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1.
Org Biomol Chem ; 2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34610069

RESUMO

A nitrogen-centered radical-mediated carbon-carbon bond cleavage strategy is described to synthesize functionalized 3-acylcoumarins. The strategy is enabled by the visible-light-induced acylation/cyclization of alkynoates with various acyl oxime compounds in acetonitrile. The difunctionalization of carbon-carbon triple bonds precedes the generation of iminyl radicals, which is followed by the formation of acyl radicals. The acyl radicals then attack the carbon-carbon triple bonds, followed by 5-exo-trig cyclization and 1,2-ester migration. This strategy has wide substrate adaptability and good substituent tolerance.

3.
Diagn Pathol ; 16(1): 90, 2021 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-34629105

RESUMO

BACKGROUND: Acute fibrinous and organizing pneumonia (AFOP) is a rare histologic interstitial pneumonia pattern characterized by the intra-alveolar fibrin deposition and organizing pneumonia. Its clinical characteristics are still not well known and there is no consensus on treatment yet. CASE PRESENTATION: We report two female cases in their fifties diagnosed with AFOP confirmed by a second lung biopsy. Case 1 was idiopathic AFOP with manifestation of 6-week fever, dyspnea, and cough, while case 2 was secondary to systemic lupus erythematosus and fever was the major symptom. Their chest CT scans revealed bilateral multiple consolidations, predominantly in the lower lobes. Both cases were initially diagnosed with pneumonia, but did not improve after treatment with broad-spectrum antibiotics. In both cases, transbronchial biopsy and bronchoalveolar lavage fluid examination were inconclusive and the pathological diagnosis was confirmed by percutaneous lung biopsy. Both patients had a good clinical response to prednisone. CONCLUSIONS: We report two rare AFOP cases to highlight the importance of awareness of this disease. We further perform the most comprehensive review to date in AFOP, including 150 patients since 2002. Consolidation was the most common imaging pattern, followed by ground-glass opacity and nodules. A lung biopsy is required for a definitive diagnosis. Corticosteroids is recommended as the most effective therapy, but treatment options should depend on the etiology and disease severity.

4.
Gut ; 2021 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-34489308

RESUMO

OBJECTIVE: The absent in melanoma 2 (AIM2) cytosolic pattern recognition receptor and DNA sensor promotes the pathogenesis of autoimmune and chronic inflammatory diseases via caspase-1-containing inflammasome complexes. However, the role of AIM2 in cancer is ill-defined. DESIGN: The expression of AIM2 and its clinical significance was assessed in human gastric cancer (GC) patient cohorts. Genetic or therapeutic manipulation of AIM2 expression and activity was performed in the genetically engineered gp130 F/F spontaneous GC mouse model, as well as human GC cell line xenografts. The biological role and mechanism of action of AIM2 in gastric tumourigenesis, including its involvement in inflammasome activity and functional interaction with microtubule-associated end-binding protein 1 (EB1), was determined in vitro and in vivo. RESULTS: AIM2 expression is upregulated by interleukin-11 cytokine-mediated activation of the oncogenic latent transcription factor STAT3 in the tumour epithelium of GC mouse models and patients with GC. Genetic and therapeutic targeting of AIM2 in gp130 F/F mice suppressed tumourigenesis. Conversely, AIM2 overexpression augmented the tumour load of human GC cell line xenografts. The protumourigenic function of AIM2 was independent of inflammasome activity and inflammation. Rather, in vivo and in vitro AIM2 physically interacted with EB1 to promote epithelial cell migration and tumourigenesis. Furthermore, upregulated expression of AIM2 and EB1 in the tumour epithelium of patients with GC was independently associated with poor patient survival. CONCLUSION: AIM2 can play a driver role in epithelial carcinogenesis by linking cytokine-STAT3 signalling, innate immunity and epithelial cell migration, independent of inflammasome activation.

5.
J Org Chem ; 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34523335

RESUMO

A convenient and efficient visible-light-induced tandem acylation/cyclization of N-propargylindoles with aryl- or alkyl-substituted acyl oxime esters for the synthesis of 2-acyl-substituted 9H-pyrrolo[1,2-a]indoles under transition-metal-free conditions, which proceeds via nitrogen-centered radical-mediated cleavage of the C-C σ-bond in acyl oxime esters, is established. The aryl or alkyl acyl radicals, which come from acyl oxime esters, attack the C-C triple bonds in N-propargylindoles and then go through intramolecular cyclization/isomerization.

6.
J Food Sci ; 86(10): 4466-4478, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34519051

RESUMO

During wine drinking, aroma release is mainly impacted by wine matrix compositions and oral physiological parameters. Notably, tannins in wine could interact with saliva protein to form aggregates which might also affect the volatility of volatiles. To explore tannins, saliva, and the interaction between them on the volatility of volatiles, the volatility of 16 aroma compounds in the model wine mixed with the commercial tannin extracts, human saliva, or both respectively, was evaluated in vitro static condition by using HS-SPME-GC/MS. The volatility of aroma compounds with high hydrophobicity or benzene ring appeared to decrease more when increasing the tannin levels. Specifically, the volatility of ethyl octanoate, ß-ionone, and guaiacol was decreased more than 20% by adding 2 g/L tannin extract. The addition of human saliva could significantly inhibit volatility of most aroma compounds in the model wine. Furthermore, the volatility of most aroma compounds in the mixture of tannins and human saliva was significantly lower than the control or the sample which were added with tannins or human saliva individually. The volatility of some aroma compounds in the mixture of the tannin and saliva was only around 50% or less, relative to the control. Two-way ANOVA analysis showed that there was a synergistic effect between tannin and saliva on decreasing the volatility of most aroma compounds (p < 0.05). Overall, understanding the effect of key factors such as tannins and saliva on volatility of volatiles could help to understand the sophisticated retronasal perceptions during wine tasting. PRACTICAL APPLICATION: The outputs of this research will be helpful in understanding the impact of tannins on retronasal aroma release during wine tasting. It might promote the control of tannins in the viticulture and brewing process to improve the retronasal perception of wine aroma.

7.
J Gene Med ; : e3390, 2021 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-34558151

RESUMO

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is a hereditary disease manifested by a thickened ventricular wall. Cysteine and glycine-rich protein 3 (CSRP3), the gene encoding muscle LIM protein, is important for initiating hypertrophic gene expression. The mutation of CSRP3 causes dilated cardiomyopathy or HCM. METHODS: In the present study, we enrolled a Chinese family with HCM across three generations. Whole-exome sequencing (WES) was performed in the proband to detect the candidate genes of the family. Sanger sequencing was performed for mutational analysis and confirmation of cosegregation. RESULTS: Through histopathological and imaging examinations, an obvious left ventricular hypertrophy was found in the proband. After WES data filtering, bioinformatic prediction and co-segregation analysis, a nonsense mutation (NM_003476.5:c.364C>T; NP_003467.1:p.Arg122*) of CSRP3 was identified in this family. This variant was predicted to be disease-causing and resulted in a truncated protein. CONCLUSIONS: This is the first HCM family case of CSRP3 (p.Arg122*) variation in Asia. The finding here not only contributes to the genetic diagnosis and counseling of the family, but also provides a new case with detailed phenotypes that may be caused by the CSRP3 variant.

8.
Food Res Int ; 147: 110493, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34399489

RESUMO

Pungency is increasingly being recognized as an important factor of overall sensory quality, palatability, and consumer preference of distilled spirits. The characterization of pungency is necessary to evaluate the potential sensory quality of distilled spirits. In this study, the temporal profiles of pungency of Baijiu with different aging times were evaluated using time-intensity (TI) and temporal dominance of sensations (TDS) methods, considering both pungency intensity and pungency sub-qualities. TI results indicated significant differences in release rate of pungency during Baijiu consumption. Compared to young Baijiu, old Baijiu tend to show higher release rate of pungency, the areas under the curve and duration of pungency were significantly decreased in old Baijiu. The TDS results showed significant differences in the combination of dominant sub-qualities, as well as in the maximum dominance rates and the dominant duration of sub-qualities among Baijiu. The young Baijiu were mainly characterized by the dominant sub-qualities of "burning" and "numbing", whereas for old Baijiu, "burning", "prickle", and "drying" were dominant. The application of TI and TDS provided dynamic and temporal profiles of pungency to fully characterize pungency differences of distilled beverages.


Assuntos
Sensação , Paladar , Bebidas , Comportamento do Consumidor
9.
Cancer Res ; 81(19): 4949-4963, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34348966

RESUMO

Hypoxia is known to be commonly present in breast tumor microenvironments. Stem-like cells that repopulate breast tumors, termed tumor-repopulating cells (TRC), thrive under hypoxic conditions, but the underlying mechanism remains unclear. Here, we show that hypoxia promotes the growth of breast TRCs through metabolic reprogramming. Hypoxia mobilized transcription factors HIF1α and FoxO1 and induced epigenetic reprogramming to upregulate cytosolic phosphoenolpyruvate carboxykinase (PCK1), a key enzyme that initiates gluconeogenesis. PCK1 subsequently triggered retrograde carbon flow from gluconeogenesis to glycogenesis, glycogenolysis, and the pentose phosphate pathway. The resultant NADPH facilitated reduced glutathione production, leading to a moderate increase of reactive oxygen species that stimulated hypoxic breast TRC growth. Notably, this metabolic mechanism was absent in differentiated breast tumor cells. Targeting PCK1 synergized with paclitaxel to reduce the growth of triple-negative breast cancer (TNBC). These findings uncover an altered glycogen metabolic program in breast cancer, providing potential metabolic strategies to target hypoxic breast TRCs and TNBC. SIGNIFICANCE: Hypoxic breast cancer cells trigger self-growth through PCK1-mediated glycogen metabolism reprogramming that leads to NADPH production to maintain a moderate ROS level.

10.
Curr Protoc ; 1(6): e144, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34101382

RESUMO

Microparticles (MPs) are heterogeneous populations of cell-derived vesicles that play an important role in intercellular communications. The release of MPs by tumor cells is a very common event in tumor microenvironments (TMEs). Tumor cell-derived MPs (T-MPs) contain a variety of bioactive molecules, thus modulating various biological processes, including the regulation of immune cell phenotype and function, as well as immune responses. Moreover, T-MPs can be used as natural carriers to deliver therapeutic drugs into tumor cells and immune cells, thus remodeling TMEs and modifying anti-tumor immune responses. These features allow T-MPs to function as potential biomaterials to be applied in tumor immunotherapies and vaccines. This article describes protocols for the isolation of T-MPs from supernatants of cultured tumor cells by multi-step centrifugations. Tools and protocols are also provided in order to characterize and validate the isolated MPs and to analyze the interaction between T-MPs and different target cells. © 2021 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Isolation of tumor cell-derived microparticles by multi-step centrifugations Basic Protocol 2: Characterization and validation of tumor cell-derived microparticles Basic Protocol 3: Functional analysis of the uptake of tumor cell-derived microparticles by different cell types.


Assuntos
Micropartículas Derivadas de Células , Neoplasias , Comunicação Celular , Humanos , Imunoterapia , Neoplasias/terapia , Microambiente Tumoral
11.
J Agric Food Chem ; 69(25): 6943-6957, 2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34143625

RESUMO

The aroma of a wine is mostly driven by not only the factors in the vineyard, such as the grape variety and harvest time, but also the fermentation process. Icewine is a unique, intensely sweet wine made from late harvested grapes that have frozen naturally on the vine. Different from normal table wines, the grapes used in icewine naturally undergo a dehydration process and freeze-thaw cycles, and the must for icewine making has to be pressed from frozen grapes. This pressing process leaves water behind as ice crystals and allows the grape juice to be concentrated with more sugars, acids, and other dissolved solids, resulting in a slower than normal fermentation. These special procedures can lead to a unique aroma characteristic of icewine. This review delves into recent advances in chemical compounds related to icewine aroma characteristics and addresses how changes in these aroma characteristics and composition are influenced by environmental, viticultural, and oenological factors in the vineyard and winery. Deficiencies in previous studies and future trends related to the flavor science of icewine were also briefly addressed.


Assuntos
Vitis , Compostos Orgânicos Voláteis , Vinho , Fermentação , Odorantes/análise , Paladar , Compostos Orgânicos Voláteis/análise , Vinho/análise
13.
Food Chem ; 357: 129761, 2021 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-33878580

RESUMO

Lactones are important flavor compounds in lots of foodstuffs. They also play an important role in brandy, but have not been studied at large. In this study, solid-phase extraction (SPE) and stir bar sorptive extraction (SBSE) combined with comprehensive two-dimensional gas chromatography and time-of-flight mass spectrometry (GC × GC-TOFMS) were applied to identify and quantify lactones in brandies between China and France. Totally 17 lactones were identified, four of which were detected only in SBSE. Among them, γ-valerolactone, γ-heptalactone, δ-octalactone, γ-undecanolactone and δ-dodecalactone were detected in brandy for the first time. The results of partial least squares-discriminant analysis (PLS-DA) revealed that lactones distinguished regional characteristics among different brandies. The omission test showed that four lactones (OAV > 1) had direct impact on the aroma of brandy, and other seven lactones at sub-threshold (0.1 < OAV < 1) provided peach and apricot aroma characteristics through synergistic effects.

14.
IEEE Trans Cybern ; PP2021 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-33822731

RESUMO

Constrained multiobjective optimization problems (CMOPs) involve both conflicting objective functions and various constraints. Due to the presence of constraints, CMOPs' Pareto-optimal solutions are very likely lying on constraint boundaries. The experience from the constrained single-objective optimization has shown that to quickly obtain such an optimal solution, the search should surround the boundary of the feasible region from both the feasible and infeasible sides. In this article, we extend this idea to cope with CMOPs and, accordingly, we propose a novel constrained multiobjective evolutionary algorithm with bidirectional coevolution, called BiCo. BiCo maintains two populations, that is: 1) the main population and 2) the archive population. To update the main population, the constraint-domination principle is equipped with an NSGA-II variant to move the population into the feasible region and then to guide the population toward the Pareto front (PF) from the feasible side of the search space. While for updating the archive population, a nondominated sorting procedure and an angle-based selection scheme are conducted in sequence to drive the population toward the PF within the infeasible region while maintaining good diversity. As a result, BiCo can get close to the PF from two complementary directions. In addition, to coordinate the interaction between the main and archive populations, in BiCo, a restricted mating selection mechanism is developed to choose appropriate mating parents. Comprehensive experiments have been conducted on three sets of CMOP benchmark functions and six real-world CMOPs. The experimental results suggest that BiCo can obtain quite competitive performance in comparison to eight state-of-the-art-constrained multiobjective evolutionary optimizers.

15.
FEBS J ; 2021 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-33844440

RESUMO

Understanding excitation and inhibition balance in the brain begins with the tale of two basic types of neurons, glutamatergic projection neurons and GABAergic interneurons. The diversity of cortical interneurons is contributed by multiple origins in the ventral forebrain, various tangential migration routes, and complicated regulations of intrinsic factors, extrinsic signals, and activities. Abnormalities of interneuron development lead to dysfunction of interneurons and inhibitory circuits, which are highly associated with neurodevelopmental disorders including schizophrenia, autism spectrum disorders, and intellectual disability. In this review, we mainly discuss recent findings on the development of cortical interneuron and on neurodevelopmental disorders related to interneuron dysfunction.

16.
Org Biomol Chem ; 19(14): 3181-3190, 2021 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-33885572

RESUMO

A visible-light-mediated tandem cyanoalkylsulfonylation/cyclization of alkynoates with cycloketone oxime compounds for the preparation of 3-cyanoalkylsulfonylcoumarins via SO2 insertion is reported. The difunctionalization of carbon-carbon triple bonds includes a radical mechanism and involves the formation of an iminyl radical, ring-opening of the cycloketone, insertion of SO2, addition of the sulfonyl radical to carbon-carbon triple bonds, ipso-cyclization and ester migration.

17.
J Orthop Surg Res ; 16(1): 277, 2021 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-33902662

RESUMO

OBJECTIVE: To explore the clinical efficacy of posterior LFF for cervical OPLL with radicular pain of upper limbs METHODS: Between January 2014 and January 2018, 48 OPLL patients with radicular pain symptoms of upper limbs who underwent a one-stage posterior laminectomy and instrumented fusion with/without foraminotomy were reviewed retrospectively and divided into two groups: LF group (laminectomy with instrumented fusion without foraminotomy) and LFF group (laminectomy with instrumented fusion and foraminotomy). Clinical data were assessed and compared between the two groups. The radicular pain of upper limbs and neck was measured using the visual analog scale (VAS). The neurological function was evaluated with the American Spinal Injury Association (ASIA) scale. Changes of sagittal alignment were investigated by postoperative plain x-ray or computed tomography (CT). Moreover, the decompression of the spinal cord was evaluated based on postoperative MRI. RESULTS: All the 48 patients were followed up for 24-42 months with an average follow-up time of 31.1±5.3 months. A total of 56 cervical intervertebral foramens were enlarged in 48 patients, including 40 cases (83.3%) with 1 intervertebral foramen enlargement and 8 cases (16.7%) with 2 intervertebral foramen enlargements. There were no significant differences in intraoperative blood loss, postoperative drainage amount, Japanese Orthopaedic Association (JOA) scores, JOA recovery rates, VAS scores for neck pain, and ASIA grade between two groups. The mean operative time was shorter in the LF group compared with the LFF group. The VAS score for arm pain was significantly lower while the surgical duration was longer in group B. No statistical difference was observed between the two groups in terms of C2-C7 SVA, cervical lordosis, focal angulation at the foraminotomy segment, and local spinal cord angle. Compared with the LF group, there was no segmental kyphosis or instability where the additional posterior foraminotomy was performed in the LFF group. CONCLUSIONS: One-stage posterior LFF can achieve satisfied clinical efficacy in improving neurological function and relieving the radicular pain of the upper limbs for OPLL patients with radiculopathy symptoms.

18.
Food Chem ; 353: 129483, 2021 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-33740506

RESUMO

This study explored the impact of perceptual interactions on the odor intensity of 222 binary mixtures designed from 72 odorants found in food products. Odor intensity was rated by 30 trained subjects. The results showed that in most cases, the components' odor was perceived within the mixture and their intensity remained the same as in the unmixed situation in 54.3% of cases. Masking was the second major effect (44.8%) and occurred more frequently when components' pleasantness was significantly different. Synergy occurred in a small number of cases (0.9%) and only for four compounds. The overall odor intensity of the mixture was determined to be equal to the strongest component in most cases (73.9%), while partial addition was observed as the second most frequent effect (21.7%), especially when the components had equal intensity. Overall, this work provides general rules about the outcome to expect when mixing key components of food aromas.


Assuntos
Odorantes/análise , Olfato/fisiologia , Adolescente , Adulto , Feminino , Análise de Alimentos/métodos , Humanos , Masculino , Análise de Componente Principal , Limiar Sensorial , Adulto Jovem
19.
Artigo em Inglês | MEDLINE | ID: mdl-33755555

RESUMO

Stochastic gradient descent (SGD) has become the method of choice for training highly complex and nonconvex models since it can not only recover good solutions to minimize training errors but also generalize well. Computational and statistical properties are separately studied to understand the behavior of SGD in the literature. However, there is a lacking study to jointly consider the computational and statistical properties in a nonconvex learning setting. In this paper, we develop novel learning rates of SGD for nonconvex learning by presenting high-probability bounds for both computational and statistical errors. We show that the complexity of SGD iterates grows in a controllable manner with respect to the iteration number, which sheds insights on how an implicit regularization can be achieved by tuning the number of passes to balance the computational and statistical errors. As a byproduct, we also slightly refine the existing studies on the uniform convergence of gradients by showing its connection to Rademacher chaos complexities.

20.
Sci Rep ; 11(1): 3065, 2021 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-33542353

RESUMO

To compare the surgical outcomes of autogenous spinous process with iliac bone graft in managing single segment lumbar pyogenic spondylitis (PS) after posterior debridement and instrumentation. We performed a retrospective study for adult patients with single level lumbar PS. 60 patients with single segment lumbar PS underwent one-stage posterior debridement, autogenous bone graft and instrumentations. The patients were divided into Group A (autogenous iliac bone) and Group B (autogenous spinous process). Preoperative Charlson comorbidity index (CCI) was analyzed to assess the comorbidity. Low back pain was evaluated using the visual analog scale (VAS). Neurological status was assessed with the American Spinal Injury Association (ASIA) scale. Clinical infection index including the C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) was also reviewed. Moreover, fusion and changes of sagittal alignment were investigated radiologically. There was a significantly longer operative time, hospital stay and greater blood loss in group A. The VAS scores improved significantly at each follow-up interval and post-operative VAS score was significantly lower in group B. At the last follow-up, ESR and CRP returned to normal for all patients. There was at least one grade level improvement in ASIA score. No statistical difference in corrected rate, loss of sagittal angle and lumbar lordosis was found between the two groups. There was no significant difference in fusion rate, mean fusion time and complications between the two groups. Compared with iliac bone graft, the autogenous spinous process bone graft can be less invasive and painful for the single segment lumbar PS. One-stage posterior debridement, autogenous spinous process bone graft and instrumentation can provide satisfactory results for appropriate cases.

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