Fluorescence bioimaging is very significant in studying biological processes. Fluorescent nanoparticles (NPs) manufactured from aggregation-induced emission (AIE) materials, as promising candidates, ...have attracted more attention. However, it is still a challenge to explore suitable AIE NPs for bioimaging. Herein, we synthesized pyrazoline-BODIPY (PZL-BDP) with a donor and acceptor (D-A) structure by a condensation reaction, cultured its single crystal, and studied its twisted intramolecular charge transfer (TICT) and AIE effects. PZL-BDP could self-assemble to form red fluorescent nanoparticles (PZL-BDP NPs) which showed a good fluorescence quantum yield of 15.8% in water. PZL-BDP NPs with excellent stability and biocompatibility exhibited a large Stokes shift (Δλ = 111 nm) which resulted in the reduction of external interference and enhancement of the fluorescence contrast. Furthermore, these nanoparticles could be readily internalized by HeLa cells and they stain the cells in just five seconds, indicating an ultrafast bioimaging protocol. Moreover, long-term tracking fluorescence signals in vivo for about 12 days were obtained. The bright red fluorescence, ultrafast cell staining ability, and long-term in vivo tracking competence outline the great potential of rational design nanomaterials with AIE characteristics for monitoring biological processes.
Photocatalysis is considered to be one of the possible routes to solve energy crises at a low cost. Graphitic-C
3
N
4
combined with other semiconductors at the nanoscale has demonstrated a promising ...potential in photocatalysis application owing to the heterojunction configuration. In this study, Ag/g-C
3
N
4
/CuNb
2
O
6
-4 (mass ratio of CuNb
2
O
6
to g-C
3
N
4
= 1:4) composites were prepared by photo-deposition of Ag particles on the hydrothermally synthesized g-C
3
N
4
/CuNb
2
O
6
-4 composites. The microstructure, morphology, and light absorption property of the photocatalysts were characterized by X-ray diffractometry, scanning electron microscopy, transmission electron microscopy, X-ray photoelectron spectroscopy, and UV–Vis diffuse reflectance spectroscopy. The photocatalytic properties of photocatalysts and active species responsible for the degradation of RhB dye under visible light were investigated. After loading Ag particles on the g-C
3
N
4
/CuNb
2
O
6
-4 composites, the resulting Ag/g-C
3
N
4
/CuNb
2
O
6
-4 composites show a bandgap of ~ 2.31 eV and a significant increase in photocatalytic efficiency. In particular, the photocatalytic activity of 11% Ag/g-C
3
N
4
/CuNb
2
O
6
-4 composite (Ag mass fraction = 11%) is nearly seven times that of orthorhombic CuNb
2
O
6
and 3.8 times that of g-C
3
N
4
/CNO-4 composite. The Z-scheme heterojunction has been successfully formed in the Ag/g-C
3
N
4
/CuNb
2
O
6
-4 composites and it enhances the photocatalytic performance significantly with the best degradation efficiency of 88% after 2 h.
As a typical class of crystalline porous materials, metal-organic framework possesses unique features including versatile functionality, structural and compositional tunability. After being reduced ...to two-dimension, ultrathin metal-organic framework layers possess more external excellent properties favoring various technological applications. In this review article, the unique structural properties of the ultrathin metal-organic framework nanosheets benefiting from the planar topography were highlighted, involving light transmittance, and electrical conductivity. Moreover, the design strategy and versatile fabrication methodology were summarized covering discussions on their applicability and accessibility, especially for porphyritic metal-organic framework nanosheet. The current achievements in the bioapplications of two-dimensional metal-organic frameworks were presented comprising biocatalysis, biosensor, and theranostic, with an emphasis on reactive oxygen species-based nanomedicine for oncology treatment. Furthermore, current challenges confronting the utilization of two-dimensional metal-organic frameworks and future opportunities in emerging research frontiers were presented.
The purpose of this study was to investigate the effects of different dietary fiber compounds (DFCs) on characteristic human flora and their metabolites mediated by the longevity dietary pattern ...analyzed by in vitro fermentation. The results show that DFC1 (cereal fiber) increased the level of Lactobacillus (p < 0.05), DFC2 (fruit and vegetable and cereal fiber) promoted the growth of Lactobacillus and Bifidobacterium more significantly than DFC3 (fruit and vegetable fiber) (p < 0.01), and all three DFCs decreased the level of Escherichia coli (p < 0.05). The metabolomic analysis showed that there was variability in the metabolites and the metabolic pathways of different DFCs. The redundancy analysis revealed that the fiber content was positively correlated with Lactobacillus, Bifidobacterium, Bacteroides, acetic acid, butyric acid, propionic acid, lactic acid, and betaine, and negatively correlated with Escherichia coli, succinic acid, alanine, choline, aspartic acid, and α-glucose. Overall, this study found that different DFCs have different positive correlations on characteristic human flora and metabolites, and DFC2 is more favorable to the proliferation of the intestinal beneficial genera Lactobacillus and Bifidobacterium after in vitro fermentation, having a probiotic role in glucose, amino acid, and lipid metabolisms. This study may provide a theoretical reference for the search of optimal dietary fiber combination strategies mediated by longevity dietary pattern.
The Rab GTPase activating protein known as Akt substrate of 160 kDa (AS160 or TBC1D4) regulates insulin-stimulated glucose uptake in skeletal muscle, the heart, and white adipose tissue (WAT). A ...novel rat AS160-knockout (AS160-KO) was created with CRISPR/Cas9 technology. Because female AS160-KO versus wild type (WT) rats had not been previously evaluated, the primary objective of this study was to compare female AS160-KO rats with WT controls for multiple, important metabolism-related endpoints. Body mass and composition, physical activity, and energy expenditure were not different between genotypes. AS160-KO versus WT rats were glucose intolerant based on an oral glucose tolerance test (P<0.001) and insulin resistant based on a hyperinsulinemic-euglycemic clamp (HEC; P<0.001). Tissue glucose uptake during the HEC of female AS160-KO versus WT rats was: 1) significantly lower in epitrochlearis (P<0.05) and extensor digitorum longus (EDL; P<0.01) muscles of AS160-KO compared to WT rats; 2) not different in soleus, gastrocnemius or WAT; and 3) ~3-fold greater in the heart (P<0.05). GLUT4 protein content was reduced in AS160-KO versus WT rats in the epitrochlearis (P<0.05), EDL (P<0.05), gastrocnemius (P<0.05), soleus (P<0.05), WAT (P<0.05), and the heart (P<0.005). Insulin-stimulated glucose uptake by isolated epitrochlearis and soleus muscles was lower (P<0.001) in AS160-KO versus WT rats. Akt phosphorylation of insulin-stimulated tissues was not different between the genotypes. A secondary objective was to probe processes that might account for the genotype-related increase in myocardial glucose uptake, including glucose transporter protein abundance (GLUT1, GLUT4, GLUT8, SGLT1), hexokinase II protein abundance, and stimulation of the AMP-activated protein kinase (AMPK) pathway. None of these parameters differed between genotypes. Metabolic phenotyping in the current study revealed AS160 deficiency produced a profound glucoregulatory phenotype in female AS160-KO rats that was strikingly similar to the results previously reported in male AS160-KO rats.
Skeletal muscle is the major site for insulin-stimulated glucose disposal, and muscle insulin resistance confers many negative health outcomes. Muscle is composed of multiple fiber types, and ...conventional analysis of whole muscles cannot elucidate fiber type differences at the cellular level. Previous research demonstrated that a brief (two weeks) high fat diet (HFD) caused insulin resistance in rat skeletal muscle. The primary aim of this study was to determine in rat skeletal muscle the influence of a brief (two weeks) HFD on glucose uptake (GU) ± insulin in single fibers that were also characterized for fiber type. Epitrochlearis muscles were incubated with
H-2-deoxyglucose (2DG) ± 100 µU/ml insulin. Fiber type (myosin heavy chain expression) and 2DG accumulation were measured in whole muscles and single fibers. Although fiber type composition of whole muscles did not differ between diet groups, GU of insulin-stimulated whole muscles from LFD rats significantly exceeded HFD values (P < 0.005). For HFD versus LFD rats, GU of insulin-stimulated single fibers was significantly (P < 0.05) lower for IIA, IIAX, IIBX, IIB, and approached significance for IIX (P = 0.100), but not type I (P = 0.776) fibers. These results revealed HFD-induced insulin resistance was attributable to fiber type selective insulin resistance and independent of altered fiber type composition.
In recent years, reactive species-based cancer therapies have attracted tremendous attention due to their simplicity, controllability, and effectiveness. Herein, we overviewed the state-of-art ...advance for photo-controlled generation of highly reactive radical species with nanomaterials for cancer therapy. First, we summarized the most widely explored reactive species, such as singlet oxygen, superoxide radical anion (O2●-), nitric oxide (●NO), carbon monoxide, alkyl radicals, and their corresponding secondary reactive species generated by interaction with other biological molecules. Then, we discussed the generating mechanisms of these highly reactive species stimulated by light irradiation, followed by their anticancer effect, and the synergetic principles with other therapeutic modalities. This review might unveil the advantages of reactive species-based therapeutic methodology and encourage the pre-clinical exploration of reactive species-mediated cancer treatments.
Reactive species-based cancer therapy modalities triggered-by light irradiation have been paid tremendous attention due to their distinct advantages. Here, we overviewed the latest advances involving the material design and biomedical application mechanism of reactive oxygen, reactive nitrogen and reactive carbon species. Display omitted
•The most widely explored reactive species, such as 1O2, O2●-, ●NO, CO, alkyl radicals are specifically summarized.•The generating mechanisms of these reactive species triggered-by light irradiation are overviewed.•This review will unveil the innate advantages of reactive species-based therapeutic methodology.
Polycystic ovary syndrome (PCOS) is a major cause of anovulatory sterility in women, and most PCOS patients exhibit hyperandrogenism (HA). Liver kinase b1 (LKB1) is a tumor suppressor that has ...recently been reported to be involved in PCOS. However, the mechanism by which LKB1 affects HA has not previously been elucidated. We report here that ovarian LKB1 levels are significantly decreased in a female mouse model of HA. Moreover, we report that LKB1 expression is inhibited by elevated androgens via activation of androgen receptors. In addition, LKB1 treatment was observed to suppress androgen synthesis in theca cells and promote estrogen production in granulosa cells by regulating steroidogenic enzyme expression. As expected, LKB1 knockdown inhibited estrogen levels and enhanced androgen levels, and LKB1‐transgenic mice were protected against HA. The effect of LKB1 appears to be mediated via IGF‐1 signaling. In summary, we describe here a key role for LKB1 in controlling sex hormone levels.
Liver kinase b1 (LKB1) inhibited the generation of androgen in theca cells and promoted the generation of estrogen in granulosa cells through reducing CYP17A1 expression and enhancing CYP19A1 expression via activating the IGF pathway in polycystic ovary syndrome (PCOS). Our findings indicate the crucial role of the LKB1‐IGF signaling network in PCOS.
Traditional genetic analysis relies on mutants with observable phenotypes. Mutants lacking visible abnormalities may nevertheless exhibit molecular differences useful for defining gene function. To ...examine this, we analyzed tissue-specific transcript profiles from Arabidopsis thaliana transcription factor gene mutants with known roles in root epidermis development, but lacking a single-gene mutant phenotype due to genetic redundancy. We discovered substantial transcriptional changes in each mutant, preferentially affecting root epidermal genes in a manner consistent with the known double mutant effects. Furthermore, comparing transcript profiles of single and double mutants, we observed remarkable variation in the sensitivity of target genes to the loss of one or both paralogous genes, including preferential effects on specific branches of the epidermal gene network, likely reflecting the pathways of paralog subfunctionalization during evolution. In addition, we analyzed the root epidermal transcriptome of the transparent testa glabra2 mutant to clarify its role in the network. These findings provide insight into the molecular basis of genetic redundancy and duplicate gene diversification at the level of a specific gene regulatory network, and they demonstrate the usefulness of tissue-specific transcript profiling to define gene function in mutants lacking informative visible changes in phenotype.
In the protein nutrition strategy of middle-aged and elderly people, some believe that low protein is good for health, while others believe high protein is good for health. Facing the contradictory ...situation, the following hypothesis is proposed. There is a process of change from lower to higher ratio of protein nutritional requirements that are good for health in the human body after about 50 years of age, and the age at which the switch occurs is around 65 years of age. Hence, in this study, 50, 25-month-old male rats were randomly divided into five groups: Control (basal diet), LP (low-protein diet with a 30% decrease in protein content compared to the basal diet), HP (high-protein diet with a 30% increase in protein content compared to the basal diet), Model 1 (switched from LP to HP feed at week 4), and Model 2 (switched from LP to HP feed at week 7). After a total of 10 weeks intervention, the liver and serum samples were examined for aging-related indicators, and a newly comprehensive quantitative score was generated using principal component analysis (PCA). The effects of the five protein nutritional modalities were quantified in descending order: Model 1 > HP > LP > Control > Model 2. Furthermore, the differential metabolites in serum and feces were determined by orthogonal partial least squares discriminant analysis, and 15 differential metabolites, significantly associated with protein intake, were identified by Spearman’s correlation analysis (
p
< 0.05). Among the fecal metabolites, 10 were positively correlated and 3 were negatively correlated. In the serum, tyrosine and lactate levels were positively correlated, and acetate levels were negatively correlated. MetaboAnalyst analysis identified that the metabolic pathways influenced by protein intake were mainly related to amino acid and carbohydrate metabolism. The results of metabolomic analysis elucidate the mechanisms underlying the preceding effects to some degree. These efforts not only contribute to a unified protein nutrition strategy but also positively impact the building of a wiser approach to protein nutrition, thereby helping middle-aged and older populations achieve healthy aging.
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