Retrograde nerve growth factor signaling modulates tooth mechanical hyperalgesia induced by orthodontic toothmovement via acid-sensing ion channel 3

INTRODUCTION Orofacial pain, with a prevalence of 16％ among general population,1 is a constellation of painful conditions in the orofacial regions and comprises...     

血浆循环核酸应用于肝细胞癌诊断与预后评价的初步探索

背景 以肝细胞肝癌(hepatocellular carcinoma,HCC)为主的肝肿瘤在中国人死亡危险因素中排第5位,肝细胞肝癌的5年生存率仅为12.5％,对确诊肝癌的患者进行分级治疗显得尤为重要.目前仍然没有被广泛接受可以在术前对肝细胞肝癌患者的微血管浸润(microvascular invasion,MVI)进...     

Phospholipase A2 inhibitor and LY6/PLAUR domain-containing protein PINLYP regulates type I interferon innate immunity

Type I interferons (IFNs) are the first frontline of the host innate immune response against invading pathogens. Herein, we characterized an unknown protein encoded by phospholipase A2 inhibitor and LY6/PLAUR domain-containing (PINLYP) gene that interacted with TBK1 and induced type I IFN in a TBK1- and IRF3-dependent manner. Loss of PINLYP impaired the activation of IRF3 and production of IFN-β induced by DNA virus, RNA virus, and various Toll-like receptor ligands in multiple cell types. Because PINLYP deficiency in mice engendered an early embryonic lethality in mice, we generated a conditional mouse in which PINLYP was depleted in dendritic cells. Mice lacking PINLYP in dendritic cells were defective in type I IFN induction and more susceptible to lethal virus infection. Thus, PINLYP is a positive regulator of type I IFN innate immunity and important for effective host defense against viral infection.

Interferon (IFN)-mediated antiviral responses serve as the first line of the host innate immune defense against viral infection. IFNs are divided into three families based on sequence homology: type I, type II, and type III (1, 2). The type I IFN family encodes 13 subtypes of IFN-α in humans (14 in mice), a single IFN-β subtype, and several poorly defined subtypes (3, 4). Type I IFNs were originally identified based on their ability to interfere with viral replication, restrain virus dissemination, and activate adaptive immune responses (5–7). They can be induced in most cell types by microbial pathogen-associated and damage-associated molecular patterns recognized by pattern recognition receptors (PRRs) (3). By inducing the expression of IFN-stimulated genes (ISGs), type I IFNs elicit antiviral innate immunity and mediate adaptive immune responses (8, 9).The induction of antiviral type I IFN response is elicited in response to the stimulation of PRRs that detect pathogen-associated molecular patterns, such as viral nucleic acids, viral replicative intermediates, and surface glycoproteins (10, 11). There are four major subfamilies of PRRs: the Toll-like receptors (TLRs), nucleotide-binding oligomerization domain/leucine-rich repeat-containing receptors, RIG-1-like receptors (RLRs), and the C-type lectin receptors, which are located at the cell surface, in the cytosol, or endosomal compartments (11–14). Among the TLR family members, TLR3, TLR7, TLR8, and TLR9 are involved in the recognition of viral nucleotides. Viral DNA enriched in CpG-DNA motifs is recognized by TLR9, single-stranded RNA is recognized by TLR7 and TLR8, and double-stranded RNA and its synthetic analog polyinosinic-polycytidylic acid (poly I:C) are recognized by TLR3 (15, 16). Some viral envelope proteins can be recognized by TLR4 or TLR2 (16, 17).Following viral infection, cytosolic DNA can be sensed by cyclic guanosine monophosphate (GMP)–adenosine monophosphate (AMP) synthase (cGAS) that induces the production of cyclic GMP-AMP (cGAMP) (18, 19). cGAMP functions as a second messenger that binds and activates the endoplasmic reticulum (ER) adaptor STING (19–22). Translocation of activated STING from the ER to the Golgi apparatus leads to the activation of kinase TBK1, which subsequently phosphorylates IRF3 and triggers the production of type I IFN (22–24). Cytosolic RNA can be recognized by the RLRs like RIG-1 and MDA5, which signal via mitochondrial antiviral signaling protein (MAVS; also known as CARDIF, IPS1, and VISA) and subsequently activate TBK1 and IRF3–IRF7, leading to the induction of type I IFNs and other antiviral genes (25–27).The lymphocyte antigen-6 (Ly6)/urokinase-type plasminogen activator receptor (uPAR) superfamily is characterized by the LU domain and a domain containing 10 cysteines that form distinct disulfide bridges, which create the three-fingered structural motif. The Ly6/uPAR family members regulate a wide range of functions in various cell types (28). Here, we uncovered the previously uncharacterized role of the Ly6/uPAR family member PINLYP in the induction of type I IFNs in response to DNA virus, RNA virus, and other TLR ligands. This study further defined the pivotal function of PINLYP in the effective host defense against virus infection.     

A 10-Year Impact Evaluation of the Universal Salt Iodization (USI) Intervention in Sarawak,Malaysia, 2008–2018

A universal salt iodization (USI) was introduced in Sarawak, Malaysia in 2008 to control the iodine deficiency disorders (IDD) among its population. The purpose of this study is to evaluate the impact of the USI among school children in Sarawak after 10 years of implementation. The data were extracted from 2008 and 2018 Sarawak state-wide IDD surveys. Briefly, both surveys were cross-sectional surveys covering information on the socio-demographic, status of goitre, urinary iodine, and the amount of iodine in the salt samples. A total of 1104 and 988 between the ages of 8 and 10 were involved in the 2008 and 2018 surveys, respectively. The overall prevalence of goitre among the school children in Sarawak was significantly lower in 2018 (0.1%) compared to 2008 (2.9%). The median urinary iodine concentration (UIC) in urine samples had risen significantly from 102.1 µg/L in 2008 to 126.0 µg/L in 2018. In terms of iodine content in salt samples, the median concentration improved significantly in 2018 (35.5 µg/L) compared to 2008 (14.7 µg/L). After 10 years of USI implementation in Sarawak, the results from both surveys confirmed the effectiveness of mandatory USI in increasing the nutritional iodine status of school children in Sarawak.     

Resovist标记神经干细胞向大鼠局灶性脑缺血区域的迁移：MRI体内追踪

摘要 背景：Resovist是一种超顺磁性氧化铁,能够标记神经干细胞。本实验成功制备Resovist标记的神经干细胞（磁标记神经干细胞）,并利用MRI技术活体内追踪磁标记神经干细胞向大鼠脑部缺血区的迁移。 目的：利用核磁共振技术（MRI）活体追踪Resovist标记的神经干细胞移植治疗大鼠局灶性脑缺血。 设计,时间,地点：体外进行细胞学研究及大鼠脑内活体追踪试验。实验从2006年12月到2009年2月在哈尔滨医科大学基础实验室及哈尔滨医科大学附属第二医院神经科和MRI室完成。 材料：哈尔滨医科大学动物中心提供的新生清洁级SD大鼠 方法：神经干细胞培养、传代;制备Resovist标记的神经干细胞;利用免疫细胞化学、透射电镜和Prussian blue 染色等方法对Resovist标记神经干细胞的生长曲线进行研究。核磁共振追踪活体磁标记神经干细胞。 主要观察指标：免疫细胞化学、透射电镜、普鲁士蓝染色和MRI等方法 结果：在原代及传代细胞中有Nestin阳性细胞即神经干细胞。Resovist与神经干细胞共同孵育后,透射电镜及Prussian blue 染色显示胞浆中含有铁颗粒,铁颗粒也可以随细胞的分裂增殖而传到子代细胞中。随Resovist浓度的增高(2.8－11.2μg/ml), Resovist对神经干细胞存活无显著性影响。当Resovist的浓度大于22.4μg/ml时,影响其存活。活体状态下,MRI成功追踪到Resovist标记神经干细胞(Resovist浓度为 11.2μg/ml)呈低信号,并随时间推移,细胞向缺血灶迁移。 结论：本实验利用Resovist作为磁标记探针,成功制备磁标记神经干细胞。利用核磁共振（MRI）技术对磁标记神经干细胞进行活体追踪,观察细胞移植后的存活、迁移状况。     

不同麻醉药物配伍在结肠镜检查中的应用与护理支持

目的:比较芬太尼复合咪唑安定与复合异丙酚两种静脉麻醉方法的用于肠镜检查中的临床麻醉效果和安全性.方法:130例美国麻醉医师协会(ASA)Ⅰ-Ⅱ级患者随机分为2组:FM组(芬太尼 咪唑安定,n=75),FP组(芬太尼 异丙酚,n=55).观察两组镇静镇痛程度、遗忘程度、起效时间、苏醒时间、镜检满意度、呼吸抑制及血压、心率及血氧饱和度的变化.结果:FFM组、FP组均取得了良好的镇静镇痛效果,FP组作用更显著(t=29.33,P<0.01;t=1 5.35,P<0.01);FP组起效时间(t=6.63,P<0.01)、苏醒时间(t=7.83,P<0.01)、遗忘率(X~2=22.70,P<0.01)、镜检满意度(P<0.01或P<0.05)明显优于组FM;对血压和血氧饱和度的影响FM组低于FP组,两组呼吸抑制(SPO2<90%)率FM组(4%)与FP组(3.6%)相比差异无著性(P>0.05).结论:芬太尼复合咪唑安定与复合异丙酚均有良好的镇静镇痛效果,是安全有效的;且护理支持中必须加强呼吸、循环监护及镇静观察.     

A novel method for preparing a protein-encapsulated bioaerogel: using a red fluorescent protein as a model

A recombinant red fluorescent protein, DsRed, was chosen as a model protein to prepare a protein-encapsulated bioaerogel, DsRed-SAG. It was prepared using sol–gel polymerization of tetraethyl orthosilicate (TEOS) with an ionic liquid as the solvent and pore-forming agent. The DsRed-SAG bioaerogel was characterized by Fourier transformation infrared, scanning electron microscopy and Brunauer–Emmett-Teller measurements. It was found that the as-prepared bioaerogel had high porosity, and the silica network exhibited little shrinkage during the drying process. The stability of the bioaerogel was monitored by fluorescence spectroscopy and confirmed by confocal laser scanning microscopy. In addition, the protection of the encapsulated proteins by the silica network was further investigated using the degradation test by a protease. The results indicated that the as-prepared protein was quite stable during formation of the protein-containing wet gel and extraction of the ionic liquid, demonstrating that the new method can be extended to prepare other protein-encapsulated bioaerogels.     

易卒中型肾血管性高血压大鼠基底动脉NPY能神经纤维的变化

本文用ABC免疫组化方法观察易卒中型肾血管性高血压大鼠高血压各时期脑基底动脉神经肽Y阳性神经纤维的变化。神经纤维定量结果显示:对照组神经肽Y能神经纤维多呈环状分布,而高血压组环状纤维减少,早、中期纤维密度与对照组无明显差异,在晚期,血管壁神经纤维多为纵行,密度明显降低,与早、中期及对照组差异均显著(P<0.01)。脑卒中症状观察结果显示:对照组及高血压组早、中期均无脑卒中发生,而高血压晚期大鼠均出现不同程度的脑卒中。提示:脑基底动脉神经肽Y能神经纤维密度降低与高血压晚期发生脑卒中可能有关。     

肠道病毒71型的快速纯化及其鉴定

目的 建立一种简单、快速有效的从细胞培养物中纯化肠道病毒71(EV71)的方法.方法 EV71病毒在恒河猴肾细胞(LLC-MK2)中增殖后,将获得的细胞培养物经反复冻融、聚乙二醇6000沉淀、超速离心、氯化铯垫层超速离心的方法纯化病毒.用聚丙烯酰胺凝胶电泳(SDS-PAGE)、免疫印迹(Western blot)和透射电镜(TEM)的方法对纯化病毒进行鉴定,并测定其感染性的滴度及回收率.结果 SDS-PAGE显示出3个条带,相对分子质量分别为3.6×103、3×103和2.6×103与EV71的VP1、VP2和VP3相符合.Western blot证实为EV71特异性条带.经磷钨酸负染后电镜观察,能看到典型病毒颗粒.采用终浓度为10%的聚乙二醇6000沉淀后的病毒的感染性回收率为82.0%,再经氯化铯垫层超速离心后浓缩病毒的感染性回性率为29.0%.结论 聚乙二醇6000沉淀结合氯化铯垫层超速离心的方法比氯化铯密度梯度区带离心方法更简便,易于操作,并且比单独聚乙二醇6000沉淀有更高的纯度,是一种简便、有效的病毒纯化方法.     

Identification of Fenton-like active Cu sites by heteroatom modulation of electronic density

Developing heterogeneous catalysts with atomically dispersed active sites is vital to boost peroxymonosulfate (PMS) activation for Fenton-like activity, but how to controllably adjust the electronic configuration of metal centers to further improve the activation kinetics still remains a great challenge. Herein, we report a systematic investigation into heteroatom-doped engineering for tuning the electronic structure of Cu-N₄ sites by integrating electron-deficient boron (B) or electron-rich phosphorus (P) heteroatoms into carbon substrate for PMS activation. The electron-depleted Cu-N₄/C-B is found to exhibit the most active oxidation capacity among the prepared Cu-N₄ single-atom catalysts, which is at the top rankings of the Cu-based catalysts and is superior to most of the state-of-the-art heterogeneous Fenton-like catalysts. Conversely, the electron-enriched Cu-N₄/C-P induces a decrease in PMS activation. Both experimental results and theoretical simulations unravel that the long-range interaction with B atoms decreases the electronic density of Cu active sites and down-shifts the d-band center, and thereby optimizes the adsorption energy for PMS activation. This study provides an approach to finely control the electronic structure of Cu-N₄ sites at the atomic level and is expected to guide the design of smart Fenton-like catalysts.

The Fenton-like process presents one of the most powerful water treatment technologies to tackle persistent organic pollutants resulting from rapid economic development and unsustainable industrial and agricultural expansion (1 –4). The peroxymonosulfate (PMS)-based advanced oxidation process has attracted extensive attention due to its high efficiency at a wide pH range and ease of transport and storage (5 –7). However, the sluggish kinetics of PMS activation during oxidation processes results in prohibitive costs and substantial chemical inputs (8, 9). Therefore, developing efficient catalysts to accelerate the reaction kinetics of PMS is crucial toward efficient catalytic oxidation of recalcitrant organics. Although homogeneous first-row transition metals (Co²⁺, Fe²⁺, Cu²⁺, and Mn²⁺) generally exhibit remarkable capabilities for PMS activation, they also suffer problems such as poor recyclability and accumulation of sludge (10 –12). Comparatively, heterogeneous catalysts [e.g., transition metal oxides (13, 14), supported nanoparticles (NPs) (15, 16), and carbon-based materials (17, 18)] can be readily recovered and regenerated and are recognized as promising candidates for PMS activation. Nevertheless, the heterogeneity of NPs results in lower utilization efficiency of surface atoms (with 81.6% atoms buried and unavailable for 6-nm nickel NPs) and generally slower reaction kinetics than their homogeneous counterparts (19).Single-atom catalysts (SACs) featuring utmost atom-utilization efficiency and tunable electronic structure can break the limitations of heterogeneous catalysts in terms of the kinetics and catalytic activity (20, 21). Thus, SACs show a great potential to address the slow reaction kinetics of PMS for the Fenton-like process via maximizing the number of catalytic sites (22). For instance, a single-site Fe catalyst exhibited much faster reaction kinetics toward the degradation of phenol than the Fe NP catalyst, owing to the maximized atomic utilization (23). In addition, the synergetic effect between the atomic center and pyrrolic N site of supports endowed Co SACs with dual reaction sites and high activity for PMS-based oxidation (24). To further accelerate the reaction kinetics of PMS, various strategies have been developed to improve the intrinsic activity of single atomic sites. By controlling the configurations of single atomic sites, PMS was more favorable for adsorption and activation on the CoN_2 + 2 site than the CoN₄ site (25). Previous work shows that manipulating the electronic structure of single sites plays an essential role in mediating the intrinsic activity (26, 27). It is highly desirable to gain insights into tuning the electronic structure of single-atom sites to achieve superior PMS activation kinetics.Recent studies demonstrate that the electronic structure of isolated metal sites can be directly modulated by altering the coordinated atom species of the metal centers, favorable for expediting catalytic activity (28, 29). Notably, controlling the long-range interactions with suitable functionalities on the substrate of SACs can be a promising approach for tuning the electronic structure of metal centers (30). Indeed, the kinetic activity of single atomic sites was successfully tuned by the introduction of electron-withdrawing oxidized S groups or electron-donating thiophene-like S species into carbon supports of SACs (31). To this end, nonmetallic heteroatoms offer a substantial potential to serve as electron-withdrawing/donating functionalities on the carbon plane by chemical substitution (32, 33). Specifically, boron (B) with a vacant 2p_z orbital conjugating with the carbon π system extracts the electrons, while phosphorus (P) with a readily available lone electron pair and low electronegativity is expected to donate electron in graphene (34, 35). With this strategy, incorporating particular heteroatoms (B/P) into the substrate is a possible route to deplete/enrich the electronic density of metal centers, tuning the electronic structure of single sites to promote PMS activation kinetics.In this work, we designed a versatile strategy to systematically tune the electronic structure of Cu-N₄ sites by integrating specific heteroatoms (B/P) into N-doped carbon substrates of Cu SACs. Subsequently, the effect of the controlled electronic features of Cu centers on facilitating PMS reaction kinetics was explored. Here, the heteroatom modified Cu-N₄ catalysts were first prepared by using a hydrogen-bonding-assisted pyrolysis approach. Synchrotron X-ray adsorption spectroscopy and the projected density of states (PDOS) analysis verified the successful regulation of the electronic configuration of the Cu-N₄ SACs by different heteroatom functionalities. Furthermore, electron paramagnetic resonance and Raman spectra were employed to elucidate the PMS activation mechanism in the Cu-N₄/C-B/PMS system. This study opens an avenue to regulating the electronic structures of single active site of SACs to accelerate PMS activation kinetics for pollutant degradation.