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1.
Sci Total Environ ; 802: 149812, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34455275

RESUMO

While ubiquitous natural organic matters (NOMs) are capable of enhancing zero-valent iron (ZVI) performance under aerobic conditions, there is limited understanding of how the properties of NOMs affect the reactivity of ZVI towards contaminants removal. Here, the corresponding activity of ZVI under aerobic conditions was investigated in the presence of humic acid (HA), fulvic acid (FA), bovine serum albumin (BSA). It was found that three models of NOMs were all effective in promoting diatrizoate (DTA) reduction via depassivating ZVI. Interestingly, fast adsorption of NOM onto ZVI surface initially caused inconspicuous impact or visible inhibition on hydrophilic DTA reduction depending on their hydrophobicity. However, subsequent exposure of more reactive sites with high hydrophilicity arising from the detachment of surfaced NOM-associated iron oxide finally contributed to the enhanced consumption of Fe0 with the ability: HA > FA ≈ BSA, and 1-2 times increase in DTA removal kinetic rate following the order: HA > FA > BSA. It further revealed that there were two key factors in determining DTA removal under aerobic conditions, including the ability of NOMs to boost Fe0 consumption as contributed by their aromaticity degree and amino groups, and the hydrophobicity of NOMs to initially affect the property of ZVI surfaces.


Assuntos
Poluentes Ambientais , Poluentes Químicos da Água , Adsorção , Substâncias Húmicas/análise , Ferro , Poluentes Químicos da Água/análise
2.
J Hazard Mater ; : 127828, 2021 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-34815121

RESUMO

Visible light catalysis has been widely coupled with persulfate activation for refractory pollutants removal, while the exact role of persulfate played in such composite system is still questionable. In this work, the relation between peroxymonosulfate (PMS) induced structure change and visible light responsive activity of inverse spinel: i.e., Zn2SnO4, was deciphered. Under the visible light illumination (λ> 420nm) PMS addition would endow the composite system with pollutant removal performance. Batch test revealed that 60% of bisphenol-A (5 mg L-1) was mineralized within 3 h reaction time, by dosing 0.81 mM PMS and 0.1 g L-1 catalyst. The above oxidative system was also effective for other refractory pollutants elimination. Further analysis indicated that PMS could reduce the band gap of spinel from 2.75 to 2.52 eV and thereby enabling its visible light activity. Photogenerated h+ induced •OH and e- mediated •O2- contributed to the pollutant removal while h+ played a leading role. Density functional theory revealed that PMS would capture oxygen atom of spinel and induce surface oxygen vacancy defect structure formation. Also, three-oxygen atom coordinated Zn was identified as the possible catalyze site. This work is valuable for deep understanding the exact role of persulfate in photocatalytic system.

3.
J Clin Invest ; 131(21)2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34720089

RESUMO

Evasion of the immune response is a hallmark of cancer, and programmed cell death 1 (PD-1) and PD-1 ligand 1 (PD-L1) are major mediators of this immunosuppression. Chitinase 3-like 1 (CHI3L1) is induced in many cancers, where it portends a poor prognosis and contributes to tumor metastasis and spread. However, the mechanism(s) that CHI3L1 uses in metastasis have not been defined. Here we demonstrate that CHI3L1 regulates the expression of PD-L1, PD-L2, PD-1, LAG3, and TIM3 and plays a critical role in melanoma progression and lymphatic spread. CHI3L1 also contributed to IFN-γ-stimulated macrophage PD-L1 expression, and RIG-like helicase innate immunity suppressed CHI3L1, PD-L1, and melanoma progression. Individual antibodies against CHI3L1 or PD-1 had discrete antitumor effects and additive antitumor responses in metastasis models and T cell-tumor cell cocultures when administered simultaneously. Synergistic cytotoxic tumor cell death was seen in T cell-tumor cell cocultures, and significantly enhanced antitumor responses were seen in in vivo tumor models treated with bispecific antibodies that simultaneously target CHI3L1 and PD-1. CHI3L1 contributes to tumor progression by stimulating the PD-1/PD-L1 axis and other checkpoint molecules. The simultaneous targeting of CHI3L1 and the PD-1/PD-L1 axis with individual and, more powerfully, with bispecific antibodies represents a promising therapy for pulmonary metastasis and progression.

4.
JCI Insight ; 6(21)2021 11 08.
Artigo em Inglês | MEDLINE | ID: mdl-34747367

RESUMO

COVID-19 is caused by SARS-CoV-2 (SC2) and is more prevalent and severe in elderly and patients with comorbid diseases (CM). Because chitinase 3-like-1 (CHI3L1) is induced during aging and CM, the relationships between CHI3L1 and SC2 were investigated. Here, we demonstrate that CHI3L1 is a potent stimulator of the SC2 receptor angiotensin converting enzyme 2 (ACE2) and viral spike protein priming proteases (SPP), that ACE2 and SPP are induced during aging, and that anti-CHI3L1, kasugamycin, and inhibitors of phosphorylation abrogate these ACE2- and SPP-inductive events. Human studies also demonstrate that the levels of circulating CHI3L1 are increased in the elderly and patients with CM, where they correlate with COVID-19 severity. These studies demonstrate that CHI3L1 is a potent stimulator of ACE2 and SPP, that this induction is a major mechanism contributing to the effects of aging during SC2 infection, and that CHI3L1 co-opts the CHI3L1 axis to augment SC2 infection. CHI3L1 plays a critical role in the pathogenesis of and is an attractive therapeutic target in COVID-19.


Assuntos
Envelhecimento , COVID-19/metabolismo , Proteína 1 Semelhante à Quitinase-3/metabolismo , Envelhecimento/efeitos dos fármacos , Aminoglicosídeos/farmacologia , Aminoglicosídeos/uso terapêutico , Enzima de Conversão de Angiotensina 2/metabolismo , COVID-19/tratamento farmacológico , Linhagem Celular Tumoral , Proteína 1 Semelhante à Quitinase-3/antagonistas & inibidores , Células HEK293 , Humanos , SARS-CoV-2/fisiologia
5.
Artigo em Inglês | MEDLINE | ID: mdl-34781406

RESUMO

OBJECTIVE: Blood blister-like aneurysms (BBAs) of the internal carotid artery (ICA) are challenging to treat. We assessed the clinical and radiologic outcomes in patients with ruptured BBAs of the ICA treated with wrap-clipping. METHODS: From November 2016 to January 2020, the clinical and radiologic data of patients with subarachnoid hemorrhage (SAH) caused by ICA BBAs who underwent wrap-clipping were retrospectively analyzed. The clinical outcomes were evaluated according to the modified Rankin Scale (mRS). Radiologic follow-up examinations included digital subtraction angiography (DSA), computed tomography angiography (CTA), and magnetic resonance angiography (MRA). RESULTS: Seven patients were enrolled in this study. All BBAs were wrap-clipped successfully, including two BBAs that exhibited intraoperative bleeding and required balloon-assistance during surgery. All patients had favorable clinical outcomes during follow-up. Among the six patients who completed the radiologic follow-up visit, one patient presented ICA occlusion at the 6-month DSA follow-up, but no neurologic dysfunction was noted. We did not observe the progression of ICA stenosis in other patients. CONCLUSION: All BBAs in this study were wrap-clipped successfully and completely occluded. Wrap-clipping is effective for BBAs of the ICA and has favorable clinical outcomes. A multicenter study with a large sample size and a longer radiologic follow-up is necessary.

6.
Transl Neurosci ; 12(1): 335-345, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34594577

RESUMO

Alzheimer's disease (AD) is a common dementia and a heterogeneous disease. Previous research has validated that microRNAs (miRNAs) are pivotal regulators in the initiation and development of tremendous diseases including AD. MicroRNA-485-5p (miR-485-5p) was reported to be an important participant implicated in several neurological diseases, but its role in AD still needs to be further investigated. In this research, we explored the biological function of miR-485-5p in AD. RT-qPCR revealed that miR-485-5p expression was downregulated in the hippocampus of APP/PS1 mice. Additionally, miR-485-5p overexpression facilitated the learning and memory capabilities of APP/PS1 mice according to Morris water maze test, fear conditioning test, and immunofluorescent staining. Moreover, CCK-8 assay, flow cytometric analysis, and western blot analysis suggested that miR-485-5p overexpression promoted pericyte viability and prohibited pericyte apoptosis in APP/PS1 mice. Mechanistically, miR-485-5p directly targeted PACS1 in pericytes, as shown in a luciferase reporter assay. In rescue assays, PACS1 overexpression countervailed the effect of miR-485-5p overexpression on pericyte viability and apoptosis. In conclusion, miR-485-5p ameliorates AD progression by targeting PACS1.

7.
Mol Neurodegener ; 16(1): 70, 2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34593014

RESUMO

BACKGROUND: N6-methyladenosine (m6A) modification of RNA influences fundamental aspects of RNA metabolism and m6A dysregulation is implicated in various human diseases. In this study, we explored the potential role of RNA m6A modification in the pathogenesis of Alzheimer disease (AD). METHODS: We investigated the m6A modification and the expression of m6A regulators in the brain tissues of AD patients and determined the impact and underlying mechanism of manipulated expression of m6A levels on AD-related deficits both in vitro and in vivo. RESULTS: We found decreased neuronal m6A levels along with significantly reduced expression of m6A methyltransferase like 3 (METTL3) in AD brains. Interestingly, reduced neuronal m6A modification in the hippocampus caused by METTL3 knockdown led to significant memory deficits, accompanied by extensive synaptic loss and neuronal death along with multiple AD-related cellular alterations including oxidative stress and aberrant cell cycle events in vivo. Inhibition of oxidative stress or cell cycle alleviated shMettl3-induced apoptotic activation and neuronal damage in primary neurons. Restored m6A modification by inhibiting its demethylation in vitro rescued abnormal cell cycle events, neuronal deficits and death induced by METTL3 knockdown. Soluble Aß oligomers caused reduced METTL3 expression and METTL3 knockdown exacerbated while METTL3 overexpression rescued Aß-induced synaptic PSD95 loss in vitro. Importantly, METTL3 overexpression rescued Aß-induced synaptic damage and cognitive impairment in vivo. CONCLUSIONS: Collectively, these data suggested that METTL3 reduction-mediated m6A dysregulation likely contributes to neurodegeneration in AD which may be a therapeutic target for AD.

8.
Artigo em Inglês | MEDLINE | ID: mdl-34672813

RESUMO

Background: Cell division cycle 45 (CDC45) plays an important role in the occurrence and development of numerous carcinomas, but its effect in laryngeal squamous cell carcinoma (LSCC) remains unclear. Materials and Methods: The messenger RNA and protein expression levels of CDC45 in LSCC were evaluated with a t test and the standard mean difference (SMD). The ability of CDC45 expression to distinguish the LSCC was assessed through receiver operating characteristic (ROC) curves. Gene set enrichment analysis (GSEA), protein-protein interaction, public databases, and online tools were used to explore the potential molecular mechanism of CDC45 in LSCC. Results: A high expression of CDC45 was identified in LSCC (SMD = 2.61, 95% confidence interval [1.62-3.61]). Through ROC curves, the expression of CDC45 makes it feasible to distinguish the LSCC group from the non-LSCC counterpart. CDC45 was relevant to the progression-free interval of LSCC patients (log-rank p = 0.03). GSEAs show that CDC45 is related to the cell cycle. CDC45, CDC6, KIF2C, and AURKB were identified as hub genes of LSCC. E2F1 may be the regulatory transcription factor of CDC45. Conclusions: High expression of CDC45 likely demonstrates carcinogenic effects in LSCC, and CDC45 is a potential target in screening and treatment of LSCC.

9.
Br J Cancer ; 2021 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-34675398

RESUMO

BACKGROUND: While emerging evidence indicates that N6-methyladenosine (m6A) regulators play crucial roles in cancer progression, their clinical significance in gastric cancer (GC) has thus far not been elucidated. METHODS: We investigated the expression of the m6A regulator genes and their prognostic potential in a large clinical cohort of 173 GC patients using qRT-PCR assays. In addition, we undertook a series of in-vitro and in-vivo functional studies to investigate the oncogenic role of FTO. RESULTS: GC patients with low expression of METTL3, METTL14, ALKBH5, WTAP and YTHDF1 demonstrated significantly poor OS, while patients with high FTO expression exhibited markedly worse OS. Furthermore, the cumulative risk-score derived from these gene panel also significantly associated with poor OS, with a corresponding hazard ratio of 5.47 (95% CI: 3.18-9.41, p < 0.0001). We observed that FTO expression was frequently upregulated in GC cell lines, with epithelial-mesenchymal-transition (EMT) features. FTO knockdown in HGC27 and AGS cells inhibited cell proliferation and migratory potential, while its overexpression in MKN28 cells resulted in enhanced proliferation and migration. Finally, confirming our in-vitro findings, FTO suppression led to significant tumour growth inhibition in a HGC27 xenograft model. CONCLUSIONS: We demonstrate that m6A regulators may serve as promising prognostic biomarkers in GC. Our functional studies reveal that FTO is an important oncogene and may be a promising therapeutic target associated with EMT-alterations in gastric cancer.

10.
Mol Cell ; 81(20): 4228-4242.e8, 2021 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-34686315

RESUMO

Central to genotoxic responses is their ability to sense highly specific signals to activate the appropriate repair response. We previously reported that the activation of the ASCC-ALKBH3 repair pathway is exquisitely specific to alkylation damage in human cells. Yet the mechanistic basis for the selectivity of this pathway was not immediately obvious. Here, we demonstrate that RNA but not DNA alkylation is the initiating signal for this process. Aberrantly methylated RNA is sufficient to recruit ASCC, while an RNA dealkylase suppresses ASCC recruitment during chemical alkylation. In turn, recruitment of ASCC during alkylation damage, which is mediated by the E3 ubiquitin ligase RNF113A, suppresses transcription and R-loop formation. We further show that alkylated pre-mRNA is sufficient to activate RNF113A E3 ligase in vitro in a manner dependent on its RNA binding Zn-finger domain. Together, our work identifies an unexpected role for RNA damage in eliciting a specific response to genotoxins.

11.
Am J Pathol ; 2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34599880

RESUMO

N6-methyladenosine (m6A), the most abundant internal modifier of mRNAs that is installed by the methyltransferase 13 (METTL3) at the (G/A)(m6A)C motif, plays a critical role in gene expression regulation. METTL3 is essential for embryonic development, and its dysregulation is linked to various diseases. However, the role of METTL3 in liver biology is largely unknown. In this study, METTL3 function was unraveled in mice depleted of Mettl3 in neonatal livers (Mettl3fl/fl; Alb-Cre). Liver-specific Mettl3 knockout (M3LKO) mice exhibited global decrease in m6A on polyadenylated RNAs and pathologic features associated with nonalcoholic fatty liver disease (eg, hepatocyte ballooning, ductular reaction, microsteatosis, pleomorphic nuclei, DNA damage, foci of altered hepatocytes, focal lobular and portal inflammation, and elevated serum alanine transaminase/alkaline phosphatase levels). Mettl3-depleted hepatocytes were highly proliferative, with decreased numbers of binucleate hepatocytes and increased nuclear polyploidy. M3LKO livers were characterized by reduced m6A and expression of several key metabolic transcripts regulated by circadian rhythm and decreased nuclear protein levels of the core clock transcription factors BMAL1 and CLOCK. A significant decrease in total Bmal1 and Clock mRNAs but an increase in their nuclear levels were observed in M3LKO livers, suggesting impaired nuclear export. Consistent with the phenotype, methylated (m6A) RNA immunoprecipitation coupled with sequencing -and RNA sequencing revealed transcriptome-wide loss of m6A markers and alterations in abundance of mRNAs involved in metabolism in M3LKO. Collectively, METTL3 and m6A modifications are critical regulators of liver homeostasis and function.

12.
Neural Plast ; 2021: 4430594, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34616448

RESUMO

Background: In recent years, a growing number of researchers showed significant interest in psychological and social interventions to manage chronic musculoskeletal (MSK) pain. Cognitive and emotional empathy is an attractive and valuable sociopsychological factor that may provide protection and resilience against chronic MSK pain. However, its effect on outpatients remains underexplored. Objective: To compare the empathy ability between chronic MSK pain outpatients and healthy controls and explore the relationship between cognitive/emotional empathy and chronic pain. Methods: Patients with chronic MSK pain (n = 22) and healthy controls (n = 26) completed the pain assessment and empathy ability task, utilizing a multidimensional empathy assessment tool with satisfactory reliability and validity (i.e., the Chinese version of the Multifaceted Empathy Test (MET-C)). Results: The data indicated that the chronic MSK pain outpatients had impaired cognitive empathy (i.e., lower squared cognitive empathy accuracy: Student's t = -2.119, P = 0.040, and longer task completion time: Student's t = 3.382, P = 0.002) compared to healthy controls, and cognitive empathy was negatively correlated with pain intensity (r = -0.614, P = 0.002). Further, the impaired cognitive empathy was present in identifying positive, but not negative emotions. Conclusion: These results indicate that chronic MSK pain is associated with impaired empathy ability. Our studies contribute to offering a potential direction for developing psychosocial interventions to treat chronic MSK pain.

13.
Artigo em Inglês | MEDLINE | ID: mdl-34499595

RESUMO

A novel cellulase-producing actinomycete, designated strain NEAU-H7T, was isolated from coconut palm rhizosphere soil collected from Wenchang City, Hainan Province, PR China. A polyphasic taxonomic study was carried out to establish the status of this strain. Results of 16S rRNA gene sequence analysis indicated that strain NEAU-H7T belonged to the genus Actinoplanes, with highest similarity to Actinoplanes hulinensis NEAU-M9T (99.2 % 16S rRNA gene sequence similarity). The diagnostic sugars in cell hydrolysates were determined to be ribose, galactose and mannose. The major fatty acids (>10%) were C16 : 0, C18 : 1 ω9c and C18 : 0. The predominant menaquinones were identified as MK-9(H4) and MK-9(H6). The major polar lipids were phosphatidylethanolamine, phosphatidylinositol and two phosphatidylinositol mannosides. The amino acid of the cell-wall peptidoglycan was determined to be meso-diaminopimelic acid. The DNA G+C content was 71.2 mol%. Phylogenetic analysis using 16S rRNA gene sequences showed that strain NEAU-H7T formed a stable phyletic line with A. hulinensis NEAU-M9T. However, whole-genome phylogeny showed strain NEAU-H7T formed a stable phyletic line with A. hulinensis NEAU-M9T (99.2%), Actinoplanes campanulatus DSM 43148T (98.6%), Actinoplanes capillaceus DSM 44859T (98.3%) and Actinoplanes lobatus DSM 43150T (97.6%). The digital DNA-DNA hybridization (dDDH) results between them were 53.6 (50.9-56.2), 54.1 (51.3-56.9), 53.1 (50.3-55.9) and 52.9 % (50.1-55.6 %), and whole-genome average nucleotide identity (ANI) values between them were 93.7, 93.6, 93.5 and 93.5 %. The low dDDH and ANI values demonstrated that strain NEAU-H7T could be distinguished from its reference strains. Moreover, genomic analysis indicated that the strain NEAU-H7T had the potential to decompose cellulose and produce bioactive compounds. On the basis of morphological, chemotaxonomic and phylogenetic characteristics, strain NEAU-H7T is proposed to represent a novel species of the genus Actinoplanes, with the name Actinoplanes flavus sp. nov. The type strain is NEAU-H7T (=CCTCC AA 2020034T=DSM 112042T).


Assuntos
Actinoplanes , Cocos/microbiologia , Filogenia , Rizosfera , Microbiologia do Solo , Actinoplanes/classificação , Actinoplanes/isolamento & purificação , Técnicas de Tipagem Bacteriana , Composição de Bases , Celulase , China , DNA Bacteriano/genética , Ácidos Graxos/química , Fosfolipídeos/química , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Vitamina K 2/análogos & derivados , Vitamina K 2/química
14.
Chem Sci ; 12(33): 10972-10984, 2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34522294

RESUMO

Transition-metal-catalyzed enantioselective C-H functionalization has emerged as a powerful tool for the synthesis of enantioenriched compounds in chemical and pharmaceutical industries. Sulfur-based functionalities are ubiquitous in many of the biologically active compounds, medicinal agents, functional materials, chiral auxiliaries and ligands. This perspective highlights recent advances in sulfur functional group enabled transition-metal-catalyzed enantioselective C-H functionalization for the construction of sulfur stereogenic centers, as well as the utilization of chiral sulfoxides to realize stereoselective C-H functionalization.

15.
J Am Chem Soc ; 143(39): 16302-16310, 2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34570969

RESUMO

The construction of main group heteroatom-stereogenic compounds is of great importance due to their intriguing chemical, physical, biological, and stereoelectronic properties. Despite that organoboron compounds are widely used in organic chemistry, the creation of a tetrahedral boron-stereogenic center in one enantiomeric form remains highly challenging. Given the labile nature of ligands attached to the tetracoordinate boron atom, only a handful of enantioenriched boron-stereogenic compounds have been reported via resolution or a chiral substrate-induced diastereoselective approach. To date catalytic asymmetric synthesis of boron-stereogenic compounds has remained unknown. Here, we demonstrate the first catalytic enantioselective construction of boron-stereogenic compounds via an asymmetric copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction. This enantioselective CuAAC reaction not only gives access to a wide range of novel highly functionalized boron-stereogenic heterocycles in high yields with good to excellent enantioselectivities but also produces optically active terminal alkyne and triazole moieties with various potential application prospects. Further transformation of the chiral tetracoordinate boron compounds delivers several complex heterocyclic entities bearing boron-stereogenic centers without the loss of enantiopurity. Moreover, the X-ray structure, the barrier to racemization, and the HOMO/LUMO gap of selected tetracoordinate boron compounds are investigated. Notably, these novel N,N π-conjugated boron-stereogenic compounds exhibit bright fluorescence. The optical properties, including circular dichroism, quantum yield, and circular polarized luminescence spectroscopies, are examined. These features expand the chemical space of the chiroptical boron-based dye platform, which could have great potential applications in chiral optoelectronic materials.

16.
Math Biosci Eng ; 18(5): 6941-6960, 2021 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-34517565

RESUMO

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is one of the most common cancers in the world, the detection and prognosis of which are still unsatisfactory. Thus, it is essential to explore the factors that may identify ESCC and evaluate the prognosis of ESCC patients. RESULTS: Both protein and mRNA expression levels of BIRC5 are upregulated in ESCC group rather than non-ESCC group (standardized mean difference > 0). BIRC5 mRNA expression is related to the age, tumor location, lymph node stage and clinical stage of ESCC patients (p < 0.05). BIRC5 expression makes it feasible to distinguish ESCC from non-ESCC (area under the curve > 0.9), and its high expression is related to poor prognosis of ESCC patients (restrictive survival time difference = -0.036, p < 0.05). BIRC5 may play an important role in ESCC by influencing the cell cycle pathway, and CDK1, MAD2L and CDC20 may be the hub genes of this pathway. The transcription factors-MAZ and TFPD1 -are likely to regulate the transcription of BIRC5, which may be one of the factors for the high expression of BIRC5 in ESCC. CONCLUSIONS: The current study shows that upregulation of BIRC5 may have essential clinical value in ESCC, and contributes to the understanding of the pathogenesis of ESCC.


Assuntos
Carcinoma de Células Escamosas , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Carcinoma de Células Escamosas/genética , Neoplasias Esofágicas/genética , Carcinoma de Células Escamosas do Esôfago/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Survivina/genética , Regulação para Cima
17.
Rev Sci Instrum ; 92(8): 083201, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-34470413

RESUMO

We design and develop a high-performance magnetic shielding system for a long baseline fountain-type atom interferometer. The shielding system is achieved by a combination of passive shielding using permalloy and active compensation with coils. An 11.4 m-long three-layer cylindrical shield is completed by the process of welding, local annealing, and entire annealing. The active compensations compress the residual magnetic field to 8.0 nT max-to-min and the corresponding gradient below 30 nT/m over 10 m along the axial direction in which external compensation, internal compensation, and constant magnetic field (C-field) compensation reduce the inhomogeneities to 25.0, 12.6, and 1.7 nT (standard deviation) sequentially. We estimate that this system could reduce the systematic error of the quadratic Zeeman shift to the 10-13 level for the weak equivalence principle test with a simultaneous 85Rb-87Rb dual-species atom interferometer.

18.
Brain Behav ; : e2364, 2021 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-34554655

RESUMO

BACKGROUND: Tobacco use is one of the most important risk factors for health, and China is the largest producer and consumer of tobacco in the world. Monitoring and controlling the tobacco epidemic is an important issue. However, the motivation underlying smoking behavior is complex and specific to the individual. The Habit, Reward and Fear Scale (HRFS) is a feasible tool to evaluate this complex motivation. OBJECTIVES: To validate the psychometric properties of the HRFS Chinese version (HRFS-C) and to assess the relationship between motivation and smoking behavior. METHOD: We recruited 967 participants through social media and assessed their smoking behavior with three instruments: the Fagerstrom Test for Nicotine Dependence-Chinese version (FTND-C), the Questionnaire on Smoking Urges-Brief Scale-Chinese version (QSU-brief-C), and the HRFS-C. Ultimately, we retained 700 valid data points. Cronbach's α and split-half tests were used to evaluate the reliability. Confirmatory factor analysis, Pearson's r and an analysis of variance (ANOVA) were used to evaluate the validity. In addition, linear regression was used to explore the relationship among the three instruments. The HRFS-C showed good homogeneity (α = 0.965), concurrent validity, and discriminant validity. A significant linear relationship was observed among the FTND-C, QSU-brief-C, and HRFS-C (p < .001). CONCLUSION: The motivation measured by the HRFS-C can significantly predict nicotine dependence and craving in the smoking population. The HRFS-C can be used to carry out targeted interventions for addicted patients (e.g., motivational enhancement therapy).

19.
Oral Dis ; 2021 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-34370371

RESUMO

Mechanical memory meant the mechanical properties of the matrix could influence the cell fate even after the matrix was changed and has been justified in many kinds of cells. To utilize the phenomenon to improve periodontal tissue engineering, we studied whether mechanical memory existed in human periodontal ligament stem cells and testified if ILK plays a role in this process. The substrate of different stiffness was fabricated by gelatin methacrylate hydrogel. Two groups of hPDLSCs with stiff (St) and soft (So) matrix, respectively, were cultivated. Then, half of the cells exchanged their matrix stiffness in the fourth passage and therefore So, St, So-St, and St-So were formed. Morphology of hPDLSCs and intracellular location of YAP was observed via fluorescence staining, osteogenic differentiation of hPDLSCs was assessed by real-time PCR, ALP staining, and Western blot. Then, all these were reassessed after the ILK gene had been knocked down. The results showed that morphology and YAP location of hPDLSCs were different between matrix changed and unchanged groups; osteogenic genes expression, ALP staining, and Western blot also varied. After the ILK gene had been knocked down, the YAP location and osteogenic activity of hPDLSCs were significantly influenced. Thus, it could be concluded that mechanical memory exists in hPDLSCs; ILK is involved in this process.

20.
Proc Natl Acad Sci U S A ; 118(35)2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34452996

RESUMO

Global genome repair (GGR), a subpathway of nucleotide excision repair, corrects bulky helix-distorting DNA lesions across the whole genome and is essential for preventing mutagenesis and skin cancer. Here, we show that METTL14 (methyltransferase-like 14), a critical component of the N6-methyladenosine (m6A) RNA methyltransferase complex, promotes GGR through regulating m6A mRNA methylation-mediated DDB2 translation and suppresses ultraviolet B (UVB) radiation-induced skin tumorigenesis. UVB irradiation down-regulates METTL14 protein through NBR1-dependent selective autophagy. METTL14 knockdown decreases GGR and DDB2 abundance. Conversely, overexpression of wild-type METTL14 but not its enzymatically inactive mutant increases GGR and DDB2 abundance. METTL14 knockdown decreases m6A methylation and translation of the DDB2 transcripts. Adding DDB2 reverses the GGR repair defect in METTL14 knockdown cells, indicating that METTL14 facilitates GGR through regulating DDB2 m6A methylation and translation. Similarly, knockdown of YTHDF1, an m6A reader promoting translation of m6A-modified transcripts, decreases DDB2 protein levels. Both METTL14 and YTHDF1 bind to the DDB2 transcript. In mice, skin-specific heterozygous METTL14 deletion increases UVB-induced skin tumorigenesis. Furthermore, METTL14 as well as DDB2 is down-regulated in human and mouse skin tumors and by chronic UVB irradiation in mouse skin, and METTL14 level is associated with the DDB2 level, suggesting a tumor-suppressive role of METTL14 in UVB-associated skin tumorigenesis in association with DDB2 regulation. Taken together, these findings demonstrate that METTL14 is a target for selective autophagy and acts as a critical epitranscriptomic mechanism to regulate GGR and suppress UVB-induced skin tumorigenesis.

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