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"Guo, Chuang"
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فهم الصين : السجلات الكاملة للدورة الثانية من المؤتمر الدولي \فهم الصين\
الوقوف على كافة مجريات وتطورات الواقع الصيني فيما يتعلق بسياسات الحزب الشيوعي الصيني بوجه عام، والأوضاع الاقتصادية بالصين على الصعيدين المحلي والدولي، ليس بالأمر الهين على الباحثين والأكاديميين بل والمهتمين بالشأن الصيني عموما، لذا فإن هذا الكتاب \"فهم الصين\" يعد محطة مهمة في قراءة وفهم حاضر الصين ومستقبلها القريب والبعيد على حد سواء، حيث يكتسب هذا الكتاب خصوصيته وأهميته، من كونه يتألف من عدة أوراق بحثية وكلمات لأهم القادة السياسيين الصينيين والدوليين كل من منطلق موقعه السياسي، والذين ألقوا كلماتهم على هامش أهم حدث سياسي يحدث في الصين كل خمس سنوات، وهو اجتماع اللجنة المركزية للحزب الشيوعي الصيني في دورته الثامنة عشرة. ويتناول هذا الكتاب عددا من المحاور الأساسية فيما يتعلق بالسياسة الخارجية للصين، ودورها الاقتصادي إقليميا وعالميا، منها : استراتيجية التنمية الاقتصادية وتعزيز التنمية المنسقة في إطار الخطة الخمسية الثالثة عشرة للصين، وتحسين الحوكمة العالمية وبناء مجتمع المصالح المشتركة على نحو شامل وكذلك المشاركة الفعالة في الحوكمة الاقتصادية العالمية والسعي لتحقيق تنمية سلمية مشتركة، وإدارة الفضاء السيبراني في الصين، بالإضافة إلى استراتيجية الدفاع الوطني الصينية، وتعزيز حماية البيئة الإيكولوجية وبناء مجتمع رغد الحياة بشكل شامل، بالإضافة إلى تحليل وعرض لمستقبل مبادرة \"الحزام والطريق\" في ظل النظام العالمي الجديد.
Book
Benchmarking spatial and single-cell transcriptomics integration methods for transcript distribution prediction and cell type deconvolution
Spatial transcriptomics approaches have substantially advanced our capacity to detect the spatial distribution of RNA transcripts in tissues, yet it remains challenging to characterize whole-transcriptome-level data for single cells in space. Addressing this need, researchers have developed integration methods to combine spatial transcriptomic data with single-cell RNA-seq data to predict the spatial distribution of undetected transcripts and/or perform cell type deconvolution of spots in histological sections. However, to date, no independent studies have comparatively analyzed these integration methods to benchmark their performance. Here we present benchmarking of 16 integration methods using 45 paired datasets (comprising both spatial transcriptomics and scRNA-seq data) and 32 simulated datasets. We found that Tangram, gimVI, and SpaGE outperformed other integration methods for predicting the spatial distribution of RNA transcripts, whereas Cell2location, SpatialDWLS, and RCTD are the top-performing methods for the cell type deconvolution of spots. We provide a benchmark pipeline to help researchers select optimal integration methods to process their datasets.
This work presents a comprehensive benchmarking analysis of computational methods that integrates spatial and single-cell transcriptomics data for transcript distribution prediction and cell type deconvolution.
Journal Article
Iron and Alzheimer's Disease: From Pathogenesis to Therapeutic Implications
As people age, iron deposits in different areas of the brain may impair normal cognitive function and behavior. Abnormal iron metabolism generates hydroxyl radicals through the Fenton reaction, triggers oxidative stress reactions, damages cell lipids, protein and DNA structure and function, and ultimately leads to cell death. There is an imbalance in iron homeostasis in Alzheimer's disease (AD). Excessive iron contributes to the deposition of β-amyloid and the formation of neurofibrillary tangles, which in turn, promotes the development of AD. Therefore, iron-targeted therapeutic strategies have become a new direction. Iron chelators, such as desferoxamine, deferiprone, deferasirox, and clioquinol, have received a great deal of attention and have obtained good results in scientific experiments and some clinical trials. Given the limitations and side effects of the long-term application of traditional iron chelators, alpha-lipoic acid and lactoferrin, as self-synthesized naturally small molecules, have shown very intriguing biological activities in blocking Aβ-aggregation, tauopathy and neuronal damage. Despite a lack of evidence for any clinical benefits, the conjecture that therapeutic chelation, with a special focus on iron ions, is a valuable approach for treating AD remains widespread.
Journal Article
A Review on Lactoferrin and Central Nervous System Diseases
Central nervous system (CNS) diseases are currently one of the major health issues around the world. Most CNS disorders are characterized by high oxidative stress levels and intense inflammatory responses in affected tissues. Lactoferrin (Lf), a multifunctional iron-binding glycoprotein, plays a significant role in anti-inflammatory, antibacterial, antiviral, reactive oxygen species (ROS) modulator, antitumor immunity, and anti-apoptotic processes. Previous studies have shown that Lf is abnormally expressed in a variety of neurological diseases, especially neurodegenerative diseases. Recently, the promotion of neurodevelopment and neuroprotection by Lf has attracted widespread attention, and Lf could be exploited both as an active therapeutic agent and drug nanocarrier. However, our understanding of the roles of Lf proteins in the initiation or progression of CNS diseases is limited, especially the roles of Lf in regulating neurogenesis. This review highlights recent advances in the understanding of the major pharmacological effects of Lf in CNS diseases, including neurodegenerative diseases, cerebrovascular disease, developmental delays in children, and brain tumors.
Journal Article
Single-cell analysis of two severe COVID-19 patients reveals a monocyte-associated and tocilizumab-responding cytokine storm
Several studies show that the immunosuppressive drugs targeting the interleukin-6 (IL-6) receptor, including tocilizumab, ameliorate lethal inflammatory responses in COVID-19 patients infected with SARS-CoV-2. Here, by employing single-cell analysis of the immune cell composition of two severe-stage COVID-19 patients prior to and following tocilizumab-induced remission, we identify a monocyte subpopulation that contributes to the inflammatory cytokine storms. Furthermore, although tocilizumab treatment attenuates the inflammation, immune cells, including plasma B cells and CD8
+
T cells, still exhibit robust humoral and cellular antiviral immune responses. Thus, in addition to providing a high-dimensional dataset on the immune cell distribution at multiple stages of the COVID-19, our work also provides insights into the therapeutic effects of tocilizumab, and identifies potential target cell populations for treating COVID-19-related cytokine storms.
Tocilizumab has been used to treat the excessive inflammatory responses in COVID-19 patients. Here, the authors use single-cell RNA sequencing results from two severe COIVD-19 patients to provide high-dimensional immune profiling data, and to implicate potential cellular and molecular insights for the therapeutic effects of tocilizumab.
Journal Article
Classification for Penicillium expansum Spoilage and Defect in Apples by Electronic Nose Combined with Chemometrics
It is crucial for the efficacy of the apple storage to apply methods like electronic nose systems for detection and prediction of spoilage or infection by Penicillium expansum. Based on the acquisition of electronic nose signals, selected sensitive feature sensors of spoilage apple and all sensors were analyzed and compared by the recognition effect. Principal component analysis (PCA), principle component analysis-discriminant analysis (PCA-DA), linear discriminant analysis (LDA), partial least squares discriminate analysis (PLS-DA) and K-nearest neighbor (KNN) were used to establish the classification model of apple with different degrees of corruption. PCA-DA has the best prediction, the accuracy of training set and prediction set was 100% and 97.22%, respectively. synergy interval (SI), genetic algorithm (GA) and competitive adaptive reweighted sampling (CARS) are three selection methods used to accurately and quickly extract appropriate feature variables, while constructing a PLS model to predict plaque area. Among them, the PLS model with unique variables was optimized by CARS method, and the best prediction result of the area of the rotten apple was obtained. The best results are as follows: Rc = 0.953, root mean square error of calibration (RMSEC) = 1.28, Rp = 0.972, root mean square error of prediction (RMSEP) = 1.01. The results demonstrated that the electronic nose has a potential application in the classification of rotten apples and the quantitative detection of spoilage area.
Journal Article
Comparison of continuous pericapsular nerve group (PENG) block versus continuous fascia iliaca compartment block on pain management and quadriceps muscle strength after total hip arthroplasty: a prospective, randomized controlled study
Background
This investigation aimed to evaluate the impact of continuous pericapsular nerve group (PENG) block and continuous fascia iliac compartment block (FICB) on postoperative pain following total hip arthroplasty (THA).
Methods
This prospective, randomized, and controlled trial recruited a cohort of fifty-seven patients with unilateral femoral neck fractures from Xi’an Aerospace General Hospital in northwest China between July 2020 and November 2021. These patients were randomly assigned to two groups: the continuous PENG block group (PENG group, n = 29) and the continuous FICB group (FICB group, n = 28). Under ultrasound guidance, PENG block and FICB procedures were performed prior to spinal anesthesia, utilizing 20 ml of 0.25% ropivacaine for PENG block and 30 ml of 0.25% ropivacaine for FICB. Subsequently, a catheter was inserted. All study participants received a standardized postoperative multimodal analgesic regimen, including intravenous administration of 30 mg Ketorolac tromethamine every eight hours and patient-controlled neural analgesia (PCNA) after surgery. Numerical rating scale (NRS) scores at rest and during exercise were recorded at various time points: prior to block (T0), 30 min post-blockade (T1), and 6 h (T2), 12 h (T3), 24 h (T4), and 48 h (T5) postoperatively. Additional data collected encompassed postoperative quadriceps muscle strength, the time of initial ambulation after surgery, the number of effective PCNA activations, rescue analgesia requirements, and occurrences of adverse events (such as nausea and vomiting, hematoma, infection, catheter detachment, or displacement) within 48 h following surgery.
Results
In the PENG group, the resting NRS pain scores exhibited lower values at T1, T4, and T5 than those at T0. Furthermore, exercise NRS pain scores at T1-T5 were lower in the PENG group than in the FICB group. Similarly, during the same postoperative period, the PENG group demonstrated enhanced quadriceps strength on the affected side compared to the FICB group. Additionally, the PENG group displayed earlier postoperative ambulation and reduced occurrences of effective PCNA activations and rescue analgesia requirements compared to the FICB group.
Conclusion
Continuous PENG block exhibited superior analgesic efficacy after THA compared to continuous FICB, promoting recovery of quadriceps strength on the affected side and facilitating early postoperative ambulation.
Trial Registration
This clinical trial was registered in the China Clinical Trials Center (
http://www.chictr.org.cn
) on 20/07/2020, with the registration number ChiCTR2000034821.
Journal Article
Activated spinal astrocytes contribute to the later phase of carrageenan-induced prostatitis pain
Background
Prostatodynia is the main symptom of chronic prostatitis and the main reason that patients go to the hospital for treatment. Although a variety of factors, including inflammatory immune response, nervous system sensitization, and psychological factors, have been shown to play important roles in the induction and development of chronic pain in prostatitis, the underlying cause of chronic prostatodynia maintenance in prostatitis patients remains unclear.
Methods
A mouse model of chronic prostatitis induced by carrageenan injection was used. The von Frey test was used to measure pain behavior. The microglial and astrocyte activations were immunohistochemically demonstrated with antibodies against Iba1 and GFAP. The expression of cytokine or signaling pathway was detected by enzyme-linked immunosorbent assay (ELISA) and Western blotting.
Results
In this study, we provide several lines of evidence to demonstrate that activated spinal astrocytes contribute to the later phase (5 weeks after carrageenan injection) of carrageenan-induced prostatitis pain. First, activation of spinal astrocytes but not microglia was found in the spinal cord dorsal horn at 5 weeks. Second, intrathecal injection of the astroglial toxin L-2-Aminoadipate acid (L-AA) but not microglial inhibitor minocycline reduced mechanical allodynia at 5 weeks. Third, chronic prostatitis induced a profound and persistent upregulation of connexin-43 hemichannels in spinal astrocytes, and spinal injection of the connexin-43 inhibitor carbenoxolone (CBX) effectively reduced pain symptoms. Fourth, increased expression and release of chemokine C-X-C motif ligand 1 (CXCL1) in the spinal dorsal horn and intrathecal injection of a CXCL1 neutralizing antibody or the CXCR2 (a major receptor of CXCL1) antagonist SB225002 significantly reduced mechanical allodynia at 5 weeks.
Conclusions
In this study, we found that a novel mechanism of activated spinal astrocytes plays a crucial role in maintaining chronic prostatitis-induced persistent pain via connexin-43-regulated CXCL1 production and secretion.
Journal Article
Comparative analysis of methodologies for detecting extrachromosomal circular DNA
Extrachromosomal circular DNA (eccDNA) is crucial in oncogene amplification, gene transcription regulation, and intratumor heterogeneity. While various analysis pipelines and experimental methods have been developed for eccDNA identification, their detection efficiencies have not been systematically assessed. To address this, we evaluate the performance of 7 analysis pipelines using seven simulated datasets, in terms of accuracy, identity, duplication rate, and computational resource consumption. We also compare the eccDNA detection efficiency of 7 experimental methods through twenty-one real sequencing datasets. Here, we show that Circle-Map and Circle_finder (bwa-mem-samblaster) outperform the other short-read pipelines. However, Circle_finder (bwa-mem-samblaster) exhibits notable redundancy in its outcomes. CReSIL is the most effective pipeline for eccDNA detection in long-read sequencing data at depths higher than 10X. Moreover, long-read sequencing-based Circle-Seq shows superior efficiency in detecting copy number-amplified eccDNA over 10 kb in length. These results offer valuable insights for researchers in choosing the suitable methods for eccDNA research.
Sequencing-based studies have advanced our understanding of the diverse functions of extrachromosomal circular DNA (eccDNA). Here the authors systematically compare the performance of several bioinformatic pipelines and experimental methods that have been developed for eccDNA detection.
Journal Article
Intranasal administration of α-synuclein preformed fibrils triggers microglial iron deposition in the substantia nigra of Macaca fascicularis
Iron deposition is present in main lesion areas in the brains of patients with Parkinson’s disease (PD) and an abnormal iron content may be associated with dopaminergic neuronal cytotoxicity and degeneration in the substantia nigra of the midbrain. However, the cause of iron deposition and its role in the pathological process of PD are unclear. In the present study, we investigated the effects of the nasal mucosal delivery of synthetic human α-synuclein (α-syn) preformed fibrils (PFFs) on the pathogenesis of PD in
Macaca fascicularis
. We detected that iron deposition was clearly increased in a time-dependent manner from 1 to 17 months in the substantia nigra and globus pallidus, highly contrasting to other brain regions after treatments with α-syn PFFs. At the cellular level, the iron deposits were specifically localized in microglia but not in dopaminergic neurons, nor in other types of glial cells in the substantia nigra, whereas the expression of transferrin (TF), TF receptor 1 (TFR1), TF receptor 2 (TFR2), and ferroportin (FPn) was increased in dopaminergic neurons. Furthermore, no clear dopaminergic neuron loss was observed in the substantia nigra, but with decreased immunoreactivity of tyrosine hydroxylase (TH) and appearance of axonal swelling in the putamen. The brain region-enriched and cell-type-dependent iron localizations indicate that the intranasal α-syn PFFs treatment-induced iron depositions in microglia in the substantia nigra may appear as an early cellular response that may initiate neuroinflammation in the dopaminergic system before cell death occurs. Our data suggest that the inhibition of iron deposition may be a potential approach for the early prevention and treatment of PD.
Journal Article