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Somatosensory abnormalities are commonly recognized as diagnostic criteria in autism spectrum disorder (ASD), and may also exist in individuals with autistic traits. The present research included two studies to explore the painful and non-painful sensation and their cognitive-neurological mechanisms of individuals with autistic traits. Study 1 included 358 participants to assess the relationship between autistic traits and pain/non-pain sensitivities using questionnaires: the Autism Spectrum Quotient (AQ), the Pain Sensitivity Questionnaire, and the Highly Sensitive Person Scale, respectively. Study 1 found that autistic traits were positively correlated with non-pain sensitivity, but not associated with pain sensitivity. Study 2 recruited 1,167 participants whose autistic traits were assessed using the AQ. Subsequently, thirty-three participants who scored within the top 10% and bottom 10% on the AQ were selected into High-AQ and Low-AQ groups, respectively, to explore the cognitive-neural responses of individuals with autistic traits to both painful and non-painful stimuli with event-related potential (ERP) technology. Results of Study 2 showed that the High-AQ group showed higher intensity ratings, more negative emotional reactions, and larger N1 amplitudes than the Low-AQ group to the non-painful stimuli, but no difference of response to the painful stimuli was found between High-AQ and Low-AQ groups. These findings suggest that individuals with autistic traits may experience enhanced non-painful sensation but intact painful sensation.
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Lysine crotonylation (Kcr) is a recently discovered histone acylation modification that is closely associated with gene expression, cell proliferation, and the maintenance of stem cell pluripotency and indicates the transcriptional activity of genes and the regulation of various biological processes. During cell culture, the introduction of exogenous croconic acid disodium salt (Nacr) has been shown to modulate intracellular Kcr levels. Although research on Kcr has increased, its role in cell growth and proliferation and its potential regulatory mechanisms remain unclear compared to those of histone methylation and acetylation. Our investigation demonstrated that the addition of 5 mM Nacr to cultured bovine fibroblasts increased the expression of genes associated with Kcr modification, ultimately promoting cell growth and stimulating cell proliferation. Somatic cell nuclear transfer of donor cells cultured in 5 mM Nacr resulted in 38.1% blastocyst development, which was significantly greater than that in the control group (25.2%). This research is important for elucidating the crotonylation modification mechanism in fibroblast proliferation to promote the efficacy of somatic cell nuclear transfer.
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Proliferação de Células , Fibroblastos , Histonas , Técnicas de Transferência Nuclear , Animais , Bovinos , Fibroblastos/metabolismo , Fibroblastos/citologia , Proliferação de Células/efeitos dos fármacos , Histonas/metabolismo , Desenvolvimento Embrionário , Blastocisto/metabolismo , Blastocisto/citologia , Lisina/metabolismo , Crotonatos/metabolismo , Células Cultivadas , Processamento de Proteína Pós-Traducional , FemininoRESUMO
Osteosarcoma (OS) is a common primary malignant bone tumor, and it is necessary to further investigate the molecular mechanism of OS progression. The expression of kinetochore associated protein 1 (KNTC1) and minichromosome maintenance 2 (MCM2) was detected by immunohistochemistry, quantitative PCR (qPCR) and Western blot. Gene knockdown or overexpression cell models were constructed and the proliferation, apoptosis, cell cycle and migration were detected in vitro, besides, xenograft models were established to explore the effects of KNTC1 downregulation in vivo. Public databased and bioinformatics analysis were performed to screen the downstream molecules and determine the expression of MCM2 in cancers. KNTC1 was overexpressed in OS tissues and positively correlated with overall survival of OS patients. KNTC1 knockdown inhibited the proliferation and migration, and arrested G2 phase, and induced apoptosis. Besides, KNTC1 downregulation restricted the xenograft tumor formation. MCM2, one of the coexpressed genes, was highly expressed in sarcoma and downregulated after KNTC1 knockdown. MCM2 overexpression heightened the proliferation and migration ability of OS cells, which was reversed the inhibiting effects of KNTC1 knockdown. KNTC1 was overexpressed in OS and promoted the progression of OS by upregulating MCM2.
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Apoptose , Neoplasias Ósseas , Movimento Celular , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Componente 2 do Complexo de Manutenção de Minicromossomo , Osteossarcoma , Animais , Feminino , Humanos , Masculino , Camundongos , Apoptose/genética , Neoplasias Ósseas/genética , Neoplasias Ósseas/patologia , Neoplasias Ósseas/metabolismo , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Camundongos Endogâmicos BALB C , Camundongos Nus , Componente 2 do Complexo de Manutenção de Minicromossomo/genética , Componente 2 do Complexo de Manutenção de Minicromossomo/metabolismo , Osteossarcoma/patologia , Osteossarcoma/genética , Osteossarcoma/metabolismo , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
The widespread existence of liquid crystal monomers (LCMs) in various environmental matrices has been demonstrated, yet studies on the toxicological effects of LCMs are considerably scarce and are urgently needed to be conducted to assess the adverse impacts on ecology and human health. Here, we conducted a bacteriological study on two representative human commensal bacteria, Escherichia coli (E. coli) and Staphylococcus epidermidis (S. epidermidis), to investigate the effect of LCMs at human-relevant dosage and maximum environmental concentration on growth, metabolome, enzymatic activity, and mRNA expression. Microbial growth results exhibited that the highest inhibition ratio of LCMs on S. epidermidis reached 33.6% in our set concentration range, while the corresponding data on E. coli was only 14.3%. Additionally, LCMs showed more dose-dependent toxicity to S. epidermidis rather than E. coli. A novel in vivo solid-phase microextraction (SPME) fiber was applied to capture the in vivo metabolites of microorganisms. In vivo metabolomic analyses revealed that dysregulated fatty acid metabolism-related products of both bacteria accounted for >50% of the total number of differential substances, and the results also showed the species-specific and concentration-dependent metabolic dysregulation in LCM-exposed bacteria. The determination of enzymatic activity and mRNA relative expression levels related to oxidative stress confirmed our speculation that the adverse effects were related to the oxidative metabolism of fatty acids. This study complements the gaps in toxicity data for LCMs against bacteria and provides a new and important insight regarding metabolic dysregulation induced by environmental LCMs in human commensal bacteria.
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BACKGROUND: Doxorubicin is an effective chemotherapeutic agent, but its use is limited by acute and chronic cardiotoxicity. Exercise training has been shown to protect against doxorubicin-induced cardiotoxicity, but the involvement of immune cells remains unclear. This study aimed to investigate the role of exercise-derived B cells in protecting against doxorubicin-induced cardiotoxicity and to further determine whether B cell activation and antibody secretion play a role in this protection. METHODS: Mice that were administered with doxorubicin (5 mg/kg per week, 20 mg/kg cumulative dose) received treadmill running exercise. The adoptive transfer of exercise-derived splenic B cells to µMT-/- (B cell-deficient) mice was performed to elucidate the mechanism of B cell regulation that mediated the effect of exercise. RESULTS: Doxorubicin-administered mice that had undergone exercise training showed improved cardiac function, and low levels of cardiac apoptosis, atrophy, and fibrosis, and had reduced cardiac antibody deposition and proinflammatory responses. Similarly, B cell pharmacological and genetic depletion alleviated doxorubicin-induced cardiotoxicity, which phenocopied the protection of exercise. In vitro performed coculture experiments confirmed that exercise-derived B cells reduced cardiomyocyte apoptosis and fibroblast activation compared with control B cells. Importantly, the protective effect of exercise on B cells was confirmed by the adoptive transfer of splenic B cells from exercised donor mice to µMT-/- recipient mice. However, blockage of Fc gamma receptor IIB function using B cell transplants from exercised Fc gamma receptor IIB-/- mice abolished the protection of exercise-derived B cells against doxorubicin-induced cardiotoxicity. Mechanistically, we found that Fc gamma receptor IIB, an important B cell inhibitory receptor, responded to exercise and increased B cell activation threshold, which participated in exercise-induced protection against doxorubicin-induced cardiotoxicity. CONCLUSIONS: Our results demonstrate that exercise training protects against doxorubicin-induced cardiotoxicity by upregulating Fc gamma receptor IIB expression in B cells, which plays an important anti-inflammatory role and participates in the protective effect of exercise against doxorubicin-induced cardiotoxicity.
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Cardiotoxicidade , Miócitos Cardíacos , Camundongos , Animais , Cardiotoxicidade/metabolismo , Miócitos Cardíacos/metabolismo , Doxorrubicina/toxicidade , ApoptoseRESUMO
Dezhou donkey is one of the representative local breeds in China, which is mainly divided into two strains: Sanfen and Wutou. There are obvious differences in coat color between the two strains. The former shows light points around the eyes, around the muzzle and under the belly, while the latter is completely solid black. In this study, genome-wide association analysis was performed for the differences in coat color traits between the Sanfen (n = 97) and Wutou (n = 108) strains using a novel donkey 40K liquid chip developed based on GenoBaits technology, to identify genomic regions and causal genes that could explain this variation. We also used FST and The cross-population composite likelihood ratio test (XPCLR) analyses to explore selected regions related to coat color differences. We identified one significant region on chromosome 15, with the most significant SNP located within the agouti signaling protein (ASIP) gene. At the same time, both FST and XPCLR methods detected the same selected region on chromosome 15, and ASIP was the gene with the strongest signal. ASIP and melanocortin 1 receptor (MC1R) control the ratio of eumelanin to pheomelanin through their protein activity. They are deeply involved in the process of melanosome organation and melanogenesis, thus affecting mammals' coat color variation. We used a range of genome-wide approach to identify the genetic basis of coat color variation in Dezhou donkeys. The results provide a supplement to the color variation study in Chinese donkeys at the genome-wide level, and preliminarily verified the reliability of the Molbreeding Donkey No. 1 40K liquid chip.
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Equidae , Estudo de Associação Genômica Ampla , Animais , Equidae/genética , Reprodutibilidade dos Testes , Radioisótopos de PotássioRESUMO
Cyclic volatile methylsiloxane (cVMS) is extensively used in consumer products and frequently detected in various environmental media, including water and air. In this study, we developed reliable and convenient methods to sample three cVMS compounds: octamethylcyclotetrasiloxane (D4), decamethylcyclopentasiloxane (D5), and dodecamethylcyclohexasiloxane (D6) in water and air samples collected from different tanks within a wastewater treatment plant (WWTP). The concentrations of D4, D5, and D6 in the water samples ranged from 0.40 to 8.0 µg L-1, 0.35 to 91 µg L-1, and 0.54 to 17 µg L-1, respectively. In the air samples, these concentrations varied from 0.34 to 20 µg m-3, 0.34 to 128 µg m-3, and 0.08 to 12 µg m-3, respectively. It is worth noting that the air-water distribution coefficient (Kaw) for these three cVMS exhibited a strong correlation with their water solubility. Moreover, fugacity fractions indicated a net evaporation process from water to the atmosphere. Furthermore, we investigated the distribution of cVMS between the gaseous and particulate phases. The results revealed a significant fraction, exceeding 72 %, of cVMS resided in the gas phase. D4 and D5 predominate in the gaseous phase, while D5 and D6 are the principal constituents within the particulate phase. The distribution coefficient characterizing the partitioning of cVMS compounds between the gaseous and particulate (Kp) exhibited a strong correlation with their corresponding octanol-air partitioning coefficients (Koa). These findings contribute to a better understanding of the distribution of cVMS in diverse environmental media and the underlying mechanism governing their dispersion.
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During deep underground coal gasification, the semicoke produced by the pyrolysis of dense coal cores is an important material for its gasification and combustion. In this paper, pressurized pyrolysis experiments were carried out on dense coal cores at 700 °C and pressures of 1, 2, and 3 MPa using a shaft furnace. The resulting semicoke and raw coal were analyzed using the characterization methods such as the N2 isothermal adsorption/desorption and scanning electron microscopy, Fourier transform infrared spectrometry (FTIR), and a pressurized thermogravimetric analyzer coupled with a FTIR spectrometer. The pyrolysis gas generation characteristics during pressurized pyrolysis were studied. The mechanisms of evolution of aliphatic functional groups and pore structures in semicoke during pressurized pyrolysis were revealed. The results indicate that the increase in pressure obviously changed the gas composition, most notably, the relative content of CH4 and H2 in the pyrolysis gas. The methane in the pyrolysis gas during pressurized pyrolysis of dense coal cores is mainly from the secondary reaction. As the pyrolysis pressure increased, the ratio of -CH2-/-CH3 became smaller, indicating that the pressure promoted the breakage of the long fat chains. With the increase of the pyrolysis pressure, the surface deformation of pressurized pyrolysis semicoke increases, and the pore structure becomes more abundant.
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BACKGROUND: Gut microbiota plays a significant role in host survival, health, and diseases; however, compared to other livestock, research on the gut microbiome of donkeys is limited. RESULTS: In this study, a total of 30 donkey samples of rectal contents from six regions, including Shigatse, Changdu, Yunnan, Xinjiang, Qinghai, and Dezhou, were collected for metagenomic sequencing. The results of the species annotation revealed that the dominant phyla were Firmicutes and Bacteroidetes, and the dominant genera were Bacteroides, unclassified_o_Clostridiales (short for Clostridiales) and unclassified_f_Lachnospiraceae (short for Lachnospiraceae). The dominant phyla, genera and key discriminators were Bacteroidetes, Clostridiales and Bacteroidetes in Tibet donkeys (Shigatse); Firmicutes, Clostridiales and Clostridiales in Tibet donkeys (Changdu); Firmicutes, Fibrobacter and Tenericutes in Qinghai donkeys; Firmicutes, Clostridiales and Negativicutes in Yunnan donkeys; Firmicutes, Fibrobacter and Fibrobacteres in Xinjiang donkeys; Firmicutes, Clostridiales and Firmicutes in Dezhou donkeys. In the functional annotation, it was mainly enriched in the glycolysis and gluconeogenesis of carbohydrate metabolism, and the abundance was the highest in Dezhou donkeys. These results combined with altitude correlation analysis demonstrated that donkeys in the Dezhou region exhibited strong glucose-conversion ability, those in the Shigatse region exhibited strong glucose metabolism and utilization ability, those in the Changdu region exhibited a strong microbial metabolic function, and those in the Xinjiang region exhibited the strongest ability to decompose cellulose and hemicellulose. CONCLUSION: According to published literature, this is the first study to construct a dataset with multi-regional donkey breeds. Our study revealed the differences in the composition and function of gut microbes in donkeys from different geographic regions and environmental settings and is valuable for donkey gut microbiome research.
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Equidae , Microbioma Gastrointestinal , Bacteroidetes , China , Clostridiales , Firmicutes , Equidae/microbiologiaRESUMO
To date, the origins, domestication, and genetic structure of Chinese Mongolian horses (CMH) are poorly understood. Furthermore, there have been sparse reports on the genetic differences between CMH and Thoroughbred. In order to determine their genetic structure, understand their genetic relationships, and explore their domestication processes, we performed an extensive survey of creatine kinase (muscle isoenzyme; CKM) variations among six populations of indigenous CMH, cultivated Sanhe horses, and imported Thoroughbred. Twenty-three single-nucleotide polymorphisms were found among the 343 horse sequences. From these, 40 haplotypes were inferred. Haplotype diversity (H) values differed from 0.6424 to 0.7881 and nucleotide diversity (π) values ranged from 0.00150 to 0.00211. The differences between Thoroughbred population and other Chinese horse populations were large, but only small differences were observed among Chinese horse populations with respect to CKM intron sequences suggesting that the domestication history, breeding measures, and origins of these horse populations are completely different. Results suggest that Sanhe and CMH are very closely related and the introgression (interbreeding) between them is serious. Our results suggest that Sanhe and Wushen require prompt and powerful protection. Overall, CKM intron was an appropriate marker for the determination of genetic relationships among horse populations and breeds.
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Variação Genética , Polimorfismo de Nucleotídeo Único , Cavalos/genética , Animais , Íntrons/genética , Filogenia , Polimorfismo de Nucleotídeo Único/genética , HaplótiposRESUMO
OBJECTIVES: Eicosapentaenoic acid in its ethyl ester form is the single active component of icosapent ethyl (IPE). This study was a phase III, multi-center trial assessing the safety and efficiency of IPE for treating very high triglyceride (TG) in a Chinese cohort. METHODS: Patients having TG levels (5.6-22.6 mmol/L) were enrolled and randomly assigned to receive a treatment of oral intake of 4 g or 2 g/day of IPE, or placebo. Before and after 12 weeks of treatment, TG levels were assessed and the median was calculated to determine the change between the baseline and week 12. In addition to examining TG levels, the impact of such treatments on other lipid changes was also investigated. The official Drug Clinical Trial Information Management Platform has registered this study (CTR20170362). RESULTS: Random assignments were performed on 373 patients (mean age 48.9 years; 75.1% male). IPE (4 g/day) lowered TG levels by an average of 28.4% from baseline and by an average of 19.9% after correction for placebo (95% CI: 29.8%-10.0%, P < 0.001). In addition, plasma concentration of non-high-density lipoprotein cholesterol (non-HDL-C), very low-density lipoprotein (VLDL) cholesterol, and VLDL-TG remarkedly reduced after IPE (4 g/day) treatment by a median of 14.6%, 27.9%, and 25.2%, respectively compared with participants in placebo group. Compared to the placebo, neither 4 nor 2 g of IPE daily elevated LDL-C levels with statistical significance. IPE was well tolerated by all the treatment groups. CONCLUSIONS: IPE at 4 g/day dramatically lowered other atherogenic lipids without a noticeable increase in LDL-C, thereby decreasing TG levels in an exceptionally high-TG Chinese population.
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Inibidores de Hidroximetilglutaril-CoA Redutases , Hipertrigliceridemia , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Ácido Eicosapentaenoico/uso terapêutico , LDL-Colesterol , Resultado do Tratamento , Hipertrigliceridemia/tratamento farmacológico , Triglicerídeos , VLDL-Colesterol , Método Duplo-Cego , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêuticoRESUMO
RATIONALE: Meningoencephalomyelitis and visceral dissemination infection are rare but life-threatening complications of either the primary infection or reactivation of varicella-zoster virus (VZV) in immunocompromised patients. To date, few studies have reported the co-existence of VZV meningoencephalomyelitis and the visceral dissemination of VZV infection. PATIENT CONCERNS: A 23-year-old male was diagnosed with lupus nephritis class III and was being treated with oral prednisone and tacrolimus. The patient exhibited herpes zoster 21-day after the initiation of therapy and experienced unbearable abdominal pain and generalized seizures 11 days after the onset of a zoster rash. Magnetic resonance imaging showed progressive lesions in the cerebrum, brainstem, and cerebellum, as well as meningeal thickening and thoracic myelitis. Computed tomography showed pulmonary interstitial infiltration, partial intestinal dilatation, and effusion. Metagenomic next-generation sequencing revealed 198,269 and 152,222 VZV-specific reads in the cerebrospinal fluid and bronchoalveolar lavage fluid, respectively. DIAGNOSES: Based on the clinical and genetic findings, this patient was finally diagnosed with VZV meningoencephalomyelitis and visceral disseminated VZV infection. INTERVENTIONS: The patient received intravenous acyclovir (0.5 g every 8 hours) combined with plasma exchange and intravenous immunoglobulin. Treatment against secondary bacterial and fungal infections, organ support therapy and rehabilitation training were given simultaneously. OUTCOME: The patient's peripheral muscle strength did not improve and repeated metagenomic next-generation sequencing showed the persistence of VZV-specific reads in the cerebrospinal fluid. The patient finally abandoned therapy due to financial constraints at the 1-month follow-up. LESSONS: Patients with autoimmune diseases receiving immunosuppressive therapy should be warned about the possibility of developing serious neurological infections and visceral disseminated VZV infections as side effects. Early diagnosis and the early initiation of intravenous acyclovir therapy are important for such cases.
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Varicela , Encefalomielite , Herpes Zoster , Nefrite Lúpica , Infecção pelo Vírus da Varicela-Zoster , Masculino , Humanos , Adulto Jovem , Adulto , Herpesvirus Humano 3 , Nefrite Lúpica/tratamento farmacológico , Herpes Zoster/tratamento farmacológico , Infecção pelo Vírus da Varicela-Zoster/complicações , Aciclovir/uso terapêuticoRESUMO
Eucommiae Folium (Duzhongye) is a traditional Chinese medicine with a long history of use in China. However, its quality-marker in Chinese Pharmacopoeia is poorly defined nowadays. The study, therefore, conducted an ultra-high-performance liquid chromatography coupled with hybrid quadrupole-orbitrap tandem mass spectrometry analysis to obtain accurate data. The obtained data were then compared with the authentic standards library using Xcalibur 4.1 software package and TraceFinder General Quan. Through the comparison, the study has putatively identified 26 bioactive compounds, which include 17 flavonoid derivatives (catechin, quercetin 3-gentiobioside, quercetin 3-O-ß-D-glucose-7-O-ß-D-gentiobioside, taxifolin, myricetin 3-O-galactoside, myricitrin, hyperoside, rutin, isoquercitrin, quercetin 3-O-ß-xylopyranoside, quercitrin, isorhamnetin 3-O-ß-D-glucoside, quercetin, kaempferol, S-eriodictyol, S-naringenin, and phloridzin), four caffeoylquinic acids (neochlorogenic acid, chlorogenic acid, isochlorogenic acid A, and isochlorogenic acid C), two alkaloids (vincamine and jervine), one lignan (pinoresinol), one xanthone (cowaxanthone B), and one steroid (cholesteryl acetate). Of these, flavonoid isoquercitrin is recommended as the new and additional pharmacopeia quality-marker candidate, which can not only overcome the unreliability of old quality-marker but also recognize the possible counterfeit.
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Quercetina , Espectrometria de Massas em Tandem , Cromatografia Líquida de Alta Pressão/métodos , Quercetina/análise , Flavonoides/análise , Folhas de Planta/químicaRESUMO
BACKGROUND: Voriconazole is a second-generation triazole that is used to prevent and treat invasive fungal infections. The purpose of this study was to evaluate the pharmacokinetic equivalency of a test formulation and reference formulation (Vfend®) of Voriconazole. MATERIALS AND METHODS: This was a randomized, open-label, single-dose, two-treatment, two-sequence, two-cycle, crossover phase I trial. The 48 subjects were equally divided into 4 mg/kg and 6 mg/kg groups. Within each group, the subjects were randomized 1:1 to the test or reference formulation.. After a 7-day washout period, crossover formulations were administered. The blood samples were collected at 0.5, 1.0, 1.33,1.42,1.5, 1.75, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 12.0, 24.0, 36.0, 48.0 h later in the 4 mg/kg group, while at 0.5, 1.0, 1.5, 1.75, 2.0, 2.08, 2.17, 2.33, 2.5, 3.0, 4.0, 6.0, 8.0, 12.0, 24.0, 36.0, 48.0 h later in the 6 mg/kg group. The plasma concentrations of Voriconazole were determined by Liquid chromatography-tandem mass spectrometry (LC-MS/MS). The safety of the drug was evaluated. RESULTS: The 90% confidence intervals (CIs) of the ratio of geometric means (GMRs) of Cmax, AUC0-t, and AUC0-∞ in both 4 mg/kg and 6 mg/kg groups were within the prespecified bioequivalence limits between 80 ~ 125%. In the 4 mg/kg groups, 24 subjects were enrolled and completed the study. The mean Cmax was (2.552 ± 0.448) µg/mL, AUC0-t was (11.875 ± 7.157) h*µg/mL and AUC0-∞ was (12.835 ± 9.813) h*µg/mL after a single dose of 4 mg/kg test formulation. The mean Cmax was (2.615 ± 0.464) µg/mL, AUC0-t was (12.500 ± 7.257) h*µg/mL and AUC0-∞ was (13.416 ± 9.485) h*µg/mL after a single dose of 4 mg/kg reference formulation. In the 6 mg/kg groups, 24 subjects were enrolled and completed the study. The mean Cmax was (3.538 ± 0.691) µg/mL, AUC0-t was (24.976 ± 12.364) h*µg/mL and AUC0-∞ was (26.212 ± 14.057) h*µg/mL after a single dose of 6 mg/kg test formulation. The mean Cmax was (3.504 ± 0.667) µg/mL AUC0-t was (24.990 ± 12.455) h*µg/mL and AUC0-∞ was (26.160 ± 13.996) h*µg/mL after a single dose of 6 mg/kg reference formulation. Serious adverse event (SAE) was not observed. CONCLUSION: In both 4 mg/kg group and 6 mg/kg group, equivalent pharmacokinetic characteristics that satisfied the criteria of bioequivalence for both test and reference formulations of Voriconazole. TRIAL REGISTRATION: NCT05330000 (15/04/2022).
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Voriconazol , Humanos , Cromatografia Líquida , População do Leste Asiático , Infusões Intravenosas , Espectrometria de Massas em Tandem , Voriconazol/farmacocinéticaRESUMO
BACKGROUND: Evidence on the temporal sequences between balance and depressive symptoms is limited, and no studies have compared the strength of each direction. This study aimed to assess the association between balance performance and depressive symptoms among community-dwelling older adults, and further to explore the driving factors in the dynamic association. METHODS: Data were obtained from the English Longitudinal Study of Aging (ELSA). Overall, 3971 community-residing adults aged 50 years or older were assessed at 2004/05, 2008/09, and 2012/13. Balance was measured using three progressively more difficult tasks (side-by-side, semi-tandem, and full-tandem). Depressive symptoms were determined with a dichotomous eight-item version of the Center for Epidemiologic Studies Depression Scale (CES-D). Cross-lagged panel models were used to test the reciprocal relationships between balance and depressive symptoms. RESULTS: Our analyses revealed that earlier poorer balance predicted later worse depressive symptoms consistently across waves (ßW2-W4 = -0.058, P < .05, ßW4-W6 = -0.067, P < .001). Conversely, the higher scores of depressive symptoms at wave 4 predicted lower level of balance at wave 6 (ßW4-W6 = -0.038, P = .018). The cross-lagged effects of balance on depressive symptoms were over all stronger than the reverse effects. CONCLUSIONS: These findings add novel insights into the temporal directionality of balance and depressive symptoms among community-dwelling older adults, and suggest that a predominance of balance disorder effects. Interventional strategy should aim to increase balance ability from earlier stages to promote successful aging.
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Envelhecimento , Depressão , Humanos , Idoso , Estudos Longitudinais , Depressão/epidemiologia , Vida IndependenteRESUMO
4',5,7-OHs are common substituents of natural flavonoids, a type of effective phenolic antioxidant. However, the antioxidant processes between 4',5,7-trihydroxyflavonoids with different structural types have not been compared systematically, and the antioxidant products are challenging to determine. This study compared four 4',5,7-trihydroxyflavonoids, including apigenin, genistein, kaempferol, and naringenin. In quantum chemical analyses, the four 4',5,7-trihydroxyflavonoids showed different thermodynamic properties, and the C4'-OH (or C3-OH of kaempferol) possessed the strongest activity. Moreover, the reaction rate constants were larger when a hydrogen atom was transferred from C4'-OH (or C3-OH of kaempferol) than from C5-OH. When different atoms were linked to 2,2-diphenyl-1-picrylhydrazyl radical (DPPHË), the C3'-DPPH adducts showed the smallest energy. In experimental assays, the scavenging ability for neutral free radicals, radical cations, and radical anions was negatively correlated with the corresponding theoretical parameters. Finally, mass spectroscopy detected the apigenin-DPPHË, genistein-DPPHË, and naringenin-DPPHË adduct peaks. In conclusion, the structural type of 4',5,7-trihydroxyflavonoids can affect the antioxidant ability, site, and speed, but not the mechanism. After hydrogen abstraction at C4'-OH, 4',5,7-trihydroxyflavones, 4',5,7-trihydroxyisoflavones, and 4',5,7-trihydroxyflavanones will produce antioxidant products via C3'-radical linking.
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Herein, we demonstrate the ability of a dual-purpose periodic mesoporous organosilica (PMO) probe to track the complex chlorinated paraffin (CP) composition in living animals by assembling it as an adsorbent-assisted atmospheric pressure chemical ionization Fourier-transform ion cyclotron resonance mass spectrometry (APCI-FT-ICR-MS) platform and synchronously performing it as the in vivo sampling device. First, synchronous solvent-free ionization and in-source thermal desorption of CP homologues were achieved by the introduction of the PMO adsorbent-assisted APCI module, generating exclusive adduct ions ([M - H]-) of individual CP homologues (CnClm) with enhanced ionization efficiency. Improved detection limits of short- and medium-chain CPs (0.10-24 and 0.48-5.0 pg/µL) were achieved versus those of the chloride-anion attachment APCI-MS methods. Second, the dual-purpose PMO probe was applied to extract the complex CP compositions in living animals, following APCI-FT-ICR-MS analysis. A modified pattern-deconvolution algorithm coupled with the sampling-rate calibration method was used for the quantification of CPs in living fish. In vivo quantification of a tilapia exposed to technical CPs for 7 days was successfully achieved, with ∑SCCPs and ∑MCCPs of the sampled fish calculated to be 1108 ± 289 and 831 ± 266 µg/kg, respectively. Meanwhile, 58 potential CP metabolites were identified in living fish for the first time during in vivo sampling of CPs, a capacity that could provide an important tool for future study regarding its expected risks to humans and its environmental fate.
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Hidrocarbonetos Clorados , Parafina , Humanos , Animais , Parafina/análise , Parafina/química , Hidrocarbonetos Clorados/análise , Hidrocarbonetos Clorados/química , Monitoramento Ambiental/métodos , Espectrometria de Massas/métodos , Peixes , Cloretos/análiseRESUMO
The present study developed a smart and novel strategy to elucidate the linkage and stereochemistry characters during phenolic antioxidant product formation. A series of phenolic isomers or analogues were treated with 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide radical, to create 16 antioxidant dimerization reactions in aqueous solution. The products were rapidly identified by ultraperformance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass-spectrometry. Through a systematic function-structure relationship analysis of these reactions and theoretical calculations, it is concluded that the phenolic antioxidant product is formed via linear linkage or furanocyclic linkage. The linear linkage is fulfilled via a radical coupling and controlled by the O-O linkage exclusion, meta-linkage exclusion, and catechol-activated principles. However, when an exocyclic π-bond conjugates with the phenolic core and is affixed at the -OH para-position, the furanocyclic linkage may occur via a subsequent intramolecular Michael addition. The intramolecular addition always lacks Re-attack to show "α,ß diastereoselectivity." The α,ß diastereoselectivity is the stereochemistry character of furanocyclic linkage during phenolic antioxidant product formation. All these novel findings can benefit not only the field food science but also other fields as well.
Assuntos
Antioxidantes , Fenóis , Antioxidantes/química , Fenóis/química , Espectrometria de Massas por Ionização por Electrospray , Cromatografia Líquida de Alta PressãoRESUMO
Antibiotic pollution has become a global environmental pollution problem. Chlorophyll fluorescence is one of the most important indicators reflecting the degree to which plants are influenced by the environment. Ofloxacin (OFL) is a highly toxic antibiotic pollutant, and there are few reports on the effects of changes in OFL levels on tomato chlorophyll fluorescence parameters. In this study, we investigated the responses of tomato growth, photosynthetic activity and chlorophyll fluorescence kinetics to exogenous OFL exposure (as the concentrations of 0, 2.5, 5, 10 and 20 mg L-1). The results showed that lower concentrations of OFL (2.5 mg L-1) had little impact on tomato growth, while plant growth was inhibited with the OFL concentration increasing. At higher OFL concentrations (5, 10 and 20 mg L-1), chloroplasts ruptured, and chlorophyll became degraded, resulting in leaf etiolation. Furthermore, the photosynthetic and photochemical efficiency and electron transfer rate were significantly inhibited by OFL. Moreover, damage to the oxygen-evolving complex on the donor side of PSâ ¡ prevented electron transfer from QA to QB and led to photoinhibition. In conclusion, higher OFL concentration reduced photosynthesis by destroying the photosynthetic mechanism in tomato, resulting in tomato leaf etiolation and plant growth inhibition.