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1.
Cancers (Basel) ; 14(1)2022 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-35008385

RESUMO

Tumors deploy various immune-evasion mechanisms that create a suppressive environment and render effector T-cells exhausted and inactive. Therefore, a rational utilization of checkpoint inhibitors may alleviate exhaustion and may partially restore antitumor functions. However, in high-tumor-burden models, the checkpoint blockade fails to maintain optimal efficacy, and other interventions are necessary to overcome the inhibitory tumor stroma. One such strategy is the use of radiotherapy to reset the tumor microenvironment and maximize systemic antitumor outcomes. In this study, we propose the use of anti-PD1 and anti-TIGIT checkpoint inhibitors in conjunction with our novel RadScopal technique to battle highly metastatic lung adenocarcinoma tumors, bilaterally established in 129Sv/Ev mice, to mimic high-tumor-burden settings. The RadScopal approach is comprised of high-dose radiation directed at primary tumors with low-dose radiation delivered to secondary tumors to improve the outcomes of systemic immunotherapy. Indeed, the triple therapy with RadScopal + anti-TIGIT + anti-PD1 was able to prolong the survival of treated mice and halted the growth of both primary and secondary tumors. Lung metastasis counts were also significantly reduced. In addition, the low-dose radiation component reduced TIGIT receptor (PVR) expression by tumor-associated macrophages and dendritic cells in secondary tumors. Finally, low-dose radiation within triple therapy decreased the percentages of TIGIT+ exhausted T-cells and TIGIT+ regulatory T-cells. Together, our translational approach provides a new treatment alternative for cases refractory to other checkpoints and may bring immunotherapy into a new realm of systemic disease control.

2.
Anim Nutr ; 8(1): 227-234, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34988304

RESUMO

The current dietary copper (Cu) requirement (8 mg/kg) of broilers is mainly based on growth, hemoglobin concentration, or hematocrit, which might not be the most sensitive indices to evaluate dietary Cu requirements of broilers. The present study was carried out to estimate dietary Cu requirements of broilers fed a conventional corn-soybean meal diet from 1 to 21 d of age using biochemical or molecular biomarkers. A total of 384 1-d-old Arbor Acres male broilers were randomly allocated to 1 of 6 treatments with 8 replicates and fed a Cu-unsupplemented corn-soybean meal basal diet containing 5.17 mg Cu/kg by analysis and the basal diet supplemented with 3, 6, 9, 12 or 15 mg Cu/kg as CuSO4⋅5H2O for 21 d. Regression analysis was performed to estimate the optimal dietary Cu level using the broken-line model. Dietary supplemental Cu level affected (P < 0.05) Cu contents in serum and liver and kidney monoamine oxidase (MAO) activity, but had no effects (P > 0.05) on the growth performance, Cu contents in heart, kidney, pancreas and spleen, Cu- and zinc-containing superoxide dismutase (CuZnSOD) activity and ceruloplasmin content in serum, CuZnSOD and cytochrome c oxidase (COX) activities and ceruloplasmin, CuZnSOD, MAO A, MAO B, COX 4 I 1 and COX 1 mRNA and protein expressions in the above tissues of broilers. As dietary supplemental Cu levels increased, Cu contents in serum and liver increased linearly (P < 0.05), but kidney MAO activity decreased linearly and quadratically (P < 0.05). The estimated dietary Cu requirement based on the fitted broken-line model (P = 0.035) of kidney MAO activity was 11.30 mg/kg. In conclusion, kidney MAO activity is a new and sensitive criterion to evaluate the dietary Cu requirement of broilers, and the dietary Cu requirement was 11.30 mg/kg for broilers fed the conventional corn-soybean meal diet from 1 to 21 d of age, which is higher than the current National Research Council (NRC) Cu requirement (8 mg/kg) of broilers.

3.
Bioresour Technol ; 344(Pt B): 126264, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34737053

RESUMO

The complex structure of lignocellulosic biomass forms the recalcitrance to prevent the embedded holo-cellulosic sugars from undergoing the biodegradation. Therefore, a pretreatment is often required for an efficient enzymatic lignocellulosic hydrolysis. Recently, glycerol organosolv (GO) pretreatment is revealed potent in selective deconstruction of various lignocellulosic biomass and effective improvement of enzymatic hydrolysis. Evidently, the GO pretreatment is capable to modify the structure of dissolved components by glycerolysis, i.e., by trans-glycosylation onto glyceryl glycosides and by hydroxylation grafting onto glyceryl lignin. Such modifications tend to protect these main components against excessive degradation, which can be mainly responsible for the obviously less fermentation inhibitors arising in the GO pretreatment. This pretreatment can provide opportunities for valorization of emerging lignocellulosic biorefinery with production of value-added biochemicals. Recent advances in GO pretreatment of lignocellulosic biomass followed by enzymatic hydrolysis are reviewed, and perspectives are made for addressing remaining challenges.


Assuntos
Glicerol , Açúcares , Biomassa , Hidrólise , Lignina
4.
Exp Ther Med ; 23(2): 126, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34970349

RESUMO

Traumatic brain injury (TBI) has been recognized as a serious public health issue and a key contributor to disability and death, with a huge economic burden worldwide. Hydrogen, which is a slight and specific cytotoxic oxygen radical scavenger, has been demonstrated to ameliorate early brain injury (EBI) through reactive oxygen species (ROS), oxidative stress injury, apoptosis and necroptosis. Necroptosis refers to a type of programmed cell death process that has a vital function in neuronal cell death following TBI. The specific function of necroptosis in hydrogen-mediated neuroprotection after TBI, however, has yet to be determined. The present study aimed to examine the neuroprotective effects and possible molecular basis that underly hydrogen-rich saline in TBI-stimulated EBI by examining neural necroptosis in the C57BL/6 mouse model. The brain water content, neurological score, neuroinflammatory cytokines (NF-κΒ, TNF-α, IL-6 and IL-1ß) and ROS were evaluated using flow cytometry. Malondialdehyde, superoxide dismutase (SOD) and glutathione (GSH) levels were evaluated using a biochemical kit. Receptor-interacting protein kinase (RIP)1, RIP3, Nrf2 and Heme oxygenase-1 (HO-1) were evaluated using western blotting. mRNA of Nrf2 and HO-1 were evaluated using quantitative PCR. Neuronal death was evaluated by TUNEL staining. The outcomes illustrated that hydrogen-rich saline treatment considerably enhanced the neurological score, increased neuronal survival, decreased the levels of serum MDA and brain ROS, increased the levels of serum GSH and SOD. In addition the protein expression levels of RIP1 and RIP3 and the cytokines NF-κB, TNF-α, IL-1ß and IL-6 were downregulated compared with the TBI group, which demonstrated that hydrogen-rich saline-induced inhibition of necroptosis and neuroinflammation ameliorated neuronal death following TBI. The neuroprotective capacity of hydrogen-rich saline was demonstrated to be partly dependent on the ROS/heme oxygenase-1 signaling pathway. Taken together, the findings of the present study indicated that hydrogen-rich saline enhanced neurological outcomes in mice and minimized neuronal death by inducing protective effects against neural necroptosis as well as neuroinflammation.

5.
Chemosphere ; 286(Pt 3): 131754, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34399263

RESUMO

The problem of deep oxidation of low concentrations of VOCs in industrial tail gas is exceptionally urgent. The preparation of VOCs ozonation catalyst with a high mineralization rate is still a challenge. In this paper, manganese oxide carriers with different morphologies were synthesized by simple methods and used to catalyze ozone mineralization of toluene after loading Pt nanoparticles efficiently. The conversion of toluene over Pt/MnOx-T catalyst was more than 98 % at ambient temperature, and the mineralization rate of toluene was close to 100 % at 70 °C. Through a variety of characterization methods, the strong metal-support interaction (SMSI) between Pt nanoparticles and carriers was successfully constructed. It was found that SMSI successfully optimized the surface oxygen species and oxygen migration ability of the catalyst, and then realized the high degree of mineralization of toluene at low temperature. This paper guides the subsequent development of Pt-Mn catalysts for catalytic organic pollutants ozonation with high activity.


Assuntos
Ozônio , Tolueno , Catálise , Oxirredução , Oxigênio , Temperatura
6.
J Anim Sci Biotechnol ; 12(1): 117, 2021 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-34872591

RESUMO

BACKGROUND: Glucocorticoid receptor (GR) mediated corticosterone-induced fatty liver syndrome (FLS) in the chicken by transactivation of Fat mass and obesity associated gene (FTO), leading to demethylation of N6-methyladenosine (m6A) and post-transcriptional activation of lipogenic genes. Nutrition is considered the main cause of FLS in the modern poultry industry. Therefore, this study was aimed to investigate whether GR and m6A modification are involved in high-energy and low protein (HELP) diet-induced FLS in laying hens, and if true, what specific m6A sites of lipogenic genes are modified and how GR mediates m6A-dependent lipogenic gene activation in HELP diet-induced FLS in the chicken. RESULTS: Laying hens fed HELP diet exhibit excess (P < 0.05) lipid accumulation and lipogenic genes activation in the liver, which is associated with significantly increased (P < 0.05) GR expression that coincided with global m6A demethylation. Concurrently, the m6A demethylase FTO is upregulated (P < 0.05), whereas the m6A reader YTHDF2 is downregulated (P < 0.05) in the liver of FLS chickens. Further analysis identifies site-specific demethylation (P < 0.05) of m6A in the mRNA of lipogenic genes, including FASN, SREBP1 and SCD. Moreover, GR binding to the promoter of FTO gene is highly enriched (P < 0.05), while GR binding to the promoter of YTHDF2 gene is diminished (P < 0.05). CONCLUSIONS: These results implicate a possible role of GR-mediated transcriptional regulation of m6A metabolic genes on m6A-depenent post-transcriptional activation of lipogenic genes and shed new light in the molecular mechanism of FLS etiology in the chicken.

7.
Biochem Biophys Res Commun ; 589: 16-22, 2021 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-34883285

RESUMO

Gretchen Hagen 3 (GH3) amido synthetases conjugate amino acids to a carboxyl group of small molecules including hormones auxin, jasmonate, and salicylic acid. The Arabidopsis genome harbors 19 GH3 genes, whose exact roles in plant development have been difficult to define because of genetic redundancy among the GH3 genes. Here we use CRISPR/Cas9 gene editing technology to delete the Arabidopsis group II GH3 genes, which are able to conjugate indole-3-acetic acid (IAA) to amino acids. We show that plants lacking the eight group II GH3 genes (gh3 octuple mutants) accumulate free IAA and fail to produce IAA-Asp and IAA-Glu conjugates. Consequently, gh3 octuple mutants have extremely short roots, long and dense root hairs, and long hypocotyls. Our characterization of gh3 septuple mutants, which provide sensitized backgrounds, reveals that GH3.17 and GH3.9 play prominent roles in root elongation and seed production, respectively. We show that GH3 functions correlate with their expression patterns, suggesting that local deactivation of auxin also contributes to maintaining auxin homeostasis. Moreover, this work provides a method for elucidating functions of individual members of a gene family, whose members have overlapping functions.

8.
J Sep Sci ; 2021 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-34865311

RESUMO

Trace amounts of components in traditional Chinese medicine are considered as pharmacological active substance used for treating many serious diseases. However, to purify all the trace substances and make clear of their structures are not easy. In this context, a high performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry based molecular networking was applied to investigate the chemical constituents of the roots of Aconitum kusnezoffii Reichb., led to identification of thirty-three nodes in different groups (N1-N33). Based on excremental fragmentation pathway of known diterpenoid alkaloids (1-9) and comparisons of characteristic ions and characteristic loss of analogues in literature, the structures of unknown ions were deduced. This work lays a foundation for the evaluation of the clinical basis and mechanism of traditional Chinese medicine from the aspects of chemistry. In this paper, the method speculation unknown natural products by means of molecular network method is expected to be applied in the discovery and change law of relevant active components in clinical pharmacology and the change of complex system caused by trace active compounds. This article is protected by copyright. All rights reserved.

9.
J Nanobiotechnology ; 19(1): 416, 2021 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-34895262

RESUMO

BACKGROUND: Combining radiotherapy with PD1 blockade has had impressive antitumor effects in preclinical models of metastatic lung cancer, although anti-PD1 resistance remains problematic. Here, we report results from a triple-combination therapy in which NBTXR3, a clinically approved nanoparticle radioenhancer, is combined with high-dose radiation (HDXRT) to a primary tumor plus low-dose radiation (LDXRT) to a secondary tumor along with checkpoint blockade in a mouse model of anti-PD1-resistant metastatic lung cancer. METHODS: Mice were inoculated with 344SQR cells in the right legs on day 0 (primary tumor) and the left legs on day 3 (secondary tumor). Immune checkpoint inhibitors (ICIs), including anti-PD1 (200 µg) and anti-CTLA4 (100 µg) were given intraperitoneally. Primary tumors were injected with NBTXR3 on day 6 and irradiated with 12-Gy (HDXRT) on days 7, 8, and 9; secondary tumors were irradiated with 1-Gy (LDXRT) on days 12 and 13. The survivor mice at day 178 were rechallenged with 344SQR cells and tumor growth monitored thereafter. RESULTS: NBTXR3 + HDXRT + LDXRT + ICIs had significant antitumor effects against both primary and secondary tumors, improving the survival rate from 0 to 50%. Immune profiling of the secondary tumors revealed that NBTXR3 + HDXRT + LDXRT increased CD8 T-cell infiltration and decreased the number of regulatory T (Treg) cells. Finally, none of the re-challenged mice developed tumors, and they had higher percentages of CD4 memory T cells and CD4 and CD8 T cells in both blood and spleen relative to untreated mice. CONCLUSIONS: NBTXR3 nanoparticle in combination with radioimmunotherapy significantly improves anti-PD1 resistant lung tumor control via promoting antitumor immune response.

10.
Front Cell Dev Biol ; 9: 760369, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34926451

RESUMO

Background: Considering the heterogeneity and complexity of epigenetic regulation in bladder cancer, the underlying mechanisms of global DNA methylation modification in the immune microenvironment must be investigated to predict the prognosis outcomes and clinical response to immunotherapy. Methods: We systematically assessed the DNA methylation modes of 985 integrated bladder cancer samples with the unsupervised clustering algorithm. Subsequently, these DNA methylation modes were analyzed for their correlations with features of the immune microenvironment. The principal analysis algorithm was performed to calculate the DMRscores of each samples for qualification analysis. Findings: Three DNA methylation modes were revealed among 985 bladder cancer samples, and these modes are related to diverse clinical outcomes and several immune microenvironment phenotypes, e.g., immune-desert, immune-inflamed, and immune-excluded ones. Then patients were classified into high- and low-DMRscore subgroups according to the DMRscore, which was calculated based on the expression of DNA methylation related genes (DMRGs). Patients with the low-DMRscore subgroup presented a prominent survival advantage that was significantly correlated to the immune-inflamed phenotype. Further analysis revealed that patients with low DMRscores exhibited less TP53 wild mutation, lower cancer stage and molecular subtypes were mainly papillary subtypes. In addition, an independent immunotherapy cohort confirmed that DMRscore could serve as a signature to predict prognosis outcomes and immune responses. Conclusion: Global DNA methylation modes can be used to predict the immunophenotypes, aggressiveness, and immune responses of bladder cancer. DNA methylation status assessments will strengthen our insights into the features of the immune microenvironment and promote the development of more effective treatment strategies.

11.
Phys Rev Lett ; 127(24): 244501, 2021 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-34951813

RESUMO

An important and unresolved issue in rotating thermal turbulence is when the flow starts to feel the centrifugal effect. This onset problem is studied here by a novel experiment in which the centrifugal force can be varied over a wide range at fixed Rossby numbers by offsetting the apparatus from the rotation axis. Our experiment clearly shows that the centrifugal force starts to separate the hot and cold fluids at the onset Froude number 0.04. Additionally, this flow bifurcation leads to an unexpected heat transport enhancement and the existence of an optimal state. Based on the dynamical balance and characteristics of local flow structures, both the onset and optimal states are quantitatively explained.

12.
Artigo em Inglês | MEDLINE | ID: mdl-34911084

RESUMO

PURPOSE: To develop a simple and clinically useful assessment tool for osteoporosis in older women with type 2 diabetes mellitus (T2DM). METHODS: A total of 601 women over 60 years of age with T2DM were enrolled in this study. The levels of serum sex hormones and bone metabolism markers were compared between the osteoporosis and non-osteoporosis groups. The least absolute shrinkage and selection operator regularization (LASSO) model was applied to generate a risk assessment tool. The risk score formula was evaluated using receiver operating characteristic analysis and the relationship between the risk score and the bone mineral density (BMD) and T-value were investigated. RESULTS: Serum sex hormone-binding globulin (SHBG), cross-linked C-telopeptide of type 1 collagen (CTX), and osteocalcin (OC) were significantly higher in the osteoporosis group. After adjustment for age and body mass index (BMI), SHBG was found to be correlated with the T-value or BMD. Then, a risk score was specifically generated with age, BMI, SHBG, and CTX using the LASSO model. The risk score was significantly negatively correlated with the T-value and BMD of the lumbar spine, femoral neck, and total hip (all P<0.05). CONCLUSION: A risk score using age, BMI, SHBG, and CTX performs well for identifying osteoporosis in older women with T2DM.

13.
Chem Commun (Camb) ; 2021 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-34927631

RESUMO

Carbon dioxide (CO2) hydrogenation can not only mitigate global warming, but also produce value-added chemicals. Herein, we report a novel three-phase catalytic system with an in situ generated and dynamically updated thin water film covered on the noble-metal-free TiO2-based catalyst for highly efficient CO2 hydrogenation, realizing a four-time enhancement compared with that with the catalyst suspended in water. The water film plays dual roles by directly participating in the reaction and removing the produced oxygenates (mainly formic acid) from the catalyst surface by dissolution. These results demonstrate an effective design for CO2 hydrogenation, which will open a new door to three-phase catalysis.

14.
Front Cell Dev Biol ; 9: 726931, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34970539

RESUMO

Background: There has been a recent appreciation that some metabolic enzymes can profoundly influence the nature of the immune response produced in macrophages. However, the role of mitochondrial phosphoenolpyruvate carboxykinase (PCK2) in immune response remains unknown. This study aims to investigate the role of PCK2 in lipopolysaccharides (LPS)-induced activation in Kupffer cells. Methods: Inflammatory cytokines were determined by real-time quantitative reverse transcription-polymerase chain action (qRT-PCR) and flow cytometric analysis using a cytometric bead array. Western blotting and immunofluorescence staining were used to determine PCK2 expression and subcellular distribution under confocal laser microscopy. qRT-PCR, flow cytometry, and high-performance liquid chromatography (HPLC) were used to determine mitochondrial function. Pharmacological inhibition, knockdown, and overexpression of PCK2 were used to confirm its function. Co-immunoprecipitation (Co-IP) was performed to determine MAPK/NF-κB phosphorylation. Results: Inflammatory response was significantly increased in LPS-treated mice and Kupffer cells. During the inflammatory process, the protein level of PCK2 was significantly upregulated in Kupffer cells. Interestingly, the localization of PCK2 was mainly in cytosol rather than mitochondria after LPS stimulation. Gain-of-function and loss-of-function analyses found that PCK2 overexpression significantly upregulated the levels of inflammation markers, whereas PCK2 knockdown or inhibition significantly mitigated LPS-induced inflammatory response in Kupffer cells. Furthermore, PCK2 promoted protein phosphorylation of NF-κB and AKT/MAPK, the major signaling pathways, controlling inflammatory cascade activation. Conclusion: We identified a novel function of PCK2 in mediating LPS-induced inflammation and provided mechanistic insights into the regulation of inflammatory response in Kupffer cells. Therefore, PCK2 may serve as a novel therapeutic target for the regulation of Kupffer cells-mediated inflammatory responses.

15.
Nat Commun ; 12(1): 6845, 2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34824246

RESUMO

Maternal obesity (MO) predisposes offspring to obesity and metabolic disorders but little is known about the contribution of offspring brown adipose tissue (BAT). We find that MO impairs fetal BAT development, which persistently suppresses BAT thermogenesis and primes female offspring to metabolic dysfunction. In fetal BAT, MO enhances expression of Dio3, which encodes deiodinase 3 (D3) to catabolize triiodothyronine (T3), while a maternally imprinted long noncoding RNA, Dio3 antisense RNA (Dio3os), is inhibited, leading to intracellular T3 deficiency and suppression of BAT development. Gain and loss of function shows Dio3os reduces D3 content and enhances BAT thermogenesis, rendering female offspring resistant to high fat diet-induced obesity. Attributing to Dio3os inactivation, its promoter has higher DNA methylation in obese dam oocytes which persists in fetal and adult BAT, uncovering an oocyte origin of intergenerational obesity. Overall, our data uncover key features of Dio3os activation in BAT to prevent intergenerational obesity and metabolic dysfunctions.

16.
G3 (Bethesda) ; 2021 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-34792546

RESUMO

Rhinogobius similis is distributed in East and Southeast Asia. It is an amphidromous species found mostly in freshwater and sometimes brackish waters. We have obtained a high-resolution assembly of the R. similis genome using nanopore sequencing, high throughput chromosome conformation capture (Hi-C) and transcriptomic data. The assembled genome was 890.10 Mb in size and 40.15% in GC content. Including 1,373 contigs with contig N50 is 1.54 Mb, and scaffold N50 is 41.51 Mb. All of the 1,373 contigs were anchored on 22 pairs of chromosomes. The BUSCO evaluation score was 93.02% indicating high quality of genome assembly. The repeat sequences accounted for 34.92% of the whole genome, with Retroelements (30.13%), DNA transposons (1.64%), simple repeats (2.34%) and etc. A total of 31,089 protein-coding genes were predicted in the genome and functionally annotated using Maker, of those genes, 26,893 (86.50%) were found in InterProScan5. There were 1,910 gene families expanded in R. similis, 1,171 gene families contracted and 170 gene families rapidly evolving. We have compared one rapidly change gene family (PF05970) commonly found in four species (Boleophthalmus pectinirostris, Neogobius melanostomus, Periophthalmus magnuspinnatus and R. similis), which was found probably related to the lifespan of those species. During 400 Ka-10 Ka, the period of the Guxiang Ice Age, the population of R. similis decreased drastically, and then increased gradually following the last interglacial period. A high-resolution genome of R. similis should be useful to study taxonomy, biogeography, comparative genomics and adaptive evolution of the most speciose freshwater goby genus, Rhinogobius.

17.
FASEB J ; 35(12): e22045, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34797942

RESUMO

Directed base substitution with base editing technology enables efficient and programmable conversion of C:G or A:T base pairs to T:A or G:C in the genome. Although this technology has shown great potentials in a variety of basic research, off-target editing is among one of the biggest challenges toward its way to clinical application. Base editing tools, especially the tools converting C to T, caused unpredictable off-target editing throughout the genome, which raise the concern that long-term application of these tools would induce genomic instability or even tumorigenesis. To overcome this challenge, we designed an inducible base editing tool that was active only in the presence of a clinically safe chemical, rapamycin. In the guidance of structural information, we designed four split-human APOBEC3A (A3A) -BE3 base editors in which these A3A deaminase enzymes were split at sites that were opposite to the protein-nucleotide interface. We showed that by inducible deaminase reconstruction with a rapamycin responsible interaction system (FRB and FKBP); three out of four split-A3A-derived base editors showed robust inducible base editing. However, in the absence of rapamycin, their editing ability was dramatically inhibited. Among these split editors, splicing at Aa85 of A3A generated the most efficient inducible editing. In addition, compared to the full-length base editor, the splitting did not obviously alter the editing window and motif preference, but slightly increased the product purity. We also expanded this strategy to another frequently used cytosine deaminase, rat APOBEC1 (rA1), and observed a similar induction response. In summary, these results demonstrated the concept that splitting deaminases is a practicable method for timely controlling of base editing tools.

18.
Materials (Basel) ; 14(21)2021 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-34771798

RESUMO

Selective laser melting (SLM) is a promising additive manufacturing (AM) process for high-strength or high-manufacturing-cost metals such as Ti-6Al-4V widely applied in aeronautical industry components with high material waste or complex geometry. However, one of the main challenges of AM parts is the variability in fatigue properties. In this study, standard cyclic fatigue and monotonic tensile testing specimens were fabricated by SLM and subsequently heat treated using the standard heat treatment (HT) or hot isostatic pressing (HIP) methods. All the specimens were post-treated to relieve the residual stress and subsequently machined to the same surface finishing. These specimens were tested in the low-cycle fatigue (LCF) regime. The effects of post-process methods on the failure mechanisms were observed using scanning electron microscopy (SEM) and optical microscopy (OM) characterization methods. While the tensile test results showed that specimens with different post-process treatment methods have similar tensile strength, the LCF test revealed that no significant difference exists between HT and HIP specimens. Based on the results, critical factors influencing the LCF properties are discussed. Furthermore, a microstructure-based multistage fatigue model was employed to predict the LCF life. The results show good agreement with the experiment.

19.
Chemosphere ; : 132874, 2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34774613

RESUMO

The Co/Ni-MOFs@CS composite derived from Co/Ni bimetallic organic framework was synthesized and characterized. Compared with a single O3 system, the synergy between carbon sphere (CS) and metal organic frameworks (MOFs) improved the electron transfer efficiency and the formation rate of •OH. The coexistence of Co and Ni in various valence states might accelerate the cyclic process of Co(II)/Co(III) and Ni(II)/Ni(III), thereby improving the catalytic activity. Taking levofloxacin as a model pollutant, the mechanism of catalytic process was discussed, and the catalytic reaction was successfully applied to the removal of residual organics in bio-treated coking wastewater (BTCW). The removal rates of chemical oxygen demand (COD) and total organic carbon (TOC) in 60 min were 50.85%-53.71% and 39.98%-43.48%. From the perspective of UV absorption and 3D EEM, catalytic ozonation was more conducive to breaking the electronic protection of inert organic molecules such as heterocyclic compounds, and achieving higher efficiency of mineralization. It provides a new idea for catalytic ozonation technology of wastewater treatment in the future from theory, technology and application.

20.
Nat Commun ; 12(1): 6752, 2021 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-34811366

RESUMO

Inactivation of the phytohormone auxin plays important roles in plant development, and several enzymes have been implicated in auxin inactivation. In this study, we show that the predominant natural auxin, indole-3-acetic acid (IAA), is mainly inactivated via the GH3-ILR1-DAO pathway. IAA is first converted to IAA-amino acid conjugates by GH3 IAA-amidosynthetases. The IAA-amino acid conjugates IAA-aspartate (IAA-Asp) and IAA-glutamate (IAA-Glu) are storage forms of IAA and can be converted back to IAA by ILR1/ILL amidohydrolases. We further show that DAO1 dioxygenase irreversibly oxidizes IAA-Asp and IAA-Glu into 2-oxindole-3-acetic acid-aspartate (oxIAA-Asp) and oxIAA-Glu, which are subsequently hydrolyzed by ILR1 to release inactive oxIAA. This work established a complete pathway for the oxidative inactivation of auxin and defines the roles played by auxin homeostasis in plant development.

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