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1.
Insect Sci ; 2021 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-33843147

RESUMO

Juvenile hormone (JH) absence induces photoperiod-mediated reproductive diapause, which is characterized by reproductive cessation. Although the role of methoprene-tolerant (Met)-mediated JH signaling in photoperiod-mediated female reproduction has been well documented, its role in male reproduction remains unclear. In this study, we investigated the role of JH in regulating photoperiod-mediated development of the male internal reproductive system (IRS) in the predatory ladybeetle Harmonia axyridis (Pallas). In a previous study, we found that adult male H. axyridis reared under either a short-day (SD) or long-day (LD) photoperiod had obvious differences in IRS development, but we were unable to identify the regulators of male reproductive diapause. In this study, we found that beetles reared under an SD photoperiod had significantly lower JH titer and a relatively undeveloped male IRS compared with those reared under an LD photoperiod. Additionally, application of the JH analog (JHA) methoprene promoted IRS development. Furthermore, Met knockdown strongly blocked JH signaling in males reared under the LD photoperiod, thereby slowing IRS development. Moreover, exogenous JHA did not reverse the suppressed development of the male IRS caused by Met knockdown. These results indicate that photoperiod regulates male IRS development in H. axyridis through a conserved Met-dependent JH signaling pathway.

2.
Nat Prod Res ; : 1-7, 2021 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-33843371

RESUMO

Two novel icetexane diterpenes were isolated from Salvia przewalskii Maxim., namely Salprzesides A (1) and B (2), together with two known abietane-type diterpenes respectively identified as sahandinone (3) and miltirone (4). The structures of isolated compounds were determined by UV, IR, HR-ESI-MS, 1D and 2D NMR analysis. The in vitro antiangiogenic activities of compounds 1-4 were studied against human umbilical vascular endothelial cells (HUVECs). The IC50 values of compounds 1-4 ranged from 4.22 ± 1.07 to 39.31 ± 2.17 µM against HUVECs.

3.
BMC Med Imaging ; 21(1): 63, 2021 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-33827457

RESUMO

BACKGROUND: Chronic allograft injury (CAI) is a significant reason for which many grafts were lost. The study was conducted to assess the usefulness of diffusional kurtosis imaging (DKI) technology in the non-invasive assessment of CAI. METHODS: Between February 2019 and October 2019, 110 renal allograft recipients were included to analyze relevant DKI parameters. According to estimated glomerular filtration rate (eGFR) (mL/min/ 1.73 m2) level, they were divided to 3 groups: group 1, eGFR ≥ 60 (n = 10); group 2, eGFR 30-60 (n = 69); group 3, eGFR < 30 (n = 31). We performed DKI on a clinical 3T magnetic resonance imaging system. We measured the area of interest to determine the mean kurtosis (MK), mean diffusivity (MD), and apparent diffusion coefficient (ADC) of the renal cortex and medulla. We performed a Pearson correlation analysis to determine the relationship between eGFR and the DKI parameters. We used the receiver operating characteristic curve to estimate the predicted values of DKI parameters in the CAI evaluation. We randomly selected five patients from group 2 for biopsy to confirm CAI. RESULTS: With the increase of creatinine, ADC, and MD of the cortex and medulla decrease, MK of the cortex and medulla gradually increase. Among the three different eGFR groups, significant differences were found in cortical and medullary MK (P = 0.039, P < 0.001, P < 0.001, respectively). Cortical and medullary ADC and MD are negatively correlated with eGFR (r = - 0.49, - 0.44, - 0.57, - 0.57, respectively; P < 0.001), while cortical and medullary MK are positively correlated with eGFR (r = 0.42, 0.38; P < 0.001). When 0.491 was set as the cutoff value, MK's CAI assessment showed 87% sensitivity and 100% specificity. All five patients randomly selected for biopsy from the second group confirmed glomerulosclerosis and tubular atrophy/interstitial fibrosis. CONCLUSION: The DKI technique is related to eGFR as allograft injury progresses and is expected to become a potential non-invasive method for evaluating CAI.

4.
Rev Cardiovasc Med ; 22(1): 159-165, 2021 03 30.
Artigo em Inglês | MEDLINE | ID: mdl-33792257

RESUMO

Coronavirus Disease 2019 (COVID-19) originated in Wuhan, China in December 2019 and rapidly spread worldwide. Herein, we conducted a systematic review and meta-analysis to find the association between COVID-19 and cardiovascular complications. We conducted a systematic literature search of the PubMed and Embase databases from 01 December 2019 to 30 November 2020. We then statistically analyzed the incidence of cardiovascular complications in COVID-19 patients. We included 3044 confirmed COVID-19 cases from 12 studies. The most common cardiovascular complications in COVID-19 patients were myocardial injury (21.2%, 95% CI 12.3-30.0%) and arrhythmia (15.3%, 95% CI 8.4-22.3%), followed by heart failure (14.4%, 95% CI 5.7-23.1%) and acute coronary syndrome (1.0%, 95% CI 0.5-1.5%). The pooled incidence of heart failure, arrhythmia and myocardial injury in non-survivors were 47.8% (95% CI 41.4-54.2%), 40.3% (95% CI 1.6-78.9%) and 61.7% (95% CI 46.8-76.6%), respectively. Also, the data separately showed significantly higher incidence of heart failure and cardiac injury in non-survivors (relative risks = 5.13, 95% CI 2.46-10.7, Z = 4.36, P = 0.017) and (relative risks = 6.91, 95% CI 3.19-14.95, Z = 4.91, P = 0.009). Myocardial injury and arrhythmia were the most common complications in COVID-19 patients. Myocardial injury and heart failure were more common in patients who died, regardless of a history of cardiovascular disease. The incidence of heart failure and myocardial injury were higher in non-survivors compared to the survivors. Accordingly, in addition to basic support, cardiac reactions of patients with confirmed COVID-19 with or without underlying cardiovascular diseases should be closely monitored.

5.
J Colloid Interface Sci ; 595: 107-117, 2021 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-33819686

RESUMO

A perfect PtCu nanocube with partial hollow structure was prepared by hydrothermal reaction and its electrocatalytic methanol oxidation reaction (MOR) was studied. The appropriate concentration of shape-control additives KI and triblock pluronic copolymers, poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO19-PPO69-PEO19) (P123) play crucial roles in the final product morphology. The PtCu nanocubes can be perfectly in situ immobilizedonto graphene under the action of P123 while the structure and cubic morphologyremain unchanged. The electrochemical tests suggest that the obtained PtCu nanocube (PtCu-NCb) exhibits better MOR activity and stability than PtCu hexagon nanosheet (PtCu-NSt), PtCu nanoellipsoid (PtCu-NEs) and commercial Pt/C in alkaline medium. When in situ immobilized onto graphene, the MOR catalytic activity and stability of PtCu cubes are further improved. The markedly enhanced electrocatalytic activity and durability maybe attributed to the special cubic morphology with partial hollow structure enclosed by highly efficient facet and the probably the synergistic effect of PtCu and intermediate state CuI decorated on the surface and graphene.

6.
Small ; : e2100140, 2021 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-33811462

RESUMO

Optical microsphere resonators working in the near- and mid-infrared regions are highly required for a variety of applications, such as optical sensors, filters, modulators, and microlasers. Here, a simple and low-cost approach is reported for batch fabrication of high-quality chalcogenide glass (ChG) microsphere resonators by melting high-purity ChG powders in an oil environment. Q factors as high as 1.2 × 106 (7.4 × 105 ) are observed in As2 S3 (As2 Se3 ) microspheres (≈30 µm in diameter) around 1550-nm wavelength. Smaller microspheres with sizes around 10 µm also show excellent resonant responses (Q ≈ 2.5 × 105 ). Based on the mode splitting of an azimuthal mode in a microsphere resonator, eccentricities as low as ≈0.13% (≈0.17%) for As2 S3 (As2 Se3 ) microspheres are measured. Moreover, by coupling ChG microspheres with a biconical As2 S3 fiber taper, Q factors of ≈1.7 × 104 (≈1.6 × 104 ) are obtained in As2 S3 (As2 Se3 ) microspheres in the mid-infrared region (around 4.5 µm). The high-quality ChG microspheres demonstrated here are highly attractive for near- and mid-infrared optics, including optical sensing, optical nonlinearity, cavity quantum electrodynamics, microlasers, nanofocusing, and microscopic imaging.

7.
J Hum Hypertens ; 2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33785906

RESUMO

Recently, the contribution of both insufficient sleep duration and gut microbiome dysbiosis to hypertension (HTN) have been revealed, yet the profile of gut flora in hypertensive patients with insufficient sleep duration remains unknown. To examine this condition, the specific shifts in the fecal microbiome of 53 participants with or without HTN were investigated. The patients were divided into those who slept short (≤6 h) or optimal (6-9 h) duration per day. Comprehensive metagenomic sequencing analysis of fecal specimens was performed in healthy controls with sufficient sleep (s-CTR, n = 10), healthy controls with insufficient sleep (ins-CTR, n = 6), hypertensive patients with sufficient sleep (s-HTN, n = 25), and HTNs complicated by short sleep duration (ins-HTN, n = 12). We found that the α-diversity and ß-diversity were quite similar between s-HTN and ins-HTN. Similarities were also observed in the enterotype distribution between s-HTN and ins-HTN subjects. In addition, the enrichment of gut bacteria was evident, such as Fusobacterium mortiferum and Roseburia inulinivorans in ins-HTN subjects. Several functional modules that were distinct between s-HTN and ins-HTN subjects were identified, which were unique to hypertensive patients with insufficient sleep duration. Overall, the data demonstrated that the gut microbial features were largely maintained in hypertensive participants with insufficient sleep duration.

8.
Ultrasonics ; 114: 106420, 2021 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-33735758

RESUMO

Graphene acoustic transducers have high sensitivity in receiving mode. However, they are used in transmitting mode with low radiation performance. A graphene acoustic transducer with high sensitivity and radiation performance is proposed in this study. The transducer is composed of graphene diaphragm, an insulating layer embedded in a copper planar coil, and a bottom layer plated with copper. The proposed capacitive transducer is driven by electrostatic and electromagnetic excitation. The sensitivity and radiation performance of the transducer are analyzed by transceiver theory and simulation models. The results demonstrate that the proposed capacitive transducer has excellent acoustic performance with sensitivity of -42 dB and the sound pressure level of 106 dB at 4 kHz with a 20-turn coil that is more than doubled compared without a copper coil. In addition, the radiation performance of the transducer is discussed by the coil parameters including coil turns and coil current, which can provide a theoretical basis for further experiments.

9.
Mol Brain ; 14(1): 49, 2021 03 06.
Artigo em Inglês | MEDLINE | ID: mdl-33676528

RESUMO

Antibiotics affect gut microbial composition, leading to Gut-Brain-Axis imbalance and neurobehavioral changes. However, the intestinal dysbacteriosis associated behavior changes are not consistently reported. It is not clear whether these changes are transient or permanent. The neuroprotective effect of probiotics against intestinal dysbacteriosis induced alternations needs to be determined either. In the present study, oral antibiotic mixture including Ampicillin, Streptomycin, and Clindamycin was utilized to induce intestinal dysbacteriosis in mice. Antibiotics application triggered mechanical allodynia in von frey test and spontaneous pain in open field test. It also resulted in increased anxiety and depressive-like behaviors and damaged spatial memory performance. After application of probiotics, the mechanical allodynia and spontaneous pain were alleviated significantly. The anxiety behaviors, depressive-like behaviors and recognitive performance were ameliorative as well. By using Fos protein as a marker, it is found that the sensory, emotion and memory related brain regions were activated in mice with intestinal dysbacteriosis. Our study is not only helpful for enriching our basic knowledge for understanding the changed pain responses and related brain disorders in antibiotics-induced dysbacteriosis mice, but also beneficial for providing a more comprehensive mechanistic explanation for the regulation of antibiotics and probiotics on gut microbiota and relevant alternations in animal neurological behaviors.

10.
Eur J Pharmacol ; 899: 174036, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33737009

RESUMO

Earlier we have shown that certain flavonoids (e.g., quercetin) are high-affinity reducing cosubstrates for cyclooxygenase (COX) 1 and 2. These compounds can bind inside the peroxidase active sites of COXs and donate an electron from one of their B-ring hydroxyl groups to hematin. Based on these earlier findings, it is postulated that some of the natural flavonoids such as galangin that are structural analogs of quercetin but lack the proper B-ring hydroxyl groups might function as novel inhibitors of COXs by blocking the effect of the reducing cosubstrates. This idea is tested in the present study. Computational docking analysis together with quantum chemistry calculation shows that galangin can bind inside the peroxidase active sites of COX-1 and COX-2 in a similar manner as quercetin, but it has little ability to effectively donate its electrons, thereby blocking the effect of the reducing cosubstrates like quercetin. Further experimental studies confirm that galangin can inhibit, both in vitro and in vivo, quercetin-mediated activation of the peroxidase activity of the COX-1/2 enzymes. The results of the present study demonstrate that galangin is a novel naturally-occurring inhibitor of COX-1 and COX-2, acting by blocking the function of the reducing cosubstrates at the peroxidase sites.

11.
Cell Death Dis ; 12(4): 312, 2021 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-33762574

RESUMO

Previous studies have suggested that hypoxic responses are regulated by hypoxia-inducible factors (HIFs), which in turn promote the malignant progression of glioblastoma (GBM) by inhibiting apoptosis and increasing proliferation; these events lead to a poor prognosis of GBM patients. However, there are still no HIF-targeted therapies for the treatment of GBM. We have conducted series of experiments and discovered that GBM cells exhibit features indicative of malignant progression and are present in a hypoxic environment. Knocking out HIF1α or HIF2α alone resulted in no significant change in cell proliferation and cell cycle progression in response to acute hypoxia, but cells showed inhibition of stemness expression and chemosensitization to temozolomide (TMZ) treatment. However, simultaneously knocking out HIF1α and HIF2α inhibited cell cycle arrest and promoted proliferation with decreased stemness, making GBM cells more sensitive to chemotherapy, which could improve patient prognosis. Thus, HIF1α and HIF2α regulate each other with negative feedback. In addition, HIF1α and HIF2α are upstream regulators of epidermal growth factor (EGF), which controls the malignant development of GBM through the EGFR-PI3K/AKT-mTOR-HIF1α signalling pathway. In brief, the HIF1α/HIF2α-EGF/EGFR-PI3K/AKT-mTOR-HIF1α signalling axis contributes to the growth of GBM through a positive feedback mechanism. Finally, HIF1α and HIF2α regulate Sox2 and Klf4, contributing to stemness expression and inducing cell cycle arrest, thus increasing malignancy in GBM. In summary, HIF1α and HIF2α regulate glioblastoma malignant progression through the EGFR-PI3K/AKT pathway via a positive feedback mechanism under the effects of Sox2 and Klf4, which provides a new tumour development model and strategy for glioblastoma treatment.

12.
Sci Total Environ ; 777: 145983, 2021 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-33677292

RESUMO

OBJECTIVES: Student dormitory rooms in China are characterized by small space and high occupancy. This study aims to investigate infection rates for common colds and influenza among college students in a Chinese university and their association with the dormitory environment. METHODS: This study involved two phases. In Phase I, 2978 students living in 998 dorm rooms in 12 buildings responded to a questionnaire survey on infections in four seasons. In Phase II, based on the data obtained from the questionnaire survey, we selected 242 dorm rooms to measure air temperature, relative humidity and CO2 concentration in both summer and winter. Ventilation rates at night were calculated based on measured CO2 concentrations. RESULTS: We found that students had infections more often in winter, and in rooms with higher occupancy and dampness problems. The median value of the ventilation rate in dorm rooms in summer was 10.7 L/s per person, while it was 4.10 L/s per person in winter. There were significant associations between ventilation rate per person at night and common cold and influenza both in summer and winter (p < 0.05). A combination of dampness and low ventilation rate significantly increased the risk of common colds (adjusted odds ratios, AOR: 1.26-1.91) and influenza (AOR: 1.49-2.20). CONCLUSION: College students living in a crowded dormitory room with low ventilation and dampness problems had more common colds and influenza infections.

13.
Microb Cell Fact ; 20(1): 70, 2021 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-33731113

RESUMO

BACKGROUND: Ascomycin is a multifunctional antibiotic produced by Streptomyces hygroscopicus var. ascomyceticus. As a secondary metabolite, the production of ascomycin is often limited by the shortage of precursors during the late fermentation phase. Polyhydroxybutyrate is an intracellular polymer accumulated by prokaryotic microorganisms. Developing polyhydroxybutyrate as an intracellular carbon reservoir for precursor synthesis is of great significance to improve the yield of ascomycin. RESULTS: The fermentation characteristics of the parent strain S. hygroscopicus var. ascomyceticus FS35 showed that the accumulation and decomposition of polyhydroxybutyrate was respectively correlated with cell growth and ascomycin production. The co-overexpression of the exogenous polyhydroxybutyrate synthesis gene phaC and native polyhydroxybutyrate decomposition gene fkbU increased both the biomass and ascomycin yield. Comparative transcriptional analysis showed that the storage of polyhydroxybutyrate during the exponential phase accelerated biosynthesis processes by stimulating the utilization of carbon sources, while the decomposition of polyhydroxybutyrate during the stationary phase increased the biosynthesis of ascomycin precursors by enhancing the metabolic flux through primary pathways. The comparative analysis of cofactor concentrations confirmed that the biosynthesis of polyhydroxybutyrate depended on the supply of NADH. At low sugar concentrations found in the late exponential phase, the optimization of carbon source addition further strengthened the polyhydroxybutyrate metabolism by increasing the total concentration of cofactors. Finally, in the fermentation medium with 22 g/L starch and 52 g/L dextrin, the ascomycin yield of the co-overexpression strain was increased to 626.30 mg/L, which was 2.11-fold higher than that of the parent strain in the initial medium (296.29 mg/L). CONCLUSIONS: Here we report for the first time that polyhydroxybutyrate metabolism is beneficial for cell growth and ascomycin production by acting as an intracellular carbon reservoir, stored as polymers when carbon sources are abundant and depolymerized into monomers for the biosynthesis of precursors when carbon sources are insufficient. The successful application of polyhydroxybutyrate in increasing the output of ascomycin provides a new strategy for improving the yields of other secondary metabolites.

14.
Sci Total Environ ; 779: 146417, 2021 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-33743454

RESUMO

While biochar (BC) is used for contaminant remediation (i.e. antibiotics) in the field, geochemical aging can alter its chemical structure, releasing nano-sized BC (NBC, sizes ranging from approximately 200 nm to 500 nm), and further influence the environmental behaviour of antibiotics affiliated with BC. In this study, we comprehensively examined the sorption behaviour of NBCs with and without aging toward ciprofloxacin (CIP), their aggregation performance, and transport behaviour in porous media. The results showed that aging improved the oxygen-containing groups within the NBCs and made their surfaces more negatively charged. The thermodynamic enhancements of specific interactions (i.e. π-π interaction or Coulombic force) with CIP resulted in the enhancement of slow sorption (from 60-64% to 40-58%) and a higher normalised sorption capacity (Qe). The aggregation of NBCs was affected by changes in individual specific interactions and interfacial forces between the NBCs before and after CIP sorption. Further, aging could enhance the transport of NBCs both in the absence and presence of CIP. In addition to the interaction with the quartz sand surface, the contributions of aggregation and chemical heterogeneity caused by rebalanced specific interactions with CIP, may explain the observed transport behaviours of the aged NBCs in porous media. Additionally, the presence of NBCs, regardless of aging, suppressed the transport of CIP. Thus, mechanisms such as increased sorption sites due to aggregation and competitive sorption between NBCs and CIP, rather than the contribution of co-transport from NBCs, might play an important role in determining the fate of CIP in the natural environment.

15.
ACS Appl Mater Interfaces ; 13(10): 11588-11596, 2021 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-33656316

RESUMO

Increasing threats from both pathogenic infections and antibiotic resistance highlight the pressing demand for nonantibiotic agents and alternative therapies. Herein, we report several new phenothiazinium-based derivatives, which could be readily synthesized via fragment-based assembly, which exhibited remarkable bactericidal activities both in vitro and in vivo. Importantly, in contrast to numerous clinically and preclinically used antibacterial photosensitizers, these compounds were able to eliminate various types of microorganisms, including Gram-(+) Staphylococcus aureus (S. aureus), Gram-(-) Escherichia coli, multidrug-resistant S. aureus, and their associated biofilms, at low drug and light dosages (e.g., 0.21 ng/mL in vitro and 1.63 ng/cm2 in vivo to eradicate S. aureus at 30 J/cm2). This study thus unveils the potential of these novel phenothiaziniums as potent antimicrobial agents for highly efficient photodynamic antibacterial chemotherapy.

16.
Ying Yong Sheng Tai Xue Bao ; 32(2): 453-466, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33650354

RESUMO

The Quaternary sediment in the Ningbo Coastal Plain was the deposit due to sea-land interaction, which recorded information of past climate changes. The region is therefore an ideal area to study paleoclimate changes and sedimentary characteristics. We determined the stratigraphic division and paleoenvironmental evolution based on 14C and paleomagnetic dating, along with detailed analyses of lithology, pollen assemblage, foraminifera and ostracodes assemblage, and grain size of sediment in core Z02 located in the southeastern Ningbo Coastal Plain. The results showed that the boundary between the Holocene and Upper Pleistocene in the core Z02 record was at 30.5 m, the boundary between the Upper and Middle Pleistocene was at 82.65 m, and the boundary between the Quaternary and Lower Cretaceous was at 90 m. The Middle Pleistocene section of the core contained few sediments, while the Lower Pleistocene section was completely missed. During the late Pleistocene, the hydrodynamic conditions experienced energy levels of medium to medium low to medium, and sedimentary facies changed from alluvial lake to overbank to river to lake to alluvial lake to lake to overbank. During the Holocene, the hydrodynamic changes experienced energy levels of medium low to low to medium, and the sedimentary facies changed from shoreland to shallow sea to shoreland lake. The Ningbo Coastal Plain had experienced tectonic uplift, weathering and erosion stage in the Early and Middle Pleistocene, from warm and humid to dry in the Late Pleistocene, and from warm and humid to dry and cool in the Holocene, as revealed by the core Z02 record. This study provided useful information in investigating past environmental changes in the subtropical coastal region of eastern China.


Assuntos
Lagos , Rios , China , Mudança Climática , Sedimentos Geológicos
17.
Toxicology ; 453: 152725, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33617914

RESUMO

Organophosphorus compounds (OP) causes prominent delayed neuropathy in vivo and cytotoxicity to neuronal cells in vitro. The primary target protein of OP's neurotoxicity is neuropathy target esterase (NTE), which can convert phosphatidylcholine (PC) to glycerophosphocholine (GPC). Recent studies reveal that autophagic cell death is important for the initiation and progression of OP-induced neurotoxicity both in vivo and in vitro. However, the mechanism of how OP induces autophagic cell death is unknown. Here it is found that GPC is an important organic osmolyte in the neuroblastoma cells, and treatment with tri-o-cresyl phosphate (TOCP), a representative OP, leads to the decrease of GPC and imbalance of extracellular and intracellular osmolality. Knockdown of GPC metabolizing enzyme glycerophosphodiester phosphodiesterase domain containing 5 (GDPD5) reverses TOCP-induced autophagic cell death, which further supports the notion that the reduced GPC level leads to the autophagic cell death. Furthermore, it is found that autophagic cell death is due to the induction of reactive oxygen species (ROS) and mitochondrial damage by imbalance of osmolality with TOCP treatment. In summary, this study reveals that TOCP treatment decreases GPC level and intracellular osmolality, which induces ROS and mitochondrial damage and leads to the cell death and neurite degradation by autophagy. This study lays the foundation for further investigations on the potential therapeutic approaches for OP neurotoxicity or NTE mutation-related neurological diseases.

18.
Neurochem Int ; 144: 104976, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33524473

RESUMO

Blood-brain barrier (BBB) damage at the early stage of ischemic stroke is a vital cause of brain parenchymal injury. The mechanism of BBB disruption has been intensively investigated, but still not fully understood. ß-1, 3-galactosyltransferase 2 (B3galt2) is expressed in the brain, but its role in the pathogenesis of cerebral ischemia remains unknown. In this study, we investigated the role of B3galt2 in cerebral ischemia in mice. Focal cerebral ischemia was induced in mice by middle cerebral artery occlusion (MCAO). B3galt2 protein levels were determined in microvessels which were isolated from ischemic brain at 12, 24 and 72 h after MCAO. Mice were administered lentiviral vectors encoding B3galt2 (LV- B3galt2) or recombinant transforming growth factor-ß1 (r-TGF-ß1) by intracerebroventricular injection. We assessed infarct volume and neurologic deficits on days 1, 3, and 14 after MCAO, blood-brain barrier (BBB) integrity at 12 and 24 h after MCAO, and the levels of TGF-ß1, TGF-ßR(Ⅱ) and p-Smad2/3 at 24 and 72 h after MCAO. Our results indicated that B3galt2 was expressed in brain microvascular endothelial cells and increased in the ischemic microvessels. Overexpression of B3galt2 by LV- B3galt2 administration reduced infarct volume and improved functional outcome after cerebral ischemia. Moreover, the neuroprotective effects were associated with preventing BBB damage. Compared with wild-type (WT) mice, heterozygous B3galt2 knockout (B3galt2-/+) mice not only showed severe BBB damage, neurologic functional deficits, but also showed reduced expression of TGF-ß1, TGF-ßR(Ⅱ) and p-Smad2/3 in microvessels after cerebral ischemia. Pre-administration of r-TGF-ß1 reduced BBB damage, and improved the neurological outcomes in both WT mice and B3galt2-/+ mice after cerebral ischemia. Our results suggested B3galt2 protected against ischemic stroke in mice, and the underlying mechanism might include TGF-ß signaling pathway in brain microvascular endothelial cells.

19.
J Org Chem ; 2021 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-33617714

RESUMO

The synthesis of multisubstituted 1-aminoindanes through catalyst-controlled diastereodivergent [3 + 2] annulation of aromatic imines with alkenes is of great interest and importance. An understanding of the exact reaction mechanism, especially for the origin of diastereoselectivity, is an essential aspect for further development of such reactions. In this study, density functional theory calculations have been carried out on the rare-earth-catalyzed diastereodivergent [3 + 2] annulation of benzaldimine with styrene. The results show that the reaction mainly involves generation of active species, olefin insertion, cyclization, and protonation steps. The noncovalent interactions, such as C-H···π and metal···π interactions, play an important role in stabilizing the key transition state or intermediate. Both steric and electronic factors account for the diastereoselectivity. The preferred cis-diastereoselectivity could be ascribed to more efficient orbital interaction, while the crowded space will induce the formation of a C-H···π interaction between the NtBu group and benzene ring in a trans-diastereoselectivity manner, thus stabilizing the trans-selective transition state. Therefore, the stereospecific product could be obtained by fine-tuning the ligand/metal combination of the catalysts.

20.
Cell Death Dis ; 12(2): 200, 2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33608500

RESUMO

Dysregulation of transforming growth factor-beta (TGFß) signaling has been implicated in liver carcinogenesis with both tumor promoting and inhibiting activities. Activation of the c-MYC protooncogene is another critical genetic event in hepatocellular carcinoma (HCC). However, the precise functional crosstalk between c-MYC and TGFß signaling pathways remains unclear. In the present investigation, we investigated the expression of TGFß signaling in c-MYC amplified human HCC samples as well as the mechanisms whereby TGFß modulates c-Myc driven hepatocarcinogenesis during initiation and progression. We found that several TGFß target genes are overexpressed in human HCCs with c-MYC amplification. In vivo, activation of TGFß1 impaired c-Myc murine HCC initiation, whereas inhibition of TGFß pathway accelerated this process. In contrast, overexpression of TGFß1 enhanced c-Myc HCC progression by promoting tumor cell metastasis. Mechanistically, activation of TGFß promoted tumor microenvironment reprogramming rather than inducing epithelial-to-mesenchymal transition during HCC progression. Moreover, we identified PMEPA1 as a potential TGFß1 target. Altogether, our data underline the divergent roles of TGFß signaling during c-MYC induced HCC initiation and progression.

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