PML Suppresses Influenza Virus Replication by Promoting FBXW7 Expression

Virologica Sinica - Influenza A viruses (IAV) are responsible for seasonal flu epidemics, which can lead to high morbidity and mortality each year. Like other viruses, influenza virus can hijack...     

Congruent spatial patterns of species richness and phylogenetic diversity in karst flora: Case study of Primulina (Gesneriaceae)

The karst landform in southern China is renowned for its high levels of species diversity and endemism. Globally, karst ecosystems are under threat from unsustainable anthropogenic disturbance and climate changes and are among the most threatened ecosystems worldwide. In this study, we used the typical karst endemic genus in southern China, Primulina Hance, as a model to identify areas within the karst landform with high diversity and to investigate congruence between phylogenetic and species‐based measures of diversity. Using phylogenetic information and species distribution data, we measured geographical patterns of diversity with four metrics: species richness (SR), corrected weighted endemism (CWE), phylogenetic diversity (PD), and phylogenetic endemism (PE). Our results revealed a high spatial congruence among SR, PD, and PE, with hotspot areas identified in the Nanling Mountains (i.e., north Guangdong and northeast Guangxi) and southeast Yungui Plateau (i.e., north and southwest Guangxi), whereas the hotspots of CWE are comparatively uniform throughout the geographic extent. The categorical analysis of neo‐ and paleoendemism identified a pattern of mixed neo‐ and paleoendemism in numerous grid cells, suggesting that karst areas in southern China have acted as both “museums” and “cradles” of plant evolution. Conservation gap analysis of hotspots revealed that the majority of prioritized hotspots (>90%) of the genus are outside of protected areas, therefore indicating the limited effectiveness of national nature reserves for the karst flora. Overall, our results suggest that the karst flora merits more conservation attention and SR can be an effective surrogate to capture PD in conservation planning.     

Th2 polarization in target organs is involved in the alleviation of pathological damage mediated by transplanting granulocyte colony-stimulating factor-primed donor T cells

Acute graft-versus-host disease(a GVHD) is caused by allo-activated donor T cells infiltrating target organs. As a regulator of immune function, granulocyte colony-stimulating factor(G-CSF) has been demonstrated to relieve the a GVHD reaction.However, the role of G-CSF-primed donor Tcells in specific target organs is still unknown. In this study, we employed a classical MHC-mismatched transplantation mouse model(C57BL/6 into BALB/c) and found that recipient mice transplanted with GCSF-primed T cells exhibited prolonged survival compared with that of the PBS-treated group. This protective function against GVHD mediated by G-CSF-primed donor T cells was further confirmed by decreased clinical and pathological scores in this a GVHD mouse model, especially in the lung and gut. Moreover, we found that Tcells polarized towards Th2 cells and regulatory T cells were increased in specific target organs. In addition, G-CSF treatment inhibited inducible co-stimulator(ICOS) expression and increased the expression of tolerance-related genes in recipient mice. Our study provides new insight into the immune regulatory effects of G-CSF on T cell-mediated a GVHD, especially for its precise regulation in GVHD target organs.     

The effect of temperature changes and K supply on the reproduction and growth of Bolboschoenus planiculmis

温度变化和钾添加对扁秆藨草生长及繁殖的影响 人类活动导致的气候变暖和农业面源污染已被认为是影响湿地植物生长和繁殖的重要因素。为了预 测和缓解这些人类活动的影响,研究沼泽植物如何响应这些环境变化具有重要意义。本研究选取在欧亚 大陆广泛分布的莎草科球茎植物扁秆藨草(Bolboschoenus planiculmis)为研究对象,考察气温变化(恒温： 15、20、25 °C及交替温度：20/10和30/15 °C)和钾添加(0、1、3、9 和18 mmol/L)对其生长和繁殖性状 的影响。研究结果表明,高的恒温(20、25 °C)比高的交替温度(30/15 °C)更有利于扁秆藨草球茎的形成, 而地上生物量和株高一般在较高温度下(30/15、25 °C)达到最大值。扁秆藨草的繁殖和生长性状均与施钾量 呈驼峰型关系,最适施钾量在1–3 mmol/L K。高恒温效应和最适钾浓度的交互作用对繁殖性状的促进作 用最大,但是,较高的温度(30/15和25 °C)和0–9 mmol/L的钾浓度只促进了生长性状的生长。综上所述, 扁秆藨草的种群优势度可能受益于全球变暖和额外的钾添加。     

Dissolvable Gelatin-Based Microcarriers Generated through Droplet Microfluidics for Expansion and Culture of Mesenchymal Stromal Cells

Microcarriers are synthetic particles used in bioreactor-based cell manufacturing of anchorage-dependent cells to promote proliferation at efficient physical volumes, mainly by increasing the surface area-to-volume ratio. Mesenchymal stromal cells (MSCs) are adherent cells that are used for numerous clinical trials of autologous and allogeneic cell therapy, thus requiring avenues for large-scale cell production at efficiently low volumes and cost. Here, a dissolvable gelatin-based microcarrier is developed for MSC expansion. This novel microcarrier shows comparable cell attachment efficiency and proliferation rate when compared to several commercial microcarriers, but with higher harvesting yield due to the direct dissolution of microcarrier particles and thus reduced cell loss at the cell harvesting step. Furthermore, gene expression and in vitro differentiation suggest that MSCs cultured on gelatin microcarriers maintain trilineage differentiation with similar adipogenic differentiation efficiency and higher chondrogenic and osteogenic differentiation efficiency when compared to MSCs cultured on 2D planar polystyrene tissue culture flask; on the contrary, MSCs cultured on conventional microcarriers appear to be bipotent along osteochondral lineages whereby adipogenic differentiation potential is impeded. These results suggest that these gelatin microcarriers are suitable for MSC culture and expansion, and can also potentially be extended for other types of anchorage-dependent cells.     

Comprehensive landscape and interference of clonal haematopoiesis mutations for liquid biopsy: A Chinese pan-cancer cohort

Tumour-derived DNA found in the plasma of cancer patients provides the probability to detect somatic mutations from circulating cell-free DNA (cfDNA) in plasma samples. However, clonal hematopoiesis (CH) mutations affect the accuracy of liquid biopsy for cancer diagnosis and treatment. Here, we integrated landscape of CH mutations in 11,725 pan-cancer patients of Chinese and explored effects of CH on liquid biopsies in real-world. We first identified 5933 CHs based on panel sequencing of matched DNA of white blood cell and cfDNA on 301 genes for 5100 patients, in which CH number of patients had positive correlation with their diagnosis age. We observed that canonical genes related to CH, including DNMT3A, TET2, ASXL1, TP53, ATM, CHEK2 and SF3B1, were dominant in the Chinese cohort and 13.29% of CH mutations only appeared in the Chinese cohort compared with the Western cohort. Analysis of CH gene distribution bias indicated that CH tended to appear in genes with functions of tyrosine kinase regulation, PI3K-Akt signalling and TP53 activity, suggesting unfavourable effects of CH mutations in cancer patients. We further confirmed effect of driver genes carried by CH on somatic mutations in liquid biopsy of cancer patients. Forty-eight actionable somatic mutations in 17 driver genes were considered CH genes in 92 patients (1.80%) of the Chinese cohort, implying potential impacts of CH on clinical decision-making. Taken together, this study exhibits strong evidence that gene mutations from CH interfere accuracy of liquid biopsies using cfDNA in cancer diagnosis and treatment in real-world.     

The coordination of spindle‐positioning forces during the asymmetric division of the Caenorhabditis elegans zygote

In Caenorhabditis elegans zygote, astral microtubules generate forces essential to position the mitotic spindle, by pushing against and pulling from the cortex. Measuring microtubule dynamics there, we revealed the presence of two populations, corresponding to pulling and pushing events. It offers a unique opportunity to study, under physiological conditions, the variations of both spindle‐positioning forces along space and time. We propose a threefold control of pulling force, by polarity, spindle position and mitotic progression. We showed that the sole anteroposterior asymmetry in dynein on‐rate, encoding pulling force imbalance, is sufficient to cause posterior spindle displacement. The positional regulation, reflecting the number of microtubule contacts in the posterior‐most region, reinforces this imbalance only in late anaphase. Furthermore, we exhibited the first direct proof that dynein processivity increases along mitosis. It reflects the temporal control of pulling forces, which strengthens at anaphase onset following mitotic progression and independently from chromatid separation. In contrast, the pushing force remains constant and symmetric and contributes to maintaining the spindle at the cell centre during metaphase.     

Mesenchymal stem cell‐conditioned medium attenuates the retinal pathology in amyloid‐β‐induced rat model of Alzheimer's disease: Underlying mechanisms

Amyloid‐beta (Aβ) oligomer is known to contribute to the pathophysiology of age‐related macular degeneration. Herein, we aimed to elucidate the in vivo and in vitro effects of Aβ_1‐42 application on retinal morphology in rats. Our in vivo studies revealed that intracerebroventricular administration of Aβ_1‐42 oligomer caused dysmorphological changes in both retinal ganglion cells and retinal pigment epithelium. In addition, in vitro studies revealed that ARPE‐19 cells following Aβ_1‐42 oligomer application had decreased viability along with apoptosis and decreased expression of the tight junction proteins, increased expression of both phosphor‐AKT and phosphor‐GSK3β and decreased expression of both SIRT1 and β‐catenin. Application of conditioned medium (CM) obtained from mesenchymal stem cells (MSC) protected against Aβ_1‐42 oligomer‐induced retinal pathology in both rats and ARPE‐19 cells. In order to explore the potential role of peptides secreted from the MSCs, we applied mass spectrometry to compare the peptidomics profiles of the MSC‐CM. Gene ontology enrichment analysis and String analysis were performed to explore the differentially expressed peptides by predicting the functions of their precursor proteins. Bioinformatics analysis showed that 3‐8 out of 155–163 proteins in the MSC‐CM maybe associated with SIRT1/pAKT/pGSK3β/β‐catenin, tight junction proteins, and apoptosis pathway. In particular, the secretomes information on the MSC‐CM may be helpful for the prevention and treatment of retinal pathology in age‐related macular degeneration.     

Sustained expression of MCP-1 induced low wall shear stress loading in conjunction with turbulent flow on endothelial cells of intracranial aneurysm

Shear stress was reported to regulate the expression of AC007362, but its underlying mechanisms remain to be explored. In this study, to isolate endothelial cells of blood vessels, unruptured and ruptured intracranial aneurysm (IA) tissues were collected from IA patients. Subsequently, quantitative real-time PCR (qRT-PCR), Western blot and luciferase assay were performed to investigate the relationships between AC007362, miRNAs-493 and monocyte chemoattractant protein-1 (MCP-1) in human umbilical vein endothelial cells (HUVECs) exposed to shear stress. Reduced representation bisulphite sequencing (RRBS) was performed to assess the level of DNA methylation in AC007362 promoter. Accordingly, AC007362 and MCP-1 were significantly up-regulated while miR-493 was significantly down-regulated in HUVECs exposed to shear stress. AC007362 could suppress the miR-493 expression and elevate the MCP-1 expression, and miR-493 was shown to respectively target AC007362 and MCP-1. Moreover, shear stress in HUVECs led to the down-regulated DNA methyltransferase 1 (DNMT1), as well as the decreased DNA methylation level of AC007362 promoter. Similar results were also observed in ruptured IA tissues when compared with unruptured IA tissues. In conclusion, this study presented a deep insight into the operation of the regulatory network of AC007362, miR-493 and MCP-1 upon shear stress. Under shear stress, the expression of AC007362 was enhanced by the inhibited promoter DNA methylation, while the expression of MCP-1 was enhanced by sponging the expression of miR-493.