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1.
Transl Cancer Res ; 11(4): 928-934, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35571657

RESUMO

Background: Primary intramedullary melanocytoma (PIM) is extremely rare, only 25 cases of PIM have been reported previously. Herein we report a case of PIM in the thoracic cord and reviewed its clinicopathological features, imaging features, therapeutic strategies and prognosis to provide helpful information in the diagnosis and treatment of PIM. Case Description: A 56-year-old man presented with weakness and numbness in both legs for several years. Contrast-enhanced magnetic resonance imaging (MRI) of the spinal cord was performed. Based on the imaging examination, cavernous malformation with subacute hematoma was considered as the initial diagnosis. However, histopathological and immunohistochemical analyses confirmed the final diagnosis of PIM in the thoracic cord after surgical resection. The patient had no signs of recurrence or metastasis during a 17-month follow-up. Conclusions: MRI is the preferred method for the evaluation of PIM. PIM is characterized by a high signal on T1WI and a low signal on T2WI. It is difficult to make the differential diagnosis from cavernous malformation with hematoma before surgery due to its rarity. However, the symptom is not sudden but gradually worsened over a relatively long period in the PIM patients, which is an important difference from the cavernous malformation with hematoma. Therefore, PIM should receive diagnostic con¬sideration for an intramedullary lesion that is high signal on T1WI and low signal on T2WI in a patient with gradually worsened symptoms rather than sudden onset. It is of great importance for neurosurgeons and radiologists to recognize the characteristics of this disease, make the correct diagnosis in time and avoid delayed treatment.

2.
J Psychopharmacol ; 36(5): 645-652, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35574908

RESUMO

RATIONALE AND OBJECTIVES: Increased levels of high-sensitivity C-reactive protein (CRP) are associated with mood symptoms in adults with bipolar disorder (BD). The few studies on this topic in youth with BD have not included controls. We, therefore, examined CRP levels in relation to symptomatic status in youth with and without BD. METHODS: Participants included 154 youth (mean age 17 years; 48 asymptomatic BD, 39 symptomatic BD, 67 healthy controls (HC)). Rank analysis of covariance test examined group differences in CRP, controlling for age and sex. Correlation between CRP and mood symptom severity was examined using Spearman's correlation within the BD group. RESULTS: There were significant group differences in CRP levels (F(2,151) = 5.06, p = 0.007, ηp2=0.06); post hoc analyses showed higher CRP levels in the symptomatic BD group compared with HC (p = 0.01). In sensitivity analyses, this finding was no longer significant after controlling for body mass index (BMI). CRP was not significantly associated with symptomatic severity. CONCLUSIONS: CRP levels are elevated among symptomatic youth with BD, partly related to BMI. As elevated BMI is associated with mood symptom burden, prospective studies are warranted to parse the associations among mood symptoms, BMI, and inflammation. Given the proportion of time that youth with BD are symptomatic, present findings raise concern about the long-term impact of elevated CRP on blood vessels, brain, and related clinical outcomes.

3.
J Nanobiotechnology ; 20(1): 212, 2022 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-35524270

RESUMO

A multifunctional nanoplatform with core-shell structure was constructed in one-pot for the synergistic photothermal, photodynamic, and chemotherapy against breast cancer. In the presence of gambogic acid (GA) as the heat-shock protein 90 (HSP90) inhibitor and the gold nanostars (AuNS) as the photothermal reagent, the assembly of Zr4+ with tetrakis (4-carboxyphenyl) porphyrin (TCPP) gave rise to the nanocomposite AuNS@ZrTCPP-GA (AZG), which in turn, further coated with PEGylated liposome (LP) to enhance the stability and biocompatibility, and consequently the antitumor effect of the particle. Upon cellular uptake, the nanoscale metal - organic framework (NMOF) of ZrTCPP in the resulted AuNS@ZrTCPP-GA@LP (AZGL) could be slowly degraded in the weak acidic tumor microenvironment to release AuNS, Zr4+, TCPP, and GA to exert the synergistic treatment of tumors via the combination of AuNS-mediated mild photothermal therapy (PTT) and TCPP-mediated photodynamic therapy (PDT). The introduction of GA serves to reduce the thermal resistance of the cell to re-sensitize PTT and the constructed nanoplatform demonstrated remarkable anti-tumor activity in vitro and in vivo. Our work highlights a facile strategy to prepare a pH-dissociable nanoplatform for the effective synergistic treatment of breast cancer.


Assuntos
Neoplasias da Mama , Estruturas Metalorgânicas , Nanocompostos , Fotoquimioterapia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Feminino , Humanos , Lipossomos/uso terapêutico , Microambiente Tumoral , Xantonas
4.
Ecol Lett ; 2022 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-35545523

RESUMO

Organic farming supports higher biodiversity than conventional farming, but at the cost of lower yields. We conducted a meta-analysis quantifying the trade-off between biodiversity and yield, comparing conventional and organic farming. We developed a compatibility index to assess whether biodiversity gains from organic farming exceed yield losses, and a substitution index to assess whether organic farming would increase biodiversity in an area if maintaining total production under organic farming would require cultivating more land at the expense of nature. Overall, organic farming had 23% gain in biodiversity with a similar cost of yield decline. Biodiversity gain is negatively correlated to yield loss for microbes and plants, but no correlation was found for other taxa. The biodiversity and yield trade-off varies under different contexts of organic farming. The overall compatibility index value was close to zero, with negative values for cereal crops, positive for non-cereal crops, and varies across taxa. Our results indicate that, on average, the proportion of biodiversity gain is similar to the proportion of yield loss for paired field studies. For some taxa in non-cereal crops, switching to organic farming can lead to a biodiversity gain without yield loss. We calculated the overall value of substitution index and further discussed the application of this index to evaluate when the biodiversity of less intensified farming system is advantageous.

5.
Nature ; 605(7910): 453-456, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35585342

RESUMO

Atoms with a highly excited electron, called Rydberg atoms, can form unusual types of molecular bonds1-4. The bonds differ from the well-known ionic and covalent bonds5,6 not only by their binding mechanisms, but also by their bond lengths ranging up to several micrometres. Here we observe a new type of molecular ion based on the interaction between the ionic charge and a flipping-induced dipole of a Rydberg atom with a bond length of several micrometres. We measure the vibrational spectrum and spatially resolve the bond length and the angular alignment of the molecule using a high-resolution ion microscope7. As a consequence of the large bond length, the molecular dynamics is extremely slow. These results pave the way for future studies of spatio-temporal effects in molecular dynamics (for example, beyond Born-Oppenheimer physics).

6.
Toxicol Appl Pharmacol ; : 116074, 2022 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-35605788

RESUMO

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver diseases worldwide. Oxidative stress has been considered a key factor in the pathogenesis of NAFLD. Phosphatidylinositol (3,4,5)-trisphosphate-dependent Rac exchanger 1 (PREX1), a guanine nucleotide exchange factor for Rac, has been associated with inflammation and oxidative stress. This study aimed to investigate the biological function of PREX1 in the progression of NAFLD. Male C57BL/6 mice were fed a high-fat diet for 12 weeks to induce NAFLD in vivo. Adeno-associated virus type 8-mediated liver-specific PREX1 depletion was employed to investigate the role of PREX1 in the progression of high-fat diet-induced NAFLD. Murine hepatocyte cell line AML-12 was stimulated with palmitic acid for 24 h to induce steatosis in vitro. PREX1 depletion was carried out by transfection with PREX1 small interfering RNA. Results showed that PREX1 depletion exerted protective effects against lipid accumulation, oxidative stress and inflammation and inhibited activation of the nuclear factor-κB (NF-κB) signaling pathway in vivo and in vitro. Subsequently, NF-κB inhibitor BAY11-7082 was applied to investigate the role of the NF-κB signaling pathway in the protective effect of PREX1 inhibition against NAFLD. We confirmed that PREX1 inhibition mitigated palmitic acid-induced hepatocellular inflammation mainly via the NF-κB signaling pathway and lipid accumulation and oxidative stress at least partly via the NF-κB signaling pathway. This study highlights the biological function of PREX1 in the pathogenesis of NAFLD.

7.
J Anim Sci ; 2022 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-35579990

RESUMO

This study evaluated the effect of an emulsifier on the energetic values of lipids fed to yellow-feathered chickens and established prediction equations for the metabolizable energy (ME) of lipids fed with and without an emulsifier. One hundred and ninety-two Chinese yellow-feathered roosters (Wen's Yellow A; initial BW = 2.37 ± 0.33 kg) were individually weighed, divided into 4 body weight blocks, and randomly assigned within block to the 16 dietary treatments with replicates of 3 roosters. The diets consisted of a corn basal diet or the basal diet supplemented with 8% of corn oil (CO), soybean oil (SO), cottonseed oil (CSO), rice bran oil (RBO), palm oil (PO), modified palm oil (MPO), or lard was evaluated with or without an emulsifier (0.02% of diet) in an 8×2 factorial arrangement. Diets were fed for 8 d, with 4 d for adaptation to diets and another 4 d for excreta collection. There was interaction between lipid sources and emulsifier on ME (apparent ME and N-corrected apparent ME) of the lipids (P < 0.05). Addition of 0.02% emulsifier had no effect on the ME of CO, SO, PO or lard, but reduced the ME of CSO (P < 0.05) and MPO (P < 0.05), and tended to increase the ME of RBO (0.05 ≤ P < 0.10). There was a quadratic relationship between ME and concentration of stearic (C18:0) (P < 0.05) or linoleic acid (C18:2) (0.05 ≤ P < 0.10), and a linear function between ME and concentration of oleic acid (C18:1) or monounsaturated fatty acids (P < 0.05) in diets without emulsifier. The ME of lipids could be predicted by the concentration of C18:0 with C18:1 or with MUFA without an emulsifier. With an emulsifier, the ME concentration was affected linearly by the concentration of myristic acid (C14:0), palmitic acid (C16:0), C18:2, polyunsaturated fatty acids, unsaturated fatty acids, saturated fatty acids, and the ratio of unsaturated to saturated fatty acids (P < 0.05). Prediction equations for the ME of lipid were established on the content of C18:0, C16:0, C14:0, SFA, and U:S. These results indicated that the ME of RBO is positively affected by emulsifiers, but the ME of CSO and MPO declines with emulsifiers. These inconsistent results may be influenced by the relationship between ME and concentration of fatty acid across sources of dietary lipids.

8.
Int J Ophthalmol ; 15(5): 766-772, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35601174

RESUMO

AIM: To determine the anatomic and visual outcomes of prophylactic juxtapapillary laser photocoagulation treatment alone in the prevention of retinal detachment (RD) in a cohort of pediatric patients diagnosed with morning glory syndrome (MGS). METHODS: A total of 24 eyes of 22 consecutive patients aged 0-15y diagnosed with MGS treated with prophylactic juxtapapillary laser photocoagulation alone were reviewed. Data including demographics, ocular examination, anatomic and visual outcomes, following treatment and complications were collected. RESULTS: Two patients had bilateral laser treatment and 20 had monocular laser treatment. The age at treatment of 13 (59.1%) patients was less than 12mo. The presenting symptoms included strabismus (6/22, 27.3%), decreased vision (2/22, 9.1%), and routine fundus screening (14/22, 63.6%). Fifteen (68.2%) patients underwent cranial magnetic resonance imaging (MRI) examinations, and 3 of those 15 (20.0%) had abnormal findings in the nervous system. Based on preoperative wide-field fundus photography and B-scan echography, all (100.0%) eyes had no obvious RD. On postoperative 1mo and 6mo and the following follow-ups, the anatomic outcomes of all eyes remained stable. The mean follow-up duration was 27.7±17.5mo. No severe complications were found. Preoperative visual acuity acquired from 2 (9.1%) patients ranged from light perception to 20/200. Postoperative acuity acquired from 11 (50.0%) patients ranged from light perception to 20/125. CONCLUSION: The preliminary anatomic and visual outcomes of prophylactic juxtapapillary laser treatment alone in pediatric MGS patients are relatively stable in a short-term follow-up. Further long-term clinical observation will be needed to confirm its efficacy and safety.

9.
World J Clin Cases ; 10(9): 2773-2782, 2022 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-35434098

RESUMO

BACKGROUND: Sedation during endoscopic ultrasonography (EUS) poses many challenges and moderate-to-deep sedation are often required. The conventional method to preform moderate-to-deep sedation is generally intravenous benzodiazepine alone or in combination with opioids. However, this combination has some limitations. Intranasal medication delivery may be an alternative to this sedation regimen. AIM: To determine, by continual reassessment method (CRM), the minimal effective dose of intranasal sufentanil (SUF) when combined with intranasal dexmedetomidine (DEX) for moderate sedation of EUS in at least 95% of patients (ED95). METHODS: Thirty patients aged 18-65 and scheduled for EUS were recruited in this study. Subjects received intranasal DEX and SUF for sedation. The dose of DEX (1 µg/kg) was fixed, while the dose of SUF was assigned sequentially to the subjects using CRM to determine ED95. The sedation status was assessed by modified observer's assessment of alertness/sedation (MOAA/S) score. The adverse events and the satisfaction scores of patients and endoscopists were recorded. RESULTS: The ED95 was intranasal 0.3 µg/kg SUF when combined with intranasal 1 µg/kg DEX, with an estimated probability of successful moderate sedation for EUS of 94.9% (95% confidence interval: 88.1%-98.9%). When combined with intranasal 1 µg/kg DEX, probabilities of successful moderate sedation at each dose level of intranasal SUF were as follows: 0 µg/kg SUF, 52.8%; 0.1 µg/kg SUF, 75.4%; 0.2 µg/kg SUF, 89.9%; 0.3 µg/kg SUF, 94.9%; 0.4 µg/kg SUF, 98.0%; 0.5 µg/kg SUF, 99.0%. CONCLUSION: The ED95 needed for moderate sedation for EUS is intranasal 0.3 µg/kg SUF when combined with intranasal 1 µg/kg DEX, based on CRM.

10.
J Neuroinflammation ; 19(1): 84, 2022 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-35413928

RESUMO

BACKGROUND: miR-203 was first indicated in maintaining skin homeostasis and innate immunity. Aberrant expression of miR-203 was found associated with pathological progressions of immune disorders, cancers, as well as neurodegenerations. Recently, increasing data on miR-203 in regulating neuroinflammation and neuronal apoptosis has raised extensive concern about the biological function of this microRNA. METHODS: Mouse model with ectopic miR-203 expression in the hippocampus was constructed by stereotactic injection of lentiviral expression vector of pre-miR-203. Association of miR-203 and mRNA of Akirin2, as well as the competition for miR-203 targeting between Akirin2 3'UTR and another recently characterized miR-203 target, 14-3-3θ, was verified using Dual-Luciferase Reporter Gene Assay and western blot. Microglia activation and pro-inflammatory cytokines expression in the hippocampus of mice overexpressing miR-203 was evaluated using immunohistochemistry analysis and western blot. Neuronal cell death was monitored using anti-caspase 8 in immunohistochemistry as well as TUNEL assay. Cognition of mice was assessed with a behavior test battery consisting of nesting behavior test, Barnes maze and fear conditioning test. RESULTS: Akirin2, an activator of NF-κB signaling, was identified as a direct target of miR-203. By also targeting 14-3-3θ, a negative regulator of NF-κB signaling, miR-203 displayed an overall pro-inflammatory role both in vitro and in vivo. Promoted nuclear translocation of NF-κB and increased expression of proinflammatory cytokines were observed in cultured BV2 cells transfected with miR-203 mimics. Microglia activation and upregulation of NF-κB, IL-1ß and IL-6 were observed in mouse hippocampus with overexpression of miR-203. In addition, promoted neuronal cell death in the hippocampus and impaired neuronal activities resulted in cognitive dysfunction of mice with ectopic miR-203 expression in the hippocampus. CONCLUSION: A pro-inflammatory and neurodisruptive role of miR-203 was addressed based on our data in this study. Given the identification of Akirin2 as a direct target of miR-203 and the competition with 14-3-3θ for miR-203 targeting, together with the findings of other signaling molecules in NF-κB pathway as targets of miR-203, we proposed that miR-203 was a master modulator, fine-tunning neuroinflammation by juggling different components of NF-κB signaling.


Assuntos
MicroRNAs , NF-kappa B , Animais , Citocinas/metabolismo , Inflamação/metabolismo , Camundongos , MicroRNAs/genética , MicroRNAs/metabolismo , Microglia/metabolismo , NF-kappa B/metabolismo , Proteínas Repressoras/metabolismo
12.
Bull Entomol Res ; : 1-6, 2022 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-35382913

RESUMO

Sampling flower-visiting insects in agricultural fields at large spatial and temporal scales is significant for understanding local insect pollinator communities. The most commonly used method, pan trap, has been criticized due to its attractant bias. A window trap (also referred to as the flight-intercept trap) is a non-attractant sampling method, which has been applied in forests and grasslands, but rarely in agricultural fields. We aim to test whether we can replace pan traps with window traps in agricultural fields by comparing species richness and species composition between the two methods, and to show whether flower-visiting insects collected in both traps can reflect flower-visiting activity recorded by camera observation. We conducted a 2-year study to compare the performance of these sampling methods in an oilseed rape field. Results showed that the relative abundance of dominant flower-visiting species was highly correlated between the window trap and the pan trap samples, while window traps caught more individuals and higher (rarefied) species richness than pan traps. The species composition of window traps was more similar to each other than that of pan traps. The proportion of honey bees (Apis spp.) collected in both traps underestimated their flower-visiting activity recorded by camera observations, while sweat bees (Halictidae) and butterflies (Lepidoptera) were overestimated. Our study suggests that the window trap has the potential to serve as an alternative sampling method of flower-visiting insects to the pan trap. However, we need to be cautious when using specimens caught in both traps as a proxy of their flower-visiting activity.

13.
DNA Res ; 2022 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-35466378

RESUMO

Sophora japonica is a medium-size deciduous tree belonging to Leguminosae family and famous for its high ecological, economic, and medicinal value. Here, we reveal a draft genome of S. japonica, which was approximately 511.49 Mb long (contig N50 size of 17.34 Mb) based on Illumina, Nanopore and Hi-C data. We reliably assembled 110 contigs into 14 chromosomes, representing 91.62% of the total genome, with an improved N50 size of 31.32 Mb based on Hi-C data. Further investigation identified 271.76 Mb (53.13%) of repetitive sequences and 31,000 protein-coding genes, of which 30,721 (99.1%) were functionally annotated. Phylogenetic analysis indicates that S. japonica separated from Arabidopsis thaliana and Glycine max about 107.53 and 61.24 million years ago, respectively. We detected evidence of species-specific and common-legume WGD events in S. japonica. We further found that multiple TF families (e.g., BBX and PAL) have expanded in S. japonica, which might have led to its enhanced tolerance to abiotic stress. In addition, S. japonica harbors more genes involved in the lignin and cellulose biosynthesis pathways than the other two species. Finally, population genomic analyses revealed no obvious differentiation among geographical groups and the effective population size continuously declined since 2 Ma. Our genomic data provide a powerful comparative framework to study the adaptation, evolution and active ingredients biosynthesis in S. japonica. More importantly, our high-quality S. japonica genome is important for elucidating the biosynthesis of its main bioactive components, and improving its production and/or processing.

15.
Artigo em Inglês | MEDLINE | ID: mdl-35255785

RESUMO

BACKGROUND: Ecliptae prostrata (L.) L. has been widely used in east Asia with reported biological activities including anti-cancer properties. OBJECTIVE: We aimed to investigate the effect of ethyl acetate extract of Ecliptae prostrata (L.) L. (EAE) and its component wedelolactone on the proliferation and migration of head and neck squamous cancer cells. METHODS: The proliferation of human SCC-4 and mouse CU110-1 tongue squamous carcinoma cells was assessed using the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) method. Scratch wound assays were performed to assesse cell migration rates. The levels of E-cadherin and vimentin were used as markers of the epithelial-to-mesenchymal transition (EMT). AhR, CYP1A1 and CYP1B1 levels were examined to uncover the mechanism of inhibition of cell migration by wedelolactone. RESULTS: We found that EAE and wedelolactone decreased the proliferation of human SCC-4 cells and mouse CU110-1 cells at doses of EAE at > 25 µg/ml and wedelolactone at > 6.25 µg/ml. Similarly, both EAE and wedelolactone produced inhibitory effects against migration but the effective doses that significantly inhibited migration were lower than those affecting proliferation. Wedelolactone below 12.5 µg/ml inhibited the epithelial-to-mesenchymal transition (EMT) with increased expression of E-cadherin and decreased expression of vimentin in SCC-4 and CU110-1 cells. Further analysis showed wedelolactone inhibited the expression of AhR and its downstream target molecules CYP1A1 and CYP1B1 in both squamous carcinoma cells at the same doses inhibiting cell migration. Addition of benzo (a)pyrene [B(a)P], an agonist of AhR, stimulated migration, especially in the CU110-1 cells with reported cancer stem cell.

16.
Ecol Evol ; 12(3): e8659, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35261747

RESUMO

The COVID-19 pandemic has strongly disrupted academic activities, particularly in disciplines with a strong empirical component among other reasons by limiting our mobility. It is thus essential to assess emergency remote teaching plans by surveying learners' opinions and perceptions during these unusual circumstances. To achieve this aim, we conducted a survey during the spring semester of 2021 in an environmental science program to ascertain learners' perceptions on online and onsite learning activities in ecology-based modules. We were particularly interested not only in comparing the performance of these two types of activities but also in understanding the role played by learners' perceptions about nature in shaping this pattern. Environmental science programs are rather heterogeneous from a conceptual point of view and, thus, learners may also be more diverse than in traditional ecology programs, which may affect their interest for ecology-based modules. We assessed connectedness to nature by computing the reduced version of the Nature Relatedness Scale. Here, we found that online activities systematically obtained significantly lower scores than onsite activities regardless of the wording employed, and that altruistic behaviors were prevalent among learners. Interestingly, scores for both onsite and online activities were strongly influenced by learners' connectedness to nature, as learners with a stronger connection to nature gave higher scores to both types of activities. Our results suggest that an effort to improve the efficacy of remote learning activities should be the focus of research about teaching methodologies in predominantly empirical scientific disciplines.

17.
J Med Chem ; 65(6): 5057-5071, 2022 03 24.
Artigo em Inglês | MEDLINE | ID: mdl-35175763

RESUMO

The catalytic properties of proteolysis targeting chimeras (PROTACs) may lead to uncontrolled off-tissue target degradation that causes potential toxicity, limiting their clinical applications. The precise control of this technology in a tissue-selective manner can minimize the potential toxicity. Hypoxia is a hallmark of most solid tumors, accompanied by elevated levels of nitroreductase (NTR). Based on this character, we presented a type of NTR-responsive PROTACs to selectively degrade proteins of interest (POI) in tumor tissues. Compound 17-1 was the first NTR-responsive PROTAC synthesized by incorporating the caging group on the Von Hippel-Lindau (VHL) E3 ubiquitin ligase ligand. It could be activated by NTR to release the active PROTAC 17 to efficiently degrade the EGFR protein and subsequently exert antitumor efficacy. Thus, a general strategy for the precise control of PROTAC to induce POI degradation in tumor tissues by NTR was established, which provided a generalizable platform for the development of NTR-controlled PROTACs to achieve selective degradation.


Assuntos
Quimera , Neoplasias , Quimera/metabolismo , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Neoplasias/metabolismo , Nitrorredutases/metabolismo , Proteólise , Ubiquitina-Proteína Ligases/metabolismo
18.
J Am Chem Soc ; 144(8): 3580-3589, 2022 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-35170947

RESUMO

Cytochrome P450s are one of the most versatile oxidases that catalyze significant and unique chemical transformations for the construction of complex structural frameworks during natural product biosynthesis. Here, we discovered a set of P450s, including SdnB, SdnH, SdnF, and SdnE, that cooperatively catalyzes the reshaping of the inert cycloaraneosene framework to form a highly oxidized and rearranged sordarinane architecture. Among them, SdnB is confirmed to be the first P450 (or oxidase) that cleaves the C-C bond of the epoxy residue to yield formyl groups in pairs. SdnF selectively oxidizes one generated formyl group to a carboxyl group and accelerates the final Diels-Alder cyclization to furnish the sordarinane architecture. Our work greatly enriches the enzyme functions of the P450 superfamily, supplies the missing skills of the P450 synthetic toolbox, and supports them as biocatalysts in further applications toward the synthesis of new chemical entities.


Assuntos
Sistema Enzimático do Citocromo P-450 , Diterpenos , Catálise , Sistema Enzimático do Citocromo P-450/metabolismo , Oxirredução , Metabolismo Secundário
19.
Langmuir ; 38(8): 2576-2589, 2022 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-35166554

RESUMO

In the United Kingdom, decommissioning of legacy spent fuel storage facilities involves the retrieval of radioactive sludges that have formed as a result of corrosion of Magnox nuclear fuel. Retrieval of sludges may re-suspend a colloidal fraction of the sludge, thereby potentially enhancing the mobility of radionuclides including uranium. The colloidal properties of the layered double hydroxide (LDH) phase hydrotalcite, a key product of Magnox fuel corrosion, and its interactions with U(VI) are of interest. This is because colloidal hydrotalcite is a potential transport vector for U(VI) under the neutral-to-alkaline conditions characteristic of the legacy storage facilities and other nuclear decommissioning scenarios. Here, a multi-technique approach was used to investigate the colloidal stability of hydrotalcite and the U(VI) sorption mechanism(s) across pH 7-11.5 and with variable U(VI) surface loadings (0.01-1 wt %). Overall, hydrotalcite was found to form stable colloidal suspensions between pH 7 and 11.5, with some evidence for Mg2+ leaching from hydrotalcite colloids at pH ≤ 9. For systems with U present, >98% of U(VI) was removed from the solution in the presence of hydrotalcite, regardless of pH and U loading, although the sorption mode was affected by both pH and U concentrations. Under alkaline conditions, U(VI) surface precipitates formed on the colloidal hydrotalcite nanoparticle surface. Under more circumneutral conditions, Mg2+ leaching from hydrotalcite and more facile exchange of interlayer carbonate with the surrounding solution led to the formation of uranyl carbonate species (e.g., Mg(UO2(CO3)3)2-(aq)). Both X-ray absorption spectroscopy (XAS) and luminescence analysis confirmed that these negatively charged species sorbed as both outer- and inner-sphere tertiary complexes on the hydrotalcite surface. These results demonstrate that hydrotalcite can form pseudo-colloids with U(VI) under a wide range of pH conditions and have clear implications for understanding the uranium behavior in environments where hydrotalcite and other LDHs may be present.

20.
Metallomics ; 14(5)2022 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-35150263

RESUMO

The growing evidence over the past few decades has indicated that the photodynamic antitumor activity of transition metal complexes, and Re(I) compounds are potential candidates for photodynamic therapy. This study reports the synthesis, characterization, and anti-tumor activity of three new Re(I)-guadinium complexes. Cytotoxicity tests reveal that complex Re1 increased cytotoxicity by 145-fold from IC50 > 180 µM in the dark to 1.3 ± 0.7 µM following 10 min of light irradiation (425 nm) in HeLa cells. Further, the mechanism by which Re1 induces apoptosis in the presence or absence of light irradiation was investigated, and results indicate that cell death was caused through different pathways. Upon irradiation, Re1 first accumulates on the cell membrane and interacts with death receptors to activate the extrinsic death receptor-mediated signaling pathway, and then is transported into the cell cytoplasm. Most of the intracellular Re1 locates within mitochondria, improving the reactive oxygen species level, and decreasing mitochondrial membrane potential and ATP levels, and inducing the activation of caspase-9 and, thus, apoptosis. Subsequently, the residual Re1 can translocate into the cell nucleus, and activates the p53 pathway, causing cell cycle arrest and eventually cell death.


Assuntos
Fármacos Fotossensibilizantes , Rênio , Apoptose , Pontos de Checagem do Ciclo Celular , Linhagem Celular Tumoral , Guanidina/farmacologia , Células HeLa , Humanos , Potencial da Membrana Mitocondrial , Mitocôndrias/metabolismo , Fármacos Fotossensibilizantes/metabolismo , Fármacos Fotossensibilizantes/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Receptores de Morte Celular/metabolismo , Rênio/farmacologia
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