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1.
Med Gas Res ; 12(3): 107-112, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34854421

RESUMO

Medical effects of hydrogen have been reported in many studies. Due to difficulties in measuring hydrogen concentration in vivo after intake and high explosive risks of hydrogen, studies about dose-response relationships and tissue concentrations of hydrogen are few. Here, for the first time, we monitored real-time hydrogen concentrations in different tissues in rats including brain, liver, spleen, kidney, thigh muscle, inguinal white adipose tissue, and gonadal white adipose tissue after inhaling different concentrations of hydrogen (4%, 42%, and 67%) using an electrochemical sensor. Hydrogen concentrations in the same tissue showed a dose-dependent response. The equilibrium concentration values were highest in the brain and lowest in the thigh muscle. The saturation and desaturation curves changed more slowly in the thigh muscle and white adipose tissues than in other tissues. These results provide fundamental information for the selection of hydrogen dose applications in basic research and clinical trials. The experiments were approved by the Laboratory Animal Ethics Committee of Shandong First Medical University & Shandong Academy of Medical Sciences (No. 2020-1028) on March 18, 2020.

2.
Bioact Mater ; 9: 475-490, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34820584

RESUMO

Sensory nerves promote osteogenesis through the release of neuropeptides. However, the potential application and mechanism in which sensory nerves promote healing of bone defects in the presence of biomaterials remain elusive. The present study identified that new bone formation was more abundantly produced after implantation of silicified collagen scaffolds into defects created in the distal femur of rats. The wound sites were accompanied by extensive nerve innervation and angiogenesis. Sensory nerve dysfunction by capsaicin injection resulted in significant inhibition of silicon-induced osteogenesis in the aforementioned rodent model. Application of extracellular silicon in vitro induced axon outgrowth and increased expression of semaphorin 3 A (Sema3A) and semaphorin 4D (Sema4D) in the dorsal root ganglion (DRG), as detected by the upregulation of signaling molecules. Culture medium derived from silicon-stimulated DRG cells promoted proliferation and differentiation of bone marrow mesenchymal stem cells and endothelial progenitor cells. These effects were inhibited by the use of Sema3A neutralizing antibodies but not by Sema4D neutralizing antibodies. Knockdown of Sema3A in DRG blocked silicon-induced osteogenesis and angiogenesis almost completely in a femoral defect rat model, whereas overexpression of Sema3A promoted the silicon-induced phenomena. Activation of "mechanistic target of rapamycin" (mTOR) pathway and increase of Sema3A production were identified in the DRG of rats that were implanted with silicified collagen scaffolds. These findings support the role of silicon in inducing Sema3A production by sensory nerves, which, in turn, stimulates osteogenesis and angiogenesis. Taken together, silicon has therapeutic potential in orthopedic rehabilitation.

3.
New Phytol ; 233(1): 344-359, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34610140

RESUMO

High-temperature stress inhibits normal cellular processes and results in abnormal growth and development in plants. However, the mechanisms by which rice (Oryza sativa) copes with high temperature are not yet fully understood. In this study, we identified a rice high temperature enhanced lesion spots 1 (hes1) mutant, which displayed larger and more dense necrotic spots under high temperature conditions. HES1 encoded a UDP-N-acetylglucosamine pyrophosphorylase, which had UGPase enzymatic activity. RNA sequencing analysis showed that photosystem-related genes were differentially expressed in the hes1 mutant at different temperatures, indicating that HES1 plays essential roles in maintaining chloroplast function. HES1 expression was induced under high temperature conditions. Furthermore, loss-of-function of HES1 affected heat shock factor expression and its mutation exhibited greater vulnerability to high temperature. Several experiments revealed that higher accumulation of reactive oxygen species occurred in the hes1 mutant at high temperature. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and comet experiments indicated that the hes1 underwent more severe DNA damage at high temperature. The determination of chlorophyll content and chloroplast ultrastructure showed that more severe photosystem defects occurred in the hes1 mutant under high temperature conditions. This study reveals that HES1 plays a key role in adaptation to high-temperature stress in rice.

4.
Neural Regen Res ; 17(6): 1387-1392, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34782586

RESUMO

There is a lack of systematic research on the expression of internal control genes used for gene expression normalization in real-time reverse transcription polymerase chain reaction in spinal cord injury research. In this study, we used rat models of spinal cord hemisection to analyze the expression stability of 13 commonly applied reference genes: Actb, Ankrd27, CypA, Gapdh, Hprt1, Mrpl10, Pgk1, Rictor, Rn18s, Tbp, Ubc, Ubxn11, and Ywhaz. Our results show that the expression of Ankrd27, Ubc, and Tbp were stable after spinal cord injury, while Actb was the most unstable internal control gene. Ankrd27, Ubc, Tbp, and Actb were consequently used to investigate the effects of internal control genes with differing stabilities on the normalization of target gene expression. Target gene expression levels and changes over time were similar when Ankrd27, Ubc, and Tbp were used as internal controls but different when Actb was used as an internal control. We recommend that Ankrd27, Ubc, and Tbp are used as internal control genes for real-time reverse transcription polymerase chain reaction in spinal cord injury research. This study was approved by the Administration Committee of Experimental Animals, Jiangsu Province, China (approval No. 20180304-008) on March 4, 2018.

5.
Neural Regen Res ; 17(4): 875-880, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34472488

RESUMO

The neutrophil-to-lymphocyte ratio (NLR) is considered a robust prognostic biomarker for predicting patient survival outcomes in many diseases. However, it remains unclear whether it can be used as a biomarker for amyotrophic lateral sclerosis (ALS). To correlate NLR with disease progression and survival in sporadic ALS, 1030 patients with ALS between January 2012 and December 2018 were included in this study. These patients were assigned into three groups according to their NLR values: Group 1 (NLR < 2, n = 544 [52.8%]), Group 2 (NLR = 2-3, n = 314 [30.5%]), and Group 3 (NLR > 3, n = 172 [16.7%]). All patients were followed up until April 2020. Patients in Group 3 had a significantly older onset age, a lower score on the Revised ALS Functional Rating Scale, and rapidly progressing disease conditions. Furthermore, faster disease progression rates were associated with higher NLR values (odds ratio = 1.211, 95% confidence interval [CI]: 1.090-1.346, P < 0.001) after adjusting for other risk factors. Compared with Groups 1 and 2, the survival time in Group 3 was significantly shorter (log-rank P = 0.002). The NLR value was considered an independent parameter for the prediction of survival in ALS patients after normalizing for all other potential parameters (hazard ratio [HR] = 1.079, 95% CI: 1.016-1.146, P = 0.014). The effects on ALS survival remained significant when adjusted for treatment (HR = 1.074, 95% CI: 1.012-1.141, Ptrend = 0.019) or when considering the stratified NLR value (HR = 1.115, 95% CI: 1.009-1.232, Ptrend = 0.033). Thus, the NLR may help to predict the rate of disease progression and survival in patients with sporadic ALS. The study was approved by the Institutional Ethics Committee of West China Hospital of Sichuan University, China (approval No. 2015 (236)) on December 23, 2015.

6.
Neural Regen Res ; 17(4): 911-919, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34472493

RESUMO

Peripheral nerve injury repair requires a certain degree of cooperation between axon regeneration and Wallerian degeneration. Therefore, investigating how axon regeneration and degeneration work together to repair peripheral nerve injury may uncover the molecular mechanisms and signal cascades underlying peripheral nerve repair and provide potential strategies for improving the low axon regeneration capacity of the central nervous system. In this study, we applied weighted gene co-expression network analysis to identify differentially expressed genes in proximal and distal sciatic nerve segments from rats with sciatic nerve injury. We identified 31 and 15 co-expression modules from the proximal and distal sciatic nerve segments, respectively. Functional enrichment analysis revealed that the differentially expressed genes in proximal modules promoted regeneration, while the differentially expressed genes in distal modules promoted neurodegeneration. Next, we constructed hub gene networks for selected modules and identified a key hub gene, Kif22, which was up-regulated in both nerve segments. In vitro experiments confirmed that Kif22 knockdown inhibited proliferation and migration of Schwann cells by modulating the activity of the extracellular signal-regulated kinase signaling pathway. Collectively, our findings provide a comparative framework of gene modules that are co-expressed in injured proximal and distal sciatic nerve segments, and identify Kif22 as a potential therapeutic target for promoting peripheral nerve injury repair via Schwann cell proliferation and migration. All animal experiments were approved by the Institutional Animal Ethics Committee of Nantong University, China (approval No. S20210322-008) on March 22, 2021.

7.
Neural Regen Res ; 17(2): 386-394, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34269214

RESUMO

Transfer RNA (tRNA)-derived small RNAs (tsRNAs) are a recently established family of regulatory small non-coding RNAs that modulate diverse biological processes. Growing evidence indicates that tsRNAs are involved in neurological disorders and play a role in the pathogenesis of neurodegenerative disease. However, whether tsRNAs are involved in traumatic brain injury-induced secondary injury remains poorly understood. In this study, a mouse controlled cortical impact model of traumatic brain injury was established, and integrated tsRNA and messenger RNA (mRNA) transcriptome sequencing were used. The results revealed that 103 tsRNAs were differentially expressed in the mouse model of traumatic brain injury at 72 hours, of which 56 tsRNAs were upregulated and 47 tsRNAs were downregulated. Based on microRNA-like seed matching and Pearson correlation analysis, 57 differentially expressed tsRNA-mRNA interaction pairs were identified, including 29 tsRNAs and 26 mRNAs. Moreover, Gene Ontology annotation of target genes revealed that the significantly enriched terms were primarily associated with inflammation and synaptic function. Collectively, our findings suggest that tsRNAs may be associated with traumatic brain injury-induced secondary brain injury, and are thus a potential therapeutic target for traumatic brain injury. The study was approved by the Beijing Neurosurgical Institute Animal Care and Use Committee (approval No. 20190411) on April 11, 2019.

8.
Holist Nurs Pract ; 36(1): 37-45, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34783699

RESUMO

This qualitative study describes the psychological experience of patients hospitalized with COVID-19. These patients went through 3 psychological stages: extremely uncertainties during the initial diagnostic stage, complicated feelings of negativity during the treatment stage, and positive growth in the recovery stage. It is important for nurses to provide holistic care.


Assuntos
COVID-19 , Emoções , Humanos , Pesquisa Qualitativa , SARS-CoV-2
9.
Artigo em Inglês | MEDLINE | ID: mdl-34843988

RESUMO

LncRNA (long noncoding RNA) is often dysregulated in tumors especially hepatocellular carcinoma (HCC). However, the dysregulation mechanism of lncRNAs is largely unknown. Here, we showed that lncRNA lncAY expression was stimulated in HCC by either endogenous or exogenous sulfatide. Elevated lncAY promoted HCC cell migration or angiogenesis, whereas lncAY silence suppressed HCC cell migration and proliferation. Interestingly, the activity of lncAY gene promoter was enhanced by sulfatide. Then Myb and MEF2C were identified as the transcription factors responsible for the stimulation of lncAY promoter activity and transcription by sulfatide. Both Myb and MEF2C enrichment on lncAY promoter was further confirmed, and their occupancy on lncAY promoter was strengthened by sulfatide for Myb or MEF2C was acetylated. Mutant Myb-K456A exhibited reduced acetylation and weak stimulation for lncAY transcription. However, Myb mutation K456/503A prevented Myb from acetylation induced by sulfatide. The mutant Myb K456/503A further was unable to occupy lncAY promoter and enhance lncAY transcription. In conclusion, this study demonstrated lncAY transcription was abnormally upregulated by sulfatide in HCC through Myb/MEF2C to promote HCC progression.

10.
Front Plant Sci ; 12: 770736, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34804103

RESUMO

Nitrogen is essential for plant growth and yield, and it is, therefore, crucial to increase the nitrogen-use efficiency (NUE) of crop plants in fields. In this study, we measured four major low-nitrogen-induced growth response (LNGR) agronomic traits (i.e., plant height, tiller number, chlorophyll content, and leaf length) of the 225-rice-variety natural population from the Rice 3K Sequencing Project across normal nitrogen (NN) and low nitrogen (LN) environments. The LNGR phenotypic difference between NN and LN levels was used for gene analysis using a genome-wide association study (GWAS) combined with 111,205 single-nucleotide polymorphisms (SNPs) from the available sequenced data from the 3K project. We obtained a total of 56 significantly associated SNPs and 4 candidate genes for 4 LNGR traits. Some loci were located in the candidate regions, such as MYB61, OsOAT, and MOC2. To further study the role of candidate genes, we conducted haplotype analyses to identify the elite germplasms. Moreover, several other plausible candidate genes encoding LN-related or NUE proteins were worthy of mining. Our study provides novel insight into the genetic control of LNGR and further reveals some related novel haplotypes and potential genes with phenotypic variation in rice.

11.
Bioengineered ; 12(2): 11041-11056, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34802380

RESUMO

Cisplatin-induced acute kidney injury (CP-AKI) is a severe complication in patients receiving CP chemotherapy. However, effective therapies for CP-AKI are currently lacking. Curcumin (CUR), a natural polyphenol, is extracted from the rhizome of turmeric and has been reported to have nephroprotective activity. However, the role of CUR in CP-AKI remains unclear. This study aimed to explore the mechanism of CUR in CP-AKI by combining a network pharmacology approach with experimental validations. The analysis revealed 176 potential targets of CUR based on the HERB database and 1,286 related targets of CP-AKI from the GeneCards, DrugBank, and OMIM databases. Further, 106 common targets of CUR against CP-AKI were obtained, and these common targets constructed a protein-protein interaction (PPI) network. In addition, the core targets were screened from the PPI network using Cytoscape. Molecular docking revealed that CUR displayed the best binding to AKT1. Gene Ontology (GO) analysis indicated that the primary biological processes of CUR against CP-AKI included cellular response to chemical stress and apoptotic regulation. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis suggested that the PI3K-Akt signaling pathway was most significantly enriched in CUR against CP-AKI. Western blotting and flow cytometry showed that CUR inhibited apoptosis induced by CP by activating the Akt signaling pathway in human kidney tubular epithelial cells (HK-2). Altogether, our findings demonstrated that CUR alleviated apoptosis by activating the Akt signaling pathway in CP-AKI in vitro. These data provide a scientific basis for future investigations into the clinical application of CUR against CP-AKI.

12.
J Agric Food Chem ; 69(46): 13831-13837, 2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34751575

RESUMO

The sesquiterpene α-humulene has been shown to have anti-inflammatory and anticancer activities, which has led to its vast application potential in medicine. However, α-humulene production methods including phytoextraction and chemical synthesis currently were limited to low yield, high costs, and expensive catalysts, which cannot meet the increasing market demand. In this study, Yarrowia lipolytica was developed as a robust cell factory for α-humulene production. The peroxisome in Y. lipolytica was first engineered to boost the synthesis of the sesquiterpene α-humulene. By compartmentalization of the α-humulene biosynthesis pathway, improving ATP and acetyl-CoA supply, and optimizing the gene copy numbers of rate-limiting enzymes, the engineered strain GQ2012 could produce 3.2 g/L α-humulene in a 5 L bioreactor, the highest α-humulene titer reported so far. Our study provides a valuable reference for highly sustainable production of terpenoids by peroxisome engineering in Y. lipolytica.


Assuntos
Yarrowia , Engenharia Metabólica , Sesquiterpenos Monocíclicos , Peroxissomos , Yarrowia/genética
14.
Front Neurosci ; 15: 749949, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34764851

RESUMO

Objective: Vascular risk factors have been reported to be associated with cognitive impairment (CI) in the general population, but their role on CI in multiple system atrophy (MSA) is unclear. This study aimed to explore the relationship between vascular risk factors and CI in patients with MSA. Methods: The clinical data and vascular risk factors were collected. The Montreal Cognitive Assessment tool was used to test the cognitive function of patients with MSA. Binary logistic regression was used to analyze the correlation between vascular risk factors and CI. Results: A total of 658 patients with MSA with a mean disease duration of 2.55 ± 1.47 years were enrolled. In MSA patients, hypertension was recorded in 20.2%, diabetes mellitus in 10.3%, hyperlipidemia in 10.2%, smoking in 41.2%, drinking in 34.8%, and obesity in 9.6%. The prevalence of CI in patients with MSA, MSA with predominant parkinsonism (MSA-P), and MSA with predominant cerebellar ataxia (MSA-C) was 45.0, 45.1, and 44.9%, respectively. In the binary logistic regression model, patients with more than one vascular risk factors were significantly more likely to have CI in MSA (OR = 4.298, 95% CI 1.456-12.691, P = 0.008) and MSA-P (OR = 6.952, 95% CI 1.390-34.774, P = 0.018), after adjusting for age, sex, educational years, disease duration, and total Unified multiple system atrophy rating scale scores. Conclusion: Multiple vascular risk factors had a cumulative impact on CI in MSA. Therefore, the comprehensive management of vascular risk factors in MSA should not be neglected.

15.
Org Lett ; 23(23): 9151-9156, 2021 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-34780172

RESUMO

A cooperative Rh(II)/Pd(0) dual-catalysis strategy that promotes a cyclization/allylic alkylation cascade of stable α-diazo-δ-keto-esters has been developed. Highly substituted 3(2H)-furanones with a C2-quaternary center can be obtained efficiently under mild conditions via one-pot synthesis. Remarkably, this binary catalytic system shows high chemo-, regio-, and stereoselectivity and excellent tolerance to various functionalities.

16.
Microorganisms ; 9(11)2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34835430

RESUMO

Lipid metabolism plays an important role in the energy economy of ruminants. However, its interactions of fat, rumen fermentation, gas emission, and microorganisms are not yet clear. This study evaluated the effect of adding raw oilseeds to high-forage diets on in vitro ruminal fermentation, gas composition, and microbial profile. Three isoenergetic and isoproteic experimental diets were designed and used as fermentation substrate: control treatment (CON group) was the basal diet lacking oilseeds, the other two treatments were the basal diet supplemented by 100 g/kg dry matter (DM) raw whole soybean (S group) and 50 g/kg DM raw flaxseed (F group), respectively. Data showed that the acetate, butyrate, and total VFA concentration of culture fluids in the S group were lower (p < 0.05) than in the F group. There was a tendency to a higher level (p = 0.094) of propionate concentration in the F group compared with the other two groups. The gas production in the F group was higher (p < 0.05) than in the control group. There was a lower abundance of Sutterella (p < 0.05) and a greater abundance of Butyrivibrio (p < 0.05) in both of the two oilseed treatments. Methanobrevibacter (p = 0.078) in the F group was the lowest. Our results suggested that CH4 emission could be inhibited with flaxseed supplementation by propionate production metabolism, biohydrogenation of unsaturated fatty acid (FA), and toxicity to Methanobrevibacter, while regarding soybean seed supplementation, the emission of CH4 was more likely to be reduced through biohydrogenation of unsaturated FA modulated by Butyrivibrio.

17.
Hum Vaccin Immunother ; : 1-10, 2021 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-34726580

RESUMO

The universal administration of pneumococcal conjugate vaccines (PCVs) had been demonstrated as an effective way to prevent Streptococcus pneumoniae infection. However, the immunity induced by PCVs protected against the infections caused by vaccine serotypes, which were usually more frequent than non-vaccine serotypes (NVTs). The prevalence and pathogenicity of NVTs after universal vaccination have caused widespread concern. We reviewed the epidemiology of non-PCV13 S. pneumoniae before and after PCV13 introduction, and explored the potential reasons for the spread of NVTs. Emerging and spreading NVTs can be regarded as the focus for future serotype epidemiological survey and vaccine optimization.AbbreviationsIPD: invasive pneumococcal disease PCV: pneumococcal conjugate vaccines VT: vaccine serotypeNVT: non-vaccine serotype.

18.
J Integr Plant Biol ; 2021 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-34726825

RESUMO

Root architecture is one of the most important agronomic traits that determines rice crop yield. The primary root (PR) absorbs mineral nutrients and provides mechanical support; however, the molecular mechanisms of PR elongation remain unclear in rice. Here, the two loss-of-function T-DNA insertion mutants of root length regulator 4 (OsRLR4), osrlr4-1 and osrlr4-2 with longer PR, and three OsRLR4 overexpression lines, OE-OsRLR4-1/-2/-3 with shorter PR compared to the wild type, Hwayoung (WT/HY), were identified. OsRLR4 is one of five members of the PRAF subfamily of the regulator chromosome condensation 1 (RCC1) family. Phylogenetic analysis of OsRLR4 from wild and cultivated rice indicated that it is under selective sweeps, suggesting its potential role in domestication. OsRLR4 controls PR development by regulating auxin accumulation in the PR tip and thus the root apical meristem activity. A series of biochemical and genetic analyses demonstrated that OsRLR4 functions directly upstream of the auxin transporter OsAUX1. Moreover, OsRLR4 interacts with the TRITHORAX-like protein OsTrx1 to promote H3K4me3 deposition at the OsAUX1 promoter, thus altering its transcription level. This work provides insight into the cooperation of auxin and epigenetic modifications in regulating root architecture and provides a genetic resource for plant architecture breeding. This article is protected by copyright. All rights reserved.

19.
J Anesth ; 2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34757497

RESUMO

Low tidal volume ventilation strategy may lead to atelectasis without proper positive end-expiratory pressure (PEEP) and recruitment maneuver (RM) settings. RM followed by individualized PEEP was a new method to optimize the intraoperative pulmonary function. We conducted a systematic review and network meta-analysis of randomized clinical trials to compare the effects of individualized PEEP + RM on intraoperative pulmonary function and hemodynamic with other PEEP and RM settings. The primary outcomes were intraoperative oxygenation index and dynamic compliance, while the secondary outcomes were intraoperative heart rate and mean arterial pressure. In total, we identified 15 clinical trials containing 36 randomized groups with 3634 participants. Ventilation strategies were divided into eight groups by four PEEP (L: low, M: moderate, H: high, and I: individualized) and two RM (yes or no) settings. The main results showed that IPEEP + RM group was superior to all other groups regarding to both oxygenation index and dynamic compliance. LPEEP group was inferior to LPEEP + RM, MPEEP, MPEEP + RM, and IPEEP + RM in terms of oxygenation index and LPEEP + RM, MPEEP, MPEEP + RM, HPEEP + RM, IPEEP, and IPEEP + RM in terms of dynamic compliance. All comparisons were similar for secondary outcomes. Our analysis suggested that individualized PEEP and RM may be the optimal low tidal volume ventilation strategy at present, while low PEEP without RM is not suggested.

20.
Cell Rep ; 37(7): 110007, 2021 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-34788619

RESUMO

CCR4-NOT deadenylase is a major regulator of mRNA turnover. It contains two heterogeneous catalytic subunits CNOT7/8 and CNOT6/6L in vertebrates. The physiological function of each catalytic subunit is unclear due to the gene redundancy. In this study, Cnot6/6l double knockout mice are generated. Cnot6l-/- female mice are infertile, with poor ovarian responses to gonadotropins. Follicle-stimulating hormone (FSH) stimulates the transcription and translation of Cnot6 and Cnot6l in ovarian granulosa cells. CNOT6/6L function as key effectors of FSH in granulosa cells and trigger the clearance of specific transcripts in granulosa cells during preantral to antral follicle transition. These results demonstrate that FSH modulates granulosa cell function by stimulating selective translational activation and degradation of existing mRNAs, in addition to inducing de novo gene transcription. Meanwhile, this study provides in vivo evidence that CNOT6/6L-mediated mRNA deadenylation is dispensable in most somatic cell types, but is essential for female reproductive endocrine regulation.

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