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1.
Biochim Biophys Acta Mol Basis Dis ; : 166213, 2021 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-34311082

RESUMO

Most pancreatic ductal adenocarcinomas (PDACs) are diagnosed at an advanced or metastatic stage. Metastasis is the one of the major obstacles to prolonging the survival time of patients with pancreatic cancer. The tripartite motif (TRIM) family member TRIM15 has been implicated in cancer development. Our bioinformatics analysis indicated that TRIM15 might be involved in the regulation of pancreatic cancer metastasis. However, the role of TRIM15 in PDAC remains unclear. Metabolic reprogramming involving dysregulated lipid synthesis is common in patients with PDAC. Targeting lipid anabolism has been proposed as a strategy to treat PDAC. In this study, we demonstrated that TRIM15 expression was elevated in PDAC tissues, and this elevated expression was associated with a poor prognosis. TRIM15 silencing suppressed the invasion and migration of pancreatic cancer cells. Importantly, the mass spectrometry analysis suggested that Apolipoprotein A1 (APOA1), the main component of high-density lipoprotein (HDL) that is involved in lipid transport and metabolism, might be one of the binding partners of TRIM15. Further experiment indicated that TRIM15 interacted with APOA1 through its PRY/SPRY domain and promoted APOA1 polyubiquitination via its RING domain. APOA1 degradation enhanced lipid anabolism and promoted lipid droplet accumulation in pancreatic cancer cells. Furthermore, we showed that TRIM15 might promote PDAC metastasis by regulating lipid metabolism via the APOA1-LDLR axis. Consequently, targeting the TRIM15-APOA1-LDLR axis may be a strategy to inhibit PDAC metastasis by blocking triglyceride synthesis.

2.
Int J Legal Med ; 2021 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-34313847

RESUMO

Electrical injury is a relatively uncommon but potentially devastating form of multi-system injury with high morbidity and mortality. In common electric injury cases, it is usually difficult to find characteristic changes of electric injury in major organs by using routine histopathological test methods unless there are landmark traces of electric injury, known as electric marks. How to determine electric shock death, especially in the absence of typical electrical marks on the body surface in some cases (which account for about two-thirds of electric injury cases), remains a challenging problem in forensic practice. Our summary shows that many current related studies have focused their efforts to find characteristic histopathological changes in major organs of the body caused by electric injury. Based on the results obtained through comparison of the literature, we find that it may be more urgent and important to find the optimal autopsy or sampling sites in cases with no typical electric marks, knowing that these sites may often reflect the most significant histopathological changes of electric injury, for instance anatomy and sampling of the anterior wrist and the medial malleolus in cases involving the hand-to-foot electric circuit pathway. In this article, we make a summary of advances in identification methods of electric injury, hoping that it could provide some new insights for further research in this field.

3.
Plant Physiol Biochem ; 166: 939-949, 2021 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-34247108

RESUMO

The root phenotype is an important aspect of plant architecture and plays a critical role in plant facilitation of the extraction of water and nutrition from the soil. MicroRNAs (miRNAs) are classes of small RNAs with important roles in regulating endogenous gene expression at the post-transcriptional level that function in a range of plant development processes and in the response to abiotic stresses. However, little is known concerning the molecular mechanism of miRNAs in regulating the generation and development of plant root architecture. Herein, we demonstrated that potato miR160a/b acted as a critical regulator and affected plant root architecture by targeting the mRNA of StARF10 and StARF16 for cleavage. The miR160a/b precursor was cloned from potato. Quantitative PCR assays showed that the expression levels of miR160 and its targets were down- or up-regulated with the development of potato roots, respectively. Moreover, transgenic lines with suppressed stu-miR160 expression were established with the short tandem targets mimic (STTM), and the results showed that the ectopic expression of miR160a/b altered the levels of auxin and the expression of auxin signaling-related genes and caused drastic change in root architecture compared with that in control plants. Suppressing the expression of miR160 led to a severe reduction in root length, an increase in the number of lateral roots, and a decrease in fresh root weight in potato. Collectively, our data established a key role of miR160 in modulating plant root architecture in potato.

4.
Clin Exp Immunol ; 2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34195995

RESUMO

The recurrence of patients with epithelial ovarian cancer (EOC) is largely attributed to tumour cells escaping from the surveillance of immune cells. However, to date there is a lack of studies that have systematically evaluated the associations between the infiltration fraction of immune cells and the recurrence risk of EOC. Based on the micro-ribonucleic acid (microRNA) expression profiles of 441 EOC patients, we constructed a microRNA-based panel with recurrence prediction potential using non-negative matrix factorization consensus clustering. Then, we evaluated the association between recurrence risk and infiltration proportions among 10 immune cell types by CIBERSORT and a multivariable Cox regression model. As a result, we identified a 72-microRNA-based panel that could stratify patients into high and low risk of recurrence. The infiltration of plasma cells and M1 macrophages was consistently significantly associated with the risk of recurrence in patients with EOC. Plasma cells were significantly associated with a decreased risk of relapse [hazard ratio (HR) = 0.58, p = 0.006), while M1 macrophages were associated with an increased risk of relapse (HR = 1.59, p = 0.003). Therefore, the 72-microRNA-based panel, M1 macrophages and plasma cells may hold potential to serve as recurrence predictors of EOC patients in clinical practice.

5.
Sci Total Environ ; 796: 148923, 2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34271391

RESUMO

Biochar is widely applied in soil for agricultural and environmental purposes. Soluble fraction of biochar may be released from bulk biochar as dissolved biochar (DBC) after irrigation or rainfall. DBC had been reported to possess high chemical activity in aqueous system, while less attention was paid to the impact of DBC on the soil environmental processes. In this work, the impact of DBC on ferric (hydro) oxides was systematically examined. Our study showed that DBC prepared from rice straw could significantly promote the dissolution of ferric oxides with unstable and metastable crystalline structures, e.g., ferrihydrite under relatively acidic condition. Organic ligand-promoted dissolution was the main mechanism for iron release from ferrihydrite, and the low-molecular-weight DBC component (less than 1000 Da) was the major contributor for this process. Furthermore, the organic carbon content normalized ligand-promoted dissolution capacity for DBC was much higher than common dissolved organic matters. More importantly, DBC could promote the release of Cr from dichromate-adsorbed ferric mineral. Our results suggest that in soils with relatively low pH and high contents of ferric hydroxides, e.g., red soil in southern China, DBC derived from applied biochar could enhance the mobility and bioavailability of iron and other heavy metals. The dissolved metals would play active roles in soil redox cycle and biotic processes. Therefore, it's necessary to evaluate the long-term impact of biochar application on acidic field soils with high iron content.

6.
Adv Sci (Weinh) ; : e2100881, 2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34319001

RESUMO

Renal cell carcinoma (RCC) is a malignant tumor of the kidneys. Approximately 70% of RCC cases are clear cell renal cell carcinoma with von Hippel-Lindau (VHL) gene mutation and activation of the vascular endothelial growth factor (VEGF) pathway. Tyrosine kinase inhibitors (TKIs) targeting VEGF have emerged as promising agents for RCC treatment. Apart from primary resistance, acquired resistance to TKIs after initial tumor regression is common in RCC. Recently, immune checkpoint inhibition, including PD-1/PD-L1 blockade, alone or in combination with TKIs has improved the overall survival of patients with RCC. Ribonucleotide reductase subunit M2 (RRM2) has been reported in many types of cancer and has been implicated in tumor progression. However, the role of RRM2 in TKIs resistance in RCC remains unclear. In this study, the authors have demonstrated that RRM2 is upregulated in sunitinib-resistant RCC cells and patient tissues. They also find that RRM2 stabilizes ANXA1 and activates the AKT pathway independent of its ribonucleotide reductase activity, promoting sunitinib resistance in RCC. Moreover, RRM2 regulated antitumor immune responses, and knockdown of RRM2 enhance the anti-tumor efficiency of PD-1 blockade in renal cancer. Collectively, these results suggest that aberrantly expressed RRM2 may be a promising therapeutic target for RCC.

7.
Environ Technol ; : 1-28, 2021 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-34238123

RESUMO

Dichloromethane (DCM) as a low-chlorinated organic compound is hardly to be degraded through reductive dechlorination pathway. In this study, the removal of DCM in Fenton-like system using activated carbon fibers supported zero-valence Fe/Ni nanoparticles (ACF-Fe/Ni) as catalyst was investigated and compared with that of traditional Fenton system (Fe2+/H2O2). The influence of vital parameters including initial solution pH, DCM concentration, catalyst and H2O2 dosages, temperature and cosolute on the removal of DCM was systematically studied. The results showed that 94.2% of DCM with an initial concentration of 5 mg/L could be removed in the Fenton-like reaction under the optimum condition: initial pH of 2.0, 0.4 g/L of ACF-Fe/Ni, 10 mM of H2O2 and temperature of 30°C. In comparison, the removal of DCM in the Fenton-like system was faster than that of the Fenton system and the corresponding activation energies were 39.69 and 33.82 kJ/mol, respectively. The coexistence of solute was adverse to the removal of DCM in the both Fenton-like and Fenton systems. Moreover, the active species for DCM removal in the Fenton-like system was confirmed as hydroxyl radical (·OH) via the quenching experiment and EPR measurement. The incomplete mineralization (41.7%) of DCM after reaction indicated that the Fenton-like technology had a potential to realize DCM non-toxic and harmless conversion and organic intermediates formed needed to take longer to be decomposed.

8.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 38(7): 667-670, 2021 Jul 10.
Artigo em Chinês | MEDLINE | ID: mdl-34247374

RESUMO

OBJECTIVE: To explore the genetic basis for a fetus with cerebellar dysplasia and widened lateral ventricles. METHODS: The couple have elected induced abortion after careful counseling. Skin tissue sample from the abortus and peripheral venous blood samples from both parents were collected for the extraction of genomic DNA, which was then subjected to whole exome sequencing. Candidate variant was verified by Sanger sequencing. RESULTS: Prenatal ultrasonography showed increased nuchal translucency (0.4 cm) and widened lateral ventricles. Magnetic resonance imaging revealed infratentorial brain dysplasia. By DNA sequencing, the fetus was found to carry compound heterozygous variants c.1A>G and c.1564G>A of the RARS2 gene, which were inherited from its father and mother, respectively. Among these, c.1A>G was known to be pathogenic, but the pathogenicity of c.1564G>A was unreported previously. Based on the American College of Medical Genetics and Genomics guidelines, the c.1564G>A variant of RARS2 gene was predicted to be likely pathogenic(PM2+PM3+PP3+PP4). CONCLUSION: The compound heterozygous variants c.1A>G and c.1564G>A of RARS2 gene contributed to the fetus suffering from pontocerebellar hypoplasia type 6, which expanded variant spectrum of RARS2 gene.


Assuntos
Atrofias Olivopontocerebelares , Feminino , Feto , Genômica , Humanos , Mutação , Gravidez , Sequenciamento Completo do Exoma
9.
Nucleic Acids Res ; 2021 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-34255842

RESUMO

Translation of eukaryotic mRNAs begins with binding of their m7G cap to eIF4E, followed by recruitment of other translation initiation factor proteins. We describe capCLIP, a novel method to comprehensively capture and quantify the eIF4E (eukaryotic initiation factor 4E) 'cap-ome' and apply it to examine the biological consequences of eIF4E-cap binding in distinct cellular contexts. First, we use capCLIP to identify the eIF4E cap-omes in human cells with/without the mTORC1 (mechanistic target of rapamycin, complex 1) inhibitor rapamycin, there being an emerging consensus that rapamycin inhibits translation of TOP (terminal oligopyrimidine) mRNAs by displacing eIF4E from their caps. capCLIP reveals that the representation of TOP mRNAs in the cap-ome is indeed systematically reduced by rapamycin, thus validating our new methodology. capCLIP also refines the requirements for a functional TOP sequence. Second, we apply capCLIP to probe the consequences of phosphorylation of eIF4E. We show eIF4E phosphorylation reduces overall eIF4E-mRNA association and, strikingly, causes preferential dissociation of mRNAs with short 5'-UTRs. capCLIP is a valuable new tool to probe the function of eIF4E and of other cap-binding proteins such as eIF4E2/eIF4E3.

10.
Sci Rep ; 11(1): 13971, 2021 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-34234167

RESUMO

To unravel the source of SARS-CoV-2 introduction and the pattern of its spreading and evolution in the United Arab Emirates, we conducted meta-transcriptome sequencing of 1067 nasopharyngeal swab samples collected between May 9th and Jun 29th, 2020 during the first peak of the local COVID-19 epidemic. We identified global clade distribution and eleven novel genetic variants that were almost absent in the rest of the world and that defined five subclades specific to the UAE viral population. Cross-settlement human-to-human transmission was related to the local business activity. Perhaps surprisingly, at least 5% of the population were co-infected by SARS-CoV-2 of multiple clades within the same host. We also discovered an enrichment of cytosine-to-uracil mutation among the viral population collected from the nasopharynx, that is different from the adenosine-to-inosine change previously reported in the bronchoalveolar lavage fluid samples and a previously unidentified upregulation of APOBEC4 expression in nasopharynx among infected patients, indicating the innate immune host response mediated by ADAR and APOBEC gene families could be tissue-specific. The genomic epidemiological and molecular biological knowledge reported here provides new insights for the SARS-CoV-2 evolution and transmission and points out future direction on host-pathogen interaction investigation.


Assuntos
COVID-19/epidemiologia , COVID-19/imunologia , Coinfecção/epidemiologia , Genômica , Imunidade Inata , Mutação , SARS-CoV-2/genética , Adulto , COVID-19/transmissão , Citidina Desaminase/genética , Feminino , Perfilação da Expressão Gênica , Genoma Viral/genética , Humanos , Masculino , Pessoa de Meia-Idade , Nasofaringe/virologia , Especificidade de Órgãos , SARS-CoV-2/imunologia
11.
PLoS One ; 16(7): e0254544, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34265010

RESUMO

OBJECTIVE: To realize the regulation of the position of corn seed planting in precision farming, an intelligent monitoring system is designed for corn seeding based on machine vision and the Genetic Algorithm-optimized Back Propagation (GABP) algorithm. METHODS: Based on the research on precision positioning seeding technology, comprehensive application of sensors, Proportional Integral Derivative (PID) controllers, and other technologies, combined with modern optimization algorithms, the online dynamic calibration controls of line spacing and plant spacing are implemented. Based on the machine vision and GABP algorithm, a test platform for the seeding effect detection system is designed to provide a reference for further precision seeding operations. GA can obtain better initial network weights and thresholds and find the optimal individual through selection, crossover, and mutation operations; that is, the optimal initial weight of the Back Propagation (BP) neural network. Field experiments verify the seeding performance of the precision corn planter and the accuracy of the seeding monitoring system. RESULTS: 1. The deviation between the average value of the six precision positioning seeding experiments of corn under the random disturbance signal and the ideal value of the distance is less than or equal to 0.5 cm; the deviation between the average value of the six precision positioning seeding experiments of corn under the sine wave disturbance signal (1 Hz) is less than or equal to 0.4 cm; the qualified rate of grain distance reaches 100%. 2. The precision control index, replay index, and missed index of the designed corn precision seeding intelligent control system have all reached the national standard. During the operation of the seeder, an alarm of the seeder leaking occurred, and the buzzer sounded and the screen displayed 100 times each; therefore, the reliability of the alarm system is 100%. CONCLUSION: The intelligent corn seeder designed based on precision positioning seeding technology can reduce the seeding rate of the seeder and ensure the stability of the seed spacing effectively. Based on the machine vision and GABP algorithm, the seeding effect detection system can provide a reference for the further realization of precision seeding operations.

12.
Artigo em Inglês | MEDLINE | ID: mdl-34269047

RESUMO

Recently, localized surface plasmon resonances (SPRs) of metallic nanoparticles (NPs) have been widely used to construct plasmonic nanohybrids for heterogeneous photocatalysis. For example, the combination of plasmonic Au NPs and TiO2 provides pure TiO2 visible-light activity. The SPR effect induces an electric field and consequently enhances light scattering and absorption, favoring the transfer of photon energy to hot carriers for catalytic reactions. Numerous approaches have been dedicated to the improvement of SPR absorption in photocatalysts. Here, we have designed a core@shell-satellite nanohybrid catalyst whereby an Ag NP core, as a plasmonic resonator featuring unique dual functions of strong scattering and near-field enhancement, is encapsulated by SiO2 and TiO2 layers in sequence, with Au NPs on the outer surface, Ag@SiO2@TiO2-Au, for efficient plasmonic photocatalysis. By varying the size and number of Ag NP cores, the Au SPR can be tailored over the visible and near-infrared spectral region to reabsorb the scattered photons. In the presence of the Ag core, the incident light is efficiently confined in the reaction suspension by undergoing multiple scattering, thus leading to an increase of the optical path to the photocatalysis. Moreover, using numerical analysis and experimental verifications, we demonstrate that the Ag core also induces a strong near-field enhancement at the Au-TiO2 interface via SPR coupling with Au. Consequently, the activity of the TiO2-Au plasmonic photocatalyst is significantly enhanced, resulting in a high H2 production rate under visible light. Thus, the design of a single structural unit with strong scattering and field enhancement, induced by a plasmonic resonator, is a highly effective strategy to boost photocatalytic activity.

13.
J Genet Genomics ; 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-34274258

RESUMO

RNA binding motif proteins (RBMs) have been widely implicated in the tumorigenesis of multiple human cancers but scarcely studied in nasopharyngeal carcinoma (NPC). Here, we compare the mRNA levels of 29 RBMs between 87 NPC and 10 control samples. We find that RBM47 is frequently upregulated in NPC specimens, and its high expression is associated with the poor prognosis of patients with NPC. Biological experiments show that RBM47 plays an oncogenic role in NPC cells. Mechanically, RBM47 binds to the promoter and regulates the transcription of BCAT1, and its overexpression partially rescues the inhibitory effects of RBM47-knockdown on NPC cells. Moreover, transcriptome analysis reveals that RBM47 regulates alternative splicing of pre-mRNA, including those cancer-related, to a large extent in NPC cells. Furthermore, RBM47 binds to hnRNPM and cooperatively regulates multiple splicing events in NPC cells. In addition, we find that knockdown of hnRNPM inhibits proliferation and migration of NPC cells. Our study, taken together, shows that RBM47 promotes the progression of NPC through multiple pathways, acting as a transcriptional factor and a modulator of alternative splicing in cooperation with hnRNPM. Our study also highlights that RBM47 and hnRNPM could be prognostic factors and potential therapeutic targets for NPC.

14.
Cancer Lett ; 2021 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-34314754

RESUMO

SGLT2 is overexpressed in various cancers, including pancreatic cancer. However, the mechanisms underlying the tumorigenic effects of SGLT2 in pancreatic cancer remain unclear. In this study, we demonstrated that SGLT2 inhibition significantly suppressed the growth of pancreatic cancer cells in vitro and in vivo. RNA sequencing, real-time PCR, and Western blot analyses revealed that SGLT2 silencing or inhibition suppressed Hippo signaling activation by downregulating YAP1 expression. Liquid chromatography-mass spectrometry and immunoprecipitation analyses showed that SGLT2 interacted with hnRNPK, promoting its nuclear translocation and thereby enhancing hnRNPK-induced YAP1 transcription. Importantly, YAP1 inhibitor enhanced the anti-pancreatic cancer effect of SGLT2 inhibitor in mice bearing pancreatic tumors. These findings suggest that SGLT2 promotes pancreatic cancer progression by activating the Hippo signaling pathway through the hnRNPK-YAP1 axis. Hence, SGLT2 inhibition alone or combined with YAP1 inhibition may represent a promising therapeutic approach for pancreatic cancer.

15.
Sci Total Environ ; 794: 148685, 2021 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-34198084

RESUMO

Simultaneous ozonation and coagulation can be realized in one unit in the developed hybrid ozonation-coagulation (HOC) process. To reveal the reaction sequence within the HOC process, the ibuprofen (IBP) removal efficiency of the ozonation only, HOC and HOC-PO43- (inhibition of the reactions between ozone and metal coagulant) processes at pH 5 and different ozone dosages were investigated. The removal efficiency is almost the same for the three processes at a low ozone dosage (4.8 mg/L), and higher removal performance can be achieved by the HOC process with increasing ozone dosage. It can be implied that ozone preferentially reacts with OH- to generate OH which react with IBP in the HOC process, and subsequently reacts with the surface hydroxyl groups of hydrolysed Al species to enhance OH generation. Moreover, based on the kinetics, X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared spectroscopy (FT-IR) analyses, the synergistic reactions between ozone and the metal coagulants (SOC) started to take effect from ozone dosage of 9.6 mg/L, which further verified that ozone will be involved in the IBP ozonation prior to the SOC reactions. The subsequent SOC reactions also resulted in the increased generation of polymeric Al species and more abundant intermediates in the HOC process.

16.
Autophagy ; : 1-18, 2021 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-34229552

RESUMO

There is increasing evidence that mitophagy, a specialized form of autophagy to degrade and clear long-lived or damaged mitochondria, is impaired in aging and age-related disease. Previous study has demonstrated the obesity-exposed oocytes accumulate and transmit damaged mitochondria due to an inability to activate mitophagy. However, it remains unknown whether mitophagy functions in oocyte and what's the regulatory mechanism in oocyte aging. In the study, when fully grown oocytes were treated with CCCP, an uncoupling agent to induce mitophagy, we found the activation of the PRKN-mediated mitophagy pathway accompanied the blockage of meiosis at metaphase I stage. Our result then demonstrated its association with the decreased activity of RAB7 and all the observed defects in CCCP treated oocytes could be effectively rescued by microinjection of mRNA encoding active RAB7Q67L or treatment with the RAB7 activator ML098. Further study indicated PRKN protein level as a rate-limiting factor to facilitate degradation of RAB7 and its GEF (guanine nucleotide exchange factor) complex CCZ1-MON1 through the ubiquitin-proteasome system. In GV oocytes collected during ovarian aging, we found the age-related increase of PINK1 and PRKN proteins and a significant decrease of RAB7 which resulted in defects of mitophagosome formation and the accumulation of damaged mitochondria. The age-related retardation of female fertility was improved after in vivo treatment of ML098. Thus, RAB7 activity is required to maintain the balance between mitophagy and chromosome stability and RAB7 activator is a good candidate to ameliorate age-related deterioration of oocyte quality.Abbreviations: ATG9: autophagy related 9A; ATP: adenosine triphosphate; CALCOCO2/NDP52: calcium binding and coiled-coil domain 2; CCCP: carbonyl cyanide 3-chlorophenylhydrazone; CCZ1: CCZ1 vacuolar protein trafficking and biogenesis associated; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GAPs: GTPase-activating proteins; GEF: guanine nucleotide exchange factor; GV: germinal vesicle; GVBD: germinal vesicle breakdown; LAMP1: lysosomal-associated membrane protein 1; MI: metaphase I stage of meiosis; MII: metaphase II stage of meiosis; Mito: MitoTracker; mtDNA: mitochondrial DNA; MON1: MON1 homolog, secretory trafficking associated; OPTN: optineurin; PINK1: PTEN induced putative kinase 1; PRKN: parkin RBR E3 ubiquitin protein ligase; RAB7: RAB7, member RAS oncogene family; ROS: reactive oxygen species; TEM: transmission electron microscopy; TOMM20/TOM20: translocase of outer mitochondrial membrane 20; TUBB: tubulin, beta; UB: ubiquitin.

17.
Proc Natl Acad Sci U S A ; 118(28)2021 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-34244445

RESUMO

The development of a versatile platform for the synthesis of 1,2-difunctionalized bicyclo[1.1.1]pentanes to potentially mimic ortho/meta-substituted arenes is described. The syntheses of useful building blocks bearing alcohol, amine, and carboxylic acid functional handles have been achieved from a simple common intermediate. Several ortho- and meta-substituted benzene analogs, as well as simple molecular matched pairs, have also been prepared using this platform. The results of in-depth ADME (absorption, distribution, metabolism, and excretion) investigations of these systems are presented, as well as computational studies which validate the ortho- or meta-character of these bioisosteres.

18.
IEEE Trans Biomed Eng ; PP2021 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-34101580

RESUMO

Traditional Potentiometric Ion-selective Electrodes (ISE) are widely used in industrial and clinical settings. The simplicity and small footprint of ISE have encouraged their recent adoption as wearable/implantable sensors for personalized healthcare and precision agriculture, creating a new set of unique challenges absent in traditional ISE. In this paper, we develop a fundamental physics-based model to describe both steady-state and transient responses of ISE relevant for wearable/implantable sensors. The model is encapsulated in a generalized Nernst formula that explicitly accounts for the analyte density, time-dynamics of signal transduction, ion-selective membrane thickness, and other sensor parameters. The formula is validated numerically by self-consistent modeling of multispecies ion-transport and experimentally by interpreting the time dynamics and thickness dependence of thin-film solid-contact and graphene-based ISE sensors for measuring soil nitrate concentration. These fundamental results will support the accelerated development of ISE for wearable/implantable applications.

19.
Org Lett ; 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-34061546

RESUMO

The development of selective catalytic reactions that utilize easily available reagents for the efficient synthesis of alcohols is a long-standing goal of chemical research. Here an intriguing strategy for the chemodivergent copper-catalyzed hydroxymethylation of alkynes with formic acid and hydrosilane has been developed. By simply tuning the amount of formic acid and reaction temperature, distinct one-carbon-extended primary alcohols, that is, allylic alcohols and ß-branched alkyl alcohols, were produced with high levels of Z/E-, regio-, and enantioselectivity.

20.
Inflammation ; 2021 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-34080089

RESUMO

Baicalin has been reported to have ameliorative effects on nerve-induced hypoxic ischemia injury; however, its role in the NLRP3 inflammasome-dependent inflammatory response during cerebral ischemia-reperfusion remains unclear. To investigate the molecular mechanisms involved in baicalin alleviating cerebral ischemia-reperfusion injury, we investigated the AMPK signaling pathway which regulates NLRP3 inflammasome activity. SD rats were treated with baicalin at doses of 100 mg/kg and 200 mg/kg, respectively, after middle cerebral artery occlusion at 2 h and reperfusion for 24 h (MCAO/R). MCAO/R treatment significantly increased cerebral infarct volume, changed the ultrastructure of nerve cells, and activated the NLRP3 inflammasome, manifesting as significantly increased expression of NLRP3, ASC, cleaved caspase-1, IL-1ß, and IL-18. Our results demonstrated that baicalin treatment effectively reversed these phenomena in a dose-dependent manner. Additionally, inhibition of NLRP3 expression was found to promote the neuroprotective effects of baicalin on cortical neurons. Furthermore, baicalin remarkably increased the expression of p-AMPK following oxygen glucose deprivation/reperfusion (OGD/R). The expression of the NLRP3 inflammasome was also increased when the AMPK pathway was blocked by compound C. Taken together, our findings reveal that baicalin reduces the activity of the NLRP3 inflammasome and consequently inhibits cerebral ischemia-reperfusion injury through activation of the AMPK signaling pathway.

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