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1.
BMC Med Genomics ; 14(1): 244, 2021 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-34627256

RESUMO

BACKGROUND: Though massively parallel sequencing has been widely applied to noninvasive prenatal screen for common trisomy, the clinical use of massively parallel sequencing to noninvasive prenatal diagnose monogenic disorders is limited. This study was to develop a method for directly determining paternal haplotypes for noninvasive prenatal diagnosis of monogenic disorders without requiring proband's samples. METHODS: The study recruited 40 families at high risk for autosomal recessive diseases. The targeted linked-read sequencing was performed on high molecular weight (HMW) DNA of parents using customized probes designed to capture targeted genes and single-nucleotide polymorphisms (SNPs) distributed within 1Mb flanking region of targeted genes. Plasma DNA from pregnant mothers also underwent targeted sequencing using the same probes to determine fetal haplotypes according to parental haplotypes. The results were further confirmed by invasive prenatal diagnosis. RESULTS: Seventy-eight parental haplotypes of targeted gene were successfully determined by targeted linked-read sequencing. The predicted fetal inheritance of variant was correctly deduced in 38 families in which the variants had been confirmed by invasive prenatal diagnosis. Two families were determined to be no-call. CONCLUSIONS: Targeted linked-read sequencing method demonstrated to be an effective means to phase personal haplotype for noninvasive prenatal diagnosis of monogenic disorders.

2.
ACS Chem Biol ; 2021 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-34618427

RESUMO

Histone posttranslational modifications (PTMs) are vital epigenetic regulators in many fundamental cell signaling pathways and diverse biological processes. Histone lysine benzoylation is a recently identified epigenetic mark associated with active transcription; however, it remains to be explored. Herein, we first report the genetic encoding of benzoyllysine and fluorinated benzoyllysines into full-length histone proteins in a site-specific manner in live cells, based on our rationally designed synthetase and fine-integrated fluorine element into benzoyllysines. The incorporated unnatural amino acids integrating unique features were demonstrated as versatile probes for investigating histone benzoylation under biological environments, conferring multiplex signals such as 19F NMR spectra with chemical clarity and fluorescence signals for benzoylation. Moreover, the site specifically incorporated lysine benzoylation within native full-length histone proteins revealed distinct dynamics of debenzoylation in the presence of debenzoylase sirtuin 2 (SIRT2). Our developed strategy for genetic encoding of benzoyllysines offers a general and novel approach to gain insights into interactions of site-specific histone benzoylation modifications with interactomes and molecular mechanisms in physiological settings, which could not be accessible with fragment histone peptides. This versatile chemical tool enables a direct and new avenue to explore benzoylation, interactions, and histone epigenetics, which will provide broad utilities in chemical biology, protein science, and basic biology research.

3.
J Clin Invest ; 2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34609966

RESUMO

Ferroptosis, an iron-dependent non-apoptotic cell death, is a highly regulated tumor suppressing process. However, functions and mechanisms of RNA binding proteins in regulation of evasion of ferroptosis during lung cancer progression are still largely unknown. Here we reported that the RNA binding protein RBMS1 participated in lung cancer development through mediating ferroptosis evasion. Through an shRNA-mediated systematic screen, we discovered that RBMS1 was a key ferroptosis regulator. Clinically, RBMS1 was elevated in lung cancer and its high expression was associated with reduced patient survival. Conversely, depletion of RBMS1 inhibited lung cancer progression both in vivo and in vitro. Mechanistically, RBMS1 interacted with the translation initiation factor eIF3d directly to bridge the 3'- and 5'-UTRs of SLC7A11. RBMS1 ablation inhibited the translation of SLC7A11, reduced SLC7A11-mediated cystine uptake and promotes ferroptosis. In a drug screen that targeted RBMS1, we further uncovered that nortriptyline hydrochloride decreased the level of RBMS1, thereby promoting ferroptosis. Importantly, RBMS1 depletion or inhibition by nortriptyline hydrochloride sensitized radioresistant lung cancer cells to radiotherapy. Our findings established RBMS1 as a translational regulator of ferroptosis and a prognostic factor with therapeutic potentials and clinical values.

4.
J Clin Sleep Med ; 17(10): 2099-2106, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34606442

RESUMO

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is a multilevel problematic disease. Major septal deviation (SD) can lead to severe nasal congestion, which, in turn, can lead to sleep apnea. Although SD seems to be related to OSA, very few studies have quantitatively examined this relationship. In this study, we investigate this using a 9-year large-scale cohort study. METHODS: The SD group was selected out of 1 million individuals randomly extracted by the National Health Insurance Service. The non-SD group was obtained through propensity score matching considering several variables. The primary end point was OSA diagnosis. RESULTS: The study (SD) group included 11,238 individuals and the non-SD group (control group) included 22,476 persons. The overall hazard ratio for OSA in the SD group was 4.39 (95% confidence interval [CI]: 3.56-5.42). In subgroup analysis, the hazard ratio for OSA of male individuals was 3.77 (95% CI: 2.83-5.03), high economic status was 1.27 (95% CI: 1.05-1.56), metropolitan area was 1.31 (95% CI: 1.07-1.62), young age was 0.79 (95% CI: 0.64-0.98), hypertension was 1.00 (95% CI: 0.37-2.7), and diabetes mellitus was 2.44 (95% CI: 1.15-5.21). In the SD group, the hazard ratio for OSA after septoplasty was 0.71 (95% CI: 0.54-0.94). CONCLUSIONS: From long-term follow-up, the prevalence of OSA was 4.39 times higher in the SD group compared with the control group. This phenomenon was more pronounced with increasing body mass index and decreased significantly after septoplasty. CITATION: Yeom SW, Chung SK, Lee EJ, et al. Association between septal deviation and OSA diagnoses: a nationwide 9-year follow-up cohort study. J Clin Sleep Med. 2021;17(10):2099-2106.

5.
Zhongguo Zhen Jiu ; 41(10): 1166-70, 2021 Oct 12.
Artigo em Chinês | MEDLINE | ID: mdl-34628752

RESUMO

OBJECTIVE: To analyze the rules of acupoint and medication selection of acupoint application therapy for functional constipation (FC) by data mining technology. METHODS: The clinical research literature regarding acupoint application therapy for FC from published to February 26, 2020 was searched in CNKI, VIP, Wanfang, SinoMed and PubMed. The prescriptions were extracted, and by using SPSS24.0 and SPSS Modeler14.0 software, the use of high-frequency acupoints and medication was summarized. The association rule analysis, cluster analysis and core prescription analysis of acupoints and medication were analyzed. RESULTS: A total of 122 prescriptions of acupoint application therapy were included, involving 32 acupoints. The core prescription of acupoints was Tianshu (ST 25), Dachangshu (BL 25), Shenque (CV 8) and Guanyuan (CV 4). The high-frequency meridians mainly included conception vessel, yangming stomach meridian of foot and taiyang bladder meridian of foot. The core prescription of medication was rheum officinale, mirabilite, immature bitter orange, mangnolia officinalis, common aucklandia root and borneol. CONCLUSION: The use of local acupoint and regulating-qi and purgating medication is an important principle of acupoint application therapy for FC.


Assuntos
Terapia por Acupuntura , Meridianos , Pontos de Acupuntura , Constipação Intestinal/tratamento farmacológico , Mineração de Dados , Humanos
6.
Chemosphere ; : 132565, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34662635

RESUMO

Natural pyrethrins are one variety of botanical pesticide, and are commonly used in organic and ecological agriculture. However, the hepatotoxicity of natural pyrethrins is unknown. In this study, the impact of natural pyrethrins on human HepG2 cells, which are prominent cell model for toxic-induced hepatotoxicity evaluations, was investigated in accordance with the ROS production and the mechanism of DNA damage and repair. And we report the liver toxicity of natural pyrethrins in zebrafish. Our result revealed a significant increase in ROS production, suggesting oxidative stress. Besides, the most notable genotoxic effect of oxidation-induced DNA damage was observed for natural pyrethrins, as detected by neutral comet assay and γH2AX/8-oxoG staining. As revealed by the results, oxidative DNA damage is responsible for the cytotoxic exposure of natural pyrethrins to HepG2 cells in humans. The observed damage is chronic toxicity, which may cause irreversible DNA damage and more severe toxic effects on human HepG2 cells. This can account for the complicated response to DNA impairment. Visual observations of zebrafish liver and oil red staining also demonstrated that natural pyrethrins induced liver degeneration, liver size changes and liver steatosis in zebrafish. In conclusion, the health of humans can be endangered by natural pyrethrins as a result of hepatotoxicity.

7.
Eur Spine J ; 2021 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-34476597

RESUMO

PURPOSE: To estimate the prevalence of depression in degenerative spine disease (DSD) patients. METHODS: The PubMed, EMBASE, and PsycINFO were systematically searched, the relevant studies that reported the depression prevalence of in DSD patients were identified. Data were extracted independently by 2 reviewers. Subgroup analysis and sensitivity analysis were also performed. RESULTS: 24 articles met the inclusion criteria and were selected for the current study. The pooled prevalence estimate of depression in DSD patients before operative treatment was 30.8% [95% CI 24.0-38.5%]. Nine articles reported the prevalence rate in DSD patients after operative treatment, and the pooled prevalence estimate was 27.0% [95% CI 19.9-35.4%]. There were significant differences for prevalence estimates before operative treatment in types of disorders (Q = 4.56, P = 0.10), spine surgery history (Q = 5.55, P = 0.02), representativeness of sample (Q = 11.00, P = 0.00), and validity of assessment method (Q = 3.32, P = 0.07). The prevalence estimates in patients with lumbar spine stenosis, lumbar disc herniation and cervical spondylotic myelopathy were 24.0%, 40.9% and 37.3%, respectively. Studies that included patients with a history of spine surgery yielded a more extreme prevalence estimate than studies excluding those (36.9% vs 24.3%). For results of patients after operative treatment, significant differences for prevalence estimates were showed in different degrees of pain (Q = 4.72, P = 0.03), screening instruments (Q = 4.83, P = 0.09), and representativeness of sample (Q = 15.70, P = 0.00). CONCLUSION: The systematic review indicated increased prevalence of depression in DSD patients. In consideration of the relationship between depression and poor surgical outcome, we should pay more attention to identifying strategies for preventing and treating depression in DSD patients.

8.
J Int Med Res ; 49(9): 3000605211042975, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34510961

RESUMO

OBJECTIVE: The aim of this study was to identify and validate ferroptosis-related markers in ulcerative colitis (UC) to explore new directions for UC diagnosis and treatment. METHODS: We screened UC chips and ferroptosis-related genes from the Gene Expression Omnibus (GEO), FerrDb, and GeneCards databases. The differentially expressed genes (DEGs) and ferroptosis-related DEGs between the UC group and normal controls were analyzed using bioinformatics methods. Enrichment analysis, protein-protein interaction analysis, and hub genes were screened. Peripheral blood chip and animal experiments were used to validate the ferroptosis-related hub genes. Finally, hub gene-transcription factor, hub gene-microRNA (miRNA), and hub gene-drug interaction networks were constructed. RESULTS: Overall, 26 ferroptosis-related DEGs were identified that were significantly enriched in energy pathways and metabolism. We identified ten ferroptosis-related hub genes from the protein-protein interaction network: IL6, PTGS2, HIF1A, CD44, MUC1, CAV1, NOS2, CXCL2, SCD, and ACSL4. In the peripheral blood chip GSE94648, CD44 and MUC1 were upregulated, which was consistent with the expression trend in GSE75214. Animal experiments showed that CD44 expression was significantly increased in the colon. CONCLUSIONS: Our findings indicate that CD44 and MUC1 may be ferroptosis-related markers in UC.


Assuntos
Colite Ulcerativa , Ferroptose , Animais , Colite Ulcerativa/genética , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Mapas de Interação de Proteínas
9.
mSystems ; : e0087921, 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34519525

RESUMO

Soil fungistasis is a phenomenon in which the germination and growth of fungal propagules is widely inhibited in soils. Although fungistatic compounds are known to play important roles in the formation of soil fungistasis, how such compounds act on soil fungi is little studied. In this study, it was found that ammonia (NH3) induced global protein misfolding marked by increased ubiquitination levels of proteins (ubiquitylome data and Western blot verification). The misfolded proteins should trigger the endoplasmic reticulum (ER) stress, which was indicated by electron microscope image and proteome data. Results from the mutants of BiP and proteasome subunit alpha 7 suggested that ER stress played a mechanistic role in inhibiting conidial germination. Results from proteome data indicated that, to survive ammonia fungistasis, conidia first activated the unfolded protein response (UPR) to decrease ER stress and restore ER protein homeostasis, and the function of UPR in surviving ammonia was confirmed by using mutant strains. Second, ammonia toxicity could be reduced by upregulating carbon metabolism-related proteins, which benefited ammonia fixation. The results that metabolites (especially glutamate) could relieve the ammonia fungistasis confirmed this indirectly. Finally, results from gene knockout mutants also suggested that the fungistatic mechanism of ammonia is common for soil fungistasis. This study increased our knowledge regarding the mechanism of soil fungistasis and provided potential new strategies for manipulating soil fungistasis. IMPORTANCE Soil fungistasis is a phenomenon in which the germination and growth of fungal propagules is widely inhibited in soil. Although fungistatic compounds are known to play important roles in the formation of soil fungistasis, how such compounds act on soil fungi remains little studied. This study revealed an endoplasmic reticulum stress-related fungistatic mechanism with which ammonia acts on Arthrobotrys oligospora and a survival strategy of conidia under ammonia inhibition. Our study provides the first mechanistic explanation of how ammonia impacts fungal spore germination, and the mechanism may be common for soil fungistasis. This study increases our knowledge regarding the mechanism of soil fungistasis in fungal spores and provides potential new strategies for manipulating soil fungistasis.

10.
Immunopharmacol Immunotoxicol ; : 1-8, 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34519594

RESUMO

The pathogenic roles for B cells in autoimmunity include produce pathogenic autoantibodies and modulate immune responses via the production of cytokines and chemokines. The B lymphocyte stimulator BLyS (also known as B-cell-activating factor, BAFF) and APRIL (a proliferation-inducing ligand) are critical factors in the maintenance of the B-cell pool and humoral immunity, namely BLyS modulates the differentiation and maturation of immature B cell, while APRIL modulates the function and survival of long-lived plasma cell, which plays a prominent role in the pathogenesis of autoimmune diseases. Telitacicept is a novel recombinant fusion protein of both the ligand-binding domain of the TACI receptor and the Fc component of human IgG and which is a BLyS/APRIL dual inhibitor. Moreover, telitacicept was developed by Remegen Co., Ltd. in China and is approved to treat systemic lupus erythematosus in China. We review the rationale, clinical evidence, and future perspectives of telitacicept for the treatment of autoimmune disease.HighlightThe B lymphocyte stimulator BLyS (also known as B-cell-activating factor, BAFF) and APRIL (a proliferation-inducing ligand), members of tumor necrosis factor (TNF) family, and which are critical factors in the maintenance of the B-cell pool and humoral immunity.BAFF and APRIL are implicated in the pathogenesis of several human autoimmune diseases with autoreactive B-cell involvement, and targeting both is beneficial for the treatment of autoimmune diseases.Telitacicept is a novel recombinant fusion protein of both the ligand-binding domain of the TACI receptor and the Fc component of human IgG, as a BLyS/APRIL dual inhibitor and which has been approved by National Medical Products Administration (MNPA) for the treatment of patients with SLE in China.With more clinical trials underway, telitacicept may also be approved for the treatment of other autoimmune diseases in the future.

11.
Nat Commun ; 12(1): 5661, 2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34580299

RESUMO

Hybrid nanocrystals combining different properties together are important multifunctional materials that underpin further development in catalysis, energy storage, et al., and they are often constructed using heterogeneous seeded growth. Their spatial configuration (shape, composition, and dimension) is primarily determined by the heterogeneous deposition process which depends on the lattice mismatch between deposited material and seed. Precise control of nanocrystals spatial configuration is crucial to applications, but suffers from the limited tunability of lattice mismatch. Here, we demonstrate that surface lattice engineering can be used to break this bottleneck. Surface lattices of various Au nanocrystal seeds are fine-tuned using this strategy regardless of their shape, size, and crystalline structure, creating adjustable lattice mismatch for subsequent growth of other metals; hence, diverse hybrid nanocrystals with fine-tuned spatial configuration can be synthesized. This study may pave a general approach for rationally designing and constructing target nanocrystals including metal, semiconductor, and oxide.

12.
Fish Shellfish Immunol ; 118: 396-404, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34571156

RESUMO

Heat shock protein 40 (Hsp40), a member of Heat shock proteins (Hsps) family, plays a crucial role in regulation of cell proliferation, survival and apoptosis in mammals. In this study, Hsp40, EcHsp40, was identified from Epinephelus coioides, an economically important marine-cultured fish in China and Southeast Asian counties. The full length of EcHsp40 was 2236 bp in length containing a 1026 bp open reading frame (ORF) encoding 341 amino acids, with a molecular mass of 37.88 kDa and a theoretical pI of 9.09. EcHsp40 has two conserved domains DnaJ and DnaJ_C. EcHsp40 mRNA was detected in all tissues examined, and the expression was significantly up-regulated response to challenged with Vibrio alginolyticus or Singapore grouper iridovirus (SGIV), one of the important pathogens of marine fish. EcHsp40 was distributed in both the cytoplasm and nucleus, over-expression of EcHsp40 can inhibit the activity of nuclear factor-κB (NF-κB) and activator protein-1 (AP-1), significantly promote SGIV-induced apoptosis, intracellular caspase-3 activity and viral replication, suggesting that the EcHsp40 may play an important role in pathogenic stimulation.

13.
Int J Pharm ; 608: 121081, 2021 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-34506924

RESUMO

Human epidermal growth factor receptor 2 (HER2) is overexpressed in some breast and gastric cancer patients. As the first HER2-targeteed therpeutic antibody, trastuzumab could significantly improve the prognosis of HER2-positive cancer patients. However, even responding patients inevitably get worse due to acquired resistance to trastuzumab after a period of treatment. Many HER2-targeted antibody drugs used wild-type tumor cells to conduct their corresponding preclinical experiments in vitro and in vivo. However, it is impossible to determine whether these newly developed drugs have antitumor effective to trastuzumab-resistant tumor cells. In the study, two trastuzumab-resistant HER2-positive tumor cell populations NCI-N87-TR and BT474-TR were generated. Then, we examined the anti-tumor effects of newly constructed immunotoxins with low immunogenicity and off-target toxicity based on the trastuzumab-resistant tumor cells both in vitro and in vivo. Results demonstrated that the immunotoxin IHP25-BT could not only effectively inhibit tumor growth but also inhibit liver metastasis of tumor cells in a mouse xenograft model. Furthermore, tumor tissue transcriptome sequencing was performed to clarify the potential mechanisms of inhibiting tumor cell distant metastasis by immunotoxin. In conclusion, this work describes a series of attractive therapeutic immunotoxins, the low immunogenicity and off-target toxicity making them promising for trastuzumab-resistant cancer therapy.


Assuntos
Neoplasias da Mama , Imunotoxinas , Neoplasias Gástricas , Animais , Neoplasias da Mama/tratamento farmacológico , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Camundongos , Receptor ErbB-2 , Neoplasias Gástricas/tratamento farmacológico , Trastuzumab , Ensaios Antitumorais Modelo de Xenoenxerto
14.
Environ Health Prev Med ; 26(1): 91, 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34521354

RESUMO

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is becoming a global health problem. Bisphenol A (BPA), one of most widely used environmental chemicals, is suspected to be a contributor to the development NAFLD. This study was performed to examine the relationship between human BPA levels and risk of NAFLD. METHODS: The data (n = 3476 adults: 1474 men and 2002 women) used in this study were obtained from the Korean National Environmental Health Survey III (2015-2017). BPA levels were measured in urine samples. NAFLD was defined using hepatic steatosis index after exclusion of other causes of hepatic diseases. RESULTS: There was a significant linear relationship between the elevated urinary BPA concentrations and risk of NAFLD. In a univariate analysis, odds ratio (OR) of the highest quartile of urinary BPA level was 1.47 [95% confidence interval (CI) 1.11-1.94] compared to the lowest quartile. After adjusted with covariates, the ORs for NAFLD in the third and fourth quartiles were 1.31 [95% CI 1.03-1.67] and 1.32 [95% CI 1.03-1.70], respectively. CONCLUSIONS: Urinary BPA levels are positively associated with the risk of NAFLD in adults. Further experimental studies are needed to understand the molecular mechanisms of BPA on NAFLD prevalence.

15.
Lipids Health Dis ; 20(1): 109, 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34544437

RESUMO

BACKGROUND: Cancer patients often exhibit chemotherapy-associated changes in serum lipid profiles, however, their prognostic value before and after adjuvant chemotherapy on survival among non-small-cell lung cancer (NSCLC) patients is unknown. METHODS: NSCLC patients undergoing radical resection and subsequent adjuvant chemotherapy from 2013 to 2017 at Sun Yat-sen University Cancer Center were retrospectively reviewed. Fasted serum lipid levels were measured before and after chemotherapy. The optimal lipid cut-off values at baseline and fluctuation were determined using X-tile™. The fluctuations in serum lipid levels and disease-free survival (DFS) were assessed. RESULTS: Serum cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), triglyceride, apolipoprotein (Apo) A-I, and ApoB all significantly increased after adjuvant chemotherapy. X-tile determined 1.52 mmol/L of HDL-C and 0.74 g/L of ApoB as the optimal cut-off values before chemotherapy. Patients with HDL-C ≥ 1.52 mmol/L (median DFS: not reached vs. 26.30 months, P = 0.0005) and a decreased HDL-C level after adjuvant chemotherapy (median DFS: 80.43 vs. 26.12 months, P = 0.0204) had a longer DFS. An HDL-C level that increased by ≥ 0.32 mmol/L after chemotherapy indicated a worse DFS. A high baseline ApoB level were associated with a superior DFS. In the univariate analysis and the multivariate Cox analyses, a high baseline HDL-C level and a HDL-C reduction after adjuvant chemotherapy were independent indicators for superior DFS. High baseline HDL-C was related to N0-1 stage (χ2 = 6.413, P = 0.011), and HDL-C fluctuation was significantly correlated with specific chemotherapy regimens (χ2 = 5.002, P = 0.025). CONCLUSIONS: Adjuvant chemotherapy increased various lipid levels in resected NSCLC patients. A higher HDL-C level before chemotherapy and a reduced HDL-C level after adjuvant chemotherapy were independent predictors of longer DFS in patients with curable NSCLC.

16.
J Org Chem ; 86(19): 13475-13480, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34549964

RESUMO

The mechanism of Pd(II)-catalyzed meta-C-H bond olefination of arenes with a carboxyl directing group (DG)-containing template has been investigated with density functional theory. The reaction includes three major steps: C-H bond activation, alkene insertion, and ß-hydride elimination. The C-H activation step, which proceeds via a concerted metalation-deprotonation pathway, is found to be the rate- and regioselectivity-determining step. We proposed a mono-N-protected amino acid (MPAA)/DG-assisted C-H activation model, in which the carboxyl DG coordinates with the Pd center and delivers it to the meta-position of arene, and the bidentate dianionic MPAA acts as a base for deprotonation. There is a hydrogen bonding interaction between the carboxyl DG and the carboxylate group of MPAA. An alternative Pd(OAc)2-catalyzed mechanism without involvement of MPAA is also operative. The template is conformationally flexible, and multiple low-energy transition-state conformations contribute to the regioselectivity.

17.
Acta Biomater ; 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34551332

RESUMO

Organisms develop unique systems in a given environment. In the process of adaptation, they employ materials in a clever way, which has inspired mankind extensively. Understanding the behavior and material properties of living organisms provides a way to emulate these natural systems and engineer various materials. Silk is a material that has been with human for over 5000 years, and the success of mass production of silkworm silk has realized its applications to medical, pharmaceutical, optical, and even electronic fields. Spider silk, which was characterized later, has expanded the application sectors to textile and military materials based on its tough mechanical properties. Because silk proteins are main components of these materials and there are abundant creatures producing silks that have not been studied, the introduction of new silk proteins would be a breakthrough of engineering materials to open innovative industry fields. Therefore, in this review, we present diverse silk and silk-like proteins and how they are utilized with respect to organism's survival. Here, the range of organisms are not constrained to silkworms and spiders but expanded to other insects, and even marine creatures which produce silk-like proteins that are not observed in terrestrial silks. This viewpoint broadening of silk and silk-like proteins would suggest diverse targets of engineering to design promising silk-based materials. STATEMENT OF SIGNIFICANCE: Silk has been developed as a biomedical material due to unique mechanical and chemical properties. For decades, silks from various silkworm and spider species have been intensively studied. More recently, other silk and silk-like proteins with different sequences and structures have been reported, not only limited to terrestrial organisms (honeybee, green lacewing, caddisfly, and ant), but also from marine creatures (mussel, squid, sea anemone, and pearl oyster). Nevertheless, there has hardly been well-organized literature on silks from such organisms. Regarding the relationship among sequence-structure-properties, this review addresses how silks have been utilized with respect to organism's survival. Finally, this information aims to improve the understanding of diverse silk and silk-like proteins which can offer a significant interest to engineering fields.

18.
ACS Sens ; 6(9): 3253-3261, 2021 09 24.
Artigo em Inglês | MEDLINE | ID: mdl-34467757

RESUMO

Reactive oxygen species (ROS) produced by an inflammatory response in the brain are associated with various neurological disorders. To investigate ROS-associated neuroinflammatory diseases, fluorescent probes with practicality are in demand. We have investigated hypochlorous acid, an important ROS, in the brain tissues of neuroinflammation and maternal immune activation (MIA) model mice, using a new fluorescent probe. The probe has outstanding features over many known probes, such as providing two bright ratio signals in cells and tissues in deep-red/near-infrared wavelength regions with a large spectral separation, in addition to being strongly fluorescent, photo- and chemo-stable, highly selective and sensitive, fast responding, and biocompatible. We have found that the level of hypochlorous acid in the brain tissue of a neuroinflammatory mouse model was higher (2.7-4.0-fold) compared with that in normal brain tissue. Furthermore, the level of hypochlorous acid in the brain tissue of a MIA mouse model was higher (1.2-1.3-fold) compared with that in the normal brain tissue. The "robust" probe provides a practical tool for studying ROS-associated neurological disorders.


Assuntos
Encéfalo , Ácido Hipocloroso , Animais , Camundongos
19.
Front Cell Infect Microbiol ; 11: 677648, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34568084

RESUMO

Vaginal dysbiosis, such as bacterial vaginosis (BV) and aerobic vaginitis (AV), is an important cause of premature birth in pregnant women. However, there is very little research on vaginal microbial distribution in AV compared to that in BV. This study aimed to analyze the composition of the vaginal microbiota of pregnant women with AV using microbial community analysis and identify the causative organism using each criterion of the AV scoring system. Also, we compared the quantification of aerobic bacteria using quantitative polymerase chain reaction (qPCR) and their relative abundances (RA) using metagenomics. This prospective case-control study included 228 pregnant Korean women from our previous study. A wet mount test was conducted on 159 women to diagnose AV using the AV scoring system. Vaginal samples were analyzed using metagenomics, Gram staining for Nugent score determination, conventional culture, and qPCR for Staphylococcus spp., Streptococcus spp., and Enterobacteriaceae. The relative abundances (RAs) of eleven species showed significant differences among the three groups (Normal flora (NF), mild AV, and moderate AV). Three species including Lactobacillus crispatus were significantly lower in the AV groups than in the NF group, while eight species were higher in the AV groups, particularly moderate AV. The decrease in the RA of L. crispatus was common in three criteria of the AV scoring system (Lactobacillary, WBC, and background flora grades), while it did not show a significant difference among the three grade groups of the toxic leukocyte criterion. Also, the RAs of anaerobes, such as Gardnerella and Megasphaera, were higher in the AV groups, particularly moderate AV, while the RAs of aerobes were very low (RA < 0.01). Therefore, qPCR was performed for aerobes (Staphylococcus spp., Streptococcus spp., and Enterobacteriaceae); however, their quantification did not show a higher level in the AV groups when compared to that in the NF group. Therefore, AV might be affected by the RA of Lactobacillus spp. and the main anaerobes, such as Gardnerella spp. Activation of leukocytes under specific conditions might convert them to toxic leukocytes, despite high levels of L. crispatus. Thus, the pathogenesis of AV can be evaluated under such conditions.


Assuntos
Microbiota , Vaginite , Estudos de Casos e Controles , Disbiose , Feminino , Humanos , Gravidez , Gestantes , Vagina
20.
Dent Mater J ; 2021 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-34408118

RESUMO

This study aimed to evaluate the effect of aging on the color stability and bond strengths of dual-cured resin cements containing amine or amine-free self-initiators. Three dual-cured and one light-cured resin cements were used. The covered (by lithium disilicate ceramic disks) and uncovered groups (n=10) were included. Color measurements were tested after 24 h, 10,000 and 20,000 thermal cycles (TCs). Micro-shear bond strengths (µSBS) were tested after 24 h, 10,000 and 20,000 TCs, and failure modes were analyzed (n=14). Two-way ANOVA and Tukey's test were implemented for color difference (ΔE*ab) and µSBS (α=0.05). The mean ΔE*ab difference was significant among groups (p<0.001). The lowest ΔE*ab values were obtained for dual-cured resin cement with amine-free self-initiators dual-cured cement after aging in all dual-cured resin cements, and the µSBS of the dual-cured resin cements on ceramic was significantly higher than that of the light-cured ones after aging (p<0.001).

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