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1.
Plant Divers ; 44(2): 135-140, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35505988

RESUMO

Despite that several studies have shown that data derived from species lists generated from distribution occurrence records in the Global Biodiversity Information Facility (GBIF) are not appropriate for those ecological and biogeographic studies that require high sampling completeness, because species lists derived from GBIF are generally very incomplete, Suissa et al. (2021) generated fern species lists based on data with GBIF for 100 km × 100 km grid cells across the world, and used the data to determine fern diversity hotspots and species richness-climate relationships. We conduct an evaluation on the completeness of fern species lists derived from GBIF at the grid-cell scale and at a larger spatial scale, and determine whether fern data derived from GBIF are appropriate for studies on the relations of species composition and richness with climatic variables. We show that species sampling completeness of GBIF is low (<40%) for most of the grid cells examined, and such low sampling completeness can substantially bias the investigation of geographic and ecological patterns of species diversity and the identification of diversity hotspots. We conclude that fern species lists derived from GBIF are generally very incomplete across a wide range of spatial scales, and are not appropriate for studies that require data derived from species lists in high completeness. We present a map showing global patterns of fern species diversity based on complete or nearly complete regional fern species lists.

2.
Front Public Health ; 10: 739880, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35509513

RESUMO

Objective: The aim was to investigate the distribution and correlation of Ca, Mg, Zn, Cu, Fe, Pb, and Cd in the blood of children aged 0-14 years in Hunan, China, which may serve to provide a basis for clinical guidance on child health. Study Design: A retrospective analysis was carried out. Concentrations of all elements were determined by atomic absorption spectrophotometry. Distributions were analyzed and compared among different age, sex, and year groups by the Kruskal-Wallis test, the chi-square test, and the Fisher's exact test. Spearman's rank correlation coefficient was used to evaluate the association between every pair of elements. Results: A total of 46,951 children were involved in this study from 2013 to 2019. The median blood levels of elements were 13.51 µmol/L (Cu), 58.69 µmol/L (Zn), 1.70 mmol/L (Ca), 1.40 mmol/L (Mg), 7.46 mmol/L (Fe), 35.00 µg/L (Pb), and 1.00 µg/L (Cd). Girls had a higher level of Ca and lower levels of Pb and Cd than boys. Cu and Ca showed an upward trend, and Mg and Pb showed a downward trend by year. Zn and Fe increased and Ca decreased significantly with age. The deficiency rates of Fe and Zn decreased significantly by year, while Ca and Cu increased significantly by year. Cd exposure in this area was relatively low. Conclusion: Most children had normal levels of the essential elements Ca, Cu, and Mg and the toxic elements Pb and Cd. Severe deficiencies in Zn and Fe were observed in the relatively younger children but improved with age. Persistent efforts in reducing Pb exposure might still be needed.


Assuntos
Cobre , Zinco , Adolescente , Cádmio/análise , Criança , Pré-Escolar , China/epidemiologia , Cobre/análise , Feminino , Humanos , Lactente , Recém-Nascido , Chumbo/análise , Masculino , Estudos Retrospectivos , Zinco/análise
3.
Zhongguo Zhong Yao Za Zhi ; 47(7): 1831-1846, 2022 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-35534253

RESUMO

In recent years, the MYB-related gene family has been found pivotal in plant growth and development. MYB-related gene family in Angelica dahurica var. formosana was systematically investigated based on "Chuanzhi No. 2" through transcriptome database search and bioinformatics and the temporal and spatial expression patterns were analyzed through real-time fluorescence-based quantitative polymerase chain reaction(PCR). The results showed that 122 MYB-related proteins family were identified, mainly including the unstable hydrophilic proteins with good thermal stability. Most of the proteins were located in nuclei. The majority of the proteins had the structures of random coil and α-helix. Five MYB-related proteins family of A. dahurica var. formosana had membrane-binding domains. The conserved domain analysis of MYB-related proteins family of A. dahurica var. formosana showed that the MYB domains of genes in five subgroups, similar to 2 R-, 3 R-, and 4 R-MYB proteins, contained three evenly distributed Trp(W) residues in the MYB repeat sequence. The phylogenetic analysis of MYB-related proteins family in A. dahurica var. formosana and Arabidopsis thaliana showed that the MYB-related members were unevenly distributed in five subgroups, and A. thaliana and A. dahurica var. formosana had almost the same number of genes in the CCA1-like subgroup. There were differences in the number, type, and distribution of motifs contained in 122 encoded proteins. Transcription factors with similar branches had similar domains and motifs. The expression pattern analysis showed that the transcription factors AdMYB53, AdMYB83, and AdMYB89 responded to hormones to varying degrees, and they were highly expressed in leaves and responded quickly in roots. This study lays a foundation for further investigating the function of MYB-related transcription factors of A. dahurica var. formosana and solving the corresponding biological problems such as bolting early.


Assuntos
Angelica , Gastrópodes , Angelica/química , Animais , Biologia Computacional , Filogenia , Folhas de Planta , Proteínas de Plantas/genética , Fatores de Transcrição/genética
4.
Clin Cancer Res ; 28(9): 1938-1947, 2022 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-35491652

RESUMO

PURPOSE: Intraductal papillary mucinous neoplasms (IPMN) are bona fide precursors to pancreatic ductal adenocarcinoma (PDAC). While genomic alterations during multistep IPMN progression have been well cataloged, the accompanying changes within the tumor immune microenvironment (TIME) have not been comprehensively studied. Herein, we investigated TIME-related alterations during IPMN progression, using multiplex immunofluorescence (mIF) coupled with high-resolution image analyses. EXPERIMENTAL DESIGN: Two sets of formalin-fixed, paraffin-embedded tissue samples from surgically resected IPMNs were analyzed. The training set of 30 samples consisted of 11 low-grade IPMN (LG-IPMN), 17 high-grade IPMN (HG-IPMN), and 2 IPMN with PDAC, while a validation set of 93 samples comprised of 55 LG-IPMN and 38 HG-IPMN. The training set was analyzed with two panels of immuno-oncology-related biomarkers, while the validation set was analyzed with a subset of markers found significantly altered in the training set. RESULTS: Cell types indicative of enhanced immune surveillance, including cytotoxic and memory T cells, and antigen-experienced T cells and B cells, were all found at higher densities within isolated LG-IPMNs compared with HG-IPMNs. Notably, the TIME of LG-IPMNs that had progressed at the time of surgical resection (progressor LGD) resembled that of the synchronous HG-IPMNs, underscoring that attenuated immune surveillance occurs even in LG-IPMNs destined for progression. CONCLUSIONS: Our findings provide a basis for interception of cystic neoplasia to PDAC, through maintenance of sustained immune surveillance using vaccines and other prevention approaches.


Assuntos
Adenocarcinoma Mucinoso , Carcinoma Ductal Pancreático , Neoplasias Intraductais Pancreáticas , Neoplasias Pancreáticas , Adenocarcinoma Mucinoso/patologia , Carcinoma Ductal Pancreático/patologia , Humanos , Neoplasias Pancreáticas/patologia , Microambiente Tumoral
5.
J Oncol ; 2022: 7315879, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35401744

RESUMO

Objective: To explore the clinical value of specific miRNA in patients with acute promyelocytic leukemia. Methods: 129 patients with acute promyelocytic leukemia diagnosed in our hospital from January 2015 to January 2020 were selected as the observation group. At the same time, 74 patients with nonacute promyelocytic leukemia who underwent bone marrow aspiration were included as the control group. The expression levels of miR-126-5p and miR-13, different characteristic parameters, and prognosis were compared between the two groups, and the clinical significance of miR-126-5p and miR-13 in acute promyelocytic leukemia was analyzed. Results: The expression of miR-126-5p (12.31 ± 2.25 versus 17.30 ± 3.28) and miR-13 (16.05 ± 3.47 versus 21.66 ± 2.18) in the observation group was significantly lower than that in the control group (P < 0.05). The expression level of miR-126-5p was significantly correlated with lactate dehydrogenase level, HGB level, NPM1 mutant type, and complete remission (P < 0.05). The expression level of miR-13 was significantly correlated with HGB level, NPM1 mutant type, and complete remission (P < 0.05). Both expression levels of miR-126-5p and miR-13 were not correlated with sex, age, WBC, PLT, proportion of bone marrow primordial cells, hepatomegaly, splenomegaly, lymph node enlargement, and FLT3-ITD (P > 0.05). Cox multivariate regression analysis showed that peripheral blood WBC, bone marrow blast cell count, and miR-126-5p and miR-13 were prognostic factors in patients with acute promyelocytic leukemia (P < 0.05). The sensitivity, specificity, accuracy, and AUC of serum miR-126-5p prediction were 75.83%, 84.56%, 82.17%, and 0.729, respectively. The sensitivity, specificity, accuracy, and AUC of serum miR-13 prediction were 78.64%, 88.49%, 86.20% and 0.882, respectively. Conclusion: Serum miR-126-5p and miR-13 are closely related to the prognosis of patients with acute promyelocytic leukemia. Serum miR-126-5p and miR-13 can be used as reliable indexes to predict the prognosis of patients.

6.
Cancer Biol Ther ; 23(1): 328-335, 2022 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-35435150

RESUMO

Curcumin, the primary bioactive component isolated from turmeric, has been found to possess a variety of biological functions, including anti-leukemia activity. However, the effect of curcumin in different leukemia cells vary. In this study, we demonstrated that curcumin induced the expression of AIM2, IFI16, and NLRC4 inflammasomes in leukemia cells U937 by increasing the expression levels of ISG3 transcription factor complex, which activated caspase 1, promoted cleavage of GSDMD, and induced pyroptosis. We also found that pyroptosis executor GSDMD was not expressed in two curcumin-insensitive cells HL60 and K562 cells. In addition, exogenous overexpression of GSDMD by lentiviral transduction in K562 cells increased the anti-cancer activity of curcumin, and inhibiting the expression of GSDMD by shRNA enhanced U937 cells to resist curcumin. The results showed that inducing pyroptosis is a novel mechanism underlying the anti-leukemia effects of curcumin.


Assuntos
Curcumina , Leucemia Mieloide Aguda , Proteínas Adaptadoras de Sinalização CARD/metabolismo , Proteínas de Ligação ao Cálcio , Curcumina/farmacologia , Proteínas de Ligação a DNA/metabolismo , Humanos , Inflamassomos/metabolismo , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Fosfoproteínas/metabolismo , Piroptose/genética , Células U937
7.
Ann Transl Med ; 10(6): 380, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35433988

RESUMO

Background: The immune microenvironment of deficient mismatch repair or microsatellite instability-high (dMMR/MSI-H) colorectal cancer exhibits better immune activity, and patients with dMMR/MSI-H colorectal cancer benefit from immunotherapy with programmed death-1 (PD-1)/PD-1 ligand (PD-L1) inhibitors and cytotoxic T-lymphocyte associated protein 4 (CTLA-4) inhibitors as a first-line treatment. However, for microsatellite-stable (MSS) colorectal cancer, which accounts for the majority of the cases of colorectal cancer, immunotherapy has yielded little success, especially in cases of patients with advanced colorectal cancer in whom multiple lines of chemotherapy have failed. Hence, safe and effective targeted treatment strategies are urgently needed to achieve greater survival benefits. Case Description: We report a case in which next-generation sequencing (NGS) and immunohistochemistry (IHC) showed that that the patient's molecular characteristics were as follows: MSS, low expression of PD-L1, and high tumor mutation burden (TMB-H). Due to the failure of multiple lines of chemotherapy and severe chemotherapeutic adverse effects, a combined targeted immunotherapy regimen was utilized. After 6 months of treatment, imaging suggested near-complete clinical remission, and at the 18-month follow-up, the patient had a good quality of life and imaging showed no tumor recurrence. Conclusions: This case suggests that a good response to a combined targeted immunotherapy regimen can be achieved in patients with MSS metastatic colorectal cancer, in addition, it also suggests that TMB-H is a predictive biomarker for clinical benefit from immunotherapy in MSS metastatic colorectal cancer.

8.
Front Public Health ; 10: 861157, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35419328

RESUMO

A comprehensive understanding of the impact of economic growth and environmental pollution on public health is crucial to the sustainable development of public health. In this paper, an individual fixed effect model is used to analyze the impact of environmental pollution and economic growth on public health, based on the panel data of 30 provinces in China from 2007 to 2018. The research finds that: First, the health status of China's four regions is not only affected by economic growth and environmental pollution, but also affected by the per capita disposable income and urbanization rate. Second, there is a long-term balanced relationship between China's economic growth, environmental pollution and public health. Third, environmental pollution harms children's health and significantly increases the perinatal mortality, while economic growth helps to reduce the perinatal mortality. Fourth, environmental pollution plays a regulatory role between economic growth and public health. Fifth, there are significant regional differences in the impact of environmental pollution and economic growth on public health. Among them, the degree of harm caused by sulfur dioxide emissions on mortality in northeastern China is significantly higher than that of the eastern China, eastern China is higher than that of the western China, and western China is higher than that of the central China. Finally, in order to reduce the adverse consequences of environmental pollution on public health in the process of economic development, this study puts forward relevant policy suggestions.


Assuntos
Desenvolvimento Econômico , Saúde Pública , Criança , China/epidemiologia , Poluição Ambiental/análise , Poluição Ambiental/estatística & dados numéricos , Humanos
9.
Front Microbiol ; 13: 876043, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35401492

RESUMO

Emerging evidence has been reported to support the involvement of the gut microbiota in the host's blood lipid and hyperlipidemia (HLP). However, there remains unexplained variation in the host's blood lipid phenotype. Herein a nonhuman primate HLP model was established in cynomolgus monkeys fed a high-fat diet (HFD) for 19 months. At month 19%, 60% (3/5) of the HFD monkeys developed HLP, but surprisingly 40% of them (2/5) exhibited strong tolerance to the HFD (HFD-T) with their blood lipid profiles returning to normal levels. Metagenomic analysis was used to investigate the compositional changes in the gut microbiota in these monkeys. Furthermore, the relative abundance of Megasphaera remarkably increased and became the dominant gut microbe in HFD-T monkeys. A validation experiment showed that transplantation of fecal microbiota from HFD-T monkeys reduced the blood lipid levels and hepatic steatosis in HLP rats. Furthermore, the relative abundance of Megasphaera significantly increased in rats receiving transplantation, confirming the successful colonization of the microbe in the host and its correlation with the change of the host's blood lipid profiles. Our results thus suggested a potentially pivotal lipid-lowering role of Megasphaera in the gut microbiota, which could contribute to the variation in the host's blood lipid phenotype.

10.
Radiology ; : 211367, 2022 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-35412367

RESUMO

Background Deep learning (DL) algorithms could improve the classification of ovarian tumors assessed with multimodal US. Purpose To develop DL algorithms for the automated classification of benign versus malignant ovarian tumors assessed with US and to compare algorithm performance to Ovarian-Adnexal Reporting and Data System (O-RADS) and subjective expert assessment for malignancy. Materials and Methods This retrospective study included consecutive women with ovarian tumors undergoing gray scale and color Doppler US from January 2019 to November 2019. Histopathologic analysis was the reference standard. The data set was divided into training (70%), validation (10%), and test (20%) sets. Algorithms modified from residual network (ResNet) with two fusion strategies (feature fusion [hereafter, DLfeature] or decision fusion [hereafter, DLdecision]) were developed. DL prediction of malignancy was compared with O-RADS risk categorization and expert assessment by area under the receiver operating characteristic curve (AUC) analysis in the test set. Results A total of 422 women (mean age, 46.4 years ± 14.8 [SD]) with 304 benign and 118 malignant tumors were included; there were 337 women in the training and validation data set and 85 women in the test data set. DLfeature had an AUC of 0.93 (95% CI: 0.85, 0.97) for classifying malignant from benign ovarian tumors, comparable with O-RADS (AUC, 0.92; 95% CI: 0.85, 0.97; P = .88) and expert assessment (AUC, 0.97; 95% CI: 0.91, 0.99; P = .07), and similar to DLdecision (AUC, 0.90; 95% CI: 0.82, 0.96; P = .29). DLdecision, DLfeature, O-RADS, and expert assessment achieved sensitivities of 92%, 92%, 92%, and 96%, respectively, and specificities of 80%, 85%, 89%, and 87%, respectively, for malignancy. Conclusion Deep learning algorithms developed by using multimodal US images may distinguish malignant from benign ovarian tumors with diagnostic performance comparable to expert subjective and Ovarian-Adnexal Reporting and Data System assessment. © RSNA, 2022 Online supplemental material is available for this article.

11.
J Nurs Res ; 2022 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-35446276

RESUMO

BACKGROUND: Patients in disaster areas require the most urgent assistance. In recent large-scale natural disasters, intensive care nurses have served as an important reserve component of disaster response teams. In disaster nursing, ability and attitude directly affect the quality and effectiveness of disaster rescues. However, few studies have examined the disaster nursing competency of intensive care nurses in China. PURPOSE: This study was designed to describe the current status of disaster nursing competency among intensive care nurses, analyze the related factors affecting the disaster response effectiveness, and evaluate the values of disaster nursing continuing education and training in cultivating professional personnel with disaster emergency rescue competence. METHODS: This cross-sectional study was conducted at six tertiary general government hospitals in Jinan, Shandong Province, China. A convenience sampling method was adopted, and the Wenjuanxing website was used to compile the network questionnaire, which participants completed via a WeChat group. Descriptive, correlation, and regression analyses were performed using SPSS software. RESULTS: The participants in this study included 285 registered intensive care nurses employed at six hospitals in Jinan. Most were female (77.9%), and the mean age was 29.9 years. The mean total disaster nursing ability score was 122.98 (SD = 31.70), and the average scores for each item ranged from 2.78 to 3.70. The incident command system item earned the highest mean score (3.70, SD = 1.22), followed by triage (3.24, SD = 0.93). The biological preparedness item earned the lowest mean score (2.78, SD = 1.04). Being male, being < 30 years old, having an understanding of disaster nursing, having previously participated in disaster emergency simulation drills or training, and having a higher self-evaluation of rescue competence were all associated with higher disaster-nursing knowledge scores. Multiple linear regression analyses indicated that understanding of disaster nursing and experience participating in disaster emergency rescue drills or training had the most significant influence on the disaster nursing emergency knowledge score, followed by positive self-evaluation of disaster nursing ability and demand for training. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: The findings of this study indicate that the participants had a moderate disaster-nursing competency and that this competency may be improved through disaster-related continuing education and training. The cognitive attitude of disaster nursing was found to correlate positively with self-efficacy. Simulated emergency drills may effectively improve the disaster nursing competency of critical care nurses. The findings emphasize that experiences other than direct clinical practice such as specialized simulated emergency drills and training as well as willingness for such training are stronger factors for identifying and developing overall disaster nursing competency.

12.
J Hazard Mater ; 434: 128859, 2022 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-35405608

RESUMO

The efficient and safe capture of volatile radioiodine is of great significance in the reprocessing of spent fuel. Herein, the millimeter-scale pitch-based hyper-cross-linked porous polymers@polyethersulfone (PHCP@PES) composite beads were firstly synthesized for the removal of volatile iodine and methyl iodide. PHCP@PES beads exhibit high iodine vapor and methyl iodide uptake capacities of 770.0 mg/g and 186.5 mg/g, respectively. More impressively, the uptake capacities of PHCP@PES (744.5 mg/g for iodine vapor and 180 mg/g for methyl iodide) remained almost unchanged after treatment with 3 mol/L of nitric acid. The rich interconnected pore structure of PHCP@PES promotes the rapid physical capture of iodine and methyl iodide. Intrinsic features such as low-cost preparation, good mechanical properties as well as thermal, acid stability and excellent performance in iodine capture indicate that PHCP@PES can be used as a potential candidate for the removal of radioactive iodine in the exhaust gas stream of post-treatment plants.

13.
Food Sci Nutr ; 10(4): 1093-1102, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35432971

RESUMO

This study aimed to evaluate the immunomodulatory effect of the polysaccharide from Sinonovacula constricta (SCP-1-1) in RAW264.7 cells. SCP-1-1 with a molecular weight of 440.0 kDa consisted of glucose and mannose. The immunomodulatory assay results showed that SCP-1-1 could significantly enhance phagocytic ability, NO production, and some cytokines (TNF-α, IL-6, and IL-1ß) secretion of RAW264.7 cell in a dose-dependent manner. Western blot analysis results demonstrated that SCP-1-1 could regulate the expression levels of the key proteins in the signaling pathways of RAW264.7 cell and might associated with NF-κß and PI3K signaling pathway. These findings could contribute to elucidate the immunomodulatory activities of the polysaccharide from Sinonovacula constricta.

14.
Expert Rev Respir Med ; : 1-12, 2022 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-35271782

RESUMO

INTRODUCTION: Risk factors of chronic cough in China have not been systematically analyzed and we hypothesized that risk factors of chronic cough might have distinct characteristics in China. Hence, we performed this meta-analysis focusing on the potential risk factors of chronic cough in China. AREAS COVERED: This systematic review was performed to explore the risk factors of chronic cough in accordance with the PRISMA checklist. Seven databases were searched for published articles using predefined inclusion criteria. A total of 33 eligible articles were identified and included in this systematic review, and 28 studies were included in the meta-analysis. EXPERT COMMENTARY: The study indicated that allergy, nasal/sinusitis diseases, family history of allergy, family history of chronic respiratory diseases, exposure to pollutants, passive smoking, and exposure to pets were risk factors for chronic cough in China. Although several potential risk factors (e.g.: sex and BMI) were not explore for the limited information in the included articles, this paper provides useful epidemiological information for managing chronic cough not only in China but around the world.

15.
Nucleic Acids Res ; 50(6): 3413-3431, 2022 04 08.
Artigo em Inglês | MEDLINE | ID: mdl-35288749

RESUMO

Heterochromatin-associated gene silencing controls multiple physiological processes in malaria parasites, however, little is known concerning the regulatory network and cis-acting sequences involved in the organization of heterochromatin and how they modulate heterochromatic gene expression. Based on systematic profiling of genome-wide occupancy of eighteen Apicomplexan AP2 transcription factors by ChIP-seq analysis, we identify and characterize eight heterochromatin-associated factors (PfAP2-HFs), which exhibit preferential enrichment within heterochromatic regions but with differential coverage profiles. Although these ApiAP2s target euchromatic gene loci via specific DNA motifs, they are likely integral components of heterochromatin independent of DNA motif recognition. Systematic knockout screenings of ApiAP2 factors coupled with RNA-seq transcriptomic profiling revealed three activators and three repressors of heterochromatic gene expression including four PfAP2-HFs. Notably, expression of virulence genes is either completely silenced or significantly reduced upon the depletion of PfAP2-HC. Integrated multi-omics analyses reveal autoregulation and feed-forward loops to be common features of the ApiAP2 regulatory network, in addition to the occurrence of dynamic interplay between local chromatin structure and ApiAP2s in transcriptional control. Collectively, this study provides a valuable resource describing the genome-wide landscape of the ApiAP2 family and insights into functional divergence and cooperation within this family during the blood-stage development of malaria parasites.


Assuntos
Malária , Plasmodium falciparum , Heterocromatina/genética , Heterocromatina/metabolismo , Humanos , Malária/parasitologia , Proteínas de Protozoários/genética , Proteínas de Protozoários/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
16.
J Immunother Cancer ; 10(3)2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35256517

RESUMO

BACKGROUND: The CD47-SIRPα pathway acts as an important myeloid cell immune checkpoint and targeting the CD47/SIRPα axis represents a promising strategy to promote antitumor immunity. Several CD47-targeting agents show encouraging early activity in clinical trials. However, due to ubiquitous expression of CD47, the antigen sink and hematologic toxicity, such as anemia and thrombocytopenia, are main problems for developing CD47-targeting therapies. Considering the limited expression of SIRPα, targeting SIRPα is an alternative approach to block the CD47-SIRPα pathway, which may result in differential efficacy and safety profiles. METHODS: SIRPα-targeting antibody BR105 was generated by hybridoma fusion and following humanization. BR105 was characterized for binding to human SIRPα alleles and blockade of the interaction with CD47. The functional activity was determined in in vitro phagocytosis assays by using human macrophages. The effect of BR105 on human T cell activation was studied using an OKT3-induced T-cell proliferation assay and an allogeneic mixed lymphocyte reaction. Human SIRPα-humanized immunodeficient mice were used in cancer models for evaluating the in vivo antitumor efficacy of BR105. Safety was addressed in a repeat-dose toxicity study in cynomolgus monkeys, and toxicokinetic analysis was further evaluated. RESULTS: BR105 shows broad binding activity across various SIRPα variants, and potently blocks the interaction of SIRPα and CD47. In vitro functional assays demonstrated that BR105 synergizes with therapeutic antibodies to promote phagocytosis of tumor cells. Moreover, the combination of BR105 and therapeutic antibody significantly inhibits tumor growth in a xenograft tumor model. Although BR105 may slightly bind to SIRPγ, it does not inhibit T cell activation, unlike other non-selective SIRPα-targeting antibody and CD47-targeting agents. Toxicity studies in non-human primates show that BR105 is well tolerated with no treatment-related adverse effects noted. CONCLUSIONS: The novel and differentiated SIRPα-targeting antibody, BR105, was discovered and displays promising antitumor efficacy in vitro and in vivo. BR105 has a favorable safety profile and shows no adverse effects on T cell functionality. These data support further clinical development of BR105, especially as a therapeutic agent to enhance efficacy when used in combination with tumor-targeting antibodies or antibodies that target other immune checkpoints.


Assuntos
Antígeno CD47 , Neoplasias , Animais , Anticorpos Antineoplásicos , Antígeno CD47/metabolismo , Humanos , Macrófagos , Camundongos , Neoplasias/terapia , Fagocitose
17.
Front Med (Lausanne) ; 9: 830754, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35355607

RESUMO

Background and Objective: Growing evidence added to the results from observational studies of lung cancer patients exhibiting eosinophilia. However, whether eosinophils contributed to tumor immune surveillance or neoplastic evolution was unknown. This study aimed to analyze the causal association between eosinophilia and lung cancer. Methods: The causal effect of eosinophil count on lung cancer from a genome-wide association study (GWAS) was investigated using the two-sample Mendelian randomization (MR) method. Secondary results according to different histological subtypes of lung cancer were also implemented. Meanwhile, we compared the measured levels of blood eosinophil counts among different subtypes of lung cancer from real-world data. Results: The median absolute eosinophilic count (unit: 109/L) [median (min, max): Lung adenocarcinoma 0.7 (0.5, 15); Squamous cell lung cancer 0.7 (0.5, 1.3); Small cell lung cancer 0.7 (0.6, 1.3); p = 0.96] and the median eosinophil to leukocyte ratio [median (min, max): Lung adenocarcinoma 8.7% (2.1, 42.2%); Squamous cell lung cancer 9.3% (4.1, 17.7%); Small cell lung cancer 8.9% (5.1, 24.1%); p = 0.91] were similar among different histological subtypes of lung cancer. MR methods indicated that eosinophilia may provide 28% higher risk for squamous cell lung cancer in East Asian [Weighted median method: odds ratio (OR) = 1.28, 95% CI: 1.04-1.57, p = 0.02]. Conclusion: Our study suggested that eosinophilia may be a potential causal risk factor in the progression of squamous cell lung cancer in East Asian.

18.
Artigo em Inglês | MEDLINE | ID: mdl-35270588

RESUMO

Analyzing the relationship between economic development and carbon emissions is conducive to better energy saving and emission reduction. This study is based on the panel data of China's carbon emissions, from 2009 to 2019, and quantitative analysis of the relationship between carbon emissions and economic development through the Tapio decoupling model and the Logarithmic Mean Divisia Index (LMDI) decomposition model. The results show that: First, carbon emission and economic development are increasing year by year, and the development trend of economic growth rate and carbon emission growth rate presents the characteristics of consistency and stage. Second, China's carbon emissions and economic development are basically in a weak decoupling state, and carbon emissions and economic development are positively correlated. Third, there are significant differences in decoupling indices among the four regions, mainly in that the central region is better than the eastern region, the eastern region is better than the northeast region, the northeast region is better than the western region, and the development of provinces in the region is unbalanced. Fourth, from the perspective of driving factors, the elasticity of population size and economic intensity can restrain the decoupling of carbon emissions, while the elasticity of energy intensity and carbon intensity have a positive effect. Finally, according to the results of empirical analysis, this paper focuses on promoting China's emission reduction and energy sustainable development from the aspects of developing low-carbon and zero carbon technology, supporting new energy industries and promoting the construction of a carbon emission trading market.


Assuntos
Carbono , Desenvolvimento Econômico , Carbono/análise , Dióxido de Carbono/análise , China , Indústrias
19.
Mitochondrial DNA B Resour ; 7(1): 303-305, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35128058

RESUMO

Rhaponticum uniflorum is commonly used as a source for traditional medicines with the main effect of clearing heat. Here, we sequenced the complete chloroplast (cp) genome of R. uniflorum to develop molecular markers for taxonomic classification and species determination of R. uniflorum. It was 152,760 bp in size and has a typical circular structure, including a pair of inverted repeats with 25,205 bp, a large single-copy region with 83,687 bp, and a small single copy region with 18,663 bp. The genome encodes 110 unique genes, including 80 protein-coding, four rRNA and 26 tRNA genes. Phylogenomic analysis shows that R. uniflorum is closely related to the Saussurea. The study is useful for phylogenetic and population genetic studies of Rhaponticum plants.

20.
J Chromatogr A ; 1667: 462904, 2022 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-35193067

RESUMO

Liquid chromatography/mass spectrometry (LC/MS) is extensively applied for the untargeted/targeted analyses of the herbal components, utilizing data-dependent acquisition (DDA) or data-independent acquisition (DIA) to record the fragmentation information useful for the structural elucidation. A new trend recently has emerged by integrating DDA and DIA to render the hybrid scan, which, unfortunately, has rarely been reported. Herein, by using the Vion™ ion-mobility quadrupole time-of-flight mass spectrometer, a hybrid scan strategy (HDMSE-HDDDA) was presented and validated by the untargeted characterization of the multicomponents from Carthamus tinctorius (safflower), in combination with reversed-phase ultra-high performance liquid chromatography (RP-UHPLC). Good chromatographic separation was achieved on an HSS T3 column within 26 min, while HDMSE-MS/MS was used to acquire the collision-induced dissociation MS2 data in the negative mode. Automatic workflows (e.g., data correction, precursors/product ions matching, and peak annotation) were well established on UNIFI™ (incorporating an in-house library recording 261 known compounds) to process the obtained MS2 data. Compared with single DDA or DIA, the hybrid approach of HDMSE-HDDDA better balanced between the coverage and reliability, led to high-definition MS spectra, offered useful collision cross section (CCS) information, and showed satisfactory identification performance comparable to MSE. A total of 141 components (involving 41 quinochalcones, 66 flavanols/flavones, 11 flavanones, 6 organic acids, 1 polyacetylene, and 16 others) were characterized from safflower. Moreover, CCS prediction could assist isomers characterization, to some extent. Conclusively, this hybrid scan approach enables a dimension-enhanced MS data acquisition strategy providing the complementary structural information, which more suits the chemical characterization of complex samples.


Assuntos
Carthamus tinctorius , Cromatografia Líquida de Alta Pressão/métodos , Íons , Reprodutibilidade dos Testes , Espectrometria de Massas em Tandem/métodos
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