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1.
Enzyme Microb Technol ; 162: 110134, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36166886

RESUMO

A convenient cell extract based metal organic frameworks (CE-MOF) strategy was used to produce self-assembled hybrid microparticles of enzymes with improved characteristics. It was shown that many metal ions and enzymes could be used to construct catalytically active CE-MOF microparticles. As a proof-of-principle study, the ß-xylosidase BH3683 was used to prepare FeSO4-CE-MOF-BH3683 microparticles to explore the factors influencing preparation of the microparticles. As a result, DNA, RNA, polysaccharides and proteins were found to play important roles in the formation of the microparticles and affected enzyme activities through interaction with enzyme molecules. Compared with the free BH3683, the optimum temperature of FeSO4-CE-MOF-BH3683 increased 5 °C, and the relative activity at 70 °C increased two times. Moreover, FeSO4-CE-MOF-BH3683 have stronger tolerance to different concentrations of various organic solvents and high-concentration xylose than the free BH3683, and the CE-MOF microparticles prepared by BH3683 and xylanase XynII could catalyze high-concentration xylan more efficiently than their free counterparts. In addition, FeSO4-CE-MOF-BH3683 exhibited about 40 % of its initial activity after reused for 10 times, showing satisfactory reusability. To sum up, this strategy might have wide application potential in the fields of biocatalysis, biofuel production, fertilizer industry, etc.


Assuntos
Estruturas Metalorgânicas , Extratos Celulares , Catálise , Proteínas , Metais
2.
Food Chem ; 403: 134309, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36191413

RESUMO

To demonstrate the roles of bacteria in fish protein degradation and related quality changes, three major grass carp spoilage bacteria were individually inoculated into grass carp flesh, and their effects on protein molecules, muscle structures, and quality indices were evaluated through peptidomics, optical microscopy and transmission electron microscope, and texture and water distribution analyses, respectively. Results showed that Pseudomonas putida degraded obscurin, nebulin, and titin, caused disarrangement of myofilaments and fragmented myofibers, and induced great loss of free water in muscle. Shewanella putrefaciens was active in hydrolyzing collagen and degraded both thick and thin filament proteins. Mutual separation of myofibers and severe texture softening were also observed in S. putrefaciens-inoculated samples. Aeromonas rivipollensis degraded myosin heavy chain and some thin filament proteins but less affected muscle microstructure and quality indices. Therefore, this study revealed the mechanisms of bacteria-induced grass carp protein degradation and provided guidance for developing quality control strategies.


Assuntos
Carpas , Animais , Carpas/metabolismo , Proteínas de Peixes/metabolismo , Proteólise , Miofibrilas/metabolismo , Água/metabolismo
3.
J Colloid Interface Sci ; 630(Pt A): 823-832, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36279841

RESUMO

Potassium-ion batteries (PIBs) have attracted enormous attention due to the increasing lithium battery cost, but their development is still in the pre-mature stage due to the limited selection of electrodes. Herein, a free-standing current-collector-integrated electrode, composed of mixed-phase WS2 nanosheets with nitrogen-doped multichannel carbon nanofibers (N-MCNFs) membrane, is reported for high-performance potassium ion batteries anode. Benefiting the unique multichannel carbon nanostructure as a current collector-integrated electrode as well as mixed-phase lamellar structure WS2 for enhanced potassium ion entry, the 1T/2H-WS2/N-MCNFs hybrid current-collector-free anode delivers an outstanding areal capacity of 2.88 mAh cm-2 (corresponding to 411 mAh/g based on the mass of both electrode and current collector) at a current of 0.7 mA cm-2 as well as long-term cycling stability for over 1000 cycles at a high current of 14 mA cm-2, surpassing the current state-of-art PIB anode. It is believed that our findings based on the high energy current collector integrated electrode at high mass loading would boost future research on practical metal ion batteries.

4.
J Colloid Interface Sci ; 630(Pt B): 580-590, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36335777

RESUMO

Anion substitution is a valid strategy to modulate the active sites of the transition metal dichalcogenides (TMDs). Herein, a series of cobalt sulfoselenide nanomeshes (CoS2(1-x)Se2x@NC) were synthesized by calcining S/Se power with ultrathin metal-organic framework (MOFs) nanosheets. The vacancy concentration of CoS2(1-x)Se2x@NC could be adjusted through changing the ratio of S/Se precursor. Interestingly, CoS1.25Se0.75@NC electrocatalyst possesses the largest vacancy concentration as well as the optimal electrocatalytic performance. CoS1.25Se0.75@NC delivers an overpotential as low as 134 mV for hydrogen evolution reaction (HER) and 270 mV for oxygen evolution reaction (OER) at the current density of 10 mA cm -2, respectively. Furthermore, CoS1.25Se0.75@NC affords a low cell voltage of 1.67 V (at 10 mA cm-2) and outstanding cycling stability for overall water splitting reaction (more than 55 h). For HER process, theoretical calculations prove that anion vacancy not only lower the free energy barrier of H2O dissociation step but also favor the desorption step of intermediate H*. For OER process, the anion vacancies could modulate the adsorption/desorption free energy of oxygen-containing intermediates. The present work demonstrates a practical approach to modulate the vacancy concentration of cobalt sulfoselenide and provides new ideas for design of efficient non-metal electrocatalysts.

5.
Food Funct ; 2022 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-36354156

RESUMO

Background: Choline has important and diverse functions in both cellular maintenance and growth. However, the relationships between the prediagnosis of the different forms of dietary choline intake and ovarian cancer (OC) survival are relatively unknown. This study is the first to investigate this topic based on the Ovarian Cancer Follow-Up Study, a prospective cohort study conducted in China. Methods: In the present study, 635 new cases of ovarian cancer between the ages of 18 and 79 were enrolled. A valid and reliable 111-item food frequency questionnaire was used to assess dietary choline intake. Deaths were ascertained until March 31, 2021, via medical records and active follow-up. Multivariable-adjusted Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Results: During a median follow-up of 37.2 months (interquartile: 24.7-50.2 months), 114 deaths were identified. Higher lipid-soluble choline intake was significantly associated with better overall survival for patients with OC (Tertile 3 vs. Tertile 1: HR = 0.56; 95% CI: 0.34, 0.92; P trend = 0.02) in the fully adjusted model. Similar associations were observed for phosphatidylcholine intake (Tertile 3 vs. Tertile 1: HR = 0.55; 95% CI: 0.33, 0.91; P trend = 0.02). However, no associations were found between total water-soluble choline (free choline, phosphocholine, and glycerophosphocholine), sphingomyelin, and betaine intake and OC survival. Significant additive interactions between higher fat-soluble choline intake and positive expression of estrogen receptor and Wilms tumor-1 as well as higher phosphatidylcholine intake and positive expression of estrogen receptor and Wilms tumor-1 on OC survival were detected. Conclusions: Our findings indicate that prediagnosis, total lipid-soluble choline and phosphatidylcholine intake were associated with improved overall survival among OC patients.

6.
Opt Express ; 30(23): 41328-41339, 2022 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-36366613

RESUMO

A functionally tunable and absorption-tunable terahertz (THz) metamaterial absorber based on vanadium dioxide (VO2) and graphene is proposed and verified numerically. Based on phase transition properties of VO2 and tunability of graphene, the switching performance between ultra-broadband and narrow-band near-perfect absorption can be achieved. We simulate and analyze the characteristics of the constructed model by finite element analysis. Theoretical calculations show that when VO2 is in the metallic state and the graphene Fermi energy is 0 eV, the designed absorber can perform ultra-broadband absorption. The absorber achieves greater than 95% absorption in the 2.85 - 10THz range. When VO2 is in the insulating state and the graphene Fermi energy is 0.7 eV, more than 99.5% absorption can be achieved at 2.3 THz. The absorption rate can be tuned by changing the conductivity of VO2 and the Fermi energy of graphene. Moreover, the proposed absorber displays good polarization insensitivity and wide incident angle stability. The design may have potential applications in terahertz imaging, sensing, electromagnetic shielding and so on.

7.
Int J Pharm ; 628: 122361, 2022 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-36332828

RESUMO

PD-1/L1 checkpoint blockade has gained approval in terms of treating patients suffering from hepatocellular carcinoma (HCC). It should be noted that the PD-1/L1 inhibitor (α-PD-1/L1) has a low overall response rate when used as a single agent. Accordingly, the combination of α-PD-1/L1 and a series of therapies to further increase the response rate has become a major research direction. In our previous study, we developed a novel norcantharidin (NCTD) liposome emulsion hybrid delivery system (NE) with enhanced anticancer activity and reduced toxicity. In this study, NE was combined with α-PD-1/L1 for treating HCC. The combination therapy exhibited an enhanced antitumor activity, which led to the up-regulated expression levels of white blood cells, interleukin 12 (IL-12), interferon γ (IFN-γ), PD-L1, as well as CD8. Furthermore, the combination of NE and α-PD-1 achieved the optimal efficiency. NCTD-based chemotherapy is capable of synergizing with α-PD-1/L1 while enhancing checkpoint immunotherapy. It follows a mechanism that NCTD agonizes the non-canonical NF-κB pathway of dendritic cells for better activating CD8+T cells. Furthermore, NCTD may enhance antitumor immunity due to the leukogenic effect. In brief, new therapeutic regimens were provided for anti-HCC treatment by integrating NE to PD-1/L1 immunotherapy.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Antígeno B7-H1 , Receptor de Morte Celular Programada 1/metabolismo , Lipossomos/uso terapêutico , NF-kappa B , Emulsões , Carcinoma Hepatocelular/patologia , Imunoterapia , Neoplasias Hepáticas/tratamento farmacológico , Linhagem Celular Tumoral
8.
Pharmacology ; : 1-13, 2022 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-36382664

RESUMO

INTRODUCTION: During breast cancer chemotherapy, the chemoresistance that frequently accompanies the treatment has become a big challenge. Long noncoding RNAs (LncRNAs) have been related to the development of chemoresistance in multiple cancer types. LncRNA DDX11-AS1 has shown a carcinogenic role in lung and colorectal cancer and was reported to enhance oxaliplatin resistance in gastric cancer and Taxol insensitivity in esophageal cancer. But its role in breast cancer chemotherapy drug resistance remains unknown. This study aimed to investigate the function and mechanism of lncRNA DDX11-AS1 in breast cancer chemoresistance. METHODS: The relationship between DDX11-AS1 and adriamycin (ADR) resistance was confirmed by qPCR, cell viability tests, and survival analysis. Then, RNA immunoprecipitation was conducted to evaluate the interaction between DDX11-AS1 and RNA-binding protein LIN28A. The regulation effect of LIN28A on autophagy-related genes ATG7 or ATG12 was detected by RNA stability assay and Western blot. Their correlation analysis was evaluated in GEO datasets and further validated by immunohistochemical results. The clinical significance of DDX11-AS1, ATG7, or ATG12 was evaluated by Kaplan-Meier Plotter analysis. RESULTS: Here, we reported DDX11-AS1 was significantly upregulated in chemoresistant breast cancer cells and overexpression of DDX11-AS1 promoted ADR resistance in breast cancer. LIN28A could interact with DDX11-AS1 and was involved in DDX11-AS1-mediated ADR resistance. Interfering with LIN28A reversed DDX11-AS1-induced ADR resistance. LIN28A could increase the protein level of ATG7 and ATG12 by increasing their mRNA stability. Survival analysis showed that ATG12 expression level was negatively correlated with the prognosis of breast cancer patients. CONCLUSION: This study clarifies the role of DDX11-AS1 in breast cancer chemoresistance and revealed a new mechanism, that is, interacting with LIN28A to stabilize ATG7 and ATG12 and jointly promote chemorefractory. These findings warrant further in vivo investigations to study DDX11-AS1 as a potential target to overcome chemoresistance.

9.
Cancer Biol Med ; 19(10)2022 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-36350006

RESUMO

OBJECTIVE: Accurate preoperative identification of benign or malignant pancreatic cystic neoplasms (PCN) may help clinicians make better intervention choices and will be essential for individualized treatment. METHODS: Preoperative ultrasound and laboratory examination findings, and demographic characteristics were collected from patients. Multiple logistic regression was used to identify independent risk factors associated with malignant PCN, which were then included in the nomogram and validated with an external cohort. The Net Reclassification Index (NRI) and Integrated Discrimination Improvement (IDI) were calculated to evaluate the improvement in the predictive power of the new model with respect to that of a combined imaging and tumor marker prediction model. RESULTS: Malignant PCN were found in 83 (40.7%) and 33 (38.7%) of the model and validation cohorts, respectively. Multivariate analysis identified age, tumor location, imaging of tumor boundary, blood type, mean hemoglobin concentration, neutrophil-to-lymphocyte ratio, carbohydrate antigen 19-9, and carcinoembryonic antigen as independent risk factors for malignant PCN. The calibration curve indicated that the predictions based on the nomogram were in excellent agreement with the actual observations. A nomogram score cutoff of 192.5 classified patients as having low vs. high risk of malignant PCN. The model achieved good C-statistics of 0.929 (95% CI 0.890-0.968, P < 0.05) and 0.951 (95% CI 0.903-0.998, P < 0.05) in predicting malignancy in the development and validation cohorts, respectively. NRI = 0.268; IDI = 0.271 (P < 0.001 for improvement). The DCA curve indicated that our model yielded greater clinical benefits than the comparator model. CONCLUSIONS: The nomogram showed excellent performance in predicting malignant PCN and may help surgeons select patients for detailed examination and surgery. The nomogram is freely available at https://wangjunjinnomogram.shinyapps.io/DynNomapp/.


Assuntos
Neoplasias Pancreáticas , Carbonitrila de Pregnenolona , Humanos , Neoplasias Pancreáticas/diagnóstico por imagem , Nomogramas , Antígeno CA-19-9 , Testes Hematológicos
10.
Nano Lett ; 2022 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-36413654

RESUMO

Protein assays with fingerprints and high sensitivity are essential for biomedical research and applications. However, the prevailing methods mainly rely on indirect or labeled immunoassays, failing to provide fingerprint information. Herein, we report a dual biomimetic recognition-driven plasmonic nanogap-enhanced Raman scattering (DBR-PNERS) strategy for ultrasensitive protein fingerprinting and quantitation. A pair of molecularly imprinted nanoantennas were rationally engineered for specifically trapping a target protein into well-defined plasmonic nanogaps through dual-terminal recognition for ultrahigh Raman signal amplification. Meanwhile, a Raman-active small molecule was embedded into the nanoantenna as an internal standard to provide a ratiometric assay for robust quantitation. DBR-PNERS exhibited several significant merits over existing approaches, including fingerprinting, ultrahigh sensitivity, quantitation robustness, speed, sample consumption, and so on. Therefore, it can be a promising tool for a protein assay and holds a great perspective in important applications.

11.
Sci Total Environ ; 858(Pt 2): 159831, 2022 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-36336049

RESUMO

Continuous measurements of volatile organic compounds (VOCs), ozone (O3), fine particulate matter (PM2.5), and related parameters were conducted between April 2020 and March 2021 in Beijing, China, to characterize potential sources of VOCs and their impacts on secondary organic aerosols (SOAs) and O3 levels. The annual average mixing ratio of VOCs was 17.4 ± 10.1 ppbv, with monthly averages ranging from 11.6 to 25.2 ppbv. According to the empirical kinetic modeling approach (EKMA), O3 formation during O3 season was "VOCs-limited", while it was in a "transition" regime during O3 pollution episodes. In the O3 season, higher ozone formation potential (OFP) of m/p-xylene, o-xylene, toluene, isopentane, and n-butane were evident during O3 pollution episodes, in line with the increasing contributions of solvent usage and coating, as well as gasoline evaporation to OFP obtained through a matrix factorization model (PMF). Aromatics contributed the most to the secondary organic aerosol formation potential (SOAFP). In the non-O3 season, the contribution of vehicle exhaust to SOAFP elevated on hazy days, thereby revealing the importance of traffic-derived VOCs for PM2.5 pollution. Our results indicate that the prior control of different VOC sources should vary by season, thereby facilitating the synergistic control of O3 and PM2.5 in Beijing.

12.
PLoS One ; 17(11): e0278126, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36417405

RESUMO

Medical studies have shown that the condition of human retinal vessels may reveal the physiological structure of the relationship between age-related macular degeneration, glaucoma, atherosclerosis, cataracts, diabetic retinopathy, and other ophthalmic diseases and systemic diseases, and their abnormal changes often serve as a diagnostic basis for the severity of the condition. In this paper, we design and implement a deep learning-based algorithm for automatic segmentation of retinal vessel (CSP_UNet). It mainly adopts a U-shaped structure composed of an encoder and a decoder and utilizes a cross-stage local connectivity mechanism, attention mechanism, and multi-scale fusion, which can obtain better segmentation results with limited data set capacity. The experimental results show that compared with several existing classical algorithms, the proposed algorithm has the highest blood vessel intersection ratio on the dataset composed of four retinal fundus images, reaching 0.6674. Then, based on the CSP_UNet and introducing hard parameter sharing in multi-task learning, we innovatively propose a combined diagnosis algorithm vessel segmentation and diabetic retinopathy for retinal images (MTNet). The experiments show that the diagnostic accuracy of the MTNet algorithm is higher than that of the single task, with 0.4% higher vessel segmentation IoU and 5.2% higher diagnostic accuracy of diabetic retinopathy classification.


Assuntos
Catarata , Diabetes Mellitus , Retinopatia Diabética , Humanos , Retinopatia Diabética/diagnóstico por imagem , Fundo de Olho , Vasos Retinianos/diagnóstico por imagem , Algoritmos
13.
Sensors (Basel) ; 22(22)2022 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-36433562

RESUMO

Infrared pedestrian detection has important theoretical research value and a wide range of application scenarios. Because of its special imaging method, infrared images can be used for pedestrian detection at night and in severe weather conditions. However, the lack of pedestrian feature information in infrared images and the small scale of pedestrian objects makes it difficult for detection networks to extract feature information and accurately detect small-scale pedestrians. To address these issues, this paper proposes an infrared pedestrian detection network based on YOLOv5, named IPD-Net. Firstly, an adaptive feature extraction module (AFEM) is designed in the backbone network section, in which a residual structure with stepwise selective kernel was included to enable the model to better extract feature information under different sizes of the receptive field. Secondly, a coordinate attention feature pyramid network (CA-FPN) is designed to enhance the deep feature map with location information through the coordinate attention module, so that the network gains better capability of object localization. Finally, shallow information is introduced into the feature fusion network to improve the detection accuracy of weak and small objects. Experimental results on the large infrared image dataset ZUT show that the mean Average Precision (mAP50) of our model is improved by 3.6% compared to that of YOLOv5s. In addition, IPD-Net shows various degrees of accuracy improvement compared to other excellent methods.

14.
Am J Hum Genet ; 109(11): 1960-1973, 2022 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-36332611

RESUMO

Sharing genomic variant interpretations across laboratories promotes consistency in variant assertions. A landscape analysis of Australian clinical genetic-testing laboratories in 2017 identified that, despite the national-accreditation-body recommendations encouraging laboratories to submit genotypic data to clinical databases, fewer than 300 variants had been shared to the ClinVar public database. Consultations with Australian laboratories identified resource constraints limiting routine application of manual processes, consent issues, and differences in interpretation systems as barriers to sharing. This information was used to define key needs and solutions required to enable national sharing of variant interpretations. The Shariant platform, using both the GRCh37 and GRCh38 genome builds, was developed to enable ongoing sharing of variant interpretations and associated evidence between Australian clinical genetic-testing laboratories. Where possible, two-way automated sharing was implemented so that disruption to laboratory workflows would be minimized. Terms of use were developed through consultation and currently restrict access to Australian clinical genetic-testing laboratories. Shariant was designed to store and compare structured evidence, to promote and record resolution of inter-laboratory classification discrepancies, and to streamline the submission of variant assertions to ClinVar. As of December 2021, more than 14,000 largely prospectively curated variant records from 11 participating laboratories have been shared. Discrepant classifications have been identified for 11% (28/260) of variants submitted by more than one laboratory. We have demonstrated that co-design with clinical laboratories is vital to developing and implementing a national variant-interpretation sharing effort. This approach has improved inter-laboratory concordance and enabled opportunities to standardize interpretation practices.


Assuntos
Bases de Dados Genéticas , Laboratórios , Humanos , Variação Genética , Austrália , Testes Genéticos
16.
Front Oncol ; 12: 913017, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36212504

RESUMO

Background: The purpose was to compare the efficacy and safety of hepatic arterial infusion (HAI) of oxaliplatin plus raltitrexed (TOMOX) to those of oxaliplatin plus 5-fluorouracil (FOLFOX) for unresectable colorectal cancer liver metastases (CRCLM). Methods: Patients with unresectable CRCLM were randomly assigned to receive HAI of TOMOX or FOLFOX. The primary end points were progression-free survival (PFS) measured from the date of randomisation until the date of disease progression and objective response rate (ORR). The secondary end points were overall survival (OS) measured from the date of randomisation until the date of death from any cause, disease control rate (DCR), and adverse events. Results: 113 patients were randomly assigned. With a median follow-up of 39.5 months, the PFS was 5.8 months [95% CI, 4.838-6.762]) and 4.6 months [95% CI, 3.419-5.781; P = 0.840], and the median OS was 17.6 months [95% CI, 13.828-21.372] and 13.1 months [95% CI, 11.215-14.985; P = 0.178] for the FOLFOX and TOMOX arm, respectively. The ORR were 26.1% vs 22.4% and DCR were 80.4% vs 71.4% in the FOLFOX and TOMOX arms. The most common severe adverse event was elevation of liver enzymes and pain, which did not differ in the two arms. Conclusion: HAI chemotherapy was effective for unresectable CRCLM. HAI of FOLFOX has similar efficacy to TOMOX, and HAI of TOMOX had shorter arterial infusion time. Clinical Trial Registration: https://clinicaltrials.gov/, identifier NCT02557490.

17.
Front Psychiatry ; 13: 991085, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36213914

RESUMO

The role of microbiological factors in the development of neurodegenerative diseases is attracting increasing attention, while the relationship remains debated. This study aimed to comprehensively summarize and evaluate the associations between microbiological factors and the risk of neurodegenerative disorders with an umbrella review. PubMed, Embase, and the Cochrane library were used to search for papers from the earliest to March 2021 for identifying meta-analyses and systematic reviews that examined associations between microbiological factors and neurodegenerative diseases. AMSTAR2 tool was employed to evaluate the methodical quality of systematic reviews and meta-analyses. The effect size and 95% confidence interval (95% CI) were recalculated with a random effect model after the overlap was recognized by the corrected covered area (CCA) method. The heterogeneity of each meta-analysis was measured by the I 2 statistic and 95% prediction interval (95% PI). Additionally, publication bias and the quality of evidence were evaluated for all 37 unique associations. Only 4 associations had above the medium level of evidence, and the rest associations presented a low level of evidence. Among them, helicobacter pylori (HP), infection, and bacteria are associated with Parkinson's disease (PD), and the other one verifies that periodontal disease is a risk factor for all types of dementia. Following the evidence of our study, eradication of HP and aggressive treatment of periodontitis are beneficial for the prevention of PD and dementia, respectively. This umbrella review provides comprehensive quality-grade evidence on the relationship between microbial factors and neurodegenerative disease. Regardless of much evidence linking microbial factors to neurodegenerative diseases, these associations are not necessarily causal, and the evidence level is generally low. Thus, more effective studies are required. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/#searchadvanced, PROSPERO, identifier: CRD42021239512.

18.
Bioresour Technol ; 365: 128178, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36279979

RESUMO

Resveratrol is a polyphenol with numerous applications in food, pharma, and cosmetics. Lack of precursors and low titer are the main problems hindering industrial scale resveratrol production. Based on previous prescreening, expressing the combination of FjTAL, Pc4CL1 and VvSTS achieved the best resveratrol titer. This was further improved to 235.1 mg/L through engineering the shikimic acid pathway, applying a modular enzyme assembly of Pc4CL1 and VvSTS, enhancing p-coumaric acid supply and diverting glycolytic flux toward erythrose-4-phosphate. The titer was increased to 819.1 mg/L following two rounds of multicopy integration of resveratrol biosynthesis and malonyl-CoA supply, respectively. The titer reached 22.5 g/L with a yield on glucose of 65.5 mg/g using an optimum fed-batch strategy in a 5 L bioreactor with morphology control. This research is the highest report on the de novo production of resveratrol in Yarrowia lipolytica and the findings lay a solid foundation for other producing polyphenols.


Assuntos
Yarrowia , Yarrowia/metabolismo , Resveratrol/metabolismo , Engenharia Metabólica , Malonil Coenzima A/metabolismo
19.
Cell Res ; 2022 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-36280710

RESUMO

STING, an endoplasmic reticulum (ER) transmembrane protein, mediates innate immune activation upon cGAMP stimulation and is degraded through autophagy. Here, we report that activated STING could be transferred between cells to promote antitumor immunity, a process triggered by RAB22A-mediated non-canonical autophagy. Mechanistically, RAB22A engages PI4K2A to generate PI4P that recruits the Atg12-Atg5-Atg16L1 complex, inducing the formation of ER-derived RAB22A-mediated non-canonical autophagosome, in which STING activated by agonists or chemoradiotherapy is packaged. This RAB22A-induced autophagosome fuses with RAB22A-positive early endosome, generating a new organelle that we name Rafeesome (RAB22A-mediated non-canonical autophagosome fused with early endosome). Meanwhile, RAB22A inactivates RAB7 to suppress the fusion of Rafeesome with lysosome, thereby enabling the secretion of the inner vesicle of the autophagosome bearing activated STING as a new type of extracellular vesicle that we define as R-EV (RAB22A-induced extracellular vesicle). Activated STING-containing R-EVs induce IFNß release from recipient cells to the tumor microenvironment, promoting antitumor immunity. Consistently, RAB22A enhances the antitumor effect of the STING agonist diABZI in mice, and a high RAB22A level predicts good survival in nasopharyngeal cancer patients treated with chemoradiotherapy. Our findings reveal that Rafeesome regulates the intercellular transfer of activated STING to trigger and spread antitumor immunity, and that the inner vesicle of non-canonical autophagosome originated from ER is secreted as R-EV, providing a new perspective for understanding the intercellular communication of organelle membrane proteins.

20.
Virus Res ; 323: 198990, 2022 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-36302471

RESUMO

Porcine circovirus type 2 (PCV2) is the causative agent of PCV2-associated disease, which causes a relevant economic impact on the global swine industry. Accumulating data have indicated host microRNAs play essential roles in numerous virus replication of pigs, while their roles in PCV2 replication remain unclear. Herein, we demonstrated that PCV2 infection downregulated the expression of miR-214-5p in PK15 cells, and miR-214-5p promoted PCV2 replication. C1q/tumor necrosis factor-related protein 1 (C1QTNF1) was then identified as a target gene of miR-214-5p, and C1QTNF1 suppressed PCV2 replication. Interestingly, miR-214-5p/C1QTNF1 axis negatively regulated AKT/mTOR signaling, and then enhanced PCV2 replication through promoting autophagy in PK15 cells. Collectively, our findings provide insight into the mechanism of PCV2 replication and highlight miR-214-5p and C1QTNF1 as potential novel targets for the treatment of PCV2 infection.

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