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1.
Biotechnol Biofuels Bioprod ; 17(1): 93, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38961423

RESUMO

BACKGROUND: Polyketide synthases (PKSs) are classified into three types based on their enzyme structures. Among them, type III PKSs, catalyzing the iterative condensation of malonyl-coenzyme A (CoA) with a CoA-linked starter molecule, are important synthases of valuable natural products. However, low efficiency and byproducts formation often limit their applications in recombinant overproduction. RESULTS: Herein, a rapid growth selection system is designed based on the accumulation and derepression of toxic acyl-CoA starter molecule intermediate products, which could be potentially applicable to most type III polyketides biosynthesis. This approach is validated by engineering both chalcone synthases (CHS) and host cell genome, to improve naringenin productions in Escherichia coli. From directed evolution of key enzyme CHS, beneficial mutant with ~ threefold improvement in capability of naringenin biosynthesis was selected and characterized. From directed genome evolution, effect of thioesterases on CHS catalysis is first discovered, expanding our understanding of byproduct formation mechanism in type III PKSs. Taken together, a whole-cell catalyst producing 1082 mg L-1 naringenin in flask with E value (evaluating product specificity) improved from 50.1% to 96.7% is obtained. CONCLUSIONS: The growth selection system has greatly contributed to both enhanced activity and discovery of byproduct formation mechanism in CHS. This research provides new insights in the catalytic mechanisms of CHS and sheds light on engineering highly efficient heterologous bio-factories to produce naringenin, and potentially more high-value type III polyketides, with minimized byproducts formation.

2.
Angew Chem Int Ed Engl ; : e202409435, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38945832

RESUMO

Visualizing lithium (Li) ions and understanding Li plating/stripping processes as well as evolution of solid electrolyte interface (SEI) are critical for optimizing all-solid-state Li metal batteries (ASSLMB). However, the buried solid-solid interfaces present a challenge for detection which preclude the employment of multiple analysis techniques. Herein, by employing complementary in situ characterizations, morphological/chemical evolution, Li plating/stripping dynamics and SEI dynamics were efficiently decoupled and Li ion behavior at interface between different solid-state electrolytes (SSE) was successfully detected. The innovative combining experiments of in situ atomic force microscopy and in situ X-ray photoelectron spectroscopy on Li metal anode revealed interfacial morphological/chemical evolution and decoupled Li plating/stripping process from SEI evolution. Though Li plating speed in Li10GeP2S12 (LGPS) was higher than Li3PS4 (LPS), speed of SSE decomposition was similar and ~85% interfacial SSE turned into SEI during plating and remained unchanged in stripping. To leverage strengths of different SSEs, an LPS-LGPS-LPS sandwich electrolyte was developed, demonstrating enhanced ionic conductivity and improved interfacial stability with less SSE decomposition (25%). Using in situ Kelvin Probe Force Microscopy, Li-ion behavior at interface between different SSEs was effectively visualized, uncovering distribution of Li ions at LGPS|LPS interface under different potentials.

3.
Nat Commun ; 15(1): 4972, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38862491

RESUMO

Molecular doping plays an important role in controlling the carrier concentration of organic semiconductors. However, the introduction of dopant counterions often results in increased energetic disorder and traps due to the molecular packing disruption and Coulomb potential wells. To date, no general strategy has been proposed to reduce the counterion-induced structural and energetic disorder. Here, we demonstrate the critical role of non-covalent interactions (NCIs) between counterions and polymers. Employing a computer-aided approach, we identified the optimal counterions and discovered that NCIs determine their docking positions, which significantly affect the counterion-induced energetic disorder. With the optimal counterions, we successfully reduced the energetic disorder to levels even lower than that of the undoped polymer. As a result, we achieved a high n-doped electrical conductivity of over 200 S cm-1 and an eight-fold increase in the thermoelectric power factor. We found that the NCIs have substantial effects on doping efficiency, polymer backbone planarity, and Coulomb potential landscape. Our work not only provides a general strategy for identifying the most suitable counterions but also deepens our understanding of the counterion effects on doped polymeric semiconductors.

4.
Curr Med Chem ; 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38676480

RESUMO

BACKGROUND: Ischemic stroke, the most common type of cerebrovascular accident, is a major cause of severe disability among adults worldwide. Although there has been progress in interventions for ischemic stroke in the past decades, there is no effective treatment to prevent brain damage in acute ischemic stroke. Therefore, it is urgent to develop novel neuroprotective agents with a wide therapeutic time window to provide a better prognosis for ischemic stroke patients. OBJECTIVE: The current study aimed to synthesize novel derivatives with substituent cinnamide scaffolds, evaluate biological activity, and obtain neuroprotective agents. METHODS: The target compounds were synthesized using classical methods of medicinal chemistry. The neuroprotective effects in vitro against Glu-induced neurotoxicity injury were evaluated in PC12 cells by MTT assay. The cell apoptosis was analyzed by flow cytometer. The proteins were detected by western blotting. The neuroprotective activities in vivo were determined in two in vivo models of global and focal cerebral ischemia. RESULTS: Among the title compounds, 9t, 9u, 9y, and 9z exhibited good neuroprotection in vivo and in vitro, which were selected and further studied to determine their mechanism of action. 9t, 9u, 9y and 9z protected PC12 cells against glutamate-induced apoptosis in a dose-dependent manner via caspase-3 pathway. Moreover, the four compounds significantly reduced brain infarct area and exhibited excellent neuroprotective activities in the in vivo MCAO model. CONCLUSION: Compounds 9t, 9u, 9y, and 9z, as potent neuroprotective agents with anti- neurotoxicity activity in vitro and anticerebral infarction efficacy in vivo, might serve as a useful molecular tool for further physiology and pathophysiology function studies, leading to potential clinical therapeutic agents for ischemic injury.

5.
J Agric Food Chem ; 72(12): 6463-6470, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38501643

RESUMO

Eugenol, the main component of essential oil from the Syzygium aromaticum clove tree, has great potential as an alternative bioresource feedstock for biosynthesis purposes. Although eugenol degradation to ferulic acid was investigated, an efficient method for directly converting eugenol to targeted natural products has not been established. Herein we identified the inherent inhibitions by simply combining the previously reported ferulic acid biosynthetic pathway and vanillin biosynthetic pathway. To overcome this, we developed a novel biosynthetic pathway for converting eugenol into vanillin, by introducing cinnamoyl-CoA reductase (CCR), which catalyzes conversion of coniferyl aldehyde to feruloyl-CoA. This approach bypasses the need for two catalysts, namely coniferyl aldehyde dehydrogenase and feruloyl-CoA synthetase, thereby eliminating inhibition while simplifying the pathway. To further improve efficiency, we enhanced CCR catalytic efficiency via directed evolution and leveraged an artificialvanillin biosensor for high-throughput screening. Switching the cofactor preference of CCR from NADP+ to NAD+ significantly improved pathway efficiency. This newly designed pathway provides an alternative strategy for efficiently biosynthesizing feruloyl-CoA-derived natural products using eugenol.


Assuntos
Acil Coenzima A , Benzaldeídos , Vias Biossintéticas , Ácidos Cumáricos , Eugenol , Eugenol/metabolismo
6.
Cell Mol Life Sci ; 81(1): 133, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38472560

RESUMO

Acute lung injury (ALI) is a common clinical syndrome, which often results in pulmonary edema and respiratory distress. It has been recently reported that phosphatidylethanolamine binding protein 4 (PEBP4), a basic cytoplasmic protein, has anti-inflammatory and hepatoprotective effects, but its relationship with ALI remains undefined so far. In this study, we generated PEBP4 knockout (KO) mice to investigate the potential function of PEBP4, as well as to evaluate the capacity of alveolar fluid clearance (AFC) and the activity of phosphatidylinositide 3-kinases (PI3K)/serine-theronine protein kinase B (PKB, also known as AKT) signaling pathway in lipopolysaccharide (LPS)-induced ALI mice models. We found that PEBP4 deficiency exacerbated lung pathological damage and edema, and increased the wet/dry weight ratio and total protein concentration of bronchoalveolar lavage fluid (BALF) in LPS-treated mice. Meanwhile, PEBP4 KO promoted an LPS-induced rise in the pulmonary myeloperoxidase (MPO) activity, serum interleuin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α levels, and pulmonary cyclooxygenase-2 (COX-2) expression. Mechanically, PEBP4 deletion further reduced the protein expression of Na+ transport markers, including epithelial sodium channel (ENaC)-α, ENaC-γ, Na,K-ATPase α1, and Na,K-ATPase ß1, and strengthened the inhibition of PI3K/AKT signaling in LPS-challenged mice. Furthermore, we demonstrated that selective activation of PI3K/AKT with 740YP or SC79 partially reversed all of the above effects caused by PEBP4 KO in LPS-treated mice. Altogether, our results indicated the PEBP4 deletion has a deterioration effect on LPS-induced ALI by impairing the capacity of AFC, which may be achieved through modulating the PI3K/AKT pathway.


Assuntos
Lesão Pulmonar Aguda , Lipopolissacarídeos , Animais , Camundongos , Lesão Pulmonar Aguda/induzido quimicamente , Lipopolissacarídeos/farmacologia , Pulmão/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , ATPase Trocadora de Sódio-Potássio/metabolismo , ATPase Trocadora de Sódio-Potássio/farmacologia , ATPase Trocadora de Sódio-Potássio/uso terapêutico , Fator de Necrose Tumoral alfa/metabolismo
7.
Microb Biotechnol ; 17(3): e14427, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38465475

RESUMO

Optimal transcriptional regulatory circuits are expected to exhibit stringent control, maintaining silence in the absence of inducers while exhibiting a broad induction dynamic range upon the addition of effectors. In the Plac /LacI pair, the promoter of the lac operon in Escherichia coli is characterized by its leakiness, attributed to the moderate affinity of LacI for its operator target. In response to this limitation, the LacI regulatory protein underwent engineering to enhance its regulatory properties. The M7 mutant, carrying I79T and N246S mutations, resulted in the lac promoter displaying approximately 95% less leaky expression and a broader induction dynamic range compared to the wild-type LacI. An in-depth analysis of each mutation revealed distinct regulatory profiles. In contrast to the wild-type LacI, the M7 mutant exhibited a tighter binding to the operator sequence, as evidenced by surface plasmon resonance studies. Leveraging the capabilities of the M7 mutant, a high-value sugar biosensor was constructed. This biosensor facilitated the selection of mutant galactosidases with approximately a seven-fold improvement in specific activity for transgalactosylation. Consequently, this advancement enabled enhanced biosynthesis of galacto-oligosaccharides (GOS).


Assuntos
Proteínas de Escherichia coli , Escherichia coli , Repressores Lac/genética , Repressores Lac/química , Repressores Lac/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Mutação , Regiões Promotoras Genéticas , Proteínas de Bactérias/genética
8.
Front Psychol ; 15: 1290310, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38298521

RESUMO

Background: Sleep problems in preschoolers are becoming increasingly prominent, and the association between sleep status and anxiety symptoms has attracted growing attention. However, studies investigating the relationship between bedtime and nighttime sleep duration in preschoolers and their anxiety symptoms remain scant. We used the large sample data from the Longhua Cohort Study of Children in Shenzhen, China (LCCS) to analyze the association between bedtime and sleep in preschoolers and their anxiety symptoms. Methods: A cross-sectional study of 69,138 preschoolers in Longhua District, Shenzhen, China was conducted in 2022. Data on sociodemographic characteristics of families, bedtime, nighttime sleep duration of preschoolers, and their anxiety symptoms (measured by the Spence Preschool Children Anxiety Scale) were collected through a structured questionnaire completed by the parents. Using binary logistic regression models, the relationship between bedtime, nighttime sleep duration, and childhood anxiety symptoms was examined. Results: The bedtimes of preschoolers were concentrated between 21:01-22:00 (52.41%). Among the preschoolers, 38.70% had bedtimes later than 22:00, and 75.49% had insufficient nighttime sleep duration. The positive screening rate for anxiety symptoms among preschoolers was 3.50%. After adjusting for confounding factors using binary logistic regression models, compared with preschoolers with bedtime ≤21:00, The OR (95%CI) values of anxiety in preschoolers with bedtime ≥23:01, 22:01-23:00 and 21:01-22:00 were 2.86 (2.21-3.69), 1.51 (1.27-1.79) and 1.48 (1.26-1.76), respectively. Compared with those with sufficient nighttime sleep duration, the OR (95%CI) of children with nighttime sleep duration less than 9 h was 1.36 (1.23-1.51). Conclusion: An association exists between bedtime and nighttime sleep duration in preschoolers and their anxiety symptoms. Preschoolers with 21:00 for bedtime and a nighttime sleep duration of 10 h may have lower anxiety symptoms. These findings support the importance of adequate sleep for preventing anxiety symptoms in children.

9.
Heliyon ; 10(1): e23489, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38192762

RESUMO

Background: Mycoplasma hominis (M. hominis) commonly colonizes the genitourinary tract of adult women and may result in neonatal meningitis through vertical transmission. Although there are few case reports, if the treatment is not conducted timely, the disease progresses rapidly, which may lead to serious complications and a poor prognosis. Case presentation: In the present study, a 10-day-old full-term neonate who presented with fever as the initial symptom and was eventually diagnosed with meningitis caused by M. hominis was reported. In the present case, the pathogen was not detected during the initial routine investigations, and the therapeutic effects of empiric antibiotic therapy were poor. Metagenomic next-generation sequencing (mNGS) in the cerebrospinal fluid (CSF) was conducted with the detection of M. hominis, and the antibiotics were adjusted to moxifloxacin combined with doxycycline. The clinical symptoms of the pediatric patient disappeared with an improvement in related laboratory results. Conclusion: It was difficult to detect M. hominis by routine bacterial culture. Therefore, M. hominis infection should be checked for in children with meningitis who had a negative result in CSF culture and poor therapeutic effects of empirical medication. mNGS in CSF should be conducted as soon as possible, and sensitive antibiotics should be administered in time to reduce the incidence of complications and improve the prognosis.

10.
Nurs Open ; 11(1): e2047, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38268295

RESUMO

AIM: To explore whether and to what extent, nurse-patient assessment differences mediate the association between nurse-to-patient ratios and readiness for hospital discharge, and examine whether nurse-patient characteristics moderate the indirect and/or direct effect of mediation model. DESIGN: A cross-sectional study was carried out from March 2021 to December 2022. METHODS: A total of 523 pairs of gastrointestinal cancer patients with PICC and their nurses were recruited. All the participants were invited to complete the general information questionnaire and the Readiness for Hospital Discharge Scale. Outcome measure was patient-reported readiness for hospital discharge. This study was reported according to the STROBE checklist. RESULTS: The patients reported a low level of readiness for hospital discharge. Nurse-patient assessment differences were positively associated with nurse-to-patient ratios but negatively associated with readiness for hospital discharge. Furthermore, nurse-patient assessment differences fully mediated the effect of nurse-to-patient ratios on readiness for hospital discharge, and age and gender of patients only moderated the indirect path of mediation model.


Assuntos
Lista de Checagem , Alta do Paciente , Humanos , Estudos Transversais , Relações Enfermeiro-Paciente , Hospitais
11.
Org Biomol Chem ; 22(6): 1299-1309, 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38259138

RESUMO

A copper-catalyzed aerobic oxidative cross-dehydrogenative coupling reaction between secondary amides and terminal alkynes has been developed. With the aid of ligands and 3 Å molecular sieves, ynamides can be efficiently synthesized at room temperature and conveniently scaled up. A legitimate mechanism involving nitrogen-centred radicals and copper trivalent intermediates has been proposed.

12.
Planta ; 259(2): 50, 2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38285114

RESUMO

MAIN CONCLUSION: The oxidosqualene cyclases (OSCs) generating triterpenoid skeletons in Cyclocarya paliurus were identified for the first time, and two uridine diphosphate (UDP)-glycosyltransferases (UGTs) catalyzing the glycosylation of flavonoids were characterized. Cyclocarya paliurus, a native rare dicotyledonous plant in China, contains an abundance of triterpenoid saponins and flavonoid glycosides that exhibit valuable pharmaceutical effects in preventing hypertension, hyperlipidemia, and diabetes. However, the molecular mechanism explaining the biosynthesis of triterpenoid saponin and flavonoid glycoside in C. paliurus remains unclear. In this study, the triterpene content in different tissues and the expression pattern of genes encoding the key enzymes associated with triterpenoid saponin and flavonoid glycoside biosynthesis were studied using transcriptome and metabolome analysis. The eight upstream oxidosqualene cyclases (OSCs) involved in triterpenoid saponin biosynthesis were functionally characterized, among them CpalOSC6 catalyzed 2,3;22,23-dioxidosqualene to form 3-epicabraleadiol; CpalOSC8 cyclized 2,3-oxidosqualene to generate dammarenediol-II; CpalOSC2 and CpalOSC3 produced ß-amyrin and CpalOSC4 produced cycloartenol, while CpalOSC2-CpalOSC5, CpalOSC7, and CpalOSC8 all produced lanosterol. However, no catalytic product was detected for CpalOSC1. Moreover, two downstream flavonoid uridine diphosphate (UDP)-glycosyltransferases (UGTs) (CpalUGT015 and CpalUGT100) that catalyze the last step of flavonoid glycoside biosynthesis were functionally elucidated. These results uncovered the key genes involved in the biosynthesis of triterpenoid saponins and flavonoid glycosides in C. paliurus that could be applied to produce flavonoid glycosides and key triterpenoid saponins in the future via a synthetic strategy.


Assuntos
Saponinas , Esqualeno/análogos & derivados , Triterpenos , Glicosídeos , Flavonoides , Saponinas/genética , Glicosiltransferases , Difosfato de Uridina
13.
Angew Chem Int Ed Engl ; 63(1): e202316781, 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-37955211

RESUMO

Lithium-carbon dioxide (Li-CO2 ) battery technology presents a promising opportunity for carbon capture and energy storage. Despite tremendous efforts in Li-CO2 batteries, the complex electrode/electrolyte/CO2 triple-phase interfacial processes remain poorly understood, in particular at the nanoscale. Here, using in situ atomic force microscopy and laser confocal microscopy-differential interference contrast microscopy, we directly observed the CO2 conversion processes in Li-CO2 batteries at the nanoscale, and further revealed a laser-tuned reaction pathway based on the real-time observations. During discharge, a bi-component composite, Li2 CO3 /C, deposits as micron-sized clusters through a 3D progressive growth model, followed by a 3D decomposition pathway during the subsequent recharge. When the cell operates under laser (λ=405 nm) irradiation, densely packed Li2 CO3 /C flakes deposit rapidly during discharge. Upon the recharge, they predominantly decompose at the interfaces of the flake and electrode, detaching themselves from the electrode and causing irreversible capacity degradation. In situ Raman shows that the laser promotes the formation of poorly soluble intermediates, Li2 C2 O4 , which in turn affects growth/decomposition pathways of Li2 CO3 /C and the cell performance. Our findings provide mechanistic insights into interfacial evolution in Li-CO2 batteries and the laser-tuned CO2 conversion reactions, which can inspire strategies of monitoring and controlling the multistep and multiphase interfacial reactions in advanced electrochemical devices.

14.
Chem Biol Interact ; 387: 110806, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-37980972

RESUMO

Cyclophosphamide (CTX), a widely used chemotherapeutic agent for cancer treatment, has been associated with long-term toxicity and detrimental effects on oocytes and ovaries, resulting in female reproductive dysfunction. This study aimed to investigate the potential impact of CTX on in vitro maturation (IVM) injury of porcine oocytes and subsequent embryonic development, as well as its effects on epigenetic modification and gene activation during early embryonic development. The results demonstrated that CTX treatment caused aberrant spindle structure and mitochondrial dysfunction during oocyte maturation, inducing DNA damage and early apoptosis, which consequently disrupted meiotic maturation. Indeed, CTX significantly reduced the in vitro developmental capacity of porcine embryos, and induced DNA damage and apoptosis in in vitro fertilization (IVF) blastocysts. Importantly, CTX induced abnormal histone modification of AcH4K12 in early porcine embryos. Moreover, addition of LBH589 before zygotic genome activation (ZGA) effectively increased AcH4K12 levels and restored the protein expression of NF-κB, which can effectively enhance the in vitro developmental potential of IVF embryos. The DNA damage and apoptosis induced by CTX compromised the quality of the blastocysts, which were recovered by supplementation with LBH589. This restoration was accompanied by down-regulation of BAX mRNA expression and up-regulation of BCL2, POU5F1, SOX2 and SOD1 mRNA expression. These findings indicated that CTX caused abnormal histone modification of AcH4K12 in early porcine embryos and reduced the protein expression of NF-κB, a key regulator of early embryo development, which may block subsequent ZGA processes.


Assuntos
Técnicas de Maturação in Vitro de Oócitos , NF-kappa B , Gravidez , Feminino , Suínos , Animais , Técnicas de Maturação in Vitro de Oócitos/métodos , Panobinostat/farmacologia , Desenvolvimento Embrionário , Ciclofosfamida/farmacologia , RNA Mensageiro
15.
Food Res Int ; 172: 113229, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37689962

RESUMO

To retard the quality deterioration of the dough during frozen storage, the effects of a compound modifier (CM) comprised of sodium stearoyl lactate, VC, and ß-glucanase on the properties of the frozen dough, as well as the quality of the frozen dough steamed bread were investigated. The results revealed that CM restricted the migration of water in the dough and improved its rheological properties. Furthermore, CM minimized the deterioration of specific volume and textural properties, and prevented starch retrogradation in the frozen dough steamed bread. Moreover, the addition of CM strengthened the secondary structure of gluten protein and formed a more resilient gluten network. The microstructure of the frozen dough steamed bread showed that CM reduced the damage caused by ice crystals on the gluten network. Overall, the use of CM strengthened the gluten network and effectively delayed the quality deterioration of the frozen dough, thus is potential as an improver for frozen dough.


Assuntos
Pão , Vapor , Água , Glutens , Reologia , Lactato de Sódio
16.
Anal Chem ; 95(39): 14754-14761, 2023 10 03.
Artigo em Inglês | MEDLINE | ID: mdl-37734030

RESUMO

Acute kidney injury (AKI) is a common medical condition with high morbidity and mortality. Although urinalysis provides a noninvasive and convenient diagnostic method for AKI at the molecular level, the low sensitivity of current chemical probes used in urinalysis hinders the time diagnosis of AKI. Herein, we achieved the sensitive and early diagnosis of AKI by the development of a chemiluminescent probe CL-Pa suitable for detection of urinary Vanin-1. Vanin-1 is considered as an early and sensitive biomarker for AKI, while few chemical probes have been applied to for its efficient detection. By virtue of the low autofluorescence interference during urine imaging in the chemiluminescence model, CL-Pa could realize the monitoring of the up-regulated urinary Vanin-1 with a high signal-to-noise ratio (∼588). Importantly, under the help of CL-Pa, the up-regulation of urinary Vanin-1 of cisplatin-induced AKI mice at 12 h post cisplatin injection was detected, which was much earlier than clinical biomarkers (sCr and BUN) and change of kidney histology (48 h post cisplatin injection). Furthermore, using this probe, the fluctuation of urinary Vanin-1 of mice with different degrees of AKI was monitored. This study demonstrated the ability of CL-Pa in sensitively detecting drug-induced AKI through urinalysis and suggested the great potential of CL-Pa for early diagnosis of AKI and evaluate the efficiency of anti-AKI drugs clinically.


Assuntos
Injúria Renal Aguda , Cisplatino , Camundongos , Animais , Razão Sinal-Ruído , Cisplatino/efeitos adversos , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/diagnóstico por imagem , Urinálise , Biomarcadores , Diagnóstico Precoce
17.
Metab Eng ; 78: 235-247, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37394056

RESUMO

cAMP receptor protein (CRP) is known as a global regulatory factor mainly mediating carbon source catabolism. Herein, we successfully engineered CRP to develop microbial chassis cells with improved recombinant biosynthetic capability in minimal medium with glucose as single carbon source. The obtained best-performing cAMP-independent CRPmu9 mutant conferred both faster cell growth and a 133-fold improvement in expression level of lac promoter in presence of 2% glucose, compared with strain under regulation of CRPwild-type. Promoters free from "glucose repression" are advantageous for recombinant expression, as glucose is a frequently used inexpensive carbon source in high-cell-density fermentations. Transcriptome analysis demonstrated that the CRP mutant globally rewired cell metabolism, displaying elevated tricarboxylic acid cycle activity; reduced acetate formation; increased nucleotide biosynthesis; and improved ATP synthesis, tolerance, and stress-resistance activity. Metabolites analysis confirmed the enhancement of glucose utilization with the upregulation of glycolysis and glyoxylate-tricarboxylic acid cycle. As expected, an elevated biosynthetic capability was demonstrated with vanillin, naringenin and caffeic acid biosynthesis in strains regulated by CRPmu9. This study has expanded the significance of CRP optimization into glucose utilization and recombinant biosynthesis, beyond the conventionally designated carbon source utilization other than glucose. The Escherichiacoli cell regulated by CRPmu9 can be potentially used as a beneficial chassis for recombinant biosynthesis.


Assuntos
Escherichia coli , Glucose , Glucose/genética , Glucose/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Glicólise , Fermentação , Carbono/metabolismo , Proteína Receptora de AMP Cíclico/metabolismo , Regulação Bacteriana da Expressão Gênica
18.
Bioresour Technol ; 384: 129288, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37315621

RESUMO

Removing erythromycin from the environment is a major challenge. In this study, a dual microbial consortium (Delftia acidovorans ERY-6A and Chryseobacterium indologenes ERY-6B) capable of degrading erythromycin was isolated, and the erythromycin biodegradation products were studied. Coconut shell activated carbon was modified and its adsorption characteristics and erythromycin removal efficiency of the immobilized cells were studied. It was indicated that alkali-modified and water-modified coconut shell activated carbon and the dual bacterial system had excellent erythromycin removal ability. The dual bacterial system follows a new biodegradation pathway to degrade erythromycin. The immobilized cells removed 95% of erythromycin at a concentration of 100 mg L-1 within 24 h through pore adsorption, surface complexation, hydrogen bonding, and biodegradation. This study provides a new erythromycin removal agent and for the first time describes the genomic information of erythromycin-degrading bacteria, providing new clues regarding bacterial cooperation and efficient erythromycin removal.


Assuntos
Carvão Vegetal , Eritromicina , Eritromicina/química , Bactérias/genética , Biodegradação Ambiental , Adsorção
19.
Food Funct ; 14(10): 4696-4705, 2023 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-37186251

RESUMO

Obesity is a global health problem strongly linked to gut microbes and their metabolites. In this study, ginsenoside Rg1 (Rg1) reduced lipid droplet size and hepatic lipid accumulation by activating uncoupling protein 1 expression in brown adipose tissue (BAT), which in turn inhibited high-fat diet (HFD)-induced weight gain in mice. Furthermore, the intestinal flora of mice was altered, the abundance of Lachnoclostridium, Streptococcus, Lactococcus, Enterococcus and Erysipelatoclostridium was upregulated, and the concentrations of fecal bile acids were altered, with cholic acid and taurocholic acid concentrations being significantly increased. In addition, the beneficial effects of Rg1 were eliminated in mice treated with a combination of antibiotics. In conclusion, these results suggest that Rg1 activates BAT to counteract obesity by regulating gut microbes and bile acid composition in HFD-fed mice.


Assuntos
Tecido Adiposo Marrom , Microbioma Gastrointestinal , Animais , Camundongos , Tecido Adiposo Marrom/metabolismo , Dieta Hiperlipídica/efeitos adversos , Ácidos e Sais Biliares/metabolismo , Obesidade/metabolismo , Camundongos Endogâmicos C57BL , Tecido Adiposo/metabolismo
20.
Bioresour Technol ; 379: 129041, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37037338

RESUMO

The microalgae Haematococcus pluvialis is a commercial source of natural astaxanthin. However, mature cells develop rigid three-layer wall structures and a repulsive odor. This study applied a liquid static fermentation system to screen hydrolyzing microorganisms for cell wall hydrolysis. Baijiu jiuqu and Gutian hongqu were found to have promising potential for application. The fermentation using 2% baijiu jiuqu and 2% glucose for pre-activation achieved comparable recovery of carotenoids to homogenizer disruption methods and produced stable fragrance which may be attributed to ethyl octanoate, hexyl formate, and phenethyl butyrate, as revealed by gas chromatography-mass spectrometry analysis. The abundance of astaxanthin molecules was slightly affected by fermentation with fold change < 2, while molecules with higher fold change (>10) were mainly carbohydrates, lipids, and steroids proving the safety of the fermentation. This study provides a new scheme for the biorefining of Haematococcus. pluvialis, potentially contributing to the industrial production of natural astaxanthin.


Assuntos
Clorofíceas , Fermentação , Biomassa , Bebidas , Parede Celular
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