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هذه هي الصين : قوة تسير نحو العالم
يركز كتاب \"هذه هي الصين\" على سرد قصص تنمية الصين في العصر الجديد. وقد غير الدكتور تشانغ وي وي طريقته المعروفة بالتوجيه والإرشاد في البرامج الأيديولوجية والنظرية في الماضي، وعبر عنها بلغة شعبية سائغة، وحجج منطقية صارمة، وبيانات حقيقية، وتصادمات صريحة للأفكار، وتقنيات عرض مبتكرة لمساعدة الجمهور على فهم النموذج الصيني والطريق الصيني، وتعزيز ثقتهم بمستقبل الصين.
Book
Knockout of circRNAs by base editing back-splice sites of circularized exons
Many circular RNAs (circRNAs) are produced from back-splicing of exons of precursor mRNAs and are generally co-expressed with cognate linear RNAs. Methods for circRNA-specific knockout are lacking, largely due to sequence overlaps between forms. Here, we use base editors (BEs) for circRNA depletion. By targeting splice sites involved in both back-splicing and canonical splicing, BEs can repress circular and linear RNAs. Targeting sites predominantly for circRNA biogenesis, BEs could efficiently repress the production of circular but not linear RNAs. As hundreds of exons are predominantly back-spliced to produce circRNAs, this provides an efficient method to deplete circRNAs for functional study.
Journal Article
SCAPTURE: a deep learning-embedded pipeline that captures polyadenylation information from 3′ tag-based RNA-seq of single cells
Single-cell RNA-seq (scRNA-seq) profiles gene expression with high resolution. Here, we develop a stepwise computational method-called SCAPTURE to identify, evaluate, and quantify cleavage and polyadenylation sites (PASs) from 3′ tag-based scRNA-seq. SCAPTURE detects PASs de novo in single cells with high sensitivity and accuracy, enabling detection of previously unannotated PASs. Quantified alternative PAS transcripts refine cell identity analysis beyond gene expression, enriching information extracted from scRNA-seq data. Using SCAPTURE, we show changes of PAS usage in PBMCs from infected versus healthy individuals at single-cell resolution.
Journal Article
The Effects of Disturbance on Hypothalamus-Pituitary-Thyroid (HPT) Axis in Zebrafish Larvae after Exposure to DEHP
Di-(2-ethylhexyl) phthalate (DEHP) has the potential to disrupt the thyroid endocrine system, but the underlying mechanism is unknown. In this study, zebrafish (Danio rerio) embryos were exposed to different concentrations of DEHP (0, 40, 100, 200, 400 μg/L) from 2 to 168 hours post fertilization (hpf). Thyroid hormones (THs) levels and transcriptional profiling of key genes related to hypothalamus-pituitary-thyroid (HPT) axis were examined. The result of whole-body thyroxine (T4) and triiodothyronine (T3) indicated that the thyroid hormone homeostasis was disrupted by DEHP in the zebrafish larvae. After exposure to DEHP, the mRNA expressions of thyroid stimulating hormone (tshβ) and corticotrophin releasing hormone (crh) genes were increased in a concentration dependent manner, respectively. The expression level of genes involved in thyroid development (nkx2.1 and pax8) and thyroid synthesis (sodium/iodide symporter, nis, thyroglobulin, tg) were also measured. The transcripts of nkx2.1 and tg were significantly increased after DEHP exposure, while those of nis and pax8 had no significant change. Down-regulation of uridinediphosphate-glucuronosyl-transferase (ugt1ab) and up-regulation of thyronine deiodinase (dio2) might change the THs levels. In addition, the transcript of transthyretin (ttr) was up-regulated, while the mRNA levels of thyroid hormone receptors (trα and trβ) remained unchanged. All the results demonstrated that exposure to DEHP altered the whole-body thyroid hormones in the zebrafish larvae and changed the expression profiling of key genes related to HPT axis, proving that DEHP induced the thyroid endocrine toxicity and potentially affected the synthesis, regulation and action of thyroid hormones.
Journal Article
Chromosome-level genome assembly of a cliff plant Taihangia rupestris var. ciliata provides insights into its adaptation and demographic history
Background
Cliffs are recognized as one of the most challenging environments for plants, characterized by harsh conditions such as drought, infertile soil, and steep terrain. However, they surprisingly host ancient and diverse plant communities and play a crucial role in protecting biodiversity. The Taihang Mountains, which act as a natural boundary in eastern China, support a rich variety of plant species, including many unique to cliff habitats. However, it is little known how cliff plants adapt to harsh habitats and the demographic history in this region.
Results
To better understand the demographic history and adaptation of cliff plants in this area, we analyzed the chromosome-level genome of a representative cliff plant,
T
.
rupestris
var.
ciliata
, which has a genome size of 769.5 Mb, with a scaffold N50 of 104.92 Mb. The rapid expansion of transposable elements may have contributed to the increasing genome and its ability to adapt to unique and challenging cliff habitats. Comparative analysis of the genome evolution between
Taihangia
and non-cliff plants in Rosaceae revealed a significant expansion of gene families associated with oxidative phosphorylation, which is likely a response to the abiotic stresses faced by cliff plants. This expansion may explain the long-term adaptation of
Taihangia
to harsh cliff environments. The effective population size of the two varieties has continuously decreased due to climatic fluctuations during the Quaternary period. Furthermore, significant differences in gene expression between the two varieties may explain the varied leaf phenotypes and adaptations to harsh conditions in different natural distributions.
Conclusion
Our study highlights the extraordinary adaptation of
T
.
rupestris
var.
ciliata
, shedding light on the evolution of cliff plants worldwide.
Journal Article
The miR‐192‐EGR1/HOXB9 Loop Regulates Glioma Cell Stemness and Malignant Phenotypes by Promoting Their Mesenchymal Transition
To clarify the regulatory effects of miR‐192 on the malignant phenotypes of glioma cells. We used PCR, WB and immunofluorescence to detect regulatory factors in glioma samples. Then, we chose lentiviral plasmid transfection to construct cell models. We used CCK‐8 and colony formation to evaluate the proliferation ability of these cells and used Transwell/scratch tests to evaluate their invasion ability. CD133‐expressing GSCs were observed under a microscope, and their stemness properties were evaluated. We constructed a tumour‐bearing model via subcutaneous inoculation. Tumour growth curves and tumour weights were determined subsequently. The proteins involved in the miR‐192‐EGR1/HOXB9 loop were evaluated via IHC staining. MiR‐192 was significantly reduced in glioma samples, and this factor downregulated EGR1 and HOXB9 via targeted binding, thus forming a semi‐open loop. Moreover, the proliferation, invasion and migration of glioma cells overexpressing miR‐192 were significantly decreased. These malignant phenotypes were abrogated completely with EGR1 or HOXB9 overexpression. Similarly, these changes were essentially consistent with MT marker expression and the stem‐like properties in glioma cells. Meanwhile, miR‐192 inhibits the tumorigenesis of glioma cells via the EGR1‐HOXB9 loop. MiR‐192 could inhibit MT in glioma cells through the EGR1‐HOXB9 loop. Thus, it reduces their stemness and abrogates their malignant phenotypes.
Journal Article
Transcriptome profiling of pumpkin (Cucurbita moschata Duch.) leaves infected with powdery mildew
Cucurbit powdery mildew (PM) is one of the most severe fungal diseases, but the molecular mechanisms underlying PM resistance remain largely unknown, especially in pumpkin (Cucurbita moschata Duch.). The goal of this study was to identify gene expression differences in PM-treated plants (harvested at 24 h and 48 h after inoculation) and untreated (control) plants of inbred line \"112-2\" using RNA sequencing (RNA-Seq). The inbred line \"112-2\" has been purified over 8 consecutive generations of self-pollination and shows high resistance to PM. More than 7600 transcripts were examined in pumpkin leaves, and 3129 and 3080 differentially expressed genes (DEGs) were identified in inbred line \"112-2\" at 24 and 48 hours post inoculation (hpi), respectively. Based on the KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway database and GO (Gene Ontology) database, a complex regulatory network for PM resistance that may involve hormone signal transduction pathways, transcription factors and defense responses was revealed at the transcription level. In addition, the expression profiles of 16 selected genes were analyzed using quantitative RT-PCR. Among these genes, the transcript levels of 6 DEGs, including bHLH87 (Basic Helix-loop-helix transcription factor), ERF014 (Ethylene response factor), WRKY21 (WRKY domain), HSF (heat stress transcription factor A), MLO3 (Mildew Locus O), and SGT1 (Suppressor of G-Two Allele of Skp1), in PM-resistant \"112-2\" were found to be significantly up- or down-regulated both before 9 hpi and at 24 hpi or 48 hpi; this behavior differed from that observed in the PM-susceptible material (cultivar \"Jiujiangjiaoding\"). The transcriptome data provide novel insights into the response of Cucurbita moschata to PM stress and are expected to be highly useful for dissecting PM defense mechanisms in this major vegetable and for improving pumpkin breeding with enhanced resistance to PM.
Journal Article
Genome-wide analysis of WRKY gene family in Cucurbita moschata and involvement of CmWRKY22/63/84 in powdery mildew resistance
Background
Powdery mildew (PM), mainly caused by
Podosphaera xanthii
, is a severe biotrophic pathogen disease of global Cucurbitaceae vegetables. However,
Cucurbita moschata
(pumpkin) strongly resists PM and shows wide adaptability. WRKY transcription factors participate in plant response to pathogen stresses, but the function of WRKY genes under PM stress in pumpkins is largely unknown.
Results
In this study, 98 members of the
CmWRKYs
family were identified in the genome of
C. moschata
and categorized into three groups.
CmWRKY
promoter regions contained many
cis
-regulatory elements closely related to light, hormone, and stress responses. A segmental duplication event drove the expansion of the pumpkin
CmWRKY
genes, and the WRKY genes were highly conserved in pumpkin and cucumber. Additionally, the expression of 13
CmWRKY
genes was altered following PM infection, of which five
CmWRKY
genes were induced, while
CmWRKY84
and
92
simultaneously responded to salicylic acid and hydrogen peroxide (H
2
O
2
) treatments. Furthermore, transient overexpression of
CmWRKY22/63/84
in pumpkin plants inhibited the hyphal growth of
P. xanthii
while enhancing the accumulation of H
2
O
2
.
Conclusions
A genome-wide analysis of the WRKY family in
C. moschata
identified the involvement of
CmWRKY22/63/84
in the PM resistance. Our results contribute to research on the function of
CmWRKY
genes in the pumpkin resistance to PM.
Journal Article
Large scale plasma proteomic profiles improve prediction of idiopathic pulmonary fibrosis in general population
Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease of unknown etiology, with poor prognosis and substantial global economic burden. Circulating proteomics holds promise for unraveling IPF pathogenesis and identifying therapeutic targets. Herein, we aimed to explore the relationship between plasma proteomics and IPF, and evaluate whether proteomics could improve IPF risk prediction.
This cohort study included 44,306 participants from the UK Biobank. The development cohort, consisting of 39,035 participants from England, was randomly divided into a 7:3 training-testing ratio. The validation cohort included 5,211 participants from Scotland and Wales. Multivariable-adjusted Cox regression models were used to explore associations between 2,920 plasma proteins and incident IPF. In the training set (27,366 participants; 295 IPF cases), an IPF protein risk score (PRS) was constructed incorporating 256 proteins selected using least absolute shrinkage and selection operator (LASSO) penalty. Predictive performance was assessed using Harrell's C-index, time-dependent area under the receiver operating characteristic curve, continuous/categorical net reclassification improvement, and integrated discrimination improvement.
The median follow-up duration was 13.6 years. We observed 464 proteins associated with IPF risk, primarily involved in pathways related to external side of plasma membrane, leukocyte cell-cell adhesion, cytokine activity, and cytokine-cytokine receptor interaction. CCL21 and CXCL9 were identified as key proteins within the protein network. In the testing set (11,729 participants; 142 IPF cases), integrating 256 LASSO-selected proteins (C-index increase 0.207; 95% CI 0.188, 0.224) and a weighted IPF-PRS (C-index increase 0.105; 95% CI 0.085, 0.112) significantly enhanced IPF prediction compared to traditional risk factors alone (C-index, 0.779; 95% CI 0.742, 0.817). Adding LASSO-selected proteins had the largest C-index of 0.986 (95% CI 0.977, 0.995), and significantly improved the continuous 10-year net reclassification (0.462; 95% CI 0.359, 0.534) and 10-year integrated discrimination index (0.747; 95% CI 0.141, 0.898). These results were verified in the external validation cohort (5,211 participants; 61 IPF cases).
Our study characterized early proteomic contributions to IPF, and demonstrated that plasma proteomic data significantly enhance IPF risk prediction beyond traditional risk factors.
Journal Article
ZEB1 promotes the immune escape of ovarian cancer through the MCSF-CCL18 axis
This study aimed to determine the molecular mechanisms underlying immune escape in ovarian cancer. Samples of ovarian cancer were used to explore the regulatory pathways involved in the malignant phenotype. Tumor cell models with different levels of factor expression were constructed via transfection, and their regulation was determined through investigation of protein expressions. Moreover, our study aimed to investigate the effects of M2 polarization and TAMs aggregation on the apoptosis of CD8 + T-cells, and determine their regulatory axis. Results revealed ZEB1 may promote CCL18 expression via upregulation of MCSF concentration. Notably, high CCL18 expression levels were associated with the aggregation of M2-TAMs and the apoptosis of CD8 + T-cells. In addition, results of the present study demonstrated that the proliferation and invasion of ovarian cancer cells with high expression levels of proteins associated with ZEB1 signal pathway were increased. At the same time the growth rate of tumors in mice was reduced following ZEB1 knockdown, and the volume/weight of tumors were markedly decreased both in vitro and
in vivo.
Moreover, our results revealed that the aggregation of M2-TAMs and the apoptosis of CD8 + T-cells were significantly decreased in tumor cells following ZEB1 knockdown. Thus, these results verified that ZEB1 may promote the M2 polarization of TAMs via the MCSF axis, leading to the increased secretion of CCL18. Moreover, the MCSF axis may mediate immune escape through the induction of CD8 + T-cell apoptosis, ultimately promoting the malignant phenotype in ovarian cancer cells.
Journal Article