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1.
Bioanalysis ; 14(5): 307-316, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35195039

RESUMO

Aim: HCP002, a phosphate-modified derivative of voriconazole, can improve solubility without using the nephrotoxic solubilizer, sulfobutylether-ß-cyclodextrin. To study pharmacokinetics in humans, LC-MS/MS methods to quantify HCP002 in human plasma and urine were developed and validated. Method: After protein precipitation by acetonitrile containing voriconazole-d3, HCP002 was separated on a ZORBAX SB-Aq column, and LCMS/MS analysis was performed in multi-response monitoring mode. Results: The analytical run time was 3 min. Linearity was observed over the ranges of 0.100-40.0 and 0.400-200 µg/ml in plasma and urine, respectively. Precision and accuracy were within acceptable limits. Sample stability was confirmed. Conclusion: Rapid and reproducible methods quantified HCP002 in urine, and plasma samples were established.


Assuntos
Plasma , Espectrometria de Massas em Tandem , Cromatografia Líquida/métodos , Humanos , Reprodutibilidade dos Testes , Espectrometria de Massas em Tandem/métodos
2.
Commun Biol ; 5(1): 779, 2022 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-35918471

RESUMO

Mutations in HNF1A cause Maturity Onset Diabetes of the Young (HNF1A-MODY). To understand mechanisms of ß-cell dysfunction, we generated stem cell-derived pancreatic endocrine cells with hypomorphic mutations in HNF1A. HNF1A-deficient ß-cells display impaired basal and glucose stimulated-insulin secretion, reduced intracellular calcium levels in association with a reduction in CACNA1A expression, and accumulation of abnormal insulin granules in association with SYT13 down-regulation. Knockout of CACNA1A and SYT13 reproduce the relevant phenotypes. In HNF1A deficient ß-cells, glibenclamide, a sulfonylurea drug used in the treatment of HNF1A-MODY patients, increases intracellular calcium, and restores insulin secretion. While insulin secretion defects are constitutive in ß-cells null for HNF1A, ß-cells heterozygous for hypomorphic HNF1A (R200Q) mutations lose the ability to secrete insulin gradually; this phenotype is prevented by correction of the mutation. Our studies illuminate the molecular basis for the efficacy of treatment of HNF1A-MODY with sulfonylureas, and suggest promise for the use of cell therapies.


Assuntos
Diabetes Mellitus Tipo 2 , Insulina , Cálcio/metabolismo , Diabetes Mellitus Tipo 2/genética , Fator 1-alfa Nuclear de Hepatócito/genética , Fator 1-alfa Nuclear de Hepatócito/metabolismo , Humanos , Insulina/metabolismo , Insulina Regular Humana , Células-Tronco/metabolismo , Sinaptotagminas
3.
Front Aging Neurosci ; 14: 935986, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35928991

RESUMO

The purposes of this perspective article were to summarize Wheelchair or Seated Tai Chi studies related to neuromuscular functions of older adults with disability; to describe the development of Wheelchair Tai Chi Ball (WTCB) exercise - a concept to combine mind-body exercise with strength training; and to propose a new Telehealth WTCB exercise for improving neuromuscular functions of old adults with spinal cord injury (SCI) and disability. With reference to neuromuscular functions, WTC intervention may have positive effects on simple reaction time, range of motion at the shoulder and trunk, static and dynamic sitting balance, handgrip strength, vagal activity, and sympathetic activity among older adults with disability. The developed WTCB intervention is a feasible and safe exercise which combines the mind-body exercise and strength conditioning into one exercise which possesses aerobic, stretching and strength trainings and may facilitate neuromuscular functions of older adults with disability. The proposed Telehealth WTCB 12 forms (TWTCB12) exercise with a "Moving Shadow" method in the telehealth may enable the learner to superimpose learner's image on an expert's demonstrating model to enhance the learning and practice effects. Since wheelchair users will learn and practice TWTCB12 movements in a seated position or sitting on a wheelchair the "Moving shadow" method on Zoom would provide an ideal telehealth learning and practice environment for the wheelchair users to learn and practice TWTCB12 exercise from home more feasible and user friendly.

4.
Front Immunol ; 13: 934040, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35924253

RESUMO

Macrophages are highly plastic cells, and the polarization-activating actions that represent their functional focus are closely related to metabolic reprogramming. The metabolic reprogramming of macrophages manifests itself as a bias toward energy utilization, transforming their inflammatory phenotype by changing how they use energy. Metabolic reprogramming effects crosstalk with the biological processes of inflammatory action and are key to the inflammatory function of macrophages. In ischemic heart disease, phenotypic polarization and metabolic shifts in circulating recruitment and tissue-resident macrophages can influence the balance of inflammatory effects in the heart and determine disease regression and prognosis. In this review, we present the intrinsic link between macrophage polarization and metabolic reprogramming, discussing the factors that regulate macrophages in the inflammatory effects of ischemic heart disease. Our aim is to estabilsh reliable regulatory pathways that will allow us to better target the macrophage metabolic reprogramming process and improve the symptoms of ischemic heart disease.


Assuntos
Ativação de Macrófagos , Isquemia Miocárdica , Humanos , Macrófagos/metabolismo , Fenótipo
5.
RSC Adv ; 12(31): 20251-20258, 2022 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-35919596

RESUMO

By combining the anionic salt meso-tetra(4-carboxyphenyl)porphyrin (TCPP4-) and the Keggin polyoxometalate cation cluster [Al13O4(OH)24(H2O)12]7+ via a simple ion-exchange method, a hybrid (C48H26N4O8)[Al13O4(OH)24(H2O)12]2(OH)10·18H2O (Al13-TCPP) was prepared and thoroughly characterized as a prototype of polyoxometalate-porphyrin hybrids for the photocatalytic degradation of the mustard gas simulant 2-chloroethyl ethyl sulfide (CEES). The experimental results showed that the catalytic degradation rate of CEES in the presence of Al13-TCPP reached 96.16 and 99.01% in 180 and 90 min in methanol and methanol-water solvent mixture (v/v = 1 : 1), respectively. The reaction followed first-order reaction kinetics, and the half-life and kinetic constant in methanol and solvent mixture were 39.8 min, -0.017 min-1 and 14.7 min, -0.047 min-1. Mechanism analysis indicated that under visible light irradiation in air, CEES was degraded through a combination of oxidation and alcoholysis/hydrolysis in methanol and the methanol-water solvent mixture. The superoxide radical (O2˙-) and singlet molecular oxygen (1O2) generated by Al13-TCPP selectively oxidized CEES into a non-toxic sulfoxide. The singlet oxygen capture experiments showed that Al13-TCPP (Φ = 0.236) had a higher quantum yield of singlet oxygen generation than H4TCPP (Φ = 0.135) under visible light irradiation in air. The material Al13-TCPP has good reusability, and the degradation rate of CEES can still reach 98.37% after being recycled five times.

6.
Research (Wash D C) ; 2022: 9780864, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35935141

RESUMO

Light hydrocarbons (LHs) separation is an important process in petrochemical industry. The current separation technology predominantly relies on cryogenic distillation, which results in considerable energy consumption. Adsorptive separation using porous solids has received widespread attention due to its lower energy footprint and higher efficiency. Thus, tremendous efforts have been devoted to the design and synthesis of high-performance porous solids. Among them, porous carbons display exceptional stability, tunable pore structure, and surface chemistry and thus represent a class of novel adsorbents upon achieving the matched pore structures for LHs separations. In this review, the modulation strategies toward advanced carbon-based adsorbents for LHs separation are firstly reviewed. Then, the relationships between separation performances and key structural parameters of carbon adsorbents are discussed by exemplifying specific separation cases. The research findings on the control of the pore structures as well as the quantification of the adsorption sites are highlighted. Finally, the challenges of carbonaceous adsorbents facing for LHs separation are given, which would motivate us to rationally design more efficient absorbents and separation processes in future.

7.
Front Cardiovasc Med ; 9: 925254, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35935626

RESUMO

Normal endothelial function plays a pivotal role in maintaining cardiovascular homeostasis, while endothelial dysfunction causes the occurrence and development of cardiovascular diseases. Yes-associated protein (YAP) and its homolog transcriptional co-activator with PDZ-binding motif (TAZ) serve as crucial nuclear effectors in the Hippo signaling pathway, which are regulated by mechanical stress, extracellular matrix stiffness, drugs, and other factors. Increasing evidence supports that YAP/TAZ play an important role in the regulation of endothelial-related functions, including oxidative stress, inflammation, and angiogenesis. Herein, we systematically review the factors affecting YAP/TAZ, downstream target genes regulated by YAP/TAZ and the roles of YAP/TAZ in regulating endothelial functions, in order to provide novel potential targets and effective approaches to prevent and treat cardiovascular diseases.

8.
Plant Dis ; 2022 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-35939756

RESUMO

Punica granatum 'Tunisia' is widely planted in several areas of Kaiyang County, Guizhou Province, China. Symptoms of leaf spot and fruit rot were observed in April 2020. Infected pomegranate leaves exhibited scattered, oval, yellow-to-brown spots (2-5 mm), and numerous melanized pycnidia were observed in the center of the lesions. All 7-year-old pomegranate trees in a private orchard (Shangyi orchard, E27°09'08", N107°10'58"), exhibited the same symptoms, and 25% of the diseased pomegranate trees had blighted leaves in the late stage. Eighty diseased P. granatum leaves were collected in the orchard. Abundant fruiting bodies were observed on the surface of diseased spots examined using a dissecting microscope. Portions of the symptomatic leaves were surface disinfected with 75% ethanol for 30 s and then in 2% NaClO for 1 min, rinsed three times with sterile distilled water, and transferred onto potato dextrose agar (PDA) at 28°C for 3 weeks. The morphological characteristics of potential pathogens were observed and photographed under a compound light microscope (Zeiss Scope 5) equipped with an AxioCam 208 color camera. Pycnidial conidiomata were erumpent, globose, black, with a central ostiole, and oozed a slimy black conidial mass. Conidiophores were reduced to conidiogenous cells, ampulliform to subcylindrical, hyaline to pale brown, and proliferated percurrently at the apex. Macroconidia were solitary, one-celled, obovoid, truncate at the base, rounded at the apex, dark brown, aseptate, granular, and thick-walled, (11.0-)12.8-18.2(-19.0) × (9.2-)10.0-15.1(-16.0) µm (av: 14.8 × 12.0 µm, n = 30). No meso- or microconidia were observed. In morphology, our fungi were very similar to Dwiroopa punicae K.V. Xavier, A.N. Kc, J.Z. Groenew, Vallad & Crous (Xavier et al., 2019). Primers ITS4 and ITS5 were used to amplify the ITS, LROR and LR5 were for the LSU (White et al. 1900), and fRPB2-5F and fRPB2-7cR for rpb2 (Liu et al. 1999). Phylogenetic analysis based on these three loci also suggested that our strain was D. punicae, since there were 100% match for ITS and LSU and only two base differences in rpb2 gene between our strain and the D. punicae (CBS 143163). The qualified sequences were submitted to GenBank (ITS: MZ816695, MZ816696, MZ816697; LSU: MZ816692, MZ816693, MZ816694; rpb2: MZ802953). To fulfill Koch's postulates, mycelial plugs (5 mm diameter) were used for an inoculation experiment, only because the fungal isolates failed to produce conidia on PDA, and conidia from diseased tissues were also fewer to make the required spore suspension. A total of 20 attached leaves were used from three pots of pomegranate seedlings in the artificial climate chamber (25°C). Each mycelial plugs cut from 1-week-old PDA cultures were placed on one healthy leaf wrapped with a plastic fresh-keeping film. As control, leaves were inoculated with sterile PDA plugs. After 24h, the plugs were removed. The inoculation experiment was performed three times. Symptoms similar to the original were observed at the 7th day after inoculation on all inoculated plant leaves and necrosis occurred in 30-50% of leaf tissue, but control plants remained healthy. Dwiroopa punicae was successfully re-isolated from the inoculated diseased tissues after morphological and phylogenetic analyses. To the best of our knowledge, this is the first report of D. punicae causing leaf spot disease on pomegranate trees in China. This first report of D. punicae in China provides a basis for the diagnosticians and researchers to identify the disease and formulate disease management strategies.

9.
Public Health Nutr ; : 1-22, 2022 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-35941082

RESUMO

OBJECTIVE: The impact of the dietary potential inflammatory effect on diabetic kidney disease (DKD) has not been adequately investigated. The present study aimed to explore the association between Dietary Inflammatory Index (DII) and DKD in US Adults. DESIGN: This is a cross-sectional study. SETTING: Data from the National Health and Nutrition Examination Survey (NHANES 2007-2016) were used. DII were calculated from 24-hour dietary recall interviews. DKD was defined as diabetes with albuminuria, impaired glomerular filtration rate (GFR), or both. Logistic regression and restricted cubic spline models were adopted to evaluate the associations. RESULTS: 4264 participants were included in this study. The adjusted odd ratio (OR) of DKD was 1.04 (95 % CI 0.81, 1.36) for quartile 2, 1.24 (95 % CI 0.97, 1.59) for quartile 3 and 1.64 (95 % CI 1.24, 2.17) for quartile 4, respectively, compared with the quartile 1 of DII. A linear dose-response pattern was observed between DII and DKD (Pnonlinearity = 0.73). In the stratified analyses, the ORs for quartile 4 of DII were significant among adults with higher educational level, (OR 1.83, 95% CI 1.26, 2.66) and overweight or obese participants (OR 1.67, 95% CI 1.23, 2.28), but not among the corresponding another subgroup. The interaction effects between DII and stratified factors on DKD were not statistically significant (all P values for interactions were >0.05). CONCLUSIONS: Our findings suggest that a pro-inflammatory diet, shown by a higher DII score, is associated with increased odd of DKD.

10.
J Integr Plant Biol ; 2022 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-35943836

RESUMO

Gravity-induced root curvature involves the asymmetric distribution of the phytohormone auxin. This response depends on the concerted activities of the auxin transporters such as PIN-FORMED (PIN) proteins for auxin efflux and AUXIN RESISTANT 1 (AUX1) for auxin influx. However, how the auxin gradient is established remains elusive. Here we identified a new mutant with a short root, strong auxin distribution in the lateral root cap and an impaired gravitropic response. The causal gene encoded an Arabidopsis homolog of the human unconventional prefoldinRPB5 interactor (URI). AtURI interacted with prefoldin 2 (PFD2) and PFD6, two ß-type PFD members that modulate actin and tubulin patterning in roots. The auxin reporter DR5 rev :GFP showed that asymmetric auxin redistribution after gravistimulation is disordered in aturi-1 root tips. Treatment with the endomembrane protein trafficking inhibitor brefeldin A indicated that recycling of the auxin transporter PIN2 is disrupted in aturi-1 roots as well as in pfd mutants. We propose that AtURI cooperates with PFDs to recycle PIN2 and modulate auxin distribution. This article is protected by copyright. All rights reserved.

11.
Biochem Biophys Res Commun ; 623: 111-119, 2022 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-35921704

RESUMO

PURPOSE: To explore the role of HS1-binding protein 3 (HS1BP3) in hepatocellular carcinoma (HCC) and the potential mechanism. METHODS: The effect of HS1BP3 in the prognosis of HCC was analyzed. The influence of HS1BP3 silence on proliferation, migration, cell cycle, and apoptosis of HCC cells (Huh-7 and Sun-449) were evaluated. The upstream transcription factors of HS1BP3 were further explored. RESULTS: The high expression of HS1BP3 in HCC was significantly associated with poor prognosis. The silencing of HS1BP3 inhibited proliferation, invasion, migration, and promoted G1 phase cell cycle arrest and apoptosis of HCC cells. Estrogen receptors 1 (ESR1) inhibited proliferation and improved the prognosis of HCC via fusion with HS1BP3 promoter. CONCLUSION: HS1BP3 may serve as a novel tumor-promoting factor transcriptionally regulated by ESR1.

12.
Front Immunol ; 13: 929040, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35928811

RESUMO

Brucellosis, caused by Brucella spp., is one of the most widespread bacterial zoonoses worldwide. Vaccination is still considered the best way to control brucellosis. An investigation into the differential proteome expression patterns of wild and vaccine strains may help researchers and clinicians differentiate between the strains to diagnose and better understand the mechanism(s) underlying differences in virulence. In the present study, a mass spectrometry-based, label-free relative quantitative proteomics approach was used to investigate the proteins expressed by the wild strain, B. melitensis biovar 3 and compare it with those expressed by B. melitensis M5-90. The higher level of virulence for B. melitensis biovar 3 compared to B. melitensis M5-90 was validated in vitro and in vivo. A total of 2133 proteins, encompassing 68% of the theoretical proteome, were identified and quantified by proteomic analysis, resulting in broad coverage of the B. melitensis proteome. A total of 147 proteins were identified as differentially expressed (DE) between these two strains. In addition, 9 proteins and 30 proteins were identified as unique to B. melitensis M5-90 and B. melitensis biovar 3, respectively. Pathway analysis revealed that the majority of the DE proteins were involved in iron uptake, quorum sensing, pyrimidine metabolism, glycine betaine biosynthetic and metabolic processes, thiamine-containing compound metabolism and ABC transporters. The expression of BtpA and VjbR proteins (two well-known virulence factors) in B. melitensis biovar 3 was 8-fold and 2-fold higher than in B. melitensis M5-90. In summary, our results identified many unique proteins that could be selected as candidate markers for differentiating vaccinated animals from animals with wild-type infections. BtpA and VjbR proteins might be responsible for the residual virulence of B. melitensis M5-90, while ABC transporters and thiamine metabolism associated proteins may be newly identified Brucella virulence factors. All of the identified DE proteins provide valuable information for the development of vaccines and the discovery of novel therapeutic targets.


Assuntos
Brucella melitensis , Brucelose , Transportadores de Cassetes de Ligação de ATP , Animais , Proteínas de Bactérias , Proteoma/metabolismo , Proteômica , Tiamina , Fatores de Virulência
13.
Chemosphere ; : 135686, 2022 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-35934093

RESUMO

Pollution of wastewater and natural waters by organic contaminants is a major health issue, yet actual remediation methods are limited by incomplete removal of recalcitrant contaminants and by secondary pollution by chlorinated contaminants and catalytic metals. To attempt to solve these issues, we tested the removal of acid orange by peracetic acid (PAA), a safe oxidant, activated by Fe-biochar that iron anchored on biochar to prevent secondary pollution by iron. Fe-biochar was synthesized using a simple, one-step pyrolysis method. We investigated the effects of PAA concentration, pH, humic acids, chloride, bicarbonate on the reaction. Radical quenching and electron paramagnetic resonance were used to identify reacting species. Results showed that the granulous structure of Fe-biochar and the presence of Fe, Fe3O4, Fe2O3, and Fe3C on Fe-biochar surface. The highest removal of acid orange of 99.9% was obtained with 1.144 mM PAA and 0.3g/L Fe-biochar at pH 7. Acid orange removal increases with Fe-biochar dose, decreases with pH, is slightly inhibited by humic acids and bicarbonate, and is not modified by chloride. Our experimental results suggest that CH3C(O)OO· and CH3C(O)O· are the main radical species, but there may also be non-radical effects in Fe-biochar/PAA process. Fe-biochar displays high re-usability, with 92.8% removal after five uses.

14.
Front Genet ; 13: 919559, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35938024

RESUMO

Family with sequence similarity 83 (FAM83) is a newly identified family of oncogenes whose members play important roles in signaling and cancer progression. However, a thorough understanding of the FAM83 family in tumors is still lacking. Here, we performed a comprehensive analysis of the expression levels of the FAM83 family across cancers and patient prognoses using bioinformatics methods. We found that the expression levels of FAM83 family genes were upregulated in most tumors, and importantly, high expression levels of FAM83 family genes were related to poor prognosis in most tumors. In addition, we analyzed the relationship of FAM83 family genes with immune subtypes and the tumor microenvironment (TME). The results showed that FAM83 family genes were significantly associated with immune infiltrative subtypes and to varying degrees with the level of stromal cell infiltration and tumor stem cells. Finally, our study also showed the relationship between FAM83 family genes and drug sensitivity. Therefore, this pan-cancer analysis demonstrates the critical role of FAM83 family genes in tumor development and provides new clues for therapeutic strategies for cancer.

15.
Front Genet ; 13: 914645, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35938039

RESUMO

Background: Parkinson's disease (PD) is a common, age-related, and progressive neurodegenerative disease. Growing evidence indicates that immune dysfunction plays an essential role in the pathogenic process of PD. The objective of this study was to explore potential immune-related hub genes and immune infiltration patterns of PD. Method: The microarray expression data of human postmortem substantia nigra samples were downloaded from GSE7621, GSE20141, and GSE49036. Key module genes were screened via weighted gene coexpression network analysis, and immune-related genes were intersected to obtain immune-key genes. Functional enrichment analysis was performed on immune-key genes of PD. In addition to, immune infiltration analysis was applied by a single-sample gene set enrichment analysis algorithm to detect differential immune cell types in the substantia nigra between PD samples and control samples. Least absolute shrinkage and selection operator analysis was performed to further identify immune-related hub genes for PD. Receiver operating characteristic curve analysis of the immune-related hub genes was used to differentiate PD patients from healthy controls. Correlations between immune-related hub genes and differential immune cell types were assessed. Result: Our findings identified four hub genes (SLC18A2, L1CAM, S100A12, and CXCR4) and seven immune cell types (neutrophils, T follicular helper cells, myeloid-derived suppressor cells, type 1 helper cells, immature B cells, immature dendritic cells, and CD56 bright natural killer cells). The area under the curve (AUC) value of the four-gene-combined model was 0.92. The AUC values of each immune-related hub gene (SLC18A2, L1CAM, S100A12, and CXCR4) were 0.81, 0.78, 0.78, and 0.76, respectively. Conclusion: In conclusion, SLC18A2, L1CAM, S100A12, and CXCR4 were identified as being associated with the pathogenesis of PD and should be further researched.

16.
Mycology ; 13(3): 195-206, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35938078

RESUMO

Polysaccharides in boletes (Boletales) are economically significant to both function food and medicinal industries. The polysaccharides were extracted from the fruit bodies of eight boletes, namely, Aureoboletus longicollis, Butyriboletus hainanensis, Crocinoboletus rufoaureus, Hemioporus japonicus, Neoboletus infuscatus, Neoboletus obscureumbrinus, Tylopilus otsuensis, Xanthoconium fusciceps, which were collected from tropical China; their physicochemical properties and antioxidant activities were characterised and evaluated, respectively. The results revealed that the polysaccharides among the eight boletes were mainly composed of glucose, mannose, and galactose, with a broad molecular weight range, and contained a pyranose ring revealed by FT-IR and NMR spectral analyses. Many factors such as different species of boletes, geographic conditions, molecular weight, configuration, and monosaccharide content may affect the antioxidant power of polysaccharides, simultaneously, instead of one single factor. The antioxidant activities of the polysaccharides were measured according to in vitro assays of DPPH scavenging, superoxide anion scavenging, and ferrous ion reducing tests. The polysaccharide of C. rufoaureus has greatly superior antioxidant activity and it could serve as potential functional food or medicine.

17.
Metab Eng ; 73: 201-213, 2022 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-35934176

RESUMO

The oxidized kaurene (Ox-Kau) compounds are the core structures of many important diterpenoids with biological activities and economical values. However, easy access to diverse Ox-Kau products is still limited by low natural abundance, and large-scale manufacture remain challenging due to lack of proper heterologous production. To achieve an abundant source alternative to natural extracts, we here report a highly effective Escherichia coli-based platform for the de novo production of multiple Ox-Kau molecules from simple carbon source. Pathway optimization in prokaryotic cells through modification of transmembrane CYP450 oxidases, cytochrome b5 co-expression and AlphaFold-based protein engineering improved a 50-fold yield of steviol (1.07 g L-1), a key intermediate in the kaurenoid biosynthesis. Combinatorial biosynthetic strategy further led to a series of oxidized derivatives (20-600 mg L-1) with rich oxygenated functional groups on C3, C7, C16 and C19 previously hard to be introduced. Our engineered strains not only laid a foundation for realizing the industrial fermentation of gram-scale ent-kaurene diterpenoids, but also provided a reliable platform for characterization and utilization of kaurene-modifying oxidases, which may generate naturally rare or unnatural ent-kaurenoids with potential bioactivity.

18.
J Nanobiotechnology ; 20(1): 372, 2022 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-35953828

RESUMO

Although combination chemoimmunotherapy shows promising clinical results for cancer treatment, this approach is largely restricted by variable objective response rate and severe systemic adverse effects of immunotherapeutic antibody and chemotherapeutic drugs. Therefore, an in situ-formed therapeutic silk-chitosan composite scaffold is fabricated in this study to allow local release of the chemotherapeutic drug doxorubicin (DOX) and JQ1 (small molecular inhibitor used for the extraterminal protein BRD4 and bromodomain) with control release kinetics. DOX-JQ1@Gel contains a pH-degradable group that releases therapeutics in a weak acidic tumor microenvironment. The released DOX could directly kill tumor cells or lead to immunogenic cell death, thereby triggering the response of antitumor immunity. Meanwhile, chemotherapy-triggered antigen release and JQ1-mediated PD-L1 checkpoint blockade cumulatively contribute to trigger the response of antitumor immunity. Finally, the DOX-JQ1@Gel is locally injected to evaluate its synergistic cancer therapeutic effect, which is expected to improve objective response rate of immunotherapy and minimize systemic side effects.


Assuntos
Hidrogéis , Microambiente Tumoral , Linhagem Celular Tumoral , Doxorrubicina/farmacologia , Concentração de Íons de Hidrogênio , Imunoterapia/métodos , Proteínas Nucleares , Fatores de Transcrição
19.
Foods ; 11(15)2022 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-35954006

RESUMO

Chrysanthemum (Chrysanthemum morifolium Ramat.) is a seasonal plant with high medicinal and aesthetic value, and drying is an effective practice to enhance its storability after harvesting. The effects of hot air drying (HAD), combined infrared and hot air drying (IR-HAD), and sequential IR-HAD and HAD (IR-HAD + HAD) on the drying behavior, color, shrinkage, aroma profiles, phenolic compounds, and microstructure of chrysanthemum cakes were studied. Results showed that the increasing temperature resulted in a decrease in drying time and an increase in drying rate and moisture diffusivity. The Logarithmic and Page models exhibited superior fit in describing the dehydration process. Among the three drying strategies, IR-HAD was more effective in reducing energy consumption, improving shrinkage, water holding capacity, water binding capacity and cellular microstructure, while IR-HAD + HAD showed better inhibitory effect on color deterioration. Furthermore, gas chromatography-mass spectrometry (GC-MS) analysis revealed that different drying strategies dramatically influenced the aroma profiles in samples, and IR-HAD obtained the highest concentration of volatiles. The results of ultra-performance liquid chromatography (UPLC) indicated that the introduction of infrared radiation contributed to increasing the contents of chlorogenic acid, luteolin, total phenolic and flavonoid. These suggested that IR-HAD was a promising technique for drying medicinal chrysanthemum.

20.
Materials (Basel) ; 15(15)2022 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-35955325

RESUMO

Although graphitic carbon nitride nanosheets (CNs) with atomic thickness are considered as promising materials for hydrogen production, the wide band gap (3.06 eV) and rapid recombination of the photogenerated electron-hole pairs impede their applications. To address the above challenges, we synergized atomically thin CNs and graphene quantum dots (GQDs), which were fabricated as 2D/0D Van der Waals heterojunctions, for H2 generation in this study. The experimental characterizations indicated that the addition of GQDs to the π-conjugated system of CNs can expand the visible light absorption band. Additionally, the surface photovoltage spectroscopy (SPV) confirmed that introducing GQDs into CNs can facilitate the transport of photoinduced carriers in the melon chain, thus suppressing the recombination of charge carriers in body. As a result, the H2 production activity of the Van der Waals heterojunctions was 9.62 times higher than CNs. This study provides an effective strategy for designing metal-free Van der Waals hetero-structured photocatalysts with high photocatalytic activity.

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