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1.
J Agric Food Chem ; 72(15): 8684-8692, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38564621

RESUMO

Polyhydroxyalkanoates (PHAs) are promising alternatives to petroleum-based plastics, owing to their biodegradability and superior material properties. Here, the controllable biosynthesis of scl-co-mcl PHA containing 3-hydroxybutyrate (3HB) and mcl 3-hydroxyalkanoates was achieved in Pseudomonas chlororaphis HT66. First, key genes involved in fatty acid ß-oxidation, the de novo fatty acid biosynthesis pathway, and the phaC1-phaZ-phaC2 operon were deleted to develop a chassis strain. Subsequently, an acetoacetyl-CoA reductase gene phaB and a PHA synthase gene phaC with broad substrate specificity were heterologously expressed for producing and polymerizing the 3HB monomer with mcl 3-hydroxyalkanoates under the assistance of native ß-ketothiolase gene phaA. Furthermore, the monomer composition of scl-co-mcl PHA was regulated by adjusting the amount of glucose and dodecanoic acid supplemented. Notably, the cell dry weight and scl-co-mcl PHA content reached 14.2 g/L and 60.1 wt %, respectively, when the engineered strain HT11Δ::phaCB was cultured in King's B medium containing 5 g/L glucose and 5 g/L dodecanoic acid. These results demonstrated that P. chlororaphis can be a platform for producing scl-co-mcl PHA and has the potential for industrial application.


Assuntos
Poli-Hidroxialcanoatos , Pseudomonas chlororaphis , Ácido 3-Hidroxibutírico , Pseudomonas chlororaphis/genética , Pseudomonas chlororaphis/metabolismo , Aciltransferases/genética , Aciltransferases/metabolismo , Glucose/metabolismo
2.
Environ Toxicol ; 39(6): 3330-3340, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38440903

RESUMO

OBJECTIVE: Phthalates (PEs) could cause reproductive harm to males. A mixture of three widely used PEs (MPEs) was used to investigate the ameliorative effects of zinc (Zn) and vitamin E (VE) against male reproductive toxicity. METHODS: Fifty male SD rats were randomly divided into five groups (n = 10). Rats in MPEs group were orally treated with 160 mg/kg/d MPEs, while rats in MPEs combined Zn and/or VE groups were treated with 160 mg/kg/d MPEs plus 25 mg/kg/d Zn and/or 25 mg/kg/d VE. After intervention for 70 days, it's was measured of male reproductive organs' weight, histopathological observation of sperms and testes, serum hormones, PIWI proteins and steroidogenic proteins. RESULTS: Compared with control, anogenital distance, testes weight, epididymides weight, and sex hormones were significantly decreased, while the sperm malformation rate was markedly increased in MPEs group (p < .05); the testicular tissues were injured in MPEs group with disordered and decreased spermatids, and arrested spermatogenesis. PIWIL1, PIWIL2, StAR, CYP11A1 and CYP19A1 were down-regulated in MPEs group (p < .05). However, the alterations of these parameters were restored in MPEs combined Zn and/or VE groups (p < .05). CONCLUSION: Zn and/or VE improved steroid hormone metabolism, and inhibited MPEs' male reproductive toxicity.


Assuntos
Ácidos Ftálicos , Ratos Sprague-Dawley , Testículo , Vitamina E , Zinco , Animais , Masculino , Testículo/efeitos dos fármacos , Testículo/patologia , Vitamina E/farmacologia , Ácidos Ftálicos/toxicidade , Espermatozoides/efeitos dos fármacos , Ratos , Reprodução/efeitos dos fármacos , Tamanho do Órgão/efeitos dos fármacos
3.
Toxicol Appl Pharmacol ; 483: 116816, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38218207

RESUMO

Phthalates (PEs), such as di(2-ethylhexyl) phthalate (DEHP), dibutyl phthalate (DBP) and butyl benzyl phthalate (BBP) could cause reproductive and developmental toxicities, while human beings are increasingly exposed to them at low-doses. Phytochemical quercetin (Que) is a flavonoid that has estrogenic effect, anti-inflammatory and anti-oxidant effects. This study was conducted to assess the alleviative effect of Que. on male reproductive toxicity induced by the mixture of three commonly used PEs (MPEs) at low-dose in rats, and explore the underlying mechanism. Male rats were treated with MPEs (16 mg/kg/day) and/or Que. (50 mg/kg/d) for 91 days. The results showed that MPEs exposure caused male reproductive injuries, such as decreased serum sex hormones levels, abnormal testicular pathological structure, increased abnormal sperm rate and changed expressions of PIWIL1 and PIWIL2. Furthermore, MPEs also changed the expression of steroidogenic proteins in steroid hormone metabolism, including StAR, CYP11A1, CYP17A1, 17ß-HSD, CYP19A1. However, the alterations of these parameters were reversed by Que. MPEs caused male reproductive injuries in rats; Que. inhibited MPEs' male reproductive toxicity, which might relate to the improvement of testosterone biosynthesis.


Assuntos
Dietilexilftalato , Ácidos Ftálicos , Humanos , Ratos , Masculino , Animais , Quercetina/farmacologia , Testosterona , Ratos Sprague-Dawley , Sêmen/metabolismo , Ácidos Ftálicos/toxicidade , Ácidos Ftálicos/metabolismo , Testículo , Dietilexilftalato/toxicidade , Proteínas Argonautas/metabolismo , Proteínas Argonautas/farmacologia
4.
Food Sci Nutr ; 11(12): 7930-7945, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38107122

RESUMO

To investigate the antidiabetic effects and mechanisms of quinoa on type 2 diabetes mellitus (T2DM) mice model. In this context, we induced the T2DM mice model with a high-fat diet (HFD) combined with streptozotocin (STZ), followed by treatment with a quinoa diet. To explore the impact of quinoa on the intestinal flora, we predicted and validated its potential mechanism of hypoglycemic effect through network pharmacology, molecular docking, western blot, and immunohistochemistry (IHC). We found that quinoa could significantly improve abnormal glucolipid metabolism in T2DM mice. Further analysis showed that quinoa contributed to the improvement of gut microbiota composition positively. Moreover, it could downregulate the expression of TAS1R3 and TRPM5 in the colon. A total of 72 active components were identified by network pharmacology. Among them, TAS1R3 and TRPM5 were successfully docked with the core components of quinoa. These findings confirm that quinoa may exert hypoglycemic effects through gut microbiota and the TAS1R3/TRPM5 taste signaling pathway.

5.
Int J Ophthalmol ; 16(11): 1867-1875, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38028524

RESUMO

AIM: To develop the 17-item Asthenopia Survey Questionnaire (ASQ)-17 by Rasch analysis, and to generate a predictiveness score. METHODS: Totally 739 participants were recruited and 680 were involved in the result analysis in this prospective, cross-sectional study. Three rounds of Rasch analysis were used to analyze the psychometric characteristics of items and options. RESULTS: Phase 1 assessed the original ASQ-19, adjusted the item scoring mode to a four-point Likert response rating scale and combined the 18th and 19th items into a new item. Phase 2 deleted the 11th item. Phases 3 and 4 assessed the new ASQ-17. All the evaluation indexes of ASQ-17 were acceptable. The Infit and Outfit MnSq values of items were 0.67-1.48, the variance explained by the principal component and the unexplained variance explained by the first contrast were 53.90%-59.40% and 1.50-1.80 in three dimensions. The curve peaks of scores in each dimension were separated and in the same order. The PSR and PSI values were 2.80 and 0.89, respectively. The mean scores of dimensions A (9.5±4.1 vs 3.5±3.2), B (7.3±3.3 vs 2.5±2.7), C (4.3±2.2 vs 1.4±2.0) and total (21.1±8.1 vs 7.4±7.0) in asthenopia participants were significantly higher than those without asthenopia (all P<0.001). The area under the curve in two groups was 0.899 (P<0.001). Youden's index was up to the maximum value of 0.784 when the cut-off value was 12.5. CONCLUSION: ASQ-17 has stronger option sorting and suitability than ASQ-19. It is an effective assessment tool for asthenopia with an optimal cut-off threshold value of 12.5, which is suitable for diagnosis and curative effect evaluation.

6.
Macromolecules ; 56(10): 3507-3516, 2023 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-37251603

RESUMO

Mimicking the structure of proteins using synthetic polymers requires building blocks with structural similarity and the use of various noncovalent and dynamic covalent interactions. We report the synthesis of helical poly(isocyanide)s bearing diaminopyridine and pyridine side-chains and the multistep functionalization of the polymers' side-chains using hydrogen bonding and metal coordination. The orthogonality of the hydrogen bonding and metal coordination was proved by varying the sequence of the multistep assembly. The two side-chain functionalizations are reversible through the use of competitive solvents and/or competing ligands. Throughout the assembly and disassembly, the helical conformation of the polymer backbone is sustained as proved by circular dichroism spectroscopy. These results open the possibility to incorporate helical domains into complex polymer architectures and create a helical scaffold for smart materials.

7.
Adv Healthc Mater ; 12(10): e2201503, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36565136

RESUMO

Reproducing in vitro the complex multiscale physical features of human tissues creates novel biomedical opportunities and fundamental understanding of cell-environment interfaces and interactions. While stiffness has been recognized as a key driver of cell behavior, systematic studies on the role of stiffness have been limited to values in the KPa-MPa range, significantly below the stiffness of bone. Here, a platform enabling the tuning of the stiffness of a biocompatible polymeric interface up to values characteristic of human bone is reported, which are in the GPa range, by using extremely thin polymer films on glass and cross-linking the films using ultraviolet (UV) light irradiation. It is shown that a higher stiffness is related to better adhesion, proliferation, and osteogenic differentiation, and that it is possible to switch on/off cell attachment and growth by solely tuning the stiffness of the interface, without any surface chemistry or topography modification. Since the stiffness is tuned directly by UV irradiation, this platform is ideal for rapid and simple fabrication of stiffness patterns and gradients, thus representing an innovative tool for combinatorial studies of the synergistic effect of tissue environmental cues on cell behavior, and creates new opportunities for next-generation biosensors, single-cell patterning, and lab-on-a-chip devices.


Assuntos
Células-Tronco Mesenquimais , Osteogênese , Humanos , Matriz Óssea , Osso e Ossos , Diferenciação Celular
8.
J Phys Chem B ; 126(49): 10327-10334, 2022 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-36448780

RESUMO

The underlying chemical and physical mechanism of avian navigation is an important issue of broad interest. One of the most famous candidates is the radical-pair mechanism, which shows that the magnetoreception is achieved by detecting the amount of chemical-reaction product from the singlet state. In the hypothesis, the surrounding nuclear spins play an important role as inducing the coherent transition between the singlet and triplet states. Recently, it was suggested that a multiradical model beyond two radicals can also realize magnetoreception without the assistance of nuclear spins. Inspired by this discovery, we explore the amount of the singlet recombination product in a multiradical model, with a radical bath described by the Lipkin-Meshkov-Glick (LMG) model, which was originally proposed for quantum phase transition (QPT). We show that the sensitivity of the bionic compass can be improved at the critical point. Our results may pave the way for the exploration of the design principle of the bionic compass.


Assuntos
Campos Magnéticos , Teoria Quântica , Animais , Biônica , Aves , Transição de Fase
9.
ACS Macro Lett ; 11(3): 336-341, 2022 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-35575362

RESUMO

We report a hydrogen-bonded supramolecular miktoarm star polymer containing three distinct helical arms. Our design involves two helical poly(methacrylamide) arms connected by a barbituric acid (Ba) at the center, prepared through the reversible addition-fragmentation chain-transfer polymerization with a bifunctional agent. Together with a telechelic helical poly(isocyanide) end-functionalized with a Hamilton Wedge (HW) that is complementary to Ba, the two components assemble into an AB2-type star copolymer. The assembly is driven by the hydrogen bonding between HW and Ba, which is quantified by 1H NMR titration and isothermal titration calorimetry. Gel-permeation chromatography provides evidence for the formation of the desired miktoarm star architecture. This strategy of site-specific functionalization on helical polymers provides a modular approach to preparing nonlinear supramolecular ensembles with topologically diverse building blocks.


Assuntos
Polímeros , Cromatografia em Gel , Ligação de Hidrogênio , Espectroscopia de Ressonância Magnética , Polimerização , Polímeros/química
11.
J Exp Clin Cancer Res ; 41(1): 74, 2022 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-35193644

RESUMO

BACKGROUND: Glioblastoma (GB) is the most common and highly malignant brain tumor characterized by aggressive growth and resistance to alkylating chemotherapy. Autophagy induction is one of the hallmark effects of anti-GB therapies with temozolomide (TMZ). However, the non-classical form of autophagy, autophagy-based unconventional secretion, also called secretory autophagy and its role in regulating the sensitivity of GB to TMZ remains unclear. There is an urgent need to illuminate the mechanism and to develop novel therapeutic targets for GB. METHODS: Cancer genome databases and paired-GB patient samples with or without TMZ treatment were used to assess the relationship between HMGB1 mRNA levels and overall patient survival. The relationship between HMGB1 protein level and TMZ sensitivity was measured by immunohistochemistry, ELISA, Western blot and qRT-PCR. GB cells were engineered to express a chimeric autophagic flux reporter protein consisting of mCherry, GFP and LC3B. The role of secretory autophagy in tumor microenvironment (TME) was analyzed by intracranial implantation of GL261 cells. Coimmunoprecipitation (Co-IP) and Western blotting were performed to test the RAGE-NFκB-NLRP3 inflammasome pathway. RESULTS: The exocytosis of HMGB1 induced by TMZ in GB is dependent on the secretory autophagy. HMGB1 contributed to M1-like polarization of tumor associated macrophages (TAMs) and enhanced the sensitivity of GB cells to TMZ. Mechanistically, RAGE acted as a receptor for HMGB1 in TAMs and through RAGE-NFκB-NLRP3 inflammasome pathway, HMGB1 enhanced M1-like polarization of TAMs. Clinically, the elevated level of HMGB1 in sera may serve as a beneficial therapeutic-predictor for GB patients under TMZ treatment. CONCLUSIONS: We demonstrated that enhanced secretory autophagy in GB facilitates M1-like polarization of TAMs to enhance TMZ sensitivity of GB cells. HMGB1 acts as a key regulator in the crosstalk between GB cells and tumor-suppressive M1-like TAMs in GB microenvironment and may be considered as an adjuvant for the chemotherapeutic agent TMZ.


Assuntos
Antineoplásicos Alquilantes/uso terapêutico , Glioblastoma/tratamento farmacológico , Macrófagos/metabolismo , Temozolomida/uso terapêutico , Animais , Antineoplásicos Alquilantes/farmacologia , Apoptose , Autofagia , Linhagem Celular Tumoral , Glioblastoma/patologia , Humanos , Masculino , Camundongos , Temozolomida/farmacologia , Microambiente Tumoral
12.
Cancer Lett ; 532: 215585, 2022 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-35131384

RESUMO

Metastasis is responsible for the high mortality rate of lung cancer, but its underlying molecular mechanisms are poorly understood. Here, we demonstrated that the expression of diacylglycerol kinase alpha (DGKA) was elevated in the metastatic lesions of non-small cell lung cancer (NSCLC) and correlated with poor survival. Mechanistic studies revealed a direct physical interaction as well as a mutual regulation among DGKA, proto-oncogene tyrosine-protein kinase Src (SRC), and focal adhesion kinase 1 (FAK) proteins. The C-terminal domain of DGKA was responsible for the SRC SH3 domain binding, while the catalytic domain of DGKA interacted with the FREM domain of FAK. DGKA phosphorylated the SRC protein at Tyr416 and the FAK protein at Tyr397 to form and activate the DGKA/SRC/FAK complex, thus initiating the downstream WNT/ß-catenin and VEGF signaling pathways, promoting epithelial-mesenchymal transition (EMT) and angiogenesis, and resulting in the metastasis of NSCLC. DGKA knockdown inhibited the invasive phenotype of NSCLC cells in vitro. Pharmacologic ablation of DGKA inhibited the metastasis of NSCLC cells in vivo, and this was reversed by the overexpression of DGKA. These results suggested that DGKA was a potential prognostic biomarker as well as a promising therapeutic target for NSCLC, especially when there was lymphatic or distant metastasis.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Diacilglicerol Quinase/metabolismo , Neoplasias Pulmonares , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Movimento Celular , Quinase 1 de Adesão Focal/genética , Quinase 1 de Adesão Focal/metabolismo , Proteína-Tirosina Quinases de Adesão Focal , Humanos , Neoplasias Pulmonares/metabolismo , Proteínas Proto-Oncogênicas pp60(c-src)/metabolismo
13.
Oncogene ; 41(4): 515-526, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34782720

RESUMO

Metastasis is the leading cause of death of patients with esophageal squamous cell carcinoma (ESCC). Although an increasing number of studies have demonstrated the involvement of G3BP2 in several human cancers, how G3BP2 interacts with long noncoding RNAs and regulates mRNA transcripts in mediating ESCC metastasis remains unclear. In this study, we uncovered that G3BP2 was upregulated in ESCC. Further analysis revealed that upregulation of G3BP2 was significantly correlated with lymph node metastasis, depth of tumor invasion and unfavorable outcomes in ESCC patients. Both in vitro and in vivo functional assays demonstrated that G3BP2 dramatically enhanced ESCC cell migration and invasion. Mechanistically, LINC01554 maintained the high G3BP2 expression in ESCC by protecting G3BP2 from degradation through ubiquitination and the interaction domains within LINC01554 and G3BP2 were identified. In addition, RNA-seq revealed that HDGF was regulated by G3BP2. G3BP2 bound to HDGF mRNA transcript to stabilize its expression. Ectopic expression of HDGF effectively abolished the G3BP2 depletion-mediated inhibitory effect on tumor cell migration. Intriguingly, introduction of compound C108 which can inhibit G3BP2 remarkedly suppressed ESCC cell metastasis in vitro and in vivo. Collectively, this study describes a newly discovered regulatory axis, LINC01554/G3BP2/HDGF, that facilitates ESCC metastasis and will provide novel therapeutic strategies for ESCC.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Carcinoma de Células Escamosas do Esôfago/genética , RNA Longo não Codificante/genética , Proteínas de Ligação a RNA/metabolismo , Animais , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Progressão da Doença , Humanos , Camundongos , Camundongos Nus , Transfecção , Regulação para Cima
14.
Cancer Lett ; 526: 236-247, 2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-34767927

RESUMO

Nuclear pore complex (NPC) embedded in the nuclear envelope, is the only channel for macromolecule nucleocytoplasmic transportation and has important biological functions. However, the deregulation of specific nucleoporins (Nups) and NPC-Nup-based mechanisms and their function in tumour progression remain poorly understood. Here, we aimed to identify the Nups that contribute to HCC progression and metastasis in 729 primary hepatocellular carcinoma (HCC) cases using molecular, cytological, and biochemical techniques. Our results revealed elevated Nup93 expression in HCC tissues, especially in cases with metastasis, and was linked to worse prognosis. Furthermore, Nup93 knockdown suppressed HCC cell metastasis and proliferation, while Nup93 overexpression promoted these activities. We observed that Nup93 promotes HCC metastasis and proliferation by regulating ß-catenin translocation. In addition, we found that Nup93 interacted with ß-catenin directly, independent of importin. Furthermore, LEF1 and ß-catenin facilitated the Nup93-mediated metastasis and proliferation in HCC via a positive feedback loop. Thus, our findings provide novel insights into the mechanisms underlying the Nup93-induced promotion of HCC metastasis and suggest potential therapeutic targets in the LEF1-Nup93-ß-catenin pathway for HCC therapeutics.


Assuntos
Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , Complexo de Proteínas Formadoras de Poros Nucleares/metabolismo , beta Catenina/metabolismo , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Fator 1 de Ligação ao Facilitador Linfoide/metabolismo , Metástase Neoplásica , Complexo de Proteínas Formadoras de Poros Nucleares/genética , Fosforilação , Transdução de Sinais , Transcrição Gênica
15.
Indian J Microbiol ; 61(4): 475-486, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34744203

RESUMO

Microorganisms are sensitive to changes in the external environment and are often used as indicators to monitor and reflect water quality. Using Illumina MiSeq sequencing, the characteristics of the microbial community in Shihou Lake water at different time points were analyzed and the key environmental factors affecting the bacterial community were identified. The microbial community diversity in Shihou Lake water was rich and showed significant differences over time. The main bacterial phyla were the Cyanobacteria, Proteobacteria, Actinobacteria, Verrucomicrobia, Bacteroidetes, Chloroflexi, Planctomycetes, Firmicutes, Chlorobi, WS6 and Saccharibacteria. The relative abundance of these major phyla in the sample accounted for 97.83%-99.07% of the total abundance; Cyanobacteria had the highest relative abundance, accounting for 13.07%-44.61% of the total, and the abundance of each dominant phylum was significantly different at different time points. The Shannon and Simpson indexes showed that the diversity of each month was as follows: August > October > July > September > November. The Chao1 and Ace indexes indicated that the order of richness was: November > October > July > August > September. Beta diversity analysis found significant differences in the samples from month to month. Environmental factors such as temperature, total nitrogen, chlorophyll-a, permanganate index, nitrite, pH and ammonia nitrogen had significant effects on microbial community structure.

16.
Med Gas Res ; 11(3): 121-123, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33942783

RESUMO

Neonatal hypoxic ischemia is one of the leading causes of permanent morbidity and mortality in newborns, which is caused by difficulty in supplying blood and oxygen to brain tissue and is often associated with epilepsy, cerebral palsy, death, short-term or long-term neurological and cognitive impairment. In recent years, the clinical therapeutic effects of noble gases have been gradually discovered and recognized. Numerous studies have shown that noble gases have unique neuroprotective effects to restore damaged nerve and relieve symptoms in patients. Although research on the neuroprotective mechanisms of xenon and argon has yielded a lot of results, studies on helium have stalled. Helium is a colorless, odorless, monoatomic inert gas. The helium has no hemodynamic or neurocognitive side effects and can be used as an ideal pre-adaptor for future clinical applications. In recent years, studies have shown that heliox (a mixture of helium and oxygen) pretreatment can protect the heart, brain, liver and intestine from damage in several animal models, where a variety of signaling pathways have been proved to be involved. There are numerous studies on it even though the mechanism of helium for protecting newborns has not been fully elucidated. It is urgent to find an effective treatment due to the high death rate and disability rate of neonatal hypoxic ischemia. It is believed that helium will be approved safely and effectively for clinical use in the near future.


Assuntos
Hélio , Fármacos Neuroprotetores , Animais , Hélio/uso terapêutico , Humanos , Recém-Nascido , Isquemia , Fármacos Neuroprotetores/uso terapêutico , Oxigênio
17.
Acc Chem Res ; 54(10): 2397-2408, 2021 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-33914498

RESUMO

Proteins contain a level of complexity-secondary and tertiary structures-that polymer chemists aim to imitate. The bottom-up synthesis of protein-mimicking polymers mastering sequence variability and dispersity remains challenging. Incorporating polymers with predefined secondary structures, such as helices and π-π stacking sheets, into block copolymers circumvents the issue of designing and predicting one facet of their 3D architecture. Block copolymers with well-defined secondary-structure elements formed by covalent chain extension or supramolecular self-assembly may be considered for localized tertiary structures.In this Account, we describe a strategy toward block copolymers composed of units bearing well-defined secondary structures mixed in a "plug-and-play" manner that approaches a modicum of the versatility seen in nature. Our early efforts focused on the concept of single-chain collapse to achieve folded secondary structures through either hydrogen bonding or quadrupole attractive forces. These cases, however, required high dilution. Therefore, we turned to the ring-opening metathesis polymerization (ROMP) of [2.2]paracyclophane-1,9-dienes (pCpd), which forms conjugated, fluorescent poly(p-phenylenevinylene)s (PPVs) evocative of ß-sheets. Helical building blocks arise from polymers such as poly(isocyanide)s (PICs) or poly(methacrylamide)s (PMAcs) containing bulky, chiral side groups while the coil motif can be represented by any flexible chain; we frequently chose poly(styrene) (PS) or poly(norbornene) (PNB). We installed moieties for supramolecular assembly at the chain ends of our "sheets" to combine them with complementary helical or coil-shaped polymeric building blocks.Assembling hierarchical materials tantamount to the complexity of proteins requires directional interactions with high specificity, covalent chain extension, or a combination of both chemistries. Our design is based on functionalized reversible addition-fragmentation chain-transfer (RAFT) agents that allowed for the introduction of recognition motifs at the terminus of building blocks and chain-terminating agents (CTAs) that enabled the macroinitiation of helical polymers from the chain end of ROMP-generated sheets and/or coils. To achieve triblock copolymers with a heterotelechelic helix, we relied on supramolecular assembly with helix and coil-shaped building blocks. Our most diverse structures to date comprised a middle block of PPV sheets, parallel or antiparallel, and supramolecularly or covalently linked, respectively, end-functionalized with molecular recognition units (MRUs) for orthogonal supramolecular assembly. We explored PPV sheets with multiple folds achieved by chain extension using alternating pCpd and phenyl-pentafluorophenyl ß-hairpin turns. Using single-molecule polarization spectroscopy, we showed that folding occurs preferentially in multistranded over double-stranded PPV sheets. Our strategy toward protein-mimicking and foldable polymers demonstrates an efficient route toward higher ordered, well-characterized materials by taking advantage of polymers that naturally manifest secondary structures. Our studies demonstrate the retention of distinct architectures after complex assembly, a paradigm that we believe may extend to other polymeric folding systems.


Assuntos
Polímeros/química , Substâncias Macromoleculares/química , Modelos Moleculares , Estrutura Molecular , Polimerização , Polímeros/síntese química
18.
J Agric Food Chem ; 69(13): 3895-3903, 2021 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-33759523

RESUMO

Polyhydroxyalkanoates (PHAs) have been reported with agricultural and medical applications in virtue of their biodegradable and biocompatible properties. Here, we systematically engineered three modules for the enhanced biosynthesis of medium-chain-length polyhydroxyalkanoate (mcl-PHA) in Pseudomonas chlororaphis HT66. The phzE, fadA, and fadB genes were deleted to block the native phenazine pathway and weaken the fatty acid ß-oxidation pathway. Additionally, a PHA depolymerase gene phaZ was knocked out to prevent the degradation of mcl-PHA. Three genes involved in the mcl-PHA biosynthesis pathway were co-overexpressed to increase carbon flux. The engineered strain HT4Δ::C1C2J exhibited an 18.2 g/L cell dry weight with 84.9 wt % of mcl-PHA in a shake-flask culture, and the 3-hydroxydodecanoate (3HDD) monomer was increased to 71.6 mol %. Thermophysical and mechanical properties of mcl-PHA were improved with an enriched ratio of 3HDD. This study demonstrated a rational metabolic engineering approach to enhance the production of mcl-PHA with the enriched dominant monomer and improved material properties.


Assuntos
Poli-Hidroxialcanoatos , Pseudomonas chlororaphis , Engenharia Metabólica , Pseudomonas chlororaphis/genética
19.
Med Gas Res ; 11(1): 42-45, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33642337

RESUMO

Peptic ulcer refers to the inflammatory response and necrotic lesions of the mucosa under the action of various pathogenic factors, which goes deeply into the mucosal muscle layer and often occurs to the gastrointestinal mucosa related to gastric acid secretion, among which the stomach and duodenum are the most common. The clinical manifestations include slow onset, prolonged course and weekly upper abdominal pain. Nitric oxide (NO) is an intracellular and intercellular signaling molecule that plays an important role in many physiological and pathological processes. Studies have found that a small amount of NO produced in vivo plays a role in many physiological homeostasis, such as regulating blood pressure, platelet aggregation, nitrogenization of hemoglobin, and regulating proliferation and differentiation of stem cells. However, under the action of some cytokines and oxidative stress, intracellular NO synthase will catalyze the synthesis of large amounts of NO and participate in the inflammatory response, causing beneficial or harmful effect on the body. Numerous basic studies have focused on the relationship between NO and peptic ulcer. The purpose of this review is to summarize the role of NO in peptic ulcer and its possible mechanism.


Assuntos
Óxido Nítrico/metabolismo , Úlcera Péptica/metabolismo , Animais , Humanos , Úlcera Péptica/patologia
20.
J Agric Food Chem ; 69(3): 974-981, 2021 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-33443412

RESUMO

Natural phenazines are a class of multifunctional secondary metabolites of bacteria that play an important role in the biocontrol of plant pathogens. In this paper, a novel bioactive phenazine derivative was isolated from Streptomyces lomondensis S015 through silica gel chromatography and preparative high-performance liquid chromatography (HPLC). The structure was identified as 1-carboxyl-6-formyl-4,7,9-trihydroxy-phenazine (CFTHP) by NMR spectroscopy in combination with ultraperformance liquid chromatography & mass spectrometry (UPLC-MS). CFTHP could inhibit Pythium ultimum, Rhizoctonia solani, Septoria steviae, and Fusarium oxysporum f. sp. niveum with minimal inhibitory concentration (MIC) values of 16, 32, 16, and 16 µg/mL, respectively. A global regulatory gene phoP could positively regulate CFTHP biosynthesis since its production was 3.0-fold enhanced by phoP overexpression and inhibited by phoP deletion in Streptomyces lomondensis S015. These studies illustrated the potential of CFTHP as a promising biopesticide and provided a reference for phenazine production improvement.


Assuntos
Proteínas de Bactérias/metabolismo , Agentes de Controle Biológico/química , Agentes de Controle Biológico/farmacologia , Fungicidas Industriais/química , Fenazinas/química , Fenazinas/farmacologia , Streptomyces/metabolismo , Ascomicetos/efeitos dos fármacos , Ascomicetos/crescimento & desenvolvimento , Proteínas de Bactérias/genética , Agentes de Controle Biológico/metabolismo , Cromatografia Líquida de Alta Pressão , Fungicidas Industriais/metabolismo , Fungicidas Industriais/farmacologia , Fusarium/efeitos dos fármacos , Fusarium/crescimento & desenvolvimento , Regulação Bacteriana da Expressão Gênica , Espectroscopia de Ressonância Magnética , Testes de Sensibilidade Microbiana , Fenazinas/metabolismo , Rhizoctonia/efeitos dos fármacos , Rhizoctonia/crescimento & desenvolvimento , Metabolismo Secundário , Streptomyces/química , Streptomyces/genética
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