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1.
Mol Biol Evol ; 41(6)2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38829799

RESUMO

Global climate change has led to shifts in the distribution ranges of many terrestrial species, promoting their migration from lower altitudes or latitudes to higher ones. Meanwhile, successful invaders have developed genetic adaptations enabling the colonization of new environments. Over the past 40 years, Rattus tanezumi (RT) has expanded into northern China (Northwest and North China) from its southern origins. We studied the cold adaptation of RT and its potential for northward expansion by comparing it with sympatric Rattus norvegicus (RN), which is well adapted to cold regions. Through population genomic analysis, we revealed that the invading RT rats have split into three distinct populations: the North, Northwest, and Tibetan populations. The first two populations exhibited high genetic diversity, while the latter population showed remarkably low genetic diversity. These rats have developed various genetic adaptations to cold, arid, hypoxic, and high-UV conditions. Cold acclimation tests revealed divergent thermoregulation between RT and RN. Specifically, RT exhibited higher brown adipose tissue activity and metabolic rates than did RN. Transcriptome analysis highlighted changes in genes regulating triglyceride catabolic processes in RT, including Apoa1 and Apoa4, which were upregulated, under selection and associated with local adaptation. In contrast, RN showed changes in carbohydrate metabolism genes. Despite the cold adaptation of RT, we observed genotypic and phenotypic constraints that may limit its ability to cope with severe low temperatures farther north. Consequently, it is less likely that RT rats will invade and overlap with RN rats in farther northern regions.


Assuntos
Aclimatação , Temperatura Baixa , Animais , Ratos , Aclimatação/genética , China , Fenótipo , Variação Genética , Adaptação Fisiológica/genética , Regulação da Temperatura Corporal/genética , Mudança Climática
2.
Nano Lett ; 24(30): 9178-9185, 2024 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-39017609

RESUMO

Lithium (Li) dendritic growth and huge volume expansion seriously hamper Li-metal anode development. Herein, we design a lightweight 3D Li-ion-affinity host enabled by silver (Ag) nanoparticles fully decorating a porous melamine sponge (Ag@PMS) for dendrite-free and high-areal-capacity Li anodes. The compact Ag nanoparticles provide abundant preferred nucleation sites and give the host strong conductivity. Moreover, the high specific surface area and polar groups of the elastic, porous melamine sponge enhance the Li-ion diffusion kinetics, prompting homogeneity of Li deposition and stripping. As expected, the integrated 3D Ag@PMS-Li anode delivered a remarkable electrochemical performance, with a Coulombic efficiency (CE) of 97.14% after 450 cycles at 1 mA cm-2. The symmetric cell showed an ultralong lifespan of 3400 h at 1 mA cm-2 for 1 mAh cm-2. This study provides a facile and cost-effective strategy to design an advanced 3D framework for the preparation of a stable dendrite-free Li metal anode.

3.
Nano Lett ; 24(28): 8770-8777, 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-38968171

RESUMO

Oxygen-mediated triplet-triplet annihilation upconversion (TTA-UC) quenching limits the application of such organic upconversion materials. Here, we report that the photooxidation of organic amines is an effective and versatile strategy to suppress oxygen-mediated upconversion quenching in both organic solvents and aqueous solutions. The strategy is based on the dual role of organic amines in photooxidation, i.e., as singlet oxygen scavengers and electron donors. Under photoexcitation, the photosensitizer sensitizes oxygen to produce singlet oxygen for the oxidation of alkylamine, reducing the oxygen concentration. However, photoinduced electron transfer among photosensitizers, organic amines, and oxygen leads to the production of superoxide anions that suppress TTA-UC. To observe oxygen-tolerating TTA-UC, we find that alkyl secondary amines can balance the production of singlet oxygen and superoxide anions. We then utilize polyethyleneimine (PEI) to synthesize amphiphilic polymers to encapsulate TTA-UC pairs for the formation of water-dispersible, ultrasmall, and multicolor-emitting TTA-UC nanoparticles.

4.
Nano Lett ; 24(8): 2544-2552, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38349341

RESUMO

Labeling the genome and envelope of a virus with multicolor quantum dots (QDs) simultaneously enables real-time monitoring of viral uncoating and genome release, contributing to our understanding of virus infection mechanisms. However, current labeling techniques require genetic modification, which alters the virus's composition and infectivity. To address this, we utilized the CRISPR/Cas13 system and a bioorthogonal metabolic method to label the Japanese encephalitis virus (JEV) genome and envelopes with different-colored QDs in situ. This technique allows one-step two-color labeling of the viral envelope and intraviral genome with QDs harnessing virus infection. In combination with single-virus tracking, we visualized JEV uncoating and genome release in real time near the endoplasmic reticulum of live cells. This labeling strategy allows for real-time visualization of uncoating and genome release at the single-virus level, and it is expected to advance the study of other viral infection mechanisms.


Assuntos
Pontos Quânticos , Viroses , Vírus , Humanos , Envelope Viral/metabolismo , Proteínas do Envelope Viral
5.
J Am Chem Soc ; 146(15): 10785-10797, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38573588

RESUMO

The anti-Stokes shift represents the capacity of photon upconversion to convert low-energy photons to high-energy photons. Although triplet exciton-mediated photon upconversion presents outstanding performance in solar energy harvesting, photoredox catalysis, stereoscopic 3D printing, and disease therapeutics, the interfacial multistep triplet exciton transfer leads to exciton energy loss to suppress the anti-Stokes shift. Here, we report near infrared-II (NIR-II) excitable triplet exciton-mediated photon upconversion using a hybrid photosensitizer consisting of lead sulfide quantum dots (PbS QDs) and new surface ligands of thiophene-substituted diketopyrrolopyrrole (Th-DPP). Under 1064 nm excitation, this photon upconversion revealed a record-corrected upconversion efficiency of 0.37% (normalized to 100%), with the anti-Stokes shift (1.07 eV) approaching the theoretical limit (1.17 eV). The observation of this unexpected result is due to our discovery of the presence of a weak interaction between the sulfur atom on Th-DPP and Pb2+ on the PbS QDs surface, facilitating electronic coupling between PbS QDs and Th-DPP, such that the realization of triplet exciton transfer efficiency is close to 100% even when the energy gap is as small as 0.04 eV. With this premise, this photon upconversion as a photocatalyst enables the production of standing organic gel via photopolymerization under 1064 nm illumination, displaying NIR-II photon-driven photoredox catalysis. This research not only establishes the foundation for enhancing the performance of NIR-II excitable photonic upconversion but also promotes its development in photonics and photoredox catalysis.

6.
J Am Chem Soc ; 146(31): 21791-21805, 2024 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-39069661

RESUMO

The diagnosis of disease biomarkers is crucial for the identification, monitoring, and prognostic assessment of malignant disease. However, biological samples with autofluorescence, complex components, and heterogeneity pose major challenges to reliable biosensing. Here, we report the self-assembly of natural proteins and the triplet-triplet annihilation upconversion (TTA-UC) pair to form upconverted protein clusters (∼8.2 ± 1.1 nm), which were further assembled into photon upconversion supramolecular assemblies (PUSA). This PUSA exhibited unique features, including a small size (∼44.1 ± 4.1 nm), oxygen tolerance, superior biocompatibility, and easy storage via lyophilization, all of which are long sought after for photon upconversion materials. Further, we have revealed that the steric hindrance of the annihilator suppresses the stacking of the annihilator in PUSA, which is vital for maintaining the water dispersibility and enhancing the upconversion performance of PUSA. In conjunction with sarcosine oxidase, this near infrared (NIR)-excitable PUSA nanoprobe could perform background-free biosensing of urinary sarcosine, which is a common biomarker for prostatic carcinoma (PCa). More importantly, this nanoprobe not only allows for qualitative identification of urinary samples from PCa patients by the unaided eye under NIR-light-emitting diode (LED) illumination but also quantifies the concentration of urinary sarcosine. These remarkable findings have propelled photon upconversion materials to a new evolutionary stage and expedited the progress of upconversion biosensing in clinical diagnostics.


Assuntos
Técnicas Biossensoriais , Fótons , Humanos , Sarcosina/urina , Sarcosina/química , Sarcosina Oxidase/química , Proteínas/análise , Proteínas/química
7.
J Transl Med ; 22(1): 558, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38862971

RESUMO

PURPOSE: The purpose of the study was to evaluate the expression and function of basic leucine zipper ATF-like transcription factor (BATF) in colorectal cancer (CRC), and its correlation with 2-deoxy-2[18F]fluoro-D-glucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) parameters. METHODS: The TIMER database, GEPIA database, TCGA, and GEO database were used to analyze the expression profile of BATF in human cancers. The reverse transcription­quantitative PCR and western blot analyses were used to evaluate the mRNA level and protein expression in different CRC cell lines. The expression of BATF in SW620 and HCT116 cells was silenced and cell counting kit-8 assays and clonogenic assay were utilized to evaluate the role of BATF in CRC proliferation. The expression of tumor BATF and glucose transporter 1 (GLUT-1) were examined using immunohistochemical tools in 37 CRC patients undergoing preoperative 18F-FDG PET/CT imaging. The correlation between the PET/CT parameters and immunohistochemical result was evaluated. RESULTS: In database, BATF was highly expressed in pan-cancer analyses, including CRC, and was associated with poor prognosis in CRC. In vitro, the results showed that knocking down of BATF expression could inhibit the proliferation of SW620 and HCT116 cells. In CRC patients, BATF expression was upregulated in tumor tissues compared with matched para-tumoral tissues, and was related with gender and Ki-67 levels. BATF expression was positively related to GLUT-1 expression and PET/CT parameters, including tumor size, maximum standard uptake value, metabolic tumor volume, and total lesion glycolysis. The multiple logistic analyses showed that SUVmax was an independent predictor of BATF expression. With 15.96 g/cm3 as the cutoff, sensitivity was 85.71%, specificity 82.61%, and area-under-the-curve 0.854. CONCLUSION: BATF may be an oncogene associated with 18F-FDG PET/CT parameters in CRC. SUVmax may be an independent predictor of BATF expression.


Assuntos
Fatores de Transcrição de Zíper de Leucina Básica , Proliferação de Células , Neoplasias Colorretais , Progressão da Doença , Fluordesoxiglucose F18 , Regulação Neoplásica da Expressão Gênica , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Humanos , Fluordesoxiglucose F18/metabolismo , Neoplasias Colorretais/patologia , Neoplasias Colorretais/genética , Neoplasias Colorretais/diagnóstico por imagem , Neoplasias Colorretais/metabolismo , Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Fatores de Transcrição de Zíper de Leucina Básica/genética , Feminino , Masculino , Linhagem Celular Tumoral , Pessoa de Meia-Idade , Transportador de Glucose Tipo 1/metabolismo , Transportador de Glucose Tipo 1/genética , Idoso
8.
J Transl Med ; 22(1): 240, 2024 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-38443933

RESUMO

BACKGROUND: Mitochondria produce adenosine triphosphate through respiratory activities to power sperm differentiation and motility, and decreased mitochondrial respiratory activity can result in poor sperm motility and asthenospermia. The mitochondrial sheath is a component of the mid-piece of the sperm flagellum, and dysfunction of the sheath can reduce sperm motility and cause male infertility. The membrane occupation and recognition nexus-motif protein 2 (MORN2) is testis enriched in mice, and the MORN motif was reported to play a role in the regulation of bioelectrical signal homeostasis in cardiomyocytes. METHODS: We generated Morn2-/- mice using CRISPR/Cas9 and evaluated the potential functions of MORN2 in spermiogenesis through histological analysis, fertility examination, RT-PCR, CASA, immunofluorescence, TUNEL, electron microscopy analysis, mitochondrial energy metabolism analysis, etc. RESULTS: The Morn2-/- mice were infertile, and their sperm showed severe motility defects. Morn2-/- sperm also had abnormal morphology characterized by bent heads, aberrant mitochondrial sheath formation, lower mitochondrial membrane potential, higher levels of reactive oxygen species, and decreased mitochondrial respiratory activity. CONCLUSIONS: Our study demonstrates that MORN2 is essential for male fertility and indicates that MORN2 functions in mitochondrial sheath formation and regulates mitochondrial respiratory activity.


Assuntos
Sêmen , Motilidade dos Espermatozoides , Animais , Masculino , Camundongos , Metabolismo Energético , Fertilidade , Mitocôndrias
9.
Metabolomics ; 20(3): 52, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38722414

RESUMO

INTRODUCTION: Metabolite signatures for blood pressure (BP) may reveal biomarkers, elucidate pathogenesis, and provide prevention targets for high BP. Knowledge regarding metabolites associated with BP in adolescence remains limited. OBJECTIVES: Investigate the associations between metabolites and adolescent BP, both cross-sectionally (in early and late adolescence) and prospectively (from early to late adolescence). METHODS: Participants are from the Project Viva prospective cohort. During the early (median: 12.8 years; N = 556) and late (median: 17.4 years; N = 501) adolescence visits, we conducted untargeted plasma metabolomic profiling and measured systolic (SBP) and diastolic BP (DBP). We used linear regression to identify metabolites cross-sectionally associated with BP at each time point, and to assess prospective associations of changes in metabolite levels from early to late adolescence with late adolescence BP. We used Weighted Gene Correlation Network Analysis and Spearman's partial correlation to identify metabolite clusters associated with BP at each time point. RESULTS: In the linear models, higher androgenic steroid levels were consistently associated with higher SBP and DBP in early and late adolescence. A cluster of 59 metabolites, mainly composed of androgenic steroids, correlated with higher SBP and DBP in early adolescence. A cluster primarily composed of fatty acid lipids was marginally associated with higher SBP in females in late adolescence. Multiple metabolites, including those in the creatine and purine metabolism sub-pathways, were associated with higher SBP and DBP both cross-sectionally and prospectively. CONCLUSION: Our results shed light on the potential metabolic processes and pathophysiology underlying high BP in adolescents.


Assuntos
Pressão Sanguínea , Metabolômica , Humanos , Adolescente , Pressão Sanguínea/fisiologia , Masculino , Feminino , Metabolômica/métodos , Estudos Transversais , Estudos Prospectivos , Criança , Biomarcadores/sangue , Estados Unidos , Metaboloma/fisiologia , Estudos de Coortes
10.
Chem Res Toxicol ; 37(7): 1104-1112, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38885202

RESUMO

Chlortoluron (CTU) is an herbicide extensively used in agricultural settings for crop cultivation. Its presence in water has been identified as a pollutant detrimental to aquatic species. The objective of the present study was to explore the metabolic activation and hepatotoxicity of CTU. Through human and rat liver microsomal incubations supplemented with CTU, nicotinamide adenine dinucleotide phosphate (NADPH), and either glutathione or N-acetyl cysteine, a benzylic alcohol metabolite (M1) was discerned, alongside a phenol metabolite (M2), a glutathione conjugate (M3), and an N-acetyl cysteine conjugate (M4). In rats exposed to CTU, biliary M3 and urinary M4 were detected in their bile and urine, respectively. The generation of M1 was detected in the presence of NADPH. The observation of M3 and M4 suggests the formation of an iminoquinone methide intermediate arising from the oxidation of M1. CYP3A4 was found to be the principal enzyme catalyzing the metabolic activation of CTU. Furthermore, CTU exhibited cytotoxic properties in cultured rat primary hepatocytes in a concentration-dependent pattern. Concomitant treatment of hepatocytes with ketoconazole mitigated their susceptibility to the cytotoxic effects of CTU.


Assuntos
Citocromo P-450 CYP3A , Hepatócitos , Microssomos Hepáticos , Animais , Ratos , Citocromo P-450 CYP3A/metabolismo , Humanos , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Masculino , Microssomos Hepáticos/metabolismo , Ratos Sprague-Dawley , Ativação Metabólica , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Estrutura Molecular , Herbicidas/toxicidade , Herbicidas/metabolismo , Relação Dose-Resposta a Droga
11.
Chem Res Toxicol ; 37(6): 935-943, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38761382

RESUMO

Amitriptyline (ATL), a tricyclic antidepressant, has been reported to cause various adverse effects, particularly hepatotoxicity. The mechanisms of ATL-induced hepatotoxicity remain unknown. The study was performed to identify the olefin epoxidation metabolite of ATL and determine the possible toxicity mechanism. Two glutathione (GSH) conjugates (M1 and M2) and two N-acetylcysteine (NAC) conjugates (M3 and M4) were detected in rat liver microsomal incubations supplemented with GSH and NAC, respectively. Moreover, M1/M2 and M3/M4 were respectively found in ATL-treated rat primary hepatocytes and in bile and urine of rats given ATL. Recombinant P450 enzyme incubations demonstrated that CYP3A4 was the primary enzyme involved in the olefin epoxidation of ATL. Treatment of hepatocytes with ATL resulted in significant cell death. Inhibition of CYP3A attenuated the susceptibility to the observed cytotoxicity of ATL. The metabolic activation of ATL most likely participates in the cytotoxicity of ATL.


Assuntos
Amitriptilina , Citocromo P-450 CYP3A , Compostos de Epóxi , Hepatócitos , Microssomos Hepáticos , Ratos Sprague-Dawley , Animais , Amitriptilina/metabolismo , Ratos , Citocromo P-450 CYP3A/metabolismo , Microssomos Hepáticos/metabolismo , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Masculino , Compostos de Epóxi/metabolismo , Compostos de Epóxi/toxicidade , Compostos de Epóxi/química , Glutationa/metabolismo , Células Cultivadas
12.
Org Biomol Chem ; 22(30): 6198-6204, 2024 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-39028029

RESUMO

We report herein a visible-light induced, Fe-catalyzed selenocyclization of 2-ethynylanilines with diselenides under ambient conditions, employing ethyl acetate as a benign solvent with no stoichiometric additive required. The simple iron salt FeBr3 serves as both a photo-induced LMCT (Ligand-to-Metal Charge Transfer) catalyst and a Lewis acid catalyst to promote the desired transformation in a sustainable manner, enabling the facile synthesis of diverse 3-selenylindoles with extended substitution patterns. Moreover, gram-scale reactions and late-stage functionalization of bioactive molecules further highlight the synthetic practicality of this method.

13.
Acta Pharmacol Sin ; 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38760544

RESUMO

Cardiac fibrosis is a detrimental pathological process, which constitutes the key factor for adverse cardiac structural remodeling leading to heart failure and other critical conditions. Circular RNAs (circRNAs) have emerged as important regulators of various cardiovascular diseases. It is known that several circRNAs regulate gene expression and pathological processes by binding miRNAs. In this study we investigated whether a novel circRNA, named circNSD1, and miR-429-3p formed an axis that controls cardiac fibrosis. We established a mouse model of myocardial infarction (MI) for in vivo studies and a cellular model of cardiac fibrogenesis in primary cultured mouse cardiac fibroblasts treated with TGF-ß1. We showed that miR-429-3p was markedly downregulated in the cardiac fibrosis models. Through gain- and loss-of-function studies we confirmed miR-429-3p as a negative regulator of cardiac fibrosis. In searching for the upstream regulator of miR-429-3p, we identified circNSD1 that we subsequently demonstrated as an endogenous sponge of miR-429-3p. In MI mice, knockdown of circNSD1 alleviated cardiac fibrosis. Moreover, silence of human circNSD1 suppressed the proliferation and collagen production in human cardiac fibroblasts in vitro. We revealed that circNSD1 directly bound miR-429-3p, thereby upregulating SULF1 expression and activating the Wnt/ß-catenin pathway. Collectively, circNSD1 may be a novel target for the treatment of cardiac fibrosis and associated cardiac disease.

14.
J Nanobiotechnology ; 22(1): 37, 2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-38263204

RESUMO

BACKGROUND: Therapeutic strategies based on scavenging reactive oxygen species (ROS) and suppressing inflammatory cascades are effective in improving functional recovery after spinal cord injury (SCI). However, the lack of targeting nanoparticles (NPs) with powerful antioxidant and anti-inflammatory properties hampers the clinical translation of these strategies. Here, CD44-targeting hyaluronic acid-selenium (HA-Se) NPs were designed and prepared for scavenging ROS and suppressing inflammatory responses in the injured spinal cord, enhancing functional recovery. RESULTS: The HA-Se NPs were easily prepared through direct reduction of seleninic acid in the presence of HA. The obtained HA-Se NPs exhibited a remarkable capacity to eliminate free radicals and CD44 receptor-facilitated internalization by astrocytes. Moreover, the HA-Se NPs effectively mitigated the secretion of proinflammatory cytokines (such as IL-1ß, TNF-α, and IL-6) by microglia cells (BV2) upon lipopolysaccharide-induced inflammation. In vivo experiments confirmed that HA-Se NPs could effectively accumulate within the lesion site through CD44 targeting. As a result, HA-Se NPs demonstrated superior protection of axons and neurons within the injury site, leading to enhanced functional recovery in a rat model of SCI. CONCLUSIONS: These results highlight the potential of CD44-targeting HA-Se NPs for SCI treatment.


Assuntos
Selênio , Traumatismos da Medula Espinal , Animais , Ratos , Ácido Hialurônico , Espécies Reativas de Oxigênio , Recuperação de Função Fisiológica
15.
Arch Toxicol ; 98(4): 1095-1110, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38369618

RESUMO

Chlorzoxazone (CZX), a benzoxazolone derivative, has been approved for the treatment of musculoskeletal disorders to relieve localized muscle spasm. However, its idiosyncratic toxicity reported in patients brought attention, particularly for hepatotoxicity. The present study for the first time aimed at the relationship between CZX-induced hepatotoxicity and identification of oxirane intermediate resulting from metabolic activation of CZX. Two N-acetylcysteine (NAC) conjugates (namely M1 and M2) and two glutathione (GSH) conjugates (namely M3 and M4) were detected in rat & human microsomal incubations with CZX (200 µM) fortified with NAC or GSH, respectively. The formation of M1-M4 was NADPH-dependent and these metabolites were also observed in urine or bile of SD rats given CZX intragastrically at 10 mg/kg or 25 mg/kg. NAC was found to attach at C-6' of the benzo group of M1 by sufficient NMR data. CYPs3A4 and 3A5 dominated the metabolic activation of CZX. The two GSH conjugates were also observed in cultured rat primary hepatocytes after exposure to CZX. Inhibition of CYP3A attenuated the susceptibility of hepatocytes to the cytotoxicity of CZX (10-400 µM). The in vitro and in vivo studies provided solid evidence for the formation of oxirane intermediate of CZX. This would facilitate the understanding of the underlying mechanisms of toxic action of CZX.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Clorzoxazona , Humanos , Ratos , Animais , Citocromo P-450 CYP3A/metabolismo , Ativação Metabólica , Ratos Sprague-Dawley , Microssomos Hepáticos/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Compostos de Epóxi/metabolismo , Glutationa/metabolismo
16.
Biomed Pharmacother ; 176: 116935, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38876050

RESUMO

Breast cancer is one of the most common malignant tumors in women and is a serious threat to women's health. The pentose phosphate pathway (PPP) is a mode of oxidative breakdown of glucose that can be divided into oxidative (oxPPP) and non-oxidative (non-oxPPP) stages and is necessary for cell and body survival. However, abnormal activation of PPP often leads to proliferation, migration, invasion, and chemotherapy resistance in breast cancer. Glucose-6-phosphate dehydrogenase (G6PD) is the rate-limiting enzyme in PPP oxidation. Nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) produced by G6PD is the raw material for cholesterol and lipid synthesis and can resist the production of oxygen species (ROS) and reduce oxidative stress damage to tumor cells. Transketolase (TKT) is a key enzyme in non-oxPPP. Ribose 5-phosphate (R5P), produced by TKT, is a raw material for DNA and RNA synthesis, and is essential for tumor cell proliferation and DNA damage repair. In this review, we describe the role and specific mechanism of the PPP and the two most important enzymes of the PPP, G6PD and TKT, in the malignant progression of breast cancer, providing strategies for future clinical treatment of breast cancer and a theoretical basis for breast cancer research.


Assuntos
Neoplasias da Mama , Progressão da Doença , Glucosefosfato Desidrogenase , Via de Pentose Fosfato , Transcetolase , Transcetolase/metabolismo , Humanos , Neoplasias da Mama/patologia , Neoplasias da Mama/enzimologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Feminino , Glucosefosfato Desidrogenase/metabolismo , Via de Pentose Fosfato/efeitos dos fármacos , Animais
17.
Quant Imaging Med Surg ; 14(2): 1323-1334, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38415126

RESUMO

Background: Post-transplant lymphoproliferative disorder (PTLD) is a significant complication after liver transplantation. Research on the diagnostic value of the Fluorine-18 fluorodeoxyglucose positron emission tomography/computerized tomography (18F-FDG PET/CT) metabolic parameters of PTLD in pediatric liver transplantation (pLT) recipients is limited. This study sought to evaluate the diagnostic efficacy of 18F-FDG PET/CT in differentiating between PTLD and non-PTLD lymphadenopathy in pLT recipients. Methods: This retrospective study collected the 18F-FDG PET/CT scans with clinical and pathological information of all consecutive children who were clinically suspected of PTLD from November 2016 to September 2022 at the Beijing Friendship Hospital. The 18F-FDG PET/CT metabolic parameters of the two groups were analyzed. We then established a diagnostic model composed of the clinical characteristics and metabolic parameters. Results: In total, 57 eligible patients were enrolled in this study, of whom 40 had PTLD and 17 had non-PTLD lymphadenopathy. Of the metabolic parameters examined in this study, total lesion glycolysis (TLG) had the highest area under the curve (AUC) value [0.757, 95% confidence interval (CI): 0.632-0.883, P=0.002]. The AUCs of the other metabolic parameters were all less than the AUC of TLG, including the maximum standardized uptake value (SUVmax) (AUC: 0.725, 95% CI: 0.597-0.853, P=0.008), mean standardized uptake value (SUVmean) (AUC: 0.701, 95% CI: 0.568-0.834, P=0.017), metabolic tumor volume total (MTVtotal) (AUC: 0.688, 95% CI: 0.549-0.827, P=0.040), TLG total (AUC: 0.674, 95% CI: 0.536-0.812, P=0.026). The diagnostic model, which was composed of clinical characteristics (digestive symptoms), the SUVmax, TLG, and the MTVtotal, showed excellent performance in the differential diagnosis (sensitivity: 0.675, 95% CI: 0.508-0.809; specificity: 0.941, 95% CI: 0.692-0.997; positive predictive value: 0.964, 95% CI: 0.798-0.998; and negative predictive value: 0.552, 95% CI: 0.360-0.730). Conclusions: The 18F-FDG PET/CT metabolic parameters can be used to distinguishing between PTLD and non-PTLD lymphadenopathy in pLT recipients.

18.
Environ Sci Pollut Res Int ; 31(17): 25147-25162, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38468006

RESUMO

The comparative study of the transformation among sediment phosphorus (P) fractions in different lake types is a global issue in lake ecosystems. However, interactions between sediment P fractions, environmental factors, and microorganisms vary with the nutrient status of lakes. In this study, we combine sequential extraction and metagenomics sequencing to assess the characteristics of P fractions and transformation in sediments from different lake types in the Inner Mongolian section of the Yellow River Basin. We then further explore the response of relevant microbial and environmental drivers to P fraction transformation and bioavailability in sediments. The sediments of all three lakes exhibited strong exogenous pollution input characteristics, and higher nutritional conditions led to enhanced sediment P fraction transformation ability. The transformation capacity of the sediment P fractions also differed among the different lake types at the same latitudes, which is affected by many factors such as lake environmental factors and microorganisms. Different drivers reflected the mutual control of weakly adsorbed phosphorus (WA-P), potential active phosphorus (PA-P), Fe/Al-bound phosphorus (NaOH-P), and Ca-bound phosphorus (HCl-P) with the bio-directly available phosphorus (Bio-P). The transformation of NaOH-P in reducing environments can improve P bioavailability, while HCl-P is not easily bioavailable in weakly alkaline environments. There were significant differences in the bacterial community diversity and composition between the different lake types at the same latitude (p < 0.05), and the role of P fractions was stronger in the sediments of lakes with rich biodiversity than in poor biodiversity. Lake eutrophication recovery was somewhat hindered by the microbial interactions of P cycling and P fractions within the sediment. This study provides data and theoretical support for exploring the commonalities and differences among different lake types in the Inner Mongolian section of the Yellow River Basin. Besides, it is representative and typical for promoting the optimization of ecological security patterns in ecologically fragile watersheds.


Assuntos
Lagos , Poluentes Químicos da Água , Poluentes Químicos da Água/análise , Ecossistema , Fósforo/análise , Congelamento , Hidróxido de Sódio , Monitoramento Ambiental , Sedimentos Geológicos , Eutrofização , China
19.
J Neural Eng ; 21(3)2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38806037

RESUMO

Objective. Motor-related brain-computer interface (BCI) have a broad range of applications, with the detection of premovement intentions being a prominent use case. However, the electroencephalography (EEG) features during the premovement phase are not distinctly evident and are susceptible to attentional influences. These limitations impede the enhancement of performance in motor-based BCI. The objective of this study is to establish a premovement BCI encoding paradigm that integrates the preparatory movement state and validates its feasibility in improving the detection of movement intentions.Methods. Two button tasks were designed to induce subjects into a preparation state for two movement intentions (left and right) based on visual guidance, in contrast to spontaneous premovement. The low frequency movement-related cortical potentials (MRCPs) and high frequency event-related desynchronization (ERD) EEG data of 14 subjects were recorded. Extracted features were fused and classified using task related common spatial patterns (CSP) and CSP algorithms. Differences between prepared premovement and spontaneous premovement were compared in terms of time domain, frequency domain, and classification accuracy.Results. In the time domain, MRCPs features reveal that prepared premovement induce lower amplitude and earlier latency on both contralateral and ipsilateral motor cortex compared to spontaneous premovement, with susceptibility to the dominant hand's influence. Frequency domain ERD features indicate that prepared premovement induce lower ERD values bilaterally, and the ERD recovery speed after button press is the fastest. By using the fusion approach, the classification accuracy increased from 78.92% for spontaneous premovement to 83.59% for prepared premovement (p< 0.05). Along with the 4.67% improvement in classification accuracy, the standard deviation decreased by 0.95.Significance. The research findings confirm that incorporating a preparatory state into premovement enhances neural representations related to movement. This encoding enhancement paradigm effectively improves the performance of motor-based BCI. Additionally, this concept has the potential to broaden the range of decodable movement intentions and related information in motor-related BCI.


Assuntos
Interfaces Cérebro-Computador , Eletroencefalografia , Movimento , Humanos , Movimento/fisiologia , Masculino , Eletroencefalografia/métodos , Feminino , Adulto , Adulto Jovem , Desempenho Psicomotor/fisiologia , Intenção , Algoritmos
20.
Biotechnol J ; 19(5): e2400014, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38719614

RESUMO

Microbial production of L-malic acid from renewable carbon sources has attracted extensive attention. The reduced cofactor NADPH plays a key role in biotransformation because it participates in both biosynthetic reactions and cellular stress responses. In this study, NADPH or its precursors nicotinamide and nicotinic acid were added to the fermentation medium of Aspergillus niger RG0095, which significantly increased the yield of malic acid by 11%. To further improve the titer and productivity of L-malic acid, we increased the cytoplasmic NADPH levels of A. niger by upregulating the NAD kinases Utr1p and Yef1p. Biochemical analyses demonstrated that overexpression of Utr1p and Yef1p reduced oxidative stress, while also providing more NADPH to catalyze the conversion of glucose into malic acid. Notably, the strain overexpressing Utr1p reached a malate titer of 110.72 ± 1.91 g L-1 after 108 h, corresponding to a productivity of 1.03 ± 0.02 g L-1 h-1. Thus, the titer and productivity of malate were increased by 24.5% and 44.7%, respectively. The strategies developed in this study may also be useful for the metabolic engineering of fungi to produce other industrially relevant bulk chemicals.


Assuntos
Aspergillus niger , Fermentação , Malatos , Engenharia Metabólica , NADP , Aspergillus niger/metabolismo , Aspergillus niger/genética , Malatos/metabolismo , Engenharia Metabólica/métodos , NADP/metabolismo , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Glucose/metabolismo , Fosfotransferases (Aceptor do Grupo Álcool)/genética , Fosfotransferases (Aceptor do Grupo Álcool)/metabolismo
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