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1.
Food Chem ; 337: 128023, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-32920275

RESUMO

In this study, the effects of fungal fermentation on green canephora coffee beans were evaluated by observing the changes to selected non-volatile parameters before roasting, and subsequently the volatile profile after roasting. Solid-state fermentation (SSF) by Aspergillus spp. and Mucor spp. on green canephora coffee beans was shown to modulate the contents of free sugars, free amino acids and polyphenolic compounds such as caffeoylquinic acids (CQAs). Significant strain-specific differences were observed in the contents of aroma compounds after roasting. A significant increase in pyrazines was observed in the Aspergillus oryzae-fermented samples, while higher levels of furans were detected in the Mucor plumbeus-fermented samples. The present work shows that fungal fermentation of green canephora coffee beans is a potentially promising method for the modulation and improvement of coffee flavour and aroma.

2.
Sci Rep ; 10(1): 16592, 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33024214

RESUMO

This study was designed to evaluate the learning curve of applying Seprafilm (modified hyaluronic acid and carboxymethylcellulose; Genzyme, Cambridge, MA, USA) during laparoscopic hysterectomy or subtotal hysterectomy with or without adnexectomy. In this retrospective cohort study, 35 patients who underwent laparoscopic hysterectomy or subtotal hysterectomy with or without adnexectomy were enrolled. The Seprafilm was cut into 4 pieces, rolled up with a trimmed plastic sleeve and delivered through an incision wound made for the 5-mm ancillary trocar. The membrane was unrolled and placed on the rough surface after hysterectomy or subtotal hysterectomy with or without adnexectomy. The time from the insertion of the first piece of membrane into the abdominal cavity to the complete removal of the trimmed plastic sleeve was recorded. The median time for Seprafilm placement was 3 min. The learning curve was analyzed using the power-law method and suggested that 10 cases were required to achieve proficiency in the procedure. The presence of adnexectomy was significantly associated with the time required for Seprafilm placement (P < 0.001). Although Seprafilm placement is more complicated compared to the liquid and gel forms of anti-adhesion barriers, surgical proficiency seemed to be attained after 10 cases for an experienced surgeon.

4.
Sci Adv ; 6(42)2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33067236

RESUMO

In a complex and dynamic environment, the brain flexibly adjusts its circuits to preferentially process behaviorally relevant information. Here, we investigated how the olfactory bulb copes with this demand by examining the plasticity of adult-born granule cells (abGCs). We found that learning of olfactory discrimination elevates odor responses of young abGCs and increases their apical dendritic spines. This plasticity did not occur in abGCs during passive odor experience nor in resident granule cells (rGCs) during learning. Furthermore, we found that feedback projections from the piriform cortex show elevated activity during learning, and activating piriform feedback elicited stronger excitatory postsynaptic currents in abGCs than rGCs. Inactivation of piriform feedback blocked abGC plasticity during learning, and activation of piriform feedback during passive experience induced learning-like plasticity of abGCs. Our work describes a neural circuit mechanism that uses adult neurogenesis to update a sensory circuit to flexibly adapt to new behavioral demands.

5.
Nucleic Acids Res ; 2020 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-33080014

RESUMO

Msh homeobox (Msx) is a subclass of homeobox transcriptional regulators that control cell lineage development, including the early stage of vertebrate limb development, although the underlying mechanisms are not clear. Here, we demonstrate that Msx1 promotes the proliferation of myoblasts and mesenchymal stem cells (MSCs) by enhancing mitogen-activated protein kinase (MAPK) signaling. Msx1 directly binds to and upregulates the expression of fibroblast growth factor 9 (Fgf9) and Fgf18. Accordingly, knockdown or antibody neutralization of Fgf9/18 inhibits Msx1-activated extracellular signal-regulated kinase 1/2 (Erk1/2) phosphorylation. Mechanistically, we determined that the phosphorylation of Msx1 at Ser136 is critical for enhancing Fgf9 and Fgf18 expression and cell proliferation, and cyclin-dependent kinase 1 (CDK1) is apparently responsible for Ser136 phosphorylation. Furthermore, mesenchymal deletion of Msx1/2 results in decreased Fgf9 and Fgf18 expression and Erk1/2 phosphorylation, which leads to serious defects in limb development in mice. Collectively, our findings established an important function of the Msx1-Fgf-MAPK signaling axis in promoting cell proliferation, thus providing a new mechanistic insight into limb development.

6.
J Chromatogr A ; 1633: 461617, 2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33096289

RESUMO

Sorptive extraction techniques have experienced increased popularity, but they face limitations in dynamic range and sensitivity. In this study, a new method combining stir bar sorptive extraction (SBSE) and thin-film solid-phase microextraction (TFSPME) was developed, and optimization for extraction temperature (70 °C) and time (120 min) was carried out. Polydimethylsiloxane (PDMS)-coated SBSE and PDMS/carboxen (PDMS/CAR)-coated TFSPME were used, and both headspace and direct immersion extraction modes were also studied. Using 40 selected volatile compounds, the combined method generally gave a wider linearity range with lower minimum limits (2 to 3 orders), satisfactory coefficient of determination (R2>0.980), and improved sensitivity when compared to SBSE-only or TFSPME-only techniques. Furthermore, despite the combined use of two extraction devices, the repeatability (<13.1 %) and reproducibility (<13.4 %) of the combined method were comparable to SBSE-only or TFSPME-only results. Higher recoveries of up to 20% were also achieved by the combined method. Compared to the conventional SBSE method, the new method provided superior performance in terms of dynamic range and sensitivity for compounds of various polarities. In conclusion, this study provided insights on the suitability of the various extraction methods for compounds of different chemical properties which could aid in future applications for volatiles analysis in food, biological, and environmental sectors.

7.
Int Immunopharmacol ; 89(Pt B): 107095, 2020 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-33096360

RESUMO

Hypoxia and the resultant decreases in cerebral blood flow in the perinatal period can lead to neonatal hypoxic-ischemic (HI) brain injury, which can, in turn, cause severe disability or even death. However, the efficacy of current treatment strategies remains limited. Several studies have demonstrated that lipoxin A4 (LXA4), as one of the earliest types of endogenous lipid mediators, can inhibit the accumulation of neutrophils, arrest inflammation, and promote the resolution of inflammation. However, research on LXA4 in the nervous system has rarely been carried out. In the present study, we sought to investigate the protective effect of LXA4 on HI brain damage in neonatal rats, as well as the underlying mechanisms. Through experiments conducted using an HI animal model, we found that the LXA4 intervention promoted the recovery of neuronal function and tissue structure following brain injury while maintaining the integrity of the blood-brain barrier in addition to reducing cerebral edema, infarct volume, and inflammatory responses. Our results suggest that LXA4 interfered with neuronal oxygen-glucose deprivation insults, reduced the expression of inflammatory factors, inhibited apoptosis, and promoted neuronal survival in vitro. Finally, the LXA4 intervention attenuated HI-induced activation of inhibitor kappa B (IκB) and degradation of nuclear factor-κB (NF-κB). In conclusion, our data suggest that LXA4 exerts a neuroprotective effect against neonatal HI brain damage through the IκB/NF-κB pathway. Our findings will help inform future studies regarding the effects of LXA4 on neuroinflammation, blood-brain barrier integrity, and neuronal apoptosis.

8.
Nat Prod Res ; : 1-10, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32998585

RESUMO

Strain SZW01 was isolated from sea sediment collected from Shenzhen in Guangdong province, China, and was later identified as Aspergillus fumigatus by16S rDNA sequence analysis. Various chromatographic processes led to the isolation and purification of three compounds from the fermentation culture of SZW01, including a new compound, 2,6'-dihydroxy-2,4'dimethoxy-8'-methyl-6-methoxy-acyl-ethyl-diphenylmethanone (1), and two known compounds: fumigaclavine C (2) and alternarosin A (3), as characterised by UV, IR, 1 D, 2 D-NMR and MS data. The antioxidant and α-glucosidase inhibitory activities of these compounds were evaluated. The result illustrated that compound 1 exhibited a moderate antioxidant activity and stronger α-glucosidase inhibitory activity than acarbose.

9.
Biomed Res Int ; 2020: 5807162, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33062685

RESUMO

Objective: The Chinese men who have sex with men (MSM) population is suffering from a high HIV infection rate owing to unprotected anal sex. The Health Belief Model (HBM) has been proven to be an effective frame associated with behavior maintenance. Based on HBM, we analyzed the beliefs associated with consistent condom use behavior with regular and nonregular partners among MSM to better provide targeted interventions and services. Methods: A study was conducted in Sichuan Province, China, from November 2018 to April 2019, and 801 eligible participants were recruited by snowball sampling. Sociodemographic characteristics, AIDS-related characteristics, sexual behaviors, condom use behavior, and dimensions of HBM were investigated. Univariate, single multivariate, and summary multivariate models were employed to analyze the factors associated with consistent condom use. Results: Of all participants, 39.1% and 53.6% had had anal sex with regular and nonregular partners in the last six months, respectively. Only 56.5% of them had used condoms consistently with regular partners, and only 60% of them had used condoms consistently with nonregular partners. When taking consistent condoms use with regular partners as the dependent variable, the dimensions of perceived threats (ORM = 1.28, 95% CI: 1.10, 1.49), perceived barriers (ORM = 0.70, 95% CI: 0.60, 0.82), self-efficacy (ORM = 1.23, 95% CI: 1.14, 1.32), and cues to action (ORM = 1.21, 95% CI: 1.02, 1.43) showed significant associations with the dependent variable. When taking consistent condoms use with nonregular partners as the dependent variable, the dimensions of perceived barriers (ORM = 0.77, 95% CI: 0.67, 0.89), self-efficacy (ORM = 1.22, 95% CI: 1.13, 1.32), and cues to action (ORM = 1.53, 95% CI: 1.30, 1.80) showed significant associations with the dependent variable. Conclusions: More attention should be focused on how to decrease the obstructive factors of condom use, how to improve the confidence of condom use, and how to layout more cues to action to promote consistent condom use behavior with regular and nonregular partners during anal sex among Chinese MSM.

10.
Life Sci Alliance ; 3(12)2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33087487

RESUMO

This study reports that parathymosin (PTMS) is secreted by hypothalamic stem/progenitor cells (htNSC) to inhibit senescence of recipient cells such as fibroblasts. Upon release, PTMS is rapidly transferred into the nuclei of various cell types, including neuronal GT1-7 cells and different peripheral cells, and it is effectively transferred into neuronal nuclei in various brain regions in vivo. Notably, brain neurons also produce and release PTMS, and because neuronal populations are large, they are important for maintaining PTMS in the cerebrospinal fluid which is further transferable into the blood. Compared with several other brain regions, the hypothalamus is stronger for long-distance PTMS transfer, supporting a key hypothalamic role in this function. In physiology, aging is associated with declines in PTMS production and transfer in the brain, and ptms knockdown in the hypothalamus versus hippocampus were studied showing different contributions to neurobehavioral physiology. In conclusion, the brain is an endocrine organ through secretion and nuclear transfer of PTMS, and the hypothalamus-brain orchestration of this function is protective in physiology and counteractive against aging-related disorders.

11.
Eur J Med Chem ; 205: 112667, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-32911308

RESUMO

48 new drugs including 38 chemical entities (33 new chemical entities, 3 new diagnostic agents, and 2 payloads of antibody drug conjugates) and 10 biologics were approved by the U.S. Food and Drug Administration (FDA) during 2019. These marketed new drugs represent privileged structures and novel action of mechanism, and thus can be served as leads to discover new drugs with the similar biological targets and improved therapeutic efficacy. This review aims to provide an overview regarding the synthetic approaches of 33 new chemical entities approved by the FDA in 2019 and their clinical applications.

12.
Medicine (Baltimore) ; 99(39): e22426, 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32991478

RESUMO

Razor back deformity is one of the most noticeable problems of severe scoliosis. Thoracoplasty has been reported to be a useful approach to correct the rib hump deformity. However, the outcomes of thoracoplasty in patients with severe, rigid, thoracic scoliosis have not yet been evaluated.To evaluate the effectiveness and safety of a modified technique of thoracoplasty (rib ends fixed under transverse process) for rib hump deformity in adults with severe thoracic scoliosis and severe pulmonary dysfunction.Patients with severe thoracic scoliosis and severe pulmonary dysfunction who underwent staged surgical strategy including halo-pelvic traction, spinal osteotomy combined with the modified thoracoplasty were included. To avoid paradoxical breathing result from multiple rib resections and enlarge the capacity of thoracis, the ends after rib resection were fixed under transverse process compared with conventional thoracoplasty. Patients were excluded on the basis of pulmonary diseases and inadequate follow-up. Data on deformity correction and pulmonary complications were reviewed. A t test was performed on the pre- and postoperative data of pulmonary function, height of the rib hump deformity, and total lung area.Eighteen patients (5 men and 13 women) with a major thoracic curve of >130° were included. The mean age of patients was 25.3 ±â€Š3.6 years (range, 19-32 years), with an average length of follow-up of 30.2 months. After application of halo-pelvic traction, the mean major thoracic curve decreased from 168.2°â€Š±â€Š14.28° to 97.3°â€Š±â€Š10.75° and the thoracic kyphosis decreased from 159.4°â€Š±â€Š20.60° to 94.8°â€Š±â€Š9.58°. On average, 6.3 (range, 4-8) ribs were resected. The height of the rib hump decreased from 84.6 ±â€Š13.3 to 15.3 ±â€Š3.4 mm. The average predicted forced vital capacity (FVC%) before surgery was 37.2 ±â€Š13.30%, indicative of severe pulmonary impairment, with a small but non-significant improvement in the FVC% at the final follow-up. The mean total lung area increased from 2583.2 ±â€Š501.36 to 2890.1 ±â€Š537.30 mL at the last follow-up. No severe pulmonary complications occurred.Our modified approach to thoracoplasty procedure is effective and safe in correcting a razor back deformity in patients with severe, rigid, scoliosis, and severe pulmonary dysfunction, without causing any significant change in long-term pulmonary function.


Assuntos
Escoliose/cirurgia , Toracoplastia/métodos , Adulto , Feminino , Humanos , Masculino , Radiografia , Estudos Retrospectivos , Escoliose/diagnóstico por imagem , Toracoplastia/efeitos adversos , Toracoplastia/estatística & dados numéricos , Adulto Jovem
13.
Eur J Med Chem ; 208: 112760, 2020 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-32883639

RESUMO

KDM5B (Lysine-Specific Demethylase 5B) erases the methyl group from H3K4me2/3, which performs wide regulatory effects on chromatin structure, and represses the transcriptional function of genes. KDM5B functions as an oncogene and associates with human cancers closely. Targeting KDM5B has been a promising direction for curing cancer since the emergence of potent KDM5B inhibitor CPI-455. In this area, most reported KDM5B inhibitors are Fe (Ⅱ) chelators, which also compete with the cofactor 2-OG in the active pockets. Besides, Some KDM5B inhibitors have been identified through high throughput screening or biochemical screening. In this reviewing article, we summarized the pioneering progress in KDM5B to provide a comprehensive realization, including crystal structure, transcriptional regulation function, cancer-related functions, development of inhibitors, and SAR studies. We hope to provide a comprehensive overview of KDM5B and the development of KDM5B inhibitors.

14.
J Alzheimers Dis ; 77(4): 1717-1732, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32925038

RESUMO

BACKGROUND: Adjuvants are important components of vaccines and effectively enhance the immune response of specific antigens. However, the role of adjuvants or combinations of adjuvants in stimulating immunogenicity of the amyloid-ß (Aß) vaccine, as well as molecular mechanisms underlying such stimulation still remain unclear. A previous study of ours developed a norovirus P particle-based active Aß epitope vaccine, PP-3copy-Aß1-6-loop123, which stimulates a high titer of Aß-specific antibodies in mouse Alzheimer's disease (AD) models. OBJECTIVE: The most effective and safe adjuvant that maximizes the immunogenicity of our protein vaccine was determined. METHODS: We investigated four adjuvants (CpG, AS02, AS03, and MF59), and combinations of those, for capacity to enhance immunogenicity, and performed transcriptome analysis to explore mechanisms underlying the role of these in AD immunotherapy. RESULTS: Addition of the adjuvant, AS02, remarkably improved the immunogenicity of the PP-3copy-Aß1-6-loop123 vaccine without triggering an Aß-specific T-cell response. Combinations of adjuvants, particularly CpG +  AS02 and CpG + AS03, elicited a significantly elevated and prolonged Aß-specific antibody response. Gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses indicated that a combination of two adjuvants was more effective in activating immune-related pathways, thereby enhancing the immunogenicity of PP-3copy-Aß1-6-loop123. CONCLUSION: These findings demonstrated that adjuvants can be used as enhancers in AD protein vaccination, and that a combination of CpG and AS-related adjuvants may be a very effective adjuvant candidate suitable for further clinical trials of the PP-3copy-Aß1-6-loop123 vaccine. Our studies also revealed potential mechanisms underlying the stimulation of immune response of protein vaccines by adjuvants.

15.
Chem Commun (Camb) ; 56(83): 12612-12615, 2020 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-32945816

RESUMO

We demonstrate herein a newly designed benzothiadiazole-based covalent organic framework through an imine linkage with high crystallinity, excellent chemical stability and significant light absorption ability, which was further applied as a high-performance platform for efficient visible-light driven hydrogen evolution.

16.
Org Lett ; 2020 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-32902992

RESUMO

We demonstrate herein that the N-heterocyclic-carbene (NHC)-metal complex (NHC-M)-involved covalent organic framework (COF) can be prepared by the direct polymerization of the NHC-M monomer with its counterpart under solvothermal conditions. The NHC-M-COF with different counterions is readily achieved via solid-state anion exchange. The obtained NHC-AuX-COF (X = Cl- and SbF6-) can be a highly active reusable catalyst to separately promote the carboxylation of the terminal alkyne with CO2 and alkyne hydration under mild conditions.

18.
J Am Chem Soc ; 142(40): 16915-16920, 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-32941016

RESUMO

Direct synthesis, postsynthetic modification, and chiral induction have been recognized as three powerful methods to synthesize chiral covalent organic frameworks (CCOFs). However, catalytic asymmetric methodology, as the most important and effective synthetic approach to access chiral organics, has not been enabled for CCOFs synthesis thus far. Herein we report, for the first time, the construction of CCOFs from prochiral monomers via catalytic asymmetric polymerization. The obtained propargylamine-linked CCOFs can be the highly reusable chiral catalysts to promote asymmetric Michael addition reactions. The concept of catalytic asymmetric polymerization might open a new route for constructing the CCOFs that are not possible with the existing CCOF synthetic methods.

19.
Acta Pharm Sin B ; 10(8): 1476-1491, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32963944

RESUMO

Ubiquitin specific peptidase 28 (USP28) is closely associated to the occurrence and development of various malignancies, and thus has been validated as a promising therapeutic target for cancer therapy. To date, only few USP28 inhibitors with moderate inhibitory activity have been reported, highly potent and selective USP28 inhibitors with new chemotypes remain to be discovered for pathologically investigating the roles of deubiquitinase. In this current study, we reported the synthesis and biological evaluation of new [1,2,3]triazolo[4,5-d]pyrimidine derivatives as potent USP28 inhibitors. Especially, compound 19 potently inhibited USP28 (IC50 = 1.10 ± 0.02 µmol/L, K d = 40 nmol/L), showing selectivity over USP7 and LSD1 (IC50 > 100 µmol/L). Compound 19 was cellularly engaged to USP28 in gastric cancer cells. Compound 19 reversibly bound to USP28 and directly affected its protein levels, thus inhibiting the proliferation, cell cycle at S phase, and epithelial-mesenchymal transition (EMT) progression in gastric cancer cell lines. Docking studies were performed to rationalize the potency of compound 19. Collectively, compound 19 could serve as a new tool compound for the development of new USP28 inhibitors for exploring the roles of deubiquitinase in cancers.

20.
Microb Cell Fact ; 19(1): 171, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32873292

RESUMO

BACKGROUND: Although recent studies have indicated that intestinal microbiota dweller are involved in the pathogenesis of allergy rhinitis (AR), the influence of gut microbiota on AR adult has not been fully elucidated yet. Hence, we carried out this study to uncover the distinctive bacterial taxa that differentiate allergy rhinitis patients from healthy individuals. Feces samples from thirty three AR patients and thirty one healthy individuals were analyzed by 16S rRNA gene sequencing. RESULTS: Results showed that the bacterial diversity in AR group was significantly higher than that of the non-AR group. Bacterial communities between AR and non-AR group were significantly differentiated as revealed by Principal coordinates analysis (PCoA) and the variation within non-AR were higher than that of the counterpart. Firmicutes, Fusobacteria, Actinobacteria, Cyanobacteria and Chloroflexi were the significantly differed phyla taxa and the top significantly distinguished bacterial genus included Prevotella_9, Phascolarctobacterium, Roseburia, Megamonas, Alistipes, Lachnoclostridium and Fusobacterium. The higher network complexity in AR group were dominated by taxa belonging to Firmicutes. The predicted function, alpha linolenic acid metabolism and bacterial invasion of epithelial cells pathway were higher in non-AR group while gonadotropin-releasing hormone (GnRH) signaling pathway, Fc γ-R mediated phagocytosis and endocytosis were higher in AR patients. Although the bacterial diversity between moderate and severe AR patients showed no significant difference, the significant correlation between featured genus and total nasal symptom score or rhinoconjunctivitis quality of life questionnaire, such as Butyricicoccus and Eisenbergiella, revealed the potential to intervene the AR status by means of gut microbiota. CONCLUSIONS: In conclusion, patients with allergy rhinitis had distinguished gut microbiota characteritics in comparison with healthy controls. The results suggest that gut microbiota might play crucial roles in influencing the course and different symptoms of AR. Trial registration ChiCTR, ChiCTR1900028613. Registered 29 December 2019, https://www.chictr.org.cn/showproj.aspx?proj=47650 .

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