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[[alternative]]The impact of administrative districts and urban landscape on the dispersal of <i>Aedes aegypti</i> via genetic differentiation
No full text[[abstract]]Mosquito-borne diseases affect millions and cause numerous deaths annually. Effective vector control, which hinges on understanding their dispersal, is vital for reducing infection rates. Given the variability in study results, likely due to environmental and human factors, gathering local dispersal data is critical for targeted disease control. To analyse the spread and differentiation of Aedes aegypti in southern Taiwan, we established a dengue vector monitoring network in Southern Taiwan's cities. This network employed GPS-equipped ovitraps to gather eggs that were subsequently hatched in the laboratory and genotyped using genome-wide SNP markers. From 168 individuals, we identified 757,238 SNPs for detailed analysis. The estimated effective dispersal distance was 154 m (95% CI: 126-180 m), consistent with prior mark-release-recapture (MRR) estimates. We discovered that geographic isolation significantly influences genetic differentiation at larger scales, such as between cities, whereas its correlation with genetic distances is considerably weaker at smaller scales, like within cities. This is likely due to the urban landscape in Taiwan, characterised by narrow roads and densely packed buildings, which facilitates extensive dispersal of Ae. aegypti. In evaluating potential barriers to Ae. aegypti dispersal, we found that roads had no significant impact, whereas administrative districts accounted for 4.8% of the population differentiation (p < 10-4). Surprisingly, this variation aligns with the effects of district-specific mosquito control measures implemented at the municipal level. These findings highlight the complex interplay between urban landscapes, administrative measures and Ae. aegypti dispersal, emphasising the need for implementing targeted control strategies that consider these local dynamics
Mrc2 deficiency alleviates the development of hfd-induced nafld via downregulating Cd147-mediated Tnf-aproduction in macrophage
No full text[[abstract]]Background: NAFLD is becoming the most common chronic liver disease worldwide, while its mechanism remains unclear and there are still no effective drugs in the clinic. MRC2 is a transmembrane glycoprotein involved in the internalization and lysosomal degradation of collagen and has been suggested to play a role in hepatocellular carcinoma (HCC), but its regulatory role in the development and progression of NAFLD is still unknown. Methods: We fed WT and Mrc2-/- mice with a high-fat diet (HFD) for 8 weeks to observe the effects of Mrc2 on NAFLD. We also isolated mouse primary hepatocytes (MPHs) and bone marrow-derived macrophages (BMDMs) for in vitro study and used palmitic acid (PA) to simulate the HFD effect. Results: Analysis of the NAFLD dataset from the GEO database showed a positive correlation between hepatic MRC2 levels and NAFLD severity. Increased Mrc2 level was observed in the liver of HFD-fed WT mice, but, surprisingly, Mrc2-/- mice showed significantly reduced levels of HFD-induced weight gain and fatty liver compared with WT mice. Besides, Mrc2 was mainly expressed in hepatic nonparenchymal cells but rare in mouse hepatocytes. Conditioned medium (CM) collected from WT-BMDMs increased PA-induced steatosis in MPHs, such effect was ameliorated by CM collected from Mrc2-/--deficient BMDMs, and the addition of TNF-α neutralizing antibody or TNFR antagonist in the co-culture. Moreover, the disruption of the MRC2-CD147 complex on the cell membrane affected CD147-mediated NF-κB signaling and reduced the release of TNF-α in BMDMs, thereby leading to a reduction in steatosis in MPHs. Conclusion: Conclusively, Macrophage MRC2 prompted HFD-mediated steatosis in hepatocytes by, at least in part, stabilizing CD147 on the membrane, and its subsequent NF-κB signaling and TNF-α release, suggesting the potential role of the MRC2-CD147 complex in NAFLD and its promise as a therapeutic target for NAFLD
Using unsupervised learning methods to explore the trajectory of long-term care service in Taiwan
No full text[[abstract]]Background: Understanding the temporal trends in long-term care (LTC) utilization enables more effective planning by government and service providers. This study employed machine learning methods to explore LTC utilization trajectories among care recipients in a southern county of Taiwan. Methods: Administrative data from the government-funded LTC programme was utilized, with a total of 24,614 participants included after excluding those with less than six months of data. Daily service utilization records, mainly focusing on caregiving services, were aggregated, and the number of days each participant used LTC services within every 30-day period post-application was calculated. Utilization rates during 6 and 12 months post-application were separately analyzed. K-means clustering, an unsupervised machine learning method, was employed to select the optimal classification and identify LTC utilization trajectories using 10-fold cross validation. Temporal frequency variations of each caregiving service within each trajectory group were visualized using heatmaps. Results: In the analysis of LTC utilization within the first 6 months post-application, trajectories were classified into 7 groups; while within 12 months, trajectories were divided into 4 groups. These trajectories can be categorized into 4 distinct patterns: High-Stable (6 mo: 21.3%; 12 mo: 35.7%), Low-Stable (6 mo: 33.1%; 12 mo: 37.2%), High-Decrease (6 mo: 12.8%; 12 mo: 10.7%), and Low-Increase (6 mo: 32.7%; 12 mo: 16.5%). We further explored differences in socio-demographic characteristics and needs factors among trajectory groups. Heatmaps were used to illustrate temporal variations in the utilization rates of specific service items, which played a significant role in determining the trajectories
Advances in nucleic acid-based cancer vaccines
No full text[[abstract]]Nucleic acid vaccines have emerged as crucial advancements in vaccine technology, particularly highlighted by the global response to the COVID-19 pandemic. The widespread administration of mRNA vaccines against COVID-19 to billions globally marks a significant milestone. Furthermore, the approval of an mRNA vaccine for Respiratory Syncytial Virus (RSV) this year underscores the versatility of this technology. In oncology, the combination of mRNA vaccine encoding neoantigens and immune checkpoint inhibitors (ICIs) has shown remarkable efficacy in eliciting protective responses against diseases like melanoma and pancreatic cancer. Although the use of a COVID-19 DNA vaccine has been limited to India, the inherent stability at room temperature and cost-effectiveness of DNA vaccines present a viable option that could benefit developing countries. These advantages may help DNA vaccines address some of the challenges associated with mRNA vaccines. Currently, several trials are exploring the use of DNA-encoded neoantigens in combination with ICIs across various cancer types. These studies highlight the promising role of nucleic acid-based vaccines as the next generation of immunotherapeutic agents in cancer treatment. This review will delve into the recent advancements and current developmental status of both mRNA and DNA-based cancer vaccines
[[alternative]]Natural fucoidans inhibit coronaviruses by targeting viral spike protein and host cell furin (vol 215,115688,2023)
No full text[[abstract]]The authors regret that they inadvertently misplaced each one small image in Figure 4A and Figure 5B due to composing layout for publication, but this does not affect the results or conclusions of the article. The authors would like to apologise for any inconvenience caused
Low birth weight and chronic kidney disease with progression to kidney failure in children
No full text[[abstract]]BACKGROUND AND HYPOTHESIS: It is unclear if low birth weight (LBW), preterm birth and small for gestational age (SGA) could synergistically cause chronic kidney disease (CKD) and end-stage kidney disease (ESKD). This cohort study was conducted to examine their individual and combined impacts on the development of CKD and ESKD in childhood. METHODS: From the Taiwan Maternal and Child Health Database, we identified 1 477 128 newborns born between January 1, 2009, and December 31, 2016. We used a multivariable Cox regression model to assess the excess risk of CKD and ESKD in children with LBW/preterm/SGA. They were followed from birth until the occurrence of outcomes or until December 31, 2018, with an average follow-up of 5.78 years. RESULTS: This study included 1 361 071 infants with birth weight ≥ 2500 g (92.14%), 104 855 infants with low birth weight (1500 g to < 2500 g) (7.10%), 6 843 infants with very low birth weight (1000 g to < 1500 g) (0.46%), and 4 349 infants with extremely low birth weight (< 1000 g) (0.29%). The multivariable-adjusted model showed that male infants with low birth weight were associated with an increased risk of CKD (aHR 1.20, 95%CI 1.08-1.32) and ESKD (aHR 1.64, 95%CI 1.37-1.97). Female infants with LBW had an increased risk of CKD (aHR 1.18, 95%CI 1.06-1.32) and ESKD (aHR 1.31, 95%CI 1.09-1.58) than those without LBW. In addition to LBW, infants with preterm or SGA condition also had a significantly and synergistically increased risk of CKD and ESKD compared to full-term infants. CONCLUSION: We found children with LBW, preterm birth, or small for gestational age had a significantly increased risk of CKD and ESKD compared to children without intrauterine growth restriction
Comparative impact of tertiary lymphoid structures and tumor-infiltrating lymphocytes in cholangiocarcinoma
No full text[[abstract]]BACKGROUND: Cholangiocarcinoma is a challenging malignancy with limited responses to conventional therapies, particularly immune checkpoint inhibitor therapy. Tumor-infiltrating lymphocytes (TILs) and tertiary lymphoid structures (TLSs) are key components of the tumor microenvironment (TME) and have been implicated in the immune response to cancer. However, the role and difference of TLSs and TILs in patients with cholangiocarcinoma remains unclear. This study elucidates their contributions to the TME. METHODS: We examined 16 tumor samples from a single-arm, phase II trial of nivolumab plus modified gemcitabine and S-1 and various datasets. Immunohistochemistry and RNA sequencing were employed to assess TLSs and TILs presence and activity. Differential gene expression and signature of immune cell composition were examined by GeoMx Digital Spatial Profiler and Cancer Transcriptome Altas analysis. RESULTS: TLS-positive (N=7) patients demonstrated significantly better immunotherapy outcomes compared with TLS-negative (N=9) patients, including higher objective response rates (71% vs 0%) and disease control rates (100% vs 67%). The presence of TLSs correlated with improved progression-free and overall survival (p=0.03). TLSs were associated with "inflamed" tumors characterized by substantial immune infiltration, particularly involving T and B cells. Gene expression analyses identified significant upregulation of B cell-related genes in TLSs. Additionally, TLSs exhibited higher properties of memory B cells and myeloid dendritic cells but lower levels of innate immune cells compared with TILs. T cells within TLSs showed elevated expression of precursor-exhausted-related genes and lower cytotoxicity signature. Furthermore, TILs in TLS-positive tumors had higher levels of exhaustion signatures compared with TILs in TLS-negative tumors. Clinical data corroborated these findings, with higher PD-L1 and LAG-3 expression in TLS-positive tumors. CONCLUSION: Our findings revealed that TILs in TLS-positive tumors have more exhausted T cell signature and PD-1 and LAG-3 protein expression in CCA which support our clinical finding. TLSs can predict favorable immunotherapy responses in patients with cholangiocarcinoma, highlighting their potential as a biomarker and therapeutic target to enhance treatment efficacy
[[alternative]]The method of the preparation of fused multicyclic compounds
No full text[[abstract]]本發明公開了一種製備喹唑啉（quinazoline）式（I）化合物之方法，特別為一種以公斤量級規模製備之方法： 於本文中定義 B, D, W, Z, R 1, R 2及 n
Method of the preparation of fused multicyclic compounds
No full text[[abstract]]The present invention discloses a process for preparing compounds of Formula (I), particularly, a process manufacturing thereof on a multikilogram scale:wherein B, D, W, Z, R1, R2, and n are defined herein
[[alternative]]Poly heterocyclic conjugates and their pharmaceutical uses
No full text[[abstract]]本揭露提供一種如下式(I)所示之化合物及包含其中一種該化合物的醫藥組成物：各變數定義於內文中。還揭露了一種以式(I)化合物治療與不受控制的細胞生長相關病症之方法