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1.
PLoS Comput Biol ; 20(5): e1012118, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38743803

RESUMO

In experiments, the distributions of mRNA or protein numbers in single cells are often fitted to the random telegraph model which includes synthesis and decay of mRNA or protein, and switching of the gene between active and inactive states. While commonly used, this model does not describe how fluctuations are influenced by crucial biological mechanisms such as feedback regulation, non-exponential gene inactivation durations, and multiple gene activation pathways. Here we investigate the dynamical properties of four relatively complex gene expression models by fitting their steady-state mRNA or protein number distributions to the simple telegraph model. We show that despite the underlying complex biological mechanisms, the telegraph model with three effective parameters can accurately capture the steady-state gene product distributions, as well as the conditional distributions in the active gene state, of the complex models. Some effective parameters are reliable and can reflect realistic dynamic behaviors of the complex models, while others may deviate significantly from their real values in the complex models. The effective parameters can also be applied to characterize the capability for a complex model to exhibit multimodality. Using additional information such as single-cell data at multiple time points, we provide an effective method of distinguishing the complex models from the telegraph model. Furthermore, using measurements under varying experimental conditions, we show that fitting the mRNA or protein number distributions to the telegraph model may even reveal the underlying gene regulation mechanisms of the complex models. The effectiveness of these methods is confirmed by analysis of single-cell data for E. coli and mammalian cells. All these results are robust with respect to cooperative transcriptional regulation and extrinsic noise. In particular, we find that faster relaxation speed to the steady state results in more precise parameter inference under large extrinsic noise.

2.
Huan Jing Ke Xue ; 45(5): 3016-3026, 2024 May 08.
Artigo em Chinês | MEDLINE | ID: mdl-38629562

RESUMO

Sweet sorghum has a large biomass and strong cadmium (Cd) absorption capacity, which has the potential for phytoremediation of Cd-contaminated soil. In order to study the Cd phytoremediation effect of sweet sorghum assisted with citric acid on the typical parent materials in southern China, a field experiment was carried out in two typical parent material farmland areas (neutral purple mud field and jute sand mud field) with Cd pollution in Hunan Province. The results showed that:① Citric acid had no inhibitory effect on the growth of sweet sorghum. After the application of citric acid, the aboveground biomass of sweet sorghum at the maturity stage increased by 10.1%-24.7%. ② Both sweet sorghum planting and citric acid application reduced the soil pH value, and the application of citric acid further reduced the soil pH value at each growth stage of sweet sorghum; this decrease was greater in the neutral purple mud field, which decreased by 0.24-0.72 units. ③ Both sweet sorghum planting and citric acid application reduced the total amount of soil Cd, and the decreases in the neutral purple mud field and jute sand mud field were 23.8%-52.2% and 17.1%-31.8%, respectively. The acid-extractable percentage of soil Cd in both places increased by 38.6%-147.7% and 4.8%-22.7%, respectively. ④ The application of citric acid could significantly increase the Cd content in various tissues of sweet sorghum. The Cd content in the aboveground part of the plant in the neutral purple mud field was higher than that in the jute sand mud field, and the Cd content in stems and leaves was 0.25-1.90 mg·kg-1 and 0.21-0.64 mg·kg-1, respectively. ⑤ After applying citric acid, the Cd extraction amount of sweet sorghum in neutral purple mud soil in the mature stage reached 47.56 g·hm-2. In summary, citric acid could enhance the efficiency of sweet sorghum in the phytoremediation of Cd-contaminated soil, and the effect was better in neutral purple mud fields. This technology has the potential for remediation coupled with agro-production for heavy metal-contaminated farmland.


Assuntos
Poluentes do Solo , Sorghum , Cádmio/análise , Biodegradação Ambiental , Solo , Areia , Ácido Cítrico , Poluentes do Solo/análise , China , Grão Comestível/química
3.
BMC Public Health ; 24(1): 1097, 2024 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-38643079

RESUMO

BACKGROUND: To analyse the association among the simultaneous effects of dietary intake, daily life behavioural factors, and frailty outcomes in older Chinese women, we predicted the probability of maintaining physical robustness under a combination of different variables. METHODS: The Fried frailty criterion was used to determine the three groups of "frailty", "pre-frailty", and "robust", and a national epidemiological survey was performed. The three-classification decision tree model was fitted, and the comprehensive performance of the model was evaluated to predict the probability of occurrence of different outcomes. RESULTS: Among the 1,044 participants, 15.9% were frailty and 50.29% were pre-frailty; the overall prevalence first increased and then decreased with age, reaching a peak at 70-74 years of age. Through univariate analysis, filtering, and embedded screening, eight significant variables were identified: staple food, spices, exercise (frequency, intensity, and time), work frequency, self-feeling, and family emotions. In the three-classification decision tree, the values of each evaluation index of Model 3 were relatively average; the accuracy, recall, specificity, precision, and F1 score range were between 75% and 84%, and the AUC was also greater than 0.800, indicating excellent performance and the best interpretability of the results. Model 3 takes exercise time as the root node and contains 6 variables and 10 types, suggesting the impact of the comprehensive effect of these variables on robust and non-robust populations (the predicted probability range is 6.67-93.33%). CONCLUSION: The combined effect of these factors (no exercise or less than 0.5 h of exercise per day, occasional exercise, exercise at low intensity, feeling more tired at work, and eating too many staple foods (> 450 g per day) are more detrimental to maintaining robustness.


Assuntos
Fragilidade , Humanos , Feminino , Idoso , Fragilidade/diagnóstico , Idoso Fragilizado , Dieta , Exercício Físico , Estilo de Vida
4.
EMBO Mol Med ; 16(5): 1143-1161, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38565806

RESUMO

Accurately predicting and selecting patients who can benefit from targeted or immunotherapy is crucial for precision therapy. Trophoblast cell surface antigen 2 (Trop2) has been extensively investigated as a pan-cancer biomarker expressed in various tumours and plays a crucial role in tumorigenesis through multiple signalling pathways. Our laboratory successfully developed two 68Ga-labelled nanobody tracers that can rapidly and specifically target Trop2. Of the two tracers, [68Ga]Ga-NOTA-T4, demonstrated excellent pharmacokinetics in preclinical mouse models and a beagle dog. Moreover, [68Ga]Ga-NOTA-T4 immuno-positron emission tomography (immunoPET) allowed noninvasive visualisation of Trop2 heterogeneous and differential expression in preclinical solid tumour models and ten patients with solid tumours. [68Ga]Ga-NOTA-T4 immunoPET could facilitate clinical decision-making through patient stratification and response monitoring during Trop2-targeted therapies.


Assuntos
Antígenos de Neoplasias , Moléculas de Adesão Celular , Neoplasias , Tomografia por Emissão de Pósitrons , Antígenos de Neoplasias/metabolismo , Antígenos de Neoplasias/imunologia , Humanos , Animais , Moléculas de Adesão Celular/metabolismo , Neoplasias/diagnóstico por imagem , Neoplasias/imunologia , Camundongos , Cães , Tomografia por Emissão de Pósitrons/métodos , Feminino , Anticorpos de Domínio Único/imunologia
5.
In Vitro Cell Dev Biol Anim ; 60(4): 343-353, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38504085

RESUMO

MicroRNAs (miRNAs) play an important role in articular cartilage damage in osteoarthritis (OA). However, the biological role of miRNAs in the chondrogenic differentiation of bone marrow mesenchymal stem cell (BMSC) remains largely unclear. Rabbit bone marrow mesenchymal stem cells (rBMSCs) were isolated, cultured, and identified. Afterwards, rBMSCs were induced to chondrogenic differentiation, examined by Alcian Blue staining. Differentially expressed miRNAs were identified in rBMSCs between induced and non-induced groups by miRNA sequencing analysis, part of which was validated via PCR assay. Cell viability and apoptosis were assessed by CCK-8 assay and Hoechst staining. Saffron O staining was utilized to assess chondrocyte hyperplasia. The expression of specific chondrogenic markers, including COL2A1, SOX9, Runx2, MMP-13, Aggrecan, and BMP-2, were measured at mRNA and protein levels. The association between beta-transducin repeat containing E3 ubiquitin protein ligase (BTRC) and miR-10a-5p in the miRNA family from rabbit (ocu-miR-10a-5p) was determined by luciferase reporter assay. A total of 76 differentially expressed miRNAs, including 52 downregulated and 24 upregulated miRNAs, were identified in rBMSCs from the induced group. Inhibition of ocu-miR-10a-5p suppressed rBMSC viability and chondrogenic differentiation, as well as downregulated the expression of ß-catenin, SOX9, COL2A1, MMP-13, and Runx2. BTRC was predicted and confirmed as a target of ocu-miR-10a-5p. Overexpression of BTRC rescued the promoting impacts of overexpressed ocu-miR-10a-5p on chondrogenic differentiation of rBMSCs and ß-catenin expression. Taken together, our data suggested that ocu-miR-10a-5p facilitated rabbit BMSC survival and chondrogenic differentiation by activating Wnt/ß-catenin signaling through BTRC.


Assuntos
Diferenciação Celular , Condrogênese , Células-Tronco Mesenquimais , MicroRNAs , Via de Sinalização Wnt , Animais , Coelhos , MicroRNAs/genética , MicroRNAs/metabolismo , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/citologia , Diferenciação Celular/genética , Condrogênese/genética , Via de Sinalização Wnt/genética , Condrócitos/metabolismo , Condrócitos/citologia , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitina-Proteína Ligases/genética , Apoptose/genética , Sobrevivência Celular , beta Catenina/metabolismo , beta Catenina/genética , Sequência de Bases , Regulação da Expressão Gênica
6.
J Lipid Res ; 65(4): 100528, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38458338

RESUMO

Dyslipidemia has long been implicated in elevating mortality risk; yet, the precise associations between lipid traits and mortality remained undisclosed. Our study aimed to explore the causal effects of lipid traits on both all-cause and cause-specific mortality. One-sample Mendelian randomization (MR) with linear and nonlinear assumptions was conducted in a cohort of 407,951 European participants from the UK Biobank. Six lipid traits, consisting of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides, apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB), and lipoprotein(a), were included to investigate the causal associations with mortality. Two-sample MR was performed to replicate the association between each lipid trait and all-cause mortality. Univariable MR results showed that genetically predicted higher ApoA1 was significantly associated with a decreased all-cause mortality risk (HR[95% CI]:0.93 [0.89-0.97], P value = 0.001), which was validated by the two-sample MR analysis. Higher lipoprotein(a) was associated with an increased risk of all-cause mortality (1.03 [1.01-1.04], P value = 0.002). Multivariable MR confirmed the direct causal effects of ApoA1 and lipoprotein(a) on all-cause mortality. Meanwhile, nonlinear MR found no evidence for nonlinearity between lipids and all-cause mortality. Our examination into cause-specific mortality revealed a suggestive inverse association between ApoA1 and cancer mortality, a significant positive association between lipoprotein(a) and cardiovascular disease mortality, and a suggestive positive association between lipoprotein(a) and digestive disease mortality. High LDL-C was associated with an increased risk of cardiovascular disease mortality but a decreased risk of neurodegenerative disease mortality. The findings suggest that implementing interventions to raise ApoA1 and decrease lipoprotein(a) levels may improve overall health outcomes and mitigate cancer and digestive disease mortality.


Assuntos
Lipídeos , Análise da Randomização Mendeliana , Humanos , Masculino , Feminino , Lipídeos/sangue , Pessoa de Meia-Idade , Fatores de Risco , Apolipoproteína A-I/sangue , Apolipoproteína A-I/genética , Lipoproteína(a)/sangue , Lipoproteína(a)/genética , Causas de Morte , Idoso
7.
Sci Rep ; 14(1): 7020, 2024 03 25.
Artigo em Inglês | MEDLINE | ID: mdl-38528015

RESUMO

Falls constitute a leading cause of unintentional injury deaths among older adults. This study aimed to examine the comprehensive characteristics of fatal falls among older individuals in Yunnan Province, China, to highlight the challenges faced in elderly care. A total of 22,798 accidental fall-related deaths were extracted from China's National Disease Surveillance Points System aged 60 and above between 2015 and 2019. Quantitative and textual data were analyzed to assess the incidence rates of initiating factors, locations, symptoms, and overall survival (OS) outcomes after falling. Hypertension emerged as the most significant intrinsic factor, especially among individuals aged between 70 and 79, female older adults, and urban residents (P < 0.001). Home was identified as the most common location where fatal falls occurred (61.19%). The head was the most commonly injured body region (58.75%). The median of OS for all fatal falls was 2 days (0.13, 30), of which deaths occurred within 24 h [9287 (49.36%)]. There were instances where timely discovery after falling did not occur in 625 cases; their median of OS was significantly shorter compared to those discovered promptly after falling (P < 0.001). Targeted interventions focusing on fall prevention and post-fall care are equally crucial for the well-being of older adults.


Assuntos
Acidentes por Quedas , Humanos , Feminino , Idoso , Acidentes por Quedas/prevenção & controle , China/epidemiologia , Fatores de Risco , População Urbana , Incidência
8.
Huan Jing Ke Xue ; 45(3): 1793-1802, 2024 Mar 08.
Artigo em Chinês | MEDLINE | ID: mdl-38471890

RESUMO

A rice pot experiment was conducted to identify the effect of silica fertilizer prepared from husk ash on the soil bioavailability of cadmium (Cd) and arsenic (As), enzyme activities, microbial community structure, and heavy metal content in brown rice at different growth stages. The results showed that the application of 0.1%-1.0% silica fertilizer-husk ash increased the pH value of soil by 0.04-0.24 units and the content of soil available silicon by 44.2%-97.5%. It also decreased the content of available Cd and available As by 16.2%-21.4% and 16.0%-24.9%, respectively. With the increase in application amount, the soil enzyme activities increased at all growth stages, and the sucrase activity and the dehydrogenase activity significantly increased by 6.3%-145.7% and 6.7%-224.1%, respectively. The analysis of the soil microbial community composition structure at mature stages showed that the application of silica fertilizer-husk ash had no effect on microbial α-diversity, but it had a significant effect on microbial ß-diversity and then promoted microbial growth and maintained the stability of the community structure. With the increase in application amount, the contents of Cd in brown rice decreased by 29.3%-89.7%, and the contents of total As and inorganic As in brown rice decreased by 7.8%-42.3% and 17.2%-44.5%, respectively. Under the application of 0.5% and 1.0% silica fertilizer-husk ash, the Cd contents in brown rice were lower than 0.2 mg·kg-1, and the inorganic As contents in brown rice were lower than 0.35 mg·kg-1. In conclusion, the silica fertilizer-husk ash can improve soil quality and reduce the contents of Cd and As in brown rice, and it is eco-friendly and can be used to remedy the paddy soil contaminated with Cd and As.


Assuntos
Arsênio , Oryza , Poluentes do Solo , Cádmio/análise , Arsênio/análise , Dióxido de Silício , Solo/química , Oryza/química , Fertilizantes/análise , Poluentes do Solo/análise
9.
Huan Jing Ke Xue ; 45(2): 1118-1127, 2024 Feb 08.
Artigo em Chinês | MEDLINE | ID: mdl-38471949

RESUMO

In this study, a field experiment was conducted to examine the effects of the application of irrigation water containing Zn at the key growth period (booting stage and filling stage) on exchangeable Cd content in the soil, Cd concentration in pore water, and Cd uptake and transport in rice in a Cd-contaminated paddy field in Liuyang City, Hunan Province. The results indicated that: ① the application of irrigation water containing Zn during the key growth period could inhibit the releasing process of exchangeable Cd from the soil into pore water. Compared with that in the control, the content of exchangeable Cd in soil was slightly changed, but the concentration of Cd in soil pore water at the mature stage was significantly reduced by 16.7%-57.6%. ② The application of irrigation water containing Zn at the key growth period could significantly reduce the Cd content in various parts of rice. Cd contents in root, stem, and brown rice with the application of irrigation water containing 20 mg·L-1 Zn before the booting and the filling stage (BF1) were significantly decreased by 56.0%, 83.8%, and 85.2%, respectively. ③ Compared with the application of 100 mg·L-1 irrigation water containing Zn, the application of 20 mg·L-1 irrigation water containing Zn significantly reduced the uptake and transport of Cd in rice, and the translocation factor (TF) of Cd from rice roots to stems was also significantly reduced by 12.5%-56.3%, with the B1 and BF1 treatments reaching significant levels. These results suggested that the application of irrigation water containing Zn could significantly reduce the uptake and accumulation of Cd in rice, and the application of 20 mg·L-1 irrigation water containing Zn before the booting and filling stage could effectively realize the safe production of Cd-contaminated paddy fields.


Assuntos
Oryza , Poluentes do Solo , Cádmio/análise , Poluentes do Solo/análise , Solo , Água , Zinco
10.
Plant Physiol Biochem ; 208: 108441, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38377887

RESUMO

The economically adaptable mulberry (Morus alba L.) has a long history of grafting in China, yet the physiological mechanisms and advantages in drought tolerance remain unexplored. In our study, we investigated the responses of self-rooted 2X (diploid), 3X (triploid), and 4X (tetraploid) plants, as well as polyploid plants grafted onto diploid seedling rootstocks (2X/2X, 3X/2X, and 4X/2X) under drought stress. We found that self-rooted diploid plants exhibited the most severe phenotypic damage, lowest water retention, photosynthetic capacity, and the least effective osmotic stress adjustment compared to tetraploid and triploid plants. However, grafted diploid and triploid plants showed effective mitigation of drought-induced damage, with higher relative water content and improved soil water retention. Grafted plants also improved the photosystem response to drought stress through elevated photosynthetic potential, closed stomatal aperture, and faster recovery of chlorophyll biosynthesis in the leaves. Additionally, grafted plants altered osmotic protective compound levels, including starch, soluble sugar, and proline content, thereby enhancing drought resistance. Absolute quantification PCR indicated that the expression levels of proline synthesis-related genes in grafted plants were not influenced after drought stress, whereas they were significantly increased in self-rooted plants. Consequently, our findings support that self-rooted triploid and tetraploid mulberries exhibited superior drought resistance compared to diploid plants. Moreover, grafting onto seedling rootstocks enhanced tolerance against drought stress in diploid and triploid mulberry, but not in tetraploid. Our study provides valuable insights for a comprehensive analysis of physiological effects in response to drought stress between stem-roots and seedling rootstocks.


Assuntos
Morus , Plântula , Plântula/metabolismo , Morus/genética , Tetraploidia , Secas , Triploidia , Água/fisiologia , Prolina/metabolismo
11.
Sci Total Environ ; 922: 171269, 2024 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-38423323

RESUMO

Soil biogeochemical cycles are essential for regulating ecosystem functions and services. However, little knowledge has been revealed on microbe-driven biogeochemical processes and their coupling mechanisms in soil profiles. This study investigated the vertical distribution of soil functional composition and their contribution to carbon (C), nitrogen (N) and phosphorus (P) cycling in the humus horizons (A-horizons) and parent material horizons (C-horizons) in Udic and Ustic Isohumosols using shotgun sequencing. Results showed that the diversity and relative abundance of microbial functional genes was influenced by soil horizons and soil types. In A-horizons, the relative abundances of N mineralization and liable C decomposition genes were significantly greater, but the P cycle-related genes, recalcitrant C decomposition and denitrification genes were lower compared to C-horizons. While, Ustic Isohumosols had lower relative abundances of C decomposition genes but higher relative abundances of N mineralization and P cycling-related pathways compared to Udic Isohumosols. The network analysis revealed that C-horizons had more interactions and stronger stability of functional gene networks than in A-horizons. Importantly, our results provide new insights into the potential mechanisms for the coupling processes of soil biogeochemical cycles among C, N and P, which is mediated by specific microbial taxa. Soil pH and carbon quality index (CQI) were two sensitive indicators for regulating the relative abundances and the relationships of functional genes in biogeochemical cycles. This study contributes to a deeper understanding of the ecological functions of soil microorganisms, thus providing a theoretical basis for the exploration and utilization of soil microbial resources and the development of soil ecological control strategies.


Assuntos
Ecossistema , Solo , Solo/química , Microbiologia do Solo , Nitrogênio/análise , Carbono/metabolismo , Fósforo/metabolismo , Concentração de Íons de Hidrogênio
12.
J Environ Manage ; 354: 120289, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38367498

RESUMO

Climate change-induced warming has the potential to intensify drought conditions in certain regions, resulting in uneven precipitation patterns. However, the impact of precipitation-induced changes on soil C-fixing bacterial community composition to changes and their subsequent effect on the accumulation of microbial necromass in the soil remains unclear. To address this knowledge gap, we conducted an in-situ simulated precipitation control experiment in semi-arid grasslands, encompassing five primary precipitation gradients: ambient precipitation as a control (contr), decreased precipitation by 80% and 40% (DP80, DP40), and increased precipitation by 40% and 80% (IP80, IP40). Our findings indicate that while an increase in precipitation promotes greater total bacterial diversity, it reduces the diversity of cbbM-harboring bacteria. The dominance of drought-tolerant Proteobacteria within the cbbM-harboring bacterial community was responsible for the observed increase in their relative abundance, ranging from 8.9% to 15.6%, under conditions of decreased precipitation. In arid environments characterized by limited soil moisture and nutrient availability, certain dominant genera such as Thiobacillus, Sulfuritalea, and Halothiobacillus, which possess cbbM genes, exhibit strong synergistic effects with other bacteria, thereby leading to a high nutrient use efficiency. Linear regression analysis shows that bacterial necromass C was significantly negatively correlated with cbbM-harboring bacterial diversity but positively correlated with cbbM-harboring bacterial community composition. Consequently, in the extreme drought environment of DP80, the contribution of bacterial necromass C to SOC was dramatically reduced by 75% relative to the control. Although bacterial necromass C was preferentially consumed as nutrients and energy for microorganisms, C-fixing microorganisms supplemented the soil C pool by assimilating atmospheric CO2. Bacterial necromass was primarily controlled by accessible C and N rather than by the total bacterial community composition and relative abundance. Our results provide compelling evidence for the critical role of the composition of the bacterial community and its necromass in the accumulation of SOC in semiarid grassland ecosystems.


Assuntos
Ecossistema , Pradaria , Microbiologia do Solo , Bactérias , Solo
13.
Ultrason Sonochem ; 103: 106783, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38364480

RESUMO

The oxide film on the surface of the grinding wheel plays a very important role in ultrasonic-assisted electrolytic in-process dressing (UA-ELID) grinding. In order to investigate the influence of ultrasonic vibration on the characteristics of oxide film on the surface of grinding wheel in compound grinding, the formation mechanism of oxide film on the surface of grinding wheel under ultrasonic action was analyzed theoretically from two aspects: the change of single grain trajectory caused by ultrasonic vibration and the effect of ultrasonic cavitation. The pre-dressing tests were conducted with different pre-dressing times to observe the oxide layer properties at different pre-dressing stages. The grinding tests were conducted after pre-dressing to verify the grinding performance of oxide layer under different pre-dressing methods. The results show that after the ultrasonic vibration of the grinding wheel is added during electrolytic in-process dressing (ELID) process, the holes and cracks of the oxide film on the surface of the grinding wheel are greatly reduced during the whole pre-dressing process. In addition, the pre-dressing current decreases more stably and the current is smaller when it reaches stability. After the pre-dressing, the thickness of the oxide film is reduced by about 35 % and the hardness is increased by about 70 % compared with the ordinary pre-dressing process. The grinding test results show that the oxide film obtained by ultrasonic vibration of the additional grinding wheel is more conducive to improving the surface quality of the grinding process. Therefore, compared with the ordinary pre-dressing process, the density and uniformity of oxide film on the surface of grinding wheel is better and the hardness is higher after the additional ultrasonic vibration of grinding wheel. It is beneficial to improve the surface quality of workpiece.

14.
J Ethnopharmacol ; 324: 117754, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38232859

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Clinical research and basic scientific experiments have shown that modified Xiaoyaosan (MXYS) has antidepressant effects, whose system mechanism however has not been thoroughly characterized. AIM OF THE STUDY: This research was aimed at evaluating the treatment effects of MXYS on chronic unpredictable mild stress (CUMS)-induced depressive mice and exploring underlying mechanisms. MATERIALS AND METHODS: Whether MXYS has effects on depression was investigated via the depressive behaviors of mice, electron microscopy, real-time quantitative polymerase chain reaction (RT-qPCR), Western blot analysis, immunofluorescence (IF) staining and the stereotaxic injection of adeno-associated viruses (AAVs). In addition, network pharmacology was applied to predict relevant molecular targets and possible mechanisms and perform further in vivo validation. RESULTS: MXYS is effective in ameliorating the depression-like symptoms of CUMS mice. It can stimulate autophagosome formation, activate the expression of microtubule-associated protein 1 light chain 3 (LC3B), autophagy-related gene 5 (Atg5), Atg7 and neuron-specific nuclear protein (NeuN), and decrease the protein expression sequestosome 1 (SQSTM1/p62). The autophagy-upregulating effect of MXYS was weakened by silencing. The network pharmacology analysis revealed that mitogen-activated protein kinase 1 (MAPK1), MAPK3, serine/threonine-protein kinase (AKT1), proto-oncogene tyrosine-protein kinase (SRC), PI 3 kinase p85 alpha (PIK3R1), catenin (cadherin-associated protein) beta 1 (CTNNB1) and human thrombin activator 1 (HRAS) may be of importance to treat depression by MXYS. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that metabolic and autophagy pathways, pathways in cancer and MAPK, phosphoinositide 3-kinase (PI3K)-Akt and rhoptry-associated protein 1 (Rap1) signaling pathways are involved in the antidepressant effects of MXYS. As suggested by Western blot, the anti-depression mechanism of MXYS is possibly associated with the extracellular signal-regulated protein kinase (ERK)/P38 MAPK signaling pathway. CONCLUSION: The findings indicate the possible antidepressant effects of MXYS on CUMS mice via triggering autophagy to alleviate neuronal apoptosis and prompting autophagy, which may involve the ERK/P38 MAPK signaling pathway.


Assuntos
Depressão , Medicamentos de Ervas Chinesas , Fosfatidilinositol 3-Quinases , Camundongos , Humanos , Animais , Depressão/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Farmacologia em Rede , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Proteínas Quinases p38 Ativadas por Mitógeno , Proteínas Proto-Oncogênicas c-akt/metabolismo
15.
Biosystems ; 236: 105128, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38280446

RESUMO

When studying stochastic gene transcription, it is important to understand how system parameters are temporally modulated in response to varying environments. Experimentally, the dynamic distribution data of RNA copy numbers measured at multiple time points are often fitted to stochastic transcription models to estimate time-dependent parameters. However, current methods require determining which parameters are time-dependent, as well as their analytical formulas, before the optimal fit. In this study, we developed a method to estimate time-dependent parameters in a classical two-state model without prior assumptions regarding the system parameters. At each measured time point, the method fitted the dynamic distribution data using a steady-state distribution formula, in which the estimated constant parameters were approximated as time-dependent parameter values at the measured time point. The accuracy of this method can be guaranteed for RNA molecules with relatively high degradation rates and genes with relatively slow responses to induction. We quantify the accuracy of the method and implemented this method on two sets of dynamic distribution data from prokaryotic and eukaryotic cells, and revealed the temporal modulation of transcription burst size in response to environmental changes.


Assuntos
RNA , Transcrição Gênica , Processos Estocásticos
16.
Aging (Albany NY) ; 16(1): 648-664, 2024 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-38194722

RESUMO

BACKGROUND: Osteoarthritis (OA) is a common chronic age-related joint disease characterized primarily by inflammation of synovial membrane and degeneration of articular cartilage. Accumulating evidence has demonstrated that Danggui-Shaoyao-San (DSS) exerts significant anti-inflammatory effects, suggesting that it may play an important role in the treatment of knee osteoarthritis (KOA). METHODS: In the present study, DSS was prepared and analyzed by high-performance liquid chromatography (HPLC). Bioinformatics analyses were carried out to uncover the functions and possible molecular mechanisms by which DSS against KOA. Furthermore, the protective effects of DSS on lipopolysaccharide (LPS)-induced rat chondrocytes and cartilage degeneration in a rat OA model were investigated in vivo and in vitro. RESULTS: In total, 114 targets of DSS were identified, of which 60 candidate targets were related to KOA. The target enrichment analysis suggested that the NF-κB signaling pathway may be an effective mechanism of DSS. In vitro, we found that DSS significantly inhibited LPS-induced upregulation of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin-6 (IL-6), matrix metalloproteinase-3 (MMP3), and matrix metalloproteinase-13 (MMP13). Meanwhile, the degradation of collagen II was also reversed by DSS. Mechanistically, DSS dramatically suppressed LPS-induced activation of the nuclear factor kappa B (NF-κB) signaling pathway. In vivo, DSS treatment prevented cartilage degeneration in a rat OA model. CONCLUSIONS: DSS could ameliorate the progression of OA through suppressing the NF-κB signaling pathway. Our findings indicate that DSS may be a promising therapeutic approach for the treatment of KOA.


Assuntos
Medicamentos de Ervas Chinesas , NF-kappa B , Osteoartrite do Joelho , Ratos , Animais , NF-kappa B/metabolismo , Lipopolissacarídeos/farmacologia , Anti-Inflamatórios/farmacologia , Transdução de Sinais , Inflamação/metabolismo , Osteoartrite do Joelho/tratamento farmacológico , Osteoartrite do Joelho/metabolismo , Condrócitos/metabolismo
17.
J Am Chem Soc ; 146(3): 1887-1893, 2024 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-38205793

RESUMO

Despite wide studies demonstrating the versatility of the metal oxide-zeolite (OXZEO) catalyst concept to tackle the selectivity challenge in syngas chemistry, the active sites of metal oxides and the mechanism of CO/H2 activation remain to be elucidated. Herein, we demonstrate experimentally the role of Cr in zinc-chromium oxides and unveil visually, for the first time, the active sites for CO activation employing scanning transmission electron microscopy-electron energy loss spectroscopy using the volumetric density of surface carbon species as a descriptor. The ZnCr2O4 spinel surface with atomic ZnOx overlayer is the most active site for C-O bond dissociation, particularly at the narrow ZnCr2O4(110) facets constrained between the (311) and (111) facets, followed by the Cr-doped wurtzite ZnO surface. In comparison, the surfaces of ZnCr2O4 with aggregated ZnOx overlayers, pure ZnO, and the stoichiometric ZnCr2O4 exhibit a significantly lower activity. In situ synchrotron-based vacuum ultraviolet photoionization mass spectrometric study on different temperature programmed surface reactions with isotopes of C18O, 13CO, and D2 validates direct CO dissociation over ZnCrn oxides in CO, forming CH2 and further to hydrocarbons if H2 is present and CH2CO intermediates in syngas. The activity of CO dissociation and hydrogenation over ZnCrn oxides correlates well with the syngas-to-light-olefins activity of ZnCrn-SAPO-18 composite catalysts as a function of the Cr/Zn ratio.

18.
ACS Appl Mater Interfaces ; 16(4): 5058-5066, 2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38231084

RESUMO

Addressing the significant obstacles of volume expansion and inadequate electronic conductivity in silicon-based anode materials during lithiation is crucial for achieving a long durable life in lithium-ion batteries. Herein, a high-strength copper-based metal shell is coated in situ onto silicon materials through a chemical combination of copper citrate and Si-H bonds and subsequent heat treatment. The formed Cu and Cu3Si shell effectively mitigates the mechanical stress induced by volume expansion during lithiation, strengthens the connection with the copper substrate, and facilitates electron transfer and Li+ diffusion kinetics. Consequently, the composite exhibits a reversible specific capacity of 1359 mA h g-1 at 0.5 A g-1 and maintains a specific capacity of 837 mA h g-1 and an 83.5% capacity retention after 400 cycles at 1 A g-1, surpassing similar reports on electrochemical stability. This facile copper plating technique on silicon surfaces may be used to prepare high-performance silicon-based anodes or functional composites in other fields.

19.
Environ Sci Pollut Res Int ; 31(2): 2987-3003, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38079046

RESUMO

Woody plants possess great potential for phytoremediation of heavy metal-contaminated soil. A pot trial was conducted to study growth, physiological response, and Cd and Pb uptake and distribution in black locust (Robinia pseudoacacia L.), as well as the rhizosphere bacterial communities in Cd and Pb co-contaminated soil. The results showed that R. pseudoacacia L. had strong physiological regulation ability in response to Cd and Pb stress in contaminated soil. The total chlorophyll, malondialdehyde (MDA), soluble protein, and sulfhydryl contents, as well as antioxidant enzymes (superoxide dismutase, peroxidase, catalase) activities in R. pseudoacacia L. leaves under the 40 mg·kg-1 Cd and 1000 mg·kg-1 Pb co-contaminated soil were slightly altered. Cd uptake in R. pseudoacacia L. roots and stems increased, while the Pb content in the shoots of R. pseudoacacia L. under the combined Cd and Pb treatments decreased in relative to that in the single Pb treatments. The bacterial α-diversity indices (e.g., Sobs, Shannon, Simpson, Ace, and Chao) of R. pseudoacacia L. rhizosphere soil under Cd and Pb stress were changed slightly relative to the CK treatment. However, Cd and Pb stress could significantly (p < 0.05) alter the rhizosphere soil microbial communities. According to heat map and LEfSe (Linear discriminant analysis Effect Size) analysis, Bacillus, Sphingomonas, Terrabacter, Roseiflexaceae, Paenibacillus, and Myxococcaceae at the genus level were notably (p < 0.05) accumulated in the Cd- and/or Pb-contaminated soil. Furthermore, the MDA content was notably (p < 0.05) negatively correlated with the relative abundances of Isosphaeraceae, Gaiellales, and Gemmatimonas. The total biomass of R. pseudoacacia L. was positively (p < 0.05) correlated with the relative abundances of Xanthobacteraceae and Vicinamibacreraceae. Network analysis showed that Cd and Pb combined stress might enhance the modularization of bacterial networks in the R. pseudoacacia L. rhizosphere soil. Thus, the assembly of the soil bacterial communities in R. pseudoacacia L. rhizosphere may improve the tolerance of plants in response to Cd and/or Pb stress.


Assuntos
Metais Pesados , Robinia , Poluentes do Solo , Cádmio/análise , Chumbo/análise , Metais Pesados/análise , Bactérias/metabolismo , Solo , Poluentes do Solo/análise , Biodegradação Ambiental
20.
Micromachines (Basel) ; 14(12)2023 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-38138393

RESUMO

Precisely controlling magnetically tagged cells in a complex environment is crucial to constructing a magneto-microfluidic platform. We propose a two-dimensional model for capturing magnetic beads from non-magnetic fluids under a micromagnetic matrix. A qualitative description of the relationship between the capture trajectory and the micromagnetic matrix with an alternating polarity configuration was obtained by computing the force curve of the magnetic particles. Three stages comprise the capture process: the first, where motion is a parabolic fall in weak fields; the second, where the motion becomes unpredictable due to the competition between gravity and magnetic force; and the third, where the micromagnetic matrix finally captures cells. Since it is not always obvious how many particles are adhered to the surface, attachment density is utilized to illustrate how the quantity of particles influences the capture path. The longitudinal magnetic load is calculated to measure the acquisition efficiency. The optimal adhesion density is 13%, and the maximum adhesion density is 18%. It has been demonstrated that a magnetic ring model with 100% adhesion density can impede the capture process. The results offer a theoretical foundation for enhancing the effectiveness of rare cell capture in practical applications.

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