Enhanced pH-sensitive anthocyanin film based on chitosan quaternary ammonium salt: A promising colorimetric indicator for visual pork freshness monitoring.

An intelligent pH response indicator film is an easy-to-use device for the real-time monitoring of meat freshness during transport and storage. Therefore, a novel pH-sensitive anthocyanin indicator film composed of polyvinyl alcohol-blueberry anthocyanin (BA)-2-hydroxypropyltrimethyl ammonium chloride chitosan (HACC) called PAH-2.0 with 1.2 mg/mL HACC to monitor meat freshness using HACC as the colorimetric enhancer has been developed. BA and HACC were mixed and immobilized in the polyvinyl alcohol matrix by hydrogen bonds, as confirmed via Fourier-transform infrared spectroscopy and X-ray diffraction. The inclusion of HACC improved the color stability and antioxidant and antibacterial properties of the PAH-2.0 film. When applied to pork for freshness monitoring at 4 °C, three freshness stages, including fresh, sub-fresh, and spoiled, could be clearly distinguished based on the color variations of the PAH-2.0 film. The distinct hierarchical color change from purple to blue-violet and finally to grayish-blue was highly correlated with the indicators of pork freshness: pH values, total volatile basic nitrogen, and total viable count. This study provides a simple and promising approach for fabricating meat freshness indicator films with high color recognition accuracy, thereby offering new possibilities for visual meat freshness monitoring.

Changes of medical staffs' subjective well-being in China (2004-2020): A cross-temporal meta-analysis.

Subjective well-being is a crucial index measuring the mental health of medical staffs, and it is necessary to examine the changes in subjective well-being (SWB) level of Chinese medical staffs with time. A cross-temporal meta-analysis was performed using papers that measured the SWB level of Chinese medical staffs between 2004 and 2020. Moreover, a time-lag analysis was conducted to define whether the macro-social indicators can explain the changes in SWB. A total of 47 papers were included in the final sample. The results revealed that score of SWB was significantly negatively correlated with the year. Score of SWB was significantly associated with six social indicators of economic condition (the residents' consumption level, housing prices, and old-age dependency ratio), social connectedness (the divorce rate and the urbanization level), and overall threat (the crime rate), which indicated that social change may account for the decline of Chinese medical staffs' SWB level. Our study revealed a decreasing trend of Chinese medical staffs' SWB level over time, which was associated with macro-social changes in diverse areas. In addition, combined with the corresponding macro-social indicators, a three-dimensional theoretical framework is proposed to explain the SWB for medical staffs as a group.

Changes in mental health levels among Chinese physical education college students from 1995 to 2019.

To explore the changes in the mental health levels of Chinese physical education college students, the present study conducted a cross-temporal meta-analysis of 43 papers that adopted the Symptom Checklist 90 (SCL-90) from 1995 to 2019. The results showed that the average scores of the seven SCL-90 factors were negatively correlated with the year of data collection. The socioeconomic indicators (GDP, per capita GDP and household consumption level) were significantly negatively correlated with the eight dimension scores of the SCL-90 (except for phobic anxiety). The mean effect sizes of the sex differences in the seven dimension scores (except depression and phobic anxiety) were lower than the small effect size. In conclusion, Chinese physical education college students' mental health levels have increased in the past 25 years. This phenomenon may be related to Chinese socioeconomic growth, the implementation of national sports policies, and the provision of mental health education for college students. In addition, although the increasing trend in the mental health level of female students was more obvious, there were no significant sex differences.

Analysis of serum fatty acid, amino acid, and organic acid profiles in gestational hypertension and gestational diabetes mellitus via targeted metabolomics.

This study aimed to characterize metabolite differences and correlations between hypertensive disorders of pregnancy (HP) and gestational diabetes mellitus (GDM) using univariate, multivariate analyses, RF, and pathway analyses in a cross-sectional study. Dietary surveys were collected and targeted metabolomics was applied to measure levels of serum fatty acids, amino acids, and organic acids in 90 pregnant women at 24-28 weeks gestation at the First Affiliated Hospital of Harbin Medical University. Principal components analysis (PCA) and partial least squares-discriminatory analysis (PLS-DA) models were established to distinguish HP, GDM, and healthy, pregnant control individuals. Univariate and multivariate statistical analyses and Random Forest (RF) were used to identify and map co-metabolites to corresponding pathways in the disease states. Finally, risk factors for the disease were assessed by receiver operating characteristics (ROC) analysis. Dietary survey results showed that HP and GDM patients consumed a high-energy diet and the latter also consumed a high-carbohydrate and high-fat diet. Univariate analysis of clinical indices revealed HP and GDM patients had glycolipid disorders, with the former possessing more severe organ dysfunction. Subsequently, co-areas with significant differences identified by basic discriminant analyses and RF revealed lower levels of pyroglutamic acid and higher levels of 2-hydroxybutyric acid and glutamic acid in the GDM group. The number of metabolites increased in the HP group as compared to the healthy pregnant control group, including pyroglutamic acid, γ-aminobutyric acid (GABA), glutamic acid, oleic acid (C18:1), and palmitic acid (C16:0). ROC curves indicated that area under curve (AUC) for pyroglutamic acid in the GDM group was 0.962 (95% CI, 0.920-1.000), and the AUC of joint indicators, including pyroglutamic acid and GABA, in the HP group was 0.972 (95% CI, 0.938-1.000). Collectively, these results show that both GDM and HP patients at mid-gestation possessed dysregulated glucose and lipid metabolism, which may trigger oxidative stress via glutathione metabolism and biosynthesis of unsaturated fatty acids.

Adenosine triphosphate (ATP) and zinc(II) ions responsive pyrene based turn-on fluorescent probe and its application in live cell imaging.

A novel highly selective and sensitive turn-on fluorescent chemosensor PCE to recognize Zn2+ has been developed. The sensor PCE displays a remarkable fluorescent enhancement at 456 nm (λex = 340 nm) with Zn2+ without the interference of other biologically important relevant metal ions in aqueous acetonitrile solution. Job's plot and mass spectral studies divulge such the interaction of PCE by Zn2+ was 1:1 binding stoichiometry. The association constant and detection limit of PCE to recognize Zn2+ was found to be 0.948 × 104 M-1 and 4.82 × 10-7 M respectively. The nature of turn-on fluorescence sensor was supported by TD-DFT calculations. And the synthesized probe PCE was able to image intracellular Zn2+ in living cells using confocal imaging techniques. PCE-Zn ensemble showed the remarkable fluorescence enhancement with ATP selectively among other biologically important phosphates. 31P NMR experiments suggesting that the triphosphates unit of ATP is intact with the PCEZn. PCE-Zn ensemble can be utilized for monitoring ATP in live cells.

Aging-related markers in rat urine revealed by dynamic metabolic profiling using machine learning.

The process of aging and metabolism is intimately intertwined; thus, developing biomarkers related to metabolism is critical for delaying aging. However, few studies have identified reliable markers that reflect aging trajectories based on machine learning. We generated metabolomic profiles from rat urine using ultra-performance liquid chromatography/mass spectrometry. This was dynamically collected at four stages of the rat's age (20, 50, 75, and 100 weeks) for both the training and test groups. Partial least squares-discriminant analysis score plots revealed a perfect separation trajectory in one direction with increasing age in the training and test groups. We further screened 25 aging-related biomarkers through the combination of four algorithms (VIP, time-series, LASSO, and SVM-RFE) in the training group. They were validated in the test group with an area under the curve of 1. Finally, six metabolites, known or novel aging-related markers, were identified, including epinephrine, glutarylcarnitine, L-kynurenine, taurine, 3-hydroxydodecanedioic acid, and N-acetylcitrulline. We also found that, except for N-acetylcitrulline (p < 0.05), the identified aging-related metabolites did not differ between tumor-free and tumor-bearing rats at 100 weeks (p > 0.05). Our findings reveal the metabolic trajectories of aging and provide novel biomarkers as potential therapeutic antiaging targets.

Metabolomics Study of Isocaloric Different Dietary Patterns on the Life Span in Healthy Population.

PURPOSE: How to prolong life by diet has been widely concerned. There are many reports about the effects of different dietary patterns on life span, but the results are not consistent. The main reason may be that total energy intake has not been considered. This study aims to explore the effects of isocaloric different dietary patterns on population life span. MATERIALS AND METHODS: From the data of the follow-up population, eligible participators were divided into normal control (NC) group (28.31% fat, 12.37% protein, 62.30% carbohydrate), isocaloric high-fat (IHF) group (38.39% fat, 12.21% protein, 51.32% carbohydrate), isocaloric high-protein (IHP) group (33.41% fat, 17.10% protein, 52.67% carbohydrate) and isocaloric high-carbohydrate (IHC) group (22.23% fat, 10.52% protein, 70.13% carbohydrate) according to the dietary structure and the age stratification. Global serum metabolic profiling analysis by UPLC-Q-TOF-MS/MS technology, fatty acid and amino acid profiles in serum were determined by GC-MS and UPLC-TQ-MS technology. One-way ANOVA followed by Dunnett post hoc test and receiver operating characteristic (ROC) curve analysis were used to statistical analysis. RESULTS: Non-targeted metabolomics was to identify 18 potential metabolites related to longevity. ROC curve analysis to identify biomarkers indicated that the areas under the ROC (AUC) of the 12 of 18 biomarkers are above 0.9. The 12 biomarkers were mainly enriched in three metabolic pathways: lipid metabolism, amino acid metabolism and tricarboxylic acid cycle. Compared to control, 11 and 10 of 12 biomarkers showed the same trend with aging in IHP and IHC groups, respectively. Conversely, no differences were observed between IHF group and NC group. CONCLUSION: Without consideration of the nature of carbohydrates, fats and proteins, IHP and IHC diets might shorten life span by influencing amino acid metabolism, lipid metabolism and tricarboxylic acid cycle metabolism, while the isocaloric IHF diet has no effects on longevity.

Evolutionarily Conserved Roles for Apontic in Induction and Subsequent Decline of Cyclin E Expression.

Cyclin E is a key factor for S phase entry, and deregulation of Cyclin E results in developmental defects and tumors. Therefore, proper cycling of Cyclin E is crucial for normal growth. Here we found that transcription factors Apontic (Apt) and E2f1 cooperate to induce cyclin E in Drosophila. Functional binding motifs of Apt and E2f1 are clustered in the first intron of Drosophila cyclin E and directly contribute to the cyclin E transcription. Knockout of apt and e2f1 together abolished Cyclin E expression. Furthermore, Apt up-regulates Retinoblastoma family protein 1 (Rbf1) for proper chromatin compaction, which is known to repress cyclin E. Notably, Apt-dependent up-regulation of Cyclin E and Rbf1 is evolutionarily conserved in mammalian cells. Our findings reveal a unique mechanism underlying the induction and subsequent decline of Cyclin E expression.

The phytochemical epigallocatechin gallate prolongs the lifespan by improving lipid metabolism, reducing inflammation and oxidative stress in high-fat diet-fed obese rats.

We have recently reported that epigallocatechin gallate (EGCG) could extend lifespan in healthy rats. This study aimed to investigate the effects and mechanisms of a high dose of EGCG in extending the lifespan of obese rats. Ninety adult male Wistar rats were randomly divided into the control (NC), high-fat (HF) and EGCG groups. Serum glucose and lipids, inflammation and oxidative stress were dynamically determined from adulthood to death, and the transcriptome and proteome of the liver were also examined. The median lifespans of the NC, HF and EGCG groups were 693, 599 and 683 days, respectively, and EGCG delayed death by 84 days in obese rats. EGCG improved serum glucose and lipids and reduced inflammation and oxidative stress associated with aging in obese rats induced by a high-fat diet. EGCG also significantly decreased the levels of total free fatty acids (FFAs), SFAs and the n-6/n-3 ratio but significantly increased the n-3 FFAs related to longevity. The joint study of the transcriptome and proteome in liver found that EGCG exerted its effects mainly by regulating the suppression of hydrogen peroxide and oxygen species metabolism, suppression of oxidative stress, activation of fatty acid transport and oxidation and cholesterol metabolism. EGCG significantly increased the protein expression of FOXO1, Sirt1, CAT, FABP1, GSTA2, ACSL1 and CPT2 but significantly decreased NF-κB, ACC1 and FAS protein levels in the livers of rats. All the results indicate that EGCG extends lifespan by improving FFA metabolism and reducing the levels of inflammatory and oxidative stress in obese rats.

Dual functions of Rack1 in regulating Hedgehog pathway.

Hedgehog (Hh) pathway plays multiple roles in many physiological processes and its dysregulation leads to congenital disorders and cancers. Hh regulates the cellular localization of Smoothened (Smo) and the stability of Cubitus interruptus (Ci) to fine-tune the signal outputs. However, the underlying mechanisms are still unclear. Here, we show that the scaffold protein Rack1 plays dual roles in Hh signaling. In the absence of Hh, Rack1 promotes Ci and Cos2 to form a Ci-Rack1-Cos2 complex, culminating in Slimb-mediated Ci proteolysis. In the presence of Hh, Rack1 dissociates from Ci-Rack1-Cos2 complex and forms a trimeric complex with Smo and Usp8, leading to Smo deubiquitination and cell surface accumulation. Furthermore, we find the regulation of Rack1 on Hh pathway is conserved from Drosophila to mammalian cells. Our findings demonstrate that Rack1 plays dual roles during Hh signal transduction and provide Rack1 as a potential drug target for Hh-related diseases.

Usp7 promotes medulloblastoma cell survival and metastasis by activating Shh pathway.

The ubiquitin-specific protease Usp7 plays roles in multiple cellular processes through deubiquitinating and stabilizing numerous substrates, including P53, Pten and Gli. Aberrant Usp7 activity has been implicated in many disorders and tumorigenesis, making it as a potential target for therapeutic intervention. Although it is clear that Usp7 is involved in many types of cancer, its role in regulating medulloblastoma (MB) is still unknown. In this study, we show that knockdown of Usp7 inhibits the proliferation and migration of MB cells, while Usp7 overexpression exerts an opposite effect. Furthermore, we establish Usp7 knockout MB cell line using the CRISPR/Cas9 system and further confirm that Usp7 knockout also blocks MB cell proliferation and metastasis. In addition, we reveal that knockdown of Usp7 compromises Shh pathway activity and decrease Gli protein levels, while P53 level and P53 target gene expression have no obvious changes. Finally, we find that Usp7 inhibitors apparently inhibit MB cell viability and migration. Taken together, our findings suggest that Usp7 is important for MB cell proliferation and metastasis by activating Shh pathway, and is a putative therapeutic target for MBs.