中欧组织间合作研究项目MIX-UP助力实现“碳中和”

随着全球塑料循环体系的变革升级,提高塑料的回收利用不仅可以减少塑料在生命周期中的碳排放,还可以解决废塑料潜在的生态环境危害。文中介绍了2019年国家自然科学基金组织间国际 (地区) 合作研究项目“废塑料资源高效生物降解转化的关键科学问题与技术 (MIXed plastics biodegradation and UPcycling using microbial communities,MIX-UP)”。该项目聚焦“塑料污染”这一全球化的问题,围绕中欧双方确定的“塑料生物降解菌群”研究领域,联合中欧双方14家优势科研单位,开展实质性的重大前沿合作研究。针对废塑料生物降解中存在的解聚与重塑两个难题,项目以难降解石油基塑料 (PP、PE、PUR、PET和PS) 以及生物可降解塑料 (PLA和PHA) 的混合废塑料作为研究对象,从塑料微生物降解途径解析及关键元件的挖掘与改造、塑料高效降解混菌/多酶体系的构建与功能调控、塑料降解物的高值化炼制途径设计与利用策略3个方面展开研究。本项目将突破废塑料生物降解转化中高效降解元件挖掘、塑料降解物高值化利用的关键科学问题与技术,探索一条废塑料资源化、高值化、循环化、低碳化的新塑料循环路线,建立以“降塑再造”为核心理念的废塑料生物炼制体系,丰富我国固废资源化生物技术利用平台。项目的实施不仅有助于提升我国塑料 (生物) 循环经济的理论基础和关键技术水平,还可以推动我国与国际科研院所的多边交流与合作,促进我国在生物技术领域的创新发展,助力我国碳中和目标的实现。     

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...     

Blocking of the PD-1/PD-L1 interaction by a novel cyclic peptide inhibitor for cancer immunotherapy

The interaction of PD-1/PD-L1 allows tumor cells to escape from immune surveillance. Clinical success of the antibody drugs has proven that blockade of PD-1/PD-L1 pathway is a promising strategy for cancer immunotherapy. Here, we developed a cyclic peptide C8 by using Ph.D.-C7 C phage display technology. C8 showed high binding affinity with h PD-1 and could effectively interfere the interaction of PD-1/PD-L1. Furthermore, C8 could stimulate CD8+T cell activation in human peripheral blood mononuclear cells(PBMCs). We also observed that C8 could suppress tumor growth in CT26 and B16-OVA, as well as anti-PD-1 antibody resistant B16 mouse model. CD8+T cells infiltration significantly increased in tumor microenvironment, and IFN-γ secretion by CD8+T cells in draining lymph nodes also increased. Simultaneously, we exploited T cells depletion models and confirmed that C8 exerted anti-tumor effects via activating CD8+T cells dependent manner. The interaction model of C8 with h PD-1 was simulated and confirmed by alanine scanning. In conclusion, C8 shows anti-tumor capability by blockade of PD-1/PD-L1 interaction, and C8 may provide an alternative candidate for cancer immunotherapy.     

黄山典型植被类型土壤真菌群落特征及其影响因素

黄山地势高差明显,植被类型多样,生态系统保存完整,是研究森林生态系统土壤真菌群落的天然实验室。本研究采集黄山典型植被下土壤样本,利用Illumina NovaSeq高通量测序技术分析土壤真菌群落结构,结合土壤理化性质探讨不同植被类型影响真菌群落组成的潜在因素。结果共检测到13个真菌门,优势真菌门依次为：担子菌门Basidiomycota,获得38目,202属,相对丰度介于7.30%-90.71%,在常绿落叶阔叶混交林、山地矮林及落叶阔叶林中出现高值,局部呈现先增后减的单峰变化格局;子囊菌门Ascomycota有56目,393属,相对丰度介于4.69%-53.07%,随着典型植被类型变化无明显变化规律;被孢霉门Mortierellomycota获得1目和2属,相对丰度介于2.88%-29.92%,随着典型植被类型变化呈现U型变化模式;5种植被类型土壤中共检测到34个不同分类单元的真菌指示类群,落叶阔叶林土壤真菌指示类群最为丰富,占67%;pH显著影响土壤真菌α多样性（Pearson,P<0.001）,是黄山土壤真菌群落变异的主控因子（Monte Corlo 检验,P<0.01）。     

Photobiomodulation suppresses JNK3 by activation of ERK/MKP7 to attenuate AMPA receptor endocytosis in Alzheimer's disease

Alzheimer's disease (AD), a severe age‐related neurodegenerative disorder, lacks effective therapeutic methods at present. Physical approaches such as gamma frequency light flicker that can effectively reduce amyloid load have been reported recently. Our previous research showed that a physical method named photobiomodulation (PBM) therapy rescues Aβ‐induced dendritic atrophy in vitro. However, it remains to be further investigated the mechanism by which PBM affects AD‐related multiple pathological features to improve learning and memory deficits. Here, we found that PBM attenuated Aβ‐induced synaptic dysfunction and neuronal death through MKP7‐dependent suppression of JNK3, a brain‐specific JNK isoform related to neurodegeneration. The results showed PBM‐attenuated amyloid load, AMPA receptor endocytosis, dendrite injury, and inflammatory responses, thereby rescuing memory deficits in APP/PS1 mice. We noted JNK3 phosphorylation was dramatically decreased after PBM treatment in vivo and in vitro. Mechanistically, PBM activated ERK, which subsequently phosphorylated and stabilized MKP7, resulting in JNK3 inactivation. Furthermore, activation of ERK/MKP7 signaling by PBM increased the level of AMPA receptor subunit GluR 1 phosphorylation and attenuated AMPA receptor endocytosis in an AD pathological model. Collectively, these data demonstrated that PBM has potential therapeutic value in reducing multiple pathological features associated with AD, which is achieved by regulating JNK3, thus providing a noninvasive, and drug‐free therapeutic strategy to impede AD progression.     

The herpesvirus accessory protein γ134.5 facilitates viral replication by disabling mitochondrial translocation of RIG-I

RIG-I and MDA5 are cytoplasmic RNA sensors that mediate cell intrinsic immunity against viral pathogens. While it has been well-established that RIG-I and MDA5 recognize RNA viruses, their interactive network with DNA viruses, including herpes simplex virus 1 (HSV-1), remains less clear. Using a combination of RNA-deep sequencing and genetic studies, we show that the γ₁34.5 gene product, a virus-encoded virulence factor, enables HSV growth by neutralization of RIG-I dependent restriction. When expressed in mammalian cells, HSV-1 γ₁34.5 targets RIG-I, which cripples cytosolic RNA sensing and subsequently suppresses antiviral gene expression. Rather than inhibition of RIG-I K63-linked ubiquitination, the γ₁34.5 protein precludes the assembly of RIG-I and cellular chaperone 14-3-3ε into an active complex for mitochondrial translocation. The γ₁34.5-mediated inhibition of RIG-I-14-3-3ε binding abrogates the access of RIG-I to mitochondrial antiviral-signaling protein (MAVS) and activation of interferon regulatory factor 3. As such, unlike wild type virus HSV-1, a recombinant HSV-1 in which γ₁34.5 is deleted elicits efficient cytokine induction and replicates poorly, while genetic ablation of RIG-I expression, but not of MDA5 expression, rescues viral growth. Collectively, these findings suggest that viral suppression of cytosolic RNA sensing is a key determinant in the evolutionary arms race of a large DNA virus and its host.     

Baicalein alleviates osteoarthritis by protecting subchondral bone,inhibiting angiogenesis and synovial proliferation

Osteoarthritis (OA) is one of the most frequent chronic joint diseases with the increasing life expectancy. The main characteristics of the disease are loss of articular cartilage, subchondral bone sclerosis and synovium inflammation. Physical measures, drug therapy and surgery are the mainstay of treatments for OA, whereas drug therapies are mainly limited to analgesics, glucocorticoids, hyaluronic acids and some alternative therapies because of single therapeutic target of OA joints. Baicalein, a traditional Chinese medicine extracted from Scutellaria baicalensis Georgi, has been widely used in anti-inflammatory therapies. Previous studies revealed that baicalein could alleviate cartilage degeneration effectively by acting on articular chondrocytes. However, the mechanisms involved in baicalein-mediated protection of the OA are not completely understood in consideration of integrality of arthrosis. In this study, we found that intra-articular injection of baicalein ameliorated subchondral bone remodelling. Further studies showed that baicalein could decrease the number of differentiated osteoblasts by inhibiting pre-osteoblasts proliferation and promoting pre-osteoblasts apoptosis. In addition, baicalein impaired angiogenesis of endothelial cells and inhibited proliferation of synovial cells. Taken together, these results implicated that baicalein might be an effective medicine for treating OA by regulating multiple targets.     

Targeting P2 receptors in purinergic signaling: a new strategy of active ingredients in traditional Chinese herbals for diseases treatment

Adenosine triphosphate (ATP) and its metabolites adenosine diphosphate, adenosine monophosphate, and adenosine in purinergic signaling pathway play important roles in many diseases. Activation of P2 receptors (P2R) channels and subsequent membrane depolarization can induce accumulation of extracellular ATP, and furtherly cause kinds of diseases, such as pain- and immune-related diseases, cardiac dysfunction, and tumorigenesis. Active ingredients of traditional Chinese herbals which exhibit superior pharmacological activities on diversified P2R channels have been considered as an alternative strategy of disease treatment. Experimental evidence of potential ingredients in Chinese herbs targeting P2R and their pharmacological activities were outlined in the study.

     

TGF-β isoforms inhibit hepatitis C virus propagation in transforming growth factor beta/SMAD protein signalling pathway dependent and independent manners

Transforming growth factor beta (TGF-β) plays an important role in the viral liver disease progression via controlling viral propagation and mediating inflammation-associated responses. However, the antiviral activities and mechanisms of TGF-β isoforms, including TGF-β1, TGF-β2 and TGF-β3, remain unclear. Here, we demonstrated that all of the three TGF-β isoforms were increased in Huh7.5 cells infected by hepatitis C virus (HCV), but in turn, the elevated TGF-β isoforms could inhibit HCV propagation with different potency in infectious HCV cell culture system. TGF-β isoforms suppressed HCV propagation through interrupting several different stages in the whole HCV life cycle, including virus entry and intracellular replication, in TGF-β/SMAD signalling pathway–dependent and TGF-β/SMAD signalling pathway–independent manners. TGF-β isoforms showed additional anti-HCV activities when combined with each other. However, the elevated TGF-β1 and TGF-β2, not TGF-β3, could also induce liver fibrosis with a high expression of type I collagen alpha-1 and α-smooth muscle actin in LX-2 cells. Our results showed a new insight into TGF-β isoforms in the HCV-related liver disease progression.