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BACKGROUND & AIMS: The liver is the main organ of ketogenesis, while ketones are mainly metabolized in peripheral tissues via the critical enzyme 3-oxoacid CoA-transferase 1 (OXCT1). We previously found that ketolysis is reactivated in hepatocellular carcinoma (HCC) cells through OXCT1 expression to promote tumor progression; however, whether OXCT1 regulates antitumor immunity remains unclear. METHODS: To investigate the expression pattern of OXCT1 in HCC in vivo, we conducted multiplex immunohistochemistry experiments on human HCC specimens. To explore the role of OXCT1 in mouse HCC tumor-associated macrophages (TAMs), we generated LysMcreOXCT1f/f (OXCT1 conditional knockout in macrophages) mice. RESULTS: Here, we found that inhibiting OXCT1 expression in tumor-associated macrophages reduced CD8+ T-cell exhaustion through the succinate-H3K4me3-Arg1 axis. Initially, we found that OXCT1 was highly expressed in liver macrophages under steady state and that OXCT expression was further increased in TAMs. OXCT1 deficiency in macrophages suppressed tumor growth by reprogramming TAMs toward an antitumor phenotype, reducing CD8+ T-cell exhaustion and increasing CD8+ T-cell cytotoxicity. Mechanistically, high OXCT1 expression induced the accumulation of succinate, a byproduct of ketolysis, in TAMs, which promoted Arg1 transcription by increasing the H3K4me3 level in the Arg1 promoter. In addition, pimozide, an inhibitor of OXCT1, suppressed Arg1 expression as well as TAM polarization toward the protumor phenotype, leading to decreased CD8+ T-cell exhaustion and slower tumor growth. Finally, high expression of OXCT1 in macrophages was positively associated with poor survival in patients with HCC. CONCLUSIONS: In conclusion, our results demonstrate that OXCT1 epigenetically suppresses antitumor immunity, suggesting that suppressing OXCT1 activity in TAMs could be an effective approach for treating liver cancer. IMPACT AND IMPLICATIONS: The intricate metabolism of liver macrophages plays a critical role in shaping hepatocellular carcinoma progression and immune modulation. Targeting macrophage metabolism to counteract immune suppression presents a promising avenue for hepatocellular carcinoma treatment. Herein, we found that the ketogenesis gene OXCT1 was highly expressed in tumor-associated macrophages (TAMs) and promoted tumor growth by reprogramming TAMs toward a protumor phenotype. Pharmacological targeting or genetic downregulation of OXCT1 in TAMs enhances antitumor immunity and slows tumor growth. Our results suggest that suppressing OXCT1 activity in TAMs could be an effective approach for treating liver cancer.
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The correlation between the size of nanoparticles, the structure and shape of mesogenic ligands and the ensuing assembly behaviour is not really understood. Closer inspection shows very surprising features. Here, 2- and 4-nm gold nanoparticles (NPs) were synthesized, and grafted with a forked ligand containing two rod-like mesogens in its branches: one cholesterol, the other with azobenzene. The 4-nm NPs also contained n-hexylthiol as co-ligand. They were found to form a FCC cubic superlattice, whereas the 2-nm NPs form hexagonal HCP with weak birefringence, hence with partially oriented ligands. The structures were compared with those of related systems containing a range of different azobenzene-to-cholesterol ratios, all giving body-centred tetragonal superlattices with various degrees of anisotropy. Geometric analysis is presented in terms of the asphericity of the NPs' surroundings, requirement for space-filling and structural anisotropy. Some general rules are derived to help design the soft corona around the NPs in order to obtain superlattices with the desired structure and anisotropy.
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Radiation-induced intestinal injury (RIII) is one of the most common abdominal and pelvic radiation therapy complications. RIII seriously affects the treatment and prognosis of cancer patients, and there are no effective interventions. Radiation can cause intestinal tissue damage, inflammatory cell infiltration, and pro-inflammatory cytokine release. We established an RIII mouse model by subjecting C57BL/6 mice to abdominal irradiation. Our results show that both pyroptosis and ferroptosis play a key role in RIII. VX-765 and Ferrostatin-1 (Fer-1) can inhibit these two types of programmed cell death and ameliorate RIII, respectively. Activation of the nuclear factor-κB (NF-κB) signaling pathway exacerbates the chemotaxis of inflammatory cells. In the present study, we hypothesized that the activation of NF-κB signaling pathway plays an important role in intestinal inflammatory injury. We demonstrated that the nuclear expression levels of the NF-κB subunit p65 increased after irradiation treatment. Reduced release of inflammatory factors and intestinal tissue damage was observed after pretreatment with pyrrolidinedithiocarbamate ammonium (PDTC). Moreover, after PDTC treatment, the indicators related to pyroptosis and ferroptosis were reversed. Collectively, these results suggest that the activation of the intestinal NF-κB signaling pathway may be associated with pyroptosis, ferroptosis, and subsequent intestinal injury after irradiation.
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Compostos de Amônio , Ferroptose , Lesões por Radiação , Animais , Citocinas/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Prolina/análogos & derivados , Piroptose , Pirrolidinas , TiocarbamatosRESUMO
BACKGROUND: Aspergillus fumigatus infection is difficult to diagnose clinically and can develop into invasive pulmonary aspergillosis, which has a high fatality rate. The incidence of Aspergillus fumigatus infection has increased die to widespread application of radiotherapy technology. However, knowledge regarding A. fumigatus infection following radiation exposure is limited, and the underlying mechanism remains unclear. In this study, we established a mouse model to explore the effect of radiation on A. fumigatus infection and the associated mechanisms. METHODS: In this study, a mouse model of A. fumigatus infection after radiation was established by irradiating with 5 Gy on the chest and instilling 5 × 107/ml Aspergillus fumigatus conidia into trachea after 24 h to explore the effect and study its function and mechanism. Mice were compared among the following groups: normal controls (CON), radiation only (RA), infection only (Af), and radiation + infection (RA + Af). Staining analyses were used to detect infection and damage in lung tissues. Changes in protein and mRNA levels of pyroptosis-related molecules were assessed by western blot analysis and quantitative reverse transcription polymerase chain reaction, respectively. Protein concentrations in the serum and alveolar lavage fluid were also measured. An immunofluorescence colocalization analysis was performed to confirm that NLRP3 inflammasomes activated pyroptosis. RESULTS: Radiation destroyed the pulmonary epithelial barrier and significantly increased the pulmonary fungal burden of A. fumigatus. The active end of caspase-1 and gasdermin D (GSDMD) were highly expressed even after infection. Release of interleukin-18 (IL-18) and interleukin-1ß (IL-1ß) provided further evidence of pyroptosis. NLRP3 knockout inhibited pyroptosis, which effectively attenuated damage to the pulmonary epithelial barrier and reduced the burden of A. fumigatus. CONCLUSIONS: Our findings indicated that the activation of NLRP3 inflammasomes following radiation exposure increased susceptibility to A. fumigatus infection. Due to pyroptosis in lung epithelial cells, it resulted in the destruction of the lung epithelial barrier and further damage to lung tissue. Moreover, we found that NLRP3 knockout effectively inhibited the pyroptosis and reducing susceptibility to A. fumigatus infection and further lung damage. Overall, our results suggest that NLRP3/GSDMD pathway mediated-pyroptosis in the lungs may be a key event in this process and provide new insights into the underlying mechanism of infection. Video abstract.
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Aspergilose , Células Epiteliais , Inflamassomos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Proteínas de Ligação a Fosfato , Proteínas Citotóxicas Formadoras de Poros , Animais , Aspergilose/metabolismo , Aspergillus fumigatus/metabolismo , Modelos Animais de Doenças , Suscetibilidade a Doenças/microbiologia , Células Epiteliais/microbiologia , Inflamassomos/metabolismo , Pulmão/metabolismo , Camundongos , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proteínas de Ligação a Fosfato/metabolismo , Proteínas Citotóxicas Formadoras de Poros/metabolismo , Piroptose , Irradiação Corporal TotalRESUMO
AIMS: Experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis (MS), is characterized by immune-mediated demyelination and neurodegeneration. NOD-like receptor protein 3 (NLRP3) inflammasome activation aggravates spinal cord inflammation in EAE. Autophagy is associated with alleviation of systemic inflammation, including that encountered in EAE. However, the effects of autophagy on NLRP3 in EAE are still unclear. Here, we evaluated the effects of the autophagy activator AZD8055 on EAE. METHODS: EAE model mice were established, histological examination was performed to assess the degree of inflammatory cell infiltration and demyelination. And the levels of autophagy and NLRP3-mediated pyroptosis in spinal cords were assessed. Western blotting and immunofluorescence analyses were performed to evaluate protein expression and localization. RESULTS: AZD8055 significantly enhanced autophagy in the spinal cords of EAE model mice, coupled with decreased abnormal clinical behavior scores and increased body weights. The degree of inflammatory cell infiltration and demyelination was mild in AZD8055-treated EAE model mice.Meanwhile, the pathway of ROS/NLRP3 was downregulated, and LC3 and NLRP3 were colocalized. CONCLUSIONS: AZD8055 ameliorated EAE through anti-inflammatory and anti-pyroptosis effects via the mammalian target of mTOR/ROS/NLRP3 pathway. These findings provide insights into the interactions between autophagy and pyroptosis and may facilitate the development of novel treatments for MS.
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Encefalomielite Autoimune Experimental/tratamento farmacológico , Morfolinas/farmacologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/antagonistas & inibidores , Espécies Reativas de Oxigênio/antagonistas & inibidores , Serina-Treonina Quinases TOR/antagonistas & inibidores , Animais , Encefalomielite Autoimune Experimental/metabolismo , Feminino , Camundongos , Camundongos Endogâmicos C57BL , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Piroptose/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Serina-Treonina Quinases TOR/metabolismoRESUMO
PURPOSE: MicroRNAs act as crucial regulators of a diverse range of biological processes, including chemoresistance. Our study aimed to investigate the effect of miR-324-3p on lung adenocarcinoma cell line A549 resistant to cis-diamminedichloroplatinum II (DDP, aka cisplatin). METHODS: The miR-324-3p expression levels in cisplatin-sensitive A549ï¼A549ï¼ and cisplatin-resistant A549 (A549/DDP) cells were determined by qRT-PCR assay. Cell proliferation was determined with the commercial kit CCK-8 and colony formation assay, whereas cell death was analyzed using flow cytometry. The target gene of miR-324-3p was identified and validated with the luciferase reporter and western blot assays. The role of miR-324-3p in modulating cisplatin resistance was evaluated in vitro. RESULTS: The expression of miR-324-3p was found to be significantly downregulated in the A549/DDP cells. Conversely, miR-324-3p overexpression reversed cisplatin resistance in the cells. With regard to the possible mechanism underlying this phenomenon, we identified the glutathione peroxidase 4 (GPX4) gene as the direct target of miR-324-3p, where overexpression of the gene reversed the miR-324-3p effect of sensitizing the A549/DDP cells to cisplatin. Furthermore, the GPX4 inhibitor RSL3 could mimic the effect of miR-324-3p upregulation in increasing the sensitivity of the cisplatin-resistant cells to the drug. Significantly, miR-324-3p enhanced cisplatin-induced ferroptosis in the A549/DDP cells. CONCLUSION: Our findings revealed the role of the miR-324-3p-GPX4 signaling axis in A549/DDP cells and how the targeting of this axis could be a potential strategy for reversing cisplatin resistance in human non small cell lung cancer (NSCLC).
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Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Cisplatino/farmacologia , Resistencia a Medicamentos Antineoplásicos/genética , Ferroptose/genética , Neoplasias Pulmonares/genética , MicroRNAs/metabolismo , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/metabolismo , Células A549 , Adenocarcinoma de Pulmão/ultraestrutura , Sequência de Bases , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/genética , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Ferroptose/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/ultraestrutura , MicroRNAs/genética , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/ultraestrutura , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/genéticaRESUMO
Specific manipulation of RNA is necessary for the research in biotechnology and medicine. The RNA-binding domains of Pumilio/fem-3 mRNA binding factors (PUF domains) are programmable RNA binding scaffolds used to engineer artificial proteins that specifically modulate RNAs. However, the native PUF domains generally recognize 8-nt RNAs, limiting their applications. Here, we modify the PUF domain of human Pumilio1 to engineer PUFs that recognize RNA targets of different length. The engineered PUFs bind to their RNA targets specifically and PUFs with more repeats have higher binding affinity than the canonical eight-repeat domains; however, the binding affinity reaches the peak at those with 9 and 10 repeats. Structural analysis on PUF with nine repeats reveals a higher degree of curvature, and the RNA binding unexpectedly and dramatically opens the curved structure. Investigation of the residues positioned in between two RNA bases demonstrates that tyrosine and arginine have favored stacking interactions. Further tests on the availability of the engineered PUFs in vitro and in splicing function assays indicate that our engineered PUFs bind RNA targets with high affinity in a programmable way.
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Domínios Proteicos , Engenharia de Proteínas , Proteínas de Ligação a RNA/química , RNA/química , Processamento Alternativo , Arginina/química , Sequência de Bases , Humanos , Modelos Moleculares , Ligação Proteica , RNA/metabolismo , Tirosina/químicaRESUMO
While tumor-infiltrating cytotoxic T lymphocytes play a critical role in controlling tumor development, they are generally impotent in an acidic tumor microenvironment. Systemic treatment to neutralize tumor acidity thus holds promise for the reversal of the anergic state of T cells and the improvement of T cell-associated immunotherapy. Herein, we report a proof-of-concept of RNAi nanoparticle-mediated therapeutic reversion of tumor acidity to restore the antitumor functions of T cells and potentiate the checkpoint blockade therapy. Our strategy utilized an in vivo optimized vesicular cationic lipid-assisted nanoparticle, as opposed to its micellar counterpart, to mediate systematic knockdown of lactate dehydrogenase A (LDHA) in tumor cells. The treatment resulted in the reprogramming of pyruvate metabolism, a reduction of the production of lactate, and the neutralization of the tumor pH. In immunocompetent syngeneic melanoma and breast tumor models, neutralization of tumor acidity increased infiltration with CD8+ T and NK cells, decreased the number of immunosuppressive T cells, and thus significantly inhibited the growth of tumors. Furthermore, the restoration of tumoral pH potentiated checkpoint inhibition therapy using the antibody of programmed cell death protein 1 (PD-1). However, in immunodeficient B6/ Rag1 -/- and NOG mice, the same treatment failed to control tumor growth, further proving that the attenuation of tumor growth by tumor acidity modulation was attributable to the activation of tumor-infiltrating immune cells.
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Imunoterapia , Melanoma Experimental/tratamento farmacológico , Nanopartículas/administração & dosagem , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Ácidos/metabolismo , Animais , Linfócitos T CD8-Positivos/imunologia , Proteínas de Transporte/genética , Proliferação de Células/efeitos dos fármacos , Proteínas de Homeodomínio/genética , Humanos , Concentração de Íons de Hidrogênio , L-Lactato Desidrogenase/genética , Ativação Linfocitária/efeitos dos fármacos , Ativação Linfocitária/imunologia , Linfócitos do Interstício Tumoral , Melanoma Experimental/genética , Melanoma Experimental/imunologia , Melanoma Experimental/patologia , Camundongos , Nanopartículas/química , Microambiente Tumoral/efeitos dos fármacosRESUMO
Penicitrinine A, a novel alkaloid with a unique spiro skeleton, was isolated from a marine-derived fungus Penicillium citrinum. In this study, the isolation, structure and biosynthetic pathway elucidation of the new compound were described. This new compound showed anti-proliferative activity on multiple tumor types. Among them, the human malignant melanoma cell A-375 was confirmed to be the most sensitive. Morphologic evaluation, apoptosis rate analysis, Western blot and real-time quantitative PCR (RT-qPCR) results showed penicitrinine A could significantly induce A-375 cell apoptosis by decreasing the expression of Bcl-2 and increasing the expression of Bax. Moreover, we investigated the anti-metastatic effects of penicitrinine A in A-375 cells by wound healing assay, trans-well assay, Western blot and RT-qPCR. The results showed penicitrinine A significantly suppressed metastatic activity of A-375 cells by regulating the expression of MMP-9 and its specific inhibitor TIMP-1. These findings suggested that penicitrinine A might serve as a potential antitumor agent, which could inhibit the proliferation and metastasis of tumor cells.
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Alcaloides/farmacologia , Antineoplásicos/farmacologia , Organismos Aquáticos/metabolismo , Penicillium/metabolismo , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Humanos , Metaloproteinase 9 da Matriz/metabolismo , Melanoma/tratamento farmacológico , Melanoma/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Inibidor Tecidual de Metaloproteinase-1/metabolismo , Proteína X Associada a bcl-2/metabolismoRESUMO
As people deeply study the electronic spectra of fluorescent compounds and photophysical behavior, enormous progress has been made in the aspect of changes and states of different systems in the use of fluorescent molecules as probes. PTC-DA is a kind of typical fluorescent molecular probe that is highly sensitive and selective in water environment. This paper makes a research on the physical mechanism of light of PTCDA by TDF (Density Functional Theory), calculates the optimal configuration the charge population and excitation spectra of PTCDA molecules under ideal condition and acquires PTCDA fluorescence emission spectra then analyses that PTCDA is a kind of quenching and dual colorimetric signal probe response. Its optical signal response mechanism belongs to ICT (Intramolecular Charge Transfer) mechanism. According to the results, this perylene derivatives is fitted with Cu2+ excited state absorption spectra. Before and after the combination with Cu2+, the peak shape of absorption spectrum is similar. When copper is added, the overall absorption peak position occurred redshift, quenching discoloration happens. By comparing with experimental values, the calculated molecular configuration is reasonable and effective and the peak of excitation spectra is realistic. Analysis shows that: PTCDA molecules divalent copper ions have better fluorescence detection activity, the optical signal response mechanisms are intramolecular charge transfer (ICT) mechanisms. When a molecule receives divalent copper ions, the absorption spectrum peak position redshifts, intramolecular charge transfer direction and intensity changes. There occur both quenching signal and discoloration signal. It is a kind of fluorescent probe material with double quenching and discoloration fluorescent signal, which has great potential for development. This paper makes an early-stage exploration of the physical mechanism of light response mechanism analysis in molecular fluorescent probe field and can be a systematically valuable theoretical reference for this field.
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A rare hexacyclic oxindole alkaloid, speradine F (1), together with two novel tetracyclic oxindole alkaloids, speradines G (2) and H (3), were isolated from the marine-derived fungus Aspergillus oryzae. Their structures were determined by spectroscopic methods and X-ray diffraction analysis. This study is the first report on cyclopiazonic acid (CPA)-type alkaloids with a hexacyclic skeleton.
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Alcaloides/isolamento & purificação , Aspergillus oryzae/química , Indóis/química , Biologia Marinha , Alcaloides/química , Fermentação , Modelos Moleculares , Espectroscopia de Prótons por Ressonância MagnéticaRESUMO
Heterostructure engineering is an effective technology to improve photo-electronic properties of two dimensional layered semiconductors. In this paper, based on first principles method, we studied the structure, stability, energy band, and optical properties of ZnSe/SnSe heterostructure change with film layer. Results show that all heterostructures are the type-II band arrangement, and the interlayer interaction is characterized by van der Waals. The electron concentration and charge density difference implies the electron (holes) transition from SnSe to monolayer ZnSe. By increasing the layer of SnSe films, the quantum effects are weakened leading to the band gap reduced, and eventually show metal properties. The optical properties also have obvious change, the excellent absorption ability of ZnSe/SnSe heterostructures mainly near the infrared spectroscopy. These works suggest that ZnSe/SnSe heterostructure has significant potential for future optoelectronic applications.
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Compostos de Selênio , Compostos de Zinco , Compostos de Selênio/química , Compostos de Zinco/química , SemicondutoresRESUMO
OBJECTIVE: To analyze the prognostic nutritional index (PNI), controlling nutritional status (CONUT) and fibrinogen/albumin ratio (FAR) levels in elderly patients with multiple myeloma (MM) and their prognostic impact. METHODS: The clinical data of 74 elderly MM patients diagnosed in Gansu Provincial Hospital from January 2020 to July 2022 were retrospectively analyzed. The optimal cut-off values for PNI, CONUT score and FAR were obtained by receiver operating characteristic (ROC) curve, which were used for grouping patients. The correlation of above three indexes with clinical parameters such as sex, serum calcium (Ca), ß2-microglobulin (ß2-MG), serum creatinine (Cr) in elderly MM patients were analyzed. The survival rates of patients with different levels of each index were compared. Univariate and multivariate analysis of the impact of clinical indicators on the prognosis of patients were performed. RESULTS: The optimal cut-off values for PNI, CONUT score and FAR were 39.775, 3.5 and 0.175, respectively, according to which the patients were divided into high and low group. Statistical analysis showed that there were significant differences in albumin level among different groups (all P < 0.05). In addition, there was a significant difference in hemoglobin between high-PNI group and low-PNI group (P < 0.05), while in sex distribution between high-FAR and low-FAR group (P < 0.05). The survival rate of elderly MM patients with increased PNI, decreased CONUT score and FAR was higher (all P < 0.05). Univariate and multivariate analysis showed that ß2-MG, Cr, PNI, CONUT score and FAR were independent prognostic factors for elderly MM patients. CONCLUSION: PNI, CONUT score and FAR are related to some clinical indicators of elderly MM patients, and have an impact on the prognosis.
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Mieloma Múltiplo , Avaliação Nutricional , Estado Nutricional , Albumina Sérica , Humanos , Mieloma Múltiplo/sangue , Prognóstico , Idoso , Estudos Retrospectivos , Masculino , Albumina Sérica/análise , Feminino , Taxa de Sobrevida , Fibrinogênio/análise , Microglobulina beta-2/sangue , Creatinina/sangueRESUMO
OBJECTIVE: To analyze the clinical characteristics and occurrence of thrombotic/bleeding events of patients with myeloproliferative neoplasm (MPN), and explore the main influencing factors, and create a risk prediction. METHODS: The clinical data of 126 MPN patients with BCR-ABL fusion gene negative in the Department of Hematology of Gansu Provincial Hospital from January 2016 to September 2021 were collected, and their clinical characteristics, occurrence of thrombotic/bleeding events and main influencing factors were analyzed and summarized retrospectively. Then, a risk prediction model for thrombotic/bleeding events in MPN patients was constructed. RESULTS: Among 126 MPN patients, 50 patients (39.7%) had experienced thrombotic/bleeding events, including 44 patients (34.9%) with thrombotic events and 6 patients (4.8%) with bleeding events. Among thrombotic diseases, cerebral thrombosis was the most common (23/44, 52.3%), followed by 9 cases of limb artery thrombosis mainly characterized by finger and toe tip artery ischemia, occlusion and gangrene (9/44, 20.5%). Bleeding events included intracerebral hemorrhage and gastrointestinal hemorrhage. Univariate analysis showed that hypertension, hyperhomocysteinemia, white blood cell (WBC) ≥10×109/L, hematocrit (HCT) ≥49%, platelet (PLT) ≥600×109/L and JAK2V617F gene mutation were risk factors for thrombotic/bleeding events in MPN patients, while CALR gene mutation was a protective factor. Multivariate analysis showed that hypertension and PLT≥600×109/L were independent risk factors for thrombotic/bleeding events in MPN patients. The goodness of fit of the constructed risk prediction model was 0.872, and the area under the ROC curve was 0.838. The model was validated with clinical data, the sensitivity, specificity and accuracy was 78.85%, 87.83% and 84.13%, respectively . CONCLUSION: The risk of thrombotic/bleeding events in MPN patients with high WBC count, hypertension and hyperhomocysteinemia is higher. Controlling hypertension and hyperhomocysteinemia and reducing WBC and PLT counts are helpful to prevent thrombotic/bleeding events and improve the life quality of patients.
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Transtornos Mieloproliferativos , Trombose , Humanos , Fatores de Risco , Estudos Retrospectivos , Trombose/etiologia , Transtornos Mieloproliferativos/complicações , Hemorragia/etiologia , Hipertensão/complicações , Hiper-Homocisteinemia/complicações , Janus Quinase 2/genética , Contagem de Leucócitos , Feminino , Masculino , Calreticulina/genética , Contagem de PlaquetasRESUMO
OBJECTIVE: To analyze the clinical characteristics and prognosis of patients with CD5+ diffuse large B-cell lymphoma (DLBCL). METHODS: The clinical data of 161 newly treated DLBCL patients in Gansu Provincial Hospital from January 2013 to January 2020 were retrospectively analyzed. According to CD5 expression, the patients were divided into CD5+ group and CD5- group. The clinical characteristics and prognosis of the two groups were statistically analyzed. RESULTS: The median age of patients in CD5+ group was 62 years, which was higher than 56 years in CD5- group (P =0.048). The proportion of women in CD5+ group was 62.96%, which was significantly higher than 41.79% in CD5- group (P =0.043). The proportion of patients with IPI score > 2 in CD5+ group was 62.96%, which was higher than 40.30% in CD5- group (P =0.031). Survival analysis showed that the median overall survival and progression-free survival time of patients in CD5+ group were 27(3-77) and 31(3-76) months, respectively, which were both shorter than 30(5-84) and 32.5(4-83) months in CD5- group (P =0.047, P =0.026). Univariate analysis showed that advanced age, positive CD5 expression, triple or double hit at initial diagnosis, high IPI score and no use of rituximab during chemotherapy were risk factors for the prognosis of DLBCL patients. Further Cox multivariate regression analysis showed that these factors were also independent risk factors except for advanced age. CONCLUSION: CD5+ DLBCL patients have a worse prognosis than CD5- DLBCL patients. Such patients are more common in females, with advanced age and high IPI score, which is a special subtype of DLBCL.
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Antígenos CD5 , Linfoma Difuso de Grandes Células B , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Antígenos CD5/metabolismo , Linfoma Difuso de Grandes Células B/diagnóstico , Prognóstico , Estudos Retrospectivos , Análise de SobrevidaRESUMO
The electronic structures and absorption properties of Cs2BX6 halide compounds are investigated with first principle calculation and exchange correlation functional of GGA-PBE. Pressure and halogen ion doping are employed to regulate band gap. All materials suffer transition from indirect to direct band gap semiconductors but with different phase transition pressure. Structural and band structure calculating results show that the value of phase transition pressure is mainly determined by the volume of octahedron. When the volume of vacancy octahedron is much less than B-ion octahedron, the lowest band point of B-d orbitals transforms to Γ point, then the indirect semiconductors transform into direct band gap semiconductors. Calculating results of optical absorption implied that the systems have obvious blue shift, which result in the optical properties reduced. Based on suitable band gap and higher absorption coefficient, Cs2ZrI4Br2 can be an ideal candidate for perovskites solar cells.
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Compostos de Cálcio , Eletrônica , Raios gama , HalogêniosRESUMO
BACKGROUND: Intracerebral hemorrhage (ICH) is a stroke with a high morbidity and mortality rate. Deferoxamine (DFX) is thought to be effective in treating Intracerebral Hemorrhage. In our study, we performed a meta-analysis to evaluate the treatment effects of DFX. METHODS: We systematically searched PubMed, Embase, Web of Science, the Cochrane Central Register of Controlled Trials, and Chinese Biomedical Literature Database in Jan 2022 for studies on DFX for ICH patients. Outcome measures included relative hematoma volume, relative edema volume, good neurological functional outcome and adverse events. Odds risk (OR) and weighted mean difference (WMD) were used to evaluate clinical outcomes. RESULTS: After searching 636 articles, 4 RCTs, 2 NRCTs, and 1cohort study were included. We found that DFX was effective in hematoma absorption on day 7 after onset, but the difference was not significant on day 14. DFX could suppress edema expansion on days 3, 7, and 14 after onset. DFX did not contribute to better outcomes after 3 and 6 months when used the modified Rankin Scale and the Glasgow Outcome Scale to evaluate neurological prognosis. The pooled results showed no statistically significant difference in Serious adverse events between the experimental and control groups. CONCLUSIONS: DFX could limit edema expansion on days 3, 7, and 14 after commencement and facilitate hematoma absorption at week 1 without significantly increasing the risk of adverse events, but it did not improve neurological prognosis.
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Desferroxamina , Acidente Vascular Cerebral , Humanos , Desferroxamina/efeitos adversos , Sideróforos/farmacologia , Sideróforos/uso terapêutico , Hemorragia Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/tratamento farmacológico , Hematoma/tratamento farmacológicoRESUMO
Long-term continuous cropping of facility soils could influence soil properties; however, the differences in soil properties among different continuous cropping years are still not well understood. The objective of this study was to explore the effects of continuous cropping years of tomato on the physical and chemical properties and biological characteristics of facility soil. Conventional analysis, high-throughput sequencing, and other methods were used to examine the soil physicochemical properties, soil microbial community diversity, and enzyme activities in facility soil after continuous tomato cropping for 1-3 years, 5-7 years, and more than 10 years. As the continuous tomato cropping years increased, soil bulk density and pH decreased; soil maximal water holding capacity increased; and organic matter, total nitrogen, and total phosphorus accumulated. As continuous cropping years increased, the total salt and EC value decreased with continuous cropping for 5-7 years and increased from 5-7 years to more than 10 years continuous cropping and showed a trend of secondary soil salinization. There was a significant increase in alkaline phosphatase for 1-3 years to 5-7 years continuous tomato cropping. There were significant differences in fungal community abundance among different cropping years. The Simpson index and Shannon index of fungi showed a trend of increasing first and then decreasing with the extension of continuous cropping years and reached the maximum value at 5 years of continuous cropping. The Chao1 index decreased continuously following the cropping years. As continuous cropping years increased, Streptomyces became the dominant bacteria, and Aspergillus and Pseudaleuria became the dominant fungi. The key factors affected by continuous cropping years were available potassium and available nitrogen based on the redundancy analysis. The results of this study lay the foundation for future research on the influence of continuous cropping years on the health of facility soil.
Assuntos
Microbiota , Solanum lycopersicum , Solo/química , Microbiologia do Solo , Rizosfera , Fungos , NitrogênioRESUMO
The objective of this study was to explore the microbial diversity and community composition under saline soil and to screen the salt-tolerant microbial flora from salinization habitats. The soil from three different habitats(primary salinization, secondary salinization, and healthy soil) in Hebei Province were sampled. The convention method and high-throughput sequencing technology were used to examine the physicochemical properties and microorganism diversity. The soil chemical properties of the three habitats were significantly different. Compared with those of field soil, the soil OM, AP, AK, TS, and EC values of greenhouse soil and TS and EC values of coastal saline soil were significantly higher. However, other chemical indexes of coastal saline soil were significantly lower. The diversity index and abundance of soil bacteria in greenhouse soil were the highest, followed by those in field soil and coastal saline soil as the lowest. The diversity index and abundance of fungi in two saline habitats were significantly lower than that in field soil. The community structure of saline soil was analyzed at the phylum and genus levels. Chloroflexi and its genera and Ascomycota and its genera, such as Trichocladium and Fusarium, were the dominant microbial groups in saline soil. EC and TS were the main factors affecting microbial diversity and community composition. EC and TS were positively correlated with unclassified_A4b, unclassified_Chloroflexi, unclassified_α-Proteobacteria, Trichocladium, unclassified_Chaetomiaceae, Crassicarpon, Cephaliophora, and Sodiomyces. The results of this study lay the foundation for future research on screening microbial resources needed for saline soil remediation.
Assuntos
Fusarium , Solo , Solo/química , Microbiologia do Solo , Bactérias , FungosRESUMO
OBJECTIVE: To analyze the clinical features and prognosis of patients with Castleman's disease (CD) and improve the diagnosis and treatment of CD. METHODS: Clinical data of patients diagnosed with CD by pathological biopsy in Gansu Provincial Hospital from January 2009 to November 2020 were retrospectively analyzed. According to clinical classification, the patients were divided into two groups: UCD (unicentric CD) group (n=20) and MCD (multicentric CD) group (n=9). The clinical manifestations, laboratory examination, treatment regimens, pathological examination and follow-up data were statistically analyzed. RESULTS: There were no significant differences in average age and gender ratio between UCD group and MCD group. In UCD patients, 80.0% were hyaline vascular type, and 20.0% were plasma cell type. In MCD patients, 33.3% were hyaline vascular type, 55.6% were plasma cell type, and 11.1% were mixed type. There was significant difference in pathological classification between the two groups (P=0.039). The UCD patients usually presented asymptomatic single lymph node enlargement with mild clinical symptoms, while the MCD patients were characterized by multiple superficial and deep lymph node enlargement throughout the body. The incidences of asthenia, splenomegaly, serous effusion in MCD group were higher than those in UCD group (P<0.05). Meanwhile, the incidences of anemia, hypoproteinemia, increased ESR, elevated serum globulin and elevated ß2-microglobulin were significantly higher than those in UCD group too (P<0.05). There was no significant difference in the incidences of abnormal WBC, PLT and elevated LDH between the two groups (P>0.05). Among 20 patients with UCD, 13 cases reached complete remission (CR), 1 case achieved partial remission (PR). Among 9 patients with MCD, 3 cases received CR and 4 cases received PR. CONCLUSION: Patients with CD requires pathological examination for diagnosis. Patients with UCD show mild clinical symptoms, good surgical treatment effect and good prognosis. Patients with MCD have diversified clinical manifestations and relatively poor prognosis, and these patients require comprehensive treatment.