MiR‐140 modulates the inflammatory responses of Mycobacterium tuberculosis‐infected macrophages by targeting TRAF6

This study aimed to examine miR‐140 expression in clinical samples from tuberculosis (TB) patients and to explore the molecular mechanisms of miR‐140 in host‐bacterial interactions during Mycobacterium tuberculosis (M tb) infections. The miR‐140 expression and relevant mRNA expression were detected by quantitative real‐time PCR (qRT‐PCR); the protein expression levels were analysed by ELISA and western blot; M tb survival was measured by colony formation unit assay; potential interactions between miR‐140 and the 3′ untranslated region (UTR) of tumour necrosis factor receptor‐associated factor 6 (TRAF6) was confirmed by luciferase reporter assay. MiR‐140 was up‐regulated in the human peripheral blood mononuclear cells (PBMCs) from TB patients and in THP‐1 and U937 cells with M tb infection. Overexpression of miR‐140 promoted M tb survival; on the other hand, miR‐140 knockdown attenuated M tb survival. The pro‐inflammatory cytokines including interleukin 6, tumour necrosis‐α, interleukin‐1β and interferon‐γ were enhanced by M tb infection in THP‐1 and U937 cells. MiR‐140 overexpression reduced these pro‐inflammatory cytokines levels in THP‐1 and U937 cells with M tb infection; while knockdown of miR‐140 exerted the opposite actions. TRAF6 was identified to be a downstream target of miR‐140 and was negatively modulated by miR‐140. TRAF6 overexpression increased the pro‐inflammatory cytokines levels and partially restored the suppressive effects of miR‐140 overexpression on pro‐inflammatory cytokines levels in THP‐1 and U937 cells with M tb infection. In conclusion, our results implied that miR‐140 promoted M tb survival and reduced the pro‐inflammatory cytokines levels in macrophages with M tb infection partially via modulating TRAF6 expression.     

Design and synthesis of novel 1-phenyl-3-(5-(pyrimidin-4-ylthio)-1,3,4-thiadiazol- 2-yl)urea derivatives with potent anti-CML activity throughout PI3K/AKT signaling pathway

In this investigation, a series of 1-phenyl-3-(5-(pyrimidin-4-ylthio)-1,3,4- thiadiazol-2-yl)urea receptor tyrosine kinase inhibitors were synthesized by a simple and efficient structure-based design. Structure-activity relationship (SAR) analysis of these compounds based on cellular assays led to the discovery of a number of compounds that showed potent activity against human chronic myeloid leukemia (CML) cell line K562, but very weak or no cellular toxicity through monitoring the growth kinetics of K562 cell during a period of 72 h using the real-time live-cell imaging. Among these compounds, 1-(5-((6-((3-morpholinopropyl) amino)pyrimidin-4-yl)thio)-1,3,4-thiadiazol-2-yl)-3-(4-(trifluoromethyl)phenyl)urea (7) exhibited the least cellular toxicity and better biological activity in cellular assays (K562, IC₅₀: 0.038 μM). Compound 7 also displayed very good induced-apoptosis effect for human CML cell line K562 and exerted its effect via a significantly reduced protein phosphorylation of PI3K/Akt signal pathway by Human phospho-kinase array analysis. In vitro results indicate that 1-phenyl-3-(5-(pyrimidin-4-ylthio)-1,3,4- thiadiazol-2-yl)urea derivatives are lead molecules for further development as treatment of chronic myeloid leukemia and cancer.     

Identification and immunological evaluation of novel TLR2 agonists through structure optimization of Pam3CSK4

Toll-like receptor 2 (TLR2) is a bridge between innate immunity and adaptive immunity. TLR2 agonists have been exploited as potential vaccine adjuvants and antitumor agents. However, no TLR2 agonists have been approved by FDA up to now. To discover drug-like TLR2 selective agonists, a novel series of Pam₃CSK₄ derivatives were designed based on the crystal structure of hTLR2-hTLR1-Pam₃CSK₄ complex, synthesized and evaluated for their immune-stimulatory activities. Among them, 35c was identified as a murine-specific TLR2 agonist, while 35f was a human-specific TLR2 agonist. Besides, 35d (human and murine TLR2 agonist) showed TLR2 agonistic activity comparable to Pam₃CSK₄, which included: elevated IL-6 expression level (EC₅₀ = 83.08 ± 5.94 nM), up-regulated TNF-α and IL-6 mRNA expression and promoted maturation of DCs through activating the NF-κB signaling pathway. TLRs antibodies test showed that 35a and 35d were TLR2/1 agonists, while 35f was a TLR2/6 agonist.     

Identification of new dual FABP4/5 inhibitors based on a naphthalene-1-sulfonamide FABP4 inhibitor

Fatty acid binding protein 4 (FABP4) and fatty acid binding protein 5 (FABP5) are mainly expressed in adipocytes and/or macrophages and play essential roles in energy metabolism and inflammation. When FABP4 function is diminished, FABP5 expression is highly increased possibly as a functional compensation. Dual FABP4/5 inhibitors are expected to provide beneficial synergistic effect on treating diabetes, atherosclerosis, and inflammation-related diseases. Starting from our previously reported selective FABP4 inhibitor 8, structural biology information was used to modulate the selectivity profile and to design potent dual FABP4/5 inhibitors with good selectivity against FABP3. Two compounds A16 and B8 were identified to show inhibitory activities against both FABP4/5 and good selectivity over FABP3, which could also reduce the level of forskolin-stimulated lipolysis in mature 3T3-L1 adipocytes. Compared with compound 8, these two compounds exhibited better anti-inflammatory effects in lipopolysaccharide-stimulated RAW264.7 murine macrophages, with decreased levels of pro-inflammatory cytokines TNFα and MCP-1 and apparently inhibited IKK/NF-κB pathway.     

贵州赤水桫椤国家级自然保护区鸟兽多样性红外相机初步监测

红外相机监测是了解野生动物多样性和威胁因素的重要手段。本研究采用网格法和分层抽样调查法, 在贵州赤水桫椤国家级自然保护区内选取20个监测位点布设红外相机, 对区内鸟兽物种多样性进行监测。2015年8月至2017年8月, 红外相机累计工作6,370个工作日, 共拍摄45,953张照片, 独立有效照片1,936张。准确鉴定出兽类4目8科19种, 鸟类4目11科28种, 其中, 国家II级重点保护野生动物7种。相对丰富度指数(RAI)排前五位的兽类依次是毛冠鹿(Elaphodus cephalophus)、鼬獾(Melogale moschata)、藏酋猴(Macaca thibetana)、小麂(Muntiacus reevesi)和野猪(Sus scrofa); 鸟类依次是紫啸鸫(Myophonus caeruleus)、红腹角雉(Tragopan temminckii)、灰胸竹鸡(Bambusicola thoracicus)、黑喉噪鹛(Garrulax chinensis)和棕颈钩嘴鹛(Pomatorhinus ruficollis)。物种积累曲线结果表明, 兽类稀疏化曲线在300天后趋于稳定, 表明监测取样已较充分, 而鸟类监测物种数随时间积累依旧保持增长趋势。     

贵州梵净山国家级自然保护区鸟兽红外相机监测

红外相机监测是了解野生动物多样性现状、动态变化和面临威胁的重要手段。本研究采用网格抽样调查法, 在贵州梵净山国家级自然保护区内选取2个监测样区共40个监测位点布设红外相机, 对区内兽类和鸟类物种进行监测调查。2017年4月至2018年12月间, 红外相机累积监测14,808个相机工作日, 共收集有效照片14,119张, 独立有效物种照片3,199张。共鉴定野生动物9目22科61种, 其中兽类26种, 隶属于4目12科; 鸟类35种, 隶属于5目10科。记录到国家I级重点保护野生动物2种: 黔金丝猴(Rhinopithecus brelichi)和白颈长尾雉(Syrmaticus ellioti), 国家II级重点保护野生动物9种; 被IUCN红色名录评估为濒危(EN)的1种、易危(VU)的5种、近危(NT)的8种。物种的相对多度指数(relative abundance index, RAI)分析结果显示, 藏酋猴(Macaca thibetana, RAI = 28.23)、毛冠鹿(Elaphodus cephalophus, RAI = 15.46)、野猪(Sus scrofa, RAI = 11.82)、小麂(Muntiacus reevesi, RAI = 9.05)、黔金丝猴(RAI = 7.70)为相对多度最高的5种兽类; 紫啸鸫(Myophonus insularis, RAI = 10.33)、红腹角雉(Tragopan temminckii, RAI = 9.59)、红腹锦鸡(Chrysolophus pictus, RAI = 6.96)、白颈长尾雉(RAI = 3.71)、勺鸡(Pucrasia macrolopha, RAI = 1.55)为相对多度最高的5种鸟类。另外, 红外相机还监测到较多的家畜活动(RAI = 11.14)和人为活动(RAI = 12.90), 保护区管理部门仍需采取相应管理措施, 进一步提高周边居民的保护意识, 促进保护区与社区的协调发展。     

Bibliometric analysis of Journal of Plant Ecology during 2017–2021

Issue Section: Editorial Journal of Plant Ecology (JPE) was founded in 2008. It is sponsored by the Botanical Society of China and the Institute of Botany, Chinese Academy of Sciences, and published by Oxford University Press, UK. JPE publishes diverse types of articles that fall into the broad scope of plant ecology, including plant ecophysiology, population ecology, community ecology, ecosystem ecology, landscape ecology, conservation ecology, evolutionary ecology, theoretical ecology and global change ecology.     

Interaction of rice dwarf virus outer capsid P8 protein with rice glycolate oxidase mediates relocalization of P8

Yeast two-hybrid and coimmunoprecipitation assays indicated that P8, an outer capsid protein of Rice dwarf phytoreovirus (RDV), interacts with rice glycolate oxidase (GOX), a typical enzyme of peroxisomes. Confocal immunofluorescence microscopy revealed that P8 was colocalized with GOX in peroxisomes. Time course analysis demonstrated that the localization of P8 in Spodoptera frugiperda cells changed from diffuse to discrete, punctuate inclusions during expression from 24 to 48 h post inoculation. Coexpression of GOX with P8 may target P8 into peroxisomes, which serve as replication sites for a number of viruses. Therefore, we conclude that the interaction of P8 with the GOX of host cells leads to translocation of P8 into peroxisomes and we further propose that the interaction between P8 and GOX may play important roles in RDV targeting into the replication site of host cells. Our findings have broad significance in studying the mechanisms whereby viruses target appropriate replication sites and begin their replication.     

Highly sensitive biosensor based on aptamer and hybridization chain reaction for detection of cadmium ions

In this work, a highly sensitive biosensor for detecting cadmium ions (Cd²⁺) was developed based on a Cd²⁺-specific DNA aptamer and a hybridization chain reaction (HCR). The Cd²⁺ aptamer (named S0) was used to recognize Cd²⁺ and trigger the HCR. Without Cd²⁺, S0 initiated the HCR to form long nicked dsDNA structures to quench the fluorescence. Then, Cd²⁺ could bind with S0 to block HCR to recover fluorescence. This biosensor had high sensitivity with a detection limit of 0.36 nM and a linear range from 0 to 10 nM. Moreover, it showed a satisfactory selectivity and recovery rates.     

Ultra-Broadband Electromagnetically Induced Transparency in Metamaterial Based on Conductive Coupling

Plasmonics - This paper proposes a structure composed of a horizontal metal strip resonator (SR) and four C-shaped ring resonators (CRR) to obtain a broadband electromagnetic induction transparency...