RIPK2: a promising target for cancer treatment

As an essential mediator of inflammation and innate immunity, the receptor-interacting serine/threonine-protein kinase-2 (RIPK2) is responsible for transducing signaling downstream of the intracellular peptidoglycan sensors nucleotide oligomerization domain (NOD)-like receptors 1 and 2 (NOD1/2), which will further activate nuclear factor kappa-B (NF-κB) and mitogen-activated protein kinase (MAPK) pathways, leading to the transcription activation of pro-inflammatory cytokines and productive inflammatory response. Thus, the NOD2-RIPK2 signaling pathway has attracted extensive attention due to its significant role in numerous autoimmune diseases, making pharmacologic RIPK2 inhibition a promising strategy, but little is known about its role outside the immune system. Recently, RIPK2 has been related to tumorigenesis and malignant progression for which there is an urgent need for targeted therapies. Herein, we would like to evaluate the feasibility of RIPK2 being the anti-tumor drug target and summarize the research progress of RIPK2 inhibitors. More importantly, following the above contents, we will analyze the possibility of applying small molecule RIPK2 inhibitors to anti-tumor therapy

Numerical study on the effects of non-uniform corrosion and confinement conditions on the bond performance of RC beams

A 3D model is established to simulate the bond performance of corroded RC beams, in which the non-uniform corrosion of tensile reinforcement and confinement conditions (characterized by the thickness-diameter ratios of 1.9–3.8 and stirrup confinement index of 0–8.3%) are investigated. In the 3D numerical model, fine modeling was adopted to consider the influences of corrosion on the steel-concrete interface and the non-uniform corrosion was considered by separating the tensile bars into two parts with inconsistent diameter loss. Meanwhile, a two-stage numerical analysis method was utilized, to reflect the corrosion-induced concrete cracking by applying forced displacement and subsequently analyzed their flexural bond performance. In comparison to the existing experiments, the proposed 3D numerical model is proved to be reasonable. In addition, the simulation results show that the increment of the (residual) bond strength generated by the increasing thickness-diameter ratio increases with the mass loss rate, while the increases of stirrup confinement index cause much more increases in the (residual) bond strength for the corroded RC beams than the un-corroded beams. Furthermore, a bond stress-slip relationship is proposed taking the non-uniform corrosion and confinement conditions into account, which correlates well with the experiments

Confirmation of Trachischium guentheri (Serpentes: Colubridae) from Tibet, China, with description of Tibetan T. monticola

Wang, Kai, Jiang, Ke, Jin, Jieqiong, Liu, Xu, Che, Jing (2019): Confirmation of Trachischium guentheri (Serpentes: Colubridae) from Tibet, China, with description of Tibetan T. monticola. Zootaxa 4688 (1): 101-110, DOI: https://doi.org/10.11646/zootaxa.4688.1.

A new species of cascade frog (Amphibia: Ranidae) in the Amolops monticola group from China

Yuan, Zhiyong, Jin, Jieqiong, Li, Jiannan, Stuart, Bryan L., Wu, Jun (2018): A new species of cascade frog (Amphibia: Ranidae) in the Amolops monticola group from China. Zootaxa 4415 (3): 498-512, DOI: https://doi.org/10.11646/zootaxa.4415.3.

Function of Graphene Oxide as the “Nanoquencher” for Hg2+ Detection Using an Exonuclease I-Assisted Biosensor

Graphene oxide is well known for its excellent fluorescence quenching ability. In this study, positively charged graphene oxide (pGO25000) was developed as a fluorescence quencher that is water-soluble and synthesized by grafting polyetherimide onto graphene oxide nanosheets by a carbodiimide reaction. Compared to graphene oxide, the fluorescence quenching ability of pGO25000 is significantly improved by the increase in the affinity between pGO25000 and the DNA strand, which is introduced by the additional electrostatic interaction. The FAM-labeled single-stranded DNA probe can be almost completely quenched at concentrations of pGO25000 as low as 0.1 μg/mL. A simple and novel FAM-labeled single-stranded DNA sensor was designed for Hg2+ detection to take advantage of exonuclease I-triggered single-stranded DNA hydrolysis, and pGO25000 acted as a fluorescence quencher. The FAM-labeled single-stranded DNA probe is present as a hairpin structure by the formation of T–Hg2+–T when Hg2+ is present, and no fluorescence is observed. It is digested by exonuclease I without Hg2+, and fluorescence is recovered. The fluorescence intensity of the proposed biosensor was positively correlated with the Hg2+ concentration in the range of 0–250 nM (R2 = 0.9955), with a seasonable limit of detection (3σ) cal. 3.93 nM. It was successfully applied to real samples of pond water for Hg2+ detection, obtaining a recovery rate from 99.6% to 101.1%

A Docosahexaenoic Acid Derivative (N-Benzyl Docosahexaenamide) as a Potential Therapeutic Candidate for Treatment of Ovarian Injury in the Mouse Model

Commonly used clinical chemotherapy drugs, such as cyclophosphamide (CTX), may cause injury to the ovaries. Hormone therapies can reduce the ovarian injury risk; however, they do not achieve the desired effect and have obvious side effects. Therefore, it is necessary to find a potential therapeutic candidate for ovarian injury after chemotherapy. N-Benzyl docosahexaenamide (NB-DHA) is a docosahexaenoic acid derivative. It was recently identified as the specific macamide with a high degree of unsaturation in maca (Lepidium meyenii). In this study, the purified NB-DHA was administered intragastrically to the mice with CTX-induced ovarian injury at three dose levels. Blood and tissue samples were collected to assess the regulation of NB-DHA on ovarian function. The results indicated that NB-DHA was effective in improving the disorder of estrous cycle, and the CTX+NB-H group can be recovered to normal levels. NB-DHA also significantly increased the number of primordial follicles, especially in the CTX+NB-M and CTX+NB-H groups. Follicle-stimulating hormone and luteinizing hormone levels in all treatment groups and estradiol levels in the CTX+NB-H group returned to normal. mRNA expression of ovarian development-related genes was positive regulated. The proportion of granulosa cell apoptosis decreased significantly, especially in the CTX+NB-H group. The expression of anti-Müllerian hormone and follicle-stimulating hormone receptor significantly increased in ovarian tissues after NB-DHA treatment. NB-DHA may be a promising agent for treating ovarian injury

CaMKIIα may modulate fentanyl-induced hyperalgesia via a CeLC-PAG-RVM-spinal cord descending facilitative pain pathway in rats.

Each of the lateral capsular division of central nucleus of amygdala(CeLC), periaqueductal gray (PAG), rostral ventromedial medulla(RVM) and spinal cord has been proved to contribute to the development of opioid-induced hyperalgesia(OIH). Especially, Ca2+/calmodulin-dependent protein kinase IIα (CaMKIIα) in CeLC and spinal cord seems to play a key role in OIH modulation. However, the pain pathway through which CaMKIIα modulates OIH is not clear. The pathway from CeLC to spinal cord for this modulation was explored in the present study. Mechanical and thermal hyperalgesia were tested by von Frey test or Hargreaves test, respectively. CaMKIIα activity (phospho-CaMKIIα, p-CaMKIIα) was evaluated by western blot analysis. CaMKIIα antagonist (KN93) was micro-infused into CeLC, spinal cord or PAG, respectively, to evaluate its effect on behavioral hyperalgesia and p-CaMKIIα expression in CeLC, PAG, RVM and spinal cord. Then the underlying synaptic mechanism was explored by recording miniature excitatory postsynaptic currents (mEPSCs) on PAG slices using whole-cell voltage-clamp methods. Results showed that inhibition of CeLC, PAG or spinal CaMKIIα activity respectively by KN93, reversed both mechanical and thermal hyperalgesia. Microinjection of KN93 into CeLC decreased p-CaMKIIα expression in CeLC, PAG, RVM and spinal cord; while intrathecal KN93 can only block spinal but not CeLC CaMKIIα activity. KN93 injected into PAG just decreased p-CaMKIIα expression in PAG, RVM and spinal cord, but not in the CeLC. Similarly, whole-cell voltage-clamp recording found the frequency and amplitude of mEPSCs in PAG cells were decreased by KN93 added in PAG slice or micro-infused into CeLC in vivo. These results together with previous findings suggest that CaMKIIα may modulate OIH via a CeLC-PAG-RVM-spinal cord descending facilitative pain pathway