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"Jing Zhen"
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إحضار الكتب المقدسة
عاش النبيل كو في بلدة تونغتايفو كان رجلا طيبا يحب الخير وعرض أن يستضيف سان تسانغ وتلاميذه لفترة طويلة، ولكنهم رفضوا رغم إلحاح عائلة النبيل؛ فلم يجدوا بدا من توديعهم. وما إن غادر سان تسانغ وتلاميذه حتى تعرض بيت النبيل للسرقة، وقتل النبيل كو، فأضمرت زوجته الضغينة لسان تسانغ وتلاميذه لأنهم لم يوافقوا على البقاء رغم الإلحاح عليهم، واتهمت الزوجة سان تسانغ وتلاميذه زورا بارتكاب الجريمة، وقدمت دعوى لمقاضاتهم. وفي طريق اللصوص للفرار، أرادوا سرقة سان تسانغ وتلاميذه أيضا، ولكن وو كونغ قبض عليهم، وحينما التقى سان تسانغ وتلاميذه بالضباط والجنود الذين جاؤوا لملاحقتهم، حدث سوء فهم أدى لاتهام سان تسانغ وتلاميذه.
Book
Circular RNA CirCHIPK3 promotes cell proliferation and invasion of breast cancer by sponging miR‐193a/HMGB1/PI3K/AKT axis
Background The aim of this study was to explore the potential mechanism of circular RNA (circRNA) CirCHIPK3 on the malignant proliferation and metastasis of breast cancer (BC). Methods Human BC samples and their matched normal adjacent tissues were obtained from 50 patients to assess the expression of CirCHIPK3 and its relationship with BC prognosis. A series of in vitro and in vivo functional experiments were carried out to elucidate the role of CirCHIPK3 in BC progression and its underlying molecular mechanisms. Moreover, the interaction of CirCHIPK3, miR‐193a, and HMGB1 was examined using bioinformatics, FISH, RIP, RNA‐pull down and luciferase reporter assays. Western blot analysis was performed to examine the expression of HMGB1, p‐PI3K, total PI3K, p‐AKT, and AKT after si‐CirCHIPK3 transfection. Results Upregulation of CirCHIPK3 was identified in BC, which predicted a worse prognosis in BC patients. Furthermore, it was found that CirCHIPK3 facilitated cell proliferation, migration, and invasion in BC by regulating miR‐193a/HMGB1/PI3K/AKT signaling. CirCHIPK3 acted as a sponge for miR‐193a to facilitate HMGB1 expression. si‐CirCHIPK3 also inhibited tumor growth of BC in nude mice. si‐CircCHIPK3 decreased HMGB1/PI3K/AKT signal expression in MDA‐MB‐231 cells, whereas overexpression of CircCHIPK3 enhanced HMGB1/PI3K/AKT signal. Conclusions CirCHIPK3 regulated miR‐193a/HMGB1/PI3K/AKT signaling to facilitate BC development and progression, providing a novel therapeutic target for BC. CirCHIPK3 regulated miR‐193a/HMGB1/PI3K/AKT signaling to facilitate BC development and progression, providing a novel therapeutic target for BC.
Journal Article
Machine learning-driven development of a stratified CES-D screening system: optimizing depression assessment through adaptive item selection
Objective
To develop a stratified screening tool through machine learning approaches for the Center for Epidemiologic Studies Depression Scale (CES-D-20) while maintaining diagnostic accuracy, addressing the efficiency limitations in large-scale applications.
Methods
Data were derived from the Chinese Psychological Health Guard Project (primary sample:
n
= 179,877; age 9–18) and China Labor-force Dynamics Survey (validation samples across age spans). We employed a two-stage machine learning approach: first applying Recursive Feature Elimination with multiple linear regression to identify core predictive items for total depression scores, followed by logistic regression for optimizing depression classification (CES-D ≥ 16). Model performance was systematically evaluated through discrimination (ROC analysis), calibration (Brier score), and clinical utility analyses (decision curve analysis), with additional validation using random forest and support vector machine algorithms across independent samples.
Results
The resulting stratified screening system consists of an initial four-item rapid screening layer (encompassing emotional, cognitive, and interpersonal dimensions) for detecting probable depression (AUC = 0.982, sensitivity = 0.945, specificity = 0.926), followed by an enhanced assessment layer with five additional items. Together, these nine items enable accurate prediction of the full CES-D-20 total score (R
2
= 0.957). This stratified approach demonstrated robust generalizability across age groups (R
2
> 0.94, accuracy > 0.91) and time points. Calibration analyses and decision curve analyses confirmed optimal clinical utility, particularly in the critical risk threshold range (0.3–0.6).
Conclusions
This study contributes to the refinement of CES-D by developing a machine learning-derived stratified screening version, offering an efficient and reliable approach that optimizes assessment burden while maintaining excellent psychometric properties. The stratified design makes it particularly valuable for large-scale mental health screening programs, enabling efficient risk stratification and targeted assessment allocation.
Journal Article
A Validated Set of Fluorescent-Protein-Based Markers for Major Organelles in Yeast (Saccharomyces cerevisiae)
Eukaryotic cells share a basic scheme of internal organization featuring membrane-based organelles. The use of fluorescent proteins (FPs) greatly facilitated live-cell imaging of organelle dynamics and protein trafficking. One major limitation of this approach is that the fusion of an FP to a target protein can and often does compromise the function of the target protein and alter its subcellular localization. The optimization process to obtain a desirable fusion construct can be time-consuming or even unsuccessful. In this work, we set out to provide a validated set of FP-based markers for major organelles in the budding yeast ( Saccharomyces cerevisiae ). Out of over 160 plasmids constructed, we present a final set of 42 plasmids, the recommendations for which are backed up by meticulous evaluations. The tool set includes three colors (green, red, and blue) and covers the endoplasmic reticulum (ER), nucleus, Golgi apparatus, endosomes, vacuoles, mitochondria, peroxisomes, and lipid droplets. The fidelity of the markers was established by systematic cross-comparison and quantification. Functional assays were performed to examine the impact of marker expression on the secretory pathway, endocytic pathway, and metabolic activities of mitochondria and peroxisomes. Concomitantly, our work constitutes a reassessment of organelle identities in this model organism. Our data support the recognition that “late Golgi” and “early endosomes,” two seemingly distinct terms, denote the same compartment in yeast. Conversely, all other organelles can be visually separated from each other at the resolution of conventional light microscopy, and quantification results justify their classification as distinct entities. IMPORTANCE Cells contain elaborate internal structures. For eukaryotic cells, like those in our bodies, the internal space is compartmentalized into membrane-bound organelles, each tasked with specialized functions. Oftentimes, one needs to visualize organelles to understand a complex cellular process. Here, we provide a validated set of fluorescent protein-based markers for major organelles in budding yeast. Yeast is a commonly used model when investigating basic mechanisms shared among eukaryotes. Fluorescent proteins are produced by cells themselves, avoiding the need for expensive chemical dyes. Through extensive cross-comparison, we make sure that each of our markers labels and only labels the intended organelle. We also carefully examined if the presence of our markers has any negative impact on the functionality of the cells and found none. Our work also helps answer a related question: are the structures we see really what we think they are?
Journal Article
Role of immune-related endoplasmic reticulum stress genes in sepsis-induced cardiomyopathy: Novel insights from bioinformatics analysis
The current study aims to elucidate the key molecular mechanisms linked to endoplasmic reticulum stress (ERS) in the pathogenesis of sepsis-induced cardiomyopathy (SIC) and offer innovative therapeutic targets for SIC.
The study downloaded dataset GSE79962 from the Gene Expression Omnibus database and acquired the ERS-related gene set from GeneCards. It utilized weighted gene co-expression network analysis (WGCNA) and conducted differential expression analysis to identify key modules and genes associated with SIC. The SIC hub genes were determined by the intersection of WGCNA-based hubs, DEGs, and ERS-related genes, followed by protein-protein interaction (PPI) network construction. Enrichment analyses, encompassing GO, KEGG, GSEA, and GSVA, were performed to elucidate potential biological pathways. The CIBERSORT algorithm was employed to analyze immune infiltration patterns. Diagnostic and prognostic models were developed to assess the clinical significance of hub genes in SIC. Additionally, in vivo experiments were conducted to validate the expression of hub genes.
Differential analysis revealed 1031 differentially expressed genes (DEGs), while WGCNA identified a hub module with 1327 key genes. Subsequently, 13 hub genes were pinpointed by intersecting with ERS-related genes. NOX4, PDHB, SCP2, ACTC1, DLAT, EDN1, and NSDHL emerged as hub ERS-related genes through the protein-protein interaction network, with their diagnostic values confirmed via ROC curves. Diagnostic models incorporating five genes (NOX4, PDHB, ACTC1, DLAT, NSDHL) were validated using the LASSO algorithm, highlighting only the prognostic significance of serum PDHB levels in predicting the survival of septic patients. Additionally, decreased PDHB mRNA and protein expression levels were observed in the cardiac tissue of septic mice compared to control mice.
This study elucidated the interplay between metabolism and the immune microenvironment in SIC, providing fresh perspectives on the investigation of potential SIC pathogenesis. PDHB emerged as a significant biomarker of SIC, with implications on its progression through the regulation of ERS and metabolism.
Journal Article
The impacts of COVID-19 outbreak on mental health in general population in different areas in China
This study aimed to explore the impacts of COVID-19 outbreak on mental health status in general population in different affected areas in China.
This was a comparative study including two groups of participants: (1) general population in an online survey in Ya'an and Jingzhou cities during the COVID-19 outbreak from 10-20 February 2020; and (2) matching general population selected from the mental health survey in Ya'an in 2019 (from January to May 2019). General Health Questionnaire (GHQ-12), Self-rating Anxiety Scale (SAS), and Self-rating Depression Scale (SDS) were used.
There were 1775 participants (Ya'an in 2019 and 2020: 537 respectively; Jingzhou in 2020: 701). Participants in Ya'an had a significantly higher rate of general health problems (GHQ scores ⩾3) in 2020 (14.7%) than in 2019 (5.2%) (
< 0.001). Compared with Ya'an (8.0%), participants in Jingzhou in 2020 had a significantly higher rate of anxiety (SAS scores ⩾50, 24.1%) (
< 0.001). Participants in Ya'an in 2020 had a significantly higher rate of depression (SDS scores ⩾53, 55.3%) than in Jingzhou (16.3%) (
< 0.001). The risk factors of anxiety symptoms included female, number of family members (⩾6 persons), and frequent outdoor activities. The risk factors of depression symptoms included participants in Ya'an and uptake self-protective measures.
The prevalence of psychological symptoms has increased sharply in general population during the COVID-19 outbreak. People in COVID-19 severely affected areas may have higher scores of GHQ and anxiety symptoms. Culture-specific and individual-based psychosocial interventions should be developed for those in need during the COVID-19 outbreak.
Journal Article
Synthesis of biomorphic tube-like CuO using pomelo white flesh as biotemplate and its sensing properties over H2S at room temperature
Biomorphic tube-like CuO was synthesized using pomelo white flesh as biotemplate for the first time. The sample showed a good selectivity to H
2
S in gasoline 92#, formaldehyde, CH
4
, H
2
, CO, toluene, acetone, and ethanol. Although there was an obvious change in response/recovery time with H
2
S concentration from 10 ppb to 10 ppm, all the response/recovery times were <60 s. Moreover, the sample exhibited stable detection performance for 5 ppm H
2
S at room temperature over a testing period of 3 months. The detection levels were uniform during cycling. This outstanding sensing performance is attributed to the unique structure, which was convenient for H
2
S molecule adsorption and facilitated the transformation of semiconducting p-type CuO to metallic CuS during H
2
S detection.
Journal Article
Polysaccharides of Fructus corni Improve Ovarian Function in Mice with Aging-Associated Perimenopause Symptoms
Objective. Perimenopause symptoms have an extremely high incidence in aging women. Development of new strategies to improve perimenopause symptoms is important topic in clinical context. Increasing studies have shown that the polysaccharides of Fructus corni (PFC) have many pharmacological activities including antiaging effects. Here, we evaluated the effects of PFC on the ovarian function in natural aging-associated perimenopause symptoms in mice. Methods. Natural aging mice (16-month old) were orally administrated with PFC at 1.11 g/kg daily for 24 days with none-treated young mice (3-month old) as control. Blood samples were collected for measurements of serum levels of estradiol, progesterone, luteinizing hormone (LH), and follicle stimulating hormone (FSH). Ovaries were isolated for histopathological and molecular exanimations. Results. We found that the aging mice had decreased number of growing follicles and corpus luteum in ovary, but treatment with PFC restored their amounts. Measurement of hormones showed that there were low serum levels of estradiol and progesterone but high levels of LH and FSH in aging mice; however PFC restored estradiol and progesterone levels but reduced LH and FSH levels. Immunohistochemical analysis with ovarian tissues also revealed that the expression of inhibin and insulin-like growth factor 1 was reduced in the ovary of aging mice but was restored by PFC. These data indicated that PFC regulated ovarian function-associated hormone levels in aging mice. Furthermore, there was reduced expression of antiapoptotic protein Bcl-2 and increased expression of proapoptotic molecules Bax and cleaved-caspase-3 in the ovary of aging mice. However, treatment with PFC upregulated Bcl-2 and downregulated Bax and cleaved-caspase-3, suggesting that PFC inhibited apoptosis of granulosa cells in the ovary of aging mice. Conclusion. PFC improved the ovarian function in mice, which had high potential to be developed as a safe and effective therapeutic remedy for aging-associated perimenopause symptoms.
Journal Article
Smooth muscle NF90 deficiency ameliorates diabetic atherosclerotic calcification in male mice via FBXW7-AGER1-AGEs axis
Hyperglycemia accelerates calcification of atherosclerotic plaques in diabetic patients, and the accumulation of advanced glycation end products
(
AGEs) is closely related to the atherosclerotic calcification. Here, we show that hyperglycemia-mediated AGEs markedly increase vascular smooth muscle cells (VSMCs) NF90/110 activation in male diabetic patients with atherosclerotic calcified samples. VSMC-specific NF90/110 knockout in male mice decreases obviously AGEs-induced atherosclerotic calcification, along with the inhibitions of VSMC phenotypic changes to osteoblast-like cells, apoptosis, and matrix vesicle release. Mechanistically, AGEs increase the activity of NF90, which then enhances ubiquitination and degradation of AGE receptor 1 (AGER1) by stabilizing the mRNA of E3 ubiquitin ligase FBXW7, thus causing the accumulation of more AGEs and atherosclerotic calcification. Collectively, our study demonstrates the effects of VSMC NF90 in mediating the metabolic imbalance of AGEs to accelerate diabetic atherosclerotic calcification. Therefore, inhibition of VSMC NF90 may be a potential therapeutic target for diabetic atherosclerotic calcification.
The accumulation of AGEs is closely related to the atherosclerotic calcification in diabetic patients. Here, the authors find that VSMC NF90 knockout attenuates diabetic atherosclerotic calcification by mediating the metabolic imbalance of AGEs.
Journal Article