Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 32
Filtrar
1.
Brief Bioinform ; 25(5)2024 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-39293802

RESUMO

Sex-biased gene expression differs across human populations; however, the underlying genetic basis and molecular mechanisms remain largely unknown. Here, we explore the influence of ancestry on sex differences in the human transcriptome and its genetic effects on a Eurasian admixed population: Uyghurs living in Xinjiang (XJU), by analyzing whole-genome sequencing data and transcriptome data of 90 XJU and 40 unrelated Han Chinese individuals. We identified 302 sex-biased expressed genes and 174 sex-biased cis-expression quantitative loci (sb-cis-eQTLs) in XJU, which were enriched in innate immune-related functions, indicating sex differences in immunity. Notably, approximately one-quarter of the sb-cis-eQTLs showed a strong correlation with ancestry composition; i.e. populations of similar ancestry tended to show similar patterns of sex-biased gene expression. Our analysis further suggested that genetic admixture induced a moderate degree of sex-biased gene expression. Interestingly, analysis of chromosome interactions revealed that the X chromosome acted on autosomal immunity-associated genes, partially explaining the sex-biased phenotypic differences. Our work extends the knowledge of sex-biased gene expression from the perspective of genetic admixture and bridges the gap in the exploration of sex-biased phenotypes shaped by autosome and X-chromosome interactions. Notably, we demonstrated that sex chromosomes cannot fully explain sex differentiation in immune-related phenotypes.


Assuntos
Locos de Características Quantitativas , Humanos , Masculino , Feminino , Povo Asiático/genética , Transcriptoma , China , Cromossomos Humanos X/genética , Caracteres Sexuais , Genética Populacional , Regulação da Expressão Gênica , Perfilação da Expressão Gênica/métodos
2.
Mol Carcinog ; 63(3): 384-399, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38116886

RESUMO

Long noncoding RNA urothelial carcinoma associated 1 (UCA1) has been identified as a key molecule in human cancers. However, its functional implications remain unspecified in the context of cervical cancer (CC). This research aims to identify the regulatory mechanism of UCA1 in CC. UCA1 was identified through microarray and confirmed through a quantitative real-time polymerase chain reaction. Proteins that bind with UCA1 were recognized using RNA pull-down assays along with RNA immunoprecipitation. Ubiquitination assays and coimmunoprecipitation were performed to explore the molecular mechanisms of the SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily d, member 3 (SMARCD3) downregulated in CC. The effects of UCA1 and SMARCD3 on the progression of CC were investigated through gain- and loss-of-function assays and xenograft tumor formation in vivo. In this study, UCA1 was found to be upregulated in CC cells as well as in human plasma exosomes for the first time. Functional studies indicated that UCA1 promotes CC progression. Mechanically, UCA1 downregulated the SMARCD3 protein stabilization by promoting SMARCD3 ubiquitination. Taken together, we revealed that the UCA1/SMARCD3 axis promoted CC progression, which could provide a new therapeutic target for CC.


Assuntos
Carcinoma de Células de Transição , MicroRNAs , RNA Longo não Codificante , Neoplasias da Bexiga Urinária , Neoplasias do Colo do Útero , Feminino , Humanos , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Neoplasias do Colo do Útero/genética , Invasividade Neoplásica/genética , Proliferação de Células/genética , MicroRNAs/genética , Regulação Neoplásica da Expressão Gênica , Linhagem Celular Tumoral
3.
Environ Sci Technol ; 58(10): 4751-4760, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38324714

RESUMO

Excited triplet states of wastewater effluent organic matter (3EfOM*) are known as important photo-oxidants in the degradation of extracellular antibiotic resistance genes (eArGs) in sunlit waters. In this work, we further found that 3EfOM* showed highly selective reactivity toward 2'-deoxyguanosine (dG) sites within eArGs in irradiated EfOM solutions at pH 7.0, while it showed no photosensitizing capacity toward 2'-deoxyadenosine, 2'-deoxythymidine, and 2'-deoxycytidine (the basic structures of eArGs). The 3EfOM* contributed to the photooxidation of dG primarily via one-electron transfer mechanism, with second-order reaction rate constants of (1.58-1.74) × 108 M-1 s-1, forming the oxidation intermediates of dG (dG(-H)•). The formed dG(-H)• could play a significant role in hole hopping and damage throughout eArGs. Using the four deoxynucleosides as probes, the upper limit for the reduction potential of 3EfOM* is estimated to be between 1.47 and 1.94 VNHE. Compared to EfOM, the role of the triplet state of terrestrially natural organic matter (3NOM*) in dG photooxidation was minor (∼15%) mainly due to the rapid reverse reactions of dG(-H)• by the antioxidant moieties of NOM. This study advances our understanding of the difference in the photosensitizing capacity and electron donating capacity between NOM and EfOM and the photodegradation mechanism of eArGs induced by 3EfOM*.


Assuntos
Águas Residuárias , Poluentes Químicos da Água , Fotólise , Antibacterianos , Oxidantes , Resistência Microbiana a Medicamentos
4.
J Nanobiotechnology ; 22(1): 408, 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38992664

RESUMO

BACKGROUND: Ovarian cancer (OC) has the highest fatality rate among all gynecological malignancies, necessitating the exploration of novel, efficient, and low-toxicity therapeutic strategies. Ferroptosis is a type of programmed cell death induced by iron-dependent lipid peroxidation and can potentially activate antitumor immunity. Developing highly effective ferroptosis inducers may improve OC prognosis. RESULTS: In this study, we developed an ultrasonically controllable two-dimensional (2D) piezoelectric nanoagonist (Bi2MoO6-MXene) to induce ferroptosis. A Schottky heterojunction between Bi2MoO6 (BMO) and MXene reduced the bandgap width by 0.44 eV, increased the carrier-separation efficiency, and decreased the recombination rate of electron-hole pairs under ultrasound stimulation. Therefore, the reactive oxygen species yield was enhanced. Under spatiotemporal ultrasound excitation, BMO-MXene effectively inhibited OC proliferation by more than 90%, induced lipid peroxidation, decreased mitochondrial-membrane potential, and inactivated the glutathione peroxidase and cystathionine transporter protein system, thereby causing ferroptosis in tumor cells. Ferroptosis in OC cells further activated immunogenic cell death, facilitating dendritic cell maturation and stimulating antitumor immunity. CONCLUSION: We have succeeded in developing a highly potent ferroptosis inducer (BMO-MXene), capable of inhibiting OC progression through the sonodynamic-ferroptosis-immunogenic cell death pathway.


Assuntos
Ferroptose , Morte Celular Imunogênica , Neoplasias Ovarianas , Ferroptose/efeitos dos fármacos , Feminino , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia , Humanos , Animais , Linhagem Celular Tumoral , Morte Celular Imunogênica/efeitos dos fármacos , Camundongos , Espécies Reativas de Oxigênio/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Bismuto/farmacologia , Bismuto/química
5.
Environ Sci Technol ; 57(13): 5433-5444, 2023 04 04.
Artigo em Inglês | MEDLINE | ID: mdl-36930043

RESUMO

Advanced oxidation processes (AOPs) are increasingly applied in water and wastewater treatment. Understanding the role of reactive species using probes and quenchers is one of the main requirements for good process design. However, much fundamental kinetic data for the reactions of probes and quenchers with reactive species is lacking, probably leading to inappropriate probe and quencher selection and dosing. In this work, second-order rate constants for over 150 reactions of probes and quenchers with reactive species such as •OH, SO4•-, and Cl• and chemical oxidants such as free chlorine and persulfate were determined. Some previously ill-quantified reactions (e.g., furfuryl alcohol and methyl phenyl sulfoxide reactions with certain chemical oxidants, nitrobenzene and 1,4-dioxane reactions with certain halogen radicals) were found to be kinetically favorable. The selection of specific probes can be guided by the improved kinetic database. The criteria for properly choosing dosages of probes and quenchers were proposed along with a procedure for quantifying reactive species free of interference from probe addition. The limitations of probe and quencher approaches were explicated, and possible solutions (e.g., the combination with other tools) were proposed. Overall, the kinetic database and protocols provided in this work benefit future research in understanding the radical chemistry in AOPs as well as other radical-involved processes.


Assuntos
Poluentes Químicos da Água , Purificação da Água , Poluentes Químicos da Água/análise , Raios Ultravioleta , Oxirredução , Cloro , Oxidantes , Purificação da Água/métodos , Cloretos
6.
Environ Sci Technol ; 57(18): 7230-7239, 2023 05 09.
Artigo em Inglês | MEDLINE | ID: mdl-37114949

RESUMO

Wastewater effluent is a major source of extracellular antibiotic resistance genes (eArGs) in the aquatic environment, a threat to human health and biosecurity. However, little is known about the extent to which organic matter in the wastewater effluent (EfOM) might contribute to photosensitized oxidation of eArGs. Triplet states of EfOM were found to dominate the degradation of eArGs (accounting for up to 85%). Photo-oxidation proceeded mainly via proton-coupled electron transfer reactions. They broke plasmid strands and damaged bases. O2•- was also involved, and it coupled with the reactions' intermediate radicals of eArGs. The second-order reaction rates of blaTEM-1 and tet-A segments (209-216 bps) with the triplet state of 4-carboxybenzophenone were calculated to be (2.61-2.75) × 108 M-1 s-1. Besides as photosensitizers, the antioxidant moieties in EfOM also acted as quenchers to revert intermediate radicals back to their original forms, reducing the rate of photodegradation. However, the terrestrial origin natural organic matter was unable to photosensitize because it formed less triplets, especially high-energy triplets, so its inhibitory effects predominated. This study advances our understanding of the role of EfOM in the photo-oxidation of eArGs and the difference between EfOM and terrestrial-origin natural organic matter.


Assuntos
Águas Residuárias , Poluentes Químicos da Água , Humanos , Antibacterianos/farmacologia , Oxirredução , Fotoquímica , Resistência Microbiana a Medicamentos/genética
7.
World J Surg Oncol ; 21(1): 3, 2023 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-36611207

RESUMO

Protein ubiquitination is closely related to tumor occurrence and development. The specific role of ubiquitination in endometrial cancer remains largely unclear. Therefore, we constructed a novel endometrial cancer prognostic model based on ubiquitination-related genes. We extracted the expression matrices of ubiquitination-related genes from the Cancer Genome Atlas database, upon which we performed univariate Cox regression and least absolute shrinkage and selection operator (LASSO) regression analyses to obtain 22 ubiquitination-related genes for the construction of the prognostic model. Survival, regression, clinical correlation, and principal component analyses were performed to assess the performance of the model. Drug sensitivity analysis was performed based on these ubiquitination-related genes. Finally, a prognostic nomogram was constructed based on the prognostic model to quantify patient outcomes. Survival, regression, clinical correlation, and principal component analyses revealed that the performance of the prognostic model was satisfactory. Drug sensitivity analysis provided a potential direction for the treatment of endometrial cancer. The prognostic nomogram could be used to effectively estimate the survival rate of patients with endometrial cancer. In summary, we constructed a new endometrial cancer prognostic model and identified 5 differentially expressed, prognosis-associated, ubiquitination-related genes. These 5 genes are potential diagnostic and treatment targets for endometrial cancer.


Assuntos
Neoplasias do Endométrio , Humanos , Feminino , Prognóstico , Neoplasias do Endométrio/genética , Nomogramas , Ubiquitinação
8.
Environ Sci Technol ; 56(1): 546-555, 2022 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-34747613

RESUMO

Dissolved organic matter (DOM) has been known to inhibit the degradation of trace organic contaminants (TrOCs) in advanced oxidation processes but quantitative understanding is lacking. Adenine (ADN) was selected as a model TrOC due to the wide occurrence of purine groups in TrOCs and the well-documented transient spectra of its intermediate radicals. ADN degradation in the presence of DOM during UV/peroxydisulfate treatment was quantified using steady-state photochemical experiments, time-resolved spectroscopy, and kinetic modeling. The inhibitory effects of DOM were found to include competing for photons, scavenging SO4•- and HO•, and also converting intermediate ADN radicals (ADN(-H)•) back into ADN. Half of the ADN(-H)• were reduced back to ADN in the presence of about 0.2 mgC L-1 of DOM. The quenching rate constants of ADN(-H)• by the 10 tested DOM isolates were in the range of (0.39-1.18) × 107 MC-1 s-1. They showed a positive linear relationship with the total antioxidant capacity of DOM. The laser flash photolysis results of the low-molecular-weight analogues of redox-active moieties further supported the dominant role of antioxidant moieties in DOM in the quenching of ADN(-H)•. The diverse roles of DOM should be considered in predicting the abatement of TrOCs in advanced oxidation processes.


Assuntos
Antioxidantes , Poluentes Químicos da Água , Matéria Orgânica Dissolvida , Oxirredução , Fotólise , Purinas , Poluentes Químicos da Água/química
9.
Environ Sci Technol ; 56(8): 5189-5199, 2022 04 19.
Artigo em Inglês | MEDLINE | ID: mdl-35349263

RESUMO

Dissolved organic matter (DOM) is a major scavenger of bromine radicals (e.g., Br• and Br2•-) in sunlit surface waters and during oxidative processes used in water treatment. However, the literature lacks quantitative measurements of reaction rate constants between bromine radicals and DOM and lacks information on the extent to which these reactions form brominated organic byproducts. Based on transient kinetic analysis with different fractions and sources of DOM, we determined reaction rate constants for DOM with Br• ranging from <5.0 × 107 to (4.2 ± 1.3) × 108 MC-1 s-1, which are comparable with those of HO• but higher than those with Br2•- (k = (9.0 ± 2.0) × 104 to (12.4 ± 2.1) × 105 MC-1 s-1). Br• and Br2•- attack the aromatic and antioxidant moieties of DOM via the electron transfer mechanism, resulting in Br- release with minimal substitution of bromine into DOM. For example, the total organic bromine was less than 0.25 µM (as Br) at environmentally relevant bromine radicals' exposures of ∼10-9 M·s. The results give robust evidence that the scavenging of bromine radicals by DOM is a crucial step to prevent inorganic bromine radical chemistry from producing free bromine (HOBr/OBr-) and subsequent brominated byproducts.


Assuntos
Poluentes Químicos da Água , Purificação da Água , Bromo , Matéria Orgânica Dissolvida , Cinética , Poluentes Químicos da Água/análise
10.
Environ Sci Technol ; 55(21): 14844-14853, 2021 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-34674525

RESUMO

The presence of dissolved organic matter (DOM) is known to inhibit the degradation of trace organic contaminants (TrOCs) in SO4•--based advanced oxidation processes (AOPs) due to filtering of the photochemically active light and radical scavenging effects. This study revealed an unexpected contribution for DOM in the degradation of nitroimidazoles (NZs) in the UV/persulfate AOP. The apparent second-order rate constants of NZs with SO4•- increased by 2.05 to 4.77 times in the presence of different DOMs. The increments were linearly related to the total electron capacity of DOM. Quinone and polyphenol moieties were found to play a dominant role. The reactive species generated from SO4•-'s oxidation of DOM, including semiquinone radical (SQ•-) and superoxide (O2•-), were found to react with NZs via Michael addition and O2•- addition. The second-order rate constants of tinidazole with SQ•- is determined to be (5.69 ± 0.59) × 106 M-1 s-1 by laser flash photolysis. Reactive species potentially generated from DOM may be considered in designing processes for the abatement of different types of TrOCs.


Assuntos
Nitroimidazóis , Poluentes Químicos da Água , Oxirredução , Poluentes Químicos da Água/análise
11.
Environ Sci Technol ; 55(15): 10502-10513, 2021 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-34296618

RESUMO

Bromine radicals can pose great impacts on the photochemical transformation of trace organic contaminants in natural and engineered waters. However, the reaction kinetics and mechanisms involved are barely known. In this work, second-order reaction rate constants with Br• and Br2•- were determined for 70 common trace organic contaminants and for 17 model compounds using laser flash photolysis and steady-state competition kinetics. The kBr• values ranged from <108 to (2.86 ± 0.31) × 1010 M-1 s-1 and the kBr2•- values from <105 to (1.18 ± 0.09) × 109 M-1 s-1 at pH 7.0. Six quantitative structure-activity relationships were developed, which allow predicting additional unknown kBr• and kBr2•- values. Single-electron transfer was shown to be a favored pathway for the reactions of Br• and Br2•- with trace organic contaminants, and this was supported by transient spectroscopy and quantum chemical calculations. This study is essential in advancing the scientific understanding of halogen radical-involved chemistry in contaminant transformation.


Assuntos
Bromo , Poluentes Químicos da Água , Halogênios , Cinética , Oxirredução , Poluentes Químicos da Água/análise
12.
J Environ Sci (China) ; 102: 24-36, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33637249

RESUMO

UV/chlorine process, as an emerging advanced oxidation process (AOP), was effective for removing micro-pollutants via various reactive radicals, but it also led to the changes of natural organic matter (NOM) and formation of disinfection byproducts (DBPs). By using negative ion electrospray ionization coupled with Fourier transform ion cyclotron resonance mass spectrometry (ESI FT-ICR MS), the transformation of Suwannee River NOM (SRNOM) and the formation of chlorinated DBPs (Cl-DBPs) in the UV/chlorine AOP and subsequent post-chlorination were tracked and compared with dark chlorination. In comparison to dark chlorination, the involvement of ClO•, Cl•, and HO• in the UV/chlorine AOP promoted the transformation of NOM by removing the compounds owning higher aromaticity (AImod) value and DBE (double-bond equivalence)/C ratio and causing the decrease in the proportion of aromatic compounds. Meanwhile, more compounds which contained only C, H, O, N atoms (CHON) were observed after the UV/chlorine AOP compared with dark chlorination via photolysis of organic chloramines or radical reactions. A total of 833 compounds contained C, H, O, Cl atoms (CHOCl) were observed after the UV/chlorine AOP, higher than 789 CHOCl compounds in dark chlorination, and one-chlorine-containing components were the dominant species. The different products from chlorine substitution reactions (SR) and addition reactions (AR) suggested that SR often occurred in the precursors owning higher H/C ratio and AR often occurred in the precursors owning higher aromaticity. Post-chlorination further caused the cleavages of NOM structures into small molecular weight compounds, removed CHON compounds and enhanced the formation of Cl-DBPs. The results provide information about NOM transformation and Cl-DBPs formation at molecular levels in the UV/chlorine AOP.


Assuntos
Poluentes Químicos da Água , Purificação da Água , Cloro/análise , Desinfecção , Halogenação , Espectrometria de Massas , Poluentes Químicos da Água/análise
13.
Environ Sci Technol ; 54(2): 1186-1195, 2020 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-31865710

RESUMO

Purines are the most widely occurring heterocyclic-N compounds. The degradation behaviors of purine derivatives, theophylline (TPL) and adenine (ADN) as representatives, in both single-component and mixture systems during UV/peroxydisulfate (PDS) treatment were explored. In the mixture system when the concentrations of SO4•- and HO• were reduced by more than half in comparison to a single-component system, the observed first-order rate constant of TPL was reduced by 11%, whereas ADN degradation was almost completely inhibited. An ADN "revert" pathway, that is, back transformation of ADN(-H)• to ADN by TPL via single electron-transfer reactions, was found. The second-order rate constant of ADN(-H)• with TPL was determined to be (1.94 ± 0.21) × 108 M-1 s-1. A kinetic model was developed, which successfully quantifies the contribution of each reaction pathway at various target compound concentrations. In the copresence of 0.1 µM TPL, 58% ADN (3.0 µM) was reduced back to ADN at the PDS dose of 290 µM. The ADN revert pathway's effectiveness is governed by the relative reduction potentials of the reactants. Purines and phenols with lower reduction potentials are able to react via the ADN revert pathway. These findings improve the understanding of the removal of mixture pollutants from real water media in advanced oxidation processes.


Assuntos
Poluentes Químicos da Água , Purificação da Água , Peróxido de Hidrogênio , Cinética , Oxirredução , Purinas , Sulfatos , Raios Ultravioleta
14.
Environ Sci Technol ; 53(19): 11170-11182, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31483622

RESUMO

Cl• and Cl2•- radicals contribute to the degradation of trace organic contaminants (TrOCs) such as pharmaceutical and personal care products and endocrine-disrupting chemicals. However, little is known about their reaction rate constants and mechanisms. In this study, the reaction rate constants of Cl• and Cl2•- with 88 target compounds were determined using laser flash photolysis. Decay kinetics, product buildup kinetics, and competition kinetics were applied to track the changes in their transient spectra. Cl• exhibited quite high reactivity toward TrOCs with reaction rate constants ranging from 3.10 × 109 to 4.08 × 1010 M-1 s-1. Cl2•- was less reactive but more selective, with reaction rate constants varying from <1 × 106 to 2.78 × 109 M-1 s-1. Three QSAR models were developed, which were capable of predicting the reaction rate constants of Cl2•- with TrOCs bearing phenol, alkoxy benzene, and aniline groups. The detection of Cl•-adducts of many TrOCs suggested that Cl• addition was an important reaction mechanism. Single electron transfer (SET) predominated in reactions of Cl• with TrOCs bearing electron-rich moieties (e.g., sulfonamides), and their cation radicals were observed. Cl• might also abstract hydrogen atoms from phenolic compounds to generate phenoxyl radicals. Moreover, Cl• could react with TrOCs through multiple pathways since more than one transient intermediate was detected simultaneously. SET was the major reaction mechanism of Cl2•- reactions with TrOCs bearing phenols, alkoxy benzenes, and anilines groups. Cl2•- was found to play an important role in TrOC degradation, though it has been often neglected in previous studies. The results improve the understanding of halogen radical-involved chemistry in TrOC degradation.


Assuntos
Halogênios , Fenol , Benzeno , Cinética
15.
Environ Sci Technol ; 52(4): 1806-1816, 2018 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-29338220

RESUMO

This study investigated the role of bromide ions in the degradation of nine pharmaceuticals and personal care products (PPCPs) during the UV/chlorine treatment of simulated drinking water containing 2.5 mgC L-1 natural organic matter (NOM). The kinetics of contributions from UV irradiation and from oxidation by free chlorine, free bromine, hydroxyl radical and reactive halogen species were evaluated. The observed loss rate constants of PPCPs in the presence of 10 µM bromide were 1.6-23 times of those observed in the absence of bromide (except for iopromide and ibuprofen). Bromide was shown to play multiple roles in PPCP degradation. It reacts rapidly with free chlorine to produce a trace amount of free bromine, which then contributes to up to 55% of the degradation of some PPCPs during 15 min of UV/chlorine treatment. Bromide was also shown to reduce the level of HO• and to change the reactive chlorine species to bromine-containing species, which resulted in decreases in ibuprofen degradation and enhancement in carbamazepine and caffeine degradation, respectively. Reactive halogen species contributed to between 37 and 96% of the degradation of the studied PPCPs except ibuprofen in the presence of 10 µM bromide ion. The effect of bromide is non-negligible during the UV/chlorine treatment.


Assuntos
Poluentes Químicos da Água , Purificação da Água , Brometos , Cloro , Raios Ultravioleta
16.
Int J Biol Macromol ; 279(Pt 1): 135133, 2024 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-39208882

RESUMO

Chiral phenyllactic acid (PLA) is a new type of antiseptic agent and a valuable precursor for active ingredients in pharmaceuticals and agrochemicals. In this study, we designed a multi-enzyme cascade that combined stereocomplementary d- and l-lactate dehydrogenases with threonine aldolase, phenylserine dehydratase, and formate dehydrogenase for the one-pot conversion of achiral glycine and benzaldehyde to synthesize d-PLA and l-PLA. To overcome the imbalance of multi-enzymes in a single cell, two enzyme modules, overexpressing four enzymes, were assembled in Escherichia coli cells to construct whole-cell catalysis systems (WCCSs). Furthermore, by optimizing reaction conditions and components, recombinant E. coli (WCCS 26) was able to produce 100 mM d-PLA with >99 % ee using a fed-batch strategy, while E. coli (WCCS 60) produced 47.2 mM l-PLA with >99 % ee. This study presents a sustainable and efficient method for synthesizing chiral PLAs from food-grade achiral starting materials.

17.
Cancer Gene Ther ; 31(8): 1221-1236, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38778089

RESUMO

Circular RNAs (circRNAs) represent a class of covalently closed, single-stranded RNAs and have been linked to cancer progression. N6-methyladenosine (m6A) methylation is a ubiquitous RNA modification in cancer cells. Increasing evidence suggests that m6A can mediate the effects of circRNAs in cancer biology. In contrast, the post-transcriptional systems of m6A and circRNA in the progression of endometrial cancer (EC) remain obscure. The current study identified a novel circRNA with m6A modification, hsa_circ_0084582 (circCHD7), which was upregulated in EC tissues. Functionally, circCHD7 was found to promote the proliferation of EC cells. Mechanistically, circCHD7 interacted with insulin-like growth factor 2 mRNA-binding protein (IGF2BP2) to amplify its enrichment. Moreover, circCHD7 increased the mRNA stability of platelet-derived growth factor receptor beta (PDGFRB) in an m6A-dependent manner, thereby enhancing its expression. In addition, the circCHD7/IGF2BP2/PDGFRB axis activated the JAK/STAT signaling pathway and promoted EC cell proliferation. In conclusion, these findings provide new insights into the regulation of circRNA-mediated m6A modification, and the new "circCHD7-PDGFRB" model of regulation offers new perspectives on circCHD7 as a potential target for EC therapy.


Assuntos
Progressão da Doença , Neoplasias do Endométrio , RNA Circular , Proteínas de Ligação a RNA , Transdução de Sinais , Humanos , Feminino , RNA Circular/genética , RNA Circular/metabolismo , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/metabolismo , Camundongos , Receptor beta de Fator de Crescimento Derivado de Plaquetas/genética , Receptor beta de Fator de Crescimento Derivado de Plaquetas/metabolismo , Animais , Proliferação de Células/genética , Fatores de Transcrição STAT/metabolismo , Fatores de Transcrição STAT/genética , Janus Quinases/metabolismo , Janus Quinases/genética , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica
18.
J Hazard Mater ; 450: 131081, 2023 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-36848840

RESUMO

To activate persulfate to generate reactive species such as sulfate radical (SO4•-) for micropollutants abatement, external energy or chemicals are often needed. In this study, a novel SO4•- formation pathway was reported during the oxidation of neonicotinoids by peroxydisulfate (S2O82-, PDS) without any other chemical additions. Thiamethoxam (TMX) was used as a representative neonicotinoid and SO4•- was the dominant specie contributing to its degradation during PDS oxidation at neutral pH. TMX anion radical (TMX•-) was found to activate PDS to generate SO4•- with the second-order reaction rate constant determined to be (1.44 ± 0.47)× 106 M-1s-1 at pH 7.0 by using laser flash photolysis. TMX•- was generated from the TMX reactions with superoxide radical (O2•-), which was formed from the hydrolysis of PDS. This indirect PDS activation pathway via anion radicals was also applicable to other neonicotinoids. The formation rates of SO4•- were found to negatively linearly correlated with Egap (LUMO-HOMO). The DFT calculations indicated the energy barrier of anion radicals to activate PDS was greatly reduced compared to the parent neonicotinoids. The pathway of anion radicals' activation of PDS to form SO4•- improved the understanding of PDS oxidation chemistry and provided some guidance to enhance oxidation efficiency in field applications.

19.
Biosens Bioelectron ; 226: 115118, 2023 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-36806764

RESUMO

As an essential biomarker associated with various diseases, Uracil-DNA Glycosylase (UDG) detection is vital for disease diagnosis, treatment selection, and prognosis assessment. In recent years, the signal amplification effect of the CRISPR-Cas12a trans-cleaved single-stranded DNA probe has provided an available strategy for constructing highly sensitive biosensors. However, its superior trans-cleavage activity has become a "double-edged sword" for building biosensors that can amplify the target signal while also amplifying the leakage signal, causing out of control. Therefore, the construction of structurally simple, extremely low-background, highly sensitive CRISPR-Cas12a-based biosensors is an urgent bottleneck problem in the field. Here, we applied CRISPR-Cas12a with a DNA hybridization reaction to develop a simple, rapid, low background, and highly sensitive method for UDG activity detection. It has no PAM restriction and the detection limit is as low as 2.5 × 10-6 U/mL. As far as we know, this method is one of the most sensitive methods for UDG detection. We also used this system to analyze UDG activity in tumor cells (LOD: 1 cell/uL) and to evaluate the ability to screen for UDG inhibitors. Furthermore, we verified the possibility of intracellular UDG activity imaging by transfecting the biosensors to the cells. We believe this novel sensor has good clinical application prospects and will effectively broaden the application space of CRISPR-Cas12a.


Assuntos
Técnicas Biossensoriais , Uracila-DNA Glicosidase , Sistemas CRISPR-Cas , Limite de Detecção , DNA de Cadeia Simples
20.
Technol Cancer Res Treat ; 21: 15330338221114497, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36062718

RESUMO

Cancer is a public health problem that threatens human health. Due to the lack of specific and rapid diagnosis and treatment methods, the 5-year survival rate of patients has not been effectively improved in the past 10 years. Abnormal gene expression is closely related to the occurrence and development of cancer. Cancer diagnosis and treatment methods based on genetic testing have received extensive attention in recent years. It is essential to explore specific and rapid cancer genetic testing methods. Taking ovarian cancer as an example, we reviewed the progress of specific and rapid nucleic acid detection methods related to cancer risk assessment, low-abundance mutation detection, and methylation detection, to provide new strategies and ideas for related research.


Assuntos
Biomarcadores Tumorais , Neoplasias Ovarianas , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma Epitelial do Ovário/genética , Detecção Precoce de Câncer , Feminino , Testes Genéticos/métodos , Humanos , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/terapia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA