Diesel exhaust particles (DEPs), a predominant component of ambient particulate matter (PM), are classified as ultrafine particles with the capacity to penetrate the cerebral blood-brain barrier ...(BBB). This penetration is implicated in the pathogenesis of central nervous system (CNS) disorders. The integrity of the BBB is inextricably linked to cerebrovascular homeostasis and the development of neurodegenerative disease, highlighting the importance of studying the effects and mechanisms of DEPs on BBB function damage.
Utilizing mouse cerebral microvascular endothelial cells (bEnd.3 cells) as an in vitro model of the BBB, we explored the detrimental effects of DEPs exposure on BBB permeability and integrity, with particular focus on inflammation, cell apoptosis, and miRNA expression profiles. Our findings revealed that exposure to DEPs at varying concentrations for 48 h resulted in the inhibition of bEND.3 cell proliferation, induction of cell apoptosis, and an upregulation in the secretion of inflammatory cytokines/chemokines and adhesion molecules. The BBB integrity was further compromised, as evidenced by a decrease in trans-epithelial electrical resistance(TEER), a reduction in cytoskeletal F-actin, , and diminished tight junction (TJ) protein expression. Microarray analysis revealed that 23 miRNAs were upregulated and 11 were downregulated in response to a 50 μg/mL DEPs treatment, with miR-466d-3p being notably differentially expressed. Wnt3 was identified as a target of miR-466d-3p, with the Wnt signaling pathway being significantly enriched. We validated that miR-466d-3p expression was downregulated, and the protein expression levels of Wnt/β-catenin and Wnt/PCP signaling components were elevated. The modulation of the Wnt signaling pathway by miR-466d-3p was demonstrated by the transfection of miR-466d-3p mimic, which resulted in a downregulation of Wnt3 and β-catenin protein expression, and the mRNA level of Daam1, as well as an enhancement of TJ proteins ZO-1 and Claudin-5 expression.
Our study further confirmed that DEPs can induce the disruption of BBB integrity through inflammatory processes. We identified alterations in the expression profile of microRNAs (miRNAs) in endothelial cells, with miR-466d-3p emerging as a key regulator of tight junction (TJ) proteins, essential for maintaining BBB integrity. Additionally, our findings primarily demonstrated that the Wnt/ β-catenin and Wnt/PCP signaling pathway can be activated by DEPs and are regulated by miR-466d-3p. Under the combined effects of Wnt/PCP and inflammation, there is an ultimate increase in BBB hyperpermeability.
Employing mouse cerebral microvascular endothelial cells (bEnd.3 cells) as an in vitro model of the BBB, we investigated the adverse effects of DEPs exposure on BBB permeability and integrity, with particular focus on inflammation, cell apoptosis, and miRNA expression profiles. Our findings revealed that exposure to DEPs at varying concentrations for 48 h resulted in the inhibition of bEND.3 cell proliferation, induction of cell apoptosis, and an increase in the release of inflammatory cytokines/chemokines and adhesion molecules. The BBB integrity was further compromised, as evidenced by a decrease in trans-epithelial electrical resistance(TEER), a reduction in cytoskeletal F-actin, loss of intercellular junctional organization, and diminished tight junction (TJ) protein expression. Microarray analysis disclosed that 23 miRNAs were upregulated and 11 were downregulated in bEND.3 cells treated with 50 μg/mL DEPs compared to the controls. In particular, miR-466d-3p was identified as a significantly differentially expressed miRNA. Wnt3 was predicted to be a target of miR-466d-3p, and the Wnt signaling pathway was identified as one of the most significantly enriched pathways. We validated that miR-466d-3p expression was downregulated, and the protein expression levels of Wnt/β-catenin and Wnt/PCP signaling components were elevated. The modulation of the Wnt signaling pathway by miR-466d-3p was demonstrated by the transfection of miR-466d-3p mimic, which resulted in a downregulation of Wnt3 and β-catenin protein expression, and the mRNA level of Daam1, as well as an enhancement of TJ proteins ZO-1 and Claudin-5 expression.
Our study further confirmed that DEPs can induce the disruption of BBB integrity by inflammation. We identified changes in the expression profile of microRNAs (miRNAs) in endothelial cells, with miR-466d-3p emerging as a regulator of tight junction (TJ) proteins, which are critical for maintaining BBB integrity. Additionally, our findings primarily demonstrated that the Wnt/ β-catenin and Wnt/PCP signaling pathway can be activated by DEPs and is regulated by miR-466d-3p, and under the combined effects of Wnt/PCP and inflammation ultimately led to hyperpermeability BBB.
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•The first study to investigatemiRNA expression alterations induced by DEPs in endothelial cells.•miR-466d-3p is identified as a novel miRNA crucial for the integrity of the BBB.•The modulation of Wnt signaling pathway is associated with the elevated BBB permeability.
Bandgap engineering plays a vital role in material development and device optimization due to its significant impact on the photovoltaic and photoelectricity properties of materials. Nevertheless, it ...is still a great challenge to accurately control the bandgap of semiconductors to achieve the targeted properties of materials. Recently, pressure-induced bandgap regulation has emerged as a novel and effective tool to regulate bandgap, reveal the intrinsic band nature, and construct the in-depth structure–property relationships therein. In this review, the unique techniques of microscopic in situ steady-state UV–Vis absorption spectroscopy and high-pressure diamond anvil cell are introduced. This technique provides a powerful method to monitor the bandgap behaviors at high pressure. Then, the pressure-triggered bandgap responses are outlined based on several typical semiconductors, including metal halide perovskites, inorganic quantum dots, piezochromic molecular compounds, and two-dimensional semiconductor materials. The summarized structural effects on bandgap evolution and the general principles for bandgap engineering under high pressure are expected to provide guidance for further material design under ambient conditions. Microscopic absorption spectroscopy detection under high pressure is proven to be an ideal platform for developing functional materials and high-performance devices.
Considering the pear in the arid region as the research object, single-factor testing and water–fertilizer coupling testing were conducted. The response of pear tree growth to water, nitrogen, and ...phosphorus was explored and provided a theoretical basis for efficient water and fertilizer management. Among them, the single-factor test set water, nitrogen, and phosphorus as the three factors, and five levels were set. Screening out W3, W4, N3, N4, P3, and P4 promoted plant nutrient uptake and fruit quality. Eight treatments were set up in the water and fertilizer coupling test: Treatment 1 (T1, W3N3P3), Treatment 2 (T2, W3N3P4), Treatment 3 (T3, W3N4P3), Treatment 4 (T4, W3N4P4), Treatment 5 (T5, W4N3P3), Treatment 6 (T6, W4N3P4), Treatment 7 (T7, W4N4P3), and Treatment 8 (T8, W4N4P4). The results showed that the leaf area index of the T1, T2, T3, and T4 treatments was significantly higher than that of the other treatments at maturity. The yield, single fruit weight, and primary fruit rate were the highest under T3 treatment. The gray correlation degree analysis of fruit quality showed that the T3 treatment had the highest degree of correlation and ranking of each fruit quality index, indicating that the T3 treatment had the highest fruit quality. The yield model showed that irrigation with 6510.06 m
hm
, nitrogen fertilizer with 337.5 kg N hm
, and phosphate fertilizer with 262.5 kg P hm
had the best yield. A detailed investigation of pear tree growth and fruit quality showed that the T3 treatment had the best fruit growth and development performance, and the pear fruit quality was the best.
Scientific fertilization is an important technical means of achieving high and stable peanut yields. Using soil testing and formula fertilization, the “3414” optimal regression design was used and ...included 14 nitrogen (N), phosphorus (P), and potassium (K) fertilization treatments. Ternary quadratic functions of the fertilizer effect were established according to three-season field experiments and the regression analysis of fertilizer–yield function was performed to explore the optimal fertilizer application mode and ratio for peanuts under mulched drip irrigation (MDI), and a suitable fertilizer application system was established. The ternary quadratic equation relating peanut yield (
) and the fertilizer application rates of N (N), P (P
), and K (K
O) was obtained after fitting, i.e.,
= 2912.528 + 21.432N + 16.324P + 6.181K − 0.051N
− 0.109P
− 0.061K
+ 0.017NP + 0.023NK + 0.086PK, and significance analysis and typicality assessment were performed. The model
was 0.9709, both values are extremely significant (
< 0.01), which indicates that the obtained ternary quadratic fertilizer effect function is typical and could be used for statistical purposes and fertilization recommendations. Three quadratic fertilizer effect functions were obtained. Among them, the equation for
is extremely significant, and the equations of
and
are significant. According to the assumption that the marginal yield is zero and the marginal profit is zero, the fertilizer application rate with the maximum yield, the fertilizer application rate with the best economic benefits, and the corresponding yields were obtained. The optimal fertilizer application rate predicted by the ternary quadratic fertilizer effect function was relatively high, so the three quadratic fertilizer effect functions were used for prediction. Under the test conditions, the recommended fertilizer application rates for peanuts under MDI are 256.6 kg N per ha, 164.2 kg P
per ha, and 213.2 kg K
O per ha, the recommended fertilization ratio is 1:0.64:0.83, and the recommended ratio under formula fertilization is 23:15:19. The study has developed a data-based decision support system for Xinjiang drip-irrigated peanut, which assists farmers and agricultural managers in making more scientific and precise fertilization decisions based on the specific growth requirements of the crops and soil conditions. This evidence-based methodology enhances the precision of agricultural management, which is conducive to increasing crop yields while reducing resource wastage and environmental impact. However, multipoint and multiyear experiments are still needed to ensure that the findings are adaptable to the diverse soil conditions and fluctuating climate patterns that may be encountered in practice.
Clostridium perfringens enterotoxin (CPE) causes the symptoms associated with several common gastrointestinal diseases. CPE is a 35 kDa polypeptide consisting of three structured domains, that is, ...C-terminal domain I (responsible for receptor binding), domain II (responsible for oligomerization and membrane insertion), and domain III (which may participate in physical changes when the CPE protein inserts into membranes). Native CPE binds to claudin receptors, which are components of the tight junction. The bound toxin then assembles into a hexameric prepore on the membrane surface, prior to the insertion of this oligomer into membranes to form an active pore. The toxin is especially lethal for cells expressing large amounts of claudin-3 or -4, which includes many cancer cells. Initial studies suggest that native CPE has potential usefulness for treating several cancers where claudin CPE receptors are overexpressed. However, some challenges with immunogenicity, toxicity, and (possibly) the development of resistance may need to be overcome. An alternative approach now being explored is to utilize C-CPE, which corresponds approximately to receptor binding domain I, to enhance paracellular permeability and delivery of chemotherapeutic agents against cancer cells. Alternatively, C-CPE fusion proteins may prove superior to use of native CPE for cancer treatment. Finally, C-CPE may have application for other medical treatments, including vaccination or increasing drug absorption. The coming years should witness increasing exploitation of this otherwise formidable toxin.
Introduction
Arid and semi-arid regions encompass nearly 40% of the Earth’s land surface and are characterized by extensive undeveloped land, scarce water resources, and fragile ecosystems. The arid ...northwestern China is a representative arid and semi-arid region. It has developed rapidly in recent years, leading to a significant increase in human activity. This increased activity has had a pronounced impact on the ecosystem, posing a major challenge to the environment. The close relationship between human activities and ecosystem service value (ESV) is crucial for the healthy development of both humans and ecosystems. However, the intricate nature of this relationship and the degree to which they are codependent remain unclear and require further investigation.
Methods
This study investigates the impact of human activities on land use intensity (LUI) and degree of urbanization (URB). It comprehensively evaluates the spatial and temporal distribution of human activities and ESV, quantifying their coordination through coupling models.
Results
This work provides valuable insights and theoretical support for promoting the coordinated development of human activities and ESV. Overall, the LUI in the arid northwestern region decreased (from 0.485 in 2000 to 0.459 in 2020), while the URB increased (from 0.060 in 2000 to 0.087 in 2020). The ESV significantly increased, with a total growth of 556.58 billion yuan. In prefecture-level cities, the growth in ESV values ranges from 75.19 yuan/hm2 to 10,062.49 yuan/hm2.The coupling coordination degree between ESV and LUI has changed over time, transitioning from uncoordinated development to coordinated development. In addition, the coordination between ESV and URB has evolved from uncoordinated development to transitional coordination. The level of coordination between human activities and ESV in provincial capital cities significantly influences the coordination in surrounding cities.
Discussion
In conclusion, effective development recommendations are provided based on the ESV, LUI, and URB of different cities, along with a proposed development strategy for ecosystem service functions that aligns with the 14th Five-Year Plan and “Vision 2035” of each province. This work provides important insights into the relationship between human activities and ESV, and its findings can be used to guide coordinated and sustainable urban development.
This work investigates the impact of pressure on the structural, optical properties, and electronic structure of CsPbBr3 quantum dots (QDs) using steady‐state photoluminescence, steady‐state ...absorption, and femtosecond transient absorption spectroscopy, reaching a maximum pressure of 3.38 GPa. The experimental results indicate that CsPbBr3 QDs undergo electronic state (ES) transitions from ES‐I to ES‐II and ES‐II to ES‐III at 0.38 and 1.08 GPa, respectively. Intriguingly, a mixed state of ES‐II and ES‐III is observed within the pressure range of 1.08–1.68 GPa. The pressure‐induced fluorescence quenching in ES‐II is attributed to enhanced defect trapping and reduced radiative recombination. Above 1.68 GPa, fluorescence vanishes entirely, attributed to the complete phase transformation from ES‐II to ES‐III in which radiative recombination becomes non‐existent. Notably, owing to stronger quantum confinement effects, CsPbBr3 QDs exhibit an impressive bandgap tuning range of 0.497 eV from 0 to 2.08 GPa, outperforming nanocrystals by 1.4 times and bulk counterparts by 11.3 times. Furthermore, this work analyzes various carrier dynamics processes in the pressure‐induced bandgap evolution and electron state transitions, and systematically studies the microphysical mechanisms of optical properties in CsPbBr3 QDs under pressure, offering insights for optimizing optical properties and designing novel materials.
CsPbBr3 quantum dots (QDs) undergo electronic state (ES) transitions from ES‐I to ES‐II to ES‐III under high pressure, accompanied by changes in fluorescence and bandgap. In the pressure range of 1.08–1.68 GPa, ES‐II and ES‐III coexist in the QDs. Pressure‐induced fluorescence quenching and disappearance are behaviors of ES‐II. Above 1.68 GPa, ES‐III is no radiative recombination.
Carrizo citrange
Citrus sinensis
(L.) Osbeck ×
Poncirus trifoliata
(L.) Raf., CC is one of the most widely used rootstocks in citriculture worldwide, but its cytogenetic study has been hampered by ...its inherent small size, morphological similarity to mitotic chromosomes, and lack of accessible cytological landmarks. In our previous study, a spontaneously occurring tetraploid CC seedling was discovered. The main goals of this study were to elucidate the chromosome constitution and construct the karyotypes of diploid CC rootstock and its corresponding spontaneously occurring tetraploid. To accomplish these, the chromosomal characteristics were investigated by sequential multicolor fluorescence
in situ
hybridization (FISH) with eight properly labeled repetitive DNA sequences, including a centromere-like repeat, four satellite repeats, two rDNAs, and an oligonucleotide of telomeric (TTTAGGG)
n
repeat. The results nicely demonstrated that these repetitive DNAs are reliable cytogenetic markers that collectively facilitate simultaneous and unequivocal identification of homologous chromosome pairs. Based on chromosome size and morphology together with FISH patterns of repetitive DNAs, an integrated karyotype of CC rootstock was constructed, consisting of 2n = 2x = 12m (1sat) + 6sm with karyotype asymmetry degree being divided into 2B category. Cytogenetically speaking, the variable and asymmetric distribution patterns of these repetitive DNAs were fully confirmed the hybrid nature of CC rootstock. In addition, comparative distribution patterns and chromosomal localizations of these repetitive DNAs convincingly showed that this tetraploid CC material arose from somatic chromosome doubling of diploid CC rootstock. This study revealed, for the first time, the integrated karyotype and chromosomal characteristics of this important citrus rootstock as well as its spontaneously occurring tetraploid plant. Furthermore, this study is a good prospective model for study species with morphologically indistinguishable small chromosomes.
We have previously shown that CLDN4 (encoding claudin-4), a cell tight junction (TJ) protein, is highly expressed in human epithelial ovarian carcinomas (EOC) but undetectable in normal ovaries. ...CLDN4 has been identified as a specific receptor for C terminus of Clostridium perfringens enterotoxin (C-CPE), a nontoxic molecule that may disrupt TJ barrier function and enhance cellular absorption. The purpose of this study was to determine the potential clinical applications of C-CPE and its effects on CLDN4 expression in EOC.
Using a 3-dimensional culture model and monolayer culture of EOC cells, we examined the effects of C-CPE on CLDN4 expression by quantitative real-time PCR, immunofluorescence, and Western blot. The synergistic effect of C-CPE to clinically relevant chemotherapies (Taxol and Carboplatin) was observed in EOC culture and xenograft mice. Furthermore, we determined through oligonucleotide microarray analysis that the transcript profile alterations dysregulated as a consequence of C-CPE treatment.
C-CPE treatment decreased protein expression and relocated CLDN4 from cell-cell contact regions to the cytoplasm. Particularly, C-CPE sensitized EOC cells to chemotherapeutic administration at low dosages and significantly inhibited tumor growth in a nontoxic manner. Furthermore, we provided genome-wide molecular evidence that C-CPE treatment is involved in the stimulation of the ubiquitin-proteasome pathway and the inhibition of cell metabolism in EOC cells.
The addition of C-CPE can enhance the effectiveness of Taxol or Carboplatin and significantly inhibited EOC cell growth in a CLDN4-dependent manner, suggesting that C-CPE may have promising therapeutic potential for EOC.
Vehicle detection is an important component of intelligent transportation systems and autonomous driving. However, in real-world vehicle detection scenarios, the presence of many complex and high ...uncertainty factors, such as illumination differences, motion blur, occlusion, weather, etc., makes accurate and real-time vehicle detection still challenging. In order to reduce the influence of these uncertainties in real scenarios and improve the accuracy and real-time performance of vehicle detection, this paper proposes a type-1 fuzzy attention (T1FA), in which fuzzy entropy is introduced to re-weight the feature map in order to reduce the uncertainty of the feature map and facilitates the detector’s focus on the target center as a way to effectively improve the accuracy of vehicle detection. Furthermore, to detect vehicles with different sizes more effectively, mixed depth convolution in MetaFormer (MDFormer) is employed as a token mixer to capture multi-scale perceptual fields. And a novel YOLO detector based on fuzzy attention (YOLO-FA) is proposed. Experimental results show that T1FA can boost 3.2% AP50 on challenging vehicle detection dataset UA-DETRAC, which is better than other commonly used attention mechanisms, especially in scenarios of rain and nighttime with higher uncertainty by 4.2% and 8.1% AP50, respectively. Finally, without pretraining on extra data, YOLO-FA achieves 70.0% AP50 and 50.3% AP on UA-DETRAC, which achieves better balance between accuracy and speed compared with state-of-the-art detectors. The remarkable improvement of T1FA in different detectors and datasets also shows the considerable generalization of T1FA.
•A type-1 fuzzy attention (T1FA) mechanism-based YOLO (YOLO-FA) detector is proposed.•Mixed depthwise convolution is employed as a token mixer in MetaFormer.•T1FA can boost 3.2% AP50 in UA-DETRAC by reducing the uncertainty.•YOLO-FA trained from scratch achieves 70.0% AP50 and 50.3% AP on UADETRACA.
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