Human skeletal muscle aging atlas.

Skeletal muscle aging is a key contributor to age-related frailty and sarcopenia with substantial implications for global health. Here we profiled 90,902 single cells and 92,259 single nuclei from 17 donors to map the aging process in the adult human intercostal muscle, identifying cellular changes in each muscle compartment. We found that distinct subsets of muscle stem cells exhibit decreased ribosome biogenesis genes and increased CCL2 expression, causing different aging phenotypes. Our atlas also highlights an expansion of nuclei associated with the neuromuscular junction, which may reflect re-innervation, and outlines how the loss of fast-twitch myofibers is mitigated through regeneration and upregulation of fast-type markers in slow-twitch myofibers with age. Furthermore, we document the function of aging muscle microenvironment in immune cell attraction. Overall, we present a comprehensive human skeletal muscle aging resource ( https://www.muscleageingcellatlas.org/ ) together with an in-house mouse muscle atlas to study common features of muscle aging across species.

Medical Image Fusion Based on Local Saliency Energy and Multi-scale Fractal Dimension.

BACKGROUND: At present, there are some problems in multimodal medical image fusion, such as texture detail loss, leading to edge contour blurring and image energy loss, leading to contrast reduction. OBJECTIVE: To solve these problems and obtain higher-quality fusion images, this study proposes an image fusion method based on local saliency energy and multi-scale fractal dimension. METHODS: First, by using a non-subsampled contourlet transform, the medical image was divided into 4 layers of high-pass subbands and 1 layer of low-pass subband. Second, in order to fuse the high-pass subbands of layers 2 to 4, the fusion rules based on a multi-scale morphological gradient and an activity measure were used as external stimuli in pulse coupled neural network. Third, a fusion rule based on the improved multi-scale fractal dimension and new local saliency energy was proposed, respectively, for the low-pass subband and the 1st closest to the low-pass subband. Layerhigh pass sub-bands were fused. Lastly, the fused image was created by performing the inverse non-subsampled contourlet transform on the fused sub-bands. RESULTS: On three multimodal medical image datasets, the proposed method was compared with 7 other fusion methods using 5 common objective evaluation metrics. CONCLUSION: Experiments showed that this method can protect the contrast and edge of fusion image well and has strong competitiveness in both subjective and objective evaluation.

A novel prognostic model based on immunogenic cell death-related genes for improved risk stratification in hepatocellular carcinoma patients.

PURPOSE: Hepatocellular carcinoma (HCC) is a prevalent primary malignant tumor with increasing incidence and mortality rates in recent years. The treatment options for advanced HCC are very limited. Immunogenic cell death (ICD) plays an important role in cancer, in particular immunotherapy. However, the specific ICD genes and their prognostic values in HCC remain to be investigated. METHODS: The TCGA-LIHC datasets were obtained from TCGA database, LIRI-JP datasets were obtained from ICGC database, and immunogenic cell death (ICD) genes datasets were obtained from previous literature. WGCNA analysis identifies ICD-related genes. Functional analysis was used to investigate the biological characteristics of ICD-related genes. Univariate Cox analysis and least absolute shrinkage and selection operator (LASSO) Cox regression analysis was used to select prognostic ICD-related genes and construct a prognostic risk score. Prognostic independence of ICD risk scores was determined by univariate and multivariate Cox regression analyses. A nomogram was then constructed and the diagnostic value was assessed using decision curve analysis. Immune infiltration analysis and drug sensitivity analysis were used to investigate immune cell enrichment and drug response in HCC patients classified as low or high risk based on their risk score. RESULTS: Most of the ICD genes were differentially expressed in normal and HCC patients, and some ICD genes were differentially expressed in different clinical groups. A total of 185 ICD-related genes were identified by WGCNA. Prognostic ICD-related genes were selected using a univariate Cox analysis. A model comprising nine prognosis ICD-related gene biomarkers was developed. Patients was divided into high-risk and low-risk groups, and patients in high-risk groups had poorer outcomes. Meanwhile, the reliability of the model was verified by external independent data. The Independent prognostic value of the risk score in HCC was investigated by univariate and multivariate Cox analyses. Diagnostic nomogram was constructed to predict prognosis. Through immune infiltration analysis, we found that some innate and adaptive immune cells were significantly different between low- and high-risk groups. CONCLUSION: We developed and validated a novel prognostic predictive classification system for HCC based on nine ICD-related genes. In addition, immune-related predictions and model could help predict the outcomes of HCC and could provide a reference for clinical practice.

T Cells With Activated STAT4 Drive the High-Risk Rejection State to Renal Allograft Failure After Kidney Transplantation.

In kidney transplantation, deteriorated progression of rejection is considered to be a leading course of postoperative mortality. However, the conventional histologic diagnosis is limited in reading the rejection status at the molecular level, thereby triggering mismatched pathogenesis with clinical phenotypes. Here, by applying uniform manifold approximation and projection and Leiden algorithms to 2,611 publicly available microarray datasets of renal transplantation, we uncovered six rejection states with corresponding signature genes and revealed a high-risk (HR) state that was essential in promoting allograft loss. By identifying cell populations from single-cell RNA sequencing data that were associated with the six rejection states, we identified a T-cell population to be the pathogenesis-triggering cells associated with the HR rejection state. Additionally, by constructing gene regulatory networks, we identified that activated STAT4, as a core transcription factor that was regulated by PTPN6 in T cells, was closely linked to poor allograft function and prognosis. Taken together, our study provides a novel strategy to help with the precise diagnosis of kidney allograft rejection progression, which is powerful in investigating the underlying molecular pathogenesis, and therefore, for further clinical intervention.

Crocins: A comprehensive review of structural characteristics, pharmacokinetics and therapeutic effects.

Crocins, as a kind of water-soluble carotenoid pigment, are a series of ester compounds formed from crocetin and gentibiose or glucose, and mainly distributed among Crocus sativus L. (CSL), Gardenia jasminoides Ellis. (GJE). Crocins exhibit a wide range of pharmacological effects on neurodegeneration, cardiovascular disease, cerebrovascular disease, depression, liver disease, arthritis, tumor, diabetes, etc. This review systematically discussed the pharmacologic study of crocins in the aspect of structural characteristic and pharmacokinetics, and summarized the mechanism of treating disease. It summarized the abundant research of crocins from 1984 to 2020 based on the above aspects, which provide a reference for the deeply development and application of crocins.

[Quality changes of Gardeniae Fructus Praeparatus processed by different frying methods: a color-component correlation analysis].

The chromatic values of the broken-fried and single-fried Gardeniae Fructus Praeparatus(GFP) were measured by the color analyzer to analyze the color variation rule, and the contents of 10 main components were determined by ultra-high performance liquid chromatography(UPLC). The multivariate statistical analysis, Pearson correlation analysis, and discriminant analysis were conducted to investigate the color and components of GFP samples. The experimental results revealed that L~*, a~*, b~*, and E~*ab decreased continuously during processing, and the color of samples gradually deepened. The trend and range of chromatic values during broken-frying and single-frying processes were basically identical. Gardenoside, crocin-Ⅰ(C-Ⅰ), and crocin-Ⅱ(C-Ⅱ) showed an obviously downward trend, while the contents of geniposidic acid and 5-hydroxymethylfurfural(5-HMF) increased significantly. Shanzhiside, deacetyl-asperulosidic acid methyl ester, and geniposide(G2) showed a downward trend. Scandoside methyl ester rose first and fell later. Genipin-1-O-gentiobioside(G1) went through a decrease-increase-decrease trend. The change trends of component contents during broken-frying and single-frying processes were generally consistent, but the change range was different. Among all the components, scandoside methyl ester and G1 showed obvious change. Because of different stir-frying time, the change rate of each component content in the process of broken-frying was higher than that in single-frying process. Additionally, geniposidic acid, gardenoside, scandoside methyl ester, C-Ⅰ, C-Ⅱ, and 5-HMF exhibited a higher correlation with apparent color. On the basis of above findings, the discriminant function of two frying processes was established, which could be applied to the discrimination of broken-fried and single-fried samples. This study analyzed the dynamic quality change rule of GFP during broken-frying and single-frying processes based on color-component correlation analysis, and found the two methods showed consistent change trend, yet with slight difference in the quality of samples. This study can provide data support for the processing of GFP.

The Event-Related Potentials Responding to Outcome Valence and Expectancy Violation during Feedback Processing.

Feedback-related negativity (FRN) is believed to encode reward prediction error (RPE), a term describing whether the outcome is better or worse than expected. However, some studies suggest that it may reflect unsigned prediction error (UPE) instead. Some disagreement remains as to whether FRN is sensitive to the interaction of outcome valence and prediction error (PE) or merely responsive to the absolute size of PE. Moreover, few studies have compared FRN in appetitive and aversive domains to clarify the valence effect or examine PE's quantitative modulation. To investigate the impact of valence and parametrical PE on FRN, we varied the prediction and feedback magnitudes within a probabilistic learning task in valence (gain and loss domains, Experiment 1) and non-valence contexts (pure digits, Experiment 2). Experiment 3 was identical to Experiment 1 except that some blocks emphasized outcome valence, while others highlighted predictive accuracy. Experiments 1 and 2 revealed a UPE encoder; Experiment 3 found an RPE encoder when valence was emphasized and a UPE encoder when predictive accuracy was highlighted. In this investigation, we demonstrate that FRN is sensitive to outcome valence and expectancy violation, exhibiting a preferential response depending on the dimension that is emphasized.

[Correlation analysis of color change and Maillard reaction during processing of Gardeniae Fructus Praeparatus].

The chromaticity space parameters of the samples during the processing of Gardeniae Fructus Praeparatus(Jiaozhizi in Chinese herbal name, JZZ) were measured by the visual analyzer to analyze the color variation rule during the processing of JZZ, and the content changes of total reducing sugar, total amino acid and 5-hydroxymethylfurfural(5-HMF) related to Maillard reaction were measured. Pearson correlation analysis and linear regression analysis of the data were carried out by SPSS 24.0 software. The experimental results showed that the objective coloration of the samples in the processing of JZZ was basically consistent with the traditional subjective color judgment; the contents of total reducing sugar and total amino acids showed a decreasing trend during the processing of JZZ, and the content of 5-HMF showed an increasing trend, which was in line with Maillard reaction law. Pearson correlation analysis results showed that there was a significant correlation between the chromaticity space parameters L~*(lightness value), a~*(red green value), b~*(yellow blue value), E~*ab(total color value) and the contents of total reducing sugar, total amino acid and 5-HMF(P<0.01), among which the values of L~*, a~*, b~*, E~*ab were positively correlated with the contents of total reducing sugar and total amino acid, and negatively correlated with the contents of 5-HMF. The results of linear regression analysis also showed that these two were highly correlated. In this study, by establishing the correspondence relationship between the color change of JZZ processing and Maillard reactants, wecan not only provide a basis for the objective digital expression of subjective color of JZZ, but also provide a reference for explaining the processing mechanism of JZZ from a new perspective.

Assessment of ramie leaf (Boehmeria nivea L. gaud) as an animal feed supplement in P.R. China.

Tropical and subtropical regions were quite short of high-quality protein forage. Ramie (Boehmeria nivea L. Gaud) leaves as crop by products, are rich in protein and widely cultivated in tropical and subtropical regions. Thence, the development and utilization of ramie is of great significance to animal production in these regions. But it contained high level of tannins and total phenols, which may produce potentially adverse effect. It is very essential to evaluate the safety of ramie leaves before they are used as feed supplements. To evaluate potential toxic level of ramie leaf, control group, low dose and high dose (0, 1, 2 g/kg·BW) groups of ramie leaf were conducted orally in Sprague-Dawley rats (SD rats). Body weight, hematology, and histopathology was assessed during 28 d of treatment and 14 d of recovery period. The results showed that there were no toxic symptoms appeared in the treated and control groups. There were a few individual indicators showed abnormal, but most indices of body weight, organ weight ratios and hematology were normal. And compared to control group, it showed no significant differences (P>0.05). Histopathological examination of the high dose group and control group showed that there was no lesions related to ramie administration. The pathological changes appeared in the liver, and lungs of rats in individual rat of both groups were common and spontaneous, and had no significant differences (P>0.05). These results suggest that under this experimental condition, up to 2 g/kg·BW intragastric administration of ramie leaf did not produce adverse effect to SD rats. These findings would provide available information for ramie leaf to utilize as a feed supplement, particularly in P.R. China.

Neighboring genes are closely related to whole genome duplications after their separation.

BACKGROUND: The gene order in a eukaryotic genome is not random. Some neighboring genes show specific similarities, while others become separated during evolution. Whole genome duplication events (WGDs) have been recognized as an important evolutionary force. The potential relationship between the separation of neighboring genes and WGDs needs to be investigated. In this study, we investigated whether there is a potential relationship between separated neighboring gene pairs and WGDs, and the mechanism by which neighboring genes are separated. Additionally, we studied whether neighboring genes tend to show intrachromosomal colocalization after their neighborhood was disrupted and the factors facilitating the intrachromosomal colocalization of separated neighboring genes. RESULTS: The separation of neighboring gene pairs is closely related to whole genome duplication events. Furthermore, we found that there is a double linear relationship between separated neighboring genes, total genes, and WGDs. The process of separation of neighboring genes caused by WGDs is also not random but abides by the double linear model. Separated neighboring gene pairs tend to show intrachromosomal colocalization. The conservativism of separated neighboring genes and histone modification facilitate the intrachromosomal colocalization of neighboring genes after their separation. CONCLUSIONS: These results provide new insight into the understanding of evolutionary roles of locations and the relationship of neighboring gene pairs with whole genome duplications. Furthermore, understanding the proposed mechanism for intrachromosomal colocalization of separated genes benefits our knowledge of chromosomal interactions in the nucleus.

Assessment of mulberry leaf as a potential feed supplement for animal feeding in P.R. China.

OBJECTIVE: Mulberry (Morus alba L.) is a cultivated shrub grown widely in the sub-tropical and tropical areas. It has been shown that mulberry leaf contains high levels of protein while having polyphenols as phytonutrients. Therefore, it is important to conduct an experiment to assess potential toxic level from mulberry on behavior, blood hematological and coagulation parameter using Sprague-Dawley (SD) rats. METHODS: Both male and female SD rats were given an intragastric administration of respective treatments of mulberry leaf intakes (control, low and high levels). Parameters of feed intake, hematological and coagulation of blood parameters, as well as liveweight changes were taken during the 7 d of adaptation, 28 d of treatment exposure, and 14 d of recovery periods, respectively. All treatment data were statistically analyzed using analysis of variance of SPSS17.0 for Windows Statistical Software following the Randomized complete block design with sex as a block. RESULTS: Most of the parameters of the physical symptoms of the SD rats, were not significantly different (p>0.05) when compared with that of the control group. Those which remain unchanged in each dose group were, body weight (BW) gain, feed intake, the hematology and coagulation indexes. Although, there were a few individual indicators that were abnormal, but the overall physiological appearance of the rats were normal. CONCLUSION: Results under this experiment revealed that most hematological and coagulation parameters of the SD rats in both male and female were normal, although the weight gain of female rats in high-dose group was significantly reduced than those of the male rats. Under this study, the use of mulberry leaf up to 2 g/kg BW did not result in abnormal phenomenon in the SD rats. These findings would offer useful information for further in vivo feeding trials in animals to extensively use of mulberry leaf to improve animal production, particularly in P.R. China.

Intrachromosomal colocalization strengthens co-expression, co-modification and evolutionary conservation of neighboring genes.

BACKGROUND: Gene order and location in chromosomes of species are non-random. Neighboring gene pairs tend to display some similarities, such as co-expression and co-modification. However, the contribution of linear proximity, spatial proximity, and evolutionary proximity to these similarities remain unclear, together with whether the presence of several types of proximity can strengthens the similarities. RESULTS: In this study, we investigated the properties of three kinds of colocalized gene pairs: intrachromosomal colocalized gene pairs, always-neighboring gene pairs, and evolutionary neighboring gene pairs. Our analysis showed that (1) Different types of colocalized genes differentially contribute to co-expression, co-modifications and conservation across species; (2) Intrachromosomal colocalization can strengthen co-expression and co-modification of neighboring gene pairs and their conservation across species; (3) The combination of the three kinds of colocalization can lead to the strongest co-modification and is most strongly conserved across species. (4) Colocalized gene pairs are indicative of phylogenetic relationships and whole genome duplications (WGDs). CONCLUSIONS: These results provide valuable clues for future efforts to understand the characteristics of colocalized gene pairs and how the neighborhood affects their interactions.

Diastereoselective synthesis of beta-substituted-alpha,gamma-diaminobutyric acids and pyrrolidines containing multichiral centers.

A convenient and efficient way for the highly diastereoselective synthesis of beta-substituted-alpha,gamma-diaminobutyric acids and pyrrolidines containing multichiral centers has been well-developed. Michael addition of chiral tricyclic iminolactones 1 and 2 to nitroalkenes afforded the adducts in good yields (up to 95%) and excellent diastereoselectivities (up to dr > 99:1) when titanium(IV) isopropoxide was used. Configuration of the second new stereocenter was decided by the substitution of nitroalkene. Selective reduction and hydrolysis of the Michael adducts furnished the desired beta-substituted-alpha,gamma-diaminobutyric acids in good yields and high enantiomeric excesses (>99% ee). Synthesis of pyrrolidines containing multichiral centers has also been accomplished in good to excellent yields and diastereoselectivities under mild conditions via Michael-Mannich tandem reactions using Cu(OTf)(2) or AgOTf as an activating reagent for aliphatic nitroalkenes.