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1.
Nano Lett ; 2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34623162

RESUMO

The formation of membrane nanopores is one of the crucial activities of cells and has attracted considerable attention. However, the understanding of their types and mechanisms is still limited. Herein, we report a novel nanopore formation phenomenon achieved through the insertion of polymeric nanotoroids into the cellular membrane. As revealed by theoretical simulations, the nanotoroid can embed in the membrane, leaving a nanopore on the cell. The through-the-cavity wrapping of lipids is critical for the retention of the nanotoroid in the membrane, which is attributed to both a relatively large inner cavity of the nanotoroid and a moderate attraction between the nanotoroid and membrane lipids. Under the guidance of the simulation predictions, experiments using polypeptide toroids as pore-forming agents were performed, confirming the unique biophysical phenomenon. This work demonstrates a distinctive pore-forming pathway, deepens the understanding of the membrane nanopore phenomenon, and assists in the design of advanced pore-forming materials.

2.
Int J Mol Sci ; 22(19)2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34638764

RESUMO

Based on their unique properties, oligonucleotide aptamers have been named a gift of biological chemistry to life science. We report the development of DNA aptamers as the first high-affinity binding molecules available for fast and rapid labeling of the human gut bacterium Akkermansia muciniphila with a certain impact on Alzheimer´s disease. Fast and reliable analyses of the composition of microbiomes is an emerging field in microbiology. We describe the molecular evolution and biochemical characterization of a specific aptamer library by a FluCell-SELEX and the characterization of specific molecules from the library by bioinformatics. The aptamer AKK13.1 exerted universal applicability in different analysis techniques in modern microbiology, including fluorimetry, confocal laser scanning microscopy and flow cytometry. It was also functional as a specific binding entity hybridized to anchor primers chemically coupled via acrydite-modification to the surface of a polyacrylamide-hydrogel, which can be prototypically used for the construction of affinity surfaces in sensor chips. Together, the performance and methodological flexibility of the aptamers presented here may open new routes not only to develop novel Akkermansia-specific assays for clinical microbiology and the analyses of human stool samples but may also be an excellent starting point for the construction of novel electronic biosensors.

3.
Sensors (Basel) ; 21(19)2021 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-34640747

RESUMO

Tuning fork gyroscopes (TFGs) are promising for potential high-precision applications. This work proposes and experimentally demonstrates a novel high-Q dual-mass tuning fork microelectromechanical system (MEMS) gyroscope utilizing three-dimensional (3D) packaging techniques. Except for two symmetrically decoupled proof masses (PM) with synchronization structures, a symmetrically decoupled lever structure is designed to force the antiparallel, antiphase drive mode motion and eliminate low frequency spurious modes. Thermoelastic damping (TED) and anchor loss are greatly reduced by the linearly coupled, momentum- and torque-balanced antiphase sense mode. Moreover, a novel 3D packaging technique is used to realize high Q-factors. A composite substrate encapsulation cap, fabricated by through-silicon-via (TSV) and glass-in-silicon (GIS) reflow processes, is anodically bonded to the wafer-scale sensing structures. A self-developed control circuit is adopted to realize loop control and characterize gyroscope performances. It is shown that a high-reliability electrical connection, together with a high air impermeability package, can be fulfilled with this 3D packaging technique. Furthermore, the Q-factors of the drive and sense modes reach up to 51,947 and 49,249, respectively. This TFG realizes a wide measurement range of ±1800 °/s and a high resolution of 0.1°/s with a scale factor nonlinearity of 720 ppm after automatic mode matching. In addition, long-term zero-rate output (ZRO) drift can be effectively suppressed by temperature compensation, inducing a small angle random walk (ARW) of 0.923°/√h and a low bias instability (BI) of 9.270°/h.

4.
Front Cell Dev Biol ; 9: 717601, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34650972

RESUMO

The tumor immune microenvironment (TIME) has been recognized to be associated with sensitivity to immunotherapy and patient prognosis. Recent research demonstrates that assessing the TIME patterns on large-scale samples will expand insights into TIME and will provide guidance to formulate immunotherapy strategies for tumors. However, until now, thorough research has not yet been reported on the immune infiltration landscape of glioma. Herein, the CIBERSORT algorithm was used to unveil the TIME landscape of 1,975 glioma observations. Three TIME subtypes were established, and the TIMEscore was calculated by least absolute shrinkage and selection operator (LASSO)-Cox analysis. The high TIMEscore was distinguished by an elevated tumor mutation burden (TMB) and activation of immune-related biological process, such as IL6-JAK-STAT3 signaling and interferon gamma (IFN-γ) response, which may demonstrate that the patients with high TIMEscore were more sensitive to immunotherapy. Multivariate analysis revealed that the TIMEscore could strongly and independently predict the prognosis of gliomas [Chinese Glioma Genome Atlas (CGGA) cohort: hazard ratio (HR): 2.134, p < 0.001; Gravendeel cohort: HR: 1.872, p < 0.001; Kamoun cohort: HR: 1.705, p < 0.001; The Cancer Genome Atlas (TCGA) cohort: HR: 2.033, p < 0.001; the combined cohort: HR: 1.626, p < 0.001], and survival advantage was evident among those who received chemotherapy. Finally, we validated the performance of the signature in human tissues from Wuhan University (WHU) dataset (HR: 15.090, p = 0.008). Our research suggested that the TIMEscore could be applied as an effective predictor for adjuvant therapy and prognosis assessment.

5.
Biochim Biophys Acta Mol Basis Dis ; 1868(1): 166281, 2021 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-34610472

RESUMO

Colorectal cancer (CRC) is one of the most common gastrointestinal malignancies. The occurrence and development of CRC are complicated processes. Obesity and dysbacteriosis have been increasingly regarded as the main risk factors for CRC. Understanding the etiology of CRC from multiple perspectives is conducive to screening for some potential drugs or new treatment strategies to limit the serious side effects of conventional treatment and prolong the survival of CRC patients. Melatonin, a natural indoleamine, is mainly produced by the pineal gland, but it is also abundant in other tissues, including the gastrointestinal tract, retina, testes, lymphocytes, and Harder's glands. Melatonin could participate in lipid metabolism by regulating adipogenesis and lipolysis. Additionally, many studies have focused on the potential beneficial effects of melatonin in CRC, such as promotion of apoptosis; inhibition of cell proliferation, migration, and invasion; antioxidant activity; and immune regulation. Meaningfully, gut microbiota is the main determinant of all aspects of health and disease (including obesity and tumorigenesis). The gut microbiota is of great significance for understanding the relationship between obesity and increased risk of CRC. Although the current understanding of how the melatonin-mediated gut microbiota coordinates a variety of physiological and pathological activities is fairly comprehensive, there are still many unknown topics to be explored in the face of a complex nutritional status and a changeable microbiota. This review summarizes the potential links among melatonin, lipid metabolism, gut microbiota, and CRC to promote the development of melatonin as a preventive and therapeutic agent for CRC.

6.
Sci Total Environ ; : 150630, 2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34597571

RESUMO

Ozone (O3) exposure not only causes lung injury and lung inflammation but also changes blood composition. Previous studies have mainly focused on inflammatory processes and metabolic diseases caused by acute or chronic ozone exposure. However, the effect of ozone on lipid expression profiles remains unclear. This study aimed to investigate the lipidomic changes in lung tissue and serum of rats after ozone exposure for three months and explore the lipid metabolic pathway involved in an ozone-induced injury. Based on the non-targeted lipidomic analysis platform of the UPLC Orbitrap mass spectrometry system, we found that sub-chronic exposure to ozone significantly changed the characteristics of lipid metabolism in lungs and serum of rats. First, the variation in sphingomyelin (SM) and triglyceride (TG) levels in the lung and serum after O3 exposure are shown. SM decreased in both tissues, while TG decreased in the lungs and increased in the serum. Further, the effect of ozone on glycerophospholipids in the lung and serum was completely different. Phosphatidylethanolamine (PE), phosphatidylserine (PS), and phosphatidylinositol (PI) were the major glycerophospholipids whose levels were altered in the lung, while phosphatidylglycerol (PG), phosphatidic acid (PA), and phosphatidylcholine (PC) levels changed dramatically in the serum. Third, after O3 exposure, the level of monogalactosyldiacylglycerol (MGDG), mainly MGDG (43, 11), a saccharolipid, declined significantly and uniquely in the serum. These results suggested that sub-chronic O3 exposure may play a role in the development of several diseases through perturbation of lipidomic profiles in the lungs and blood. In addition, changes in the lipids of the lung and blood may induce or exacerbate respiratory diseases.

7.
Front Genet ; 12: 741858, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34594365

RESUMO

MicroRNAs (miRNAs) and their target genes play vital roles in crops. However, the genetic variations in miRNA-targeted sites that affect miRNA cleavage efficiency and their correlations with agronomic traits in crops remain unexplored. On the basis of a genome-wide DNA re-sequencing of 210 elite rapeseed (Brassica napus) accessions, we identified the single nucleotide polymorphisms (SNPs) and insertions/deletions (INDELs) in miRNA-targeted sites complementary to miRNAs. Variant calling revealed 7.14 million SNPs and 2.89 million INDELs throughout the genomes of 210 rapeseed accessions. Furthermore, we detected 330 SNPs and 79 INDELs in 357 miRNA target sites, of which 33.50% were rare variants. We also analyzed the correlation between the genetic variations in miRNA target sites and 12 rapeseed agronomic traits. Eleven SNPs in miRNA target sites were significantly correlated with phenotypes in three consecutive years. More specifically, three correlated SNPs within the miRNA-binding regions of BnSPL9-3, BnSPL13-2, and BnCUC1-2 were in the loci associated with the branch angle, seed weight, and silique number, respectively; expression profiling suggested that the variation at these 3 miRNA target sites significantly affected the expression level of the corresponding target genes. Taken together, the results of this study provide researchers and breeders with a global view of the genetic variations in miRNA-targeted sites in rapeseed and reveal the potential effects of these genetic variations on elite agronomic traits.

8.
Front Neurol ; 12: 735758, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34659095

RESUMO

Objective: The objective of this study was to evaluate the effect of blood pressure (BP) management with transcranial Doppler (TCD) guidance in patients with large-vessel occlusion in the anterior circulation after endovascular thrombectomy (EVT) on the long-term prognosis. Methods: This was a prospective study; 232 patients were nonrandomized assigned to TCD-guided BP management (TBM) group or non-TCD-guided BP management (NBM) group. In the TBM group, BP was controlled according to TCD showing cerebral blood flow fluctuation. In the NBM group, BP was controlled according to the guidelines. The primary endpoint was a modified Rankin scale (mRS) score of 2 or lower at 90 days. The safety outcomes were the rates of symptomatic or any intracerebral hemorrhage (ICH) and mortality at 90 days. Results: One hundred sixty-three patients were assigned to the TBM group, and 69 were assigned to the NBM group. In the propensity score-matched cohort (65 matches in both groups), there was significant difference in the proportion of participants with mRS 0-2 at 90 days according to BP management (adjusted odds ratio 3.34, 95% CI 1.36 to 8.22). There was no difference in the rates of symptomatic or any ICH and mortality between two groups. In inverse probability-weighted regression adjustment analysis, mortality decreased significantly in the TBM group than in the NBM group (adjusted odds ratio 0.86, 95% CI 0.76-0.99, p = 0.03). Conclusion: In patients with acute ischemic stroke from large-vessel occlusion in the anterior circulation, BP management under TCD was superior to NBM in improving the clinical outcomes at 90 days. Clinical Trial Registration: (URL: https://www.chictr.org.cn/showproj.aspx?proj=55484; Identifier: ChiCTR2000034443.

9.
Blood Cancer Discov ; 2(4): 388-401, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34661159

RESUMO

The PML/RARα fusion protein is the oncogenic driver in acute promyelocytic leukemia (APL). Although most APL cases are cured by PML/RARα-targeting therapy, relapse and resistance can occur due to drug-resistant mutations. Here we report that thermal stress destabilizes the PML/RARα protein, including clinically identified drug-resistant mutants. AML1/ETO and TEL/AML1 oncofusions show similar heat shock susceptibility. Mechanistically, mild hyperthermia stimulates aggregation of PML/RARα in complex with nuclear receptor corepressors leading to ubiquitin-mediated degradation via the SIAH2 E3 ligase. Hyperthermia and arsenic therapy destabilize PML/RARα via distinct mechanisms and are synergistic in primary patient samples and in vivo, including three refractory APL cases. Collectively, our results suggest that by taking advantage of a biophysical vulnerability of PML/RARα, thermal therapy may improve prognosis in drug-resistant or otherwise refractory APL. These findings serve as a paradigm for therapeutic targeting of fusion oncoprotein-associated cancers by hyperthermia. Significance: Hyperthermia destabilizes oncofusion proteins including PML/RARα and acts synergistically with standard arsenic therapy in relapsed and refractory APL. The results open up the possibility that heat shock sensitivity may be an easily targetable vulnerability of oncofusion-driven cancers.See related commentary by Wu et al., p. 300.

10.
Int J Stroke ; : 17474930211045805, 2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34550833

RESUMO

OBJECTIVE: To determine the influence of renal impairment on clinical outcomes in patients presenting emergent anterior circulation occlusion treated with mechanical thrombectomy. METHODS: Consecutive patients with anterior circulation stroke treated with mechanical thrombectomy at 41 academic tertiary care centers were included. renal impairment was defined as glomerular filtration rate <60 mL/min/1.73 m2 at the time of admission. The primary outcome was the distribution of scores on the modified Rankin scale, and safety outcomes were mortality within 90 days and hemorrhagic complications. Binary and ordinal logistic regression was used to evaluate the associations between renal impairment and categorical outcomes. Linear regression was used to assess continuous outcomes. RESULTS: A total of 607 patients (47 renal impairment and 600 non-renal impairment) who underwent mechanical thrombectomy were included in this study. Multivariate regression analysis showed that renal impairment was independently associated with the increase of the modified Rankin scale at 90 days. The proportion of patients with successful reperfusion was 71.7% in the renal impairment group and 83.3% in the non-renal impairment group. Renal impairment was an independent predictor of 90-day mortality. No significant treatment for the ordinal modified Rankin scale or 90-day mortality was observed by renal impairment interaction. The risk of asymptomatic intracranial hemorrhage was higher in the mechanical thrombectomy plus IVT group (53.6%) than in the mechanical thrombectomy alone group (15.8%) for renal impairment, but was similar between the mechanical thrombectomy plus IVT group (34.6%) and the mechanical thrombectomy alone group (36.4%) for non-renal impairment (p = 0.01). CONCLUSION: These results demonstrated that the outcomes of mechanical thrombectomy alone and mechanical thrombectomy plus IVT group did not differ significantly in acute stroke patients with and without renal impairment. Also, renal impairment was an independent predictor of worse functional independence and higher mortality at 90 days.

11.
J Hematol Oncol ; 14(1): 153, 2021 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-34563230

RESUMO

The 3-hydroxyanthranilic acid (3-HAA), a derivative of kynurenine, was reported to suppress tumor growth. However, the function of 3-HAA largely remains unclear. Here, we report that 3-hydroxyanthranilic acid (3-HAA) is lower in tumor cells, while adding exogenous 3-HAA induces apoptosis in hepatocellular carcinoma by binding YY1. This 3-HAA binding of YY1 leads to phosphorylation of YY1 at the Thr 398 by PKCζ, concomitantly enhances YY1 chromatin binding activity to increase expression of target genes. These findings demonstrate that 3-HAA is a ligand of YY1, suggesting it is a promising therapeutic candidate for HCC.

13.
Cell Regen ; 10(1): 29, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34467458

RESUMO

Organoid has become a novel in vitro model to research human development and relevant disorders in recent years. With many improvements on the culture protocols, current brain organoids could self-organize into a complicated three-dimensional organization that mimics most of the features of the real human brain at the molecular, cellular, and further physiological level. However, lacking positional information, an important characteristic conveyed by gradients of signaling molecules called morphogens, leads to the deficiency of spatiotemporally regulated cell arrangements and cell-cell interactions in the brain organoid development. In this review, we will overview the role of morphogen both in the vertebrate neural development in vivo as well as the brain organoid culture in vitro, the strategies to apply morphogen concentration gradients in the organoid system and future perspectives of the brain organoid technology.

14.
Cell Death Dis ; 12(8): 779, 2021 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-34365463

RESUMO

The PD-L1 overexpression is an important event of immune escape and metastasis in triple-negative breast cancer (TNBC), but the molecular mechanism remains to be determined. Interferon gamma (IFNγ) represents a major driving force behind PD-L1 expression in tumor microenvironment, and histone deacetylase 2 (HDAC2) is required for IFN signaling. Here, we investigated the regulation of HDAC2 on the IFNγ-induced PD-L1 expression in TNBC cells. We found the HDAC2 and PD-L1 expression in TNBC was significantly higher than that in non-TNBC, and HDAC2 was positively correlated with PD-L1 expression. HDAC2 promoted PD-L1 induction by upregulating the phosphorylation of JAK1, JAK2, and STAT1, as well as the translocation of STAT1 to the nucleus and the recruitment of STAT1 to the PD-L1 promoter. Meanwhile, HDAC2 was recruited to the PD-L1 promoter by STAT1, and HDAC2 knockout compromised IFNγ-induced upregulation of H3K27, H3K9 acetylation, and the BRD4 recruitment in PD-L1 promoter. In addition, significant inhibition of proliferation, colony formation, migration, and cell cycle of TNBC cells were observed following knockout of HDAC2 in vitro. Furthermore, HDAC2 knockout reduced IFNγ-induced PD-L1 expression, lymphocyte infiltration, and retarded tumor growth and metastasis in the breast cancer mouse models. This study may provide evidence that HDAC2 promotes IFNγ-induced PD-L1 expression, suggesting a way for enhanced antitumor immunity when targeting the HDAC2 in TNBC.

15.
Pharmaceuticals (Basel) ; 14(8)2021 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-34451919

RESUMO

Epidemiological studies have indicated that obesity is an independent risk factor for colitis and that a high-fat diet (HFD) increases the deterioration of colitis-related indicators in mice. Melatonin has multiple anti-inflammatory effects, including inhibiting tumor growth and regulating immune defense. However, the mechanism of its activity in ameliorating obesity-promoted colitis is still unclear. This study explored the possibility that melatonin has beneficial functions in HFD-induced dextran sodium sulfate (DSS)-induced colitis in mice. Here, we revealed that HFD-promoted obesity accelerated DSS-induced colitis, while melatonin intervention improved colitis. Melatonin significantly alleviated inflammation by increasing anti-inflammatory cytokine release and reducing the levels of proinflammatory cytokines in HFD- and DSS-treated mice. Furthermore, melatonin expressed antioxidant activities and reversed intestinal barrier integrity, resulting in improved colitis in DSS-treated obese mice. We also found that melatonin could reduce the ability of inflammatory cells to utilize fatty acids and decrease the growth-promoting effect of lipids by inhibiting autophagy. Taken together, our study indicates that the inhibitory effect of melatonin on autophagy weakens the lipid-mediated prosurvival advantage, which suggests that melatonin-targeted autophagy may provide an opportunity to prevent colitis in obese individuals.

16.
J Neuroinflammation ; 18(1): 188, 2021 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-34461942

RESUMO

BACKGROUND: Innate immunity can facilitate early brain injury (EBI) following subarachnoid hemorrhage (SAH). Numerous studies suggest that pyroptosis could exacerbate extracellular immune responses by promoting secretion of inflammatory cytokines. Transforming growth factor-ß-activated kinase 1 (TAK1) is a quintessential kinase that positively regulates inflammation through NF-κB and MAPK signaling cascades. However, the effects of TAK1 on neuroinflammation in EBI following SAH are largely unknown. METHODS: Two hundred and forty-six male C57BL/6J mice were subjected to the endovascular perforation model of SAH. A selective TAK1 inhibitor, 5Z-7-oxozeaenol (OZ) was administered by intracerebroventricular (i.c.v) injection at 30 min after SAH induction. To genetic knockdown of TAK1, small interfering RNA (siRNA) was i.c.v injected at 48 h before SAH induction. SAH grade, brain water content, BBB permeability, neurological score, western blot, real-time PCR, ELISA, transmission electron microscope, and immunofluorescence staining were performed. Long-term behavioral sequelae were evaluated by the rotarod and Morris water maze tests. Furthermore, OZ was added to the culture medium with oxyhemoglobin (OxyHb) to mimic SAH in vitro. The reactive oxygen species level was detected by DCFH-DA staining. Lysosomal integrity was assessed by Lyso-Tracker Red staining and Acridine Orange staining. RESULTS: The neuronal phosphorylated TAK1 expression was upregulated following SAH. Pharmacologic inhibition of TAK1 with OZ could alleviate neurological deficits, brain edema, and brain-blood barrier (BBB) disruption at 24 h after SAH. In addition, OZ administration restored long-term neurobehavioral function. Furthermore, blockade of TAK1 dampened neuronal pyroptosis by downregulating the N-terminal fragment of GSDMD (GSDMD-N) expression and IL-1ß/IL-18 production. Mechanistically, both in vivo and in vitro, we demonstrated that TAK1 can induce neuronal pyroptosis through promoting nuclear translocation of NF-κB p65 and activating nucleotide-binding oligomerization domain (NOD)-like receptor pyrin domain containing 3 (NLRP3) inflammasome. TAK1 siRNA treatment mitigated SAH-induced neurobehavioral deficits and restrained phosphorylated NF-κB p65 expression and NLRP3 inflammasome activation. TAK1 blockade also ameliorated reactive oxygen species (ROS) production and prevented lysosomal cathepsin B releasing into the cytoplasm. CONCLUSIONS: Our findings demonstrate that TAK1 modulates NLRP3-mediated neuronal pyroptosis in EBI following SAH. Inhibition of TAK1 may serve as a potential candidate to relieve neuroinflammatory responses triggered by SAH.

17.
Adv Sci (Weinh) ; 8(19): e2101031, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34365741

RESUMO

IRF8 is a key regulator of innate immunity receptor signaling and plays diverse functions in the development of hematopoietic cells. The effects of IRF8 on hematopoietic stem cells (HSCs) are still unknown. Here, it is demonstrated that IRF8 deficiency results in a decreased number of long-term HSCs (LT-HSCs) in mice. However, the repopulation capacity of individual HSCs is significantly increased. Transcriptomic analysis shows that IFN-γ and IFN-α signaling is downregulated in IRF8-deficient HSCs, while their response to proinflammatory cytokines is unchanged ex vivo. Further tests show that Irf8-/- HSCs can not respond to CpG, an agonist of Toll-like receptor 9 (TLR9) in mice, while long-term CpG stimulation increases wild-type HSC abundance and decreases their bone marrow colony-forming capacity. Mechanistically, as the primary producer of proinflammatory cytokines in response to CpG stimulation, dendritic cells has a blocked TLR9 signaling due to developmental defect in Irf8-/- mice. Macrophages remain functionally intact but severely reduce in Irf8-/- mice. In NK cells, IRF8 directly regulates the expression of Tlr9 and its deficiency leads to no increased IFNγ production upon CpG stimulation. These results indicate that IRF8 regulates HSCs, at least in part, through controlling TLR9 signaling in diverse innate immune cells.

18.
J Exp Bot ; 2021 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-34338731

RESUMO

Phytophthora root and stem rot in soybean [Glycine max (L.) Merr.] is a destructive disease worldwide. Improving soybean resistance to the causal pathogen, Phytophthora sojae, is a major target for breeders; however, it remains largely unclear how the pathogen regulates the various affected signaling pathways in the host, which consist of complex networks including key transcription factors and their targets. We previously demonstrated that GmBTB/POZ enhances soybean resistance to P. sojae and associated defense response. Here, we report that GmBTB/POZ interacts with transcription factor GmAP2 and promotes the ubiquitination of GmAP2. The GmAP2-RNAi transgenic soybean hairy roots exhibited an enhanced resistance to P. sojae, whereas GmAP2-overexpressing hairy roots showed P. sojae hypersensitivity. Subsequently, GmWRKY33 was identified as a target of GmAP2, which represses its expression by directly binding to the GmWRKY33 promoter. GmWRKY33 acts as a positive regulator in the response of soybean to P. sojae. Additionally, the overexpression of GmBTB/POZ released the GmAP2-regulated suppression of GmWRKY33 expression in the GmAP2-OE soybean hairy roots and increased their resistance to P. sojae. Taken together, these results indicate a novel regulatory mechanism, the GmBTB/POZ-GmAP2 modulation of the P. sojae resistance response, which putatively regulates the downstream target gene GmWRKY33 in soybean.

19.
J Clin Lab Anal ; 35(9): e23937, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34396586

RESUMO

OBJECTIVE: To deal with COVID-19, various countries have made many efforts, including the research and development of vaccines. The purpose of this manuscript was to summarize the development, application, and problems of COVID-19 vaccines. METHODS: This article reviewed the existing literature to see the development of the COVID-19 vaccine. RESULTS: We found that different types of vaccines had their own advantages and disadvantages. At the same time, the side effects of the vaccine, the dose of vaccination, the evaluation of the efficacy, and the application of the vaccine were all things worth studying. CONCLUSION: The successful development of the COVID-19 vaccine concerns almost all countries and people in the world. We must do an excellent job of researching the immunogenicity and immune reactivity of the vaccines. We hope this review can help colleagues at home and abroad.


Assuntos
Vacinas contra COVID-19 , COVID-19/prevenção & controle , SARS-CoV-2/imunologia , Vacinas contra COVID-19/administração & dosagem , Vacinas contra COVID-19/efeitos adversos , Vacinas contra COVID-19/classificação , Relação Dose-Resposta a Droga , Desenvolvimento de Medicamentos/métodos , Humanos
20.
Chem Commun (Camb) ; 57(69): 8652-8655, 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34373865

RESUMO

An efficient copper-catalyzed radical ring-opening halogenation with HX (aq) is described. This protocol features redox-neutral conditions, green halogen sources, and a broad substrate scope, providing practical access to distally chlorinated, brominated and iodinated alkyl ketones and alkyl nitriles with moderate to good yields.

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