20 research outputs found
Shen jing yuan wang luo ding xiang you xiao lian tong xing de chong jian yu fen xi
No full textPh.D.The study of networks has become increasingly important in many areas ranging from physics to biology. Knowledge of connectivity in a network is useful for understanding its function. The reconstruction of the structure of neuronal networks can reveal the operation mechanism of nervous systems. However, it is very difficult to directly measure the synaptic connections of neurons and only the nervous system of Caenorhabditis elegans has been mapped out by direct experimental measurements. Neuronal networks have also been actively studied using in-vitro neuronal cultures and multi-electrode array to record the electrical activity of the neurons. It is highly challenging to infer neuronal cultures connectivity from the recordings. A general reconstruction method has been developed recently that extracts links in a directed and weighted network subject to noise solely from node dynamics.In this thesis, we apply the above-mentioned network reconstruction method to neuronal networks with suitable modifications in the real problem. Networks structure and coupling strength of links can be extracted from experimental timeseries data. The reconstructed networks are further tested by studying how well the measured spiking activity can be reproduced in the simulation using the Leaky Integrate-and-Fire model. Network properties like degrees, mixing patterns and physical length are analyzed. Also, we study the relation between spiking activity and network structure and find distinguishable network features in the spike rate of nodes. Consequently, these network features are used for spike rate prediction.在從物理學到生物學的許多領域中，網絡的研究已變得越來越重要。了解網絡中的連通性對於理解其功能非常有用。對神經元網絡結構的重構可以揭示神經系統的運行機制。然而，直接測量神經元的突觸連接非常困難，目前只有秀麗隱桿線蟲的神經系統通過直接實驗測量繪製出了神經系統的圖譜。也有人利用體外神經元培養物和多電極陣列記錄神經元的電活動，積極研究神經元網絡。從動態記錄中推斷體外神經元的連通性具有很高的挑戰性。最近已經發表了一種通用的網絡重構方法，該方法基於噪聲，在有向加權網絡中成功提取鏈路。在本論文中，我們將上述網絡重構方法應用到神經元網絡中，並在實際問題中進行了適當的修改。從實驗時間序列數據中提取網絡結構和鏈路的耦合強度。重構後的網絡通過研究在仿真中使用洩漏集成和激發模型，進一步檢驗所測得的尖峰活動在仿真中的重現程度。我們分析了網絡屬性，例如度，混合特征和物理長度。此外，我們研究了激發活動和網絡結構之間的關係，並在節點的激發速率中發現了可區分的網絡特徵。因此，這些網絡特征可用於激發速率預測。Sun, Chumin = 神經元網絡定向有效連通性的重建與分析 / 孫楚旻.Thesis Ph.D. Chinese University of Hong Kong 2020.Includes bibliographical references (leaves 97-109).Abstracts also in Chinese.Title from PDF title page (viewed on November 4, 2021).Sun, Chumin = Shen jing yuan wang luo ding xiang you xiao lian tong xing de chong jian yu fen xi / Sun Chumin
Investigating Radiosensitivity of HPV-positive and HPV-negative Head and Neck Squamous Cell Carcinoma Spheroids by PARP Inhibition
No full textHead and neck squamous cell carcinoma (HNSCC) is the sixth most-common cancer over the world, and it remains a significant public health concern in the UK. A number of studies have indicated HPV type-16 infection is one of the main risk factors related with nearly 50% HNSCC cases. Interestingly, the survival rate of HPV-positive HNSCC patients is shown to be higher than HPV-negative status, due to an improved prognosis and better response to chemo- and/or radiotherapeutic strategies. Previously published studies in our group have demonstrated the increased radiosensitivity of HPV-positive HNSCC has been largely linked with defects in the signalling and the efficiency of DNA double strand break (DSB) repair.
Therefore in this project, I demonstrate that HPV-positive oropharyngeal squamous cell carcinoma (OPSCC) spheroids show higher radiosensitivity compared to HPV-negative OPSCC spheroids, due to the defective efficacy of DNA DSB repair. Subsequently, PARP inhibitors Olaparib and Talazoparib presented significant enhancement of radio-sensitisation on HPV-negative HNSCC spheroids. Moreover, HNSCC spheroid growth was more effectively suppressed by proton beam therapy in combination these PARP inhibitors. This research suggested that the combination of clinical PARPi and proton irradiation can become a potent treatment for HPV-negative HNSCC patients in the future
The radiobiology of HPV-positive and HPV-negative head and neck squamous cell carcinoma
No full textHead and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide, with reported incidences of ~800 000 cases each year. One of the critical determinants in patient response to radiotherapy, particularly for oropharyngeal cancers, is human papillomavirus (HPV) status where HPV-positive patients display improved survival rates and outcomes particularly because of increased responsiveness to radiotherapy. The increased radiosensitivity of HPV-positive HNSCC has been largely linked with defects in the signalling and repair of DNA double-strand breaks. Therefore, strategies to further radiosensitise HPV-positive HNSCC, but also radioresistant HPV-negative HNSCC, have focussed on targeting key DNA repair proteins including PARP, DNA-Pk, ATM and ATR. However, inhibitors against CHK1 and WEE1 involved in cell-cycle checkpoint activation have also been investigated as targets for radiosensitisation in HNSCC. These studies, largely conducted using established HNSCC cell lines in vitro, have demonstrated variability in the response dependent on the specific inhibitors and cell models utilised. However, promising results are evident targeting specifically PARP, DNA-Pk, ATR and CHK1 in synergising with radiation in HNSCC cell killing. Nevertheless, these preclinical studies require further expansion and investigation for translational opportunities for the effective treatment of HNSCC in combination with radiotherapy
Emerg Infect Dis
No full textWe prospectively assessed 49 coronavirus disease cases in Guangdong, China, to estimate the frequency and duration of detectable severe acute respiratory syndrome coronavirus 2 RNA in human body fluids. The prolonged persistence of virus RNA in various body fluids may guide the clinical diagnosis and prevention of onward virus transmission
A systematic review and meta-analysis of acupoint autohemotherapy and western medicine therapy in treating chronic obstructive pulmonary disease
No full textEfficacy and safety of acupoint autohemotherapy in treating stable chronic obstructive pulmonary disease
No full textFunctional Composition Changes of a Subtropical Monsoon Evergreen Broad-Leaved Forest Under Environmental Change
No full textLong-term studies have revealed that forest species composition was shifting under environment change and disturbance induced by loss of large trees. Yet, few studies explicitly analyzed their impacts on composition concurrently. To learn more about impacts of environment change and disturbance on driving forest community, we investigated shifts in functional composition over past 24 years in an old-growth subtropical forest in southern China. We analyzed nine traits that are mainly related to leaf nutrients, photosynthetic capacity, hydraulic conductivity, and drought tolerance of plants and examined hypotheses: (1) The functional composition change over time was directional instead of random fluctuation, (2) drought-tolerant species increased their abundance under soil dryness, (3) both environmental change and disturbance related to changes of functional composition significantly, and (4) initial trait values of quadrats strongly influenced their subsequent change rates in quadrat level (10 × 10 m). We found that species composition had shifted to favor species with high leaf nutrient content, high photosynthesis rate, high hydraulic conductivity, low water-use efficiency, and high drought tolerance traits, which was due to soil dryness and disturbance. These two factors explained 47–58% of quadrats’ trait value changes together. Considering rapidly increasing stem density, this pattern may indicate ecological processes of which disturbance provided numerous recruits of resource-acquisition strategy species and soil dryness conducted a selecting effect on shaping composition in the forest. Additionally, quadrats with initial trait values at the far end of change direction shifted faster in three traits, which also indicated that functional composition changes in quadrats were directional and homogenized. Our results implied that environment change and accompanied disturbance events possibly drove species composition change along a different trajectory in the subtropical forest that experienced high climatic variability
Immunity Dynamics of Neisseria meningitidis Serogroups ACYW from Birth and Following Vaccination
No full textBackground: Serosurveillance of epidemic cerebrospinal meningitis (ECM) in healthy individuals is crucial for assessing disease risk and evaluating the effectiveness of vaccinations. However, this practical work is rare in China. Methods: We conducted cross-section serosurveillance in Guangzhou, Zhanjiang, and Heyuan in Guangdong Province, measuring Anti-Nm IgG with serogroups A, C, Y, and W, and analyzed the trends using a generalized additive model (GAM). Results: During 2019–2022, 7752 participants were included. The overall antibody positivity rate for serogroups A, C, Y, and W were 60.75%, 15.51%, 32.83%, and 14.56%, respectively. High Anti-Nm IgG was in children aged 0–5 and 5–10 years old. Geometric mean concentrations (GMCs) of Anti-Nm IgG were higher and correlated positively with vaccine doses compared with unvaccinated individuals. The GMC showed a consistent decrease trend in the vaccinated and a U-shaped curve in populations. The declined rates of GMC were 1.59 (95% CI: 1.03, 2.14) µg/mL, 1.65 (95% CI: 1.28, 2.03), 0.62 (95% CI: 0.22, 1.03), and 0.31 (95% CI: 0.08, 0.53) µg/mL per year for serogroups A, C, Y, and W, respectively. Conclusions: There were differences in antibody positivity rate and GMC for the four serogroups of ECM in the healthy individuals of Guangdong Province, with serogroup A showing the highest, and the demographic differences highlighted the high seroprevalence of Neisseria meningitidis in younger people. The variable prevalence rates among serogroups A, C, Y, and W and the observed decline in antibody titers underscore the need for adjustments in the immunization program targeting the meningococcal vaccine
HIF-1–regulated TPM3 links hypoxia to motility and invasion beyond the hypoxic fraction in triple-negative breast cancer
No full texttle:f347c889-7fc7-44be-88e0-b04622e4e36b:afee126f-04b2-41a9-a6dd-b29b7c6c20ab:1Hypoxia is a defining feature of triple-negative breast cancer (TNBC), driving invasion, metastasis, and therapy resistance. Understanding the molecular effectors of hypoxia is essential to identify new therapeutic targets. Here, we investigated tropomyosin 3 (TPM3), an actin-binding protein that regulates filament stability. TPM3 is significantly upregulated in breast cancer, including in TNBC, where elevated levels correlate with poor overall survival. Using validated hypoxia signatures and TNBC cell models, we show that TPM3 is induced in physiologically relevant hypoxic conditions in a HIF-1–dependent manner. Both mRNA and protein levels of TPM3 increased in response to hypoxia, and TPM3 colocalised with F-actin, supporting cytoskeletal organisation. Functional assays demonstrated that depletion or inhibition of TPM3 impaired cell morphology, motility, and invasion in hypoxic TNBC cells, while not affecting viability. Notably, TPM3 inhibition synergised with Paclitaxel and Doxorubicin, enhancing therapeutic efficacy. In addition, TPM3 was incorporated into extracellular vesicles (EVs), with hypoxia increasing EV-mediated transfer of TPM3 to normoxic cells and promoting their motility. These findings establish TPM3 as a hypoxia-inducible, HIF-1–regulated effector of cytoskeletal dynamics and intercellular communication, underscoring its potential as a therapeutic target to limit TNBC aggressiveness and improve treatment outcomes
