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1.
J Environ Manage ; 300: 113736, 2021 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-34521000

RESUMO

Despite the various benefits of humus, the changes in its chemical characteristics during composting in response to biochar addition and varying bulking agents remain to be further explored. In this study, three treatments were conducted, in which swine manure, bulking agent, and biochar were mixed at ratios of 4:1:0, 8:1:0, and 8:1:1. Fourier transform infrared spectroscopy (FTIR), carbon nuclear magnetic resonance spectroscopy (13C-NMR), three-dimensional excitation-emission matrix fluorescence spectroscopy (3D-EEM), and near-edge X-ray absorption fine structure (NEXAFS) were employed to characterize the chemical and structural properties of humus from multiple perspectives. The 3D-EEM spectra in this study showed a larger increase in humic acids (HAs) content (56%) and HAs to fulvic acids ratio (128%) during composting, indicating stronger humification in biochar-amended treatment. FTIR, 13C-NMR, and NEXAFS all confirmed the essential properties of HA as the core agronomic functional substance with rich aromatic and carboxyl groups, and that its aromaticity increased gradually during composting. In addition, 13C-NMR demonstrated that biochar addition and a relatively higher bulking agent ratio aided an increase in the carboxyl C proportion in HA after composting. In particular, NEXAFS revealed that biochar addition promoted the diversification of C, N, and O species in HA, with the emergence of quinone C and O-alkyl C as the main representatives. This work suggests that biochar addition and a relatively high bulking agent ratio could enhance humification and improve the agronomic function of humus.

2.
Biochem Biophys Res Commun ; 577: 95-102, 2021 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-34509725

RESUMO

OBJECTIVE: Long non-coding RNAs (lncRNAs) are implicated in cancer-related cellular behaviors. Our research aimed to explore the biological functions of lncRNA AL592284.1 (AL592284.1) in cervical cancer (CC). METHODS: qRT-PCR was performed to examine AL592284.1 expressions in cell lines and tumor specimens. To study the roles of AL592284.1 on malignant behaviors in both in vitro and in vivo, Loss-of-function assays were carried out. Besides, bioinformatics prediction and dual-luciferase reporter assays were performed to reveal the interaction among AL592284.1 and its target genes. The functions of the AL592284.1/miR-30a-5p/Vimentin axis in CC cells was clarified by rescue assays. RESULTS: We observed that the levels of AL592284.1 in CC were distinctly increased. Functional assays revealed that knockdown of AL592284.1 suppressed the proliferation, migration, invasion and EMT progress of CC cells. Luciferase reporter assay confirmed that miR-30a-5p/Vimentin regulatory axis is the direct downstream of AL592284.1. Rescue experiments indicated that AL592284.1 induced overexpression of Vimentin via sponging miR-30a-5p, resulting in the promotion of CC progression. CONCLUSION: The present study proves that AL592284.1 plays an tumor-promotive role in CC via regulating the miR-30a-5p/Vimentin axis, and inhibition of AL592284.1 may pave the way for CC treatment.

3.
Org Biomol Chem ; 2021 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-34528986

RESUMO

2-Alkenyl-tetrahydropyrans belong to a rare class of natural products that exhibit broad antifungal activities. Their structural instability and rareness in nature have restrained their discovery and drug development. In this study, the heterologous expression of a single highly reducing polyketide synthase (HR-PKS, App1) from Trichoderma applanatum in Aspergillus nidulans leads to the formation of seven 2-alkenyl-tetrahydropyran derivatives including one known compound virensol C (1) and six new compounds (2-7). However, introducing App1 into Saccharomyces cerevisiae resulted in the identification of additional two 2-alkenyl-tetrahydropyrans lacking the hydroxyl or methoxyl group at the C-2 position (8 and 9). The structures of the isolated compounds were elucidated by extensive spectroscopic analysis using NMR and HR-ESI-MS.

4.
J Clin Anesth ; 75: 110498, 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34488061

RESUMO

STUDY OBJECTIVE: To determine the effect of dexmedetomidine on acute kidney injury (AKI) following endovascular aortic repair (EVAR) for Stanford type B aortic dissection (TBAD). DESIGN: Randomized, double-blind, placebo-controlled, pilot study. SETTING: University Hospital. PATIENTS: 102 TBAD patients undergoing EVAR procedures were enrolled. Patients with dissection involving aortic arch or renal artery were excluded. INTERVENTIONS: Patients were randomly assigned, in a 1:1 ratio, to a dexmedetomidine group (intravenous dexmedetomidine 0.4 µg/kg/h immediately after anesthesia induction and 0.1 µg/kg/h after extubation, which was maintained until 24 h) or a normal saline control group. MEASUREMENTS: The primary outcome was the incidence of AKI within the first two days after surgery, based on the Acute Kidney Injury Network (AKIN) criteria. The secondary outcomes included serum cystatin C and estimated glomerular filtration rate on postoperative days 1, 2, and 7, and in-hospital need for renal replacement therapy (RRT). Long-term outcomes included RRT and all-cause mortality. MAIN RESULTS: Ninety-eight patients completed the study (dexmedetomidine, n = 48; control, n = 50). AKIN stage 1 AKI occurred in 3/48 (6.3%) patients receiving dexmedetomidine, compared with 11/50 (22%) patients receiving normal saline (odds ratio = 0.24, 95% CI: 0.07 to 0.89, P = 0.041). This difference remained significant after adjusting for baseline covariates (adjusted odds ratio = 0.21, 95% CI: 0.05 to 0.84; P = 0.028). Dexmedetomidine led to a lower serum cystatin C on postoperative day 1 (median [IQR] mg/L: 1.31 [1.02-1.72] vs. 1.58 [1.28-1.96]). There were no between-group differences in other secondary or long-term outcomes. During the follow-up (median = 28.4 months), 1 patient in the dexmedetomidine group and 3 patients in the control group required RRT. CONCLUSIONS: Dexmedetomidine reduced the incidence of AKI in TBAD patients after EVAR procedures. The long-term benefits of dexmedetomidine in this patient population warrant further investigation. TRIAL REGISTRATION: ChiCTR-IPR-15006372.

5.
Fish Shellfish Immunol ; 118: 197-204, 2021 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-34509628

RESUMO

Tongue sole tissue factor pathway inhibitor 2 (TFPI-2) C-terminus derived peptide, TC38, has previously been shown to kill Vibrio vulnificus cells without lysing the cell membrane; thus, the remaining bacterial shell has potential application as an inactivated vaccine. Therefore, this study aimed to evaluate the immune response induced by the novel V. vulnificus vaccine. The protective potential of TC38-killed V. vulnificus cells (TKC) was examined in a turbot model. Fish were intramuscularly vaccinated with TKC or FKC (formalin-killed V. vulnificus cells) and challenged with a lethal-dose of V. vulnificus. The results showed that compared with FKC, TKC was effective in protecting fish against V. vulnificus infection, with relative percent of survival (RPS) rates of 53.29% and 63.64%, respectively. The immunological analysis revealed that compared with the FKC and control groups, the TKC group exhibited: 1) significantly higher respiratory burst ability and bactericidal activity of macrophages at 7 d post-vaccination; 2) increased alkaline phosphatase, acid phosphatase, lysozyme, and total superoxide dismutase levels post-vaccination; 3) higher serum agglutinating antibody titer with corresponding higher serum bactericidal ability, and a more potent serum agglutination effect, as well as an increased IgM expression level; 4) higher expression of immune relevant genes, which were involved in both innate and adaptive immunity. Taken together, this is the first study to develop a novel V. vulnificus inactivated vaccine based on AMP inactivation, and TKC is an effective vaccine against V. vulnificus infection for aquaculture.

6.
Environ Toxicol ; 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34520102

RESUMO

The crucial roles of the long noncoding RNAs (lncRNAs) in the development of ovarian cancer (OC) have been extensively studied. According to the prediction result from the Kaplan-Meier Plotter database, high expression of lncRNA proteasome subunit α type-3 antisense RNA1 (PSMA3-AS1) is associated with the poor prognosis in patients with OC. Thus, the study aimed to investigate the role of lncRNA PSMA3-AS1 in OC. Reverse transcription quantitative polymerase chain reaction analysis revealed that PSMA3-AS1 expression was significantly upregulated in OC cells and tissues. PSMA3-AS1 silencing inhibited OC cell proliferation, migration, and invasion, as shown by results of cell counting kit-8, colony formation, wound healing, and Transwell assays, respectively. Additionally, PSMA3-AS1 deficiency suppressed tumor growth in vivo. Mechanistically, luciferase reporter and RNA pulldown assays implied that PSMA3-AS1 served as a competing endogenous RNA for miR-378a-3p to upregulate the expression of polypeptide N-acetylgalactosaminyltransferase 3 (GALNT3). GALNT3 was a target gene of miR-378a-3p in OC. Moreover, PSMA3-AS1 activated the PI3K/Akt pathway by upregulating GALNT3 expression. Overall, PSMA3-AS1 promotes OC cell proliferation, migration, invasion, and xenograft tumor growth by activating the PI3K/Akt pathway via the miR-378a-3p/GALNT3 axis.

7.
Int J Biol Sci ; 17(13): 3343-3355, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34512151

RESUMO

Mesangial cell (MC) proliferation and matrix expansion are basic pathological characteristics of IgA nephropathy (IgAN). However, the stepwise mechanism of MC proliferation and the exact set of related signaling molecules remain largely unclear. In this study, we found a significant upregulation of miR-214-3p in the renal cortex of IgAN mice by miRNA sequencing. In situ hybridization analysis showed that miR-214-3p expression was obviously elevated in MCs in the renal cortex in IgAN. Functionally, knockdown of miR-214-3p alleviated mesangial hypercellularity and renal lesions in IgAN mice. In vitro, the inhibition of miR-214-3p suppressed MC proliferation and arrested G1-S cell cycle pSrogression in IgAN. Mechanistically, a luciferase reporter assay verified PTEN as a direct target of miR-214-3p. Downregulation of miR-214-3p increased PTEN expression and reduced p-JNK and p-c-Jun levels, thereby inhibiting MC proliferation and ameliorating renal lesions in IgAN. Moreover, these changes could be attenuated by co-transfection with PTEN siRNA. Collectively, these results illustrated that miR-214-3p accelerated MC proliferation in IgAN by directly targeting PTEN to modulate JNK/c-Jun signaling. Therefore, miR-214-3p may represent a novel therapeutic target for IgAN.

8.
Biomed Res Int ; 2021: 2202888, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34513987

RESUMO

The proliferation of pulmonary artery smooth muscle cells (PASMCs) is an important cause of pulmonary vascular remodeling in pulmonary hypertension (PH). It has been reported that miR-137 inhibits the proliferation of tumor cells. However, whether miR-137 is involved in PH remains unclear. In this study, male Sprague-Dawley rats were subjected to 10% O2 for 3 weeks to establish PH, and rat primary PASMCs were treated with hypoxia (3% O2) for 48 h to induce cell proliferation. The effect of miR-137 on PASMC proliferation and calpain-2 expression was assessed by transfecting miR-137 mimic and inhibitor. The effect of calpain-2 on PASMC proliferation was assessed by transfecting calpain-2 siRNA. The present study found for the first time that miR-137 was downregulated in pulmonary arteries of hypoxic PH rats and in hypoxia-treated PASMCs. miR-137 mimic inhibited hypoxia-induced PASMC proliferation and upregulation of calpain-2 expression in PASMCs. Furthermore, miR-137 inhibitor induced the proliferation of PASMCs under normoxia, and knockdown of calpain-2 mRNA by siRNA significantly inhibited hypoxia-induced proliferation of PASMCs. Our study demonstrated that hypoxia-induced downregulation of miR-137 expression promoted the proliferation of PASMCs by targeting calpain-2, thereby potentially resulting in pulmonary vascular remodeling in hypoxic PH.

9.
Leg Med (Tokyo) ; 53: 101957, 2021 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-34481193

RESUMO

The Microreader™ 19X Direct ID System was a newly developed multiplex PCR kit, which could detect 19 X-chromosomal STR loci (DXS6795, DXS9907, DXS6803, GATA172D05, DXS6807, GATA31E08, DXS7423, DXS6810, DXS101, DXS9902, DXS7133, DXS6800, DXS981, DXS10162, DXS6809, DXS10135, HPRTB, GATA165B12, DXS10079) and the sex determination locus of AMEL simultaneously. Different from other X-STR multiplex PCR kits, no linkage groups are included in this system, so the likelihood ratios could be calculated without the consideration of linkage groups. In this study, PCR conditions, sensitivity, species specificity, stability, DNA mixtures, concordance, stutter, sizing precision and population studies were conducted according to the SWGDAM developmental validation guidelines. The results indicated that this new X-STRs multiplex system was an efficient and reliable detection system, which could facilitate human kinship analysis and identification testing, as a powerful supplementary to autosomal STR kits.

10.
BMC Genomics ; 22(1): 653, 2021 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-34511071

RESUMO

BACKGROUND: As non-coding RNA molecules of more than 200 bp in length, long non-coding RNAs (lncRNAs) play a variety of roles in biological processes, including regulating the immune responses to bacterial infections. In recent years, there have been many in-depth studies on mammalian lncRNAs, but the relevant studies in fish are very limited. Meanwhile, since lncRNAs are not conserved among species, it is difficult to apply the existing results directly to unstudied species. RESULTS: To obtain the information of lncRNAs in Megalobrama amblycephala, one of the most economically important freshwater fish in China, also to better understand the biological significance of lncRNAs in the immunity system, the fish liver at 0, 4, 12, 24, and 72 h post Aeromonas hydrophila infection (hpi) were obtained for lncRNA-sequencing (lncRNA-seq). A total of 14,849 lncRNAs were identified, and 2196 lncRNAs showed significant differences at different time points post A. hydrophila infection. Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses showed that the target genes of the differentially expressed lncRNAs were enriched in several pathways related to immune such as apoptosis, inflammation, and immune response. Time-specific modules were then identified, using weighted correlation network analysis (WGCNA), and 28 modules significantly correlated with different time point after infection were found. Furthermore, four immune-related genes and six lncRNAs in the time-specific modules were subsequently verified by RT-qPCR. CONCLUSIONS: The above findings reveal the discovery of widespread differentially expressed lncRNAs in the M. amblycephala liver post A. hydrophila infection, suggesting that lncRNAs might participate in the regulation of host response to bacterial infection, enriching the information of lncRNAs in teleost and providing a resources basis for further studies on the immune function of lncRNAs.


Assuntos
Cyprinidae , RNA Longo não Codificante , Aeromonas hydrophila , Animais , Cyprinidae/genética , Fígado , RNA Longo não Codificante/genética , RNA Mensageiro/genética
11.
Neurosci Lett ; : 136209, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34480999

RESUMO

Alzheimer's disease (AD) is one of the most common causes of neurodegenerative diseases in the elderly. Cholinergic dysfunction is one of the pathological hallmarks of AD and leads to learning and memory impairment. Transient receptor potential vanilloid 4(TRPV4), a nonselective cation channel, is involved in learning and memory functions. HC067047, a TRPV4 specific inhibitor, has been reported to protect neurons against cerebral ischemic injury and amyloid-ß -(Aß) 40-induced hippocampal cell death. However, whether HC067047 could improve scopolamine (SCP)-induced cognitive dysfunction in mice is still unknown. The aims of this study were to verify whether HC067047 could ameliorate the SCP-induced learning and memory impairments in mice and to elucidate its underlying mechanisms of action. In this study, we examined the neuroprotective effect of the HC067047 against cognitive dysfunction induced by SCP (5 mg/kg, i.p.), a muscarinic receptor antagonist. The results showed that administration of HC067047(10 mg/kg, i.p.) significantly ameliorated SCP-induced cognitive dysfunction as assessed by the novel place recognition test (NPRT) and novel object recognition test (NORT). In the Y-maze test, HC067047 significantly enhanced the time spent in the novel arm in SCP mice. To further investigate the molecular mechanisms underlying the neuroprotective effect of HC067047, expression of several proteins involved in apoptosis was examined. The results demonstrated that HC067047 treatment decreased the protein levels of proapoptotic proteins such as Bax and caspase-3 in the hippocampus of SCP mice. In addition, HC067047 enhanced expression of the neurogenesis marker DCX and improved levels of the mature neuronal marker NeuN in SCP mice. These findings suggest the neuroprotective potential of the TRPV4 inhibitor HC067047 for the management of dementia with learning and memory loss.

12.
ISA Trans ; 2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34482954

RESUMO

This paper aims to tackle the controller design issue of highly nonlinear and stochastic inflatable robotic arms (IRAs). A novel control scheme, i.e., hybrid adaptive disturbance rejection control (HADRC), is devised to handle the challenging tracking control of hard-to-model IRAs. The model-free adaptive control (MFAC) that linearizes the dynamics by leveraging solely the online input and output (I/O) data of plants is analytically enhanced for superlinear convergence. Both internal and external disturbances are rejected via the active disturbance rejection control (ADRC) that requires little prior model information. The fuzzy logic control (FLC) is subsequently implemented to correlate the two sub-controllers and contribute to attaining smooth motions. The superiority of the proposed scheme is demonstrated by the comparative simulations and experiments on a 2-degree-of-freedom (DOF) IRA.

13.
Artigo em Inglês | MEDLINE | ID: mdl-34473628

RESUMO

State-of-the-art methods in the image-to-image translation are capable of learning a mapping from a source domain to a target domain with unpaired image data. Though the existing methods have achieved promising results, they still produce visual artifacts, being able to translate low-level information but not high-level semantics of input images. One possible reason is that generators do not have the ability to perceive the most discriminative parts between the source and target domains, thus making the generated images low quality. In this article, we propose a new Attention-Guided Generative Adversarial Networks (AttentionGAN) for the unpaired image-to-image translation task. AttentionGAN can identify the most discriminative foreground objects and minimize the change of the background. The attention-guided generators in AttentionGAN are able to produce attention masks, and then fuse the generation output with the attention masks to obtain high-quality target images. Accordingly, we also design a novel attention-guided discriminator which only considers attended regions. Extensive experiments are conducted on several generative tasks with eight public datasets, demonstrating that the proposed method is effective to generate sharper and more realistic images compared with existing competitive models. The code is available at https://github.com/Ha0Tang/AttentionGAN.

14.
J Med Chem ; 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34477384

RESUMO

CDK9 is an essential drug target correlated to the development of acute myeloid leukemia (AML). Starting from the hit compound 10, which was discovered through a screening of our in-house compound library, the structural modifications were carried out based on the bioisosterism and scaffold hopping strategies. Consequently, compound 37 displayed the optimal CDK9 inhibitory activity with an IC50 value of 5.41 nM, which was nearly 1500-fold higher than compound 10. In addition, compound 37 exhibited significant antiproliferative activity in broad cancer cell lines. Further investigation of in vivo properties demonstrated that compound 37 could be orally administrated with an acceptable bioavailability (F = 33.7%). In MV-4-11 subcutaneous xenograft mouse model, compound 37 (7.5 mg/kg) could significantly suppress the tumor progression with a T/C value of 27.80%. Compound 37 represents a promising lead compound for the development of a novel class of CDK9 inhibitors for the treatment of acute myeloid leukemia.

15.
Zhongguo Dang Dai Er Ke Za Zhi ; 23(9): 882-888, 2021.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-34535201

RESUMO

OBJECTIVES: To evaluate the quality of life and related demographic factors in long-term survivors of childhood non-Hodgkin's lymphoma (NHL). METHODS: A retrospective analysis was performed on the medical and demographic data of the NHL patients who received treatment in the Sun Yat-sen University Cancer Center and achieved long-term survival at follow-up, with an age of <18 years at initial diagnosis and a present age of ≥18 years. A questionnaire survey was performed using 36-Item Short-Form Health Survey (SF-36) and the symptom subscale of the Chinese version of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (QLQ-C30). The health status of long-term survivors of NHL was evaluated by comparing the scores of various dimensions of the SF-36 scale of general adult population in the United States (American norm) and those of the SF-36 scale of general adult population in Hong Kong, China (Hong Kong norm). The correlation between the score of each dimension of the scale and demographic characteristics was evaluated. The symptoms of long-term NHL survivors were evaluated according to the score of QLQ-C30 scale. RESULTS: A total of 23 patients with NHL with complete follow-up data were enrolled. The pathological types included diffuse large B-cell lymphoma in 10 patients, Burkitt lymphoma in 4 patients, T-cell lymphoblastoma in 5 patients, B-cell lymphoblastoma in 3 patients, and natural killer/T cell lymphoma in 1 patient. All patients received the chemotherapy regimen containing anthracyclines and alkylating agents. The median present age was 26.2 years (range: 16.9-55.8 years), and the median age at initial diagnosis was 10.4 years (range: 2.4-17.6 years). Among the 23 patients, 6 were married and had children and 2 had chronic diseases. There was no significant difference between the long-term survivors and the US norm in role physical, general health, role-emotional, and mental health (P>0.05), while the long-term survivors had significantly better scores of the other dimensions than the US norm (P<0.05). Similar results were obtained for the comparison between the long-term survivors and the China Hong Kong norm. Age at initial diagnosis was negatively correlated with the scores of social functioning, role physical, and general health in the SF-36 scale (P<0.05), and the present age of patients was positively correlated with the score of physical functioning and was negatively correlated with the score of general health (P<0.05). The urban and rural distribution of patients was related to the general health status (P<0.05). In addition, the long-term survivors of childhood NHL had relatively low scores of the symptom domain of QLQ-C30, and few moderate or severe symptoms were found. CONCLUSIONS: Long-term survivors of childhood NHL tend to have a good overall health status, with no significant differences compared with the general population. Age at initial diagnosis is the main demographic factor that affects patients' quality of life. Citation.

16.
Zhongguo Dang Dai Er Ke Za Zhi ; 23(8): 814-820, 2021 Aug 15.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-34511171

RESUMO

OBJECTIVES: To study the survival rate and the incidence of complications of very preterm infants and the factors influencing the survival rate and the incidence of complications. METHODS: The medical data of the very preterm infants with a gestational age of <32 weeks and who were admitted to the Department of Neonatology in 11 hospitals of Jiangsu Province in China from January 2018 to December 2019 were retrospectively reviewed. Their survival rate and the incidence of serious complications were analyzed. A multivariate logistic regression analysis was used to evaluate the risk factors for death and serious complications in very preterm infants. RESULTS: A total of 2 339 very preterm infants were enrolled, among whom 2 010 (85.93%) survived and 1 507 (64.43%) survived without serious complications. The groups with a gestational age of 22-25+6 weeks, 26-26+6 weeks, 27-27+6 weeks, 28-28+6 weeks, 29-29+6 weeks, 30-30+6 weeks, and 31-31+6 weeks had a survival rate of 32.5%, 60.6%, 68.0%, 82.9%, 90.1%, 92.3%, and 94.8% respectively. The survival rate tended to increase with the gestational age (P<0.05) and the survival rate without serious complications in each gestational age group was 7.5%, 18.1%, 34.5%, 52.2%, 66.7%, 75.7%, and 81.8% respectively, suggesting that the survival rate without serious complications increased with the gestational age (P<0.05). The multivariate logistic regression analysis showed that high gestational age, high birth weight, and prenatal use of glucocorticoids were protective factors against death in very preterm infants (P<0.05), and 1-minute Apgar score ≤3 was a risk factor for death in very preterm infants (P<0.05); high gestational age and high birth weight were protective factors against serious complications in very preterm infants who survived (P<0.05), while 5-minute Apgar score ≤3 and maternal chorioamnionitis were risk factors for serious complications in very preterm infants who survived (P<0.05). CONCLUSIONS: The survival rate is closely associated with gestational age in very preterm infants. A low 1-minute Apgar score (≤3) may increase the risk of death in very preterm infants, while high gestational age, high birth weight, and prenatal use of glucocorticoids are associated with the reduced risk of death. A low 5-minute Apgar score (≤3) and maternal chorioamnionitis may increase the risk of serious complications in these infants, while high gestational age and high birth weight may reduce the risk of serious complications.


Assuntos
Doenças do Prematuro , Recém-Nascido Prematuro , Feminino , Idade Gestacional , Humanos , Lactente , Recém-Nascido , Recém-Nascido de muito Baixo Peso , Gravidez , Estudos Retrospectivos , Taxa de Sobrevida
17.
Cancer Sci ; 2021 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-34533861

RESUMO

Diverse metabolic changes are induced by various driver oncogenes during the onset and progression of leukemia. By upregulating glycolysis, cancer cells acquire a proliferative advantage over normal hematopoietic cells; in addition, these changes in energy metabolism contribute to anticancer drug resistance. Because leukemia cells proliferate by consuming glucose as an energy source, an alternative nutrient source is essential when glucose levels in bone marrow are insufficient. We profiled sugar metabolism in leukemia cells and found that mannose is an energy source for glycolysis, the tricarboxylic acid (TCA) cycle, and the pentose phosphate pathway (PPP). Leukemia cells express high levels of phosphomannose isomerase (PMI), which mobilizes mannose to glycolysis; consequently, even mannose in the blood can be used as an energy source for glycolysis. Conversely, suppression of PMI expression or a mannose load exceeding the processing capacity of PMI inhibited transcription of genes related to mitochondrial metabolism and TCA cycle, thus suppressing the growth of leukemia cells. High PMI expression was also a poor prognostic factor for acute myeloid leukemia. Our findings reveal a new mechanism for glucose starvation resistance in leukemia. Furthermore, the combination of PMI suppression and mannose loading has potential as a novel treatment for driver oncogene-independent leukemia.

19.
Inorg Chem ; 2021 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-34503331

RESUMO

Half-sandwich Os-arene complexes exhibit promising anticancer activity, but their photochemistry has hardly been explored. To exploit the photocytotoxicity and photochemistry of Os-arenes, O,O-chelated complexes [Os(η6-p-cymene)(Curc)Cl] (OsCUR-1, Curc = curcumin) and [Os(η6-biphenyl)(Curc)Cl] (OsCUR-2), and N,N-chelated complexes [Os(η6-biphenyl)(dpq)I]PF6 (OsDPQ-2, dpq = pyrazino[2,3-f][1,10]phenanthroline) and [Os(η6-biphenyl)(bpy)I]PF6 (OsBPY-2, bpy = 2,2'-bipyridine), have been investigated. The Os-arene curcumin complexes showed remarkable photocytotoxicity toward a range of cancer cell lines (blue light IC50: 2.6-5.8 µM, photocytotoxicity index PI = 23-34), especially toward cisplatin-resistant cancer cells, but were nontoxic to normal cells. They localized mainly in mitochondria in the dark but translocated to the nucleus upon photoirradiation, generating DNA and mitochondrial damage, which might contribute toward overcoming cisplatin resistance. Mitochondrial damage, apoptosis, ROS generation, DNA damage, angiogenesis inhibition, and colony formation were observed when A549 lung cancer cells were treated with OsCUR-2. The photochemistry of these Os-arene complexes was investigated by a combination of NMR, HPLC-MS, high energy resolution fluorescence detected (HERFD), X-ray adsorption near edge structure (XANES) spectroscopy, total fluorescence yield (TFY) XANES spectra, and theoretical computation. Selective photodissociation of the arene ligand and oxidation of Os(II) to Os(III) occurred under blue light or UVA excitation. This new approach to the design of novel Os-arene complexes as phototherapeutic agents suggests that the novel curcumin complex OsCUR-2, in particular, is a potential candidate for further development as a photosensitizer for anticancer photoactivated chemotherapy (PACT).

20.
Anal Chim Acta ; 1178: 338791, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34482866

RESUMO

Biomarkers play an important role in disease diagnosis and prognosis, which demand reliable, sensitive, rapid, and economic detection platform to conduct simultaneous multiple-biomarkers analysis in serum or body liquid. Here, we developed a universal biosensing platform through integrating the advantages of unique nanostructure and biochemistry properties of graphene oxide quantum dots and high throughput and low cost of microfluidic chip for reliable and simultaneous detection of multiple cancer antigen and antibody biomarkers. The performance of the proposed biosensing platform is validated through the representative cancer biomarkers including carcino-embryonic antigen (CEA), carbohydrate antigen 125 (CA125), α-fetoprotein (AFP), carbohydrate antigen 199 (CA199) and carbohydrate antigen 153 (CA153). It has a large linear quantification detection regime of 5-6 orders of magnitude and an ultralow detection limit of 1 pg/mL or 0.01 U/mL. Moreover, the proposed biosensing chip is capable of conducting 5-20 kinds of biomarkers from at least 60 persons simultaneously in 40 min with only 2 µL serum of each patient, which essentially reduces the detection cost and time to at least 1/60 of current popular methods. Clinical breast cancer and healthy samples detection results indicated its promising perspective in practical applications including cancer early diagnosis, prognosis, and disease pathogenesis study.


Assuntos
Técnicas Biossensoriais , Neoplasias da Mama , Grafite , Pontos Quânticos , Biomarcadores Tumorais , Neoplasias da Mama/diagnóstico , Feminino , Humanos , Limite de Detecção , Microfluídica
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