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1.
Front Microbiol ; 15: 1422471, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39006754

RESUMO

The fermentation process for Jiang-flavored baijiu using sorghum as the raw material involves a variety of microorganisms. However, the specific physicochemical characteristics of sorghum and microbial composition on its surface have not been fully elucidated. We aimed to perform a comprehensive comparative analysis of the variations in physicochemical properties and surface microflora in waxy sorghum samples from three prominent production regions in China (Renhuai, Jinsha, and Duyun). Multivariate statistical assessments were conducted that incorporated local soil and climate variables. The results showed that Cyanobacteria, unclassified bacteria, Proteobacteria, Firmicutes, and Bacteroidota were the dominant bacteria in these regions. These bacteria were associated with ethyl acetate, ethyl caprylate, ethyl lactate, and butyl groups, which synergistically produce flavorful compounds. The surface bacterial communities were affected by soil total phosphorus, altitude, diurnal temperature range, monthly mean temperature, precipitation, and effective accumulated temperature. The findings of this study provide a new perspective on microorganisms related to Jiang-flavored baijiu and can help establish a reference for the stability of liquor quality.

2.
Am J Epidemiol ; 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38918040

RESUMO

Prenatal exposures to ambient particulate matter (PM2.5) from traffic may generate oxidative stress, and thus contribute to adverse birth outcomes. We investigated whether PM2.5 constituents from brake and tire wear affect levels of oxidative stress biomarkers (malondialdehyde (MDA), 8-hydroxy-2'-deoxyguanosine (8-OHdG)) using urine samples collected up to three times during pregnancy in 156 women recruited from antenatal clinics at the University of California Los Angeles. Land use regression models with co-kriging were employed to estimate average residential outdoor concentrations of black carbon (BC), PM2.5 mass, PM2.5 metal components, and three PM2.5 oxidative potential metrics during the 4-weeks prior to urine sample collection. 8-OHdG concentrations in mid-pregnancy increased by 24.8% (95% CI: 9.0, 42.8) and 14.3% (95% CI: 0.4%, 30.0%) per interquartile range (IQR) increase in PM2.5 mass and BC, respectively. The brake wear marker (barium) and the oxidative potential metrics were associated with increased MDA concentration in the 1st sample collected (10-17 gestational week), but 95% CIs included the null. Traffic-related air pollution contributed in early to mid-pregnancy to oxidative stress generation previously linked to adverse birth outcomes.

3.
Chemosphere ; 362: 142649, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38901699

RESUMO

Little is known about the effect of surface coatings on the fate and toxicity of CeO2 nanoparticles (NPs) to aquatic plants. In this study, we modified nCeO2 with chitosan (Cs) and alginate (Al) to obtain positively charged nCeO2@Cs and negatively charged nCeO2@Al, respectively, and exposed them to a representative aquatic plant, duckweed (Lemna minor L.). Uncoated nCeO2 could significantly inhibit the growth of duckweed, induce oxidative damage and lead to cell death, whereas nCeO2@Cs and nCeO2@Al exhibited lower toxicity to duckweed. ICP-MS analysis revealed that the Ce content in duckweed from the nCeO2 group was 1.74 and 2.85 times higher than that in the nCeO2@Cs and nCeO2@Al groups, respectively. Microscopic observations indicated that the positively charged nCeO2@Cs was more readily adsorbed on the root surface of duckweed than the negatively charged nCeO2@Al. The results of XANES and LCF demonstrated that a certain percentage of Ce(Ⅳ) was reduced to Ce(Ⅲ) after the interaction of the three NPs with duckweed, but the degree of biotransformation differed among the treatments. Specifically, the absolute contents of Ce(III) produced of nCeO2@Cs and nCeO2@Al through biotransformation were reduced by 55.5% and 83.5%, respectively, compared with that of the nCeO2 group, which might be the key factor for the diminished phytotoxicity of the coated nCeO2 to the duckweed. These findings were valuable for understanding the toxicity of metal-based NPs to aquatic plants and for the synthesis of environmentally friendly nanomaterials.

4.
Water Sci Technol ; 89(9): 2483-2497, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38747962

RESUMO

In this study, a multi-functional layer was developed based on the commercially available cellulose triacetate (CTA) forward osmosis (FO) membrane to improve its antifouling property. Tannic acid/ferric ion (TA/Fe3+) complexes were firstly coated as a precursor layer on the membrane surface via self-assembly. Afterwards, the tannic acid/diethylenetriamine (TA/DETA) hydrophilic functional layer was further coated, following Ag/polyvinylpyrrolidone (PVP) anti-bacterial layer was formed in situ through the reducibility of TA to obtain TA/Fe3+-TA/DETA-Ag/PVP-modified membrane. The optimized precursor layer was acquired by adjusting the buffer solution pH to 8, TA/Fe3+ ratio to 4 and the number of self-assembled layers to 5. The permeability testing results illustrated that the functional layer had an insignificant effect on the membrane transport parameters. The TA/Fe3+-TA/DETA-Ag/PVP-modified membrane simultaneously exhibited excellent physical and chemical stability. The coated membrane also demonstrated enhanced anti-bacterial properties, achieving 98.63 and 97.30% inhibition against Staphylococcus aureus and Escherichia coli, respectively. Furthermore, the dynamic fouling experiment showed a 12% higher water flux decrease for the TA/Fe3+-TA/DETA-Ag/PVP CTA membrane compared to the nascent CTA membrane, which proved its excellent antifouling performance. This work provides a feasible strategy to heighten the antifouling property of the CTA FO membrane.


Assuntos
Incrustação Biológica , Membranas Artificiais , Osmose , Staphylococcus aureus , Incrustação Biológica/prevenção & controle , Staphylococcus aureus/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Taninos/química , Fenóis/química , Antibacterianos/farmacologia , Antibacterianos/química , Purificação da Água/métodos
5.
BMC Ophthalmol ; 24(1): 231, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38822280

RESUMO

BACKGROUND: The main purpose of this paper is to introduce a method that can accurately locate the posterior capsule of the lens to facilitate a relatively complete resection of the anterior vitreous body. METHODS: A total of 51 patients in the experimental group and control group were enrolled in this study. Phacoemulsification combined with vitrectomy was performed in all cases. After the cataract procedure was completed in the control group, the surgeon performed a conventional anterior vitrectomy with the operative eye. In the experimental group, anterior vitrectomy was performed according to the threadiness corrugation of the posterior capsule of the lens. During the operation, with the help of triamcinolone, two surgeons confirmed the resection of the anterior vitreous cortex; the best corrected visual acuity and intraocular pressure of all patients were recorded at 1 week, 1 month and 3 months after surgery. RESULTS: Fifty patients underwent phacoemulsification combined with vitrectomy, except one patient in the experimental group who was lost to follow-up. After surgery, no significant complications were observed in all patients except two patients in the control group with temporary increases in intraocular pressure. There was no significant difference in preoperative visual acuity between the two groups (t = 0.83, P = 0.25). Both groups had varying degrees of improvement in best corrected visual acuity at 1 week, 1 month and 3 months after surgery. Moreover, there was no significant difference in BCVA between the two groups at the three follow-up time points (t=-1.15, -1.65, -1.09, P = 0.53, 0.21, 0.23). After surgery, no significant complications were observed in all patients except two patients in the control group with temporary increases in intraocular pressure. Incomplete resection of the anterior vitreous cortex was observed in 2 patients in each group, but there was no significant difference (χ2 = 7.81, P > 0.05). CONCLUSION: In the process of cataract surgery combined with vitrectomy, thready corrugation appears in the posterior capsule of the lens and is an important sign of its localization. Anterior vitrectomy can be accomplished safely and effectively with the help of thread-like corrugation, and the surgical effect is almost the same as that of traditional surgery. Especially suitable for beginners in vitreous surgery.


Assuntos
Pressão Intraocular , Facoemulsificação , Acuidade Visual , Vitrectomia , Corpo Vítreo , Humanos , Vitrectomia/métodos , Facoemulsificação/métodos , Feminino , Masculino , Idoso , Pessoa de Meia-Idade , Corpo Vítreo/cirurgia , Pressão Intraocular/fisiologia , Cápsula Posterior do Cristalino/cirurgia , Idoso de 80 Anos ou mais
6.
Proc Natl Acad Sci U S A ; 121(18): e2307090121, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38648487

RESUMO

G protein-coupled receptors (GPCRs) transduce the effects of many neuromodulators including dopamine, serotonin, epinephrine, acetylcholine, and opioids. The localization of synthetic or endogenous GPCR agonists impacts their action on specific neuronal pathways. In this paper, we show a series of single-protein chain integrator sensors that are highly modular and could potentially be used to determine GPCR agonist localization across the brain. We previously engineered integrator sensors for the mu- and kappa-opioid receptor agonists called M- and K-Single-chain Protein-based Opioid Transmission Indicator Tool (SPOTIT), respectively. Here, we engineered red versions of the SPOTIT sensors for multiplexed imaging of GPCR agonists. We also modified SPOTIT to create an integrator sensor design platform called SPOTIT for all GPCRs (SPOTall). We used the SPOTall platform to engineer sensors for the beta 2-adrenergic receptor (B2AR), the dopamine receptor D1, and the cholinergic receptor muscarinic 2 agonists. Finally, we demonstrated the application of M-SPOTIT and B2AR-SPOTall in detecting exogenously administered morphine, isoproterenol, and epinephrine in the mouse brain via locally injected viruses. The SPOTIT and SPOTall sensor design platform has the potential for unbiased agonist detection of many synthetic and endogenous neuromodulators across the brain.


Assuntos
Receptores Acoplados a Proteínas G , Animais , Receptores Acoplados a Proteínas G/agonistas , Receptores Acoplados a Proteínas G/metabolismo , Humanos , Camundongos , Células HEK293 , Receptores de Dopamina D1/agonistas , Receptores de Dopamina D1/metabolismo , Receptores Adrenérgicos beta 2/metabolismo , Receptores Adrenérgicos beta 2/genética , Receptor Muscarínico M2/agonistas , Receptor Muscarínico M2/metabolismo , Isoproterenol/farmacologia , Receptores Opioides mu/agonistas , Receptores Opioides mu/metabolismo , Morfina/farmacologia , Encéfalo/metabolismo , Encéfalo/efeitos dos fármacos , Encéfalo/diagnóstico por imagem , Receptores Opioides kappa/agonistas , Receptores Opioides kappa/metabolismo , Técnicas Biossensoriais/métodos
7.
Transl Neurodegener ; 13(1): 24, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38671492

RESUMO

BACKGROUND: Adult neurogenesis occurs in the subventricular zone (SVZ) and the subgranular zone of the dentate gyrus in the hippocampus. The neuronal stem cells in these two neurogenic niches respond differently to various physiological and pathological stimuli. Recently, we have found that the decrement of carboxypeptidase E (CPE) with aging impairs the maturation of brain-derived neurotrophic factor (BDNF) and neurogenesis in the SVZ. However, it remains unknown whether these events occur in the hippocampus, and what the role of CPE is in the adult hippocampal neurogenesis in the context of Alzheimer's disease (AD). METHODS: In vivo screening was performed to search for miRNA mimics capable of upregulating CPE expression and promoting neurogenesis in both neurogenic niches. Among these, two agomirs were further assessed for their effects on hippocampal neurogenesis in the context of AD. We also explored whether these two agomirs could ameliorate behavioral symptoms and AD pathology in mice, using direct intracerebroventricular injection or by non-invasive intranasal instillation. RESULTS: Restoration of CPE expression in the hippocampus improved BDNF maturation and boosted adult hippocampal neurogenesis. By screening the miRNA mimics targeting the 5'UTR region of Cpe gene, we developed two agomirs that were capable of upregulating CPE expression. The two agomirs significantly rescued adult neurogenesis and cognition, showing multiple beneficial effects against the AD-associated pathologies in APP/PS1 mice. Of note, noninvasive approach via intranasal delivery of these agomirs improved the behavioral and neurocognitive functions of APP/PS1 mice. CONCLUSIONS: CPE may regulate adult hippocampal neurogenesis via the CPE-BDNF-TrkB signaling pathway. This study supports the prospect of developing miRNA agomirs targeting CPE as biopharmaceuticals to counteract aging- and disease-related neurological decline in human brains.


Assuntos
Doença de Alzheimer , Carboxipeptidase H , Hipocampo , Transtornos da Memória , Neurogênese , Regulação para Cima , Animais , Neurogênese/efeitos dos fármacos , Neurogênese/fisiologia , Doença de Alzheimer/genética , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Carboxipeptidase H/genética , Carboxipeptidase H/biossíntese , Camundongos , Transtornos da Memória/genética , Transtornos da Memória/etiologia , Fator Neurotrófico Derivado do Encéfalo/biossíntese , Fator Neurotrófico Derivado do Encéfalo/genética , Fator Neurotrófico Derivado do Encéfalo/metabolismo , MicroRNAs/genética , MicroRNAs/biossíntese , Masculino , Camundongos Transgênicos , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças
8.
Environ Int ; 185: 108573, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38484609

RESUMO

BACKGROUND: Air pollution is a global health concern, with fine particulate matter (PM2.5) constituents posing potential risks to human health, including children's neurodevelopment. Here we investigated associations between exposure during pregnancy and infancy to specific traffic-related PM2.5 components with Autism Spectrum Disorder (ASD) diagnosis. METHODS: For exposure assessment, we estimated PM2.5 components related to traffic exposure (Barium [Ba] as a marker of brake dust and Zinc [Zn] as a tire wear marker, Black Carbon [BC]) and oxidative stress potential (OSP) markers (Hydroxyl Radical [OPOH] formation, Dithiothreitol activity [OPDTT], reactive oxygen species [ROS]) modeled with land use regression with co-kriging based on an intensive air monitoring campaign. We assigned exposures to a cohort of 444,651 children born in Southern California between 2016 and 2019, among whom 11,466 ASD cases were diagnosed between 2018 and 2022, Odds ratios (ORs) and 95% confidence intervals (CIs) were obtained with logistic regression for single pollutant and PM2.5 mass co-adjusted models, also adjusting for sociodemographic characteristics. RESULTS: Among PM2.5 components, we found the strongest positive association with ASD for our brake wear marker Ba (ORper IQR = 1.29, 95 % CI: 1.24, 1.34). This was followed by an increased risk for all PM2.5 oxidative stress potential markers; the strongest association was with ROS formation (ORper IQR = 1.22, 95 % CI: 1.18, 1.25). PM2.5 mass was linked to ASD in Hispanic and Black children, but not White children, while traffic-related PM2.5 and OSP markers increased ASD risk across all groups. In neighborhoods with the lowest socioeconomic status (SES), associations with ASD were stronger for all examined pollutants compared to higher SES areas. CONCLUSIONS: Our findings suggest that brake wear-related PM2.5 and PM2.5 OSP are associated with ASD diagnosis in Southern California. These results suggest that strategies aimed at reducing the public health impacts of PM2.5 need to consider specific sources.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Transtorno do Espectro Autista , Criança , Gravidez , Feminino , Humanos , Poluentes Atmosféricos/análise , Transtorno do Espectro Autista/etiologia , Transtorno do Espectro Autista/induzido quimicamente , Espécies Reativas de Oxigênio , Poluição do Ar/análise , Material Particulado/análise , Poeira , California/epidemiologia , Metais , Estresse Oxidativo , Exposição Ambiental/efeitos adversos , Exposição Ambiental/análise
9.
Artigo em Inglês | MEDLINE | ID: mdl-37951286

RESUMO

In recent years, carbon nanotubes (CNTs) have gained tremendous attention due to their widespread application. Previous research indicated that carbon nanomaterials can affect the toxicity of some pollutants. In this study, we investigated the influence of multi-walled CNTs (MWCNTs) on the toxicity of ZnO nanoparticles (ZnONPs) in the intestine of common carp (Cyprinus carpio). After four-week exposure, histopathological observation and TUNEL assay showed concentration ratio-dependent intestinal lesions and apoptosis, with the most severe in the HSC-ZnONPs group (50 mg L-1 ZnONPs and 2.5 mg L-1 MWCNTs), less severe in the ZnONPs group (50 mg L-1 ZnONPs) and the least in the LSC-ZnONPs group (50 mg L-1 ZnONPs and 0.25 mg L-1 MWCNTs). Furthermore, ICP-OES indicated that intercellular zinc accumulation was significantly decreased by the presence of the MWCNTs, which suggested the varied contribution of ZnONPs to intestine injury in different groups. Moreover, 16 s rDNA sequencing revealed that ZnONPs alone and in combination with MWCNTs significantly altered the microbial community diversity and composition of the gut microbiota compared with controls. In addition, the predominant phylum, class, order, family, and genus were significantly different among these groups. In conclusion, the influence of MWCNTs on the toxicity of ZnONPs was related to the concentration and concentration ratio of the mixture.


Assuntos
Carpas , Microbiota , Nanotubos de Carbono , Óxido de Zinco , Animais , Óxido de Zinco/toxicidade , Nanotubos de Carbono/toxicidade , Intestinos , Apoptose
10.
Environ Health Perspect ; 131(10): 107012, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37878796

RESUMO

BACKGROUND: Although many studies have linked prenatal exposure to PM2.5 to adverse birth outcomes, little is known about the effects of exposure to specific constituents of PM2.5 or mechanisms that contribute to these outcomes. OBJECTIVES: Our objective was to investigate effects of oxidative potential and PM2.5 metal components from non-exhaust traffic emissions, such as brake and tire wear, on the risk of preterm birth (PTB) and term low birth weight (TLBW). METHODS: For a birth cohort of 285,614 singletons born in Los Angeles County, California, in the period 2017-2019, we estimated speciated PM2.5 exposures modeled from land use regression with cokriging, including brake and tire wear related metals (barium and zinc), black carbon, and three markers of oxidative potential (OP), including modeled reactive oxygen species based on measured iron and copper (ROS), OH formation (OPOH), and dithiothreitol (DTT) loss (OPDTT). Using logistic regression, we estimated odds ratios (OR) and 95% confidence intervals (CI) for PTB and TLBW with speciated PM2.5 exposures and PM2.5 mass as continuous variables scaled by their interquartile range (IQR). RESULTS: For both metals and oxidative potential metrics, we estimated increased risks for PTB (ORs ranging from 1.01 to 1.03) and TLBW (ORs ranging from 1.02 to 1.05) per IQR exposure increment that were robust to adjustment for PM2.5 mass. Associations for PM2.5 mass, black carbon, metal components, and oxidative potential (especially ROS and OPOH) with adverse birth outcomes were stronger in Hispanic, Black, and mixed-race or Native American women. DISCUSSION: Our results indicate that exposure to PM2.5 metals from brake and tire wear and particle components that contribute to oxidative potential were associated with an increased risk of PTB and TLBW in Los Angeles County, particularly among Hispanic, Black, and mixed-race or Native American women. Thus, reduction of PM2.5 mass only may not be sufficient to protect the most vulnerable pregnant women and children from adverse effects due to traffic source exposures. https://doi.org/10.1289/EHP12196.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Nascimento Prematuro , Criança , Recém-Nascido , Feminino , Humanos , Gravidez , Material Particulado/análise , Poluentes Atmosféricos/análise , Los Angeles/epidemiologia , Espécies Reativas de Oxigênio , Nascimento Prematuro/epidemiologia , Nascimento Prematuro/induzido quimicamente , Metais , Carbono , Estresse Oxidativo , Poluição do Ar/análise
11.
Expert Opin Drug Deliv ; 20(11): 1467-1488, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37814582

RESUMO

INTRODUCTION: Intravenous nanocrystals (INCs) have shown intrinsic advantages in antitumor applications, particularly their properties of high drug loading, low toxicity, and controllable size. Therefore, it has a very bright application prospect as a drug delivery system. AREAS COVERED: The ideal formulation design principles, fabrication, solidification, in vivo fate of INCs, the applications in drug delivery system (DDS) and the novel applications are covered in this review. EXPERT OPINION: It is vital to select a suitable formulation and fabrication method to produce a stable and sterile INCs. Besides, the type of stabilizers and physical characteristics can also influence the in vivo fate of INCs, which is worthy of further studying. Based on wide researches about applications of INCs in cancer, biomimetic INCs are concerned increasingly for its favorable compatibility. The output of these studies suggested that INCs-based drug delivery could be a novel strategy for addressing the delivery of the drug that faces solubility, bioavailability, and toxicity problems.


Assuntos
Nanopartículas , Neoplasias , Humanos , Sistemas de Liberação de Medicamentos/métodos , Preparações Farmacêuticas/química , Disponibilidade Biológica , Nanopartículas/química , Solubilidade , Neoplasias/tratamento farmacológico
12.
Chemosphere ; 345: 140421, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37839741

RESUMO

The metal organic frameworks (MOFs) are considered as the effective adsorbents for phosphate removal, while their ultrafine powders limit their practical application. In this study, we fabricate two chitosan (CS) gel beads added with different cerium-based MOFs and coated with PDA for phosphate adsorption. The MOFs doped in beads are CM1 and CM2, in which the Ce(III)/Ce(IV) ratio is 0.36 and 1.46, indicating CM2 is Ce(III) dominated and more suitable for phosphate removal. However, during the process of preparing gel beads, the mixture of chitosan and CM1/CM2 are added drop-by-drop to NaOH solution, leading to the decrease of Ce(III) contents in both of the two beads on account of oxidization. On this basis, in order to improve the phosphate uptake performance and enhance the mechanical strength, polydopamine (PDA) is applied to be coated on the outside. The adsorption capacities of CS-CM1 and CS-CM2 are no more than 20 mg/g higher than that of pure CS, which is also quite equal with the phosphate uptake of CS@PDA (63 mg/g). Due to the reduction of PDA, the content of Ce(III) increasing evidently in the two adsorbents. The maximum phosphate adsorption capacities are 146.8 mg/g and 114.8 mg/g for CS-CM1@PDA and CS-CM2@PDA, respectively. CS-CM2@PDA exhibits the largest treatment volume of ∼1166 BV in the fix-bed column study, much higher than that of CS-CM1@PDA (976 BV). The main reason is that Ce(III) could form binding with phosphate through ligand exchange and precipitation. Those inner-sphere interactions are much stronger than the electrostatic attraction between Ce(IV) and phosphate. Thus, due to this strong affinity, CS-CM2@PDA possessing a higher content of Ce(III) can capture phosphate more easier at low concentration. In summary, owing to reduction of PDA, the Cerium-based MOFs are successfully introduced in CS to realize excellent phosphate removal and exhibit a great prospect in application.


Assuntos
Cério , Quitosana , Estruturas Metalorgânicas , Poluentes Químicos da Água , Fosfatos/química , Cério/química , Quitosana/química , Adsorção , Poluentes Químicos da Água/química , Cinética
13.
Int J Biol Macromol ; 253(Pt 4): 127003, 2023 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-37739280

RESUMO

Fusion protein which encompasses more than one functional component, has become one of the most important representatives of macromolecular drugs for disease treatment since that monotherapy itself might not be effective enough to eradicate the disease. In this study, we sought to construct a bifunctional antibody fusion protein by fusing anti-PCSK9 scFv with Exendin-4 for simultaneously lowering both LDL-C and TG. Firstly, three Ex4-anti-PCSK9 scFv fusion proteins were constructed by genetically connecting the C-terminal of Exendin-4 to the N-terminal of anti-PCSK9 scFv through various flexible linker peptides (G4S)n (n = 2, 3, 4). After soluble expression in E. coli, the most potent Ex4-(G4S)4-anti-PCSK9 scFv fusion protein was selected based on in vitro activity assays. Then, we investigated the in vivo therapeutic effects of Ex4-(G4S)4-anti-PCSK9 scFv on the serum lipid profile and bodyweight changes as well as underlying molecular mechanism in HFD-fed C57BL/6 mice. The data showed that Ex4-(G4S)4-anti-PCSK9 scFv exhibits enhanced effects of lowering both LDL-C and TG in serum, reducing food intake and body weight via blocking PCSK9/LDLR, activating AMPK/SREBP-1 pathways, and up-regulating sirt6. Conclusively, Ex4-(G4S)4-anti-PCSK9 has the potential to serve as a promising therapeutic agent for effectively treating dyslipidemia with high levels of both LDL-C and TG.


Assuntos
Escherichia coli , Pró-Proteína Convertase 9 , Camundongos , Animais , Pró-Proteína Convertase 9/genética , Pró-Proteína Convertase 9/metabolismo , Exenatida/farmacologia , LDL-Colesterol , Escherichia coli/genética , Escherichia coli/metabolismo , Camundongos Endogâmicos C57BL , Transdução de Sinais
14.
Nanomaterials (Basel) ; 13(18)2023 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-37764551

RESUMO

As one of the most widely used nanomaterials, CeO2 nanoparticles (NPs) might be released into the aquatic environment. In this paper, the interaction of CeO2 NPs and Ce3+ ions (0~10 mg/L) with duckweed (Lemna minor L.) was investigated. CeO2 NPs significantly inhibited the root elongation of duckweed at concentrations higher than 0.1 mg/L, while the inhibition threshold of Ce3+ ions was 0.02 mg/L. At high doses, both reduced photosynthetic pigment contents led to cell death and induced stomatal deformation, but the toxicity of Ce3+ ions was greater than that of CeO2 NPs at the same concentration. According to the in situ distribution of Ce in plant tissues by µ-XRF, the intensity of Ce signal was in the order of root > old frond > new frond, suggesting that roots play a major role in the uptake of Ce. The result of XANES showed that 27.6% of Ce(IV) was reduced to Ce(III) in duckweed treated with CeO2 NPs. We speculated that the toxicity of CeO2 NPs to duckweed was mainly due to its high sensitivity to the released Ce3+ ions. To our knowledge, this is the first study on the toxicity of CeO2 NPs to an aquatic higher plant.

15.
Nat Methods ; 20(10): 1454-1455, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37640937
16.
bioRxiv ; 2023 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-37398137

RESUMO

GPCRs transduce the effects of many neuromodulators including dopamine, serotonin, epinephrine, acetylcholine, and opioids. The localization of synthetic or endogenous GPCR agonists impacts their action on specific neuronal pathways. In this paper, we show a series of single-protein chain integrator sensors to determine GPCR agonist localization in the whole brain. We previously engineered integrator sensors for the mu and kappa opioid receptor agonists called M- and K-SPOTIT, respectively. Here, we show a new integrator sensor design platform called SPOTall that we used to engineer sensors for the beta-2-adrenergic receptor (B2AR), the dopamine receptor D1, and the cholinergic receptor muscarinic 2 agonists. For multiplexed imaging of SPOTIT and SPOTall, we engineered a red version of the SPOTIT sensors. Finally, we used M-SPOTIT and B2AR-SPOTall to detect morphine, isoproterenol, and epinephrine in the mouse brain. The SPOTIT and SPOTall sensor design platform can be used to design a variety of GPCR integrator sensors for unbiased agonist detection of many synthetic and endogenous neuromodulators across the whole brain.

17.
J Child Neurol ; 38(6-7): 454-465, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37431191

RESUMO

In this study, we reviewed the safety and efficacy of botulinum toxin type A (BoNT-A) injection with respect to motor development in children with spastic cerebral palsy aged <2 years. Randomized controlled trials of BoNT-A published between July 1993 and May 2021 were searched in PubMed, WANFANG, CNKI (Chinese National Knowledge Infrastructure), and Cochrane Library Central Register of Controlled Trials using keywords "Botulinum Toxin," "cerebral palsy," "nao xing tan huan," "nao tan," and "rou du du su." The 11-item PEDro Scale was used to rate the quality of all the identified studies. Twelve studies, involving 656 subjects, met the inclusion criteria, and of these, 2 involved patients aged <2 years. Treatment safety was assessed based on adverse event (AE) number and frequency, and efficacy was assessed based on spasticity, range of movement, and motor development. We observed that 3 self-limiting adverse events that were frequently reported included weakness, dysesthesia of the skin, and pain at the injection site. Moreover, there was a significant decrease in the incidence of spasticity and a notable improvement in the range of movement of BoNT-A-treated patients. Therefore, BoNT-A injection shows great safety and efficacy in the treatment of children with cerebral palsy aged <2 years.


Assuntos
Toxinas Botulínicas Tipo A , Paralisia Cerebral , Fármacos Neuromusculares , Criança , Humanos , Toxinas Botulínicas Tipo A/efeitos adversos , Paralisia Cerebral/complicações , Fármacos Neuromusculares/efeitos adversos , Espasticidade Muscular/tratamento farmacológico , Espasticidade Muscular/etiologia , Dor , Resultado do Tratamento
18.
Sci Total Environ ; 900: 165736, 2023 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-37495143

RESUMO

Reactive oxygen species (ROS) play a central role in chemistry in cloud water, as well as in other aqueous phases such as lung fluid and in wastewater treatment. Recently, work simulating nascent cloud droplets showed that aerosol particles produce a large burst of OH radicals when they first take up water. This activity stops abruptly, within two minutes. The source of the OH radicals is not well understood, but it likely includes the aqueous phase chemistry of ROS and/or organic hydroperoxides and redox active metals such as iron and copper. ROS and their precursors are in general highly reactive and labile, and thus may not survive during traditional sampling methods, which typically involve multi-hour collection on a filter or direct sampling into water or another collection liquid. Further, these species may further decay during storage. Here, we develop a technique to grow aerosol particles into small droplets and capture the droplets directly into a vial containing the terephthalate probe in water, which immediately scavenges OH radicals produced by aerosol particles. The method uses a Liquid Spot Sampler. Extensive characterization of the approach reveals that the collection liquid picks up substantial OH/OH precursors from the gas phase. This issue is effectively addressed by adding an activated carbon denuder. We then compared OH formation measured with the direct-to-reagent approach vs. filter collection. We find that after a modest correction for OH formed in the collection liquid, the samples collected into the reagent produce about six times those collected on filters, for both PM2.5 and total suspended particulate. This highlights the need for direct-to-reagent measurement approaches to accurately quantify OH production from ambient aerosol particles.

19.
Ann Hematol ; 102(11): 3115-3124, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37400729

RESUMO

The objective of this study was to develop a nomogram including parameters assessed by 18F-FDG PET/CT and clinical parameters for patients with diffuse large B-cell lymphoma (DLBCL) to predict progression-free survival (PFS). A total of 181 patients with pathologically diagnosed DLBCL at Sichuan Cancer Hospital and Institute from March 2015 to December 2020 were enrolled in this retrospective study. The area under the receiver operating characteristic (ROC) curve (AUC) was used to calculate the optimal cutoff values of the semiquantitative parameters (SUVmax, TLG, MTV, and Dmax) for PFS. A nomogram was constructed according to multivariate Cox proportional hazards regression. The predictive and discriminatory capacities of the nomogram were then measured using the concordance index (C-index), calibration plots, and Kaplan-Meier curves. The predictive and discriminatory capacities of the nomogram and the International Prognostic Index of the National Comprehensive Cancer Network (NCCN-IPI) were compared via the C-index and AUC. Multivariate analysis demonstrated that male gender and pretreatment Ann Arbor stage III-IV, non-GCB, elevated lactate dehydrogenase (LDH), number of extranodal organ involvement (Neo)>1, MTV≥152.8 cm3, and Dmax ≥53.9 cm were associated with unfavorable PFS (all p<0.05). The nomogram, including gender, Ann Arbor stage, pathology type, Neo, LDH levels, MTV, and Dmax, showed good prediction accuracy, with a C-index of 0.760 (95% CI: 0.727-0.793), which was higher than that of NCCN-IPI (0.710; 95% CI: 0.669-751). The calibration plots for 2-year demonstrated good consistency between the predicted and observed probabilities for survival time. We established a nomogram including MTV, Dmax, and several clinical parameters to predict the PFS of patients with DLBCL, and the nomogram showed better predictability and higher accuracy than NCCN-IPI.

20.
Anal Chem ; 95(15): 6391-6398, 2023 04 18.
Artigo em Inglês | MEDLINE | ID: mdl-37019686

RESUMO

The development of nanotechnology has transformed many cutting-edge studies related to single-molecule analysis into nanoparticle (NP) detection with a single-NP sensitivity and ultrahigh resolution. While laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) has been successful in quantifying and tracking NPs, its quantitative calibration remains a major challenge due to the lack of suitable standards and the uncertain matrix effects. Herein, we frame a new approach to prepare quantitative standards via precise synthesis of NPs, nanoscale characterization, on-demand NP distribution, and deep learning-assisted NP counting. Gold NP standards were prepared to cover the mass range from sub-femtogram to picogram levels with sufficient accuracy and precision, thus establishing an unambiguous relationship between the sampled NP number in each ablation and the corresponding mass spectral signal. Our strategy facilitated for the first time the study of the factors affecting particulate sample capture and signal transductions in LA-ICP-MS analysis and culminated in the development of an LA-ICP-MS-based method for absolute NP quantification with single-NP sensitivity and single-cell quantification capability. The achievements would herald the emergence of new frontiers cut across a spectrum of toxicological and diagnostic issues related to NP quantification.


Assuntos
Terapia a Laser , Nanopartículas , Espectrometria de Massas/métodos , Análise Espectral , Lasers
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