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2.
Int J Endocrinol ; 2021: 2520806, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34804156

RESUMO

Background: To investigate indicators for prediabetes risk and construct a prediction model for prediabetes incidences in China. Methods: In this study, 551 adults aged 40-70 years had normal glucose tolerance (NGT) and normal hemoglobin A1c (HbA1c) levels at baseline. Baseline data including demographic information, anthropometric measurements, and metabolic profile measurements were collected. The associations between possible indicators and prediabetes were assessed by the Cox proportional-hazards model. The predictive values were evaluated by the area under the receiver operating characteristic (ROC) curve (AUC). Results: During an average of 3.35 years of follow-up, the incidence of prediabetes was found to be 19.96% (n = 110). In the univariate analyses, fasting plasma glucose (FPG), fasting serum insulin (FINS), 2 h plasma glucose (2hPG), HbA1c, serum uric acid (SUA), waist circumference (WC), smoking, and family history of diabetes (FHD) were found to be significantly correlated with prediabetes. In the multivariable analyses, WC (hazard ratio (HR): 1.032; 95% confidence interval (CI): 1.010, 1.053; p = 0.003), FHD (HR: 1.824; 95% CI: 1.250, 2.661; p = 0.002), HbA1c (HR: 1.825; 95% CI: 1.227, 2.714; p = 0.003), and FPG (HR: 2.284; 95% CI: 1.556, 3.352; p < 0.001) were found to be independent risk factors for prediabetes. A model that encompassed WC, FHD, HbA1c, and FPG for predicting prediabetes exhibited the largest discriminative ability (AUC: 0.702). Conclusions: WC, FHD, HbA1c, and FPG are independently correlated with the risk of prediabetes. Furthermore, the combination of these predictors enhances the predictive accuracy of prediabetes.

4.
PLoS One ; 16(11): e0259974, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34780567

RESUMO

Transportation infrastructure, which has always been regarded as an important element to promote regional innovation, accelerates factor flows and productivity spillovers. In February 2021, the State Council of China issued the outline of national integrated multidimensional transportation network planning (2021-2050), which proposed that during the 14th Five-Year Plan period, the Yangtze River Delta would speed up the construction of an integrated transport network to serve the dual circulation development pattern in China. However, few studies have systematically investigated the development of integrated transport in the Yangtze River Delta, especially the relationship between transport operating efficiency and regional innovation based on the theory of flow space. This study aims to calculate the integrated transport efficiency of 26 cities in the Yangtze River Delta and analyse the spillover effect of efficiency improvement on urban innovation. The results reveal that integrated transport efficiency is relatively stable at approximately 0.92. We find that the local innovation value would increase by 0.119% with every 1% increase in transport efficiency, and it would exceed 0.26% after introducing spatial factors. The spillover effect on the surrounding cities is significantly higher than that in the cities themselves, and the result is 0.292 under the economic spatial distance weight matrix. These findings will support the construction of the integrated transport network and provide useful references for government decision makers in the Yangtze River Delta.

5.
Front Pharmacol ; 12: 709528, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34603024

RESUMO

Purpose: Lung cancer is the largest cause of cancer deaths in the world. Platinum-based chemotherapy is a foundation of first-line chemotherapy. However, the prognosis of lung cancer treated with platinum-based chemotherapy is still a challenge. Single nucleotide polymorphism of non-coding RNA has the potential to be a biomarker, but its effectiveness has yet to be comprehensively assessed. In this study, we explored the association between polymorphisms of non-coding RNA and prognosis of lung cancer patients receiving platinum-based chemotherapy. Materials and Methods: For 446 lung cancer patients receiving platinum-based chemotherapy, 22 single nucleotide polymorphisms of microRNA and long noncoding RNA were genotyped by MALDI-TOF mass spectrometry. Cox regression analysis, Kaplan-Meier method, and long-rank test have been performed to assess the association of overall and progression-free survival with polymorphisms. Results: In the additive and dominant models, genetic polymorphism of ANRIL rs1333049 (G > C) was significantly associated with progression-free survival. Additive model: CC vs GC vs GG [HR = 0.84, p = 0.021, 95% CI (0.73-0.97)]; Recessive model: CC vs GG + GC [HR = 0.77, p = 0.026, 95% CI (0.61-0.97)]. In the dominant model, compared with the CC genotype patients, lower risk of death [HR = 0.81, p = 0.036, 95% CI (0.66-0.99)] and lower risk of progression [HR = 0.81, p = 0.040, 95% CI (0.67-0.99)] have been observed on the patients with CG or GG genotype in miR-146A rs2910164. Conclusion: Our research demonstrated the potential of using ANRIL rs1333049 (G > C) and miR-146A rs2910164 (C > G) as biomarkers to support the prediction of a better prognosis for lung cancer patients receiving platinum-based chemotherapy.

6.
Front Microbiol ; 12: 742040, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34690988

RESUMO

Introduction: Diabetic foot infections (DFIs) pose a huge challenge for clinicians. Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA), is one of the most significant pathogens of DFI. Early pathogen identification will greatly benefit the diagnosis and treatment of the disease. However, existing diagnostic methods are not effective in early detection. Methods: We developed an assay that coupled loop-mediated isothermal amplification (LAMP) and clustered regularly interspaced short palindromic repeats (CRISPR) techniques to enable quick and specific detection of Staphylococcus aureus and differentiate MRSA in samples from patients with DFI. Furthermore, the results were compared using a reference culture, quantitative real-time polymerase chain reaction (qRT-PCR), and metagenomics next generation sequencing (mNGS). Results: The CRISPR-LAMP assay targeting nuc and mecA successfully detected S. aureus strains and differentiated MRSA. The limit of detection (LoD) of the real-time LAMP for nuc and mecA was 20 copies per microliter reaction in comparison to two copies per µL reaction for the qRT-PCR assay. The specificity of the LAMP-CRISPR assay for nuc was 100%, without cross-reactions with non-S. aureus strains. Evaluating assay performance with 18 samples from DFI patients showed that the assay had 94.4% agreement (17/18 samples) with clinical culture results. The results of mNGS for 8/18 samples were consistent with those of the reference culture and LAMP-CRISPR assay. Conclusion: The findings suggest that the LAMP-CRISPR assay could be promising for the point-of-care detection of S. aureus and the differentiation of MRSA in clinical samples. Furthermore, combining the LAMP-CRISPR assay and mNGS provides an advanced platform for molecular pathogen diagnosis of DFI.

7.
Pharmacol Res ; 174: 105934, 2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34648968

RESUMO

Drug resistance in small cell lung cancer (SCLC) significantly affects the efficacy of chemotherapy treatment. However, due to the lack of tumor tissue samples, especially serial tumor samples during chemotherapy, the mechanism of chemotherapy resistance has not been fully studied. Circulating tumor DNA, which can be obtained in a noninvasive manner, can complement tumor sampling approaches for research in this field. We identified an SCLC patient with acquired drug resistance from 52 SCLC patients for whom follow-up data were available. By comparing somatic mutations in circulating tumor DNA before and after chemotherapy, for the first time, we found that the somatic mutation eIF3A R803K may be related to acquired chemotherapy resistance. Then, the association between the eIF3A R803K mutation and chemotherapy resistance was confirmed by samples from 254 lung cancer patients receiving chemotherapy. We found that the eIF3a R803K mutation weakened the proliferation ability of tumor cells but increased their resistance to chemotherapy. Further studies revealed that the eIF3A R803K mutation promotes cellular senescence. In addition, fisetin showed a synergistic effect with chemotherapy in eIF3A R803K mutant cells. These results suggest that the eIF3A R803K somatic mutation has the potential to predict chemotherapy resistance in SCLC. Moreover, the eIF3A R803K mutation promotes chemotherapy resistance by inducing senescence. Furthermore, a senolytic drug, fisetin, can reverse chemotherapy resistance mediated by the eIF3A R803K mutation.

8.
Ecotoxicol Environ Saf ; 226: 112812, 2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-34571423

RESUMO

Contact toxicity assessments of six reduced risk insecticides were carried out to compare their selectivity and sensitivity toward the minute pirate bug Orius strigicollis and its prey Thrips hawaiiensis. Additionally, and their potential exposure risk were evaluated for O. strigicollis. The LR50 value of acetamiprid, emamectin benzoate, cyetpyrafen, and indoxacarb to T. hawaiiensis were 0.126, 2.093, 7.486, and 2.264 g a.i. ha-1, respectively, far less than the maximum field recommended rate (MFRR) for each. These four insecticides showed higher selectivity for predator and prey with selectivity ratio values of 37.3, 14.8, 22.1, and 119.3, respectively. However, the LR50 value of acetamiprid and emamectin benzoate were lower than MFRR, and unacceptable (approximately unacceptable for emamectin benzoate) risk to O. strigicollis in in-field, and the opposite results were shown in cyetpyrafen and indoxacarb. Although T. hawaiiensis was more sensitive to abamectin than O. strigicollis, the insecticide had poor selectivity for both test insects. The LR50 value of spirotetramat was more than 3 fold MFRR for T. hawaiiensis and O. strigicollis, showing extremely low contact toxicity and selectivity. In general, acetamiprid, emamectin benzoate, cyetpyrafen, and indoxacarb showed high bioactivity against T. hawaiiensis, but only cyetpyrafen and indoxacarb could be well compatible with O. strigicollis, the combination of two insecticides with O. strigicollis indicated a potential strategy for the efficient and safe control of T. hawaiiensis.


Assuntos
Heterópteros , Inseticidas , Tisanópteros , Animais , Insetos , Inseticidas/toxicidade
9.
Chemistry ; 2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34591343

RESUMO

The formation of imine bond is reversible. This feature has been taken advantage of by chemists for accomplishing high yielding self-assembly. On the other hand, it also jeopardizes the intrinsic stability of these self-assembled products. However, some recent discoveries demonstrate that some of these imine bond containing molecules could be rather stable or kinetically inert. A deep investigation indicated that such enhanced stability results from, at least partially, multivalence. Such results also inspire chemists to use imine condensation for self-assembly in water, a solvent that is considered not compatible with imine bond for a long time.

11.
Int J Oral Sci ; 13(1): 27, 2021 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-34408132

RESUMO

Nanomaterial-based drug sustainable release systems have been tentatively applied to bone regeneration. They, however, still face disadvantages of high toxicity, low biocompatibility, and low drug-load capacity. In view of the low toxicity and high biocompatibility of polymer nanomaterials and the excellent load capacity of hollow nanomaterials with high specific surface area, we evaluated the hollow polydopamine nanoparticles (HPDA NPs), in order to find an optimal system to effectively deliver the osteogenic drugs to improve treatment of bone defect. Data demonstrated that the HPDA NPs synthesized herein could efficiently load four types of osteogenic drugs and the drugs can effectively release from the HPDA NPs for a relatively longer time in vitro and in vivo with low toxicity and high biocompatibility. Results of qRT-PCR, ALP, and alizarin red S staining showed that drugs released from the HPDA NPs could promote osteogenic differentiation and proliferation of rat bone marrow mesenchymal stem cells (rBMSCs) in vitro. Image data from micro-CT and H&E staining showed that all four osteogenic drugs released from the HPDA NPs effectively promoted bone regeneration in the defect of tooth extraction fossa in vivo, especially tacrolimus. These results suggest that the HPDA NPs, the biodegradable hollow polymer nanoparticles with high drug load rate and sustainable release ability, have good prospect to treat the bone defect in future clinical practice.


Assuntos
Nanopartículas , Preparações Farmacêuticas , Animais , Regeneração Óssea , Indóis , Osteogênese , Polímeros , Ratos
12.
Proteins ; 2021 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-34392570

RESUMO

The presence of receptors and the specific binding of the ligands determine nearly all cellular responses. Binding of a ligand to its receptor causes conformational changes of the receptor that triggers the subsequent signaling cascade. Therefore, systematically studying structures of receptors will provide insight into their functions. We have developed the triangular spatial relationship (TSR)-based method where all possible triangles are constructed with Cα atoms of a protein as vertices. Every triangle is represented by an integer denoted as a "key" computed through the TSR algorithm. A structure is thereby represented by a vector of integers. In this study, we have first defined substructures using different types of keys. Second, using different types of keys represents a new way to interpret structure hierarchical relations and differences between structures and sequences. Third, we demonstrate the effects of sequence similarity as well as sample size on the structure-based classifications. Fourth, we show identification of structure motifs, and the motifs containing multiple triangles connected by either an edge or a vertex are mapped to the ligand binding sites of the receptors. The structure motifs are valuable resources for the researchers in the field of signal transduction. Next, we propose amino-acid scoring matrices that capture "evolutionary closeness" information based on BLOSUM62 matrix, and present the development of a new visualization method where keys are organized according to evolutionary closeness and shown in a 2D image. This new visualization opens a window for developing tools with the aim of identification of specific and common substructures by scanning pixels and neighboring pixels. Finally, we report a new algorithm called as size filtering that is designed to improve structure comparison of large proteins with small proteins. Collectively, we provide an in-depth interpretation of structure relations through the detailed analyses of different types of keys and their associated key occurrence frequencies, geometries, and labels. In summary, we consider this study as a new computational platform where keys are served as a bridge to connect sequence and structure as well as structure and function for a deep understanding of sequence, structure, and function relationships of the protein family.

13.
Front Microbiol ; 12: 712212, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34381436

RESUMO

Administration of all-trans retinoic acid (ATRA) to pregnant sows improves developmental defects of Hoxa1-/- fetal pigs, and this study aimed to explore the influence of maternal ATRA administration during pregnancy on gut microbiota of neonatal piglets. Samples of jejunal and ileal meconium of neonatal piglets before suckling were collected including 5 Hoxa1-/- and 20 non-Hoxa1-/- (Hoxa1+/+ and Hoxa1+/-) neonatal piglets from the control group and 5 Hoxa1-/- and 7 non-Hoxa1-/- neonatal piglets from the experimental group. Results indicated that Hoxa1 mutation shaped the bacterial composition of the jejunum and ileum of neonatal piglets and Hoxa1-/- neonatal piglets had significantly higher diversity and species richness, higher relative abundance of phylum Bacteroidetes, lower relative abundances of phylum Firmicutes and genus Lactobacillus, and lower ratio of Firmicutes to Bacteroidetes than non-Hoxa1-/- neonatal piglets. After maternal ATRA administration, Hoxa1-/- neonatal piglets had significantly higher diversity and species richness, higher relative abundances of two bacterial phyla (Bacteroidetes and Proteobacteria), and lower relative abundances of phylum Firmicutes and genus Lactobacillus in the jejunum than non-Hoxa1-/- neonatal piglets. Hoxa1-/- neonatal piglets delivered by sows with maternal ATRA administration had lower diversity and species richness and higher relative abundance of phylum Firmicutes in the jejunum than Hoxa1-/- neonatal piglets born by sows with no maternal ATRA administration. Non-Hoxa1-/- neonatal piglets delivered by sows with maternal ATRA administration had higher diversity and species richness and significantly lower relative abundances of phyla Firmicutes and Actinobacteria and genus Lactobacillus in the ileum than non-Hoxa1-/- neonatal piglets born by sows with no maternal ATRA administration. Hoxa1 mutation decreased the expression of bacterial genes involved in ABC transporters, purine metabolism, and aminoacyl-tRNA biosynthesis and increased the expression of bacterial genes involved in two-component system, starch and sucrose metabolism, and arginine and proline metabolism. Maternal ATRA administration decreased the expression of bacterial genes involved in arginine and proline metabolism, peptidoglycan biosynthesis, and fatty acid biosynthesis. Hoxa1 mutation resulted in bacterial dysbiosis of the small intestine of Hoaxa1-/- neonatal piglets, and maternal ATRA administration restored the bacterial dysbiosis of Hoxa1-/- neonatal piglets and altered the bacterial composition of the small intestine of non-Hoxa1-/- neonatal piglets.

14.
J Orthop Surg Res ; 16(1): 530, 2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34433474

RESUMO

BACKGROUND: Volar locking plating remains a popular method for the surgical management of distal radius fractures. Dorsal metaphyseal comminution (DMC) is a common fracture pattern which weakens the stability during fracture fixation. In this study, we aimed to compare the radiographic and functional outcome of the intra- and extra-articular distal radius fractures with DMC following single volar locking plate fixation. MATERIALS AND METHODS: Patients suffered from a distal radius fracture with DMC were reviewed in the clinical database of the authors' institution between Jan 2016 and Jan 2020. The included patients were classified into the extra-articular (A3) group or the intra-articular (C2 and C3) group according to the AO/OTA system. The radiological parameters, wrist range of motion, and functional outcomes were evaluated following open reduction and volar locking plate fixation. RESULTS: A total of 130 patients were included in this study with a mean follow-up length of 17.2 months. Compared with the A3 fracture group, no significant fracture re-displacement or reduced wrist ROMs was observed in the C2 fractures after 12-month's follow-up. However, significantly decreased volar tilt (P = 0.003) as well as the extension/flexion ROMs were observed in the C3 fractures comparing to the A3 fractures. Most of the patients achieved an excellent (n = 75) or good (n = 51) Gartland and Werley wrist score. Four patients with C3 fractures resulted in a fair functional outcome due to a significant loss of volar tilt during follow-up. CONCLUSIONS: The single volar locking plate fixation provided sufficient stability for distal radius fractures with DMC, and resulted in similar radiological and functional outcomes in the intra-articular distal radius fractures with a simple articular component (C2 fractures) as those in the extra-articular fractures. Considering the intra-articular fractures with multifragmentary articular component (C3 fracture), despite of the subsequent loss of volar tilt, the majority of the patients achieved good to excellent wrist function following single volar locking plating. TRIAL REGISTRATION: This study has been registered on the ClinicalTrials.gov.

15.
Vaccines (Basel) ; 9(8)2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34451954

RESUMO

To date, SARS-CoV-2 pandemic has caused more than 188 million infections and 4.06 million deaths worldwide. The receptor-binding domain (RBD) of the SARS-CoV-2 spike protein has been regarded as an important target for vaccine and therapeutics development because it plays a key role in binding the human cell receptor ACE2 that is required for viral entry. However, it is not easy to detect RBD in Western blot using polyclonal antibody, suggesting that RBD may form a complicated conformation under native condition and bear rare linear epitope. So far, no linear epitope on RBD is reported. Thus, a monoclonal antibody (mAb) that recognizes linear epitope on RBD will become valuable. In the present study, an RBD-specific rabbit antibody named 9E1 was isolated from peripheral blood mononuclear cells (PBMC) of immunized rabbit by RBD-specific single B cell sorting and mapped to a highly conserved linear epitope within twelve amino acids 480CNGVEGFNCYFP491 on RBD. 9E1 works well in Western blot on S protein and immunohistochemistry on the SARS-CoV-2 infected tissue sections. The results demonstrated that 9E1 can be used as a useful tool for pathological and functional studies of SARS-CoV-2.

16.
Nat Commun ; 12(1): 5131, 2021 08 26.
Artigo em Inglês | MEDLINE | ID: mdl-34446736

RESUMO

Protein delivery with cell-penetrating peptide is opening up the possibility of using targets inside cells for therapeutic or biological applications; however, cell-penetrating peptide-mediated protein delivery commonly suffers from ineffective endosomal escape and low tolerance in serum, thereby limiting in vivo efficacy. Here, we present an intracellular protein delivery system consisting of four modules in series: cell-penetrating peptide, pH-dependent membrane active peptide, endosome-specific protease sites and a leucine zipper. This system exhibits enhanced delivery efficiency and serum tolerance, depending on proteolytic cleavage-facilitated endosomal escape and leucine zipper-based dimerisation. Intravenous injection of protein phosphatase 1B fused with this system successfully suppresses the tumour necrosis factor-α-induced systemic inflammatory response and acetaminophen-induced acute liver failure in a mouse model. We believe that the strategy of using multifunctional chimaeric peptides is valuable for the development of cell-penetrating peptide-based protein delivery systems, and facilitate the development of biological macromolecular drugs for use against intracellular targets.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Falência Hepática Aguda/tratamento farmacológico , Peptídeos/química , Proteína Fosfatase 1/administração & dosagem , Animais , Peptídeos Penetradores de Células/química , Peptídeos Penetradores de Células/genética , Peptídeos Penetradores de Células/metabolismo , Endossomos/genética , Endossomos/metabolismo , Humanos , Concentração de Íons de Hidrogênio , Falência Hepática Aguda/genética , Falência Hepática Aguda/metabolismo , Camundongos Endogâmicos BALB C , Peptídeos/genética , Peptídeos/metabolismo , Proteína Fosfatase 1/química , Proteína Fosfatase 1/genética , Proteína Fosfatase 1/metabolismo , Transporte Proteico
17.
Sci Rep ; 11(1): 15892, 2021 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-34354119

RESUMO

Neurogenic bowel dysfunction, including hyperreflexic and areflexic bowel, is a common complication in patients with spinal cord injury (SCI). We hypothesized that removing part of the colonic sympathetic innervation can alleviate the hyperreflexic bowel, and investigated the effect of sympathectomy on the hyperreflexic bowel of SCI rats. The peri-arterial sympathectomy of the inferior mesenteric artery (PSIMA) was performed in T8 SCI rats. The defecation habits of rats, the water content of fresh faeces, the intestinal transmission function, the defecation pressure of the distal colon, and the down-regulation of Alpha-2 adrenergic receptors in colon secondary to PSIMA were evaluated. The incidence of typical hyperreflexic bowel was 95% in SCI rats. Compared to SCI control rats, PSIMA increased the faecal water content of SCI rats by 5-13% (P < 0.05), the emptying rate of the faeces in colon within 24 h by 14-40% (P < 0.05), and the defecation pressure of colon by 10-11 mmHg (P < 0.05). These effects lasted for at least 12 weeks after PSIMA. Immunofluorescence label showed the secondary down-regulation of Alpha-2 adrenergic receptors after PSIMA occurred mainly in rats' distal colon. PSIMA mainly removes the sympathetic innervation of the distal colon, and can relieve the hyperreflexic bowel in rats with SCI. The possible mechanism is to reduce the inhibitory effect of sympathetic activity, and enhance the regulatory effect of parasympathetic activity on the colon. This procedure could potentially be used for hyperreflexic bowel in patients with SCI.


Assuntos
Intestino Neurogênico/fisiopatologia , Traumatismos da Medula Espinal/fisiopatologia , Simpatectomia/métodos , Animais , Colo/fisiopatologia , Defecação/fisiologia , Fezes , Feminino , Motilidade Gastrointestinal/fisiologia , Masculino , Modelos Animais , Intestino Neurogênico/complicações , Intestino Neurogênico/cirurgia , Ratos , Ratos Sprague-Dawley , Traumatismos da Medula Espinal/complicações
18.
J Pharm Anal ; 11(3): 340-350, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34277122

RESUMO

Lipotoxicity, caused by intracellular lipid accumulation, accelerates the degenerative process of cellular senescence, which has implications in cancer development and therapy. Previously, carnitine palmitoyltransferase 1C (CPT1C), a mitochondrial enzyme that catalyzes carnitinylation of fatty acids, was found to be a critical regulator of cancer cell senescence. However, whether loss of CPT1C could induce senescence as a result of lipotoxicity remains unknown. An LC/MS-based lipidomic analysis of PANC-1, MDA-MB-231, HCT-116 and A549 cancer cells was conducted after siRNA depletion of CPT1C. Cellular lipotoxicity was further confirmed by lipotoxicity assays. Significant changes were found in the lipidome of CPT1C-depleted cells, including major alterations in fatty acid, diacylglycerol, triacylglycerol, oxidative lipids, cardiolipin, phosphatidylglycerol, phosphatidylcholine/phosphatidylethanolamine ratio and sphingomyelin. This was coincident with changes in expressions of mRNAs involved in lipogenesis. Histological and biochemical analyses revealed higher lipid accumulation and increased malondialdehyde and reactive oxygen species, signatures of lipid peroxidation and oxidative stress. Reduction of ATP synthesis, loss of mitochondrial transmembrane potential and down-regulation of expression of mitochondriogenesis gene mRNAs indicated mitochondrial dysfunction induced by lipotoxicity, which could further result in cellular senescence. Taken together, this study demonstrated CPT1C plays a critical role in the regulation of cancer cell lipotoxicity and cell senescence, suggesting that inhibition of CPT1C may serve as a new therapeutic strategy through induction of tumor lipotoxicity and senescence.

19.
Chem Commun (Camb) ; 57(64): 7966-7969, 2021 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-34286745

RESUMO

A new copper/silver-co-mediated three-component bicyclization of benzene-linked 1,6-enynes with ICF2CO2Et with TMSN3 was reported, and used to produce a wide range of hitherto unreported difluorinated tetrahydroindeno[1,2-c]azepine-3,6-diones with moderate to good yields. The mechanistic pathway consists of radical-induced 1,6-addition-cyclization, oxidative addition, reductive elimination, nitrene insertion and N-O cleavage, resulting in continuous multiple bond-forming events including C-C and C-N bonds to build up a 6/5/7 tricyclic framework.

20.
Sci Transl Med ; 13(606)2021 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-34285130

RESUMO

Multiple safe and effective vaccines that elicit immune responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are necessary to respond to the ongoing coronavirus disease 2019 (COVID-19) pandemic. Here, we developed a protein subunit vaccine composed of spike ectodomain protein (StriFK) plus a nitrogen bisphosphonate-modified zinc-aluminum hybrid adjuvant (FH002C). StriFK-FH002C generated substantially higher neutralizing antibody titers in mice, hamsters, and cynomolgus monkeys than those observed in plasma isolated from COVID-19 convalescent individuals. StriFK-FH002C also induced both TH1- and TH2-polarized helper T cell responses in mice. In hamsters, StriFK-FH002C immunization protected animals against SARS-CoV-2 challenge, as shown by the absence of virus-induced weight loss, fewer symptoms of disease, and reduced lung pathology. Vaccination of hamsters with StriFK-FH002C also reduced within-cage virus transmission to unvaccinated, cohoused hamsters. In summary, StriFK-FH002C represents an effective, protein subunit-based SARS-CoV-2 vaccine candidate.


Assuntos
COVID-19 , Animais , Anticorpos Neutralizantes , Anticorpos Antivirais , Vacinas contra COVID-19 , Cricetinae , Humanos , Camundongos , Subunidades Proteicas , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus/genética
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