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1.
Mol Ther ; 2022 Jan 08.
Artículo en Inglés | MEDLINE | ID: mdl-35017116

RESUMEN

Endocytosis of cell surface receptors is essential for cell migration and cancer metastasis. Rab5, a small GTPases of Rab family, is a key regulator of endosome dynamics and thus cell migration, however, how its activity is regulated yet remains to be addressed. Here, we identified a Rab5 inhibitor, a long non-coding RNA namely HITT (HIF-1α inhibitor at translation level). Our data show that HITT expression is inversely associated with advanced stages and poorly prognosis of lung adenocarcinoma patients with area under receiver operating characteristics (ROC) curve (AUC) 0.6473. Further study reveals that both endogenous and exogenous HITT inhibits single cell migration by repressing ß1 integrin endocytosis in lung adenocarcinoma. Mechanistically, HITT is physically associated with Rab5 at switch I via 1248-1347nt and suppresses ß1 integrin endocytosis and subsequent cancer metastasis by interfering with guanine nucleotide exchange factors (GEFs) for Rab5 binding. Collectively, these findings suggest that HITT directly participates in the regulation of Rab5 activity, leading to a decreased integrin internalization and cancer metastasis, which provides important insights into a mechanistic understanding of endocytosis and cancer metastasis.

2.
J Diabetes ; 2022 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-35001531

RESUMEN

BACKGROUND: Research on the relationship between creatinine to body weight ratios (Cre/BW ratios) and the prevalence of diabetes is still lacking. The intention of this research was to explore the potential relationship between Cre/BW ratio and diabetes prevalence in Chinese adults. METHODS: This retrospective study was conducted on 199 526 patients in the Chinese Rich Healthcare Group from 2010 to 2016. The participants were divided into four groups on the basis of the quartiles of the Cre/BW ratios. Multivariate multiple imputation and dummy variables were used to handle missing values. Multivariate regression analysis was applied to detect the relationship between Cre/BW and diabetes. A smoothing plot was also used to identify whether there were nonlinear relationships. RESULTS: After handling missing values and adjusting for potential confounders, the multivariate Cox regression analysis results showed that Cre/BW was inversely correlated with diabetes risk (hazard ratio [HR]: 0.268; 95% confidence interval [CI]: 0.229-0.314, p < 0.00001). For men, the HR of incident diabetes was 0.255 (95% CI: 0.212-0.307) and for women it was 0.297 (95% CI: 0.218-0.406). Moreover, sensitivity analysis confirmed the stability of the results. Furthermore, the smoothing plot revealed that there was a saturation effect between Cre/BW and the incidence of diabetes. CONCLUSIONS: This study demonstrated that increased Cre/BW is negatively correlated with diabetes in Chinese adults. It also found that Cre/BW has a nonlinear relationship with the incidence of diabetes.

3.
Chem Commun (Camb) ; 2022 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-35005752

RESUMEN

A benzothiadiazole-involving donor-acceptor (D-A) covalent organic framework (COF), which has high crystallinity and strong light-harvesting capability (ranging from 300 to 800 nm), can serve as a highly effective photocatalyst for window ledge aerobic cross-dehydrogenative coupling (CDC) reactions (such as Mannich and aza-Henry reactions) even at a gram level.

4.
Opt Lasers Eng ; 1502022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-35027783

RESUMEN

Nanoscale macromolecular biological structures exhibit time-dependent behavior, yet a quantitative understanding of their time-dependent mechanical behavior remains elusive, largely due to experimental challenges in attaining sufficient spatial and temporal resolution and control of stress or strain in conditions that guarantee their molecular integrity. To address this gap, an experimental methodology was developed to conduct creep and stress relaxation experiments with individual mammalian collagen fibrils. An image-based edge detection method implemented with high magnification optical microscopy and combined with closed-loop proportional-integral-derivative (PID) control was implemented and calibrated to apply constant force or stretch ratio values to individual collagen fibrils via a Microelectromechanical Systems (MEMS) device. This experimental methodology allowed for real-time control of uniaxial tensile stress or strain with 27 nm displacement resolution. The overall experimental system was tuned to apply step inputs with rise times below 0.5 s, less than 2.5% overshoot, and steady-state error less than 0.5%. Three individual collagen fibrils with diameters 101-121 nm were subjected to creep and stress relaxation tests in the range 4-20% engineering strain, under partially hydrated conditions. The collagen fibrils demonstrated non-linear viscoelastic behavior that was described well by the adaptive quasi-linear viscoelastic model. The results of this study demonstrate for the first time that mammalian collagen fibrils, the building blocks of connective tissues, exhibit nonlinear viscoelastic behavior in their partially hydrated state.

5.
Food Sci Nutr ; 10(1): 169-178, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-35035919

RESUMEN

The study aimed to evaluate the effects of Allium mongolicum Regel (AMR) and its water- and fat-soluble extracts on the quality of fermented mutton sausages. Sausages were produced with mutton and fat. Four treatments: CO, without Allium mongolicum Regel and its extracts, used as control; AMR with Allium mongolicum Regel; AWE with water-soluble extract of Allium mongolicum Regel; and AFE with liposoluble extract from Allium mongolicum Regel, were produced and analyzed for pH, water activity (a w), free amino acids, fatty acids, and volatiles were, respectively, in fermented mutton sausages during processing (0, 2, 5, and 7 days). The results showed that the pH values of the liposoluble extract from Allium mongolicum Regel (AFE), respectively, are lower than that of sample CO at the end of fermentation and ripening. The a w in all group of sausages significantly dropped to 0.88 at the end of ripening (Day 7). Adding Allium mongolicum Regel and its water-soluble extract can improve the serine (SER) content of fermented mutton sausage. The contents of five essential amino acids (EAA) were added when adding Allium mongolicum Regel and its fat-soluble extract. The total fatty acid (TFA) in the treatments increased during drying and ripening. The addition of Allium mongolicum Regel and its extract can increase the content of volatile flavor substances such as 3-hydroxy-2-butanone, 3-methylbutyraldehyde, hexanal, octanal, and nonanal at the later stage of maturity, so as to improve the flavor substances in fermented mutton sausage. Water-soluble extract of Allium mongolicum Regel (AWE) and AFE treatments had more intense flavor at the end of ripening (Day 7). The flavor of fermented mutton sausage can be improved by adding Allium mongolicum Regel and its extracts into fermented mutton sausage.

6.
J Biomed Sci ; 29(1): 4, 2022 Jan 17.
Artículo en Inglés | MEDLINE | ID: mdl-35039060

RESUMEN

BACKGROUND: SLCO4A1-AS1 was found to be upregulated in several cancer types, including colorectal cancer (CRC). However, the detailed roles of SLCO4A1-AS1 in CRC remain to be elucidated. Therefore, we investigated the functions, mechanism, and clinical significance of SLCO4A1-AS1 in colorectal tumourigenesis. METHODS: We measured the expression of SLCO4A1-AS1 in CRC tissues using qRT-PCR and determined its correlation with patient prognosis. Promoter methylation analyses were used to assess the methylation status of SLCO4A1-AS1. Gain- and loss-of-function assays were used to evaluate the effects of SLCO4A1-AS1 on CRC growth in vitro and in vivo. RNA pull-down, RNA immunoprecipitation, RNA-seq, luciferase reporter and immunohistochemistry assays were performed to identify the molecular mechanism of SLCO4A1-AS1 in CRC. RESULTS: SLCO4A1-AS1 was frequently upregulated in CRC tissues based on multiple CRC cohorts and was associated with poor prognoses. Aberrant overexpression of SLCO4A1-AS1 in CRC is partly attributed to the DNA hypomethylation of its promoter. Ectopic SLCO4A1-AS1 expression promoted CRC cell growth, whereas SLCO4A1-AS1 knockdown repressed CRC proliferation both in vitro and in vivo. Mechanistic investigations revealed that SLCO4A1-AS1 functions as a molecular scaffold to strengthen the interaction between Hsp90 and Cdk2, promoting the protein stability of Cdk2. The SLCO4A1-AS1-induced increase in Cdk2 levels activates the c-Myc signalling pathway by promoting the phosphorylation of c-Myc at Ser62, resulting in increased tumour growth. CONCLUSIONS: Our data demonstrate that SLCO4A1-AS1 acts as an oncogene in CRC by regulating the Hsp90/Cdk2/c-Myc axis, supporting SLCO4A1-AS1 as a potential therapeutic target and prognostic factor for CRC.

7.
Sci Rep ; 12(1): 823, 2022 Jan 17.
Artículo en Inglés | MEDLINE | ID: mdl-35039590

RESUMEN

Wind is one of the cleanest renewable energy resources. Through the "Thousand Wind Turbines Project", Taiwan is planning to increase the proportion of power generation from renewable energy and has set a target of 5.7 GW for offshore wind by 2025. The effects of future offshore wind farms (OWFs) over the Taiwan Strait on the atmospheric environment have not been evaluated. This study examined the potential effects of proposed OWFs on the atmospheric environment if the OWFs had existed during Tropical Storm Haitang (2017) by using Weather Research and Forecasting (WRF) model. A small set of ensemble simulations was conducted for studying the sensitivity of the ambient conditions in the region to the wind farm locations, the number and density of the turbines, and the initial time of simulations. Following the landfall and northward movement of Tropical Storm Haitang, a series of complex interactions between the typhoon circulation and the wind farm emerged, including small time slots of wake effect and mountain blocking effect. The combination of these rapidly changing OWFs-related effects contributed to a weak reduction in precipitation (- 1.08 mm) and hub-height wind speed (- 0.25 m s-1), as well as minimal warming near the surface (+ 0.13 °C) over southern Taiwan.

8.
Biochem Genet ; 2022 Jan 18.
Artículo en Inglés | MEDLINE | ID: mdl-35039981

RESUMEN

Neuroblastoma is a malignant tumor originating from the primitive neural crest. Circular RNA (circRNA) Kinesin Superfamily Protein 2A (circKIF2A, also known as hsa_circ_0129276) has been reported to be upregulated in neuroblastoma. However, the molecular mechanism of circKIF2A participated in neuroblastoma is poorly defined. We analyzed the expression levels of circKIF2A, microRNA-377-3p (miR-377-3p), and phosphoribosyl pyrophosphate synthetase 1 (PRPS1) in neuroblastoma tissues and cell lines (SK-N-AS and LAN-6) and explored their roles. The expression levels of CircKIF2A and PRPS1 were increased and that of miR-377-3p were decreased in 21 neuroblastoma tissues and cells. Functionally, the silencing of circKIF2A inhibited cell proliferation, migration, invasion, and glycolysis, boosted apoptosis in neuroblastoma cells in vitro, and blocked the growth of subcutaneously transplanted tumors in nude mice. Mechanically, circKIF2A could work as a sponge of miR-377-3p to enhance PRPS1 expression. CircKIF2A knockdown impedes cell proliferation, metastasis, and glycolysis partly by regulating the miR-377-3p/PRPS1 axis, suggesting that targeting circKIF2A can be a feasible therapeutic strategy for neuroblastoma.

9.
Hum Brain Mapp ; 2022 Jan 18.
Artículo en Inglés | MEDLINE | ID: mdl-35040524

RESUMEN

Sleep disturbance is known to be associated with various mental disorders and often precedes the onset of mental disorders in youth. Given the increasingly acknowledged bidirectional influence between sleep disturbance and mental disorders, we aim to identify a shared neural mechanism that underlies sleep disturbance and mental disorders in preadolescents. We analyzed a dataset of 9,350 9-10 year-old children, among whom 8,845 had 1-year follow-up data, from the Adolescent Brain Cognitive Development (ABCD) study. Linear mixed-effects models, mediation analysis, and longitudinal mediation analysis were used to investigate the relationship between sleep disturbance, mental disorders, and resting-state network connectivity. Out of 186 unique connectivities, the effect of total sleep disturbance (TSP, from Sleep Disturbance Scale) and mental problems (MP, from Child Behavior Checklist) converged in the default mode network (DMN) and the dorsal attention network (DAN). Within- and between-network connectivities (DMN-DAN, DMN-DMN, DAN-DAN) mediated the relationship between baseline TSD and MP at 1-year follow-up and the relationship between baseline MP and TSD at 1-year follow-up. The pathway model in which sleep disturbance and mental problems affect each other through two anticorrelated brain networks (DMN and DAN) suggests a common neural mechanism between them. Longitudinally, a less segregated DMN and DAN is associated with negative outcomes on mental well-being and sleep disturbance a year later. These findings have important implications for the design of prevention and neurofeedback intervention for mental disorders and sleep problems.

10.
Aging (Albany NY) ; 13(undefined)2022 Jan 04.
Artículo en Inglés | MEDLINE | ID: mdl-34983878

RESUMEN

Autophagy is an important regulator of cellular homeostasis and its dysregulation often results in cancer. Aberrant glycosylation induced by oncogenic transformation contributes to tumor invasion and metastasis. In a previous study, we have demonstrated that EpCAM, a glycosylation protein, is associated with cell growth and metastasis in breast cancer. But the effect of EpCAM glycosylation on autophagy is not clear. the precise mechanism of regulation remains largely unknown. In this study, breast cancer cells were transfected with N-glycosylation mutation EpCAM plasmid to express deglycosylated EpCAM. The result showed that deglycosylated EpCAM promoted autophagy in breast cancer cells. We further confirmed this conclusion with the activator (Rapamycin, RAP) and inhibitor (Wortmannin) of autophagy. We also found that deglycosylated EpCAM promoted apoptosis and inhibited proliferation through activating autophagy by suppressing Akt/mTOR signaling pathway in breast cancer cells. These findings represent a novel mechanism by which deglycosylated EpCAM inhibits proliferation by enhancing autophagy of breast cancer cells via PI3K/Akt/mTOR pathway. In conclusion, the combination of autophagy modulation and EpCAM targeted therapy is a promising therapeutic strategy in the treatment of breast cancer.

11.
Analyst ; 2022 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-34985055

RESUMEN

Urinary tract infections (UTIs) are a severe public health problem caused by mono- or poly-bacteria. Culture-based methods are routinely used for the diagnosis of UTIs in clinical practice, but those are time consuming. Rapid and unambiguous identification of each pathogen in UTIs can have a significant impact on timely diagnoses and precise treatment. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) is an alternative method for the identification of pathogens in clinical laboratories. However, a certain number of pure bacteria are required for MALDI-TOF MS analysis. Here, we explored a strategy combining magnetic enrichment and MALDI-TOF MS for the rapid identification of pathogenic bacterial mixtures in urine. Fragment crystallizable mannose-binding lectin-modified Fe3O4 (Fc-MBL@Fe3O4) was used for rapid enrichment and the individual-peak-based similarity model as the analytical tool. Within 30 min, a mixture of the four most prevalent UTI-causing bacteria, Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus, and Pseudomonas aeruginosa, was successfully identified using this method. This rapid MALDI-TOF MS-based strategy has potential applications in the clinical identification of UTI pathogens.

12.
ACS Appl Bio Mater ; 2022 Jan 19.
Artículo en Inglés | MEDLINE | ID: mdl-35043619

RESUMEN

Light/ultrasound/magnetic-responsive nanomaterials exhibit excellent performance in imaging and therapy and play an important role in precision theranostics of tumors. In contrast to deep organs, urinary organs (such as bladder and prostate) can easily be studied via intervention mode, which has greatly brought promising applications of stimuli-responsive nanoprobes in visualized theranostics of urinary tumors. Therefore, it has been very critical to develop stimuli-responsive nanoprobes with high safety, stability, and reliability against urinary tumors. In this review, recent advances in light/ultrasound/magnetic-responsive nanoprobes in visualized theranostics of urinary tumors are summarized, including magnetic resonance/fluorescence/ultrasound/photoacoustic imaging and multimodal imaging, photothermal/photodynamic/sonodynamic therapy and combination therapy, and single-modal/multimodal-imaging-guided visualized theranostics. Finally, the future perspectives of light/ultrasound/magnetic-responsive nanoprobes against urinary tumors are also prospected.

13.
Microbiol Spectr ; : e0162021, 2022 Jan 19.
Artículo en Inglés | MEDLINE | ID: mdl-35044199

RESUMEN

The opportunistic pathogen Pseudomonas aeruginosa often adapts to its host environment and causes recurrent nosocomial infections. The extracytoplasmic function (ECF) sigma factor enables bacteria to alter their gene expression in response to host environmental stimuli. Here, we report an ECF sigma factor, HxuI, which is rapidly induced once P. aeruginosa encounters the host. Host stresses such as iron limitation, oxidative stress, low oxygen, and nitric oxide induce the expression of hxuI. By combining RNA-seq and promoter-lacZ reporter fusion analysis, we reveal that HxuI can activate the expression of diverse metabolic and virulence pathways which are critical to P. aeruginosa infections, including iron acquisition, denitrification, pyocyanin synthesis, and bacteriocin production. Most importantly, overexpression of the hxuI in the laboratory strain PAO1 promotes its colonization in both murine lung and subcutaneous infections. Together, our findings show that HxuI, a key player in host stress-response, controls the in vivo adaptability and virulence of P. aeruginosa during infection. IMPORTANCE P. aeruginosa has a strong ability to adapt to diverse environments, making it capable of causing recurrent and multisite infections in clinics. Understanding host adaptive mechanisms plays an important guiding role in the development of new anti-infective agents. Here, we demonstrate that an ECFσ factor of P. aeruginosa response to the host-inflicted stresses, which promotes the bacterial in vivo fitness and pathogenicity. Furthermore, our findings may help explain the emergence of highly transmissible strains of P. aeruginosa and the acute exacerbations during chronic infections.

14.
J Neurovirol ; 2022 Jan 19.
Artículo en Inglés | MEDLINE | ID: mdl-35044643

RESUMEN

HIV-associated neurocognitive disorders (HAND) remain highly prevalent in people with HIV (PWH). Studies suggested that certain sociodemographic factors are associated with the risk of HAND in PWH. Here we investigated the impact of HIV infection and demographics on functional brain networks. One run of 8.5 min resting state functional MRI (fMRI) data was collected from 101 PWH (41-70 years old) and 40 demographically comparable controls. Functional connectivity (FC) was calculated using average wavelet coherence. The impact of demographic factors on FCs was investigated using canonical correlation analysis (CCA). Wavelet coherence analysis revealed a reduced within-network connectivity in the dorsal somatomotor network (dSMN), along with a reduced between-network connectivity between dSMN and medial temporal lobe (MTL) in PWH (compared to controls). Across all participants, CCA revealed that older age and HIV infection had negative impacts on network connectivity measures (mainly reduced within- and between-network FCs), whereas education had an opposite effect. In addition, being female at birth or a member of a minority ethnic/racial group was also associated with network disruptions. Our data suggested that advanced age and HIV infection are risk factors for functional brain network disruptions, whereas higher educational attainment was linked to better preserved functional network connectivity.

15.
J Med Virol ; 2022 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-35005794

RESUMEN

Influenza virus infections pose a continuous threat to human health. Although vaccines function as a preventive and protective tool, they may not be effective due to antigen drift or an inaccurate prediction of epidemic strains. Monoclonal antibodies (mAbs) have attracted wide attention as a promising therapeutic method for influenza virus infections. In this study, three hemagglutinin (HA)-specific mAbs, named 2A1, 2H4, and 2G2, respectively, were derived from mice immunized with the HA protein from A/Michigan/45/2015(H1N1). The isolated mAbs all displayed hemagglutination inhibition activity and the 2G2 mAb exhibited the strongest neutralization effect. Two amino acid mutations (A198E and G173E), recognized in the process of selection of mAb-resistant mutants, were located in antigenic site Sb and Ca1, respectively. In prophylactic experiments, all three mAbs could achieve 100% protection in mice infected with a lethal dose of A/Michigan/45/2015(H1N1). A dose of 1 mg/kg for 2H4 and 2G2 was sufficient to achieve a full protective effect. Therapeutic experiments showed that all three mAbs could protect mice from death if they received the mAb administration at 6 h postinfection, and 2G2 was still protective after 24 h. Our findings indicate that these three mAbs may have potential prevention and treatment value in an H1N1 epidemic, as well as in the study of antigen epitope recognition.

16.
Environ Res ; 208: 112694, 2022 Jan 08.
Artículo en Inglés | MEDLINE | ID: mdl-35007540

RESUMEN

Detailed prediction of the adsorption amounts of organic pollutants in water is essential to the clean development and management of water resources. In this study, Kriging and polyparameter linear free energy relationship model are coupled to predict adsorption capacity of organic pollutants by biochar and resin. It's based on 1750 adsorption experimental data sets which contains 73 organic compounds on 50 biochars and 30 polymer resins. The Kriging-LFER model shows better accuracy and predictive performance for adsorption (R2 are 0.940 and 0.976) than the published NN-LFER model (R2 are 0.870 and 0.880). Local sensitivity analysis method is adopted to evaluate the influence of each variable on the adsorption coefficient of resin and find out that top sensitive parameters are V and log Ce, to guide parameter optimization. Data's uncertainty analysis is presented by Monte Carlo method. It predicts that the adsorption coefficient will range from 0.062 to 0.189 under the 95% confidence interval. The Kriging-LFER model provides great significance for understanding the importance of various parameters, reducing the number of experiments, adjusting the direction of experimental improvement, and evaluating the fate of organic pollutants in the environment.

17.
Int Immunopharmacol ; 104: 108506, 2022 Jan 07.
Artículo en Inglés | MEDLINE | ID: mdl-35008007

RESUMEN

BACKGROUND: Myeloid-derived suppressor cells (MDSCs) and cyclooxy-genase-2 (COX-2)/Prostaglandin E2 (PGE2) axis are important contributors to sepsis-induced immune-suppression. The purpose of present study is to explore whether COX-2 inhibitor can improve immunological disorder after sepsis via regulating MDSCs. METHODS: A ''two-hit'' model reflecting clinical sepsis development was performed. Cecal ligation and puncture (CLP) and Legionella pneumophila infection were used as the first and the second hit, respectively. NS398, a selective COX-2 inhibitor, was utilized to treat septic mice. The motality, bacterial counts in the lung, systematic inflammatory reaction and CD4 + T cells response after sepsis were assessed, so as the frequency and function of MDSCs. In some experiments, the number of MDSCs was manipulated by adoptive transfer or neutralizing antibody before induction of secondary infection. RESULTS: Mice surviving CLP showed a marked expansion and activation of MDSCs in spleen, accompanied by suppressed proliferating capability, impaired secreting functionand increased apoptosis of CD4 + T cells. Majority of CLP survivors became succumbed to L. pneumophila invasion, associated with defective bacteria elimination ability. NS398 treatment was found to ameliorate these adverse outcomes significantly. CONCLUSION: MDSCs contribute greatly to the sepsis-induced immune dysfunction. Inhibiting COX-2 may become a promising therapy that targets MDSCs-induced immunosuppression.

18.
Mater Today Bio ; 13: 100202, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-35036897

RESUMEN

Polycaprolactone (PCL) is a polymer material suitable for being prepared into porous scaffolds used in bone tissue engineering, however, insufficient osteogenic ability and mechanical strength limit its application. Zinc (Zn) alloy with proper mechanical strength and osteogenesis is a promising biodegradable metal that have attracted much attention. Herein, we combined the advantages of PCL and Zn by fabricating PCL/Zn composite scaffolds with different Zn powder contents (1 â€‹wt%, 2 â€‹wt%, 3 â€‹wt%) through fused deposition modelling. The â€‹mechanical property, cytocompatibility and Zn â€‹ions release â€‹behavior of PCL/Zn scaffolds were analyzed â€‹in vitro. The osteogenesis and osteoclastogenesis properties of the scaffolds were evaluated by being implanted into Sprague-Dawley rats calvaria defect. Results showed that the PCL/Zn scaffolds exhibited improved mechanical properties and cytocompatibility compared with the pure PCL scaffolds. At 8 weeks after in vivo implantaion, the addition of Zn powder promoted new bone formation, in a dose-dependent manner. The scaffolds with 2 â€‹wt% Zn displayed the best osteogenic effect, while the osteogenic effect was slightly reduced in the scaffolds with 3 â€‹wt% Zn. In the studied Zn contents, the PCL/Zn scaffolds gradually promoted osteoclastogenesis with increasd Zn content. In the 3 â€‹wt% Zn group, TRAP-positive cells were observed on the newly formed bone edges around the scaffolds. These dose-dependent effects were verified in vitro using MC3T3-E1 and RAW264.7 â€‹cells. Finally, we revealed that Zn2+ regulated osteogenesis and osteoclastogenesis by activation of the Wnt/ß-catenin and NF-κB signalling pathways, respectively.

19.
Plant Signal Behav ; : 2013646, 2022 Jan 17.
Artículo en Inglés | MEDLINE | ID: mdl-35034573

RESUMEN

Calmodulin (CaM) and calmodulin-like (CML) genes are widely involved in plant growth and development and mediating plant stress tolerance. However, the whole genome scale studies about CaM and CML gene families have not been done in wheat, and the possible functions of most wheat CaM/CML gene members are still unknown. In this study, a total of 18 TaCaM and 230 TaCML gene members were identified in wheat genome. Among these genes, 28 TaCaM/CML gene members have 74 duplicated copies, while 21 genes have 48 transcript variants, resulting in 321 putative TaCaM/CML transcripts totally. Phylogenetic tree analysis showed that they can be classified into 7 subfamilies. Similar gene structures and protein domains can be found in members of the same gene cluster. The TaCaM/CML genes were spread among all 21 chromosomes with unbalanced distributions, while most of the gene clusters contained 3 homoeologous genes located in the same homoeologous chromosome group. Synteny analysis showed that most of TaCaM/CMLs gene members can be found with 1-4 paralogous genes in T. turgidum and Ae. Tauschii. High numbers of cis-acting elements related to plant hormones and stress responses can be observed in the promoters of TaCaM/CMLs. The spatiotemporal expression patterns showed that most of the TaCaM/TaCML genes can be detected in at least one tissue. The expression levels of TaCML17, 21, 30, 50, 59 and 75 in the root or shoot can be up-regulated by abiotic stresses, suggesting that TaCML17, 21, 30, 50, 59 and 75 may be related with responses to abiotic stresses in wheat. The spatiotemporal expression patterns of TaCaM/CML genes indicated they may be involved widely in wheat growth and development. Our results provide important clues for exploring functions of TaCaMs/CMLs in growth and development as well as responses to abiotic stresses in wheat in the future.

20.
Artículo en Inglés | MEDLINE | ID: mdl-35000122

RESUMEN

Metabolic engineering of microbial cell factories through integrating the heterologous synthetic pathway into the chromosome is most commonly used for industrial applications. However, the position of the foreign gene in the chromosome can affect its transcriptional level. As a microorganism that is generally regarded as safe (GRAS) and commonly applied in industrial manufacture with large-scale operations, Saccharomyces cerevisiae is also confronted with this position effect. In this study, we characterized 12 different chromosome sites by inserting the lycopene biosynthetic pathway as a reporter cassette. Due to the different integration loci, the gene transcription and lycopene yield exhibited more than 58-fold and 3.8-fold differences, respectively. Furthermore, changing the gene order also revealed a remarkable influence (30-fold and 14-fold) on gene transcription and lycopene yield. Besides, the upstream activation sequence of a strong promoter (defined as an insulator) in S. cerevisiae could reduce the impact by gene order, and increased the gene transcription (tenfold) and lycopene yield (sevenfold). Taken together, our results demonstrated that gene order and insulator affected gene transcription and heterogeneous biosynthesis, opening the opportunity to regulate gene transcription by insulator against position effect in S. cerevisiae.

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