786, 2023 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-35989309

RESUMO

Humans often need to deal with various forms of information conflicts that arise when they receive inconsistent information. However, it remains unclear how we resolve them and whether the brain may recruit similar or distinct brain mechanisms to process different domains (e.g. social vs. nonsocial) of conflicts. To address this, we used functional magnetic resonance imaging and scanned 50 healthy participants when they were asked to perform 2 Stroop tasks with different forms of conflicts: social (i.e. face-gender incongruency) and nonsocial (i.e. color-word incongruency) conflicts. Neuroimaging results revealed that the ventral lateral prefrontal cortex was generally activated in processing incongruent versus congruent stimuli regardless of the task type, serving as a common mechanism for conflict resolving across domains. Notably, trial-based and model-based results jointly demonstrated that the dorsal and rostral medial prefrontal cortices were uniquely engaged in processing social incongruent stimuli, suggesting distinct neural substrates of social conflict resolving and adaptation. The findings uncover that the common but unique brain mechanisms are recruited when humans resolve and adapt to social conflicts.


Assuntos
Mapeamento Encefálico , Conflito Psicológico , Humanos , Encéfalo/diagnóstico por imagem , Córtex Pré-Frontal/diagnóstico por imagem , Imageamento por Ressonância Magnética , Teste de Stroop , Tempo de Reação
6.
Angew Chem Int Ed Engl ; 63(21): e202401344, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38422378

RESUMO

The development of high-performance photocatalytic systems for CO2 reduction is appealing to address energy and environmental issues, while it is challenging to avoid using toxic metals and organic sacrificial reagents. We here immobilize a family of cobalt phthalocyanine catalysts on Pb-free halide perovskite Cs2AgBiBr6 nanosheets with delicate control on the anchors of the cobalt catalysts. Among them, the molecular hybrid photocatalyst assembled by carboxyl anchors achieves the optimal performance with an electron consumption rate of 300±13 µmol g-1 h-1 for visible-light-driven CO2-to-CO conversion coupled with water oxidation to O2, over 8 times of the unmodified Cs2AgBiBr6 (36±8 µmol g-1 h-1), also far surpassing the documented systems (<150 µmol g-1 h-1). Besides the improved intrinsic activity, electrochemical, computational, ex-/in situ X-ray photoelectron and X-ray absorption spectroscopic results indicate that the electrons photogenerated at the Bi atoms of Cs2AgBiBr6 can be directionally transferred to the cobalt catalyst via the carboxyl anchors which strongly bind to the Bi atoms, substantially facilitating the interfacial electron transfer kinetics and thereby the photocatalysis.

7.
Anim Cogn ; 26(5): 1505-1519, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37302101

RESUMO

Social comparison is a fundamental human characteristic; however, long-term social comparison may induce psychological stress and can lead to depression and anxiety. Recent studies have shown that nonhuman primates compare themselves with others; however, no studies have investigated whether social comparisons exist among rodents. In the present study, we established a rat model of social comparison. This model was subsequently used to examine the effects of the differential environment of a partner on depression- and anxiety-like behaviors in male rats, as well as to assess the changes in serum, medial prefrontal cortex (mPFC), and dorsal hippocampus brain-derived neurotrophic factor (BDNF) levels induced by long-term social comparison. Compared to rats whose partners were exposed to the same environment, rats whose partners were exposed to two combined enriched environmental stimuli for 14 days showed significantly decreased social novelty preference and sucrose consumption. No anxiety-like behaviors were observed. Rats whose partners were exposed to one enriched environment for 31 days showed significantly increased immobility time in the forced swimming test, and significantly decreased time spent in the center area in the open-field test. Further, rats whose partners were exposed to one enriched environment for 31 days showed lower BDNF levels in the mPFC and dorsal hippocampus, but not following partner exposure for 14 days. These results suggest that social comparisons exist in rats and can induce psychosocial stress and other negative affect. This model will not only provide the possibility to reveal the neurobiological basis of the emotional impact of social comparison, but could also be used to confirm the conservative evolutionary characteristics of social comparison as a behavioral attribute.


Assuntos
Fator Neurotrófico Derivado do Encéfalo , Depressão , Animais , Humanos , Masculino , Ratos , Ansiedade/metabolismo , Ansiedade/psicologia , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Depressão/metabolismo , Depressão/psicologia , Hipocampo/metabolismo , Comparação Social , Estresse Psicológico/metabolismo , Estresse Psicológico/psicologia
8.
J Immunol ; 207(1): 101-109, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-34135065

RESUMO

pH sensing by GPR65 regulates various inflammatory conditions, but its role in skin remains unknown. In this study, we performed a phenome-wide association study and report that the T allele of GPR65-intronic single-nucleotide polymorphism rs8005161, which reduces GPR65 signaling, showed a significant association with atopic dermatitis, in addition to inflammatory bowel diseases and asthma, as previously reported. Consistent with this genetic association in humans, we show that deficiency of GPR65 in mice resulted in markedly exacerbated disease in the MC903 experimental model of atopic dermatitis. Deficiency of GPR65 also increased neutrophil migration in vitro. Moreover, GPR65 deficiency in mice resulted in higher expression of the inflammatory cytokine TNF-α by T cells. In humans, CD4+ T cells from rs8005161 heterozygous individuals expressed higher levels of TNF-α after PMA/ionomycin stimulation, particularly under pH 6 conditions. pH sensing by GPR65 appears to be important for regulating the pathogenesis of atopic dermatitis.


Assuntos
Dermatite Atópica/imunologia , Prótons , Animais , Movimento Celular/imunologia , Concentração de Íons de Hidrogênio , Camundongos , Camundongos Endogâmicos C57BL , Neutrófilos/imunologia , Receptores Acoplados a Proteínas G/análise , Receptores Acoplados a Proteínas G/deficiência , Receptores Acoplados a Proteínas G/imunologia
9.
Ecotoxicol Environ Saf ; 263: 115251, 2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37451095

RESUMO

Endocrine-disrupting chemicals (EDCs) can cause serious harm to human health and the environment; therefore, it is important to rapidly and correctly identify EDCs. Different computational models have been proposed for the prediction of EDCs over the past few decades, but the reported models are not always easily available, and few studies have investigated the structural characteristics of EDCs. In the present study, we have developed a series of artificial intelligence models targeting EDC receptors: the androgen receptor (AR); estrogen receptor (ER); and pregnane X receptor (PXR). The consensus models achieved good predictive results for validation sets with balanced accuracy values of 87.37%, 90.13%, and 79.21% for AR, ER, and PXR binding assays, respectively. Analysis of the physical-chemical properties suggested that several chemical properties were significantly (p < 0.05) different between EDCs and non-EDCs. We also identified structural alerts that can indicate an EDC, which were integrated into the web server SApredictor. These models and structural characteristics can provide useful tools and information in the discrimination and mechanistic understanding of EDCs in drug discovery and environmental risk assessment.


Assuntos
Inteligência Artificial , Disruptores Endócrinos , Humanos , Disruptores Endócrinos/análise , Receptores de Estrogênio/metabolismo , Medição de Risco
10.
Mol Cancer ; 21(1): 93, 2022 04 02.
Artigo em Inglês | MEDLINE | ID: mdl-35366894

RESUMO

BACKGROUND: Circular RNAs (circRNAs) regulate various biological activities and have been shown to play crucial roles in hepatocellular carcinoma (HCC) progression. However, only a few coding circRNAs have been identified in cancers, and their roles in HCC remain elusive. This study aimed to identify coding circRNAs and explore their function in HCC. METHODS: CircMAP3K4 was selected from the CIRCpedia database. We performed a series of experiments to determine the characteristics and coding capacity of circMAP3K4. We then used in vivo and in vitro assays to investigate the biological function and mechanism of circMAP3K4 and its protein product, circMAP3K4-455aa, in HCC. RESULTS: We found circMAP3K4 to be an upregulated circRNA with coding potential in HCC. IGF2BP1 recognized the circMAP3K4 N6-methyladenosine modification and promoted its translation into circMAP3K4-455aa. Functionally, circMAP3K4-455aa prevented cisplatin-induced apoptosis in HCC cells by interacting with AIF, thus protecting AIF from cleavage and decreasing its nuclear distribution. Moreover, circMAP3K4-455aa was degraded through the ubiquitin-proteasome E3 ligase MIB1 pathway. Clinically, a high level of circMAP3K4 is an independent prognostic factor for adverse overall survival and adverse disease-free survival of HCC patients. CONCLUSIONS: CircMAP3K4 is a highly expressed circRNA in HCC. Driven by m6A modification, circMAP3K4 encoded circMAP3K4-455aa, protected HCC cells from cisplatin exposure, and predicted worse prognosis of HCC patients. Targeting circMAP3K4-455aa may provide a new therapeutic strategy for HCC patients, especially for those with chemoresistance. CircMAP3K4 is a highly expressed circRNA in HCC. Driven by m6A modification, IGF2BP1 facilitates circMAP3K4 peptide translation, then the circMAP3K4 peptide inhibits AIF cleavage and nuclear distribution, preventing HCC cells from cell death under stress and promoting HCC progression.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Adenosina/análogos & derivados , Apoptose , Carcinoma Hepatocelular/patologia , Humanos , Neoplasias Hepáticas/patologia , Peptídeos
11.
J Hepatol ; 76(3): 608-618, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34793865

RESUMO

BACKGROUND & AIMS: The prognostic value and clinical relevance of tertiary lymphoid structures (TLSs) in intrahepatic cholangiocarcinoma (iCCA) remain unclear. Thus, we aimed to investigate the prognostic value and functional involvement of TLSs in iCCA. METHODS: We retrospectively included 962 patients from 3 cancer centers across China. The TLSs at different anatomic subregions were quantified and correlated with overall survival (OS) by Cox regression and Kaplan-Meier analyses. Multiplex immunohistochemistry (mIHC) was applied to characterize the composition of TLSs in 39 iCCA samples. RESULTS: A quaternary TLS scoring system was established for the intra-tumor region (T score) and peri-tumor region (P score) respectively. T scores positively correlated with favorable prognosis (p <0.001), whereas a high P score signified worse survival (p <0.001). mIHC demonstrated that both T follicular helper and regulatory T cells were significantly increased in intra-tumoral TLSs compared to peri-tumoral counterparts (p <0.05), and regulatory T cell frequencies within intra-tumoral TLSs were positively associated with P score (p <0.05) rather than T score. Collectively, the combination of T and P scores stratified iCCAs into 4 immune classes with distinct prognoses (p <0.001) that differed in the abundance and distribution pattern of TLSs. Patients displaying an immune-active pattern had the lowest risk, with 5-year OS rates of 68.8%, whereas only 3.4% of patients with an immune-excluded pattern survived at 5 years (p <0.001). The C-index of the immune class was statistically higher than the TNM staging system (0.73 vs. 0.63, p <0.001). These results were validated in an internal and 2 external cohorts. CONCLUSIONS: The spatial distribution and abundance of TLSs significantly correlated with prognosis and provided a useful immune classification for iCCA. T follicular helper and regulatory T cells may play a critical role in determining the functional orientation of spatially different TLSs. LAY SUMMARY: Tertiary lymphoid structures (TLSs) are associated with favorable prognosis in a number of cancers. However, their role in intrahepatic cholangiocarcinoma (iCCA) remains unclear. Herein, we comprehensively evaluated the spatial distribution, abundance, and cellular composition of TLSs in iCCA, and revealed the opposite prognostic impacts of TLSs located within or outside the tumor. This difference could be mediated by the different immune cell subsets present within the spatially distinct TLSs. Based on our analysis, we were able to stratify iCCAs into 4 immune subclasses associated with varying prognoses.


Assuntos
Distribuição da Gordura Corporal/classificação , Contagem de Células/classificação , Colangiocarcinoma/complicações , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Estruturas Linfoides Terciárias/fisiopatologia , Idoso , China , Colangiocarcinoma/mortalidade , Colangiocarcinoma/fisiopatologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde/métodos , Prognóstico , Estudos Retrospectivos , Estruturas Linfoides Terciárias/classificação
12.
J Cardiovasc Pharmacol ; 79(6): 781-790, 2022 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-35507915

RESUMO

ABSTRACT: Levosimendan and milrinone are 2 effective inotropic drugs used to maintain cardiac output in acute heart failure (AHF). Using data from patients with AHF with and without abnormal renal function, we performed this single-center, retrospective cohort study to compare the effectiveness and safety of milrinone and levosimendan for the initial management of AHF. Patients admitted for heart failure between December 2016 and September 2019 who received levosimendan or milrinone as initial inotrope therapy in the cardiology department were identified. A total of 436 levosimendan and 417 milrinone patients with creatinine clearance (CrCl) ≥30 mL/min and 50 levosimendan and 71 milrinone patients with CrCl <30 mL/min or on dialysis were included. The primary outcome was a composite of changes in clinical status at 15 and 30 days after initial inotrope therapy discontinuation. Between subgroups of patients with CrCl ≥30 mL/min, there were no significant differences in primary outcomes; milrinone was associated with more frequent hypotension and cardiac arrhythmias during the infusion period (P < 0.01), while levosimendan was associated with more frequent cardiac arrhythmias within 48 hours after discontinuation (P < 0.05). Of the patients with CrCl <30 mL/min or on dialysis, more initial levosimendan than milrinone patients and those who switched to alternative inotropes experienced clinical worsening at 15 days and 30 days (P < 0.05). According to our results, patients with AHF with severe renal dysfunction should avoid initial inotrope therapy with levosimendan.


Assuntos
Insuficiência Cardíaca , Nefropatias , Piridazinas , Cardiotônicos/efeitos adversos , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/tratamento farmacológico , Humanos , Hidrazonas/efeitos adversos , Nefropatias/tratamento farmacológico , Milrinona/efeitos adversos , Piridazinas/efeitos adversos , Estudos Retrospectivos , Simendana/efeitos adversos
13.
BMC Public Health ; 22(1): 1403, 2022 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-35869459

RESUMO

Social norms can coordinate individuals and groups during collective threats. Pandemic-related social norms (e.g., wearing masks, social distancing) emerged to curb the spread of COVID-19. However, little is known about the psychological consequences of the emerging norms. We conducted three experiments cross-culturally, during the early period of the COVID-19 pandemic in China (Study 1), the recovery period in China (Study 2), and the severe period in the United States and Canada (Study 3). Across the three studies, we first distinguished the opposite effects of social norms and risk perception on individuals' psychological characteristics during the COVID-19 pandemic and further revealed that individuals who perceived stronger pandemic norms reported a lower level of COVID-19 risk perception, which in turn would be associated with fewer negative emotions, lower pressure, more positive emotions, higher levels of trusts, and more confidence in fighting against COVID-19. Our findings show that perceived tighter social norms are linked to beneficial psychological outcomes. This research helps governments, institutions, and individuals understand the mechanism and benefits of social norms during the pandemic, thereby facilitating policy formulation and better responses to social crises.


Assuntos
COVID-19 , COVID-19/epidemiologia , Humanos , Máscaras , Pandemias , Percepção , Normas Sociais , Estados Unidos/epidemiologia
14.
Molecules ; 27(13)2022 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-35807320

RESUMO

Phytotherapy offers obvious advantages in the intervention of Coronary Artery Disease (CAD), but it is difficult to clarify the working mechanisms of the medicinal materials it uses. DGS is a natural vasoprotective combination that was screened out in our previous research, yet its potential components and mechanisms are unknown. Therefore, in this study, HPLC-MS and network pharmacology were employed to identify the active components and key signaling pathways of DGS. Transgenic zebrafish and HUVECs cell assays were used to evaluate the effectiveness of DGS. A total of 37 potentially active compounds were identified that interacted with 112 potential targets of CAD. Furthermore, PI3K-Akt, MAPK, relaxin, VEGF, and other signal pathways were determined to be the most promising DGS-mediated pathways. NO kit, ELISA, and Western blot results showed that DGS significantly promoted NO and VEGFA secretion via the upregulation of VEGFR2 expression and the phosphorylation of Akt, Erk1/2, and eNOS to cause angiogenesis and vasodilation. The result of dynamics molecular docking indicated that Salvianolic acid C may be a key active component of DGS in the treatment of CAD. In conclusion, this study has shed light on the network molecular mechanism of DGS for the intervention of CAD using a network pharmacology-driven strategy for the first time to aid in the intervention of CAD.


Assuntos
Doença da Artéria Coronariana , Medicamentos de Ervas Chinesas , Animais , Doença da Artéria Coronariana/tratamento farmacológico , Simulação de Acoplamento Molecular , Farmacologia em Rede , Fosfatidilinositol 3-Quinases/metabolismo , Fitoterapia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Peixe-Zebra/metabolismo
15.
Neuroimage ; 244: 118644, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34637906

RESUMO

Gender discrimination is a serious social issue that has been shown to increase negative consequences, especially in females when accompanied by acute or chronic pain. Experiencing social pain through discrimination can increase an individual's evaluation of evoked physical pain. However, few studies have explored the mechanism underlying how gender discrimination modulates brain responses when individuals experience physical pain evoked by noxious stimuli. In this study, we addressed this issue using a gender discrimination fMRI paradigm with thermal pain stimulation. We found that discrimination indeed affected participants' own behavioral self-evaluation of noxious stimuli. Discrimination-encoded brain activations were identified in the temporopolar cortex, while brain activations to thermal stimuli after viewing pictures of discrimination were found in the dorsal anterior cingulate cortex (dACC). Brain activations in the temporopolar cortex and the dACC were correlated. Furthermore, pain perception-specific functional connectivity of the dACC-SII in the cue stage and the dACC-frontal in the pain stage were identified, suggesting a facilitative effect of gender discrimination on females' experience of physical pain. Our results indicate that the dACC may play a central role in mediating the affective aspect of physical pain after experiencing discrimination. These findings provide novel insights into the underlying mechanism of how gender discrimination facilitates females' experience of physical pain.


Assuntos
Encéfalo/diagnóstico por imagem , Dor Crônica/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Sexismo , Adolescente , Adulto , Mapeamento Encefálico , Córtex Cerebral/diagnóstico por imagem , Feminino , Giro do Cíngulo/diagnóstico por imagem , Humanos , Vias Neurais , Adulto Jovem
16.
Chemistry ; 27(7): 2305-2309, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33107087

RESUMO

Capping ligands are indispensable for the preparation of metal-halide-perovskite (MHP) nanocrystals (NCs) with good stability; however, the long alkyl-chain capping ligands in conventional MHP NCs will be unfavorable for CO2 adsorption and hinder the efficient carrier separation on the surface of MHP NCs, leading to inferior catalytic activity in artificial photosynthesis. Herein, CsPbBr3 nanocrystals with short-chain glycine as ligand are constructed through a facile ligand-exchange strategy. Owing to the reduced hindrance of glycine and the presence of the amine group in glycine, the photogenerated carrier separation and CO2 uptake capacity are noticeably improved without compromising the stability of the MHP NCs. The CsPbBr3 nanocrystals with glycine ligands exhibit a significantly increased yield of 27.7 µmol g-1 h-1 for photocatalytic CO2 -to-CO conversion without any organic sacrificial reagents, which is over five times higher than that of control CsPbBr3 NCs with conventional long alkyl-chain capping ligands.

17.
J Sep Sci ; 44(13): 2663-2673, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33914393

RESUMO

Pleurospermum (Apiaceae) species possess a wide range of biological properties viz. analgesic, anti-inflammatory, antimalarial, and so on. Pleurospermum candollei (DC.) Benth. Ex C. B. Clark. is reported to cure diarrhea, gastric, respiratory, stomach, abdominal, joint, and back pain problems. In addition, it is also used for both male and female infertility. The present study deals with an efficient technique using high-speed countercurrent chromatography for separation of chemical components from the methanol extract of P. candollei. Notably, nine main compounds namely luteolin 7-O-glucoside (1), oxypeucedanin hydrate (2), pabulenol (3), bergapten (4), heptadecanoic acid (5), (E)-isoelemicin (6), trans-asarone (7), α-linolenic acid (8), and isoimperatorin (9) were very efficiently separated and isolated in pure form. Multiple injections were applied followed by two off-line recycling high-speed countercurrent chromatography. The inhibitory effect of nitric oxide production of all compounds was tested in the presence of 200 ng/mL lipopolysaccharide in RAW264.7 mice macrophage cells. The results demonstrated that compounds 7 and 8 effectively inhibited nitric oxide production, with IC50 values of 28.44 and 53.18 µM, respectively. This study thus validates the traditional claim of using P. candollei. Taken together, these findings will be useful in future research to find a potential candidate with anti-inflammatory properties.


Assuntos
Anti-Inflamatórios , Apiaceae/química , Distribuição Contracorrente/classificação , Extratos Vegetais , Animais , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Distribuição Contracorrente/métodos , Furocumarinas/isolamento & purificação , Furocumarinas/farmacologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Óxido Nítrico/antagonistas & inibidores , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Pirogalol/análogos & derivados , Pirogalol/isolamento & purificação , Pirogalol/farmacologia , Células RAW 264.7
18.
Fungal Divers ; 111(1): 1-335, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34899100

RESUMO

This article is the 13th contribution in the Fungal Diversity Notes series, wherein 125 taxa from four phyla, ten classes, 31 orders, 69 families, 92 genera and three genera incertae sedis are treated, demonstrating worldwide and geographic distribution. Fungal taxa described and illustrated in the present study include three new genera, 69 new species, one new combination, one reference specimen and 51 new records on new hosts and new geographical distributions. Three new genera, Cylindrotorula (Torulaceae), Scolecoleotia (Leotiales genus incertae sedis) and Xenovaginatispora (Lindomycetaceae) are introduced based on distinct phylogenetic lineages and unique morphologies. Newly described species are Aspergillus lannaensis, Cercophora dulciaquae, Cladophialophora aquatica, Coprinellus punjabensis, Cortinarius alutarius, C. mammillatus, C. quercoflocculosus, Coryneum fagi, Cruentomycena uttarakhandina, Cryptocoryneum rosae, Cyathus uniperidiolus, Cylindrotorula indica, Diaporthe chamaeropicola, Didymella azollae, Diplodia alanphillipsii, Dothiora coronicola, Efibula rodriguezarmasiae, Erysiphe salicicola, Fusarium queenslandicum, Geastrum gorgonicum, G. hansagiense, Helicosporium sexualis, Helminthosporium chiangraiensis, Hongkongmyces kokensis, Hydrophilomyces hydraenae, Hygrocybe boertmannii, Hyphoderma australosetigerum, Hyphodontia yunnanensis, Khaleijomyces umikazeana, Laboulbenia divisa, Laboulbenia triarthronis, Laccaria populina, Lactarius pallidozonarius, Lepidosphaeria strobelii, Longipedicellata megafusiformis, Lophiotrema lincangensis, Marasmius benghalensis, M. jinfoshanensis, M. subtropicus, Mariannaea camelliae, Melanographium smilaxii, Microbotryum polycnemoides, Mimeomyces digitatus, Minutisphaera thailandensis, Mortierella solitaria, Mucor harpali, Nigrograna jinghongensis, Odontia huanrenensis, O. parvispina, Paraconiothyrium ajrekarii, Parafuscosporella niloticus, Phaeocytostroma yomensis, Phaeoisaria synnematicus, Phanerochaete hainanensis, Pleopunctum thailandicum, Pleurotheciella dimorphospora, Pseudochaetosphaeronema chiangraiense, Pseudodactylaria albicolonia, Rhexoacrodictys nigrospora, Russula paravioleipes, Scolecoleotia eriocamporesi, Seriascoma honghense, Synandromyces makranczyi, Thyridaria aureobrunnea, Torula lancangjiangensis, Tubeufia longihelicospora, Wicklowia fusiformispora, Xenovaginatispora phichaiensis and Xylaria apiospora. One new combination, Pseudobactrodesmium stilboideus is proposed. A reference specimen of Comoclathris permunda is designated. New host or distribution records are provided for Acrocalymma fici, Aliquandostipite khaoyaiensis, Camarosporidiella laburni, Canalisporium caribense, Chaetoscutula juniperi, Chlorophyllum demangei, C. globosum, C. hortense, Cladophialophora abundans, Dendryphion hydei, Diaporthe foeniculina, D. pseudophoenicicola, D. pyracanthae, Dictyosporium pandanicola, Dyfrolomyces distoseptatus, Ernakulamia tanakae, Eutypa flavovirens, E. lata, Favolus septatus, Fusarium atrovinosum, F. clavum, Helicosporium luteosporum, Hermatomyces nabanheensis, Hermatomyces sphaericoides, Longipedicellata aquatica, Lophiostoma caudata, L. clematidis-vitalbae, Lophiotrema hydei, L. neoarundinaria, Marasmiellus palmivorus, Megacapitula villosa, Micropsalliota globocystis, M. gracilis, Montagnula thailandica, Neohelicosporium irregulare, N. parisporum, Paradictyoarthrinium diffractum, Phaeoisaria aquatica, Poaceascoma taiwanense, Saproamanita manicata, Spegazzinia camelliae, Submersispora variabilis, Thyronectria caudata, T. mackenziei, Tubeufia chiangmaiensis, T. roseohelicospora, Vaginatispora nypae, Wicklowia submersa, Xanthagaricus necopinatus and Xylaria haemorrhoidalis. The data presented herein are based on morphological examination of fresh specimens, coupled with analysis of phylogenetic sequence data to better integrate taxa into appropriate taxonomic ranks and infer their evolutionary relationships.

19.
Small ; 16(29): e2002140, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32510866

RESUMO

The judicious design of efficient electron mediators to accelerate the interfacial charge transfer in a Z-scheme system is one of the viable strategies to improve the performance of photocatalysts for artificial photosynthesis. Herein, ultrathin and small-size graphene oxide (USGO) nanosheets are constructed and employed as the electron mediator to elaborately exploit an efficient CsPbBr3 -based all-solid-state Z-scheme system in combination with α-Fe2 O3 for visible-light-driven CO2 reduction with water as the electron source. CsPbBr3 and α-Fe2 O3 can be closely anchored on USGO nanosheets, owing to the existence of interfacial strong chemical bonding behaviors, which can significantly accelerate the photogenerated carrier transfer between CsPbBr3 and α-Fe2 O3 . The resultant improved charge separation efficiency endows the Z-scheme system exhibiting a record-high electron consumption rate of 147.6 µmol g-1 h-1 for photocatalytic CO2 -to-CO conversion concomitant with stoichiometric O2 from water oxidation, which is over 19 and 12 times higher than that of pristine CsPbBr3 nanocrystals and the mixture of CsPbBr3 and α-Fe2 O3 , respectively. This work provides a novel and effective strategy for improving the catalytic activity of halide-perovskite-based photocatalysts, promoting their practical applications in the field of artificial photosynthesis.

20.
BMC Cancer ; 20(1): 607, 2020 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-32600297

RESUMO

BACKGROUND: Small hepatocellular carcinoma (sHCC) is a special subtype of HCC with the maximum tumor diameter ≤ 3 cm and excellent long-term outcomes. Surgical resection or radiofrequency ablation provides the greatest chance for cure; however, many patients still undergo tumor recurrence after primary treatment. To date, there is no clinical applicable method to assess biological aggressiveness in solitary sHCC. METHODS: In the current study, we retrospectively evaluated tumor necrosis of 335 patients with solitary sHCC treated with hepatectomy between December 1998 and 2010 from Sun Yat-sen University Cancer Center. RESULTS: The presence of tumor necrosis was observed in 157 of 335 (46.9%) sHCC patients. Further correlation analysis showed that tumor necrosis was significantly correlated with tumor size and vascular invasion (P = 0.026, 0.003, respectively). The presence of tumor necrosis was associated closely with poorer cancer-specific overall survival (OS) and recurrence-free survival (RFS) as evidenced by univariate (P <  0.001; hazard ratio, 2.821; 95% CI, 1.643-4.842) and multivariate analysis (P = 0.005; hazard ratio, 2.208; 95% CI, 1.272-3.833). Notably, the combined model by tumor necrosis, vascular invasion and tumor size can significantly stratify the risk for RFS and OS and improve the ability to discriminate sHCC patients' outcomes (P <  0.0001 for both). CONCLUSIONS: Our results provide evidence that tumor necrosis has the potential to be a parameter for cancer aggressiveness in solitary sHCC. The combined prognostic model may be a useful tool to identify solitary sHCC patients with worse outcomes.


Assuntos
Carcinoma Hepatocelular/cirurgia , Hepatectomia , Neoplasias Hepáticas/cirurgia , Fígado/patologia , Recidiva Local de Neoplasia/epidemiologia , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Intervalo Livre de Doença , Estudos de Viabilidade , Feminino , Seguimentos , Humanos , Fígado/cirurgia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Necrose/epidemiologia , Necrose/patologia , Invasividade Neoplásica/patologia , Prognóstico , Estudos Retrospectivos , Medição de Risco/métodos , Fatores de Risco , Carga Tumoral
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